OECD SIDS

SODIUM SULFATE

FOREWORD

INTRODUCTION

Sodium sulfate CAS N: 7757-82-6

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SIDS Initial Assessment Report For SIAM 20

Paris, France, 19 22 April 2005

1. Chemical Name: 2. CAS Number: 3. Sponsor Country:

Sodium sulfate 7757-82-6 Slovak Republic Contact Point: Centre for Chemical Substances and Preparations, Bratislava Contact Person: Peter Rusnak, Ph.D. Director Czech Republic Contact Point: Ministry of Environment Contact Person: Karel Blha, Ph.D. Director Department of Environmental Risks Prague Sodium Sulfate Producers Association (SSPA) and TOSOH

Co-sponsor Country:

4. Shared Partnership with: 5. Roles/Responsibilities of the Partners:

Name of industry sponsor /consortium Process used

Sodium Sulfate Producers Association (SSPA) Documents were drafted by the consortium, then peer reviewed by sponsor countries experts Nominated by ICCA in the framework of the ICCA HPV program

6. Sponsorship History

How was the chemical or category brought into the OECD HPV Chemicals Programme?

7. Review Process Prior to the SIAM: 8. Quality check process:

Two drafts were reviewed by the Slovakian/Czech authorities; third draft subject to review by OECD membership Data was reviewed against the OECD criteria as described in the SIDS manual. These criteria were used to select data for extraction into the SIDS dossier. Original data was sought wherever possible. Originally reported work was deemed reliable if sufficient information was reported (according to the manual) to judge it robust. Reviews were only judged reliable if reported
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SODIUM SULFATE by reputable organisations/authorities or if partners had been directly involved in their production Deadline for circulation: 21 January 2005 13 January 2005

9. Date of Submission: 10. Date of last Update: 11. Comments:

The HPV dossier on Sodium sulphate was sponsored by the European Sodium sulphate Producers Association (SSPA). At the time of writing the dossier, members were: Adisseo France Akzo Nobel Nederland NV Alkim Alkali Kimya A.S. Cordenka Crimidesa Elementis Chromium FMC Foret SA Lenzing AG Minera de Santa Marta Perstorp AB Steri Oy Sulquisa Tessenderlo Chemie SA FRANCE THE NETHERLANDS TURKEY GERMANY SPAIN UNITED KINGDOM SPAIN AUSTRIA SPAIN SWEDEN FINLAND SPAIN BELGIUM Co Sponsored by: TOSOH CORPORATION Japan

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SIDS INITIAL ASSESSMENT PROFILE CAS No. Chemical Name 7757-82-6 Sodium sulfate

SODIUM SULFATE

Structural Formula

SUMMARY CONCLUSIONS OF THE SIAR

Human Health Sulfate (and sodium) ions are important constituents of the mammalian body and of natural foodstuffs and there is a considerable daily turnover of both ions (several grams/day expressed as sodium sulfate). Near-complete absorption of dietary sulfates may occur at low concentration, depending on the counter-ion, but absorption capacity can be saturated at higher artificial dosages resulting in cathartic effects. Absorption through skin can probably be ignored since sodium sulfate is fully ionised in solution. One source suggests that very high levels of sulfate in urine may occur due to absorption from dust inhalation. At dietary levels, excretion is mainly in the urine. Sulfates are found in all body cells, with highest concentrations in connective tissues, bone and cartilage. Sulfates play a role in several important metabolic pathways, including those involved in detoxification processes. The acute toxicity (LD50) of sodium sulfate has not been reliably established but is probably far in excess of 5000 mg/kg. In an inhalation study with an aerosol, no adverse effects were found at 10 mg/m3. Also human data indicate a very low acute toxicity of sodium sulfate. Human clinical experience indicates that very high oral doses of sodium sulfate, 300 mg/kg bw up to 20 grams for an adult, are well tolerated, except from (intentionally) causing severe diarrhoea. WHO/FAO did not set an ADI for sodium sulfate. There is no data on acute dermal toxicity, but this is probably of no concern because of total ionisation in solution. Sodium sulfate is not irritating to the skin and slightly irritating to the eyes. Respiratory irritation has never been reported. Based on wide practical experience with sodium sulfate, in combination with the natural occurrence of sulfate in the body, sensitising effects are highly unlikely. No suitable dermal and inhalation repeated-dose toxicity studies are available. Valid oral repeated dose toxicity studies with 21, 28 and 35 day studies in hens and pigs are available. Toxicity was confined to changes in bodyweight, water and feed intake and diarrhoea. These changes occurred only at very high doses of sodium sulfate. In ruminants, high concentrations of sulfate in food may result in the formation of toxic amounts of sulfites by bacterial reduction the rumen, leading to poly-encephalomalacia. The available data do not allow the derivation of a NOAEL. Based on available consumer data, a daily dose of around 25 mg/kg/day is well tolerated by humans. There are no data on in vitro and in vivo genotoxicity, apart from a negative Ames test. There is no valid oral carcinogenicity study. Limited data from experimental studies support the notion that a substance that is abundantly present in and essential to the body is unlikely to be carcinogenic. Limited data of poor validity did not provide an indication of toxicity to reproduction. There are considerable data gaps and the data that are available are not all of standard quality or from animals commonly used for toxicity testing. Nevertheless the weight of evidence, combined with previous assessments of both the sodium ion and sulfic ions lead to the conclusion that the identified data gaps need not necessarily be filled.

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OECD SIDS
Environment

SODIUM SULFATE

Sodium sulphate is a solid inorganic salt well soluble in water (161-190 g/l at 20 oC) with a melting point of 884 o C and density of 2.7 g/cm3. In water solutions it is fully dissociated to sodium and sulfate ions. In water sodium sulfate completely dissociates into sodium and sulfate ions. The ions cannot hydrolyse. In anaerobic environments sulfate is biologically reduced to (hydrogen) sulphide by sulfate reducing bacteria, or incorporated into living organisms as source of sulphur, and thereby included in the sulphur cycle. Sodium sulfate is not reactive in aqueous solution at room temperature. Sodium sulfate will completely dissolve, ionise and distribute across the entire planetary "aquasphere". Some sulfates may eventually be deposited, the majority of sulfates participate in the sulphur cycle in which natural and industrial sodium sulfate are not distinguishable The BCF of sodium sulfate is very low and therefore significant bioconcentration is not expected. Sodium and sulfate ions are essential to all living organisms and their intracellular and extracellular concentrations are actively regulated. However some plants (e.g. corn and Kochia Scoparia), are capable of accumulating sulfate to concentrations that are potentially toxic to ruminants. Algae were shown to be the most sensitive to sodium sulfate; EC50 120h = 1,900 mg/l. For invertebrates (Daphnia magna) the EC50 48h = 4,580 mg/l and fish appeared to be the least sensitive with a LC50 96h = 7,960 mg/l for Pimephales promelas. Activated sludge showed a very low sensitivity to sodium sulfate. There was no effect up to 8 g/l. Sodium sulfate is not very toxic to terrestrial plants. Picea banksiana was the most sensitive species, an effect was seen at 1.4 g/l. Sediment dwelling organisms were not very sensitive either, with an LC50 96h = 660 mg/l for Trycorythus sp. Overall it can be concluded that sodium sulfate has no acute adverse effect on aquatic and sediment dwelling organisms. Toxicity to terrestrial plants is also low. No data were found for long term toxicity. The acute studies all show a toxicity of sodium sulfate higher than 100 mg/l, no bioaccumulation is expected, therefore it can be considered that no further chronic studies are required. Exposure Production: production of sodium sulfate is 4.6 million tonnes/year (1999), of which approximately 50% a byproduct of the chemical industry and the remainder is extracted from natural deposits. Use: The main uses are manufacturing of glass and detergents. Other users are from a wide range of industries, including dyeing technology, electrochemical metal treatment, (animal) feeds, pharmaceuticals, textile, semiconductors, intermediates, agriculture. Release: Releases to water come from natural sources as well as from detergents and nearly all industrial sources listed above. Occupational exposure: Exposure to sodium sulfate-containing dusts or aerosols is possible Consumer products: Exposure to sodium sulfate occurs via drinking water and through naturally occurring or added amounts in foodstuffs. The maximum acceptable concentration for drinking water is 200 500 mg/l sulfate, and is based on taste rather than toxicity.

RECOMMENDATION AND RATIONALE FOR THE RECOMMENDATION AND NATURE OF FURTHER WORK RECOMMENDED
The chemical is of low priority for further work due to its low hazard profile.

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SIDS Initial Assessment Report

1
1.1 IDENTITY Identification of the Substance 7757-82-6 Sodium sulfate Na2SO4

CAS Number: IUPAC Name: Molecular Formula: Structural Formula:

Molecular Weight: Synonyms:

142.04 Sulfuric acid , disodium salt Sodium sulfate anhydrous

Sodium sulfate may also occur in hydrated form, usually the hepta- or decahydrate (Glaubers salt) 1.2 Purity/Impurities/Additives

Purity: above 99.5 %. The nature and amounts of impurities are dependent on the production process used., which are quite numerous and may include recycling of waste sulfuric acid from a multiude of industrial processes. Therefore the impurities cannot be specified.

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OECD SIDS 1.3 Physico-Chemical properties Table 1

Property Physical state Melting point

SODIUM SULFATE

Summary of physico-chemical properties

Value Solid 884 C Ullmann, 1979 and Handbook of chemistry and Physics, 1997/1998 Ullmann, 2004 Ullmann, 1979 Chemiekaarten, 2000 expected to be extremely low Handbook of chemistry and Physics, 1997/1998 Chapmann & Hall, 1992 Chemiekaarten, 2000 The substance is an inorganic salt and it will dissociate in water, therefore it is not of importance. Reference Comment

Boiling point Density

Decomposition occurs above 884C. 2.7 g/cm3 at 20 C 2.7 g/cm3 at 25 C No data 161 g/l at 20 C

Vapour pressure Water solubility

430 g/l at 100 C Partition coefficient noctanol/water (log value) Henrys law constant -3 No data

Sodium sulfate occurs in nature as mineral salts (e.g. thenardite also known as salt cake, and mirabilite also known as Glaubers salt) and is present in almost all fresh and salt waters. Sodium sulfate exists as white crystals or powder, is odourless and has a bitter saline taste. 1.4 Category Justification

A category is not proposed1

Although most of the data presented in this monograph are probably applicable to sulfate ions in general, 4 irrespective of the source, care should be taken in extrapolating to other substances. The physico-chemical properties and the toxicity of other sulphate containing compounds will to a large extent be dependent on the counter-ion (e.g. metals other than sodium or organic compounds) and should be assessed separately. 7 UNEP PUBLICATIONS

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2
2.1

GENERAL INFORMATION ON EXPOSURE Production Volumes and Use Pattern

Estimated world-wide production of sodium sulfate was 4.6 million tons in 1999 (U.S. Geological Survey, 2000). The production in the USA is approximately 20% of the world production and in Western Europe this amounts to 35 %. The total production is for approximately 50% a by-product of the chemical industry and the remainder is being extracted from natural deposits. The main users of sodium sulfate are manufacturers of glass and detergents. Tonnages of sodium sulfate going to detergents (SSPA, 2003) are as follows: World total, 1,058,000 Tons, Europe, 652,000 Tons (ca. 62 % of world). These data are valid only for SSPA members. It is difficult to acquire data on glass production and from producers that are not a member of the CEFIC Sodium Sulfate Production Association. The average concentration of sodium sulfate in detergents (SSPA, 2003) based on a representative sample of 50 commercial detergents, powders and tablets collected in 10 different EU countries (including Eastern) was 20.8 % with a range of 0.0 % to 56.7 %. Other users are from a wide range of industries, including dyeing technology, electrochemical metal treatment, (animal) feeds, pharmaceuticals, textile, semi-conductors, intermediates, agriculture. 2.2. Environmental Exposure and Fate. In anaerobic environments sulfate is biologically reduced to (hydrogen)sulfide by sulfate reducing bacteria, or incorporated into living organisms as source of sulfur. Sodium sulfate is not reactive in aqueous solution at room temperature. In moist air sodium sulfate will take up water (hygroscopic) to form hydrates. Sodium sulfate is also soluble in glycerol, but insoluble in alcohol. Sodium sulfate has no oxidising properties, is not explosive and is non-flammable. 2.2.1. Sources of Environmental Exposure Mineral deposits of sodium sulfate occur naturally around the world. The deposit results from evaporation of inland seas and terminal lakes. Sulfate is a major anion in natural fresh and salt waters and drinking water. The occurrence is mainly due to natural causes, but also to use of sodium sulfate in washing detergents, discharge of industry, mining activities and runoff from fertilized agricultural lands. Sulfate (sulfur) is an essential nutrient for plants and concentrations of at least 0.5 mg/l in irrigation water are required to prevent detrimental effects on growth. 2.2.2. Photodegradation There are no data available because no photodegradation can be reasonably expected, based on the character of the substance. 2.2.3. Stability in Water In water sodium sulfate completely dissociates into sodium and sulfate ions. The ions cannot hydrolyze

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OECD SIDS 2.2.4. Transport between Environmental Compartments

SODIUM SULFATE

There are no data available on transport between environmental compartments. However, it can be estimated that due to low vapour pressure there is no transfer to or via the atmosphere and that given the very low log Kow (-3 (Chemiekaarten, 2000) and -4.38 (EPI-Suite, 2000)), sodium sulfate is not expected to sorb to sewage sludge or sediments. Some sodium sulfate may be expected in soil due to agricultural use and via irrigation water from rivers. 2.2.5. Biodegradation Sodium sulfate may be used as an electron acceptor in anaerobic sulfate reduction by sulfate reducing bacteria. Sulfate is converted to (hydrogen)sulfide (Greben, et al., 2000 and Henry et al., 2000). In the presence of organic substances sodium sulfate is reduced as described in the following reactions: Sugar: C12H22O11 + 5 H2O + 4 SO42- 4 CO2 + 8 H2 + 4 HS- + 8 HCO3- + 4 H+ 8 H2 + 2 SO42- + 2 H+ 2 HS- + 8 H2O C12H22O11 + 8 H2SO4 8 S + 12 H2CO3 + 7 H2O Ethanol: 2 C2H5OH + 3 SO42- 3 HS- + 3 HCO3- + 3 H2O + CO2 C2H5OH + H2SO4 2 S + 2 H2CO3 + 3 H2O The sulfur cycle (College of Biological sciences, 2003): Assimilative sulfate reduction: sulfate (SO42-) is reduced to organic sulfhydryl groups (RSH) by plants, fungi and various prokaryotes. Desulfuration: organic molecules containing sulfur can be desulfurated, producing hydrogen sulfide gas (H2S). Oxidation of hydrogen sulfide produces elemental sulfur (So). This reaction is done by the photosynthetic green and purple sulfur bacteria and some chemolithotrophs. Further oxidation of elemental sulfur by sulfur oxidizers produces sulfate. Dissimilative sulfur reduction: elemental sulfur can be reduced to hydrogen sulfide. Dissimilative sulfate reduction: sulfate reducers generate hydrogen sulfide from sulfate.

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A schematic representation of the sulfur cycle (http://www.lenntech.com/sulfur-cycle.htm):

2.2.6. Bioaccumulation Bioconcentration of sodium sulfate was predicted using the EPI-Suite program (2000). The predicted BCF is 0.5, which is very low and does not suggest any concern with respect to bioaccumulation. Sodium and sulfate ions are essential to all living organisms and their intracellular and extracellular concentrations are actively regulated. Some plants (e.g. corn and Kochia Scoparia), are capable of accumulating sulfate to concentrations that are potentially toxic to ruminants. (Gould, 1991)

2.2.7. Other Information on Environmental Fate The following sulfate concentrations in rivers were found on an internet page of United States Environment Program (2001). In the last 100 years sulfate concentrations have greatly increased in some North American rivers because of increased industrial and agricultural activities. In the Volga river the concentration has increased as well due to human activities, from 50 mg/L (natural background) to 60 mg/L since the 1950's. In the Ob river basin of Siberia no significant changes could be observed. The sulfate ion concentration is highly variable in surface waters where it is linked to sulfur-bearing minerals. Sulfate concentrations range from 2 to 30 mg/l for most rivers and lakes in British Columbia. However, some lakes in the Cariboo region and in Richter pass near Osoyoos have particularly high natural sulfate levels of the thousands of mg/l (Ministry of water, land and air protection, British Columbia, Canada, 2000). Most freshwaters contain at least a few parts per million of sulfate, but 20 to 50 ppm or more are common in the eastern United States and most of Europe. Seawater contains levels of about 2700 ppm (Hitchcock, 1975). Sea salt aerosols are produced in large quantities but do not appear to be a significant source of atmospheric sulfate, except near the place where they are produced due to the fact that they are too
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large to remain in the air. Hitchcock (1975) also states that levels of sulfate in air samples in plumes from fossil fuel power-generating plants decline very rapidly with distance from the source even when atmospheric conditions produce minimal dispersion of the plume. The author measured the following concentrations in the air in North-east America: Non-urban sites: 4.9-8.6 g/m3 Coastal urban sites in New York: 8.1-11.3 g/m3 Other coastal sites: 10.7-12.2 g/m3 Inland New York cities: 6.0-10.3 g/m3

Urbanisation does not appear to influence the sulfate levels in North-east America. Most of the sulfate observed in the non-urban sites appears to be of local origin. Hydrogen sulfide derived from the energy metabolism of bacterial sulfate reducers is the principal source of the 100 to 200 million ton of sulfur annually contributed to the global atmosphere. Since sodium sulfate is soluble in water it is expected to infiltrate the soil. Most of the ions will migrate downwards through the soil with the penetrating water, for it does not interact with soil given the very low log Kow. Sodium sulfate may run off with surface water when the soil is saturated with moisture e.g. after a rainfall (Environment Canada, 1985). 2.3. Human Exposure 2.3.1. Occupational Exposure

Sodium sulfate can exist as dust (by-product) during manufacturing of various chemicals. Occupational exposure to sodium sulfate is likely by dermal contact and inhalation of the dust The occupational exposure limit value (OEL) is determined at 10 mg/m3 (UK) for an 8 hour exposure 2.3.2.Consumer Exposure Exposure to sodium sulfate occurs via drinking water and through naturally occurring amounts in foodstuffs. In drinking water (wells) concentrations up to 2 g/l were measured in the USA. The taste threshold for sodium sulfate is 250 900 mg/l. The maximum acceptable concentration for drinking water is 200 500 mg/l sulfate, and is based on taste (Ministry of Environment, Lands and Parks Province of British Columbia, Canada, 2000). No data on the sulfate content of foodstuffs were found; however, according to WHO, sulfates are used as additives in the food industry and the estimated average daily intake of sulfate in food in the USA is 453 mg/person, based on data on food consumption and reported usage of sulfates as additives (WHO, 2003). An Acceptable Daily Intake for sodium sulfate has not been established. Potential exposure to consumers also occurs from the use of detergents. WHO/FAO did not set an ADI for sodium sulfate, since they consider this to be a substance of no concern. This was re-confirmed in the joint WHO/FAO meeting of June 2001.

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3
3.1 3.1.1

HUMAN HEALTH HAZARDS Effects on Human Health Toxicokinetics, Metabolism and Distribution

Sulfate is a normal constituent of the blood and is a normal metabolite of sulfur-containing amino acids, and excess sulfate is excreted in the urine. Daily sulfate excretion is reported to be 0.20 to 0.25 mmol/kg bw/day and higher in children (Health Canada, 1994). In humans, absorption of small amounts of sulfate from the gut occurs rapidly and almost completely. In a study with 8 volunteers, small amounts (60-80 Ci) of radioactive sulfate-35 (35S) were administered orally or intravenously. Plasma equilibrium was reached within 60 to 105 and 60 to 90 minutes respectively, and in both cases 80% or more of the administered amount of radioactivity was recovered in the urine within 24 hours (Bauer et al, 1976). In contrast, absorption studies with very large amounts of sodium sulfate (18.1 gram as decahydrate = 8 g as Na2SO4) demonstrated incomplete absorption (53% urinary recovery of sulfate in 72 hours), which was associated with severe diarrhea (Cocchetto and Levy , 1981). When the same amount was given in four fractions over several hours, urinary recovery was 62% in 72 hours and no or only mild diarrhea occurred. Similar results were obtained with magnesium sulfate, although absorption seems to be less complete and more erratic, thus leading to more adverse effects (Morris and Levy, 1983). Apparently, the capacity of intestinal transport mechanism for sulfates can be exceeded. In a human volunteer study described 3.1.2 (Heizer 1999) , 40-80% of a single dose of 63 mg/kg of sodium sulfate was resorbed and excreted in urine. Effects of saturation of absorption could not be detected over a dose range of 21-63 mg/kg/day in the range-finding part of this study. After absorption free sulfate ions rapidly distribute over the extracellular space, the apparent volume of distribution being ~ 20% of the body volume. The serum concentration of sulfate in humans ranges between 1.4 and 4.8 mg/100 mL, with a mean of about 3.1 mg/100 mL. Excretion is mainly in urine. The renal clearance is approximately one third of the glomerular filtration rate, indication tubular re-absorption. However, the total free sulfate excretion rate is not dependent on urine flow rate. Organically bound sulfate may follow different excretion patterns. (Cocchetto and Levi, 1981). About 800 mg of elemental sulfur are eliminated daily through the urine of humans, compared with 140 mg in the faeces. (ICRP, 1984) Some 85% of urinary sulfur is present as inorganic sulfates and a further 10% as organic sulfates, whereas the remainder is excreted as conjugated alkyl sulfates (Diem, 1972). Similar data are available from experimental animals: In a study on male wistar rats using 35S labeled Na2SO4, rapid and almost complete absorption occurred. When the radioactively labeled material was added to a large amount of unlabeled sodium sulfate and subsequently orally administered, the plasma peak occurred at the same time, but the amount of radioactivity decreased as the dose of unlabeled sulfate increased. This indicates that there is a saturation of the absorption mechanism (Krijgsheld, 1979). In male adult Wistar rats, approximately 73% of dietary calcium or magnesium sulfate salts was absorbed, although absorption was partly dependent on other dietary elements (Health Canada, 1994). Since disturbances in sulfate metabolism are possibly associated with only one rare form of inherited dwarfism, this area is largely unexplored. Therefore, no attempts have been made to fully describe sulfate metabolism. Sulfate incorporation has been observed with such biologically important compounds as chondroitin, fibrinogen, l-tyrosine derivatives, bilirubin, and steroids. A
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number of amino acids contain sulfur and take part in the sulfate cycle. Hydrolytic (sulfatase) activity has been demonstrated in liver, kidney, pancreas, serum, and urine. Sulfates play an important role in sulfoconjugation processes, which are of great importance in a variety of detoxification/excretion processes (Percy, 1964). In ruminants, excess amounts of sodium sulfate in feed may result in considerable toxicity due to formation of sulfides through bacterial action in the rumen (see section 3.1.5.) Conclusion: relatively large amounts of sodium sulpfate are normally taken up by the gut from food and drinking water through a saturatable mechanism. Absorbed sodium and sulfate ions circulate freely throughout the entire body and form part of a large intra- and extracellular sodiun and sulfate pool respectively. Sulfates are normally incorporated in a great variety of body compounds and as such essential to life. 3.1.2 Acute Toxicity

The acute toxicity studies conducted with sodium sulfate that could be checked are summarised in the following tables. Studies in Animals Oral Table 2
Ref. (year) Okahara, (1963) Henkel, unpublished

Acute oral toxicity studies with sodium sulfate

Species, strain Mouse rat Protocol non-standard unknown Administration oral (?) Oral Endpoint LD50 LD50 Value (mg/kg) 5989 mg/kg bw > 10.000 mg/kg bw

Only one LD50 value appears to have been reported in the open literature (in Japanese) (Okahara, 1963). A summary report from Henkel (Henkel, unpublished) stated oral administration of 2-5 ml of a solution in water (concentration not given) to 10 rats (mean body weight 270 gram), with an observation period of 8 days. No symptoms were observed and the LD50 was given as > 10 g/kg. Other data quoted in previous editions of IUCLID could not be found. Dermal No valid data are available on the acute dermal toxicity for sodium sulfate. Given the complete dissociation in solution, penetration through the intact skin is not to be expected. Inhalation Table 3 Acute inhalation toxicity studies with animals exposed to sodium sulfate
Ref. (year) Last et al. (1980) Species (strain) Rat (Sprague Dawley) Protocol non-standard protocol Source of mists particle aerosol Exposure Time 72 h Particle size (MMAD, m) 1.15 Endpoint LOEC > 10 mg/m3

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No standard inhalation studies with Na2SO4 are available. There is one study (Last et al, 1980) in which rats were exposed to 10 mg/m3 of Na2SO4 as a dry particle aerosol in air with 50% humidity (particle size 1.15 m Mean Mass Aerodynamic Diameter;, g = 2.5) for 72 hours. These six male rats served as negative controls for rats exposed to various concentrations of sodium sulfite and sodium hydroxymethane sulfonate. Clinical effects were not reported. Compared to the filtered-air control group, no significant changes in various inflammation-related lung tissue parameters, determined post-mortem, were found (DNA, RNA, protein, wet-to-dry weight ratio, glycoprotein secretion in trachea explants). In a study discussed in more detail in section 3.1.4, effects on serum liver cholinesterase concentration, blood coagulation time, brain irritability and spermatogenesis were claimed after 8 hours exposure to 60 mg/ m3 Na2SO4 as well as after longer exposures to lower concentrations but these results were considered implausible (Denisov, 1989) Studies in Humans Oral There is one fully controlled study on the effects of sodium sulfate in humans (Heizer 1997). In a range-finding study, four healthy volunteers received controlled amounts of drinking water with stepwise increasing concentrations of sulfate, up to 1200 mg/l of sulfate, over six consecutive twoday periods. The calculated dose of sodium sulfate was 0, 21, 31.5, 42, 52,5 and 63 mg/kg/day. Apart from a faster stool passage, no abnormalities were found. In a subsequent two-day studys en volunteers received of 0 mg on the first and 63 mg sodium sulfate on the second day. A clinically insignificant increase in stool volume, decrease in stool consistency and passage time was noted, but no change in stool frequency or diarrhea. In another study (US-EPA 1999, Backer L, abstract only) volunteers received bottled water containing 0 to 1200 mg/ l of sulfate for three days and plain water on twos days before and one day after the sulfate exposure. Atually received dose was calculated from returned bottles. There was no effect on bowel movements at any concentration and sulfate dose, although not reported, was stated not be a predictor for diarrhea. . In another abstract of a case-control study (US-EPA,1999, no relationship between sulfate levels and diarrhea was found in infants receiving tap water with sulfate concentrations below 500 mg/l. Sulfate concentrations above 600 mg/l (equivalent to more than 875 mg/l of sodium sulfate) in well water, used to prepare infant formula was described as a cause of diarrhea without any other sign or symptom of disease in three infants (Chien 1967). The estimated daily dose would have been around 70- 100 mg/kg/day. Although the clinical cause and effect relationship is absolutely clear in these three cases, the number of cases versus the population at risk (i.e. infants with similar oral exposure) is unknown and a dose-effect relationship or threshold concentration cannot be established from three cases. Nevertheless, the author's recommendation not to use water with more than 400 mg of sulfates is in line with WHO standards. In clinical practice sodium sulfate, alone or with magnesium sulfate, was used as a laxative to induce rapid emptying of the gut, in doses of 300 mg/kg up to 20 grams maximum for an adult. The laxative action is ascribed to fecal fluid retention caused by the hygroscopic action of unresorbed sodium sulfate in the large intestine (Gilman et al, 1980). Use of sodium sulfate has been gradually abandoned and the substance has been replaced by other laxatives because of the uncontrollable watery diarrhea and accompanying abdominal cramping it tends to produce.

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OECD SIDS Other Routes of Exposure

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An isotonic (3.89%) solution of sodium sulfate decahydrate, administered intravenously, was used as an antihypercalcemic (Remington, 1980). This practice is considered obsolete. Conclusion Only limited data on the acute toxicity of sodium sulfate are available. However, in view of the large body pool of sulfate anions and the high body turnover, the acute toxicity of sulfates must be low, as long as the counter-ion is not toxic. . The laxative effect of oral ingestion is well known and was used medicinally. High dosages given in medical practice with the purpose of inducing diarrhoea were usually accompanied by severe abdominal cramps. Apart from that, no side effects are mentioned in the medical literature." 3.1.3. Irritation Skin Irritation Studies in Animals Table 4
Ref. (year) Bayer AG (1991)

Skin irritation testing with sodium sulfate

Species, Test Type Rabbit, Skin irritation test on intact skin Protocol OECD 404, Acute Dermal Irritation/ Corrosion Doses 500 mg, Occlusive Result Not irritating

Sodium sulfate appears not to be irritating to the skin in rabbit. The study was performed under GLP, and according to international well-accepted guidelines. Endpoint determination was based on the DRAIZE scoring system. The exposure period was 4 hours, under occlusion, and the result was scored after 14 days (Bayer, 1991 unpublished). Studies in humans No reports on acute studies in humans are available. Skin problems were not found in a group of 119 workers with long-term exposure to sodium sulfate (see 3.1.4; Kelada & Euinton, 1978) A human repeated insult skin sensitisation test (see 3.1.4.) was performed with a bath salt allegedly containing 80.8% sodium sulfate on 61 human volunteers, mainly females of all ages. It this test, te test substance was applied under semi-occlusion in a concentration of 1.25%, 8 times for 24 hours and once for 48 hours and induced mild irritation only once in one volunteer.However, the validity of this report could not be assessed (CTFA 1976) Another , unavailable CTFA report (1985) is quoted elsewhere as stating that a 10% solution of sodium sulfate under occlusion for 24 hours produced mild irritation in one out of 19 volunteers. Eye Irritation Studies in Animals Table 5
Ref. (year) Bayer AG, (1991)

Eye irritation testing with sodium sulfate

Species, Test type Rabbit, Eye Irritation test Protocol OECD Guideline 405, Eye Irritation Doses 90 mg, pulverized Result Slightly irritating

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Sodium sulfate appears to be slightly irritating to the eye in rabbit. The study was performed under GLP, and according to international well-accepted guidelines. Endpoint determination was based on the DRAIZE scoring system. Sodium sulfate had no adverse effect on the iris and cornea. The substance was instilled into the conjunctival sac of the eye. The positive effects were primarily based on the conjuctivea (redness) observed in the test. The effects were reversible within 7 days. (Bayer, 1991 unpublished). Conclusion : Sodium sulfate was not a skin irritant in a well conducted study. It is a slight eye irritant with redness of the conjunctiva observed. The redness was reversible within 7 days. Respiratory Tract Irritation Studies in Animals In the acute inhalation toxicity test with 72 hours of exposure described in 3.1.2 (Last et al, 1980), no signs of irritation of the respiratory tract were described. In an experiment set up to determine the difference in inhalatory effects of various sulfur oxide species which occur in ambient air, 5 male rabbits were exposed for one hour to aerosols containing an actual mass concentration of 1800-1950 g/m3 sodium sulfate particles. Mean mass aerodynamic diameter of the aerosol particles was 0.4 m (g =1.6). Animals served as their own controls through sham exposures. Mucociliary clearance served as an indication of pulmonary irritation. This was determined by means of retention measurements of previously inhaled radioactively labeled microspheres. No effects on mucociliary clearance were found. Since similar exposures with acid sulfates (H2SO4, NH4HSO4) resulted in significant increase in retention time, i.e. lowering of the clearance, whereas (NH4)2SO4 also had no effect, the conclusion is that any irritative effects are not caused by the sulfate ion but by the hydrogen sulfate ion (Schlessinger, 1984) Studies in humans An abstract only is available of a study describing the effects of 10 minute inhalation of sodium sulfate aerosols with a mass median aerodynamic diameter of 0.5 m in concentrations of 2 and 3 3 mg/m3 on asthmatic and normal adults., with sodium chloride aerosols of the same size as controls. Two out of 5 asthmatics showed an immediate but not dose-dependent drop in FEV1,but group mean values of respiratory resistance, FEV1 and VC were comparable up to 60 minutes postexposure. In a second series, 6 asthmatics and 6 normal adults were followed for 3 hours after 10minute inhalation of 3 mg/m3 and no differences were found in the same volume/flow parameters nor in various diffusion capacity parameters (Sackner et al, 1979) Symptoms indicating local upper respiratory tract irritation were observed in the study by Kelada and Euinton (1978). Workers from natural sodium sulfate mines developed symptoms such as nasal irritation and runny noses (see section 3.1.5). Conclusion: It is unlikely that short-term inhalation of respirable sodium sulfate particles cause pulmonary irritation. 3.1.4. Sensitisation Skin and inhalation Studies in Animals No valid study was identified for skin sensitisation potential with sodium sulfate.

