REVIEWS

PVC as pharmaceutical packaging material

A literature survey with special emphasis on plasticized PVC bags

A.A. Van Dooren

Introduction other substances, leading to a great variety of

Partly because of recent discoveries of traces of flexibilities, appearances etc.;
dioxins in the milk of cows meadowing in the - relatively low m a n u f a c t u r i n g costs [3];
vicinity of solid-waste incinerators, the use of - low oxygen and C02 permeability (compared
polyvinyl chloride (PVC) as a packaging material with polyolefins) (Table 1);
has recently been severely questioned in the - predictable and long-term stability;
Netherlands [1]. This has, for instance, led to - being tasteless and practically odourless.
m a r k i n g by environmentalists of food packed in PVC demand amounts to approximately 4.1 mil-
PVC in several Dutch shops, as well as to a flow lion tons per a n n u m in Western Europe, of which
of negative publicity, and the withdrawal of PVC 5% is used in the Netherlands [4 5]. Approxi-
packaging for food by one of the leading Dutch mately 2.8% of PVC sales are for medical use [6].
supermarkets. PVC has earned its place in health care be-
PVC is used as a widespread packaging ma- cause of its versatility, sterilizability, safety, ap-
terial in pharmacy. Thus, it is likely that the pearance and favourable cost/performance ratio.
pharmacist will be confronted more and more It cannot only be applied in various durables,
with questions about PVC from the lay public, like renal dialysis units, oxygen tents, contact
hospital staff etc. lenses, protheses and heart valves, but also in
This article gives the main facts about (medical disposables, such as tablet strips and blisters,
grade) PVC, w i t h emphasis on fluid containers. sets and tubing, container bags (blood bags, in-
The information m a y be used by the pharmacist fusion bags, nutrition bags, drain bags and di-
in order to fulfil his role as a pharmaceutical ad- alysis bags) and catheters and other components.
viser.
PVC production
Occurrence of PVC The production of PVC can be subdivided into
The first patent on PVC dates back as early as the following processes:
1913 [2], and since its first industrial manufac- - production of vinyl chloride monomer (VCM);
ture in 1931, PVC has gained widespread appli- - polymerization of VCM into PVC;
cation as a universal plastic. Indeed, without -compounding of basic material, including
PVC modern lifestyle would have been very dif- granulation;
ferent. Its common use is due to a great variety - formation of end-product.
of suitable properties, such as:
- o p t i m u m versatility in designing character- Production of V C M
istics; VCM is made from chlorine and ethene (eth-
- high-frequency weldability; ylene) through the pyrolysis of the intermediate
- ability to be combined with a wide range of 1,2-dichloro-ethane (ethylene dichloride) (EDC).

Van Dooren AA. PVC as pharmaceutical packaging material. A literature survey with
special emphasis on plasticized PVC bags. Pharm Weekbl [Sci] 1991;13(3):109-18.

Abstract
In this report the state of the art with respect to PVC as pharmaceutical packaging
material is described. A general introduction into the applications of PVC is followed by a
description of its production process. The metabolic effects of the monomer of PVC, vinyl
chloride and of the most commonly used plasticizer diethylhexylphthalate are mentioned.
Special attention is given to the pharmaceutical properties of plasticized PVC bags in
Keywords comparison to other plastics and the environmental aspects of waste PVC disposal. Although
Chemistry there are emotional and political queries regarding the future use of PVC as a
Consumer product safety (pharmaceutical) packaging material, we conclude that there is no scientific justification for
Drug packaging a total or partial ban of PVC. PVC will remain a fact of life as a cheap, versatile,
Environmental pollution high-performance and well-investigated plastic material for medical and pharmaceutical
Plasticizers applications, to be replaced by newer plastics only for certain well-defined indications where
Polyvinyls the requirements of the plastic to be used are so specific that it will economically and
technically be justified to use another polymer. Community and hospital pharmacists have
Dr. A.A. Van Dooren: Medistad to be prepared for a role in intake of waste plastic disposables, probably against deposit
Holland BV, P.O. Box 99, money, in order to fulfil the logistics needed for recycling.
1670 AB Medemblik, the
Netherlands. Accepted 10 January 1991.