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SODIUM SULFATE

An incomplete report is available on a repeated insult patch test in human volunteers with 10 different cosmetic products, among them bath salt crystals allegedly containing 80.8% sodium sulfate, tested in a concentration of 1.25% under semi-occlusion on 61 human volunteers, mainly females of all ages. The conclusion of the report is that the substance did not demonstrate any potential for inducing allergic sensitization. The validity of this report could not be assessed. (CTFA, 1976) Sodium sulphate is unlikely to cause allergy, since the body contains large amounts of sulfate (~0.33 mmol/L in serum and about 50 times higher concentration intracellularly) as well as large amounts of sodium ions. Various metal sulfates (e.g. nickel sulfate, cobalt sulfate) are used as standard allergens in routine skin allergy testing, but positive reactions are related to the metal ion, not to the sulfate, as can be deduced from the definitely non-allergenic zinc sulfate (ECETOC, 1999). Based on the above, it may be concluded that sodium sulfate is not an allergen in humans, and that animal testing for sensitisation potential would not provide any information relevant for hazard identification and risk assessment. Conclusion Despite the absence of formal study results, it can be concluded, based on the natural intra- and extracellular occurrence of the substance, that sensitisation to sodium sulfate is highly unlikely 3.1.5. Repeated Dose Toxicity Studies in Animals Oral Validated (reliability 1 or 2) repeated dose toxicity studies with sodium sulfate are summarised in the Table 6. Two reliable non-standard repeated dose toxicity studies were reported. A nonstandard. Non-GLP study feeding study in rats was reported and given reliability 2. An invalid carcinogenicity study is reported here since it has (very) limited reliability as a repeated dose study Two veterinary clinical studies are also described which provide valuable clinical observations and could also be given a reliability 2 despite deficiencies with respect to control groups. The reported clinical effects are so severe that they may safely be assumed absent from any control group. Two more studies assigned validity 3 are mentioned in the text but not included in table 6.

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OECD SIDS Table: 6: Repeated dose toxicity studies with sodium sulfate
Ref. (year) Species (strain, sex) Duration, frequency Administration In food Doses 0.84 % in diet, 320400 mg/kg/day 0.0; ~0.01%ww; Incremental 0.125,0.250, 0.5, 1% 2% (estimated 2000 mg /kg/d) End-point Mortality, tumours , body weight, food and water consumption Value (unit)/ results NOAEL ~320-400 mg/kg/day

SODIUM SULFATE

Blunck & Crowther Rat, Sprague- 27 and 44 (1975) Dawley, weeks, daily 5 / Male Moinuddinand Wing-Tsit Lee Rat, 24, male 4 weeks, Spraguedaily Dawley

In food

NOAEL 2000 mg/kg/d Food & water consumption, body weight gain, food conversion efficiency, urine production, diarrhoea, blood hemoglobin & white blood count, serum alkaline phosphatase, inorganic phosphate, gross organ pathology LC100; Body weight, Histopathology, Food and water consumption, Egg production 23328 mg /l at 4,000 mg/l depressed feed consumption and egg production. Increase in water consumption was observed at 4,000 mg/l.

Adams et al. (1975)

Hen (48 White Leghorn

4 weeks, daily

Drinking water

Concentrations : 25023328 mg/l Calculated doses per group of 6 hens: 34 mg/kg/d; 45 mg/kg/d 120 mg/kg/d 210 mg/kg/d 550 mg/kg/d 1670 mg/kg/d 4900 mg/kg/d 1650 mg/kg/d

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OECD SIDS Table: 6: Repeated dose toxicity studies with sodium sulfate (continued)
Ref. (year) Veen-huizen et al. (1992) Species (strain, sex) Pig (415, weaned) Duration, frequency 28 days, daily Administration Drinking water Doses End-point Value (unit)/ results

SODIUM SULFATE

Body weight, food-water 54-1800 mg/l (water consumption/animal & consumption, gastrointestinal infections body weights not given)

Increased prevalence of diarrhea was a trend as sulfate concentration increased. A non-significant trend in increased water intake was observed with increasing sulfate. No differences in feed intake were observed between various sulfate concentrations. Body weight increased at 600 mg/l and higher. Five out of nine animals developed symptoms and signs of polioencephalomalacia (PEM), onset correlating well with formation of sulfide in rumen All low-dose animals microscopic signs of PEM, all others macroscopic signs of PEM. Onset of symptoms correlated well with formation of sulfide in rumen.

Gould (1991)

Cattle (9 21 days, young steers) daily

In food

0.8 % Na-sulfate (0.36% sulfur)

Neurological symptoms, histopathological brain damage, Sulfide formation in rumen Neurological symptoms, histopathological brain damage, Sulfide formation in rumen

Niles et al (2002)

Cattle (15 heifers)

35 days

In food

3860 ppm, 5540 ppm and 7010 ppm of sulfur

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In the study by Blunck and Crowther (1975), also described under Carcinogenicity, two groups of 5 male rats were fed 2% sodium sulfate in the diet for 27 and 44 weeks respectively. No adverse effects were detected with respect to the limited number of endpoints reported from this study. Obviously, group size is too limited to draw firm conclusions bit a tentative NOAEL of >= 320 mg.kg may be deduced. . In a non-standard non-GLP 4 week repeated dose study comparing the effects of Mg SO4, Mn SO4 and Na2 SO4, rats were fed an artificial diet enhanced with minimal amounts of MgS04 and MnSO4 but not Na2SO4; the pure sulfates were added on a mmole/kg food basis. At the top dose, the food contained around 2% of the respective sulfates (calculated to be around 2000 mg/kg/d). While the Mn SO4 and Mg SO4-exposed rats showed various functional and even gross pathological aberrations at the top dose, the Na2SO4 -exposed rats were comparable to to the controls in every aspect (see table) except slight diarrhoea in one animal for a few days (Moinuddin & Wing-tstit Lee, 1960). Thus the NOAEL from this study is 2000 mg/kg/day In the studies of Adams et al (1975) and Veenhuizen et al (1992) the test animals were exposed to sodium sulfate in the drinking water which was available on a daily basis. The primary end-points were food and water intake, body weight (occurrence of diarrhoea) and clinical signs of dehydration. In the study (Adams et al., 1975) with 48 hens, small and not clearly dose-related effects on food consumption and egg production were observed at concentrations up to and including 4,000 mg/l of sodium sulfate, compared to two weeks of pre-test observations (calculated dose ~ 550 mg/kg/d of sodium sulfate). Water consumption was strongly increased at concentrations of 4000, 5832 mg/l and 16000 mg/l and dramatically decreased at the top level of 23328 mg/l. At 5832 mg/l a serious decline in egg production and decrease of food consumption was observed. At this concentration, the calculated dose was about 1670 mg/kg/d due to increased water consumption. No mortality was observed at 16.000 mg/l ( 4900 mg/kg/d) but 100 % mortality was observed at 23328 mg/l (only 1644 mg/kg/d due to strongly reduced water consumption) . Necropsy of hens receiving 23340 mg/l sodium sulfate and above showed extreme emaciation and visceral urate deposits. Microscopic examination of kidney tissues showed urate accumulation of individual glomeruli and tubules losing cellular detail in animals receiving 5832 mg/l or more Examinations of other organs were not reported. The above data seem to indicate that the mortality in the top dose was due more to dehydration because of inpalatable drinking water than to the dose of sodium sulfate. In the study with 415 weaned pigs (Veenhuizen 1992) diarrhoea was observed with increasing test concentrations. No significant effects were observed in feed and water intake at the tested concentrations. Body weight gain was observed at 600 mg/l or higher. Weight gain to feed ratios for all treatments were not different. Isolates of E-coli were found in 14% of the pigs, from 1 pig rotavirus was isolated. No pigs were exposed to transmissible gastroenteritis virus. None of the treatments had an adverse effect on nursery pig performance. During the study one pig died at a concentration of 600 mg/l. Daily doses could not be calculated in the absence of body weigh and water consumption data; percentages only were given. Another oral study (Upton, 1976) with rats (exposure 6 weeks) indicated that daily dietary supplementation (1-2%) with sodium sulfate did not significantly affect food/water intake and liveweight gain of rats. In an oral chicken study (Sibblad, 1976) effects on weight gain were reported with increasing sodium sulfate in the drinking water (1-5%). The exposure period was 11 days, and no mortality was observed. In a study with 9 young Holstein steers, a concentrate diet containing 0.8 % sodium sulfate (total sulfur content approximately 0.36%) was given during 21 days. 3 controls were given the same diet without added sodium sulfate (total sulfur or sulfate content not reported). Five out of nine test animals vs. no controls developed clinically manifest poli-encephalomalacia (PEM) as well as
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OECD SIDS

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macroscopically visible and histologically recognisable cerebral lesions (brain histology of notaffected animals not reported). The onset of the disease correlated well with increasing concentrations of sulfide in the rumen. Thiamine concentrations in serum (another alleged cause of PEM) were not significantly affected. (Gould et al., 1991)Similar disease due to high sulfur content of food was allegedly also reported earlier in sheep In another study three groups of young heifers (5 heifers per group) were fed diets with 3860 ppm, 5540 ppm and 7010 ppm of sulfur respectively during 5 weeks. Sulfur concentrations were reached by adding sodium sulfate to the desired level. Microscopic signs of PEM were seen in all four lowdose animals, macroscopic signs in 4/5 medium-dose and 4/5 high-dose animals. Clinical signs of PEM were seen in all animals. Onset of PEM correlated highly with sulfide concentrations in rumen. Other potential causes of PEM were excluded. (Niles et al, 2002). Dermal No data have been found with respect to repeated dermal toxicity Combined Inhalation/ oral exposure An inhalation study on rats was found describing inhalation exposures of 8, 12, 44, 90 and 720 hours duration to Na2 SO4 concentrations of 60.45, 40.05, 18.03, 11.06 and 3 mg/m3 respectively, with concurrent exposure to sodium sulfate in drinking water at a concentration of 500 mg/l. (estimated dose at the lowest level / longest duration 60 mg/kg/day orally and 1.8 mg/kg/d by inhalation). Small but statistically significant effects were claimed at all concentrations on serum liver cholinesterase concentration (first appearing at 6, 12, 44, 90 and 720 hours respectively), prolongation of blood coagulation time (first appearing at 4, 8, 30, 64 and 510 hours respectively) and brain irritability as measured by "summated threshold potential", (first appearing at 4, 8, 24, 45 and 288 hours respectively), and these effects were stated to be worse at end-of exposure (no data provided). (Denisov et al, 1989). Depression of spermatogenesis (presumably at end-of-exposure), was also at all concentrations and all effects were stated to be completely reversible within one month post-exposure (size of recovery groups not given). No abnormalities were observed in number of erythrocytes and leucocytes, total haemoglobin, meth- and sulfhaemoglobin, blood histamine, presence of Heinz-Ehrlich bodies brain cholinesterase, number of sulfhydryl groups, basic phosphatase activity in blood serum and content of ascorbic acid in the adrenals. However, the documentation of this study is insufficient, some of the results are clearly artificially constructed and incredible and the effects are biologically implausible (see below) Similar effects were described in a follow-up 90-day study (Denisov and, Tkachev, 1990) in which rats were exposed to 1 mg/m3 sodium sulfate, or 0.1 and 1 mg/m3 of sodium sulfite or 1 mg/m3 of an unspecified mixture of both, together with 500 mg/l in drinking water, i.e an estimated dose of 60 mg/kg/d orally and 0.6 mg/kg/day by inhalation. Apart from the neuro-physiological and biochemical parameters described above, body weight was also depressed, relative liver weight was decreased, histopathological evidence of serious lung damage and testicular damage was described. Effects were similar for sulfites, sulfates and the mixture, but more severe and earlier for the sulfites. Again, the description of the experiment is insufficient and no actual data are presented. The biological plausibility of such relatively severe effects at such low concentrations, from a compound normally abundantly present in drinking water and food is very much in doubt. There is no reason why a simple, non-reactive and freely circulating ion like sulfate would exert systemic effects when absorbed through the lungs at a fraction of the amount absorbed from the gastrointestinal tract. These findings also strongly contrast with all other available data. A possible explanation of the findings from these two studies, if accepted at face value, is contamination of the dust used for the inhalation studies with heavy metals, e.g. cadmium. Spent
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sulfuric acid commonly contains heavy metals, so pre-refinery sodium sulfate made from such recycled material may well be contaminated.. In the absence of any analytical data, this cannot be verified. Studies in Humans Oral/dermal No information found. Inhalation The effects of long-term inhalation of sodium sulfate dust were determined in a cross-sectional study among 119 male workers from natural sodium sulfate mines (Kelada and Euinton, 1978). Age of the subjects ranged from 17 to 58, exposure duration from two months to 31 years (no control group, study outcomes compared with "normal values", source not given). Dust exposures ranged from less than 5 mg/m3 to 150 mg/m3 during specific tasks (sampling method, strategy, number, frequency and timespan of sampling not given). General medical screening, lung function tests, blood pressure, skin condition, gastro-intestinal functioning, serum sodium, calcium, potassium chloride and sulfate content were all within normal ranges (i.e. presumably as found in the general population). Mean urinary excretion of inorganic sulfate exceeded 2.2 g/liter in all workers and thirty percent of the workers excreted more than 3 g of inorganic sulfate per day, indicating massive uptake from recent exposure. The only subjective symptom indicated by the workers was nasal irritation and runny noses on exposure to dust. An internal comparison between workers from this group with less than 10 years of exposure (n=77, mean age 28.0 +-10, mean exposure duration 3.1 + 2.8 years) with those with more than 10 years exposure (n=42, mean age 45.5 + 8.8, mean exposure duration 19.9 + 3.6 years) did not show any differences that could not be explained by normal ageing processes There are differences between the group with longer and the group with shorter exposure, but these differences appear to be normal for the respective ages and are therefore attributed to the substantial age difference between groups rather than to exposure to sodium sulfate.No abnormalities were detected that could be explained by exposure to sodium sulfate. (The possibility of a "healthy worker effect" was not addressed in this study). The study by Denisov and Tkachev (1990) also mentions exposure concentrations in working atmosphere. Shift averages of 88 mg/m3 are given, yet there is no mention of any clinical or biochemical effects on the workers. Conclusion: A clear NOAEL cannot be derived from the available data. Tentatively a chronic NOAEL of >= 320 mg/kg/day may be deduced from a 27 / 44 week study and a sub-chronic NOAEL of 2000 mg/kg from a 28 day study in rats. Ruminating animals are at risk at much lower levels because of the potential formation of sulfide in the rumen. Since this substance has no discernable systemic toxicity, the tentative chronic NOAEL of >= 320 mg/kg in rats would seem to provide a reasonable margin of safety compared to the estimated daily intake of 453 mg/person/day or around 6.5 to 7.5 mg/kg/day (see 2.3.2)

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OECD SIDS 3.1.6. Mutagenicity In vitro studies Table 7

Ref. (year) Bayer AG, (1988)

SODIUM SULFATE

Genetic toxicity in vitro with sodium sulfate

Species, Test type S. Typhimurium, Ames test Protocol Salmonella/ Microsome test Doses Result

312-5000 g with and without Negative activation

Sodium sulfate has been shown to be without effect in the Ames test using various strains of S. typhimurium (TA1535, TA1537, TA100, TA98) both with and without S9 activation in a GLP standardised test. In a paper describing cytogenicity studies with sodium bisulfite in human cultured lymphocytes, Meng and Zhang (1992) state that sodium sulfate did not increase the frequencies of chromosomal aberrations, sister chromatid exchanges or micronuclei , nor did it cause changes in mitotic index or cell cycle at concentrations ranging from 5 x 10-5 to 5 x 10-3 M. However, no data are shown and it is not clear from the study description how, when and why these determinations were made. Therefore this study is assigned reliability 4. Based on the natural intra- and extracellular occurrence of the substance it can be concluded that sodium sulfate is highly unlikely to be mutagenic 3.1.7. Carcinogenicity Valid standard carcinogenicity studies with sodium sulfate are not available. The carcinogenicity studies listed in Table 8 and described below are those involving the longest exposure to sodium sulfate. Their power to detect any carcinogenic potential that sodium sulfate might possess is extremely low Table 8
Ref. (year) Blunck & Crowther (1975) Toth (1987)

Carcinogenicity studies with sodium sulfate

Duration, Frequency 27 and 44 weeks, daily Animal/group 5 / Male Dose 0.84 % in diet, 320-400 mg/kg/day 31 g in 0.01 ml sodium chloride (0.9%) per g body weight, s.c. injected Result No mortality, no tumors

Test Type, Species, Strain Carcinogenicity, Rat, SpragueDawley

Carcinogenicity, 26 weeks, Swiss albino mice weekly

50 male, 50 female

Tumor of subcutis and/or skin in 1% of the female and 4% in male.(normal for this strain in this lab)

In the study of Blunck and Crowther animals were fed an additional 0.84% sodium sulfate in the diet. Because of protocolled food restrictions, the actual additional dose could be calculated and was around 320-400 mg/kg /day. These animals served as controls for animals in which the enhancing effect was studied of the same amount of sodium sulfate on the carcinogenicity of various azo dyes. No carcinogenic effects (tumors) were observed in these control animals. No significant differences in overall body weight gain were observed during the study. Liver weight was not changed. No
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evidence of hyperplastic and/or dysplastic change, and no cholangiofibrosis or mild cirrhosis was observed as compared to controls. In addition, no changes in the water or food intake was reported. In the experimental animals fed additional sodium sulfate together with carcinogenic azo dyes, the latency period of tumor development appeared to be reduced, supporting the hypothesis that sulfotransferase plays an important role in the activation of azo dyes. In a study with mice (Toth, 1987), animals S.C. injected with 31 g in 0.01 ml of saline per gram body weight (31 mg/kg bw) during 26 weeks served as controls for animals injected with a carcinogenic substance, 4-HMBD. The tumor incidences of the subcutis and skin and of tumors in other organs in the sodium sulfate injected animals were in the normal range observed in the historical untreated control Swiss mice in the same test laboratory. Conclusion The limited available data do not allow firm conclusions with respect to carcinogenicity of sodium sulfate. However, they do not contradict the notion that a substance that is abundantly present in and essential to the body, is unlikely to be carcinogenic. 3.1.8. Toxicity for Reproduction Studies in Animals Effects on Fertility One study was found with reliability 4 (Non-standard protocol, non-GLP, insufficient data for assessment, in which 10 female mice per group were exposed to sulfate in the drinking water onwards from one week prior to mating with untreated males. Sodium sulfate concentrations in drinking water were 0 mg/l (distilled water control), 0 mg/l (Na control), .924 mg/l, 1848 mg/l, 3696 mg/l and 7.392 mg/l with sodium concentrations in the Na control and all sodium sulfate groups made identical by addition of NaHCO3 as required.water concentrations correspond to calculated doses of around 140, 280, 560 and 1120 mg/kg/d. Dams with litters from each group were re-bred immediately after weaning. No effects on maternal weight gain, lactational performance, litter size, pup survival and weaning weight at maximum treatment levels over 2 parities were found. However, since it is stated in the paper that only animals with two subsequent litters were involved in the analysis, i.e. ultimately 4 animals/group, and full data on reproductive succes are not given, the effects on fertility cannot be properly assessed. (Andres & Cline, 1989). The available data on fertility are quite limited but in view of the fact that the substance is abundantly occurring in the body, toxicity for reproduction is unlikely.

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OECD SIDS Developmental Toxicity Table 9

Ref. (year) Arcuri & Gautieri (1973)

SODIUM SULFATE

Developmental toxicity/teratogenicity studies with sodium sulfate

Protocol Administration Other SC, single injection Exposure time, Doses frequency Day 8 or 9 of 60 gestation, single mg/kg dose bw Results Increased maternal weight gain, normal litters/ litter size, statistically significant increase in delayed ossifications no other abnormalities, no maternal mortality, normal litters/litter size, 100% survival, no visible abnormalities (no necropsy) Increased litter weight on day 1 pn, normal on day 3

Species, Strain Mouse, CF-1

Seidenberg et al Mouse, (1986) ICR/SIM

other

gavage

day 8-12

2800 mg/kg bw

Two studies of limited validity were found in the literature. In the study of Arcuri and Gautieri, (1973), which was aimed at documenting teratogenic effects of morhine sulfate, atropine sulfate and physostigmine sulfate, sodium sulfate served as anion control, with sodium chloride as negative control. The study was well documented, with various endpoints (clinical observations, maternal weight ratio, uterine lef/righ horn fetal ratio and resorption ration, fetal weight, sex ratio, skeletal abnormalities, ,soft tissue abnormalities, more specifically exencephaly, cryptorchid test and axial skeletal fusions, but covered only the 8-9 day period of gestation for exposure and the dose of 60 mg/kg was relatively small. There was a statistically significant increase in skeletal abnormalities, described as delayed ossification in the phalanges, sternebrae and skull. Such variations are quite common in tests with rodents and, in the absence of skeletal malformations, generally not regarded as indicative of developmental toxicity. No abnormalities for any of the other end-points were reported. In another study (Seidenberg et al., 1986) the developmental effects of sodium sulfate in the mouse were examined as part of a validation effort of a developmental screening test. The test substance was administered (2800 mg/kg/day) by gavage on gestation days 8 through 12. No mortality, an unchanged average weight gain, and normal number of litters and neonates/litter were found. A 100 % perinatal survival was found, with an increased postnatal weight at day 1, normal weight at day 3 in the absence of externally visible abnormalities. In a later paper (Seidenberg et al, 1987) that summarised the results of this validation test, the outcome of the screening test was considered positive for sodium sulfate, based solely on the increased postnatal weight on day 1 post-partum. However, the significance of such an effect, in the absence of any other effect, is unclear and the reasons for taking this as a positive result are not given In a summary report (Paterson et al., 1979) the effects of various concentrations of sulfate in drinking water were described on the pregnancy and lactation of sows and gilts (primiparous sows), 58 in total, divided in three groups. Sodium sulfate in drinking water was given in concentrations of 320, 1820 and 3320 mg/l respectively from 30 days post-breeding through 28 days of lactation (body weights and water consumption not given). No effects were found on gestation and lactation in terms of weight gain during gestation, number or weight of piglets at birth or development during lactation. 41 of the newborn piglets, equally representing all treatment groups, were taken from the litters. These newborns were split in three groups and were raised for 28 days on a 18% protein diet plus drinking water containing either 3000 mg/l added sulfate from sodium sulfate, 3000 mg/l

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sulfate from magnesium/sodium sulfate or no sulfate added; no differences in development were found between the groups. The study is of not assignable validity. Studies in Humans No data. Conclusion The limited available data give no indication that sodium sulfate is toxic for reproduction. With regard to the natural occurrence of the substance in the body, developmental toxicity is very unlikely. 3.2 Initial Assessment for Human Health

Sodium sulfate is not known to have acute oral effects other than laxative effects, caused by its hygroscopy. It is not irritating to the skin and is a slight eye irritant. The substance is unlikely to be sensitiser. Oral repeated dose toxicity is limited to diarrhoea and subsequent dehydration at dosages far higher than the normal daily intake from food and water. Ruminant animals may develop serious brain disorders from high sulfate content in food and water due to formation of sulfides in the rumen but this is not relevant to humans. Limited inhalation data from humans do not indicate serious concerns with respect to acute or chronic dust inhalation. There is limited data on reproduction which give not indication that sodium sulfate is toxic for reproduction. There is no valid data on carcinogenicity. However, given the natural occurrence in the body of this substance which is essential to life, carcinogenicity and toxicity for reproduction is not an issue.

4
4.1

HAZARDS TO THE ENVIRONMENT Aquatic Effects

Acute toxicity Effects in fish Three studies were reliable with restrictions as the studies were not performed according to standardised guidelines, but were performed using an adequate scientific methodology and described with enough details (see table 10). No studies were performed under GLP. All three tests were performed in reconstituted water. In two tests a concentration range of the test substance and determination of test parameters are described. The study with Pimephales promelas was performed according to EPA guideline with determination of test substance concentrations (ionchromatography). During two studies (with Lepomis macrochirus, Trama (1954) and Pimephales promelas, Mount et al. (1997)) the critical confounding factors pH and oxygen were within acceptable ranges, while in the third study (with Lepomis macrochirus, Patrick et al. (1968)) these parameters were not indicated. The acute toxicity for fish is very low, with LC50 values far above 1,000 mg/l for both species, Lepomis macrochirus and Pimephales promelas.

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OECD SIDS Table 10

Acute/ prolonged toxicity to fish

SODIUM SULFATE Validated data (validity 1 or 2) on acute toxicity to fish.

Ref. (year) Trama (1954) Species Lepomis macrochirus Lepomis macrochirus Pimephales promelas Method/ Protocol Concentration range in reconstituted water 96 hours test, based on Cairns et al. (1964) 96 hours test, based on EPA/600/4-90/ 027 (1991) guideline. Results LC50 96h = 13,500 mg/l; LC0 = 8,700 mg/l. LC50 96h = 13,500 mg/l

Patrick et al. (1968) Mount et al. (1997)

LC50 96h = 7,960 mg/l

Effects in aquatic invertebrates Only one reference describing a Daphnia magna test in 48 hours (Mount et al., 1997) was assigned validity 2. This test was not performed under GLP, but was performed according to EPA guideline, with determination of test substance (ion-chromatography), and details on test performance and statistics. As indicated the toxicity of sodium sulfate for Daphnia is very low, with an EC50 value far above 1000 mg/l. Table 11
Acute toxicity to aquatic invertebrates

Validated data (validity 2) on acute toxicity to aquatic invertebrates.

Ref. (year) Mount et al. (1997) Species Daphnia magna Method/Protocol 48 hours test, based on EPA/600/4-90/ 027 (1991) guideline. Results EC50 48h = 4,580 mg/l; EC50 24 h = 6,290 mg/l.

Effects in aquatic plants / algae The only valid study was a 120-hour growth test with Nitzschia linearis (Patrick et al., 1968). It was classified as valid with restrictions, as a different species was used and a greater test duration than recommended in the OECD-guidelines. An EC50 value of 1,900 mg/l was calculated. Table 12
Acute toxicity to aquatic plants

Validated data (validity 2) on acute toxicity to aquatic plants.

Ref. (year) Patrick et al. (1968) Species Nitzschia linearis Method/Protocol 120 hours test, based on Cairns et al. (1964) Results EC50 120h = 1,900 mg/l

Effects in sediment dwelling organisms There are four studies found with sediment dwelling organisms (Lymnea and Polychaeta) of which the publications are not available. There was one study found that was considered valid with restrictions. It was an acute semi static test with Trycorythus sp. performed in river water (Goetsch and Palmer, 1997). The method used was not a standard method but it was described in detail and considered appropriate. The EC50 values for Lymnea sp. and Lymnea sp. eggs are 799 and 3,553 mg/l respectively. The toxicity for the marine worm Ophryotrocha labronica was determined at 5.4 mg/l (Saliba and Ahsanullah, 1973), which deviates enormously from the effects to other
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invertebrates. As the original publication(s) are not available, conclusions on the sensitivity of soil dwelling organisms cannot be drawn. Three studies on mosquito and mosquito larvae (Culex sp.) were found (Dowden, 1961; Dowden and Bennet, 1965), two were not available and one was documented insufficiently. The toxicity data of these tests indicate that the toxicity of sodium sulfate for these terrestrial organisms is low (EC50 values of > 1000 mg/l for both adults and larvae). Chronic Toxicity No data were found in the literature search for long term toxicity. Toxicity to Microorganisms Four studies on activated sludge bacteria, motile protozoa and stalked ciliates were reliable with restrictions as the studies were not performed according to standardised guidelines, but were described with enough details. There was no effect on the microorganisms up to approximately 8 g/l (Tokuz & Eckenfelder (1979), Tokuz (1986), Gilli & Comune (1980)). Two studies on the toxicity to Pseudomonas fluorescens and Pseudomonas putida were found but were not available. Table 13
Acute toxicity to micro-organisms

Validated data (validity 1 or 2) on acute toxicity to microorganisms.

Ref. (year) Tokuz & Eckenfelder (1979), Tokuz (1986) Tokuz & Eckenfelder (1979), Tokuz (1986) Tokuz & Eckenfelder (1979), Tokuz (1986) Gilli & Comune (1980) Species Bacteria in activated sludge Motile protozoa in activated sludge Stalked ciliates in activated sludge Activated sludge Method/Protocol 37 days test with increasing concentration Results NOEC ca. 26 g/l

37 days test with increasing concentration

NOEC ca. 26 g/l

37 days test with increasing concentration

NOEC ca. 8 g/l

ca. 40 days test with increasing concentration

NOEC ca. 30 g/l

With respect to the high NOEC values sodium sulfate is not expected to be hazardous for activated sludge. 4.2 Terrestrial Effects

Effects in soil dwelling biota There are no data available

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OECD SIDS Table 14

Acute toxicity to sediment dwelling organisms

SODIUM SULFATE Validated data (validity 2) on acute toxicity to sediment dwelling organisms.
Ref. (year) Species Method/Protocol 96 hours semi static test in river water Results LC50 96h = 0.66 g/l Goetsch and Trycorythus Palmer (1997) sp.

Effects in terrestrial plants There were six studies found on terrestrial plants. Three (Navarro, et al., 2002; Banet, et al., 1996; Egan and Ungar, 1998) were considered invalid because it was not clear at what concentrations significant effects occurred. In two of these studies the test concentration was expressed in osmotic potential and it is not clear what the equivalent sodium sulfate concentration is. Three studies were valid with restrictions. The methods were not standardised, but described in detail. Pinus banksiana appeared to be the most sensitive to sodium sulfate and the roots appeared to be the most sensitive part of the plant. Root length and the number of lateral roots were affected at 10 mM (1.4 g/l) (Croser, et al., 2001). Table 15
Toxicity to terrestrial plants

Validated data (validity 1 or 2) on toxicity to terrestrial plants

Ref. (year) Croser, et al. (2001) Species Picea glauca Method/Protocol Test with seeds in sand Results Emergence: decrease in 20 mM and higher Survival: decrease in 50 mM and higher Root length: reduction in 20 mM and higher Lateral roots: decrease in 50 mM and higher Leaf necrosis: in 50 mM and higher Fresh weight: reduced in 50 mM and higher Photosynthesis: not changed Emergence: decrease in 20 mM and higher Survival: decrease in 50 mM and higher Root length: reduction in 10 mM and higher Shoot length: reduced in 50 mM and higher Lateral roots: decrease in 10 mM and higher Leaf necrosis: in 50 mM and higher Fresh weight: reduced in 50 mM and higher PHOTOSYNTHESIS: NOT CHANGED Emergence: decrease in 100 mM and higher Survival: decrease in 100 mM and higher Shoot length: reduced in 50 mM and higher Root length: reduction in 20 mM and higher Lateral roots: decrease in 50 mM and higher Leaf necrosis: no necrosis Fresh weight: reduced in 50 mM and higher Photosynthesis: not changed

Croser, et al. (2001)

Pinus banksiana

Test with seeds in sand

Croser, et al. (2001)

Picea mariana

TEST WITH SEEDS IN SAND

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OECD SIDS 4.3 Other Environmental Effects

SODIUM SULFATE

No data on other environmental effects are available. 4.4 Initial Assessment for the Environment

For short term toxicity many studies were performed, but most were not considered reliable. There were no studies with reliability 1, but for every SIDS endpoint at least one study was found which was valid with restrictions. Algae were shown to be the most sensitive to sodium sulfate; EC50 120h = 1,900 mg/l. For invertebrates (Daphnia magna) the EC50 48h = 4,580 mg/l and fish appeared to be the least sensitive with a LC50 96h = 7,960 mg/l for Pimephales promelas. Activated sludge showed a very low sensitivity to sodium sulfate. There was no effect on the stalked ciliates in the activated sludge up to 8 g/l, the bacteria and motile protozoa showed no effect up to 26 g/l. Sodium sulfate is not very toxic to terrestrial plants. Picea banksiana was the most sensitive species. The roots appeared to be the most sensitive part of the plant and showed effects at 1.4 g/l. Sediment dwelling organisms were not very sensitive either, with an LC50 96h = 660 mg/l for Trycorythus sp. Overall it can be concluded that sodium sulfate has no acute adverse effect on aquatic and sediment dwelling organisms. For terrestrial plants it is not very toxic either. Sulfate can be reduced anaerobically by sulfate reducing bacteria to sulfide, but will not be aerobically degraded. No data were found in the literature search for long term toxicity. The acute studies all show LC50s and EC50s for sodium sulfate that are substantially higher than the EU (European Union, 1967) and GHS (United Nations, 2003) threshold for classification as dangerous for the environment (100 mg/l). The calculated BCF is 0.5, which means that no bioaccumulation is expected. From these results it can be considered that no further chronic studies are required.

RECOMMENDATIONS

Because of low toxicity to humans and the environment, the chemical is of low priority for further work.

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REFERENCES

References cited in SIAR: Adams, A.W., Cunningham, F.E., Munger, L.L. (1975). Some effects on layers of sodium sulfate and magnesium sulfate in their drinking water. Poultry Sci. 54(3):707-714. Andres, C.J. and Cline, T.R. (1989). Influence of Sulfate in Drinking Water on Mouse Reproduction during two Parities. J. Anim. Sci. 67:1313-1317. Arcuri, P. and Gautieri, F. J. (1973). Morphine-induced fetal malformations. 3. Possible mechanisms of action. Pharmaceut. Sci. 62(10): 1626-1634. Banet, G., Wininger, S., Badani, H., BenDor, B., Friedman and Y., Kapulnik, Y. (1996). Toxic and osmotic effects of salinity on growth and nodulation of Medicago sativa. Symbiosis. 21:209-222. Bauer, J.H. (1976). Oral administration of radioactive sulfate to measure extracellular fluid space in man. J. Appl. Physiol. 40(4):648-650. Bayer, A.G. (1988). Salmonella/Microsome test to evaluate for point mutagenic effects. Unpublished report. Study no. T9027163, Report no. 16839, Wuppertal, Germany. Bayer, A.G. (1991). Study for skin and eye irritation/corrosion in rabbits. Unpublished report. Study no. T7039997, Report no. 20338, Wuppertal, Germany. Blunck, J.M. and Crowther, C.E. (1975). Enhancement of azo dye carcinogenesis by dietary sodium sulphate. Europ. J. Cancer. 11(1): 23-31. CFTA (1976). Allergic contact sensitization test (Test No. <intentionally blanked-out>.003-76) on Bubble Bath 60082-C containing 80.8% Sodium Sulfate. Unpublished report. Study no. <intentionally blanked-out>.003-76, Report no. Not stated. Chapmann and Hall (1992). Dictionary of Inorganic Compounds. Vol.3. Chemiekaarten (2000). pp. 921, C0979, The Netherlands. Chein, L., Robertson, H., Gerrard, J.W. (1968). Infantile gastroenteritis due to water with high sulfate content Canadian Medical Association Journal 99: 102-104. Cocchetto, D.M. and Levy, G. (1981). Absorption of orally administered sodium sulfate in humans. J. Pharm. Sci. 70(3):331-333. College of Biological Sciences. Lecture 23: The Sulfur Cycle. Available: http://www.biosci.ohiostate.edu/~mgonzalez/Micro521/23.html. [Accessed: 22-09-2005] Croser, C., Renault, S., Franklin, J. and Zwiazek, J. (2001). The effect of salinity on the emergence and seedling growth of Picea mariana, Picea glauca and Pinus bankciana. Environmental pollution. 115(1):9-16. Denisov, Y.N. and Tkachev, P.G. (1989). Hygienic characteristics of small doses of sodium sulfate after its inhalation. Gigiena i sanitaria. 4:69-71. Denisov, Y.N., and Tkachev, P.G. (1990). Health aspects of sodium salts of sulfurous and sulfuric acids as environmental pollutants. Gigiena i sanitariia. 9:11-13.

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Diem, K. (ed.) (1972). Documenta Geigy scientific tables. 6th edition. J.R. Geigy S.A., Basle, Switzerland. 533 pp. Dowden, B.F. (1961). Cumulative toxicities of some inorganic salts to Daphnia maena as determined by median tolerance limits. Proc. La. Acad. Sci. 23:77-85. Dowden, B.F. and Bennett H.J. (1965). Toxicity of selected chemicals to certain animals. J. Water Pollut. Control Fed. 37(9):1308-1316. ECETOC (1999). Skin and respiratory sensitisers: Reference chemical data bank. ISSN 07738072-77. ECETOC, Brussels. Egan, T.P. and Ungar, I.A. (1998) Effect of different salts of sodium and potassium on the growth of Atriplex prostrata (Chenopodiaceae). Journal of plant nutrition, 21(10):21932205. Environment Canada (1985) Tech Info for Problem Spills: Sodium sulfate. EPI Suite (2000). U.S. Environmental Protection Agency. EU Dangerous Substances Directive 67/548/EEC, Annex VI. Gilli, G. And Comune, P.M. (1980). Effetti della salinit su sistemi biologici. Inquinamento 22(100):31-35 Gilman, A.G., Goodman, L.S., Gilman, A. (eds). (1980). Goodman and Gilmans The Pharmalogical Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co. Inc. p.1005. Goetsch, P.A. and Palmer, C.G. (1997). Salinity tolerance of selected macroinvertebrates of the Sabie river, Kruger national park, South Africa. Arch. Environ. Contam. Toxicol. 32:32-41. Gould, D.H., McAllister, M.M., Savage, J.C., Hamar, D.W. (1991). High sulfide, concentrations in rumen fluid associated with nutritionally induced polioencephalomalacia in calves. Am. J. Vet. Res.51(7):1164-1169. Greben, H.A., Maree, J.P., Mnqanqeni, S. (2000). Comparison between sucrose, ethanol and methanol as carbon and energy source for biological sulphate reduction. Water Science and Technol. 41(12):247-253. Handbook of chemistry and Physics (1997-1998). 78th ed. CRC press, pp. 4-87. Hawley, G.G. (1981). The Condensed Chemical Dictionary, 10th ed. New York, Van Nostrand Reinhold Co. USA. Health Canada, November 1987 (updated http://www.hc-sc.gc.ca/. [Accessed 09-22-2005] September 1994), Sulphate. Avialable:

Heizer, W.D., Sandler, R.S., Seal, E., Murray, S.C., Busby, M.G., Schliebe, B.G., Pusek, S.N. (1997). Intestinal effects of sulfate in drinking water on normal human subjects. Digestive Diseases and Sciences 42(5):1055-1061. Henkel (1971). Orientierende toxizitt. Unpulished Henry, J.G. and Prasad, D., (2000). Anaerobic treatment of landfill leachate by sulphate reduction. Water Science and Tecnol. 41(3):239-246.

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Hitchcock, D.R. (1975). Biogenic contribution to atmospheric sulfate levels. Water's interface with energy, air and solids: proceedings of the second national conference on complete waterreuse, Chicago, Illinois, May 4-8, 1975. pp 291-310. ICRP (1984). International Commission on Radiological Protection: Report no. 23: Report of the Task Group on Reference Man. Pergamon Press, Oxford, UK. Kelada, F. and Euinton, L.E. (1978). Health effects of long term exposure to sodium sulfate dust. J. Occup. Med. 20(12):812-814. Krijgsheld, K.R., Frankena, H., Scholtens, E., Zweens, J. and Mulder, G.J. (1979). Absorption, serum levels and urinary excretion of inorganic sulfate after oral administration of sodium sulfate in the conscious rat. Biochim. Biophys. Acta, 586(3):492-500. Last, J.A. Purnendu, K.D., Ethinson, J.R. (1980). Inhalation Toxicology of Sodium Sulfite Aerosol in Rats. Toxicol. Appl. Pharmacol. 55:229-234. Laury, N.A. (1927). Hydrochloric acid and sodium sulfate. American Chemical Society. Monograph series 36. Chemical catalog Co, USA. Lenntech Water treatment & air purification Holding B.V. (2003) Lenntech: Sulfur cycle. Available: http://www.lenntech.com/sulfur-cycle.htm. [Accessed 2003]. Meng, Z.Q. and Zhang, L.Z. (1992). Cytogenetic damage induced in human lymphocytes by sodium bisulfite. Mutation Research. 298:63-69 Merck 12ed (1996). pp. 1483, Merck&Co, NJ, USA. Ministry of water, land and air protection (2000). Ambient water quality guidelines for sulfate. Overview report. British Columbia, Canada. Available: http://wlapwww.gov.bc.ca/wat/wq/BCguidelines/sulphate.html [Accessed 09-22-2005] Moinuddin, J.F., Wing-Tsit Lee, H. (1960). Alimentary, blood and the other changes due to feeding MnSO4, MgSO4 and Na2SO4. American Journal of Physiology. 199(1): 77-83. Morris, M.E. and Levy, G. (1983). Serum concentration and renal excretion by normal adults of inorganic sulfate after acetaminophen, ascorbic acid, or sodium sulfate. Clin. Pharmacol. Ther. 33(4):529-536. Mount, D.R., Gulley, D.D., Hockett, J.R., Garrison, T.D., Evans, J.M. (1997). Statistical models to predict the toxicity of major ions to Ceriodaphnia dubia, Daphnia magna, and fathead minnows (Pimephales promelas). Environ. Toxicol. Chem. 16(10):2009-2019. Navarro, J.M., Garrido, C., Carvajal, M and Martinez, V. (2002). Yield and fruit quality of pepper plants under sulphate and chloride salinity. Journal of Horticulture and Biotechnology. 77(1):5257. Niles, G.A. , Morgan, S., Edwards, W.C. , Lalman, D. (2002). Effects of Dietary Sulfur Concentrations on Incidence and Pathology of Polioencephalomalicia in Beef Calves. Vet. Human Toxicol. 44(2):70-72. Okahara. (1963). Food Hygiene Journal (Shokuhin Eiseigaku Zassi) 4:15. Paterson, D.W., Whalstrom, R.C., Libal, G.W. Olson, O.E. (1979). Effects of sulfate in water on reproduction in swine and young pig performance. J.Anim. Sci. 49(S1):105.

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Patrick, R.J., Cairns, J., Scheier, A. (1968). The relative sensitivity of diatoms, snails, and fish to twenty common constituents of industrial wastes. The Progressive Fish-Culturist. 30(3):137140. Percy, A.K. and Yaffe, S.J. (1964). Sulfate metabolism during mammalian development. Pediatrics. 33(6):965-974. Research Triangle Inst. (1998). Toxicological profile for sulfur trioxide and sulfuric acid. U.S. Department of Commerce, National Technical information Service. Remington's pharmaceutical sciences (1980).16th ed. Easton, Pennsylvania: Mack publishing co. Sackner, M.A., Ford, D. Kim, C. (1979). Effect of brief exposure to high concentrations of sodium chloride and sodium sulfate aerosols with mass median aerodynamic diameter of 0.5 m on pulmonary function of normal and asthmatic adults. American Review of Respiratory Disease. 119(4):.233. Saliba, L.J. and Ahsanullah, M. (1973). Acclimation and Tolerance of Artemia salina and Ophryotrocha labronica to Copper Sulphate. M. Mar.Biol. 23(4):297302. Schlessinger, R.B. (1984). Comparative irritant potency of inhalated sulfate aerosolsEffects on bronchial mucociliary clearance. Environ. Res. 34(2):268-279. Seidenberg, J.M., Anderson, D.G., Becker, R.A. (1986). Validation of an in vivo developmental toxicity screen in the mouse. Teratogenesis, Carcinogenesis and Mutagenesis. 6:361-374. Seidenberg, J.M. and Becker, R.A. (1987). A summary of the results of 55 chemicals screened for developmental toxicity in mice. Teratogenesis, Carcinogenesis, mutagenesis. 7:17-28. Sibblad, I.R. and Cave, N.A. (1976). The responses of chicks to ammonium, calcium, magnseium, potassium and sodium sulphates and to ammonium and potassium carbonates. Poult. Sci. 55:22092213. SSPA (2003) Internal report. Tokuz, R.Y. and Eckenfelder, W.W. (1979). The effect of inorganic salts on the activated sludge process performance. Water Res. 13(1):99-104. Tokuz, R.Y. (1986). The effect of high salinity on activated sludge effluent quality. Curr. Pract. Environ. Sci. Eng. 2:143-154. Toth, B. (1987). Cancer Induction by the sulfate form of 4-(Hydroxymethyl)-benzenediazonium ion of Agaricus bisporus. In Vivo 1:39-42. Trama, F.B. (1954). The acute toxicity of some common salts of sodium potassium and calcium to the common Bluegill. (Lepomis Macrochirus Rafinesque). Proc. Acad. Nat. Sci. Philadelphia. 106: 185-205. Ullmann's Encyclopedia of Industrial Chemistry (2004). 7th ed. John Wiley & Sons, Inc. United Nations (2003). The Globally Harmonized System of Classification and Labelling of Chemicals (GHS). United States Environment Program. Global Environmental Monitoring System. Freshwater Quality Program (GEMS)."Salts and Salinization of Surface Waters". Available: http://www.gemswater.org/atlas-gwq/salts-e.html. [Accessed 09-22-2005]

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US-EPA (1999). Health effects from exposure to sulfate in Drinking water Workshop CDC protocol #1779; Office of Water 4607; EPA 815-R-99-002. Upton, P.K. and LEstrange, J.L. (1976). Effects of high intakes of dietary sodium sulphate and sodium chloride on voluntary food intake of rats. Proc. Nutr. Soc. 20A21A. U.S. Geological Survey (2000). Mineral Commodity Summaries. February 2000. Veenhuizen, M.F., Shurson, G.C., Kohler, E.M. (1992). Effect of concentration and source of sulfate on nursery pig performance and health. JAVMA. 201(8):1203-1208. WHO (2003). Sulfate in drinking-water. Background document for preparation of WHO Guidelines for drinking-water quality. Geneva, World Health Organization (WHO/SDE/WSH/03.04/114). References checked but not used Bird, P.R. (1972). Sulfur metabolism and excretion studies in ruminants. Secretion of sulfur and nitrogen in sheep pancreatic and bile fluids.Aust. J. Biol. Sci. 25:817. Dziewiatkowski, D.D. (1962). Intracellular synthesis of chondroitin sulfate. J. Cell Biol. 13: 359. Dziewiatkowski, D.D. (1951). Isolation of chondroitin sulfate-35S from articular cartilage of rats. J. Biol. Chem. 189:187. Dziewiatkowski, D.D. (1970). Sulfur in animal nutrition. In: Proceedings of a Symposium on Sulfur in Nutrition. D.H. Muth and J.E. Oldfield (eds.). Ari Publishing Co., Westport, CT. Kristensen P. (1993). Inorganic acid aerosols. Arbete och Halsa, 1, 7-54. Laidlaw, J.C. and Young, L. (1953). A study of ethereal sulfate formation in vitro using radioactive sulfate. Biochem. J., 54:142. Mulder, G.J. (ed.). (1981). Sulphation of drugs and related compounds.CRC Press, Boca Raton, FL. Mulder, G.J. and Kevelmans, K. (1978). The metabolism of inorganic sulfate in the isolated perfused rat liver. Effect of sulfate concentration on the rate of sulphation by phenolsulphotransferase. Biochem. J., 176: 959. Murer, H. (1988). Transport of sulfate and phosphate in small intestine and renal proximal tubule: methods and basic properties. Comp. Biochem. Physiol. 90A:749. Rosner G. (1994) Fraunhofer-Institut fur Toxikologie und aerosolforschung. Whiting, S.J. and Cole, D.E. (1986) Effect of dietary anion composition on acid-induced hypercalciuria in the adult rat. J. Nutr., 116: 388.

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I U C L I D D a t a S e t

Existing Chemical CAS No. EINECS Name EC No. TSCA Name Molecular Formula Producer Related Part Company: Creation date:

ID: 7757-82-6 7757-82-6 sodium sulphate 231-820-9 Sulfuric acid disodium salt H2O4S.2Na

Akzo Nobel Salt and Basic Chemical Division 06-SEP-2001

Substance Related Part Company: Akzo Nobel Salt and Basic Chemical Division Creation date: 06-SEP-2001 Memo: OECD HPV Chemical Programme, SIDS DOssier, approved at SIAM 20 ( 19-22 April 2005) 07-AUG-2006 07-AUG-2006

Printing date: Revision date: Date of last Update:

Number of Pages:

123

Chapter (profile): Chapter: 1, 2, 3, 4, 5, 6, 7, 8, 10 Reliability (profile): Reliability: without reliability, 1, 2, 3, 4 Flags (profile): Flags: without flag, confidential, non confidential, WGK (DE), TA-Luft (DE), Material Safety Dataset, Risk Assessment, Directive 67/548/EEC, SIDS

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1.0.1 Applicant and Company Information 24-OCT-2001 1.0.2 Location of Production Site, Importer or Formulator 1.0.3 Identity of Recipients 1.0.4 Details on Category/Template 1.1.0 Substance Identification IUPAC Name: Mol. Formula: Mol. Weight: Petrol Class: 22-JUN-2005 1.1.1 General Substance Information Purity type: Substance type: Physical status: Purity: Source: 31-OCT-2001 1.1.2 Spectra 1.2 Synonyms and Tradenames Alcan recovered Cryolite Source: 30-OCT-2001 Bisodium sulfate Source: 30-OCT-2001 Akzo Nobel Chemicals, Amersfoort Henkel KGaA Duesseldorf Henkel Hellas S.A. Atalanti Henkel KGaA Duesseldorf other inorganic solid > 99.5 United States Pharmacopeial (2000) sodium sulfate Na2SO4 142.04 other

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Dibasic sodium sulfate Source: 30-OCT-2001 Dinatriumsulfat 37 UNEP PUBLICATIONS Akzo Nobel Chemicals, Amersfoort Henkel KGaA Duesseldorf Henkel Hellas S.A. Atalanti

OECD SIDS 1. GENERAL INFORMATION

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Source: 01-NOV-2001

Henkel KGaA Duesseldorf

Disodio monosolfato Source: 30-OCT-2001 Disodium Source: 30-OCT-2001 Disodium sulfate Source: 30-OCT-2001 Disodium sulphate Source: 30-OCT-2001 E 514 Source: 30-OCT-2001 Kemsol Source: 01-NOV-2001 Na-sulfat Source: 30-OCT-2001 Natrii sulfas Source: 30-OCT-2001 Henkel KGaA Duesseldorf Henkel KGaA Duesseldorf Henkel KGaA Duesseldorf Henkel KGaA Duesseldorf Akzo Nobel Chemicals, Amersfoort Henkel KGaA Duesseldorf Henkel Hellas S.A. Atalanti Akzo Nobel Chemicals, Amersfoort Henkel KGaA Duesseldorf Henkel Hellas S.A. Atalanti Luigi Stoppani SpA Milano

monosulfate Akzo Nobel Chemicals, Amersfoort Henkel KGaA Duesseldorf Henkel Hellas S.A. Atalanti

Natrium sulfuricum Source: 30-OCT-2001 natriumsulfaatti Source: 30-OCT-2001 Sateri Oy Valkeakoski SYNTANA Handelsges. Muhlheim-Ruhr

Natriumsulfat rein UNEP PUBLICATIONS 38

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SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Source: 30-OCT-2001

Hoechst AG Frankfurt/Main Celanese GmbH Frankfurt am Main Faserwerk Kelheim GmbH Kelheim

Natriumsulfate wasserfrei Source: 30-OCT-2001 Ningunoso Source: 01-NOV-2001 CRIMIDESA Madrid Hoechst AG Frankfurt/Main Celanese GmbH Frankfurt am Main Faserwerk Kelheim GmbH Kelheim

Sal disodica del acido sulfurico Source: 30-OCT-2001 Salt cake Source: 30-OCT-2001 Courtaulds Fibres Limited Grimsby Henkel KGaA Duesseldorf Occidental Chemical Corporation Niagara Falls, NY 14302-0728 FMC FORET SA Barcelona

saureregualator E 514 Source: 01-NOV-2001 Henkel KGaA Duesseldorf

Schwefelsaure, di-Na-Salz Source: 30-OCT-2001 Henkel KGaA Duesseldorf

Schwefelsaure-Natriumsalz Source: 30-OCT-2001 MERCK Darmstadt

Sodium sulfate (anydyrous) Source: 30-OCT-2001 Amway Europe Zaventem

Sodium sulphate anhydrous Source: 30-OCT-2001 Solfato di sodio Source: 30-OCT-2001 Laporte Italia SPA Divisione SILO Torino Henkel KGaA Duesseldorf Henkel Hellas S.A. Atalanti

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Sulfate de Sodium Source: 30-OCT-2001 Produits Chimiques de Loos Loos

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Sulfato de sodio anidro Source: 01-NOV-2001 Sulfato sodico Source: 01-NOV-2001 FMC FORET SA Barcelona Industrias Lever Portugesa LDA. Sacavem; ECB - Existing Chenicals Ispra (VA); Henkel KGgA Dueseldorf

Sulfato sodico anhidro Source: 30-OCT-2001 S.A. Sulquisa Bilbao

Sulfuric acid, disodium salt Source: 30-OCT-2001 Thenardite Source: 30-OCT-2001 Trona Source: 01-NOV-2001 1.3 Impurities 1.4 Additives 1.5 Total Quantity Quantity: 22-SEP-2005 Quantity: 22-SEP-2005 ca. 4928000 tonnes produced in 1991 (94) ca. 4600000 tonnes produced in 1999 (100) Chemie GmbH Bitterfeld-Wolfen Wolfen Chemie GmbH Bitterfeld-Wolfen Wolfen Henkel KGaA Duesseldorf Henkel Hellas S.A. Atalanti Novo Nordisk A/S Bagsvaerd

1.6.1 Labelling 30-OCT-2001 UNEP PUBLICATIONS 40

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SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

1.6.2 Classification Classified: 30-OCT-2001 1.6.3 Packaging 1.7 Use Pattern Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: industrial other: Detergent industry industrial Textile processing industry industrial Public domain industrial Personal and domestic use industrial Paper, pulp and board industry industrial Paints, lacquers and varnishes industry industrial Metal extraction, refining and processing of metals industrial Chemical industry: used in synthesis industrial Basic industry: basic chemicals industrial Agricultural industry no classification required (no dangerous properties)

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30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 Type: Category: 30-OCT-2001 1.7.1 Detailed Use Pattern use Semiconductors use Process regulators use Pharmaceuticals use Pesticides use Laboratory chemicals use Intermediates use Food/foodstuff additives use Fillers use Conductive agents use Cleaning/washing agents and disinfectants industrial other: Glassindustry

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

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1.7.2 Methods of Manufacture 1.8 Regulatory Measures 01-NOV-2001 1.8.1 Occupational Exposure Limit Values Type of limit: Remark: Reliability: 22-SEP-2005 Type of limit: Remark: Reliability: 22-SEP-2005 1.8.2 Acceptable Residues Levels 1.8.3 Water Pollution Classified by: Labelled by: Class of danger: 22-SEP-2005 Classified by: Labelled by: Class of danger: 22-SEP-2005 Classified by: Labelled by: Class of danger: 19-JUN-2003 1.8.4 Major Accident Hazards 1.8.5 Air Pollution 1.8.6 Listings e.g. Chemical Inventories KBwS (DE) KBwS (DE) 0 (generally not water polluting) KBwS (DE) KBwS (DE) 0 (generally not water polluting) KBwS (DE) KBwS (DE) 0 (generally not water polluting) MAC (NL) not determined (4) not assignable no data available OES (UK) O.E.L. : O.E.L. : (4) not Original

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(24)

10 mg/m3 8hr. TWA total inhalable dust. 5 mg/m3 8hr. TWA total respirable dust. assignable reference not available (75)

(19)

(2)

(18)

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1.9.1 Degradation/Transformation Products 1.9.2 Components 1.10 Source of Exposure Source of exposure: Human: exposure by production Exposure to the: Substance Remark:

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Sodium sulfate in solution is a by product from the manufacture of Sodium Dichromate. The solution, after separation of the minimal Sodium Dichromate content, is evaporated to saturation.The resultant crystals of Sodium sulfate are separated from solution by centrifuge prior to drying. (17)

22-SEP-2005 1.11 Additional Remarks Memo: Remark: Clinical use as laxative

Reliability: 13-JAN-2005 Memo: Remark: 01-NOV-2001 Memo: Remark: 16-NOV-2001 Memo: Remark: 22-JUN-2005 Memo: Remark: 01-NOV-2001 Memo: Remark: 01-NOV-2001

Sodium sulfate, recommended dose: 300 mg/kg up to 20 grams maximum for an adult. Probable mode of action: fluid retention caused by the hygroscopic action of unresorbed sodium sulfate in the large intestine. (4) not assignable textbook reference (41) Drinking Water Quality Standards Sulfate Sulfate Maximum Acceptable Concentration: 200 mg/l Maximum Allowable Concentration : 250 mg/l (74) Drinking Water Quality Standards The taste threshold concentrations for sodium sulfate is 250 - 900 mg/l. (3) Drinking Water Quality for Poultry Sulfate : Level considered average : 125 mg/l Sulfate : MAC : 250 mg/l (88) Ground water Quality Standards for Drinking water purposes Sulphate Sulphate Maximum Acceptable Concentration: 200 mg/l Maximum Allowable Concentration : 250 mg/l (74) Secondary Maximum Contaminant Level SMCL value : 250 mg/l Sulfate (76) UNEP PUBLICATIONS 44

OECD SIDS 1. GENERAL INFORMATION

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

urinary sulfur

Memo: Remark: Reliability: 13-JAN-2005 Memo: Remark: Reliability: 13-JAN-2005 Memo: Remark: 22-JUN-2005

Speciation of

85% of urinary sulfur as s inorganic sulfates 10% as organic sulfates, 5% as conjugated alkyl sulfates (4) not assignable textbook reference (31) Sulfate elimination Daily elimination of sulfate in human urine: ~ 800 mg as elemental sulfur are Daily elimination of sulfate in human feces: : ~ 140 mg (4) not assignable textbook reference (57) Water Quality Guidelines for Sulfate Drinking water (Aesthetics) : 500 mg/l dissolved sulfate Freshwater Aquatic Life : 100 mg/l sulfate maximum concentration, 50 mg/l sulfate Alert level.

(3)

1.12 Last Literature Search 1.13 Reviews

45

UNEP PUBLICATIONS

OECD SIDS 2. PHYSICO-CHEMICAL DATA

2.1 Melting Point Value: Reliability: 01-NOV-2001 Value: Reliability: = 884 degree C = 800 degree C (2) valid with restrictions Results from handbook

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(67)

07-NOV-2001 Value: Reliability: Flag: 31-OCT-2001 Value: Reliability: 07-NOV-2001 2.2 Boiling Point Value: Decomposition: Test substance: Result: Reliability: Flag: 01-DEC-2004 Value: Remark: Reliability: 16-NOV-2001 Value:

(2) valid with restrictions Studies performed according to appropriate guidelines and GLP are not available. However, there is no need to perform such studies because: - Exisiting data are available from at least 3 different sources from which the results are not conflicting. (101) ca. 884 degree C (2) valid with restrictions Results from handbook Critical study for SIDS endpoint (47) ca. 888 degree C (2) valid with restrictions Results from handbook (49)

yes as prescribed by 1.1 - 1.4 Decomposes at temperatures above melting point (884 degree C). (2) valid with restrictions Results from handbook Critical study for SIDS endpoint (102) ca. 103.5 degree C Determined in a saturated solution (2) valid with restrictions Results from handbook > 1700 degree C

(63)

UNEP PUBLICATIONS

46

OECD SIDS 2. PHYSICO-CHEMICAL DATA

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Reliability: 31-OCT-2001 2.3 Density Type: Value: Reliability: Flag: 13-JUN-2003 Type: Value: Reliability: 13-JUN-2003 Type: Value: Reliability: 13-JUN-2003 Type: Value: Reliability: 31-OCT-2001

(2) valid with restrictions Results from handbook (24)

relative density = 2.7 g/cm at 20 degree C (2) valid with restrictions Results from handbook Critical study for SIDS endpoint relative density = 2.7 g/cm at 25 degree C (2) valid with restrictions Results from handbook (24) relative density = 2.671 g/cm (2) valid with restrictions Results from handbook (49) relative density ca. 2.7 g/cm (2) valid with restrictions Results from handbook (47)

(101)

2.3.1 Granulometry 2.4 Vapour Pressure Remark: 13-JUN-2003 2.5 Partition Coefficient Partition Coeff.: octanol-water log Pow: = -4.38 Method: Reliability: 47 other (calculated) (2) valid with restrictions UNEP PUBLICATIONS The melting point is 800-888 degree C. therefore, the vapour pressure will be extremely low.

OECD SIDS 2. PHYSICO-CHEMICAL DATA

Result calculated with computer program 01-SEP-2003 Partition Coeff.: octanol-water log Pow: = -3 Method: Reliability: 19-JUN-2003 other (calculated)

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(38)

(2) valid with restrictions Studies performed according to appropriate guidelines and GLP are not available. Data obtained from handbook.

(24)

2.6.1 Solubility in different media Solubility in: Value: Reliability: 31-OCT-2001 Solubility in: Value: Reliability: 07-NOV-2001 Solubility in: Value: Reliability: 16-JUN-2003 Solubility in: Value: Reliability: 07-NOV-2001 Solubility in: Value: Reliability: 15-NOV-2004 Solubility in: Remark: other: Glycerol Sodium sulfate is soluble in glycerol UNEP PUBLICATIONS 48 Water ca. 161 g/l at 20 degree C (2) valid with restrictions Results from handbook (47) Water ca. 162 g/l at 20 degree C (2) valid with restrictions Results from handbook (24) Water = 190 g/l at 20 degree C (2) valid with restrictions Results from handbook Water ca. 430 g/l at 100 degree C (2) valid with restrictions Results from handbook

(101)

(23)

Water ca. 195 g/l at 20 degree C (4) not assignable Results from handbook (63)

OECD SIDS 2. PHYSICO-CHEMICAL DATA

Reliability: 16-JUN-2003 Solubility in: Remark: Reliability: 16-JUN-2003 other: Alcohol

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(4) not assignable Secondary literature. Reference not available. (67)

sodium sulfate is not soluble in alcohol (4) not assignable Secondary literature. Reference not available.

(67)

2.6.2 Surface Tension 2.7 Flash Point 2.8 Auto Flammability 2.9 Flammability Result: Reliability: 31-OCT-2001 non flammable (2) valid with restrictions Studies performed according to appropriate guidelines and GLP are not available. Data obtained from handbook.

(24)

2.10 Explosive Properties Result: Reliability: 31-OCT-2001 not explosive (2) valid with restrictions Studies performed according to appropriate guidelines and GLP are not available. Data obtained from handbook.

(24)

2.11 Oxidizing Properties Result: Reliability: 23-NOV-2001 no oxidizing properties (2) valid with restrictions Studies performed according to appropriate guidelines and GLP are not available. Data obtained from handbook.