13(3) 1991 Pharmaceutisch Weekblad Scientific edition 109

 Ethene, the basic raw material for nearly all nyl chloride monomer into PVC is an exothermal
polymers, is obtained through the cracking of reaction resulting from applying high pressure
natural oil or gas, which are fundamentally at slightly elevated temperatures to a suspension
scarce resources. Total polymer production ac- of VCM particles in the presence of an initiator,
counts for approximately 4% of the use of these surface-active agent and protective colloid. By
resources. means of this so-called 'suspension' process, ac-
Polyolefins are for nearly 100% dependent on counting for over 90% of all PVC production, a
oil or gas, whilst PVC is for less than half of its white powder is formed with a particle size of 100
weight, since it contains 57% of chlorine. Chlor- to 200 #m.
ine is not scarce. It is obtained through the elec-
trolysis of brine (NaC1), either with the help of a Compounding of basic material
transport medium (mercury) or increasingly In the compounding phase the powdered poly-
through diaphragm and membrane processes. A mer is prepared for further processing by the ad-
discussion of chlorine chemistry falls beyond the dition of auxiliaries. During tubular extrusion,
scope of this article. the PVC powder and additives are molten (160-
About one third of the chlorine production is 200~ plasticized and homogenized in a cylin-
used for the manufacture of PVC. Other import- der by the action of a screw. Cooling is done with
ant uses are in bleaching paper, in solvents and filtered cold air.
titanium dioxide production [Nisbet A, unpub- It is the preferred method for the production of
lished observations]. Chlorine production con- tubings and extruded foil for use in, e.g., infusion
curs with the formation of sodium hydroxide, bags. Due to the high reaction temperature the
which is one of the basic materials for the manu- product is internally sterile, practically free of
facture of glass, aluminium, detergents, textiles particulate matter and free of pyrogens.
and paper [Nisbet A, unpublished observations.] PVC foils as used in, e.g., blood bags or urine
drain bags are made by calandering or flat-die
Polymerization of VCM extrusion. The product is normally neither ster-
The most common polymerization process of vi- ile nor pyrogen free, and contains more particu-

Table 1
Comparison of various sterile fluid container materials

Glass PVC Polypropylene Polyethylene

Volume range 1 ml-1 1 20 ml-100 1 100 ml-3 1 100 ml-1 l

Weight per emtpy container
(0,5 l) (g) 250 32 25 not available
as empty
container
Density (kg/m 8) 2.4-2.8 1.25 0.89 0.92
Hardness (shore D) 28 70 5O
Water permeability g/m 2 (24 h,
0.040 mm) 11 1.5 2.5
(over-
wrapping
needed)
Oxygen permeability g/m 2
(24 h, 0.0"40 mm) < 1 900 1,500 3,200
C02 permeability g/m ~ (24 h,
0.040 mm) < 1 10,000 9,000 17,000
Energy contents (MJ/kg) 10 53 73 69
Reusability yes no no no
Microporosity excellent good fair excellent
Cracking risk yes no yes a t ~ 10~ no
Resistance against cold good moderate poor good
Clarity excellent good fair fair
Particulate matter present practically flee practically flee practically flee
(rubber)
Autoclavability (~
(steam/water) 121 121 121 ~ 108
Aeration necessary (during
infusion) yes no no no
Pressure infusion possible no yes no no
Multicontainer systems
possible no yes no no
Possibility for hospital filling
of sterile fluids yes yes yes no

110 Pharmaceutisch Weekblad Scientific edition 13(3) 1991

 late matter than the extruded tubular foil. On - it is possible to incorporate a wide variety of
the other hand, it is valued for its uniform thick- substances into its microstructure. Because of
ness. this, the properties of PVC can be varied
enormously, which is one of the principal
Formation of the end-product reasons for its large variety of applications.
Medical PVC bags are made of extruded or cal- The Dutch and European Pharmacopoeias give a
endered foil by means of radiofrequency welding. positive listing of acceptable PVC additives for
This welding technique in which material is blood and infusion bags [14].
brought in a high-frequency alternating current The main additives are:
field (27.12 MHz), is only suitable for polar - t h e r m a l stabilizers, which are able to scav-
plastics like PVC or ethylene vinyl acetate enge HC1 formed during decomposition (cal-
(EVA) but not for, e.g., polyolefines, which can cium or zinc stearate, epoxidized linseed or
only be welded by thermosealing processes. The soya oil). Lead-based or cadmium-based stabil-
thermosealing process is not suitable for multi- izers are not permitted in medical-grade PVC
port designs due to microporosity along the seals, [14];
particularly in connections between tubings and -lubricants, like stearates and amide waxes
a flat surface. (the latter ones also having antiblocking
Tubings can be welded into PVC bags by the properties);
same high-frequency welding process. Connec- -colouring agents. The Dutch Pharmacopoeia
tors or joints, but also infusion sets, are mounted excludes colouring agents for blood bags [14].
by adhesion. The adhesives mainly used in prac- For infusion bags, tinted material (containing
tice are cyclohexanone and tetrahydrofurane. several ppm's of, e.g., ultramarine blue) is still
in use, without any advantage other than
Vinyl chloride m o n o m e r better appearance;
After initial reports concerning its carcinogen- - plasticizers, when a flexible PVC compound is
icity in animals [7 8], VCM was soon suspected of needed. The percentage can vary from 5 to
being carcinogenic in man as well, particularly even 70%. The Dutch Pharmacopoeia allows a
in operators exposed to high air VCM levels in percentage of not more than 40% diethylhexyl-
PVC production plants [9]. Nowadays, there is a phthalate (DEHP) for blood bags [14].
general consensus that VCM leads to a rare but The maximum amount of additives in PVC is
lethal form of cancer called liver angiosarcoma much higher than allowed for polyolefin ma-
[10]. terials. The Dutch Pharmacopoeia stipulates
In humans, VCM is metabolized into chloro- that low-density polyethylene (LDPE) should not
ethylene oxide [11] which is believed to be the contain additives, whilst high-density polyethyl-
most potent mutagenic metabolite [12]. Since ene (HDPE) and polypropylene (PP) containers
macromolecular adduct formation, detoxification for parenteral preparations may contain small
and excretion are in competition with each other, amounts of antioxidants and lubricants [16].
the carcinogenic action of VCM is thought to be
largely dose-dependent [10]. Plasticizers
Since 1974, the PVC industry has jointly taken The list of proposed plasticizers includes:
measures to reduce the risks of VCM intake to - phthalic acid esters, e.g. di-n-octyl phthalate
their operators and plant neighbours, by means (D-n-OP), diethylhexyl phthalate (DEHP), di-
of automated production, closed reaction vessels nonyl phthalate (DNP), didecyl phthalate
and better cleaning procedures. An average ex- (DDP);
posure to VCM not exceeding 5 ppm is now - a d i p i c acid esters, e.g. diethylhexyl adipate
judged to give no increase in cancer incidence (DEHA);
[13]. The European and Dutch Pharmacopoeias - c i t r i c acid esters, e.g. acetyltributyl citrate
require a maximum VCM concentration of 1 ppm (ATBC);
in virgin PVC powder [14]. Modern 'medical - esters of the trimellitate type such as tri-(2-
grade' PVC is believed to contain less than ethylhexyl)trimellitate (TOTM).
10 ppb VCM, which is below the current analyti- The only plasticizer mentioned explicitly in the
cal detection level (20 ppb) [15]. Dutch Pharmacopoeia monograph for blood bags
Although it cannot be maintained that current is DEHP [14].
VCM levels pose a toxicological problem, it TOTM is a newer plasticizer, which does not
should be stated that the theoretical zero ppm have a similar inhibitory effect on erythrocyte
level has not yet been reached. We believe that deterioration as compared to DEHP [17 18]. On
a further reduction should be strived for, even the other hand, it is stated that it migrates from
though this might require a substantial econ- the PVC matrix to a lesser extent [19] and is able
omic effort. to increase platelet survival from 3 to 5 days [20],
probably due to a better gas exchange [21].
Additives Meanwhile DEHP-containing PVC bags with
PVC is mixed with additives for the following better gas exchange properties have been de-
reasons: scribed [22].
- a t the extrusion temperature, 160-200~ DEHP is probably one of the best studied
autocatatytic degradation of PVC may occur. substances in the world. It is estimated that over
Antioxidants and organometallic stabilizers 3,000 scientific papers on its biological activity
may be added in order to prevent this decom- have appeared to date, amongst them very com-
position; prehensive review studies [23-31].