(24)

2.12 Dissociation Constant 2.13 Viscosity Value: 49 = 2.481 mPa s (dynamic) at 20 degree C UNEP PUBLICATIONS

OECD SIDS 2. PHYSICO-CHEMICAL DATA

Result: Test substance: Reliability: 02-DEC-2004 2.14 Additional Remarks Memo: Source: 16-NOV-2001 Data refer to dehydrated Na2SO4 Enichem S.p.A Milan Henkel S.p.A Duesseldorf 22% solution as prescribed by 1.1 - 1.4

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(2) valid with restrictions Studies performed according to appropriate guidelines and GLP are not available. Data obtained from handbook. (48)

UNEP PUBLICATIONS

50

OECD SIDS 3. ENVIRONMENTAL FATE AND PATHWAYS

3.1.1 Photodegradation 3.1.2 Stability in Water Type: Remark: Reliability: 22-SEP-2005 abiotic

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Na2SO4 dissociates in water completely in sodium and sulfate ions. The ions cannot hydrolyze and therefore it is not scientifically necessary to perform a hydrolysis study. (2) valid with restrictions Studies performed according to appropriate guidelines and GLP are not available. Data obtained from handbook. (47)

3.1.3 Stability in Soil 3.2.1 Monitoring Data (Environment) Type of measurement: background concentration Medium: surface water Concentration: ca. 3 - 30 mg/l Remark: Reliability: 22-SEP-2005 Sulfate concentrations measured in Canadian Lakes, British Columbia, Canada. (2) valid with restrictions Study well documented, meets generally accepted scientific principles, acceptable for assessment (58)

Type of measurement: background concentration Medium: surface water Concentration: ca. .001 - 3 g/l Remark: Reliability: 22-SEP-2005 Sulfate concentrations measured in rivers in Western Canada, British Columbia, Canada (4) not assignable Reference not available

(37)

Type of measurement: background concentration Medium: surface water Concentration: ca. 2 - 30 mg/l Remark: Reliability: 22-SEP-2005 Sulfate concentrations measured in the Liard river, British Columbia, Canada (4) not assignable Reference not available (15)

Type of measurement: background concentration Medium: surface water Concentration: > .4 - g/l Remark: Reliability: Sulfate concentration measured in the Great Plains shales, USA. (2) valid with restrictions Study well documented, meets generally accepted scientific UNEP PUBLICATIONS

51

OECD SIDS 3. ENVIRONMENTAL FATE AND PATHWAYS

principles, acceptable for assessment 22-SEP-2005 Type of measurement: background concentration Medium: surface water Concentration: ca. 10 - mg/l Remark: Reliability: 22-SEP-2005

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(103)

Sulfate concentration measured in the Ob River, Siberia, USSR. (2) valid with restrictions Study well documented, meets generally accepted scientific principles, acceptable for assessment (103)

Type of measurement: background concentration Medium: surface water Concentration: ca. 50 - 60 mg/l Remark: Reliability: 22-SEP-2005 Sulfate concentrations measured in the Volga river, USSR. (2) valid with restrictions Study well documented, meets generally accepted scientific principles, acceptable for assessment (103)

Type of measurement: background concentration Medium: drinking water Concentration: ca. .006 - 1.6 g/l Remark: Reliability: 26-SEP-2005 Sulfate concentrations measured at swine farms in Ohio, USA (2) valid with restrictions Study well documented, meets generally accepted scientific principles, acceptable for assessment (107)

Type of measurement: background concentration Medium: drinking water Concentration: ca. 1 - 2 g/l Remark: Reliability: 22-SEP-2005 Medium: Result: Sulfate concentrations measured in drinking water wells in North and South Dakota, USA (2) valid with restrictions Study well documented, meets generally accepted scientific principles, acceptable for assessment (69) air North America: Non urban sites: 4.9-8.6 g/m3 Coastal urban sites in New York: 8.1-11.3 g/m3 Other coastal sites: 10.7-12.2 g/m3 Inland New York cities: 6.0-10.3 g/m3 (2) valid with restrictions Study well documented, meets generally accepted scientific principles, acceptable for assessment. (54)

Reliability: 22-SEP-2005

3.2.2 Field Studies

UNEP PUBLICATIONS

52

OECD SIDS 3. ENVIRONMENTAL FATE AND PATHWAYS

01-NOV-2001 3.3.1 Transport between Environmental Compartments 3.3.2 Distribution 3.4 Mode of Degradation in Actual Use 3.5 Biodegradation Type: Remark: 13-JUN-2003 Type: Inoculum: Result: Method: Year: Test substance: Result: anaerobic anaerobic sludge other: see freetext other: see freetext 2000 as prescribed by 1.1 - 1.4 aerobic

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

It is not possible to have aerobic biodegratation of sulfate.

Test condition:

Reliability: 22-SEP-2005 Type: Remark:

Sulfate was reduced according to the following reactions: - Sugar: C12H22O11 + 5 H2O + 4 SO42- --> 4 CO2 + 8 H2 + 4 HS- + 8 HCO3- + 4 H+ 8 H2 + 2 SO42- + 2 H+ --> 2 HS- + 8 H2O C12H22O11 + 8 H2SO4 --> 8 S + 12 H2CO3 + 7 H2O - Ethanol: 2 C2H5OH + 3 SO42- --> 3 HS- + 3 HCO3- + 3 H2O + CO2 C2H5OH + H2SO4 --> 2 S + 2 H2CO3 + 3 H2O - Inoculum: Anaerobic sludge obtained from the local municipal sewage treatment plant. - Concentrations of test chemicals: CaSO4 and COD (sugar and technical ethanol) both 1500 mg/l - Temperature: 21 degree C - Analytical determinations: All concentrations, alkalinity and pH were measured according to standard analytical procedures (APHA, 1985). (2) valid with restrictions No guideline study, but includes detailed information on used method and endpoints. (46) anaerobic Na2SO4 may be used as an electron acceptor in anaerobic sulfate reduction by sulfate reducing bacteria. Sulfate is converted to (hydrogen)sulfide. (3) invalid Test is not applicable, but it gives some results about sulfate reduction. UNEP PUBLICATIONS

Reliability:

53

OECD SIDS 3. ENVIRONMENTAL FATE AND PATHWAYS

22-SEP-2005 3.6 BOD5, COD or BOD5/COD Ratio 3.7 Bioaccumulation BCF: Method: Remark: = .5 other: calculated

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(53)

Reliability: 22-SEP-2005

This result is calculated on the basis of log Kow = -2.20 from Sulfuric acid, because it cannot be calculated for Sodium. It is not expected that the value will be different for Sodium sulfate. (2) valid with restrictions Result calculated with computer program (38)

3.8 Additional Remarks Memo: Remark: BIOGENIC CONTRIBUTION Study on the biogenic contribution to atmospheric levels of sulfate. study performed in the USA. Results: Hydrogen sulfide derived from the energy metabolism of bacterial sulfate reducers is the principal source of the 100 to 200 million ton of sulfur annually contributed to the global atmosphere. Most of the sulfate observed in the nonurban sites appears to be of local origin in the north-east of the USA. Urbanization does not appear to influence the sulfate levels in the north-east of the USA. (2) valid with restrictions Study well documented, meets generally accepted scientific principles, acceptable for assessment (54) PLANT NUTRIENTS Sulfate concentrations of less than 0.5 mg/l in water is detrimental for plant growth, as sulfur is an essential element in living organisms. (4) not assignable Reference not available (3)

Reliability: 22-JUN-2005 Memo: Remark: Reliability: 11-JUL-2003

UNEP PUBLICATIONS

54

OECD SIDS 4. ECOTOXICITY

4.1 Acute/Prolonged Toxicity to Fish Type: Species: Exposure period: Unit: LC50: Limit Test: Method: static Lepomis macrochirus 96 hour(s) mg/l = 12500 - 13000 no (Fish, fresh water)

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Analytical monitoring: no

Year: GLP: Test substance: Method:

other: see freetext, method based on Doudoroff et al (1951). Bio-assays methods for the evaluation of acute toxicity of industrial wastes to fish. Sewage and Industrial Wastes, 23, (11):1380-1397. 1959 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: Doudoroff et al (1951). Tests performed in standardized test medium. Test parameters pH, oxygen and temperature not reported. Concentration ranges not known. Study performed to evaluate differences between three size ranges of fish. STATISTICAL METHODS: not described. METHOD OF CALCULATION: not described RESULTS: EXPOSED - Nominal/measured concentrations: not described - Effect data (Mortality): TLm small size fish : 13000 mg/l TLm medium size fish : 12750 mg/l TLm large size fish : 12500 mg/l - Concentration / response curve: not described - Effect concentration vs. test substance solubility: not described - Other effects: not described TEST ORGANISMS - Strain: Raf. - Supplier: Pennsylvanian Fish Commission, Pennsylvania, USA - Wild caught: no - Age/size/weight/loading: size small : 3.88 cm - 0.96 gram size medium : 6.09 cm - 2.80 gram size large : 14.24 cm - 54.26 gram - Feeding: cooked shrimp - Pretreatment: not described - Feeding during test: no STABILITY OF THE TEST CHEMICAL SOLUTIONS: not described REFERENCE SUBSTANCE: no DILUTION WATER - Source: artificial - Aeration: artificial aeration - Alkalinity: not described - Hardness: not described - Salinity: not described - TOC: not described - TSS: not described - pH: not described - Oxygen content: 5 - 9 ppm - Conductance: not described - Holding water: artificial TEST SYSTEM - Test type: static UNEP PUBLICATIONS

Result:

Test condition:

55

OECD SIDS 4. ECOTOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

- Concentrations: not described - Dosing rate: singlefold - Renewal of test solution: no - Exposure vessel type: glass jarrs - Number of replicates, fish per replicate: 1, 5-10 - Test temperature: 19 - 21 degree C - Dissolved oxygen: 5 - 9 ppm - pH: not described - Adjustment of pH: not described - Intensity of irradiation: not described - Photoperiod: not described DURATION OF THE TEST: 96 hours (3) invalid Documentation insufficient for assessment (21) static Poecilia latipinna 48 hour(s) mg/l = 15996 no (Fish, estuary) Analytical monitoring: no

Reliability: 26-SEP-2005 Type: Species: Exposure period: Unit: LC50: Limit Test: Method: Year: GLP: Test substance: Method:

other: see freetext, method based on Freeman, L. "A standardized method for determining toxicity of pure compounds to fish", Sewage and Industrial wastes, 25, 7, 845 (1953) 1965 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: 96 hours static test. Test parameters were monitored, but not reported. METHOD OF CALCULATION: not described Median Tolerance Limit (TLm), not reported. Only up to 48 hours a TLm was determined. RESULTS: EXPOSED - Nominal/measured concentrations: nominal - Effect data (Mortality): 24 hours LC50 : 20040 mg/l - Concentration / response curve: not described - Effect concentration vs. test substance solubility: not described - Other effects: not described TEST ORGANISMS - Strain: not described - Supplier: Local pet shop - Wild caught: no - Age/size/weight/loading: not described - Feeding: not described - Pretreatment: not described - Feeding during test: no DILUTION WATER - Source: reconstituted water - Aeration: yes - Alkalinity: not described - Hardness: not described - Salinity: not described - TOC: not described - TSS: not described - pH: not described UNEP PUBLICATIONS 56

Result:

Test condition:

OECD SIDS 4. ECOTOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

- Oxygen content: not described - Conductance: not described - Holding water: reconsituted water TEST SYSTEM - Test type: static - Concentrations: geometric series, not known - Dosing rate: not described - Renewal of test solution: no - Exposure vessel type: not described - Number of replicates, fish per replicate: 1, 10 - Test temperature: not described - Dissolved oxygen: not described - pH: not described - Adjustment of pH: not described - Intensity of irradiation: not described - Photoperiod: not described DURATION OF THE TEST: 48 hours TEST PARAMETER: Mortality (3) invalid Documentation insufficient for assessment static Morone saxatilis 96 hour(s) g/l ca. 56000 -

Reliability: 26-SEP-2005 Type: Species: Exposure period: Unit: LC50: Result:

(34)

(Fish, estuary, marine) Analytical monitoring:

Reliability: 26-SEP-2005 Type: Species: Exposure period: Unit: LC50: Limit Test: Method: Year: GLP: Test substance: Method:

RESULTS: EXPOSED - Nominal/measured concentrations: nominal - Effect data (Mortality): 24 hours LC50 : 450 mg/l 48 hours LC50 : 220 mg/l 72 hours LC50 : 110 mg/l - Concentration / response curve: not determined - Effect concentration vs. test substance solubility: not determined - Other effects: not determined RESULTS: CONTROL - Number/percentage of animals showing adverse effects: not determined - Nature of adverse effects: not determined (4) not assignable Reference not available (56) static Gambusia affinis 96 hour(s) mg/l = 120 no (Fish, fresh water) Analytical monitoring: no

other: see freetext 1980 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: 96 hours static test. Test parameters were monitored, but UNEP PUBLICATIONS

57

OECD SIDS 4. ECOTOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

not reported. METHOD OF CALCULATION: LC50, method not described. RESULTS: EXPOSED - Nominal/measured concentrations: nominal - Concentration / response curve: not described - Effect concentration vs. test substance solubility: not described - Other effects: not described TEST ORGANISMS - Strain: - Supplier: Local fish market - Wild caught: no - Age/size/weight/loading: not described/15-18 cm/5-10 gram/50 - 100 gram - Feeding: oil cake - Pretreatment: no - Feeding during test: no DILUTION WATER - Source: obtained from upper lake of Bhopal - Aeration: yes - Alkalinity: 95.0 CaCO3 - Hardness: 84.0 mg CaCO3 - Salinity: not described - TOC: not described - TSS: Total dissolved solids : 160 mg/l - pH: 8.3 - Oxygen content: 7.9 mg/l - Conductance: not described - Holding water: Upper lake of Bhopal TEST SYSTEM - Test type: static - Concentrations: not described - Dosing rate: not described - Renewal of test solution: no - Exposure vessel type: glass 40 liter - Number of replicates, fish per replicate: 2, 10 - Test temperature: 30 degree C - Dissolved oxygen: > 6.0 mg/l - pH: not described - Adjustment of pH: not described - Intensity of irradiation: not described - Photoperiod: not described DURATION OF THE TEST: 96 hours TEST PARAMETER: Mortality (3) invalid Test was performed in natural dilution water with relative high content of dissolved solids and sulfate. Effects of these solids are not known. pH and oxygen concentrations during test were not reported. This is a significant methodological deficiency, which makes documentation insufficient for assessment. (81) static Gambusia affinis (Fish, fresh water) 96 hour(s) mg/l Analytical monitoring: no = 16500 no other: see freetext UNEP PUBLICATIONS 58

Result:

Test condition:

Reliability:

26-SEP-2005 Type: Species: Exposure period: Unit: LC50: Limit Test: Method:

OECD SIDS 4. ECOTOXICITY

Year: GLP: Test substance: Method: 1957 no as prescribed by 1.1 - 1.4

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Result:

Test condition:

Reliability:

METHOD FOLLOWED: Test was run in singlefold with 5 concentrations with turbid natural water (high concentration suspended solids) as test medium. METHOD OF CALCULATION: Median tolerance limit (TLm) was calculated based on dose-effect plot on log-paper. RESULTS: EXPOSED - Nominal/measured concentrations: nominal - Effect data (Mortality): 24 hours LC50 : 24000 mg/l 48 hours LC50 : 17500 mg/l 6 days LC50 : 10000 mg/l - Concentration / response curve: not described - Effect concentration vs. test substance solubility: not described - Other effects: possible adverse effects of high turbidity of test medium TEST ORGANISMS - Wild caught: Stillwater Creek, Oklahoma, USA - Age/size/weight/loading: adult female - Feeding: Plancton/detritus, artificial food - Pretreatment: Tetramycin in holding tanks to prevent tail-rot - Feeding during test: no DILUTION WATER - Source: obtained from local farm ponds - Aeration: artificial aeration - Alkalinity: low < 100 ppm - Hardness: not described - Salinity: not described - TOC: not described - TSS: 650 mg/l (initial) and < 25 mg/l (final) - pH: 7.8 - 8.3 - Oxygen content: not described - Conductance: not described - Holding water: local farm ponds TEST SYSTEM - Test type: static - Concentrations: geometric series between 1000 and 56000 mg/l - Dosing rate: single-fold - Renewal of test solution: no - Exposure vessel type: pyrex cylindrical 15 liter vessel - Number of replicates, fish per replicate: 1, 10 - Test temperature: 22 - 25 degree C - Dissolved oxygen: not described - pH: 7.0 - 8.8 - Adjustment of pH: no - Intensity of irradiation: not described - Photoperiod: not described TEST PARAMETER : Mortality DURATION OF THE TEST: 6 days (3) invalid The dilution water was turbid, which may have influenced the test result. Although sodium sulfate does not adsorb substantially on to soil particles, effects of turbidity can UNEP PUBLICATIONS

59

OECD SIDS 4. ECOTOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

not be excluded. Oxygen concentrations during test are not reported. This means that documentation is insufficient for assessment. (109) static Lepomis macrochirus 96 hour(s) mg/l = 8700 = 13500 no (Fish, fresh water) Analytical monitoring: no

26-SEP-2005 Type: Species: Exposure period: Unit: LC0: LC50: Limit Test: Method: Year: GLP: Test substance: Method:

other: see freetext 1954 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: Test performed in duplicate with five concentrations. Main testparameters determined during test. Defined dilution water used. STATISTICAL METHODS: not described METHOD OF CALCULATION: Median tolerance limit determined using estimation from log dose-response plot. RESULTS: EXPOSED - Nominal/measured concentrations: nominal - Concentration / response curve: not described - Effect concentration vs. test substance solubility: not described - Other effects: not described TEST ORGANISMS - Strain: Raf. - Supplier: private supplier Maryland, USA - Wild caught: no - Age/size/weight/loading: size 5 - 9 cm, weight 1 - 9 gram , on average 2.5 g/l - Feeding: cooked shrimp - Pretreatment: not described - Feeding during test: no DILUTION WATER - Source: reconsituted water (Chu 14 modified) - Aeration: yes - Alkalinity: 36.8 - 37.0 mg/l ppm CaCO3 - Hardness: 37.4 - 40.6 mg/l ppm CaCO3 - Salinity: not described - TOC: not described - TSS: not described - pH: 7.3 - 8.7 - Oxygen content: 4.4 - 8.9 ppm - Conductance: 1.43x10-4 - 1.73x10-4 mhos 20 degree C - Holding water: reconstituted water TEST SYSTEM - Test type: static - Concentrations: 8700, 10000, 11500, 13500, 14000, 14500 mg/l - Dosing rate: singlefold - Renewal of test solution: no - Exposure vessel type: Pyrex jarrs - Number of replicates, fish per replicate: 2, 10 - Test temperature: 19 - 21 degree C UNEP PUBLICATIONS 60

Result:

Test condition:

OECD SIDS 4. ECOTOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

- Dissolved oxygen: 4.4 - 8.9 mg/l - Alkalinity: 44 - 56 mg/l ppm CaCO3 - Hardness: 35 - 62 mg/l ppm CaCO3 - pH: 7.1 - 9.2 - Adjustment of pH: no - Conductance: 60x10-4 -143x10-4 - Intensity of irradiation: not described - Photoperiod: not described DURATION OF THE TEST: 96 hours TEST PARAMETER: Mortality (2) valid with restrictions Although not all test criteria were met, results are reliable for assessment. Study with enough details. Loading is not according to the guidelines, but because of aeration during the test this is not considered as having an impact on the test. The low oxygen content (4.4 mg/l) had no impact on the fish considering the percentage of survival and oxygen content in the replicate. (98) static Lepomis macrochirus 96 hour(s) mg/l = 13500 no (Fish, fresh water) Analytical monitoring: no

Reliability:

26-SEP-2005 Type: Species: Exposure period: Unit: LC50: Limit Test: Method: Year: GLP: Test substance: Method:

other: see freetext, based on Cairns, J. et al, The effects of alkyl benzene sulfonate on aquatic organisms. Industrial Water and Wastes Journal, vol.9, no.1:22-28. 1968 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: static 96 hours test in reconstituted water. STATISTICAL METHODS: not described METHOD OF CALCULATION: not described RESULTS: EXPOSED - Nominal/measured concentrations: nominal - Concentration / response curve: not described - Effect concentration vs. test substance solubility: not described - Other effects: not described - Reference substance: Potassium dichromate, TLm = 113 mg/l TEST ORGANISMS - Strain: not described - Supplier: not described - Wild caught: not described - Age/size/weight/loading: not described - Feeding: not described - Pretreatment: not described - Feeding during test: no DILUTION WATER - Source: reconstituted water - Aeration: yes - Alkalinity: not described - Hardness: not described - Salinity: not described UNEP PUBLICATIONS

Result:

Test condition:

61

OECD SIDS 4. ECOTOXICITY

- TOC: not described - TSS: not described - pH: not described - Oxygen content: 5 - 9 ppm - Conductance: not described - Holding water: reconsituted water TEST SYSTEM

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Reliability:

26-SEP-2005 Type: Species: Exposure period: Unit: LC50: Result:

- Test type: static - Concentrations: geometric series, not known - Dosing rate: not described - Renewal of test solution: no - Exposure vessel type: 18 liter vessels - Number of replicates, fish per replicate: not described - Test temperature: 16 - 20 degree C - Dissolved oxygen: 5 - 9 ppm - pH: not described - Adjustment of pH:not described - Intensity of irradiation: not described - Photoperiod: not described DURATION OF THE TEST: 96 hours TEST PARAMETER: Mortality (2) valid with restrictions When the result of Potassium dichromate (96 h, LC50) used as a reference substance, is compared with the result from another study (96 h, LC50 183 mg/l, Brachydanio rerio), it can be seen that it is in the same order of magnitude. This means that the result supports the accuracy of the result of the test substance, sodium sulfate. This study would be considered as validity 3 because of the shortcomings. However, based on the other data, Sodium sulfate is a substance of very low toxicity and the results of this study confirm this, therefore this study is evaluated as valid with restrictions. (80) static Morone saxatilis 96 hour(s) g/l ca. 81000 (Fish, estuary, marine) Analytical monitoring:

Reliability: 26-SEP-2005

RESULTS: EXPOSED - Nominal/measured concentrations: - Effect data (Mortality): 24 hours LC50 : 650 mg/l 48 hours LC50 : 320 mg/l 72 hours LC50 : 160 mg/l - Concentration / response curve: - Effect concentration vs. test substance solubility: - Other effects: RESULTS: CONTROL - Number/percentage of animals showing adverse effects: - Nature of adverse effects: RESULTS: TEST WITH REFERENCE SUBSTANCE - Concentrations: - Results: (4) not assignable Reference not available (56) UNEP PUBLICATIONS 62

OECD SIDS 4. ECOTOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

static Morone saxatilis 96 hour(s) g/l ca. 790000 -

Type: Species: Exposure period: Unit: LC50: Result:

(Fish, estuary, marine) Analytical monitoring:

Reliability: 26-SEP-2005 Type: Species: Exposure period: Unit: LC50: Result:

RESULTS: EXPOSED - Nominal/measured concentrations: - Effect data (Mortality): 24 hours LC50 : 790 mg/l 48 hours LC50 : 790 mg/l 72 hours LC50 : 790 mg/l - Concentration / response curve: - Effect concentration vs. test substance solubility: - Other effects: RESULTS: CONTROL - Number/percentage of animals showing adverse effects: - Nature of adverse effects: RESULTS: TEST WITH REFERENCE SUBSTANCE - Concentrations: - Results: (4) not assignable Reference not available static Morone saxatilis 96 hour(s) g/l ca. 1100000 -

(56)

(Fish, estuary, marine) Analytical monitoring:

Reliability: 26-SEP-2005 Type: Species: Exposure period: Unit: LC50: Limit Test: Method: 63

RESULTS: EXPOSED - Nominal/measured concentrations: - Effect data (Mortality): 24 hours LC50 : 1100 mg/l 48 hours LC50 : 1100 mg/l 72 hours LC50 : 1100 mg/l - Concentration / response curve: - Effect concentration vs. test substance solubility: - Other effects: RESULTS: CONTROL - Number/percentage of animals showing adverse effects: - Nature of adverse effects: RESULTS: TEST WITH REFERENCE SUBSTANCE - Concentrations: - Results: (4) not assignable Reference not available static Pimephales promelas 96 hour(s) mg/l = 7960 no

(56)

(Fish, fresh water) Analytical monitoring: yes

other: see freetext, based on EPA/600/4-90/027 (1991) UNEP PUBLICATIONS

OECD SIDS 4. ECOTOXICITY

Year: GLP: Test substance: Method: 1997 no as prescribed by 1.1 - 1.4

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Result:

Test condition:

METHOD FOLLOWED: 96-hours static test in reconstituted water. STATISTICAL METHODS: logistic multiple regression METHOD OF CALCULATION: Probability regression model. measured values used for calculation whenever concentration was < 80% of initial concentration. ANALYTICAL METHODS: anion analyses by ion-chromatograpy RESULTS: EXPOSED - Nominal/measured concentrations: both - Effect data (Mortality): 24-hours LC50 : > 8080 mg/l 48 hours LC50 : > 7960 mg/l - Concentration / response curve: yes - Effect concentration vs. test substance solubility: no - Other effects: Not described RESULTS: CONTROL - Number/percentage of animals showing adverse effects: Not described - Nature of adverse effects: Not described TEST ORGANISMS - Strain: not described - Supplier: ENSR, Fort Collins, CO, USA, in-house culture - Wild caught: no - Age/size/weight/loading: according to EPA, 1 to 7 days old - Feeding: yes, brine shrimp nauplii - Pretreatment: no - Feeding during test: yes, after 48 hours 100 microliter concentrated brine shrimp nauplii. DILUTION WATER - Source: reconstituted - Aeration: yes - Alkalinity: moderately - Hardness: not described - Salinity: not described - TOC: not described - TSS: not described - pH: 7.5 - 9.0 - Oxygen content: > 40% saturation - Conductance: not described - Holding water: tap water (purified by activated carbon) TEST SYSTEM - Test type: static - Concentrations: 4 concentrations with dilution factor 0.5 - Dosing rate: single-fold - Renewal of test solution: no - Exposure vessel type: plastic beakers 30 ml with 10 ml of water - Number of replicates, fish per replicate: 3-5, 5 - Test temperature: 25 degree C - Dissolved oxygen: > 40% saturation - pH: 7.5 - 9 - Adjustment of pH: no - Intensity of irradiation: not described - Photoperiod: not described DURATION OF THE TEST: 96 hours TEST PARAMETER: mortality SAMPLING: no UNEP PUBLICATIONS 64

OECD SIDS 4. ECOTOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

MONITORING OF TEST SUBSTANCE CONCENTRATION: yes (2) valid with restrictions Test performed according to standardized EPA guideline for testing of effluents, with determination of test concentrations. Test parameters pH and oxygen measured but not all reported. No information about survival in controls. Replicate test performance. Critical study for SIDS endpoint (71) static other: Morone saxatilis (striped bass, fingerlings) 96 hour(s) mg/l Analytical monitoring: = 3500 other TS:Na2SO4 tech. grade (4) not assignable Reference not available static other: Morone saxatilis ,striped bass, larvea 96 hour(s) mg/l Analytical monitoring: = 250 other TS:Na2SO4 tech. grade (4) not assignable Reference not available (56) Cyprinus carpio 24 hour(s) mg/l = 15000 (Fish, fresh water) Analytical monitoring:

Reliability:

Flag: 26-SEP-2005 Type: Species: Exposure period: Unit: LC50: Test substance: Reliability: 26-SEP-2005 Type: Species: Exposure period: Unit: LC50: Test substance: Reliability: 26-SEP-2005 Species: Exposure period: Unit: LC0: Reliability: 26-SEP-2005 Species: Exposure period: Unit: LC50: Reliability: 26-SEP-2005 Species: Exposure period: Unit: LC50: Reliability: 65

(56)

(4) not assignable Reference not available (65) Gambusia affinis 48 hour(s) mg/l = 17500 (Fish, fresh water) Analytical monitoring:

(4) not assignable Reference not available Lepomis gibbosus 96 hour(s) mg/l = 13500 (4) (Fish, fresh water) Analytical monitoring:

(36)

not assignable UNEP PUBLICATIONS

OECD SIDS 4. ECOTOXICITY

Reference not available 13-JUN-2003 Species: Exposure period: Unit: LC50: Limit Test: Method: Year: GLP: Test substance: Method: Lepomis macrochirus 24 hour(s) mg/l = 17500 no (Fish, fresh water)

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(83)

Analytical monitoring: no

other: see freetext, method based on Freeman, L. "A standardized method for determining toxicity of pure compounds to fish", Sewage and Industrial wastes, 25, 7, 845 (1953) 1965 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: 96 hours static test. Test parameters were monitored, but not reported. METHOD OF CALCULATION: not described Median Tolerance Limit (TLm), not reported. Only a 24 hours TLm was determined. RESULTS: EXPOSED - Nominal/measured concentrations: nominal - Effect data (Mortality): - Concentration / response curve: not described - Effect concentration vs. test substance solubility: not described - Other effects: not described TEST ORGANISMS - Strain: not described - Supplier: Local pet shop - Wild caught: no - Age/size/weight/loading: not described - Feeding: not described - Pretreatment: not described - Feeding during test: no DILUTION WATER - Source: reconstituted water - Aeration: yes - Alkalinity: not described - Hardness: not described - Salinity: not described - TOC: not described - TSS: not described - pH: not described - Oxygen content: not described - Conductance: not described - Holding water: reconsituted water TEST SYSTEM - Test type: static - Concentrations: geometric series, not known - Dosing rate: not described - Renewal of test solution: no - Exposure vessel type: not described - Number of replicates, fish per replicate: 1, 10 - Test temperature: not described - Dissolved oxygen: not described - pH: not described - Adjustment of pH: not described - Intensity of irradiation: not described UNEP PUBLICATIONS 66

Result:

Test condition:

OECD SIDS 4. ECOTOXICITY

- Photoperiod: not described DURATION OF THE TEST: 96 hours TEST PARAMETER: Mortality (3) invalid Documentation insufficient for assessment Pimephales promelas 96 hour(s) mg/l ca. 13500 - 14500 (Fish, fresh water) Analytical monitoring:

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Reliability: 26-SEP-2005 Species: Exposure period: Unit: LC50: Reliability: 26-SEP-2005 Species: Exposure period: Unit: LC100: Result:

(34)

(4) not assignable Reference not available Salmo gairdneri 48 hour(s) mg/l = 7000 (Fish, estuary, fresh water) Analytical monitoring:

(36)

Reliability: 26-SEP-2005 Species: Exposure period: Unit: LC0: Reliability: 26-SEP-2005 Species: Exposure period: Unit: MLc : Reliability: 26-SEP-2005

RESULTS: EXPOSED - Nominal/measured concentrations: 24 hours: LC50 705 mg/l - Effect data (Mortality): - Concentration / response curve: - Effect concentration vs. test substance solubility: - Other effects: RESULTS: CONTROL - Number/percentage of animals showing adverse effects: - Nature of adverse effects: RESULTS: TEST WITH REFERENCE SUBSTANCE - Concentrations: - Results: (4) not assignable Reference not available (65) other: Cyprinus carpio 24 hour(s) mg/l Analytical monitoring: < 2000 (4) not assignable Reference not translated (99) other: Notropis spilopterus 120 hour(s) mg/l Analytical monitoring: = 100 (4) not assignable Reference not available (105)

67

UNEP PUBLICATIONS

OECD SIDS 4. ECOTOXICITY

4.2 Acute Toxicity to Aquatic Invertebrates Type: Species: Exposure period: Unit: EC50: Limit Test: Method: Year: GLP: Test substance: Method: static Daphnia magna 48 hour(s) mg/l = 9124 no (Crustacea)

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Analytical monitoring: no

other: see freetext 1995 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: 48-hours static test in reconstituted water. STATISTICAL METHODS: not described METHOD OF CALCULATION: not described ANALYTICAL METHODS: no RESULTS: EXPOSED - Nominal/measured concentrations: nominal - Effect data (Immobilisation): not described - Concentration / response curve: not described - Cumulative immobilisation: not described - Effect concentration vs. test substance solubility: not described - Other effects: not described TEST ORGANISMS - Breeding method: in-house in reconsituted water - Age: < 24 hours - Feeding: no - Pretreatment: not described - Feeding during test: no - Control group: yes DILUTION WATER - Source: reconstituted water - Aeration: not described - Alkalinity: not described - Hardness: not described - Salinity: not described - TOC: not described - Ca/Mg ratio: not described - Na/K ratio: not described - TSS: not described - pH: not described - Oxygen content: not described - Conductance: not described - Holding water: reconstituted water TEST SYSTEM - Test type: semi-static - Concentrations: not described - Renewal of test solution: yes - Exposure vessel type: 100 ml solution - Number of replicates, individuals per replicate: 2, 10 - Test temperature: 20 degree C Dissolved oxygen: not described pH: not described Adjustment of pH: not described Intensity of irradiation: not described Photoperiod: dark UNEP PUBLICATIONS 68

Result:

Test condition:

OECD SIDS 4. ECOTOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

DURATION OF THE TEST: 48 hours TEST PARAMETER: immobility SAMPLING: no MONITORING OF TEST SUBSTANCE CONCENTRATION: no (3) invalid documentation was insufficient for assessment (8) static Daphnia magna 48 hour(s) mg/l = 2564 no (Crustacea) Analytical monitoring: no

Reliability: 26-SEP-2005 Type: Species: Exposure period: Unit: EC50: Limit Test: Method:

Year: GLP: Test substance: Method:

other: see freetext, based on Anderson, B.G. et al. The evaluation of aquatic invertebrates as assay organisms for the determination of the toxicity of industrial wastes. Report of the Ohio State University (1948) 1965 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: 48 - 96 hours static test. Test parameters were monitored, but not reported. METHOD OF CALCULATION: not described Median Tolerance Limit (TLm), not reported. RESULTS: EXPOSED - Nominal/measured concentrations: nominal - Effect data (Immobilisation): 24 hours EC50 : 8384 mg/l 72 hours EC50 : 725 mg/l 96 hours EC50 : 630 mg/l - Concentration / response curve: not described - Cumulative immobilisation: not described - Effect concentration vs. test substance solubility: not described - Other effects: not described TEST ORGANISMS - Strain: not described - Source/supplier: Put-In Bay, Ohio, USA - Breeding method: In-house, not described - Age: not defined, but designated as a) young, b) adult. - Feeding: not described - Pretreatment: not described - Feeding during test: no - Control group: not described (3) invalid Documentation insufficient for assessment (34) static Daphnia magna 48 hour(s) mg/l = 4580 no (Crustacea) Analytical monitoring: yes

Result:

Test condition:

Reliability: 26-SEP-2005 Type: Species: Exposure period: Unit: EC50: Limit Test: Method: 69

other: see freetext, based on EPA/600/4-90/027 (1991) UNEP PUBLICATIONS

OECD SIDS 4. ECOTOXICITY

guideline 1997 no as prescribed by 1.1 - 1.4

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Year: GLP: Test substance: Method:

Result:

Test condition:

METHOD FOLLOWED: 48-hours static test in reconstituted water. STATISTICAL METHODS: logistic multiple regression METHOD OF CALCULATION: Probability regression model. Measured values used for calculation whenever concentration was < 80% of initial concentration. ANALYTICAL METHODS: anion analyses by ion-chromatograpy RESULTS: EXPOSED - Nominal/measured concentrations: both - Effect data (Immobilisation): 24 hours EC50 : 6290 mg/l - Concentration / response curve: yes - Cumulative immobilisation: not described - Effect concentration vs. test substance solubility: not described - Other effects: not described TEST ORGANISMS - Strain: not described - Source/supplier: ENSR, Fort Collins, CO, USA - Breeding method: in-house in reconsituted water at 20 degree C - Age: < 24 hours - Feeding: yeast/cerophyl/trout chow (YCT) - Pretreatment: no - Feeding during test: yes, 100 microliter concentrated algae/ YCT 1:1 mixture at start test - Control group: yes DILUTION WATER - Source: reconstituted hard water (EPA) - Aeration: yes - Alkalinity: not described - Hardness: not described - Salinity: not described - TOC: not described - Ca/Mg ratio: not described - Na/K ratio: not described - TSS: not described - pH: 7.5 - 9.0 - Oxygen content: > 40% of saturation value - Conductance: not described - Holding water: reconstituted water (hard, EPA) TEST SYSTEM - Test type: static - Concentrations: 4 concentrations in geometric series with factor 0.5 - Renewal of test solution: no - Exposure vessel type: plastic vessels 30 ml with 10 ml dilution water. - Number of replicates, individuals per replicate: 3-5, 5 - Test temperature: 20 degree C - Dissolved oxygen: > 40% saturation - pH: 7.5 - 9.0 - Adjustment of pH: no - Intensity of irradiation: not described - Photoperiod: 16:8 hour light-dark DURATION OF THE TEST: 48 hours UNEP PUBLICATIONS 70

OECD SIDS 4. ECOTOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

TEST PARAMETER: immobility SAMPLING: no MONITORING OF TEST SUBSTANCE CONCENTRATION: yes (2) valid with restrictions Test performed according to standardized EPA guideline for testing of effluents, with determination of test concentrations. Test parameters pH and oxygen measured but not all reported. No information about controls. Replicate test performance. Critical study for SIDS endpoint (71) static Daphnia magna 96 hour(s) mg/l = 4547 no (Crustacea) Analytical monitoring: no

Reliability:

Flag: 26-SEP-2005 Type: Species: Exposure period: Unit: EC50: Limit Test: Method: Year: GLP: Test substance: Method:

other:see freetext 1953 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: A 100 hours static test with 9 concentrations in three-fold. STATISTICAL METHODS: not described METHOD OF CALCULATION: Toxicity Threshhold, defined by Anderson et al., Report by Ohio State Univ. Research Found. To Amer. Petrol. Inst., New York, N.Y. (1948). Toxicity Threshold is comparable with LC50 value. ANALYTICAL METHODS: not described RESULTS: EXPOSED - Nominal/measured concentrations: nominal - Effect data (Immobilisation): - Concentration / response curve: not described - Cumulative immobilisation: not described - Effect concentration vs. test substance solubility: not described - Other effects: not described TEST ORGANISMS - Strain: not described - Source/supplier: West Virginia University, USA - Breeding method: in-house - Age: < 12 hours - Feeding: yeast - Pretreatment: not described - Feeding during test: no - Control group: yes DILUTION WATER - Source: reconstituted water - Aeration: not described - Alkalinity: not described - Hardness: not described - Salinity: not described - TOC: not described - Ca/Mg ratio: not described - Na/K ratio: not described - TSS: not described - pH: not described - Oxygen content: not described UNEP PUBLICATIONS

Result:

Test condition:

71

OECD SIDS 4. ECOTOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

- Conductance: not described - Holding water: reconsituted water TEST SYSTEM - Test type: static - Concentrations: 9 concentrations, not defined - Renewal of test solution: no - Exposure vessel type: pyrex vessels, 100 ml - Number of replicates, individuals per replicate: 3, 10 - Test temperature: 22 - 24 degree C - Dissolved oxygen: not described - pH: < 7.7 - Adjustment of pH: not described - Intensity of irradiation: not described - Photoperiod: not described DURATION OF THE TEST: 100 hours TEST PARAMETER: Immobility (3) invalid Documentation insufficient for assessment (36) static Daphnia magna 48 hour(s) mg/l = 2564 (Crustacea) Analytical monitoring:

Reliability: 26-SEP-2005 Type: Species: Exposure period: Unit: EC50: Result:

Reliability: 26-SEP-2005 Type: Species: Exposure period: Unit: EC100: Reliability: 26-SEP-2005

RESULTS: EXPOSED - Nominal/measured concentrations: - Effect data (Immobilisation): 24 hours EC50 : 8384 mg/l - Concentration / response curve: - Cumulative immobilisation: - Effect concentration vs. test substance solubility: - Other effects: RESULTS CONTROL: RESULTS: TEST WITH REFERENCE SUBSTANCE - Concentrations: - Results: (4) not assignable Reference not available static Daphnia magna 48 hour(s) mg/l = 5200 -

(33)

(Crustacea) Analytical monitoring:

(4) not assignable Reference not available

(65)

4.3 Toxicity to Aquatic Plants e.g. Algae Species: Exposure period: Unit: EC100 : Chlorella pyrenoidosa 8 day(s) mg/l = 57700 (Algae) Analytical monitoring:

UNEP PUBLICATIONS

72

OECD SIDS 4. ECOTOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

other (4) not assignable Reference not translated other algae: Nitzschia linearis 120 hour(s) mg/l Analytical monitoring: no = 1900 no other: see freetext, based on Cairns J. et al. Industrial water and Wastes Journal. 9 (1), 22-28 (1964). 1968 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: a static 120 hours test in defined test medium. STATISTICAL METHODS: not described METHOD OF CALCULATION: Median tolerance limit (TLm) method not defined. RESULTS: EXPOSED - Nominal/measured concentrations: nominal - Effect data/Element values: growth (cell counts) - Cell density data: not described - Growth curves: not described - Reference substance: Potassium dichromate, TLm = 0.208 mg/l TEST ORGANISMS - Strain: W.Sm. - Source/supplier: not described - Laboratory culture: not described - Method of cultivation: not described - Pretreatment: no - Controls: yes - Initial cell concentration: not described DILUTION WATER - Source: reconstituted water - Aeration: not described TEST SYSTEM - Test type: static - Concentrations: geometric series - Renewal of test solution: no - Exposure vessel type: 150 ml glass - Number of replicates: not described - Concentrations: not described - Test temperature: 16 - 22 degree C - pH: not described - Intensity of irradiation: not described - Photoperiod: not described TEST PARAMETER: growth (2) valid with restrictions In this test a different algae species is used than recommended in the OECD-guidelines. When the results of Potassium dichromate (72 h, EbC50) used as a reference substance, are compared with the results given in the EC-directive 92/69/EEC (mean 0.53 mg/l, range 0.20 - 0.75 mg/l) the sensitivity of Nitzschia linearis is not UNEP PUBLICATIONS

Method: Reliability: 26-SEP-2005 Species: Exposure period: Unit: EC50: Limit Test: Method: Year: GLP: Test substance: Method:

(77)

Result:

Test condition:

Reliability:

73

OECD SIDS 4. ECOTOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

significantly different from that of Selenastrum capricornutum or Scenedesmus subspicatus. It is recognised that the duration of this study was greater than the recommended OECD study time but as the reference result from this study is on the lower boundary of the EC recommendation, the two results are considered comparable. This study would be considered as validity 3 because of the shortcomings. However, based on the other data, Sodium sulfate is a substance of very low toxicity and the results of this study confirm this, therefore this study is evaluated as valid with restrictions (2). Critical study for SIDS endpoint (80)

Flag: 26-SEP-2005 Species:

other aquatic plant: Myrophilium spicatum (Eurasian watermilfoil) Endpoint: other: root weight Exposure period: 32 day(s) Unit: mg/l Analytical monitoring: no EC50: = 10228 EC50 shoot length : = 4120 EC50 shoot weight : = 9376 EC50 root length : = 10370 Limit Test: no Method: Year: GLP: Test substance: Method: other: see freetext 1974 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: A 32 days test with plants cultivated in liquid/soil medium under continuous illumination. STATISTICAL METHODS: not described METHOD OF CALCULATION: root weight and shoot length, quotient of effect of test substance added in soil fraction and effect of test substance added to water phase, corrected for control effect ANALYTICAL METHODS: not described RESULTS: EXPOSED - Nominal/measured concentrations: nominal - Effect data/Element values: not described - Cell density data: not described - Growth curves: yes TEST ORGANISMS - Strain: L. - Source/supplier: Clone from Friesland, The Netherlands - Laboratory culture: yes - Method of cultivation: cultivated in greenhouse in woods earth/ferric silicate/tap water mixture - Pretreatment: CuSO4 to reduce algae growth - Controls: yes - Initial cell concentration: not described DILUTION WATER - Source: Tap water - Aeration: no UNEP PUBLICATIONS 74

Result:

Test condition:

OECD SIDS 4. ECOTOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

GROWTH/TEST MEDIUM CHEMISTRY - Alkalinity: not described - Hardness: not described - Salinity: not described - TOC: not described - EDTA: not described - TSS: not described - pH: not described - Dissolved oxygen: not described TEST SYSTEM - Test type: static - Concentrations: not described - Renewal of test solution: not described - Exposure vessel type: flatt-bottom tubes 200 ml - Number of replicates: 10 - Concentrations: not described - Test temperature: 20 degree C - pH: not described - Intensity of irradiation: 300 fc - Photoperiod: continuous TEST PARAMETER: root weight and shoot length (3) invalid Non-standardized test method, and insufficient documentation (92)

Reliability: 26-SEP-2005

4.4 Toxicity to Microorganisms e.g. Bacteria Type: Species: Exposure period: Unit: NOEC: Method: Year: GLP: Test substance: Test condition: aquatic activated sludge 37 day(s) g/l ca. 26 -

Analytical monitoring:

other: see freetext 1986 no as prescribed by 1.1 - 1.4 TEST ORGANISMS - Bacteria in activated sludge - Supplier: obtained from a local municipal wastewater treatment plant. - Pretreatment: acclimated for a period of over a month. - Substrate: synthetic substrate TEST SYSTEM - Concentrations: concentrations were increased from 8 to 35 g/l over a time period of 37 days. Concentration steps were 2 - 5 g/l. - Exposure vessel: 10 l reactor of which 8 l were aeration chamber and 2 l settling basin. - Analyses: BOD, COD, TSS etc. analyses were done according to APHA standard methods. - Dissolved oxygen: 6 - 8 mg/l - Temperature: 18.5 - 22.5 degree C (2) valid with restrictions Although it is not a standard test and not all test parameters were reported, the results are reliable for assessment. Study with enough details. (95) (96) UNEP PUBLICATIONS

Reliability:

26-SEP-2005 75

OECD SIDS 4. ECOTOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

aquatic activated sludge 37 day(s) g/l ca. 26 -

Type: Species: Exposure period: Unit: NOEC: Method: Year: GLP: Test substance: Test condition:

Analytical monitoring:

other: see freetext 1986 no as prescribed by 1.1 - 1.4 TEST ORGANISMS - Motile protozoa in activated sludge - Supplier: obtained from a local municipal wastewater treatment plant. - Pretreatment: acclimated for a period of over a month. - Substrate: synthetic substrate TEST SYSTEM - Concentrations: concentrations were increased from 8 to 35 g/l over a time period of 37 days. Concentration steps were 2 - 5 g/l. - Exposure vessel: 10 l reactor of which 8 l were aeration chamber and 2 l settling basin. - Analyses: BOD, COD, TSS etc. analyses were done according to APHA standard methods. - Dissolved oxygen: 6 - 8 mg/l - Temperature: 18.5 - 22.5 degree C (2) valid with restrictions Although it is not a standard test and not all test parameters were reported, the results are reliable for assessment. Study with enough details. (95) (96) aquatic activated sludge 37 day(s) g/l ca. 8 -

Reliability:

26-SEP-2005 Type: Species: Exposure period: Unit: NOEC: Method: Year: GLP: Test substance: Test condition:

Analytical monitoring:

other: see freetext 1986 no as prescribed by 1.1 - 1.4 TEST ORGANISMS - Stalked ciliates in activated sludge - Supplier: obtained from a local municipal wastewater treatment plant. - Pretreatment: acclimated for a period of over a month. - Substrate: synthetic substrate TEST SYSTEM - Concentrations: concentrations were increased from 8 to 35 g/l over a time period of 37 days. Concentration steps were 2 - 5 g/l. - Exposure vessel: 10 l reactor of which 8 l were aeration chamber and 2 l settling basin. - Analyses: BOD, COD, TSS etc. analyses were done according to APHA standard methods. - Dissolved oxygen: 6 - 8 mg/l - Temperature: 18.5 - 22.5 degree C UNEP PUBLICATIONS 76

OECD SIDS 4. ECOTOXICITY

Reliability:

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(2) valid with restrictions Although it is not a standard test and not all test parameters were reported, the results are reliable for assessment. Study with enough details. (95) (96) aquatic activated sludge 40 day(s) g/l ca. 30 -

26-SEP-2005 Type: Species: Exposure period: Unit: NOEC: Method: Year: GLP: Test substance: Test condition:

Analytical monitoring:

other: see freetext 1980 no as prescribed by 1.1 - 1.4 TEST ORGANISMS - Activated sludge - Supplier: not described - Pretreatment: not described - Substrate: not described TEST SYSTEM - Concentrations: concentrations were increased from 10 to 40 g/l over a time period of ca. 40 days. Concentration steps were 10 g/l. - Exposure vessel: 10 l - Analyses: effluent analyses were done according to APHA standard methods. - pH: 7 - 7.5 - Temperature: 20 - 23 degree C - Dissolved oxygen: 2.3 - 3.5 mg/l (2) valid with restrictions Although it is not a standard test and not all test parameters were reported, the results are reliable for assessment. Study with enough details. (40) aquatic Pseudomonas fluorescens (Bacteria) 24 hour(s) mg/l Analytical monitoring: = 10000 other: Bestimmung der biologichen Schadwirkung toxischer Abwaesser gegen Bakterien. DEV, L8 (1968) modifiziert (4) not assignable Reference not available (14) aquatic Pseudomonas putida 16 hour(s) mg/l > 1000 (Bacteria) Analytical monitoring:

Reliability:

26-SEP-2005 Type: Species: Exposure period: Unit: EC0: Method: Reliability: 13-JUN-2003 Type: Species: Exposure period: Unit: EC10: Method: Reliability:

other: DIN 38412 Teil 8 (4) not assignable Reference not available UNEP PUBLICATIONS

77

OECD SIDS 4. ECOTOXICITY

26-SEP-2005 4.5 Chronic Toxicity to Aquatic Organisms 4.5.1 Chronic Toxicity to Fish 4.5.2 Chronic Toxicity to Aquatic Invertebrates TERRESTRIAL ORGANISMS 4.6.1 Toxicity to Sediment Dwelling Organisms Species: Endpoint: Expos. period: Unit: LC50: Result: other: Lymnaea (Pond snail) Mortality 96 other: hours other: mg/l = 1151 -

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(55)

Reliability: 26-SEP-2005 Species: Endpoint: Expos. period: Unit: LC50: Result:

RESULTS: EXPOSED - Nominal/measured concentrations: - Effect data (Immobilisation): 24 hours LC50 : 1750 mg/l 48 hours LC50 : 1750 mg/l 72 hours LC50 : 1750 mg/l - Concentration / response curve: - Cumulative immobilisation: - Effect concentration vs. test substance solubility: - Other effects: RESULTS CONTROL: RESULTS: TEST WITH REFERENCE SUBSTANCE - Concentrations: - Results: (4) not assignable Reference not available (33) other: Lymnaea (Pond snail) Mortality 96 other: hours other: mg/l = 799 RESULTS: EXPOSED - Nominal/measured concentrations: - Effect data (Immobilisation): 24 hours LC50 : 1215 mg/l 48 hours LC50 : 1215 mg/l 72 hours LC50 : 1215 mg/l - Concentration / response curve: - Cumulative immobilisation: - Effect concentration vs. test substance solubility: - Other effects: RESULTS CONTROL: RESULTS: TEST WITH REFERENCE SUBSTANCE - Concentrations: - Results: (4) not assignable UNEP PUBLICATIONS 78

Reliability:

OECD SIDS 4. ECOTOXICITY

Reference not available 26-SEP-2005 Species: Endpoint: Expos. period: Unit: LC50: Reliability: 26-SEP-2005 Species: Endpoint: Expos. period: Unit: LC50: Result: other: Lymneae sp. (eggs) Mortality 96 other: hour(s) other: mg/l = 3553 other: Ophryotrocha labronica (Polychaete) Mortality 20 other: hours other: mg/l = 5.4 (4) not assignable Reference not available

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(33)

(85)

Reliability: 26-SEP-2005 Species: Endpoint: Expos. period: Unit: LC50: Method: Year: GLP: Test substance: Method:

RESULTS: EXPOSED - Nominal/measured concentrations: - Effect data (Immobilisation): 24 hours LC50 : 5401 mg/l 48 hours LC50 : 5400 mg/l 72 hours LC50 : 5400 mg/l - Concentration / response curve: - Cumulative immobilisation: - Effect concentration vs. test substance solubility: - Other effects: RESULTS CONTROL: RESULTS: TEST WITH REFERENCE SUBSTANCE - Concentrations: - Results: (3) invalid Documentation insufficient for assessment (34) other: Trycorythus sp. Mortality 96 other: hours other: g/l = .66 other: see freetext 1996 no data as prescribed by 1.1 - 1.4 METHOD FOLLOWED: 96-hours acute semi static test in river water. STATISTICAL METHODS: one-way ANOVA METHOD OF CALCULATION: probit analysis ANALYTICAL METHODS: nutrient concentrations by spectrophotometer Full chemical analyses by ICP-ES, AAS and autoanalyzer RESULTS: EXPOSED - Nominal/measured concentrations: nominal - Effect data (Immobilisation): 96 hours LC50 : 0.66 g/l UNEP PUBLICATIONS

Result:

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SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

NB. The probit analysis could not be used since there was no normal distribution of concentration response data. - Concentration / response curve: no - Cumulative immobilisation: yes - Effect concentration vs. test substance solubility: not described - Other effects: not described TEST ORGANISMS - Source/supplier: Sabie river, Kruger national park, South Africa - Pretreatment: 25 individuals were acclimated unfed per raceway for 36 h. All dead animals were removed and numbers were equalized between the raceways, before addition of salt solutions. - Feeding during test: no - Control group: yes DILUTION WATER - Source: Sabie river water - Salinity: not described - TOC: not described - Ca/Mg ratio: not described - Na/K ratio: not described - TSS: not described - pH: not described Conductance: not described - Holding water: Sabie river water TEST SYSTEM - Test type: semi static - Concentrations: 4 concentrations, 0.20, 0.66, 1.46 and 4.40 g/l. - Renewal of test solution: yes, 20% of the water was replaced daily. - Exposure vessel type: 12.5 l perspex experimental stream system; raceways. Four kaolinite stones were placed in the channel to serve as a substrate. - Number of replicates, individuals per replicate: 3, not known - Current: 0.75 or 1 m/s - Test temperature: 9-16 degree C - Dissolved oxygen: 65.0-105.0% saturation - pH: 6.93-7.20 - Adjustment of pH: no - Aeration: no - Alkalinity: 62-101 mg/l - Hardness: approx. 69.4 mg/l - Intensity of irradiation: not described - Photoperiod: 12:12 hour light-dark DURATION OF THE TEST: 96 hours TEST PARAMETER: immobility (2) valid with restrictions No standard test, but test with a lot of detailed information. The test results did not give a normal dose respons curve. Critical study for SIDS endpoint (42)

Test condition:

Reliability:

Flag: 26-SEP-2005

4.6.2 Toxicity to Terrestrial Plants Species: Endpoint: other terrestrial plant: Capsicum annuum L. other: Number and size of fruit UNEP PUBLICATIONS 80

OECD SIDS 4. ECOTOXICITY

Expos. period: Method: Year: GLP: Test substance: Method: 4 month other: see freetext 2000 no data as prescribed by 1.1 - 1.4

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Result:

Test condition:

Reliability:

26-SEP-2005 Species: Endpoint: Expos. period: Method: Year: GLP: Test substance: Method:

METHOD FOLLOWED A 4 months test in a greenhouse. - Endpoints: Fruit was collected at ripening (at the red stage) and weight, total number and yield were recorded. STATISTICAL METHOD Data were statistically analysed by ANOVA. RESULTS - Effect data: Fruit number: Increased with concentration Fruit size: decreased with concentration Yield: decreased with concentration Fructose, glucose and amino acids significantly decreased with higher concentrations. The pulp thickness became less with increasing concentration. TEST SPECIES - Capsicum annuum L. - Source: not known - pretreatment: No - Substrate: Hoagland nutrient solution TEST SYSTEM - Concentrations: 2 (control), 3, 4, 6 and 8 dS/m solution (this is 0, 6.1, 12.2, 24.1 and 36.7 mM Sodium sulfate) in Hoagland nutrient solution. - Test vessel: 120 l container - Number of plants per replicate: 1 - Replicates: 5 - Temperature: 18-35 degree Celsius - Relative humidity: 55-75% - pH: 5.5-6.0 - Photoperiod: not known - Watering: daily addition of deionized water - Solutions were analysed weekly and readjusted to initial nutrient concentrations (3) invalid No standard method. The method is described in detail but the results are not in much detailed. It is not clear at what concentration a significant decrease or increase occurs. (72) other terrestrial plant: Picea glauca other: emergence, survival, shoot and root length, number of lateral roots, leaf necrosis, fresh weight and photosynthesis 42 day(s) other: see freetext 2000 no data as prescribed by 1.1 - 1.4 METHOD FOLLOWED A six weeks test in sand. - Endpoints: Percentage emergence was noted daily. After six UNEP PUBLICATIONS

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SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

weeks survival, leaf necrosis, shoot and root length, number of lateral roots, fresh weight and photosynthesis were recorded. Photosynthesis was determined spectrophotometrically from methanol extract and calculated using MacKinney equation. STATISTICAL METHOD - Emergence data was analyzed using a general linear model (GLM) repeated measure technique. - Growth data were analyzed with a glm using one-way ANOVA. - The means were compared using Duncan's multiple range test. RESULTS - Effect data: Emergence: percentage germination was significantly less in 20 mM and higher Survival: significant decrease at 50 mM and higher Root length: significant reduction in length from 20 mM and higher Number of lateral roots: significant decrease from 50 mM and higher Leaf necrosis: significant necrosis in 50 mM and higher Fresh weight: reduction in 50 mM and higher Photosynthesis: Chlorophyll content did not change compared to the control TEST SPECIES - Picea glauca - Source: Pine Ridge Nursery, Alberta, Canada (seedlot DL 68-12-4-83) - pretreatment: No - Substrate: quartz-feldspar sand (particle size range 0.19-3 mm) TEST SYSTEM - Concentrations: 0, 10, 20, 50, 100 and 250 mM solution in deionized water. - Test vessel: 4 l germination trays. - Number of seeds per replicate: 40 - Replicates: 5 trays per concentration. - Moisture content of sand: 13% - Thermoperiod: 20/15 degree Celsius - Photoperiod: 18 hours - High humidity was obtained by covering the trays with transparant plastic lids - After two weeks the lids were removed - Watering: Every other day after removing the lids, 500 ml of deionized water was sprayed over the sand. Every seven days 50 ml of Hoagland's mineral solution was sprayed on the sand. (2) valid with restrictions No standard method, but study with enough details. (28) other terrestrial plant: Pinus banksiana other: emergence, survival, shoot and root length, number of lateral roots, leaf necrosis, fresh weight and photosynthesis 42 day(s) other: see freetext 2000 no data as prescribed by 1.1 - 1.4

Result:

Test condition:

Reliability: 26-SEP-2005 Species: Endpoint: Expos. period: Method: Year: GLP: Test substance:

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Method:

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

METHOD FOLLOWED A six weeks test in sand. - Endpoints: Percentage emergence was noted daily. After six weeks survival, leaf necrosis, shoot and root length, number of lateral roots, fresh weight and photosynthesis were recorded. Photosynthesis was determined spectrophotometrically from methanol extract and calculated using MacKinney equation. STATISTICAL METHOD - Emergence data was analyzed using a general linear model (GLM) repeated measure technique. - Growth data were analyzed with a glm using one-way ANOVA. - The means were compared using Duncan's multiple range test. RESULTS - Effect data: Emergence: germination was significantly enhanced at 20 mM. At 250 mM the germination was only 7% Survival: significant decrease at 50 mM and higher Shoot length: significant reduction in 50 mM and higher Root length: significant reduction in length from 10 mM and higher Number of lateral roots: significant decrease from 10 mM and higher Leaf necrosis: significant from 50 mM on Fresh weight: reduction in 50 mM and higher Photosynthesis: Chlorophyll content did not change compared to the control TEST SPECIES - Pinus banksiana - Source: Pine Ridge Nursery, Alberta, Canada (seedlot SJ 75-15-4-77) - pretreatment: No - Substrate: quartz-feldspar sand (particle size range 0.19-3 mm) TEST SYSTEM - Concentrations: 0, 10, 20, 50, 100 and 250 mM solution in deionized water. - Test vessel: 4 l germination trays. - Number of seeds per replicate: 40 - Replicates: 5 trays per concentration. - Moisture content of sand: 13% - Thermoperiod: 20/15 degree Celsius - Photoperiod: 18 hours - High humidity was obtained by covering the trays with transparant plastic lids - After two weeks the lids were removed - Watering: Every other day after removing the lids, 500 ml of deionized water was sprayed over the sand. Every seven days 50 ml of Hoagland's mineral solution was sprayed on the sand. (2) valid with restrictions No standard method, but study with enough details. (28) other terrestrial plant: Picea mariana other: emergence, survival, shoot and root length, number of lateral roots, leaf necrosis, fresh weight and photosynthesis 42 day(s) other: see freetext UNEP PUBLICATIONS

Result:

Test condition:

Reliability: 26-SEP-2005 Species: Endpoint: Expos. period: Method: 83

OECD SIDS 4. ECOTOXICITY

Year: GLP: Test substance: Method: 2000 no data as prescribed by 1.1 - 1.4

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

METHOD FOLLOWED A six weeks test in sand. - Endpoints: Percentage emergence was noted daily. After six weeks survival, leaf necrosis, shoot and root length, number of lateral roots, fresh weight and photosynthesis were recorded. Photosynthesis was determined spectrophotometrically from methanol extract and calculated using MacKinney equation. STATISTICAL METHOD - Emergence data was analyzed using a general linear model (GLM) repeated measure technique. - Growth data were analyzed with a glm using one-way ANOVA. - The means were compared using Duncan's multiple range test. RESULTS - Effect data: Emergence: percentage germination was significantly less in 100 mM. Survival: significant decrease at 100 mM and higher Shoot length: significant reduction in 50 mM and higher Root length: significant reduction in length from 20 mM and higher Number of lateral roots: significant decrease from 50 mM and higher Leaf necrosis: no significant necrosis Fresh weight: reduction in 50 mM and higher Photosynthesis: Chlorophyll content did not change compared to the control TEST SPECIES - Picea mariana - Source: Pine Ridge Nursery, Alberta, Canada (seedlot MW 61-13-5-9) - pretreatment: No - Substrate: quartz-feldspar sand (particle size range 0.19-3 mm) TEST SYSTEM - Concentrations: 0, 10, 20, 50, 100 and 250 mM solution in deionized water. - Test vessel: 4 l germination trays. - Number of seeds per replicate: 40 - Replicates: 5 trays per concentration. - Moisture content of sand: 13% - Thermoperiod: 20/15 degree Celsius - Photoperiod: 18 hours - High humidity was obtained by covering the trays with transparant plastic lids - After two weeks the lids were removed - Watering: Every other day after removing the lids, 500 ml of deionized water was sprayed over the sand. Every seven days 50 ml of Hoagland's mineral solution was sprayed on the sand. (2) valid with restrictions No standard method, but study with enough details. (28)

Result:

Test condition:

Reliability: 26-SEP-2005

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Species: Endpoint: Method: Year: GLP: Test substance: Method: other terrestrial plant: Medicago sativa L. other: plant growth, nodule number and weight other: see freetext 1995 no data as prescribed by 1.1 - 1.4

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Result:

Test condition:

Reliability:

26-SEP-2005 Species: Endpoint: Expos. period: Method: Year: GLP: 85

METHOD FOLLOWED A 55 days test in a greenhouse. - Endpoints: Plant dry weight and nodule number and dry weight. STATISTICAL METHOD Data were statistically analysed by ANOVA. RESULTS - Effect data: Plant growth: decreased with concentration, dry weight was 50% of control at 130 mOsm at the end of the test. Nodule specific weight: did not change much at any osmotic level Number of nodules: decreased with concentration, 71% reduction in the highest concentration. TEST SPECIES - Medicago sativa L. - Source: not known - pretreatment: seeds were surface-steriized with 70% ethanol for 7 minutes, rinsed in sterile distilled water, and allowed to germinate on 1% water agar for 20 h. 10 germinated seeds were planted in a sterile-modified Leonard jar containing sand, and inoculated with R. meliloti. Plants were thinned out to 5 plants per jar, 14 days after planting. - Substrate: Hoagland nutrient solution TEST SYSTEM - Concentrations: 0, 70, 130, 200 or 250 mOsm in N-free nutrient solution. Salt was added 72 h after planting and checked weekly - Number of plants per replicate: 5 - Replicates: 6 - Temperature: 27/21 degree Celsius (day/night) - Relative humidity: not known - Photoperiod: 14 h - Plants were watered every following day - Watering: daily addition of deionized water - Solutions were analysed weekly and readjusted to initial nutrient concentrations (3) invalid No standard method. The method is described in detail but the results are not in much detailed. It is not clear at what concentration a significant decrease or increase occurs. (11) other terrestrial plant: Altriplex prostrata other: survival, height, nodes, branches, leaves, dry mass and photosynthesis 1 month other: see freetext 1996 no UNEP PUBLICATIONS

OECD SIDS 4. ECOTOXICITY

Test substance: Method: as prescribed by 1.1 - 1.4

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Result:

Test condition:

Reliability:

26-SEP-2005

METHOD FOLLOWED A one month semi static test in defined test medium. - Endpoints: Plant height, number of leaves, nodes and branches were recorded weekly. Photosynthesis was measured once before harvesting and dry mass was determined after one month. Photosynthesis was measured using a infra-red gas analyzer. STATISTICAL METHOD Two-way ANOVA was used to determine differences among treatments. The Bonferroni test was used for other comparisons. RESULTS - Effect data: Survival: All plants survived in every concentration Plant height: The height decreased as osmotic potential was lowered Number of nodes: The number decreased as osmotic potential was lowered Number of branches: The number decreased as osmotic potential was lowered Number of leaves: The number decreased from -1.00 MPa on Dry mass: Mass decreased from -1.00 MPa on Photosynthesis: Photosynthesis decreased from -1.00 MPa on TEST SPECIES - Atriplex prostrata - Source: Salt marsh in Rittman, Ohio (Wayne county) - Size of seeds: 1.5-2.0 mm diameter - pretreatment: Seeds were germinated in an incubator. 12h thermoperiod of 5:25 degree celcius. 12h photoperiod 20.0 micromol/m2/s, 400-700 nm. Acclimated to greenhouse conditions for two days in individual pots. Grown for 15 days under natural light conditions. Plants were acclimated to the test solutions by placing them at lower osmotic potential every two days until the final osmotic potential was reached - Substrate: Sand TEST SYSTEM - Concentrations: 0.00, -0.75, -1.00 and -1.50 MPa solution, dissolved in half strength Hoagland and Arnon's no. 2 solution. Solutions were replaced after two weeks. - Test vessel: 9x9 cm black plastic pots. - Replicates: 10 per concentration. (3) invalid Study with a lot of details on the method, but in the results no statistics is mentioned. It is not clear were significant differences were found. (35)

4.6.3 Toxicity to Soil Dwelling Organisms 4.6.4 Toxicity to other Non-Mamm. Terrestrial Species Species: Endpoint: Expos. period: Unit: LC50: other: Culex mortality 48 hour(s) other: mg/l = 4325 (Mosquito)

UNEP PUBLICATIONS

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SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

RESULTS: EXPOSED (4) not assignable Reference not available (33) other: Culex (Mosquito) mortality 48 hour(s) other: mg/l = 3004 RESULTS: EXPOSED (4) not assignable Reference not available other: Culex sp. larvea mortality 48 hour(s) other: mg/l = 13350 METHOD FOLLOWED: not described in detail. METHOD OF CALCULATION: not described RESULTS: EXPOSED - Nominal/measured concentrations: - Effect data (Immobilisation): 24 hours LC50 : 11430 mg/l - Concentration / response curve: - Cumulative immobilisation: - Effect concentration vs. test substance solubility: - Other effects: RESULTS CONTROL: RESULTS: TEST WITH REFERENCE SUBSTANCE - Concentrations: - Results: (3) invalid Documentation insufficient for assessment (34)

Result: Reliability: 26-SEP-2005 Species: Endpoint: Expos. period: Unit: LC50: Result: Reliability: 26-SEP-2005 Species: Endpoint: Expos. period: Unit: LC50: Method: Result:

(33)

Reliability: 26-SEP-2005

4.7 Biological Effects Monitoring 4.8 Biotransformation and Kinetics 4.9 Additional Remarks Memo: Remark: TOXICITY TO FISH Method: Acute toxicity to Lake Emerald shiner (Notropis a. atherinoides) and spotfin shiner (Notropis spilopterus). 96 hours testing according to Powers, E.B. Biol. Monograpgs IV, No. 2 pp.1-73 (1917). 18 degree C in 2-liter vessels. Oxygen > 4 mg/l. UNEP PUBLICATIONS

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SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Results: Minimum Lethal Concentration (NOEC) : 100.0 mg/l for both fish. 100% survival in controls. (106) TOXICITY TO INVERTEBRATES Method: Static bioassay, 28.5 +/-1.5 degree C: Effect parameters determined graphically. Tests with three replications + control. Dilution water: Unchlorinated bore-hole water.,pH=7, DO 7.5 mg/l, alkalinity 110 mg/l CaCO3. Results: 96h; LC 100 - LC 50 - LC 0 (mg/l). Branchiura sowerbyi (worm) 12000 - 7700 - 4750 Cyclops viridis (plankton) 4500 - 2000 - 1000 Lymnaea luteola (mollusc) 9500 - 8250 - 4000 (44) TOXICITY TO INVERTEBRATES Method: Static test with Daphnia magna, 48 hours in Lake Erie (USA) water. Method according to Anderson, B.G. Sewage Works J. 16(6):1156-1165 (1944). Results: Threshold concentration for immobilization: 5960 mg/l (16 hours) 7105 mg/l (48 hours) (6) TOXICITY TO INVERTEBRATES Marine invertebrates; salinity of sea water 30g/kg, static =========================================================== length 24h EC50 mm mg/l ----------------------------------------------------Annelida: Lepidonotus squamatus 15 >6400 Polydora sp. >6400 Crustacea: Balanus crenatus (Rock barnacle) 6 >6400 Eupagurus bernhardus (Hermit crab) 11.4 >6400 Carcinus maenas (shore or green crab) 12.6 >6400 Mollusca: Lepidochitona cinerea (Chiton) 6.5 >800 Acmaea testudinalis (Limpet) 2.5 >6400 Aphorrhais pespelicani (Pelicans foot) 43 >3200 Thais (Nucella) lapillus (Dow whelk) 15 >6400 Buccinum undatum (Large whelk) 31 >6400 Onchidoris fusca (Sea slug) 13 >6400 Mytilus edulis (Common bay mussel) 28 >6400 Anomia ephippium (False saddle oyster) 6.5 >6400 Hiatella (Saxicava) arctica (Red nose) 23 >1600 Echinodermata: Asterias rubens (Starfish) 59 >6400 Psammechinus miliaris (Sea urchin) 31 >6400 Urochordata: Ascidiella scabra (Sea squirt) >6400

26-SEP-2005 Memo: Remark:

15-OCT-2001 Memo: Remark:

15-OCT-2001 Memo: Remark:

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17-OCT-2001 Memo: Remark: TOXICITY TO INVERTEBRATES

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(82)

Toxicity of sodium sulfate in vitro on the fish nematode Procamallanus sp. was examined. Complete mortality was observed after 48 hours with 0.5% solution, and after 20 hours in 1.0% solution. (61) TOXICITY TO INVERTEBRATES (5) TOXICITY TO MICROORGANISMS Stimulation of growth (117 observed after addition of added to vessel of 110x230 soil, due to activation of period was 107 days. TOXICITY TO PLANTS 48 hours test with bulbs/seeds in a liquid test medium and with Na2SO4 in a semi-static test. Test parameter root length. Allium cepa, bulbs (Modified Allium test) : 7756 mg/l IC50 Lepidium sativum, seeds (Lepidium test): 8533 mg/l IC50 - 120 %) of Spruce seedlings was sodium sulfate (84 mg NaSO4 mm with 150 mm soil layer) to soil microflora. The total test (64)

11-JUL-2003 Memo: 26-SEP-2005 Memo: Remark:

15-OCT-2001 Memo: Remark:

15-OCT-2001 Memo: Remark: TOXICITY TO PLANTS

(8)

15-OCT-2001 Memo: Remark:

Method: greenhouse equipped with an activated charcoal air filtration system, 22 degree C day/18 degree C night, 50-55 % rel. air humidity, 12h photoperiod, treatment 3 x/week: 0.5, 1, 3, 5 g Na2SO4 as dust / 6 moistened plants Pinto-beans, 28d old "Veemore" tomatoes, 35d old Results: Pinto-beans; Progressive decrease in growth and dry weight with increasing Na2SO4 conc. over 4w "Veemore" tomatoes; 1w with 3 and 5 g/l or 2w with 1 g/l : growth inhibition 3w with 0.5 g/l : no inhibition (93) TOXICITY TO PLANTS Effect of Na2SO4 on the symbiotic effectiveness of the host Vigna radiata (mungo bean) and Rhizobium, 30 d: Initiation of nodulation was delayed by one day at 0.05 %; Total number of nodules and total nitrogen content of plant was maximum at 0.05 %; Nodulation was caused only upto 0.3 %. Method: Test tube method acc. to: Vincent, J.M.: Manual for the practical study of root nodule UNEP PUBLICATIONS

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SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

bacteria, Blackwell Scientific Publications, Oxford (1970) (10) TOXICTY TO AQUATIC PLANTS / INVERTEBRATES Na2SO4, dissolved in tap water, neutralized with Ca(OH)2: ============================================================ Hydra oligactis (Coelenterata): disintegration in 0.5% within 20-36h Turbellaria: Planaria gonocephala: death and disintegration in 1% after 48 h Stenostomum: death and disintegration in 0.5% after 24h Mollusca: Limnaea stagnalis Planorbis carinata in 1.5% after 24h dead, in 1% within Valvata piscinalis 3-14d dead Bythinia tentaculata Crustacea: Daphnia hyalina 0.25% lethal Insects: Limnophilus (Caddisfly,larvae): in 0.5% within 15-19d dead, in 1 und 1.5% within 4d dead Fishes: Carassius vulgaris (Gold fish): 0.5-1.25% no effect; 1.5% within 24d dead; 2% within 7-8d dead Tinca vulgaris (Tench) : 0.5% no effect; 1% within 21d dead; 2% within 1-2d dead Perca fluviatilis (Perch) : 0.5% no effect; in 2% within 2-7d dead Alburnus bipunctatus (Bleak) : in 1% within 16-17d dead Scardinius erythrophtalmus (Rudd) : in 1.5% within 7d dead Squalis leuciscus (Chub) : in 2% within 2d dead Salmo fario and : in 1.5% after 48h dead; Salmo gairdneri (Trout) 15-20 cm in 2% after 36h dead Tadpoles in 2% after 3.25-9h dead; in 1.1 % after 6h dead Submerse plants: Potamogeton luceus (pondweed): in 1.5 and 2% within 26d disintegration Ceratophyllum demersum (horn wort): in 0.3% no damage; in 1.5% within 40d disintegration Myriophyllum verticillatum (milfoil): in 1.5% within 12d dead; in 1% within 40d disintegration Elodea canadensis (pondweed): in 0.1% no damage; in 0.25% within 18d disintegration Lemna minor (duckweed): in 1% after 30d end of leaf reproduction; in 0.5% no damage Callitriche: in 0.8% permanent damage and deformation; in 1% dead Fontinalis : in 0.8% within 25d no damage; in 1.5% dead and disintegrated Chara foetida (filamentous green alga): in 0.5 and 0.75% up to 60d increased growth; UNEP PUBLICATIONS 90

24-OCT-2001 Memo: Remark:

OECD SIDS 4. ECOTOXICITY

within 72d dead 26-SEP-2005 09-NOV-2001

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(86)

91

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5.0 Toxicokinetics, Metabolism and Distribution In Vitro/in vivo: Type: Species: No. of animals, males: No. of animals, females: Doses, males: Route of administration: Exposure time: Year: GLP: Test substance: Remark: Result:

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

In vivo Absorption other: homo sapiens 7 0 13.9 g (8.6 g of the anhydrous salt) oral unspecified 3 hour(s)

1983 no other TS: Mg2SO4 Conclusion: Magnesium sulfate is less completely absorbed than sodium sulfate as described by Cocchetto et al, 1981 prior to study, three consecutive 24-hour periods for urine volume determination (twice, one -week interval). Subjects received either above dose in four hourly increments or just water; one week later the alternative. 72 -hour urine was collected at 4-hourly intervals (8 at night) Urinary sulfate excretion corrected for baselien was about 30.2% +- 17.2 in the first 24 hours, negligible in the following 48 hours. All subjects given the sulfate had gastro-intestinal complaints and loose stools or diarrhea. Frequency of treatment: once Post exposure period: 72 hours Control group: No; subject as own control (2) valid with restrictions non-standard study (70) In vivo Distribution other: homo sapiens 8 0 60-80 microCurie other: intravenously and oral

Test condition: Reliability: 26-SEP-2005

In Vitro/in vivo: Type: Species: No. of animals, males: No. of animals, females: Doses, males: Route of administration: Year: GLP: Test substance: Result:

1976 no other TS: Na2SO4 (35S-labeled) Volunteers received above dose IV, followed by 24-hours fluid restriction and blood and urine collection to determine radio-activity and creatinine concentration Same volunteers received same amount orally 14 days later, followed by same regimen. Plasma equilibrium iwas reached within 90 and 105 minutes respectively. Calculated mean extracelluar fluid space was 16.8 +- 1.1 and 15.3 +- 1.2 respectively or only 9%. Conclusion: 35S-labeled sulfate is absorbed completely and rapidly. Exposure period: single dose I.Vl, single dose oral 14 days later Frequency of treatment: once daily Post exposure period: 24 hours Control group: No; subject as own control UNEP PUBLICATIONS 92

Test condition:

OECD SIDS 5. TOXICITY

Reliability: (12) In Vitro/in vivo: Type: Species: No. of animals, males: No. of animals, females: Doses, males: Route of administration: Year: GLP: Test substance: Remark: Result: (2) valid with restrictions non-standard study

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

In vivo Absorption other: homo sapiens 5 0 18.1 g Na2SO4 decahydrate (800 g of the anhydrous salt) oral unspecified

1981 no as prescribed by 1.1 - 1.4 Conclusion: Sodium sulfate is better absorbed from the intestine when given in divided dose than from a single large dose, indicating saturation of the transport system. Prior to exposure three separate 24-hour periods for urine volume and baseline sulfate excretion determination (twice, one -week interval). Subjects received either above dose in a single dose or in four hourly increments; one week later the alternative dosing schedule. 72 -hour urine was collected in 24-hour portions. Urinary free sulfate excretion corrected for baseline was about 53.4 +-16.8 for the single dose and 61.8 +-7.8 for the divided dose. Single dose causeds severe diarrhoea, divided dose did not. Excretion of free sulfate is not influenced by urine flow, but excretion of organicaly bound sulfate is.in a linear fashion. Exposure period: single oral dose or divided over three hours Frequency of treatment: twice with one week interval Post exposure period: 72 hours Control group: No; subject as own control (2) valid with restrictions non-standard study (27) Absorption rat Absorption of inorganic sulfate after ingestion in rats (male, Wistar (30-330 g body weight) was investigated. A inorganic sulfate concentration was measured in the serum after 2 hours of oral administration of 5 mmol Na2SO4. A threefold increase in serum sulfate concentration was measured. Compete absorption from the gastrointestinal tract was measured using 35S labelled sulfate. (2) valid with restrictions non-standard study (60)

Test condition:

Reliability: 26-SEP-2005 Type: Species: 26-SEP-2005 Result:

Reliability: 26-SEP-2005

93

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5.1 Acute Toxicity 5.1.1 Acute Oral Toxicity Type: Species: No. of Animals: Vehicle: Doses: Value: Method: Year: GLP: Test substance: Method: Result: LD50 rat 10 water 2-5 ml/100 g body weight oral > 10000 mg/kg bw other: not defined 1971 no data as prescribed by 1.1 - 1.4

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Test condition:

METHOD FOLLOWED: not described STATISTICAL METHODS: not described METHOD OF CALCULATION: not described MORTALITY: - Time of death: after 8 days - Number of deaths at each dose: not described CLINICAL SIGNS: no clinical signs observed NECROPSY FINDINGS: not described POTENTIAL TARGET ORGANS: not described SEX-SPECIFIC DIFFERENCES: not described TEST ORGANISMS: - Source: not described - Age: not described - Weight at study initiation: mean weight 270 gram - Controls: not described ADMINISTRATION: - Doses: as described - Doses per time period: not described - Volume administered or concentration: 2-5 ml - Post dose observation period: 8 days EXAMINATIONS: not described (4) not assignable Original reference not available LD50 mouse = 5989 mg/kg bw 1963 no data as prescribed by 1.1 - 1.4 (4) not assignable Original reference in Japanese not available (78) other: human drinking-water study human male/female 10 water dose ranging study: 0, 400, 600, 800, 1000 and 1200 mg/l. UNEP PUBLICATIONS 94

Reliability: 27-SEP-2005 Type: Species: Value: Year: GLP: Test substance: Reliability: 27-SEP-2005 Type: Species: Sex: No. of Animals: Vehicle: Doses:

(52)

OECD SIDS 5. TOXICITY

Single dose study: 0 and 1200 mg/l. Method: Year: GLP: Test substance: Method: other 1997 no as prescribed by 1.1 - 1.4

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

TEST ORGANISMS: 10 Normal Human Subjects, 80% caucasian. - Source: - Age: 24-45 years - Weight at study initiation: - Controls: ADMINISTRATION: - Doses: dose ranging study: 0, 400, 600, 800, 1000 and 1200 mg/l. Single dose study: 0 and 1200 mg/l. - Doses per time period: dose ranging study: 4 subjects (2 male, 2 female) received a dialy dose in the order listed above for 6 consectutive 2 day periods. Single dose study: 6 subjects (3 male, 3 female) received a dialy dose of 0 and 1200 mg/l for 2 consecutive 6 day periods. Colored markers were given at the beginning of each change in drinking water sulfate concentration. - Volume administered or concentration: volume 36 ml/kg/d. - Post dose observation period: EXAMINATIONS: The health of the subjects was determined by studying their history, physical examination, urineanalysis, blood cell counts and serum chemistries. During the study stool mass, frequency and consistency in mouth to anus appearance of colored markers were measured. Wilcoxon signed rank test was used to compare the effects of specific concentrations of sulfate compared to distilled water. MORTALITY: - Time of death: - Number of deaths at each dose: CLINICAL SIGNS: No significant change in bodyweight. All blood and urine test results were normal. At 1200 mg/l 8 subjects rated the taste of the water as neutral-slightly unpleasant, 1 subject as moderately unpleasant and 1 subject as very unpleasant. Dose ranging study: Increasing the sulfate concentration in drinking water every 48 hours from 0 - 1200 mg/l produced no significant trend in stool mass per hours (based on Page's L-statistic test). During the six periods the mean number of stools were 2.5, 3.0, 2.3, 3.0 2.0 and 2.8 respectively, and the mean consistency ratings were 3.5, 3.3, 3.1, 3.4, 3.0 and 2.7 respectively. There was a significant trend toward decreasing mouth to anus appearance time with increasing sulfate concentration. The mean appearance times were (hours) 27.3, 17.9, 26.0, 16.1, 19.2, 17.2 respectively. No diarrhea during daily diaries were reported during the entire study. Mild abdominal cramps were reported by one subject for two days while receiving distilled water. Single dose study: Compared to distilled water, water containing 1200 mg/l sulfate produced a statistically significant increase in the

Result:

95

UNEP PUBLICATIONS

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

mean stool mass per six-day pool, from 629 to 922 g and in mean stool mass per hour from 4.8 to 6.6 g. Each subject showed an increase in stool mass per pool and in stool mass per hour. Stool frequencey, stool consistency, and mouth to anus appearance time were not significantly different. Two of the six subjects reported abdominal cramps, no other symptoms were recorded. When combing the results from both studies for 0 an 1200 mg/l significant decreases in stool consistency and appearance time were noted at 1200 mg/l. NECROPSY FINDINGS: POTENTIAL TARGET ORGANS: SEX-SPECIFIC DIFFERENCES: Anhydrous sodium sulfate from UPS was used. (2) valid with restrictions Acceptable, well documented study. The results of the blood and urine test an bodyweights are not shown. (51)

Test substance: Reliability:

27-SEP-2005

5.1.2 Acute Inhalation Toxicity Type: Species: Strain: Sex: No. of Animals: Vehicle: Doses: Exposure time: Value: Method: Year: GLP: Test substance: Method: LCLo rat Sprague-Dawley male 6 water 10 mg/m3 72 hour(s) > 10 mg/m other: see freetext, not a guideline study: method according to Last and Cross, J. Lab. Clin. Med. 91:328-339 (1978) 1980 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: rats were exposed to well characterized aerosols of sodium sulfate at levels of 10 mg/m3 and particle sizes of around 1 micron. the responses to breathing these aerosols for three days were evaluated by measurements of glycoprotein, RNA and DNA contents of homogenates of the lungs and quantification of wet to dry weight ratios of the lung lobs. STATISTICAL METHODS: not described METHOD OF CALCULATION: not described ANALYTICAL METHODS: Ion chromatography as described by Asgupta et al., Amer. Ind.Hyg. Assn. J. (1980) in prep. MORTALITY: no death reported CLINICAL SIGNS: RNA, DNA and protein levels in lung homogenates (control = 100) RNA: 99, DNA: 100, protein content: 107. (mean values form 6 rats) NECROPSY FINDINGS: Lung wet to dry ratio: (control = 4.5). 4.35 and 4.5 for exp. 1 and 2 resp. POTENTIAL TARGET ORGANS: Lungs SEX-SPECIFIC DIFFERENCES: not determined TEST ORGANISMS: rat UNEP PUBLICATIONS 96

Result:

Test condition:

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

- Source: Charles River, Portage, MI, USA - Age: 70-80 days - Weight at study initiation: not described - Number of animals: 6 rats per exposure - Controls: yes ADMINISTRATION: - Type of exposure: inhalation - Concentrations: 10 mg/m3 - Particle size: app. 1 m - Type or preparation of particles: Babington (1-15 mg/m3) and Retec nebulizers (> 0.1 mg/m3) EXAMINATIONS: Lungs: RNA, DNA, protein from homogenates. Quantification of wet to dry weight ratios of right apical lung lobs. (2) valid with restrictions Acceptable, well documented study. (62) other: effect on pulmonary function human other 1, 2 and 3 mg/m3 10 minute(s) other: unspecified 1979 no no data TEST ORGANISMS: human - Source: - Age: - Weight at study initiation: - Number of animals: 5 astmatic and 5 normal humans and 6 astmatic and 6 normal humans - Controls: ADMINISTRATION: - Type of exposure: aerosols - Concentrations: 1, 2, 3 mg/m3 and 3 mg/m3 in the second experiment - Particle size: 0.5 micrometer mass mediam aerodynamic diameter - Type or preparation of particles: particles were generated by an ultrasonic nebulizer and sized by elctron micrographs and an electrical aerosol size analyzer. EXAMINATIONS: Respiratory resistance (Rrs) was meaured continuesly during exposure. Rrs, Forced Expiratory Volume1 and VC were measured 5, 15, 30, 45 and 60 minutes after exposure. In the second experiment lung volumes by spirometer and plethysmography, dynamic mechanisms of breathing by Rrs: specified airway conductance and flow volume curve, distribution of ventilation by single and multiple breath nitrogen washouts, random noise oscillations and diffuse capacity. MORTALITY: - Time of death: - Number of deaths at each dose: CLINICAL SIGNS: In the first experiment 2 of 5 astmatic people experienced a UNEP PUBLICATIONS

Reliability: 27-SEP-2005 Type: Species: Vehicle: Doses: Exposure time: Method: Year: GLP: Test substance: Method:

Result:

97

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

15-20% fall in FEV1 at 1 mg/m3. This did not get worse at higher concentrations. The groups means were not altered as comapred with NaCl. In the second experiment no adverse effect on pulmonary function was found over 3 hours compared to NaCl. 2 of 6 astmatic people experienced a 15-20% fall in FEV1 at 1 mg/m3 after breathing NaCl and sodium sulfate aerosols. NECROPSY FINDINGS: POTENTIAL TARGET ORGANS: SEX-SPECIFIC DIFFERENCES: No data on sodium sulfate supplier, purity or storage. (4) not assignable Not assignable. Only abstract available. (84) other: irritant potency (mucociliary clearance) rabbit other: mixed breed male 5 1800-1950 microgram particles/m3 1 hour(s) other 1984 no no data TEST ORGANISMS: Mixed breed rabbits. - Source: - Age: - Weight at study initiation: 2.5-2.7 kg - Number of animals: 5 males - Controls: animals served as their own controls in 'sham'-control experiments. 10 of these experiments were performed exposing the animals for 1 hour to temperature and humidity conditioned air. ADMINISTRATION: - Type of exposure: inhalation. - Concentrations: 1800-1950 microgram particles/m3. - Particle size: mean mass aerodynamic diameter 0.4 micrometer. - Type or preparation of particles: Aerosols were prpared by nebulization using a Laskin nebulizer. The aerosols were mixed with filtered room air which had been temperature and humidity conditioned. EXAMINATIONS: The bronchial mucociliary clearance was measured by brief inhalation of radiolabelled, insoluble tracer microspheres (99mTc-tagged ferric oxide). The thoracic retention was measured externally in vivo. These measuerments began within 2 min. After the inhalation and were repeated after 24 hours to determine a value for residual activity (R24). It is expected that the tracer is completely cleared after 24 hours. The mucociliary clearance was determined as mean residence time (MRT) of the tracer. MORTALITY: - Time of death: - Number of deaths at each dose: CLINICAL SIGNS: No effect on mucociliary clearence was found (one way ANOVA, two tailed). UNEP PUBLICATIONS 98

Test substance: Reliability: 26-SEP-2005 Type: Species: Strain: Sex: No. of Animals: Doses: Exposure time: Method: Year: GLP: Test substance: Method:

Result:

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

NECROPSY FINDINGS: POTENTIAL TARGET ORGANS: SEX-SPECIFIC DIFFERENCES:No details on where the sodium sulfate was obtained or on purity are given. (2) valid with restrictions Limited documentation but sufficient for assessment of primary effects. (87) other: irritant potency guinea pig other: random bred no data 10 no data 0.90 +/- 0.11 mg/m3 1 hour(s) other 1978 no no data TEST ORGANISMS: guinea pigs - Source: - Age: - Weight at study initiation: 200-300 g - Number of animals: 10 - Controls: during a 30 min. control period before exposure to the test substance measurements were taken every 5 min. The same animals were used in the exposure. ADMINISTRATION: - Type of exposure: inhalation. - Concentrations: 0.90 +/- 0.11 mg/m3 - Particle size: 0.11 micrometer - Type or preparation of particles: aerosols were prepared witha Dautrebande D30 aerosol generator. EXAMINATIONS: The respiratory meachanisms of the guinea pigs were measured. Intrapleural pressure, tidal volume, and rate flow of gas in and out of the respiratory system are recorded. From these data the pulmonary flow resistance may be obtained. Pulmonary flow resistance and the compliance are in cm water/ml/s and mm/cm water, respectively. MORTALITY: - Time of death: - Number of deaths at each dose: CLINICAL SIGNS: Pulmonary resistance and compliance of sodium sulphate was not significantly different from the control. NECROPSY FINDINGS: POTENTIAL TARGET ORGANS: SEX-SPECIFIC DIFFERENCES: No details on where the sodium sulfate was obtained or on purity are given. (4) not assignable Documentation insufficient for assessment (4)

Test substance: Reliability: 27-SEP-2005 Type: Species: Strain: Sex: No. of Animals: Vehicle: Doses: Exposure time: Method: Year: GLP: Test substance: Method:

Result:

Test substance: Reliability: 27-SEP-2005

99

UNEP PUBLICATIONS

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

5.1.3 Acute Dermal Toxicity 5.1.4 Acute Toxicity, other Routes Type: Species: Route of admin.: Value: Reliability: 26-SEP-2005 Type: Species: Route of admin.: Value: Reliability: 26-SEP-2005 5.2 Corrosiveness and Irritation 5.2.1 Skin Irritation Species: Concentration: Exposure: Exposure Time: No. of Animals: Vehicle: Result: EC classificat.: Method: Year: GLP: Test substance: Method: rabbit 500 mg Occlusive 4 hour(s) 3 other: polyetyleneglycol 400 not irritating not irritating OECD Guide-line 404 "Acute Dermal Irritation/Corrosion" 1991 yes as prescribed by 1.1 - 1.4 METHOD FOLLOWED: Determination of irritant/corrosive effects were examined using rabbits, according to OECD 404. DEVIATIONS FROM GUIDELINE: no deviations reported GLP: yes STATISTICAL METHODS: DRAIZE score system was used METHOD OF CALCULATION: not described ANALYTICAL METHODS: not applied AVERAGE SCORE - Erythema: score = 0, after 14 days - Edema: score = 0 after 14 days REVERSIBILITY: not described OTHER EFFECTS: Irrit. index : edema = 0.0; erytheme = 0.0. Body weight, 3.7 - 4.2 kg TEST ANIMALS: Rabbits - Strain: HC:NZW - Sex: not described - Source: Interfauna, Ltd, UK UNEP PUBLICATIONS 100 LD50 mouse i.p. 2400 - 3400 mg/kg bw (4) not assignable Reference not translated (20) LD50 rat i.p. 3000 - 4100 mg/kg bw (4) not assignable Reference not translated (20)

Result:

Test condition:

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

- Age: adults - Weight at study initiation: not described - Number of animals: 3 - Controls: Contralateral skin area not treated ADMINISTRATION/EXPOSURE - Preparation of test substance: 500 mg pulverized in PEG 400 - Area of exposure: dorso-lateral areas of the trunk. - Occlusion: Patches hypoallergenic Hansamed (Beiersdorf) - Vehicle: PEG 400 - Concentration in vehicle: 500 mg - Total volume applied: not described - Postexposure period: 14 days - Removal of test substance: washed with water EXAMINATIONS - Scoring system: DRAIZE scores - Examination time points: 1, 24, 48, 72 hours, 7, 14 days. (1) valid without restriction Guideline study (13)

Reliability: 26-SEP-2005

5.2.2 Eye Irritation Species: Concentration: Dose: Exposure Time: No. of Animals: Vehicle: Result: EC classificat.: Method: Year: GLP: Test substance: Method: rabbit 90 mg 100 other: l 24 hour(s) 3 no data slightly irritating irritating Directive 84/449/EEC, B.5 "Acute toxicity (eye irritation)" 1991 yes as prescribed by 1.1 - 1.4 METHOD FOLLOWED: Determination of irritant/corrosive effects were examined using rabbits, according to OECD 405. DEVIATIONS FROM GUIDELINE: no deviations reported GLP: yes STATISTICAL METHODS: DRAIZE score system was used METHOD OF CALCULATION: not described ANALYTICAL METHODS: not applied AVERAGE SCORE - Cornea: 0 no effect (7 days), irrit. index 0.0 - Iris: 0 no effect (7 days) irrit. index 0.0 - Conjuntivae (Redness): 1 (48 hours) irrit. index 1.0 - Conjuntivae (Chemosis): 0 (7 days) - Overall irritation score: 1.3 (slightly irritating) DESCRIPTION OF LESIONS: no REVERSIBILITY: within 7 days Test condition: OTHER EFFECTS: TEST ANIMALS: Rabbits - Strain: HC:NZW - Sex: not described - Source: Interfauna, Ltd, UK UNEP PUBLICATIONS

Result:

101

OECD SIDS 5. TOXICITY

Age: adults Weight at study initiation: not described Number of animals: 3 Controls: other eye

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

ADMINISTRATION/EXPOSURE - Preparation of test substance: Pulverized powder - Amount of substance instilled: 90 mg - Vehicle: not described - Postexposure period: 21 days - exposure : 24 hours EXAMINATIONS - Ophtalmoscopic examination: yes - Scoring system: DRAIZE system - Observation period: 21 days - Tool used to assess score: optical instrument (hand slit lamp) (1) valid without restriction Guideline study (13)

Reliability: 26-SEP-2005 5.3 Sensitization

Type: Species: Concentration 1st: 2nd: No. of Animals: Vehicle: Result: Classification: Method: Year: GLP: Test substance: Method:

Patch-Test human Induction 1.25 % semiocclusive Challenge 1.25 % semiocclusive 65 water not sensitizing not sensitizing

other: not specified 1976 no other TS TEST ANIMALS: human - Strain: - Sex: male/female - Source: - Age: 16-70 - Weight at study initiation: - Number of animals: 56 male and 5 female - Controls: ADMINISTRATION/EXPOSURE - Study type: Patch test. - Preparation of test substance for induction: A 1.25% aqueous solution was prepared. This concentration represents a 100 fold increase of the normal use level. - Induction schedule: Subjects were exposed on their backs. The test patch unit consited of a strip of two-inch wide blenderm surgical tape with two rows of five 12.7 mm filter paper discs each. The first application lasted for 48 hours. All other inductions were for 24 hours. Reactions tohe initial site were scored 48 and 96 hours after patch removal. 8 other 24 hour inductions were done on mondays, Wednesdays and Fridays (3.5 weeks)on 3 alternate sites (unless the reaction or tape irritation was severe than UNEP PUBLICATIONS 102

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

other sites were used). Reactions were recorded 3-9 hours before application and 24 hours after patch removal. - Concentrations used for induction: 1.25% aqueous solution. - Concentration in Freuds Complete Adjuvant (FCA): - Challenge schedule: On monday in week 7 subjects were challenged on a previously unpatched site. After 48 hours the patches were removed. The patches were scored 48 hours 48 following removal. - Concentrations used for challenge: 1.25% aqueous solution. - Rechallenge: subjects that showed signs of sentisation in the challenge phase were tested again after a 2 week rest period. At the original concentration under occlusion, in a dilution of original strenght (1:3) under occlusion, as used in practice (subject applied the project to the flex part of the arm 3 times/day for 5 days. - Positive control: EXAMINATIONS - Grading system: patch reactions were scored by experienced technitians. According to teh following scoring system: 0 No evidence of any effect +/- Barely perceptible. Minimal faint unifrom spotty erythema. 1 Mild. Pink unifrom erythema covering most of the contact site. 2 Moderate. Pink-red erythema visibly uniform in the whole contact site. 3 Marked. Bright red erythrema with accompanying edema, petechiae or papules. 4 Severe. Deep red erythema with vesiculation or weeping with or without edema. - Pilot study: RESULTS OF PILOT STUDY: RESULTS OF TEST - Sensitization reaction: One subject showed a score 1 reaction during the induction period. Other subjects did not react to the application (data not shown). - Clinical signs: Mild. Pink unifrom erythema covering most of the contact site. - Rechallenge: Data not shown. Bath salt crystals allegedly containing 80.8% sodium sulfate. (4) not assignable The report is incomplete and unsigned. Lab and authors are unknown and there is no quality control. Individual data are not shown. (22)

Result:

Test substance: Reliability:

26-SEP-2005

5.4 Repeated Dose Toxicity Type: Species: Strain: Route of administration: Exposure period: Frequency of treatment: 103 Sub-acute rat Sex: male Sprague-Dawley oral feed 4 weeks diets were provided ad libitum for 4 weeks UNEP PUBLICATIONS