13(3) 1991 Pharmaceutisch Weekblad Scientific edition 111

 Although the aqueous solubility of DEHP is studies were extremely high and it can be ques-
low (<0.04 mg/ml at 20~ [27 32], it is not co- tioned whether the animals under trial had a
valently bound in the PVC matrix and may normal metabolic response. Since, moreover, the
therefore migrate out of the plastic [18], es- metabolism in rats is very different from that in
pecially in the presence of solubilizing lipids, primates, as mentioned above, it is now gener-
lipoproteins and albumin. The migration de- ally agreed that it is not justified to simply ex-
pends on temperature [29], storage time and trapolate rodent findings to humans [29 30 47].
nature of the solution, like anticoagulant in Mutagenicity of phthalate esters was also
blood bags [33]. studied [29]. Although it was found that MEHP
Since 1970, it has been known that DEHP is in vitro induces chromosomal aberrations in
present in blood stored in PVC bags [34 35]. hamster embryo cells [55], the majority of in vivo
Various extraction rates have been reported, tests report negative results with both DEHP
such as 0.25+_0.03 mg/100 ml blood/day at 4~ and MEHP [29].
[36], 1 rag/unit blood/day or 6 mg/unit platelet The toxicity of DEHP to the reproductive
concentrate/day (room temperature) [37], 10- system was tested as well. It can be concluded
50 rag/1 plasma in vitro [34], or 11.5 mg/100 ml that testicular atrophy is observed in all
plasma [38]. species, particularly in rodents at doses of
DEHP interacts with the red-cell membrane 100 mg. kg -1. d -1, whilst teratogenic effects are
[17 18] and improves the survival time of eryth- only observed after high doses of DEHP (above
rocytes and their osmotic fragility and flexibility 100 m g . k g - l . d -1) administered orally. MEHP
after prolonged storage, both in vitro [39 40] and appears to have no teratogenic effect [56-59].
in vivo [41]. It has little effect on platelet function Where does this abundance of data lead to in
or survival [42]. terms of risks in the case of human exposure? If
Although existing data should be viewed with we estimate the average content of DEHP in
care due to poor DEHP stability in water to arti- whole blood (21 days at 4~ at 100 mg/1, a 70 kg
facts contributed by phthalate-solubilizer inter- adult being given 2 units of blood would receive
actions, environmentally present DEHP or to 1.5 mg/kg of DEHP. If a haemodialysis session
analytical problems [26 38 43], DEHP was de- releases 200 mg of DEHP (from perfusion
tected in organs of deceased humans, in doses as tubings) an adult undergoing 3 sessions per week
high as 25 mg/kg spleen to 91.5 mg/kg lung [34], would receive a dose of 8.5 mg. kg -1 each week
and was shown to have a significant effect on (440 mg. kg -1 a year) [29]. Taking a safety factor
various biological responses [44]. of 100 when extrapolating animal results to
DEHP metabolism takes place very rapidly in man, an adult receiving 1 1 of blood is at the limit
mammals [26 45]. More than half of the perfused of the doses capable of inducing toxic effects and
doses of DEHP are eliminated in the urine with- a haemodialysis patient would be exposed to a
in 8 h [37], and liver, kidney and gastro-intes- dose even above this limit'[29].
tinal tract probably accumulate phthalate esters In view of the species differences mentioned,
as a mechanism of excretion and may therefore and the many individual factors and experimen-
inappropriately be labelled as repositories [26]. tal conditions noted to affect results on DEHP
The main metabolite of DEHP is the monoester bioactivity, benefits and risks should be accu-
MEHP [37]. In rodents, further metabolism takes rately weighed here [31]. Up till now, no human
place through oxidation of the end site of the impairment or death has been reported in con-
aliphatic chain [46] and successive oxidation to nection with DEHP intake.
ketone and carboxylic acid bodies [26 47]. In pri- In fact, in June 1989, the European Pharmaco-
mates and man, primarily glucuronide conju- poeia Committee concluded that the incidence of
gates of MEHP are formed [37]. liver tumours in rodents should be seen as a
The acute toxicity of DEHP is low. LD50 values species-specific characteristic and that there is
of 30-50 g/kg bodyweight are generally reported sufficient safety margin between the dose caus-
[24 25 29]. However, the main metabolite MEHP ing toxic effects in animals and the dose to which
has a far greater acute toxicity [23 48]. humans may be exposed. It was therefore stated
In chronic toxicity testing, no-effect doses that, although research into plasticizer-free
of about 60 m g . k g - l - d -1 during i year to plastics should continue, there is no fundamental
200 m g . k g - l - d -1 in rats were reported [23 48]. reason not to use medical accessories containing
DEHP is regarded to be hepatotoxic in rats [49], DEHP [60].
leading to hepatomegaly and enhanced enzyme
activity [50]. Also, in rhesus monkeys after blood Pharmaceutical properties of plasticized
transfusion hepatic changes were found [51], PVC bags
although the number of animals in this study Plasticized PVC containers possess a number
was too small to draw definite conclusions. of advantages which make PVC still a widely
Microscopically, a proliferation of peroxisomes used material suitable for pharmaceutical pack-
could be detected [52]. These peroxisomes are in- aging. The main ones are:
volved in cell respiratory phenomena which - its ability to undergo high-frequency welding
generate H202, in gluconeogenesis, lipid metab- (which leads to essentially leakage-free prod-
olism and thrombogenesis [29]. ucts and nearly indefinite design possibilities);
In 1982, it was found that DEHP is carcino- - its ability to be steam-sterilized at 121~
genic in mice and rats after feeding them for - its favourable cost/performance ratio;
2 years with high doses (3,000-12,000 ppm/day) - its low weight leading to low storage and dis-
[53 54]. However, the doses in these rodent tribution costs;