OECD SIDS 5. TOXICITY

Post exposure period: Doses: none Experiment a 0.88 mmol/kg feed Experiment b 8.64 mmol/kg feed 17.28 mmol/kg feed 34.56 mmol/kg feed 65.12 mmol/kg feed Experiment c 138 mmol/kg feed yes, concurrent no treatment ca. 2000 mg/kg

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

day day day day

1-8 9-16 17-24 25 for 4-6 days

Control Group: NOAEL: Method: Year: GLP: Test substance: Method:

other: not specified 1960 no as prescribed by 1.1 - 1.4 TEST ORGANISMS: Sprague Dawley rats - Age: weanling, young - Weight at study initiation: - Number of animals: 6 rats per group ADMINISTRATION / EXPOSURE - Duration of test/exposure: 4 weeks - Type of exposure: oral feed, diet avaialable ad libitum - Post exposure period: none - Vehicle: basal diet, cornstarch diet, 67% cornstarch, 24% 'vitamin free' casein, 5% crisco (cristalized cottonseed oil) and 4% salt mixture (3.8% magnesium sulfate, anhydrous and 0.02% maganous sulfate. No sodium sulfate.) and vitamins. - Concentration in vehicle: see doses - Total volume applied: the feed intake in week 4 of the rats receiving sodium sulfate is presented: 408 (371-453) g. - Doses: Experiment a 0.88 mmol/kg feed Experiment b 8.64 mmol/kg feed day 1-8 17.28 mmol/kg feed day 9-16 34.56 mmol/kg feed day 17-24 65.12 mmol/kg feed day 25 for 4-6 days Experiment c 138 mmol/kg feed SATELLITE GROUPS AND REASONS THEY WERE ADDED: CLINICAL OBSERVATIONS AND FREQUENCY: - Clinical signs: records of any diarrhea that occurred were kept. In experiment c teeth were examined. - Mortality: - Body weight: at the beginning of the study, at the end of each week and just before study termination. - Food consumption: feed intakes and feed:gain ratios were obtained for each week. - Water consumption: In experiment c the amount of water drunk during the first 48 h of the third week was recorded. - Ophthalmoscopic examination: - Haematology: In experiment c blood was colelcted from the tail after 3.5 weeks for red and white bloodcell counts and hemoglobin was determined. At termination of the study bllod was collected from the neck vain and analyzed for alkaline phosphate, inorganic phosphate and protein. - Biochemistry: - Urinalysis: In experiment c the volume of urine was determined. ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC): - Macroscopic: gastrointestinal organs were examined. The UNEP PUBLICATIONS 104

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

small intestine and colon plus rectum were hung full length were measured. Organs were clenaed dried and weighed. I - Microscopic: In experiment c a small snip of the stomach was removed for histological examination. OTHER EXAMINATIONS: STATISTICAL METHODS: In experments b and c the numerical results were analyzed statistically by analysis of variance, the hypothesis in every case being that the groups were equal. A multiple range test was performed when it was indicated that there was a difference among the groups at the 5% level or less. results were significantly different if P<0.05. NOAEL (NOEL), LOAEL (LOEL): At the top dose, the food contained around 2% of the respective sulfates, calculated to be around 2000 mg/kg/d. ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX: - Time of death: - Number of deaths at each dose: 0 TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: Data for experiment a are not presented in the article because at this low dose level no effects were seen. - Mortality and time to death: - Clinical signs: Experiment c teeth: no changes compared with control group. Two slight cases of diarrhea that lasted for a day were observed in experiment b in the sodium sulfate group. One rat in experiment c showed diarrhea on 4 different days (3 conseccutive days) in the middle of the feeding period. - Body weight gain: Experiment b and c: no changes compared with control group. - Food/water consumption: Experiment c: no changes compared with control group. - Ophthalmoscopic examination: - Clinical chemistry: - Haematology: Experiment c: no changes compared with control groups or other dose groups In red or white blood cell counts, hemoglobin, protein, alkaline phosphatase orminorganic phosphatase. - Urinalysis: Experiment c urine volume: no changes compared with control groups or other dose groups. - Organ weights: Experiment b and c: no changes compared with control group. - Gross pathology: - Histopathology: - Other: STATISTICAL RESULTS: see above Sodium Sulfate was obatined as anhydrous powder from Merck, A.C.S. (2) valid with restrictions Old study non-GLP and not according to standard guideline. (68) rat Sex: male no data inhalation 8, 12, 44, 90, 720 hrs continuous (?) 1 month (size of recovery group not given) 3, 11.06, 18.03, 40.05, 60.45 mg respectively, with concurrent exposure to 500 mg/l in drinking water other: one control group for each exposure group, size UNEP PUBLICATIONS

Result:

Test substance: Reliability: 26-SEP-2005

Species: Strain: Route of administration: Exposure period: Frequency of treatment: Post exposure period: Doses: Control Group: 105

OECD SIDS 5. TOXICITY

not specified Year: GLP: Remark: 1989 no

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Result:

Reliability:

ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX: cannot be calculated Aerosol generation not described. Aerosol size, stability not described. exposure duration / day not given Concentrations measured by potentiometric method Calculated daily dose from inhalation at 3 mg/m3 is 0.66 (8 hr/day) to 2 mg/kg/day (24hr/day), compared to intake from drinking water 60 mg/kg/day. LOAEC: 2 mg/m3 log(time-to-first appearance) plotted against log(concentration) shows 100% linear correlation for 2 of the 3 reported effect parameters. Such precision is unlikely to occur in biological systems. Number of animals: 200; 5 exposure groups and 5 control groups, size not given. Report mentions complete recovery at 1 month post-exposure but size of recovery group not given. method for monthly isnpections of inner organs not given. Time of death: n/a Nr. of of deaths at each dose: none TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: - Mortality and time to death: n/a Clinical signs: not specifed At concentrations of 60, 40, 16, 11 and 3 mg/m3: small but statistically significant effects on serum liver cholinesterase concentration (first appearing at 6, 12, 44, 90 and 720 hours respectively ), prolongation of blood coagulation time (first appearing at 4, 8, 30, 64 and 510 hours respectivey) and brain irritablity as measured by "summated threshold potential (?)", (first appearing at 4, 8, 24, 45 and 288 hours respectively), effects stated to be worse at end-of exposure (no data provided). Depression of spermatogenesis (presumably at end-of-exposure), at al concentrations. All effects stated to be completely reversible within one month post-exposure (size of recovery groups not given). Body weight gain: - Food/water consumption: drinking water contained 500 mg sodium sulfate/liter. Consumptio data not given Ophthalmoscopic examination: - Clinical chemistry: no abnormalities in blood histamine, brain cholinesterase, number of sulfhydryl groups,basic phosphatase activity in blood serum and content of ascorbic acid in the adrenals. - Haematology: No abnormalities were observed in number of erythrocytes and leucocytes, total haemoglobin, meth- and sulfhaemoglobin, presence of Heinz-Ehrlich bodies - Urinalysis: - Organ weights: - Gross pathology: - Histopathology: (? method not given) suppression of spermatogenesis - Other: STATISTICAL RESULTS: see above (3) invalid results biologically implausible / insufficient UNEP PUBLICATIONS 106

OECD SIDS 5. TOXICITY

documentation for assessment 26-SEP-2005 Type: Species: Strain: Route of administration: Exposure period: Frequency of treatment: Post exposure period: Doses: Control Group: Year: GLP: Remark: 1990 no

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(29) Chronic rat Sex: male no data inhalation 3 months not given 1 month (size of recovery group not given) dust concentration 1 mg/m3, with concurrent exposure to 500 mg/l in drinking water yes

Dust generation, particle size, aerosol stability etc not described exposure duration per day not given Measured exposures in workplace atmosphere (shift average) 88 mg/m3, yet apparenty no clinical symptoms or complaints from humans Method for "monthly ispection of inner organs" not given Sulfate concentration in drinking water 500 mg/l; caluculated maximum uptake from air < 0.1 (8-hr exposure) to .6 mg/kg/day (24hr/day exposure) vs. 60 mg/kg/day from drinking water small but significant changes in "summarized threshold potential" (measure of brain irritability), liver cholinesterase, blood cholinesterase, number of lymphocytes and neutrophils, body weight, relative liver weigt; depression of spermotagenesis, histopathological changes in liver and testes, serious histopathological changes in the lungs and several cases of pneumonomia, all fully reversible after 1 month recovery. results similar to those found in concurrent studies with sodium sulfite at 01. and 1 mg/m3 and a mixture of sulfite/sulfate at 1 mg/m3. Na2SO4 dust, not specified (3) invalid Results biologically implausible; insufficient documentation for assessment (30) rat Sex: oral feed 6 weeks daily (feeding study) 1 or 2 % in diet other: saline in equal concentrations

Result:

Test substance: Reliability: 26-SEP-2005

Species: Route of administration: Exposure period: Frequency of treatment: Doses: Control Group: Method: Year: GLP: Test substance: Method:

other: not described 1976 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: In two experiments the direct effect of dietary intake of sodium sulfate was examined. One experiment with weanling rats, and another with adults, over UNEP PUBLICATIONS

107

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

a 6 weeks exposure period. STATISTICAL METHODS: not described METHOD OF CALCULATION: not described NOAEL (NOEL), LOAEL (LOEL): not determined TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: - Mortality and time to death: not described - Clinical signs: not described - Body weight gain: exp1 weanling rats upto 10 g S/kg dm and exp2 adult rats upto 20 g S/kg dm (exp1/exp2) control exp1 : 4.54 g/d control exp2 : -1.42 g/d exp1 : 4.49 g/d exp2 : -1.95 g/d - Food/water consumption: water: control exp1 : 28.0 ml/d control exp2 : 36.8 ml/d exp1 : 36.2 ml/d exp2 : 57.4 ml/d food: control exp1 : 13.4 g/d control exp2 : 13.8 g/d exp1 : 13.5 g/d exp2 : 15.2 g/d STATISTICAL RESULTS: not described, Overall dietary supplementation with sodium sulfate did not significantly affect food/water intake and live-weight gain of rats. TEST ORGANISMS - Age: not described - Weight at study initiation: not described - Number of animals: eight weaning and eight adult animals ADMINISTRATION / EXPOSURE - Duration of test/exposure: 6 weeks - Type of exposure: oral - Post exposure period: not described - Vehicle: commercial diet - Concentration in vehicle: 10-20 gram S/kg dm - Total volume applied: not described - Doses: in daily diet CLINICAL OBSERVATIONS AND FREQUENCY: - Clinical signs: no - Mortality: not described - Body weight: yes - Food consumption: yes - Water consumption: yes - Ophthalmoscopic examination: no - Haematology: no - Biochemistry: no - Urinalysis: no STATISTICAL METHODS: not described (3) invalid documentation was insufficient for assessment (104) Chronic hen other: White Leghorn drinking water 3-4 weeks continuous 250-23328 mg/l UNEP PUBLICATIONS Sex: female

Result:

Test condition:

Reliability: 26-SEP-2005

Type: Species: Strain: Route of administration: Exposure period: Frequency of treatment: Doses:

108

OECD SIDS 5. TOXICITY

Control Group: LC100 : Method: Year: GLP: Test substance: Method: yes ca. 23328 mg/l other: not a guideline study, see freetext 1974 no as prescribed by 1.1 - 1.4

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Result:

METHOD FOLLOWED: Commercial strain hens were supplied with sodium sulfate containing drinking water for a period of 4 weeks. Egg production, body weight, water en feed consumption and mortality were examined. STATISTICAL METHODS: performance of treatement were compared to performance during pretreatment. METHOD OF CALCULATION: not described ANALYTICAL METHODS: no NOAEL (NOEL), LOAEL (LOEL): not described TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: - Mortality and time to death: at 16000 mg/l Na2SO4 cumulative death of 100% was observed at day 14, while death was already apparent at day 5. - Clinical signs: not described Conc. (mg/l weight 250 370 1000 1480 4000 5920 16000 23328 egg production Na2SO4) +6.5 -16.1 +26.7 -15.6 +0.5 -24.4 -43.7 -73.8 water consumption -2.3 -12.9 -2.0 -14.9 -12.0 +58.8 +146.7 -47.1 food consumtion +13.3 -3.7 +1.3 -1.7 +8.1 -14.2 -25.5 -77.8 body +9.0 -0.6 +1.3 +2.0 +1.1 -0.3 -14.7 *

* all animals died - Ophthalmoscopic examination: - Clinical chemistry: - Haematology: - Urinalysis: - Organ weights: - Gross pathology: Necropsis of birds receiving 16000 mg/l sulphate showed extreme emaciation and visceral gouit. - Histopathology: Microscopic examination of kidney tissues showed urate accumulation of individual glomeruli and tubules losing cellular detail. - Other: none STATISTICAL RESULTS: not described TEST ORGANISMS - Age: not described - Weight at study initiation: not described - Number of animals: 2 hens per cage, 6 per block in 2 or 3 cage rows in ADMINISTRATION / EXPOSURE - Duration of test/exposure: 4 weeks with 4 weeks pretreatment - Type of exposure: continuous in drinking water - Post exposure period: no - Vehicle: water - Concentration in vehicle: 250, 1000, 4000 and 16000 mg/l UNEP PUBLICATIONS

Test condition:

109

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SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

Na2SO4 - Total volume applied: n.a. - Doses: not described CLINICAL OBSERVATIONS AND FREQUENCY: - Clinical signs: no - Mortality: yes - Body weight: yes - Food consumption: yes - Water consumption: yes - Ophthalmoscopic examination: no - Haematology: no - Biochemistry: no - Urinalysis: no ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC): - Macroscopic: gout - Microscopic: kidneys OTHER EXAMINATIONS: egg production STATISTICAL METHODS: all data were converted to performance percentages using the formula performance during treatment/performance during pretreatement x 100. Data were analyzed by analysis of variance when warranted. (2) valid with restrictions No guideline study, but includes detailed information on used method, endpoints and statistical evaluation procedures. Sub-acute other: Cattle other: Holstein oral feed 21 days ad lib not applicable 0.8% in diet yes ca. .8 %

Reliability:

07-AUG-2006

(1)

Type: Species: Strain: Route of administration: Exposure period: Frequency of treatment: Post exposure period: Doses: Control Group: LOAEL: Method: Year: GLP: Test substance: Remark: Result:

Sex: male

other: non-protocol 1991 no other TS only three controls, sulfur content of diet not reported. However, effects so serious that they can safely be assumed to be absent in any control population. In a study with 9 young Holstein steers (validity 3, controls insufficiently desribed), a concentrate diet containing 0.8 % sodium sulfate (total sulfur content appoximately 0.36%) was given during 21 days. 3 controls were given the same diet without added sodium sulfate (total sulfur or sulfate content not reported). Five out of nine test animals vs. no controls developed clinically manifest poli-encephalomalacia (PEM) as well as macroscopically visible and histologically recognisable cerebral lesions (brain histology of not-affected animals not reported) . The onset of the disease correlated well with increasing concentrations of sulfide in the rumen. Thiamine concentrations in serum (another alleged cause of PEM) were not significantly affected. Similar disease due to high sulfur content of food was allegedly also reported earlier UNEP PUBLICATIONS 110

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

in sheep Test substance: dosing based on total sulfur content of feed, brought up to required level by adding sodium sulfate (2) valid with restrictions (45) Sub-acute other: cattle oral feed 5 weeks ad lib not applicable 3860 ppm; 5540 ppm; 7010 ppm no ca. 3860 ppm other: non-protocol 2002 no other TS three groups of 5 young heifers / group were fed diets with 3860 ppm, 5540 ppm and 7010 ppm of sulfur respectively during 5 weeks. Sulfur concentrations were reached by adding sodium sulfate to the desired level. Microscopic signs of PEM were seen in all four low-dose animals, macroscopic signs in 4/5 medium-dose and 4/5 high-dose animals. Clinical signs of PEM were seen in all animals. Onset of PEM correlated highly with sulfide concentrations in rumen. Other potential causes of PEM were excluded. (Niles, 2002.) Test substance: dosing based on total sulfur content of feed, brought up to required level by adding sodium sulfate (2) valid with restrictions No control group. Effects so serious that they can safely be assumed to be absent in any control population. (73) Chronic other: chicken other: S.C.W.L. oral feed 11 days Daily (feeding study) 1,2,3,4 or 5 % in diet yes Sex: Sex: male

Test substance: Reliability: 26-SEP-2005

Type: Species: Route of administration: Exposure period: Frequency of treatment: Post exposure period: Doses: Control Group: LOAEL: Method: Year: GLP: Test substance: Result:

Test substance: Reliability: 26-SEP-2005

Type: Species: Strain: Route of administration: Exposure period: Frequency of treatment: Doses: Control Group: Method: Year: GLP: Test substance: Method:

other: no guideline study, see freetext 1976 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: The response of chicks of 14 days of age to increasing levels of dietary sodium sulfate were investigated. Weight gain and feed intake were observed. STATISTICAL METHODS: not described METHOD OF CALCULATION: not described NOAEL (NOEL), LOAEL (LOEL): not determined - Number of deaths at each dose: No death recorded TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: yes - Mortality and time to death: No mortality UNEP PUBLICATIONS

Result:

111

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SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

- Clinical signs: not described - Body weight gain: weight gain decreased with increasing sulfate concentration. - Food/water consumption: not reported STATISTICAL RESULTS: not described TEST ORGANISMS - Age: 14 day-old male chicks - Weight at study initiation: weight was main test parameter - Number of animals: randomized block design with 60 treatments arranged as a 2x5x6 factorial, with two replications. ADMINISTRATION / EXPOSURE - Duration of test/exposure: 11 days - Type of exposure: oral - Post exposure period: not described - Vehicle: commercial diet (basal diet wth 18% crude protein) - Concentration in vehicle: 0 - 5 gram sulfate per 100 gram food - Total volume applied: water ad libitum - Doses: in daily diet 30 diets in total CLINICAL OBSERVATIONS AND FREQUENCY: - Clinical signs: no - Mortality: yes - Body weight: yes - Food consumption: yes - Water consumption: not described - Ophthalmoscopic examination: no - Haematology: no - Biochemistry: no - Urinalysis: no STATISTICAL METHODS: analysis of variance for determination of weight gain and gain:feed ration according to Snedecor, G.W. Statistical Methods, Coll. Press Ames, Iowa, USA (1956). (3) invalid documentation was insufficient for assessment (91) pig drinking water 28 days daily 54-1800 mg/l yes, concurrent vehicle Sex: no data

Test condition:

Reliability: 26-SEP-2005

Species: Route of administration: Exposure period: Frequency of treatment: Doses: Control Group: Method: Year: GLP: Test substance: Method:

other: see freetext 1992 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: The effect of sulfate in drinking water on nursery pig performance and health was examined over 28 days with 415 weaned pigs. STATISTICAL METHODS: not described METHOD OF CALCULATION: not described NOAEL (NOEL), LOAEL (LOEL): not determined ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX - Time of death: 1 pig died within the first week UNEP PUBLICATIONS 112

Result:

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

- Number of deaths at each dose: 1 pig at 600 mg/l TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: - Clinical signs: Increased prevalence of diarrhea was a trend as sulfate concentration increased. - Body weight gain: cumulative weight in kg of body-weight/kg (sd) __________________________________________________________ Week Control 600 mg/l 1800 mg/l

__________________________________________________________ 1 0.79 (0.61) 0.94 (0.78) 0.80 (0.63) 2 2.56 (1.14) 2.78 (1.90) 2.4 (1.05) 3 4.30 (1.70) 5.05 (2.67) 4.49 (1.94) 4 6.53 (2.31) 7.59 (3.37) 7.16 (2.75) __________________________________________________________ Observations in week 4 were for both 600 and 1800 mg/l statistically significantly different Increased - Food/water consumption: A non-significant trend in increase water intake was observed with increasing sulfate concentration.No differences in feed intake were observed between various sulfate concentrations. Feed to gain ratios for all treatments were not different. - Clinical chemistry: isolates of E-coli were found in 14% of the pigs, from 1 pig rotavirus was isolated. No pigs were exposed to transmissible gastroenteritis virus. None of the treatments had an adverse effect on nursery pig performance. Test condition: STATISTICAL RESULTS: not described separately TEST ORGANISMS - Age: 28 +/- 2 days - Weight at study initiation: 6.8 kg mean weight - Number of animals: 415 (male/female, males were castrated) ADMINISTRATION / EXPOSURE - Duration of test/exposure: 4 weeks - Type of exposure: drinking water - Post exposure period: not described - Vehicle: farm well water - Concentration in vehicle: 54, 600 and 1800 mg/l - Doses: continuous in drinking water - Feeding: pelleted 22% crude protein corn-soybean meal containing 20% dried whey. At the start of the third week the crude protein content was 18%. CLINICAL OBSERVATIONS AND FREQUENCY: - Clinical signs: Diarrhea, pathogenic E.coli and rota virus detection, enteropathogenicity in ligated intestinal loops, transmissable gastroentritus. - Mortality: yes - Body weight: yes, feed to gain ratio - Food consumption: yes - Water consumption: yes - Ophthalmoscopic examination: no - Haematology: yes - Biochemistry: no - Urinalysis: no ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC): - Macroscopic: no UNEP PUBLICATIONS

113

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SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

- Microscopic: no OTHER EXAMINATIONS: STATISTICAL METHODS: 7 replicates of 8 pigs/pen on water and 6 replicates of 8 pigs/pen for treatment with sulfate. Statistical evaluation compared mean water consumption, feed consumption, cumulative gain and feed-gain ratios by treatment group and week. Analysis of variance with repeated measures was used to account for the differences in treatment group over time. Initial weight was used as covariate in all analysis. Diarrhea scores were evaluated on an individual basis, using a non-parametric repeated measures design. (2) valid with restrictions Acceptable, well documented publication which meets basic scientific principles. (108)

Reliability: 26-SEP-2005

5.5 Genetic Toxicity 'in Vitro' Type: System of testing: Concentration: Cytotoxic Concentration: Metabolic activation: Result: Method: Year: GLP: Test substance: Method: Ames test S. Typhimurium TA1535, TA1537, TA100, TA98 312.5 to 5000 g per plate with 4 dilutions no cytotoxicity observed with and without negative

other: Salmonella/Microsome test, Ames et al, Mutation Res. 31, 347-364 (1975) 1988 yes as prescribed by 1.1 - 1.4 METHOD FOLLOWED: Ames test as described by Ames et al (1975). Test was performed in duplicate with varying concentration range. DEVIATIONS FROM GUIDELINE: no guideline study GLP: yes STATISTICAL METHODS: not applicable METHOD OF CALCULATION: not applicable ANALYTICAL METHODS: not described EFFECTS: - With metabolic activation: both tests, no effects - Without metabolic activation: both tests, no effects FREQUENCY OF EFFECTS: n.a. PRECIPITATION CONCENTRATION: not described MITOTIC INDEX: not described CYTOTOXIC CONCENTRATION: no toxicity observed up to 5000 mg/l TEST-SPECIFIC CONFOUNDING FACTORS: not described STATISTICAL RESULTS: n.a. SYSTEM OF TESTING - Species/cell type: Salmonella typhimurium LT2 mutants: TA 1535, TA 100, TA 1537, TA 98 - Deficiences/Proficiences: Histidine - Metabolic activation system: LT2 system - No. of metaphases analyzed: not described ADMINISTRATION: - Dosing: 4 concentrations, 312.5-625-1250-2500-5000 mg/l and 8-40-200-1000-5000 mg/l - Number of replicates: 4 per test UNEP PUBLICATIONS 114

Result:

Test condition:

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

- Application: plate - Positive and negative control groups and treatment: pos. control: sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine and 2-aminoanthracene; negative control - Pre-incubation time: not described CRITERIA FOR EVALUATING RESULTS: Based on Maron and Ames (1983). (1) valid without restriction Comparable to guideline study (13) Cytogenetic assay human blood lymphocytes 5*10e-5 to 5*10e-3 M no data no data negative

Reliability: 26-SEP-2005

Type: System of testing: Concentration: Cytotoxic Concentration: Metabolic activation: Result: Method: Year: GLP: Test substance: Method:

other: not specified 1992 no no data SYSTEM OF TESTING - Species/cell type: human lymphocytes - Deficiences/Proficiences: - Metabolic activation system: - No. of metaphases analyzed: ADMINISTRATION: - Dosing: - Number of replicates: - Application: - Positive and negative control groups and treatment: - Pre-incubation time: DESCRIPTION OF FOLLOW UP REPEAT STUDY: CRITERIA FOR EVALUATING RESULTS: GENOTOXIC EFFECTS: - With metabolic activation: - Without metabolic activation: FREQUENCY OF EFFECTS: PRECIPITATION CONCENTRATION: MITOTIC INDEX: CYTOTOXIC CONCENTRATION: - With metabolic activation: - Without metabolic activation: TEST-SPECIFIC CONFOUNDING FACTORS: STATISTICAL RESULTS: The frequency of chromosomal abberations, sister chromatid exchanges, and micronuclei was not increased in human blood lymphocytes in this experiment. Also there were no changes in mitotic index or lymphocyte cell cycle. No data on the test substance sodium sulfate. (4) not assignable Not assignable. Results are given but this is just a statement. No expsrimental data are given. The study is non-GLP and non-guideline. (66)

Result:

Test substance: Reliability:

26-SEP-2005

115

UNEP PUBLICATIONS

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

5.6 Genetic Toxicity 'in Vivo' 5.7 Carcinogenicity Species: Strain: Route of administration: Exposure period: Frequency of treatment: Doses: Result: Control Group: Method: Year: GLP: Test substance: Method: rat Sprague-Dawley oral feed up to 27 or 44 weeks daily (feeding study) 0.84 % in diet negative yes Sex: male

other: no standardized method used 1975 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: Male rats were fed diets containing Na2SO4. The study was part of a toxicity study on Azo Dyes. The sodium sulfate were included as control series. METHOD OF CALCULATION: not described MORTALITY: no mortality was observed (10 surviving rats in both series) in both test series after 27 and 44 weeks of exposure as compared to control (10 surviving rats). CLINICAL SIGNS: No tumors were detected. No evidence of hyperplastic and/or dysplatic change after 16 weeks. No cholangiofibrosis or mild cirrhosis in the liver after 16 weeks were observed as compared to control. BODY WEIGHT CHANGES: No significant differences in overall body weight gain or in liver weight were observed. ____________________________________________________________ _group Eff.no. starting no. of Terminal Terminal of rats weight g rats body wght liver wght +/- SD surviving g +/- SD g +/- SD mean mean mean ____________________________________________________________ _ Control a 5 230.8-18.6 2 358.5 10.11 b 5 193.4 33.6 5 358.4-16.0 10.2-0.49 Na2SO4 a 5 252.0-30.2 3 414.7-39.5 14.3-1.42 b 5 194.2-35.7 5 332.0-53.7 10.03-0.99 ____________________________________________________________ _ FOOD AND WATER CONSUMPTION CHANGES: no changes observed TEST ORGANISMS - Age: not described - Weight at study initiation: mean weight of animals 211.6 gram - Number of animals: total 90 , 5 in a cage ADMINISTRATION / EXPOSURE - Duration of test/exposure: Study was divided in two series. One series lasted 27 weeks, and the other 44 weeks - Type of exposure: feeding study, daily feeding UNEP PUBLICATIONS 116

Result:

Test condition:

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

- Post exposure period: no FOR ORAL STUDIES: - Vehicle: maize oil - Concentration in vehicle: 8.4 gram/kg - Total volume applied: 30 ml - Doses: 0.84 % in diet CLINICAL OBSERVATIONS AND FREQUENCY - Body weight: yes - Food consumption: Basal diet consited of pellets with 15-16% protein, 6-8% fat and 8-9 % fibre (Victoria Wheat growers Corp. Ltd, Melbourne, Aus.). The consumption rate was 10 g/rat per day at the start up to 17 g/rat per day at the end of the study. - Water consumption: free acces to tap water - Clinical signs: not described - Mortality: yes - Macroscopic examination: yes - Ophthalmoscopic examination: not described - Haematology: yes, haemoglobin estimations were performed. - Clinical chemistry: not described - Urinalysis: not described ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC): - Macroscopic: spleen, liver - Microscopic: not described OTHER EXAMINATIONS: lung sections were examined after staining with haematoxylin, eosin and the PAS method. STATISTICAL METHODS: The probability of observing liver tumors of 1 cm or more in diameter, and evidence of metastatic spread or multiple tumors at death was calculated by an actuarial method, as described by Pilgrim and Dowd, Cancer Res. 23, 45 (1963). Differences between numbers rats bearing tumours of at least 1 cm diameter, were compared using Fisher's exact test. (3) invalid No guideline study, 5 male animals only (16) mouse Swiss Sex: male/female

Reliability: 26-SEP-2005 Species: Strain:

Route of administration: Exposure period: Frequency of treatment: Doses: Result: Control Group: Method: Year: GLP: Test substance: Method:

s.c. 26 weeks weekly 31 g in 0.01 ml sodium chloride (0.9%) per g body weight / week negative other: Na2SO4 served as control for 4-HMBD / historical controls

other: see freetext 1987 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: Test was control test of investigation of carcinogenity of 4-(hydroxymethyl)benzenediazonium ion in mice. Mice were treated for 26 weeks, and observed for 150 weeks, to test substance and control (Na2SO4) METHOD OF CALCULATION: not described MORTALITY AND TIME TO DEATH: see attachement, table I UNEP PUBLICATIONS

Result: 117

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

CLINICAL SIGNS: see attachment, table II BODY WEIGHT GAIN: not described FOOD/WATER CONSUMPTION: not described GROSS PATHOLOGY: see attachment, table II HISTOPATHOLOGY: see attachementm, table II OTHER: see attachment, table II TIME TO TUMOURS: see attachment, table II STATISTICAL RESULTS: not described TEST ORGANISMS - Age: 6 weeks (50:50 male/female) - Weight at study initiation: not described - Number of animals: 50 male and 50 female ADMINISTRATION / EXPOSURE - Duration of test/exposure: 26 weeks - Type of exposure: subcutaneously injections weekly - Post exposure period: not described FOR ORAL STUDIES: - Vehicle: 0.9 %v sodium chloride - Concentration in vehicle: 31 g per 0.01 ml vehicle per g body weight - Total volume applied: not described - Doses: weekly CLINICAL OBSERVATIONS AND FREQUENCY - Body weight: yes - Food consumption: no - Water consumption: no - Clinical signs: yes - Mortality: yes - Macroscopic examination: yes - Ophthalmoscopic examination: no - Haematology: no - Clinical chemistry: no - Urinalysis: no ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC): - Macroscopic Histological study: skin, subcutis, liver, spleen, kidneys, bladder, thyroid, heart, pancreas, testes, ovaries, uterus, nasal turbinals, lungs - Microscopic: Yes, after staining with hematoxylin and eosin OTHER EXAMINATIONS: All other pathological changes STATISTICAL METHODS: not described RS2-Toth.doc (3) invalid (97)

Test condition:

Attached doc.: Reliability: 26-SEP-2005

5.8.1 Toxicity to Fertility Type: Species: Sex: Strain: Route of administration: Exposure Period: Frequency of treatment: Premating Exposure Period male: female: Duration of test: No. of generation studies: Doses: other: two parities using the same mice mouse female ICR drinking water 1 week prior to breeding until study termination drinking water was avaialble ad libitum no exposure 1 week 1 week prior to breeding until study termination 1 0, 0.924, 1.848, 3.696, 7.392 g/liter UNEP PUBLICATIONS 118

OECD SIDS 5. TOXICITY

Control Group:

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

other: One control group received deionized distilled water and one received deionized distilled water with 2,392 ppm Na NOAEL Parental: >= 7392 mg/l NOAEL F1 Offspring: >= 7392 mg/l other: NOAEL F1 Offspring 2 : >= 7392 mg/l Result: No effects on litter size and weaning weight were seen. Reproductive performance is not affected in this study. Method: Year: GLP: Test substance: Method: other: not specified 1988 no as prescribed by 1.1 - 1.4 TEST ORGANISMS: ICR mouse ADMINISTRATION / EXPOSURE - Type of exposure: drinking water - Duration of test/exposure: 1 week before study until study termination. - Treatment: drinking water was available ad libitum - Control group and treatment: One control group received deionized distilled water and one received deionized distilled water with 2,392 ppm Na - Vehicle: deionized water - Concentration in vehicle: 0, 0.924, 1.848, 3.696, 7.392 g/liter - Total volume applied: - Doses: drinking water with 0, 0.924, 1.848, 3.696, 7.392 g/liter sodium sulfate ad libitum. - Concentrations: - Particle size: - Type or preparation of particles:MATING PROCEDURES: After one week a male mouse that had received tap water only was randomely bred withe ach female mouse. The female was checked every day for a vaginal plug. When a vaginal plug was observed the male was removed. STANDARDIZATION OF LITTERS: The litter were standardized to 8 pups per litter. The dams with fewer tahn 8 pups received pups from other dams in the same dose group. If these were not available they were assigned pups from a lower dose group. PARAMETERS ASSESSED DURING STUDY P AND F1(1) AND F1(2): - Clinical observations: water consumption was measured daily during the 2nd and 3rd week of gestationa and 1st and 2nd week of lacation. (the measureemnts during week 1 of gestation were discarted due to leakage from drinking bottles, the measurements performed during week 3 of lacation were also discarted because the pups started drinking water). Bodyweights of the dams were recorded at parturition and litter sizes were determined. At 21 days pp the dams and litters were weighed. - Estrous cycle: - Sperm examination: - Others: OFFSPRING: ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC): - Organ weights P and F1: UNEP PUBLICATIONS

119

OECD SIDS 5. TOXICITY

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

- Histopathology P and F1: - Histopathology F1 not selected for mating, F2: OTHER EXAMINATIONS: STATISTICAL METHODS: The description of the statistical analysis remains unclear: The least square mean analysis of variance technique was used to analyze the data. One contrast was used to compare the different groups. Sulfate treatment effects were partitioned into linear, quadratic and cubic components using orthogonal contrasts. Student's t-test were used to determine the difference in water consumption between weeks in both gestation and lactation. NOAEL (NOEL): 7392 mg/l = 5000 ppm ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX: TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: - Parental data and F1: - Body weight: gestational and lactational body weight gian was not influenced by level of sulfate consumed. - Food/water consumption: a decrease in water consumption was seen. It is suggested that the amials became acclimated to the high sulfate levels because the water consumtion levels ere higher during the 2nd week of lactation comared to the 1st week during the 2nd parity. - Description, severity, time of onset and duration of clinical signs: - Fertility index: - Precoital interval: - Duration of gestation: - Gestation index: - Changes in lactation: - Changes in estrus cycles: - Effects on sperm: - Hematological findings incidence and severity:- Clinical biochemistry findings incidence and severity: - Mortality: 0 - Gross pathology incidence and severity: - Number of implantations: - Number of corpora lutea: - Ovarian primordial follicle counts: - Organ weight changes: - Histopathology incidence and severity: - Offspring toxicity F1 and F2: - Litter size and weights: litter size was not affected by treatment. - Sex and sex ratios: - Viability index: none of the pups died. - Post natal survival until weaning: none of the pups died. - Effects on offspring: - Postnatal growth, growth rate: - Vaginal opening (F) or preputial separation (M): - Other observations; STATISTICAL RESULTS: Sodium sulfate, reagent grade. (4) not assignable Non-GLP and non-guideline study. Not sufficiently detailed. The set up of the study differs from the standard. Mice were exposed from 1 week before the study until study termination. The same female mice gave birth to the first and the second litter. The litter was weaned at 21 days pp and the mice were mated again.The males were not exposed. Possibly only the mice with two subsequent litters were UNEP PUBLICATIONS 120

Result:

Test substance: Reliability:

OECD SIDS 5. TOXICITY

involved in the analysis. 27-SEP-2005 5.8.2 Developmental Toxicity/Teratogenicity Species: Strain: Route of administration: Exposure period: Frequency of treatment: Duration of test: Doses: Control Group: Method: Year: GLP: Result:

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(7)

mouse Sex: female other: ICR/SIM other: oral (gavage) 4 days (gestation day 8-12) once daily up to day 22 of pregnancy 2800 mg/kg/day other: yes (N=28, vehicle alone H2O)

other: no guideline study 1986 no As part of a validation of a developmental screen, pregnant mice were exposed to 55 compounds, composed of known teratogens, known non-teratogens or equivocal substances. Exposure: single daily dose by gavage; dose level at or near induction of maternal toxicity. Vehicle alone (H20): 15 control groups of 28-30 mice. Vehicle alone (Corn oil): 13 control groups of 28-30 mice. Endpoints: maternal weight gain, delivery rate, litter size, % live birhts, pup weight day 1 and day 3, neonatal survival rate, macrospoci visceral and skeletal abnormalities Statistical analysis: maternal weight :two-tailed analysis of variance live and dead litter size: one-tailed analysis of variance neonatal survival rate: Fisher one-tailed exact probability. neonatal weight: two-tailed analysis of variance with litter size as co-variant Overal results: reported "Seidenberg JM , Becker RA: A summary of the results of 55 chemiclas screened for developmental toxicity im mice. Teratogenesis, Carcinogenesis, Mutagenesis 7:17-28 (1987) Results for sodium sulfate: Compared to controls, slight increase in neonatal body weigh at day 1 pp.(1.80+0.14 vs 1.72 + 0.13 grams). Normal maternal weight gain, normal delivery rate, normal litter size, normal nr. of live births, normal weight of pups on day 3, no macroscopic visceral or sceletal abnormalities Na2SO4, not specified (2) valid with restrictions non-standard screening test. (90) mouse Sex: female other: ICS/SIM other: oral (gavage) 4 days (gestation day 8-12) once daily up to day 22 of pregnancy Na2SO4: 2800 mg/kg other: yes (N=28, vehicle alone H2O)

Test substance: Reliability: 26-SEP-2005

Species: Strain: Route of administration: Exposure period: Frequency of treatment: Duration of test: Doses: Control Group: Method: 121

other: no guideline study UNEP PUBLICATIONS

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Year: GLP: Remark: Result: 1987 no

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Test substance: Reliability: 27-SEP-2005

Reviewer disagrees, slight increase in body weight of neonates on day 1 p.p. only is not an adverse effect and is biologically totally irrelevant. Summary of results of a screening study fully described in: Seidenberg JM, Anderson DG, ecker RA: validation of an in vivo developmental screen in the mouse. Teratogenesis, Carcinogenesis and Mutagenesis, 6:361-374 (1986) See RS Overal results: 24 of 26 substances previously reported as positive in teratogenicity / embryotoxicity tests scored positive in this screen. 93% of substances previously reported as negative scored negative in this screen. equivocal substances 4of 5 positive in this screen no data: 3 out of 9 considered positive, among them sodium sulfate. Results for sodium sulfate: Compared to controls, slight increase in neonatal body weigh at day 1 pp.(1.80+ -0.14 vs 1.72 + -0.13 grams). Normal maternal weight gain, normal delivery rate, normal litter size, normal nr. of live births, normal weight of pups on day 3, no macroscopic visceral or sceletal abnormalities; Considered by authors as a positive outcome of screening test. Na2SO4, not specified (2) valid with restrictions non-standard screening test.; scoring criteria too strict. (89) mouse Sex: female other: CF-1 s.c. single injection at day 8 or 9 of gestation not described 60 mg/kg bw yes increased maternal weight gain, no soft tissue abnormalities, increase of skeletal abnormalities (delayed ossification)

Species: Strain: Route of administration: Frequency of treatment: Duration of test: Doses: Control Group: Result:

Method: Year: GLP: Test substance: Method:

other: no standardized method used 1973 no as prescribed by 1.1 - 1.4 METHOD FOLLOWED: The teratogenic effects of sodium sulfate injected s.c. in albino mice was investigated. The study examined mice after administration at day 8 and 9 of gestation. STATISTICAL METHODS: not described METHOD OF CALCULATION: not described NOAEL (NOEL), LOAEL (LOEL): not determined MATERNAL TOXIC EFFECTS BY DOSE LEVEL: - Mortality and day of death: not described - Number aborting: not described - Number of resorptions: See attachement - Duration of Pregnancy: not described UNEP PUBLICATIONS 122

Result:

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- Body weight: see attachement - Food/water consumption: not described - Description, severity, time of onset and duration of clinical signs: Soft tissue abnormalities were not significantly different from the control group. Skeletal abnormalities , described as delayed ossification, especially in phalanges, sternebrae and skull, were statistically different form control group . - Hematological findings incidence and severity: not described - Clinical biochemistry findings incidence and severity: not described - Gross pathology incidence and severity: - Organ weight changes: - Histopathology incidence and severity: FETAL DATA: - Litter size and weights: 6, no weight determined - Number viable: 51 fetuses -Sex ratio: not determined - Postnatal growth: not described - Postnatal survival: not described - Grossly visible abnormalities: no abnormalities - External abnormalities: see attachement, no abnormalities - Soft tissue abnormalities: see attachement, no abnormalities - Skeletal abnormalities: see attachement, no abnormalities

Test condition:

Attached doc.: Reliability:

STATISTICAL RESULTS: not described TEST ORGANISMS: Albino mice (CF-1) (25-30 gram), obtained from Carworth Farms, Inc. New York, USA. ADMINISTRATION / EXPOSURE - Type of exposure: injection subcutaneous - Duration of test/exposure: as described by Iuliucci, J.D., Gautieri, R.F., J. Pharm. Sci, 60:420 (1971). - Treatment: at day 8 or 9 of gestation - Control group and treatment: yes, untreated (saline) - Vehicle: distilled water - Concentration in vehicle: 10 mg/ml - Total volume applied: not described - Doses: one injection - Concentrations: 60 mg/kg body weight PARAMETERS ASSESSED DURING STUDY: - Body weight gain: yes, ratio between start and end of study - Food consumption: no - Clinical observations: yes, soft tissue abnormalities, skeletal abnormalities and resorption uterine horns - Examination of uterine content: no - Examination of fetuses: yes - Litter : yes ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC): OTHER EXAMINATIONS: Exencephaly, Axial skeletal fusions and cryptorchid testes. STATISTICAL METHODS: as described by Iuliucci, J.D., Gautieri, R.F., J. Pharm. Sci, 60:420 (1971). RS1-Arcuri&Gautieri.doc (2) valid with restrictions Not a guideline study. Experiment described in detail. Not UNEP PUBLICATIONS

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all parameters determined. Endpoints are not all clearly described.

27-SEP-2005 5.8.3 Toxicity to Reproduction, Other Studies 5.9 Specific Investigations 5.10 Exposure Experience Type of experience: Method: Human - Epidemiology

(9)

Result:

Method: Cross-sectional study, internal sub-cohort study Subjects: 119 male workers from natural sodium sulfate mines. Age range: 17 to 58 exposure duration: 0.6-31 years (no control group, study outcomes compared with "normal values", source not given). Exposure: Na2SO4 dust ,range 5 mg/m3 to 150 mg/m3 (sampling method, strategy, number, frequency and timespan of sampling not given). General medical screening, lung function tests, blood pressure, skin condition, gastro-intestinal functioning, serum sodium, calcium, potassium chloride and sulfate content were all within normal ranges ( i.e presumably as found in the general population). Mean urinary excretion of inorganic sulfate exceeded 2.2 gr/liter in all workers and thirty percent of the workers excreted more than 3 gr of inorganic sulfate per day, indicating massive uptake from recent exposure. The only subjective symptom indicated by the workers was nasal irritation and runny noses on exposure to dust. Internal sub-cohort study: Short exposure duration subcohort: subjects: More than 10 years of exposure (n=77) age 28.0 +-10, exposure duration 3.1 + 2.8 years Long exposure duration subcohort: Subjects: more than 10 years exposure (n=42) age 454.5 + 8.8, exposure duration 19.9 + 3.6 years Results: No differences other than explained by age difference. (2) valid with restrictions Absence of control group, incomplete description of exposure and possibility for healthy worker effect severely restrict extrapolation (59) Livestock - Exposure through Feeding Method: 31 sows and 27 gilts were each allotted to three treatments to study the effect of water quality during gestation and lactation. Sulfate was added to the water at concentrations UNEP PUBLICATIONS 124

Reliability:

01-DEC-2004 Type of experience: Remark:

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SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

in three treatments (1) 320 - 620 mg/l (2) 1820 - 2840 mg/l (3) 3320 - 5080 mg/l. Water was offered ad libitum. from 30 days post-breeding through 28 days lactation. Results: There was no significant difference in gestation or lactation, number or weight of pigs at birth or at weaning. Water consumption did not differ during gestation, but increased as salt levels increased. Water consumption was 13.6, 14.2 and 16.8 liter/day for lactating females in treatment 1, 2 and 3. These results suggests that sulfates up to and including 3320 mg/l, in water have no significant effect on reproduction in the gilt or sow. (3) invalid Documentation insufficient for assessment other: Human - controlled study METHOD: The objective of the study was to provide additional information regarding whether sensitive populations (infants and transients) may be adversely affected by sudden exposure to drinking water containing high levels of sulfate. One hundred and five study participants were divided among the dose groups as follows: 24 received 0 mg/L sulfate; 10 received 250 mg/L sulfate; 10 received 500 mg/L sulfate; 33 received 800 mg/L sulfate; and 28 received 1200 mg/L sulfate. The number of bowel movements recorded each day by study participants were analyzed. There were no statistically significant differences in the bowel movements among the groups on days 3, 4, 5, or 6. There were also no statistically significant differences in the bowel movements reported when comparing days 1 and 2 (the days when there was no sulfate in the water) with days 3, 4, and 5 within each dose group. To examine the data for a trend toward increased frequency of reports of diarrhea with increased dose of sulfate, a logistic regression model were the dose as an ordinal variable was included for osmotic diarrhea was included. There was no statistically significant increase in reports of diarrhea with increasing dose (one-sided p = 0.099). RESULTS: One hundred five study participants were divided among the dose groups as follows: 24 received 0 mg/L sulfate; 10 received 250 mg/L sulfate; 10 received 500 mg/L sulfate; 33 received 800 mg/L sulfate; and 28 received 1200 mg/L sulfate. The demographic information for the study population was as follows: the mean age of participants was 42 years; the majority (62%) was female; the races included in the study population were white (80%), black (13%), and Asian/Pacific Islander (7%). Ninety-five percent of the participants were non-Hispanic. (79)

Reliability: 07-NOV-2001 Type of experience: Remark:

125

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In the experimental trials with adult volunteers, no significant dose-response association between acute exposure to sodium sulfate in water (up to 1200 mg/L) and reports of diarrhea were found. However, a weak (not statistically significant) increase in reports of diarrhea at the highest dose level when it was compared to the combined lower doses was observed. Remark: concentration in drinking water known, but not actual dose. (4) not assignable Documentation insufficient for assessment: Abstract only. (76) Human Inhalation of sodium sulfate dust causes irritation of the mucuous membranes, and prolonged skin contact has a drying effect. (3) invalid Documentation insufficient for assessment. (101) Livestock - Exposure through Feeding Association between sulfate in drinking water and diarrhea in swine was investigated. Sulfate concentrations ranged from 5.99 to 1629 mg/l recorded at 54 farms in Ohio USA. Associations between sulfate concentrations and prevalence of diarrhea could not be established. (3) invalid Documentation insufficient for assessment (107) Human - Epidemiology Evaluation of infant diarrhea associated with elevated levels of sulfate in drinking water. Method: 274 households were investigated in South-Dakota USA. Sulfate concentrations in drinking water was determined. Data on infant diarrhea were collected using questionnaires. Logistic regression was used to estimate the risk for diarrhea. Results: 69% of the households drank municipal water and 54% used it in the infants diet. 39 infants developed diarrhea. Of the 170 households that submitted water samples, 141 were using the water in the infants diet. The median sulfate concentration of the water was 264 mg/l. 25 infants developed diarrhea. Average infant daily sulfate intake was not significantly associated with an increase diarrhea rate. There was no significant association between sulfate intake and the incidence of diarrhea for the range of sulfate studies. There was no effect of a dose-response or threshold effect. (4) not assignable UNEP PUBLICATIONS 126

Reliability: 27-SEP-2005 Type of experience: Remark: Reliability: 27-SEP-2005 Type of experience: Remark:

Reliability: 26-SEP-2005 Type of experience: Remark:

Reliability:

OECD SIDS 5. TOXICITY

Only secondary literature available 09-NOV-2001 Type of experience: Remark: Livestock - Exposure through Feeding

SODIUM SULFATE ID: 7757-82-6 DATE: 06.07.2006

(39)

Artificially reared neonatal piglets were used to study the effect of inorganic sodium sulfate on bowel function in human infants. Method: Two experiments were conducted to evaluate the effect of high levels of inorganic sulfate intake on the growth, feed intake and feaces consistency. 40 pigs with an average age of 5d were individually caged abd reared with an automatic feeding device. Ten pigs per dietary treatment were fed one of four diets containing the following levels of inorganic sodium sulfate (mg/l diet): 0, 1200, 1600, 2000 for exp 1 (18 days study), and 0, 800, 2000, 22000 for exp. 2 (16 days study). Results: The levels of sulfate did not affect (P>0.05) the growth of piglets, or their food intake. 1200 mg/l sulfate had no effect on feaces consistency, while 1800 mg/l sulfate did (non-pathogenic diarrhea). Added sulfate did not affect (P> 0.05) relative kidney weight. The results suggest that the level of added dietary inorganic sulfate at which 50% of piglets develop nonpathogenic diarrhea is between 1600 and 1800 mg/l. (2) valid with restrictions Acceptable, well documented study. (43) Direct observation, poisoning incidents Two outbreaks of poisoning (eosinophilic meningoencephalitis) in pigs due to treatment with sodium sulfate. Experimental reproduction indicated a similar syndrome. Method: 8 12 weeks old pigs were each given by drneching gun 50 gram of sodium sulfate, dissolved in a minimum amount of water daily for 3 consecutive days. Controls were treated with water. Results: 2 of the treated pigs were found dead on day 4, and 3 were in prostrate and in extremis. The latter 3 animals were killed for examination. The three were all inco-ordination, blind and had epileptiform convulsions. Histopathological examination revelaed lesions of the central nervous system, vacuolation, nueronal degeneration, cortical laminar malacia. Large numbers of eosinophils and some macrophages were present in the meninges and in the perivascular spaces in the cortical white matter. (3) invalid Documentation insufficient for assessment (32) Human - Exposure through Food UNEP PUBLICATIONS

Reliability: 22-JUN-2005 Type of experience: Remark:

Reliability: 22-JUN-2005 Type of experience: 127

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Three illustrative cases of diarrhea in infants in Canada following ingestion of well waters with a sulfate content above 600 mg/l. Other causes such as infections or other presence of chemicals were excluded. The estimated daily dose would have been around 70- 100 mg/kg/day. It is recommended that water with more than 400 mg/l sulphate be regarded as unsuitable for infant feeding. Remark: clinically, cause and effect relationship clearly established. Extrapolation to general population not possible in the absence of data on the population at risk and incidence (4) not assignable (25)

Remark:

Reliability: 27-SEP-2005

5.11 Additional Remarks Type: Remark: Toxicokinetics Review: Sulfate is a normal constituent of the blood and is a normal metabolite of sulfur-containing amino acids, and excess sulfate is excreted in the urine. Daily sulfate excretion is reported to be 0.20 to 0.25 mmol/kg bw/day and higher in children. In male adult Wistar rats, approximately 73% of dietary calcium or magnesium sulfate salts was absorbed, although absorption was partly dependent on other dietary elements. (4) not assignable (50) other: Oral toxicity to pigs Sodium sulfate (Glauber's salt) toxicity was observed in pigs after drenching eight-week old pigs with 50 g sodium sulfate for three days, and restricting their water supply. The animals showed nervous signs, twitching, tremors and convulsions. The most noticeable lesion at post mortem was widespread vacuolation and necrosis of the cerebral cortex. The sodium concentration of the cerebrospinal fluid was significantly higher than normal. (3) invalid Documentation insufficient for assessment (26)

Reliability: 29-SEP-2005 Type: Remark:

Reliability: 26-SEP-2005

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(1) Adams, A.W., Cunningham, F.E., Munger, L.L. (1975). Some effects on layers of sodium sulfate and magnesium sulfate in their drinking water. Poultry Sci. 54(3):707-714. (2) Allgemeine Verwaltungsvorschrift (1990). Uber die nahere bestimmung wassergefahrdender stoffe und ihre einstufung entsprechend ihrer gefahrlichkeit-VwV wassergefahrende stoffe (VwVwS) 9.3.1990. (3) Ambient water Quality Guidelines for sulphate (2000). Ministry of Environment, Lands and Parks Province of British Columbia, Water Quality Section Water Management Branch Victoria, BC, Canada. (4) Amdur M.O., Bayles, J., Ugro, V., Underhill, D.W. (1978). Comparative irritant potency of sulphate salts. Environ. Res. 16(1-3):1-8. (5) Anderson, B.G. (1944). The toxicity thresholds of various substances found in industrial wastes as determined by the use of daphnia magna. Sewage Works J. 16(6):1156-1165. (6) Anderson, B.G. (1946). Industrial wastes - The toxicity thresholds of various sodium salts determined by the use of daphnia magna. Sewage Works J. 18(1):82-87. (7) Andres, C.J. Cline, T.R. (1989). Influence of Sulfate in Drinking Water on Mouse Reproduction during two Parities. Journal of Animal. Sciences. 67:1313-1317. (8) Arambasic, M.B., Bjelic, S., Subakov, G. (1995). Acute toxicity of heavy metals (copper, lead, zinc), phenol and sodium on Allium cepa l., Lepidium sativum l. and Daphnia magnaSt.: comparitive investigations and the practical applications. Water Res. 29(2):497-503. (9) Arcuri, P. and Gautieri, F. J. (1973). Morphine-induced fetal malformations. 3. Possible mechanisms of action. Pharmaceut. Sci. 62(10): 1626-1634. (10) Awasthi, S.P.(1989). Effect of different salts on the nodulation of Vigna radiata (L.) Wilczeck. J. Phytol. Res. 2(1): 109-112. (11) Banet, G., Wininger, S., Badani, H., Ben-Dor, B., Friedman andY., Kapulnik, Y. (1996). Toxic and osmitic effects of salinity on growth and nodulation of Medicago sativa. Symbiosis. 21:209-222. (12) Bauer, J.H. (1976) Oral administration of radioactive sulfate to measure extracellular fluid space in man. J. Appl. Physiol. 40(4):648-650. (13) Bayer A.G. (1988). Salmonella/Microsome test to evaluate for point mutagenic effects. Unpublished report. Study no. T9027163, Report no. 16839, Wuppertal, Germany.

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(14) Bayer AG data

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(15) BC Ministry of Environment, Lands and Parks, and Environment Canada, (1996)ac. State of water Quality of Liard river at Fort Liard, 1984-1995, Canada-British Columbia water Quality Monitoring agreement. (16) Blunck, J.M. and Crowther, C.E. (1975). Enhancement of azo dye carcinogenesis by dietary sodium sulphate. Europ. J. Cancer. 11(1): 23-31. (17) British Chrome & Chemicals, Cleveland, producers data. (18) Bundesminister des Innern (1990): Gemeinsames Ministerialblatt Nr.41 Jahrgang 8 (1990). (19) Bundesminister des Innern (1996). Gemeinsames Ministerialblatt Nr.16, 47, Jahrgang 345, Kenn-nr. 286 (29-04-1996). (20) Bycov, L.A. et al. (1977). Neftepererab. Neftekhim. (Moscow) ISS 4:40-41. (21) Cairns, J.C.J., and Scheier, A. (1959). The relationship of Bluegill sunfish body size to tolerance for some common chemicals. Proc. 13th Ind. Waste. Conf., Purdue Univ. Eng. Bull 96:243-252. (22) CFTA (1976). Allergic contact sensitization test (Test No. <intentionally blanked-out>.003-76) on Bubble Bath 60082-C containing 80.8% Sodium Sulfate. Unpublished report. Study no. <intentionally blanked-out>.003-76, Report no. Not stated. (23) Chapmann and Hall (1992). Dictionary of Inorganic Compounds. Vol.3. (24) Chemiekaarten (2000). pp. 921, C-0979, The Netherlands. (25) Chien, L., Robertson, H., Gerrard, J. (1968). Infantile gastroenteritis due to water with high sulfate content. Can. Med. Assoc. J. 99:102-104. (26) Clarke, M., Harvey, D.G., Humphreys, D.J. (1981). Sodium sulphate. Veterinary Toxicology. 2nd ed. London:Bailliere Tindall, p.42. (27) Cocchetto, D.M. and Levy, G. (1981). Absorption of orally administered sodium sulfate in humans. J. Pharm. Sci. 70(3):331-333. (28) Croser, C., Renault, S., Franklin, J and Zwiazek, J. (2001). The effect of salinity on the emergence and seedling growth of Picea mariana, Picea glauca and Pinus bankciana. Environmentla pollution. 115:9-16. (29) Denisov, Y.N. and Tkachev, P.G. (1989). Hygienic characteristics of small doses of sodium sulfate after its inhalation. Gigiena i sanitaria. 4:69-71. (30) Denisov, Y.N. and Tkachev, P.G. (1990). Health aspects of UNEP PUBLICATIONS 130

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sodium salts of sulfurous and sulfuric acids as environmental pollutants. Gigiena i sanitariia. 9:11-13.

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(31) Diem, K. (ed.) (1972). Documenta Geigy scientific tables. 6th edition. J.R. Geigy S.A., Basle, Switzerland. 533 pp. (32) Dow, C., Lawson, G.H.K., Todd, J.R. (1963). Sodium sulphate toxicity in pigs. Vet. Rec. 75:1052-1055. (33) Dowden, B.F. (1961). Cumulative toxicities of some inorganic salts to Daphnia maena as determined by median tolerance limits. Proc. La. Acad. Sci. 23:77-85. (34) Dowden, B.F. and Bennett H.J. (1965). Toxicity of selected chemicals to certain animals. J. Water Pollut. Control Fed. 37(9):1308-1316. (35) Egan, T.P. and Ungar, I.A. (1998). Effect of different salts of sodium and potassium on the growth of Atriplex prostrata (Chenopodiaceae). Journal of plant nutrition. 21(10):2193-2205. (36) Environment Canada (1985). Tech Info for Problem Spills: Sodium sulfate. (37) Environment Canada. (1984). Detailed surface water quality data, Northwest Territories 1980-1981, Alberta 1980-1981, Saskatchewan 1980-1981. Manitoba 1980-1981. Unpublished results provided by Inland Waters Directorate, Ottawa. Cited from Health Canada, 1996. (38) EPI Suite (2000). U.S. Environmental Protection Agency. (39) Esteban, E., Rubin, C., McGeehin, M., Flanders, D., Baker, M.J., Sinks, T.H. (1997). Evaluation of human health effects associated with elevated levels of sulfate in drinking water: a cohort investigation in South Dakota. manuscript submitted. Int. J. Occup. Med. Environ. Health. 3:171-176. (40) Gilli, G. and Comune, P.M. (1980). Effetti della salinit su sistemi biologici. Inquinamento 22(100):31-35. (41) Gilman, A.G., Goodman, L.S., Gilman, A. (eds). (1980). Goodman and Gilman's The Pharmalogical Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co. Inc. p.1005. (42) Goetsch, P.A. and Palmer, C.G. (1997). Salinity tolerance of selected macroinvertebrates of the Sabie river, Kruger national park, South Africa. Arch. Environ. Contam. Toxicol. 32:32-41. (43) Gomez, G.G., Sandler, R.S., Seal, E., Jr. (1995). High levels of inorganic sulfate cause diarrhea in neonatal piglets. J. Nutr. 125:2325-2322. (44) Gosh, T.K., Konar, S.K. (1980). Toxicity of chemicals and wastewaters of paper and pulp mills to worms plankton and 131 UNEP PUBLICATIONS

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molluscs. Indian J. Environ. Hlth. 22(4):278-285.

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(45) Gould, D.H., McAllister, M.M., Savage, J.C., Hamar, D.W. (1991). High sulfide, concentrations in rumen fluid associated with nutritionally induced polioencephalomalacia in calves. Am. J. Vet. Res.51(7):1164-1169. (46) Greben, H.A., Maree, J.P., Mnqanqeni, S., (2000). Comparison between sucrose, ethanol and methanol as carbon and energy source for biological sulphate reduction. Water Science and Technol. 41(12):247-253. (47) Handbook of chemistry and Physics (1997-1998). 78th ed. CRC press, pp. 4-87. (48) Handbook of Chemistry and Physics (2003-2004). 84th ed. CRC press. (49) Hawley, G.G. (1981). The Condensed Chemical Dictionary, 10th ed. New York, Van Nostrand Reinhold Co. USA. (50) Health Canada, November 1987 (updated September 1994), Sulphate. Avialable: http://www.hc-sc.gc.ca/. [Accessed 09-22-2005] (51) Heizer, W.D., Sandler, R.S., Seal, E., Jr., Murray, S.C., Busby, M.G., Schliebe, B.G., Pusek, S.N. (1997). Intestinal effects of sulfate on drinking water on normal human subjects. Dig. Dis. Sci. 42(5):1055-1061. (52) Henkel, KGgA, unpublished data, Archive-No. TBD 710056. (53) Henry, J.G. and Prasad, D., (2000). Anaerobic treatment of landfill leachate by sulphate reduction. Water Science and Tecnol. 41(3):239-246. (54) Hitchcock, D.R., (1975). Biogenic contribution to atmospheric sulfate levels. Water's interface with energy, air and solids: proceedings of the second national conference on complete water-reuse, Chicago, Illinois, May 4-8, 1975. pp 291-310. (55) Hoechst, A.G. (1989). Unveroffentl. Unters. (V-88-0938). (56) Hughes, J.S. (1973) Acute Toxicity of Thirty Chemicals to Striped Bass (Morone saxatilis). La.Dep.Wildl.Fish.318-343-2417:15p. (57) ICRP (1984). International Commission on Radiological Protection: Report No. 23: Report of the Task Group on Reference Man. Pergamon Press, Oxford, UK. (58) Katz, M. (1977). The Canadian Sulphur Problem. In: Sulphur and its inorganic derivatives in the Canadian Environment. NRCC No. 15015, Associate Committee on Scientific Criteria for Environmental Quality, National Research Council of Canada. Ottawa. 21pp. (59) Kelada, F. and Euinton, L.E. (1978). Health effects of long term exposure to sodium sulfate dust. J. Occup. Med. 20(12):812-814. UNEP PUBLICATIONS 132

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(60) Krijgsheld, K.R., Frankena, H., Scholtens, E., Zweens, J. and Mulder, G.J. (1979). Absorption, serum levels and urinary excretion of inorganic sulfate after oral administration of sodium sulfate in the conscious rat. Biochim. Biophys. Acta, 586(3):492-500. (61) Lal, S.S. and Mithal, R.P. (1979) On the control of some nematode parasites of fishes. Bioresearch 3(1):15-17. (62) Last, J.A. Purnendu, K.D., Ethinson, J.R. (1980). Inhalation Toxicology of Sodium Sulfite Aerosol in Rats. Toxicol. Appl. Pharmacol. 55:229-234. (63) Laury, N.A. (1927). Hydrochloric acid and sodium sulfate. American Chemical Society. Monograph series 36. Chemical catalog Co, USA. (64) Lettl, A. (1981). Effects of some sulpher compounds on soil microflora of Spruce rizosphere. Folia Microbio. 26(3):243-252. (65) Mckee, J.E. and Wolf, H.W. (1963). Water Quality criteria, The Resources Agency of California, State Water Quality Control Board, Publ. No.3-A, USA. (66) Meng, Z.Q. and Zhang, L.Z. (1992). Cytogenetic damage induced in human lymphocytes by sodium bisulfite. Mutation Research. 298:63-69. (67) Merck 12ed (1996). pp. 1483, Merck&Co, NJ, USA. (68) Moinuddin, J.F., Wing-Tsit Lee, H., (1960) Alimentary, blood and the other changes due to feeding MnSO4, MgSO4 and Na2SO4. American Journal of Physiology. 199(1): 77-83. (69) Moore, F.W. (1952). Physiological effects of the consumption of saline drinking water. A progress report to the 16th meeting of the subcommittee on Sanitary Engineering and Environment. Appendix B. January 1952. Washington D.C., National Acadamy of Sciences. (70) Morris, M.E. and Levy, G. (1983). Absorption of sulfate from orally adminsitered magnesium sulfate in man. J. Toxicol-clinical toxicol 20(2)107-114. (71) Mount, D.R., Gulley, D.D., Hockett, J.R., Garrison, T.D., Evans, J.M. (1997) Statistical models to predict the toxicity of major ions to Ceriodaphnia dubia, Daphnia magna and Pimephales promelas (Fathead minnows). Environ. Toxicol. Chem. 16(10):2009-2019. (72) Navarro, J.M., Garrido, C., Carvajal, M and Martinez, V. (2002). Yield and fruit quality of pepper plants under sulphate and chloride salinity. Journal of Horticulture and biotechnology. 77(1):52-57. (73) Niles G.A. , Morgan S., Edwards W.C. , Lalman D. (2002). Effects of Dietary Sulfur Concentrations on Incidence and Pathology of Polioencephalomalicia in Beef Calves. Vet. Human Toxicol. 44(2):70-72. 133 UNEP PUBLICATIONS

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