112 Pharmaceutisch Weekblad Scientific edition 13(3) 1991

 -its strength (resistance to breakage) and like dynamic headspace gas chromatography-
transparency; mass spectrometry [72], it was even found that
- its flexibility (no need for aeration during in- caprolactam monomer from overwrapping
fusion or transfusion; possibility to give in- layers containing polyamide, can be traced in
fusion under pressure); an infusion solution [71]. The presence of
- its low energy content and low use of scarce plasticizers in infusion solutions can be as-
raw materials; sayed by means of gas chromatography [73].
- its favourable effect on erythrocyte survival - Physical properties of the plastic can be modi-
[61]; fied by drug action. Examples of such drugs
- its low acute toxicity as measured according are fat emulsions used in total parenteral nu-
to the USP [62]; trition and surfactants like polysorbate [65]
- the extensive knowledge about its pharma- and Cremophor| [70].
ceutical properties. The major part of the information on d r u g -
In Table 1, a comparison is made between Vari- plastic interactions pertains to PVC infusion con-
ous container materials. When using PVC con- tainers. This undoubtedly is due to the fact that
tainers for large-volume parenterals, the follow- such containers were the first flexible containers
ing aspects should be considered. to be commercially available, but also because of
the complex nature of the PVC matrix in which
Evaporation of water a number of components are necessarily present
PVC is permeable to water, thus causing an in- [14].
crease in concentration of infusion solutions However, even polyolefin container materials,
upon storage. Evaporation can be decreased by which essentially contain fewer components,
storing bags in a carton or, better still, by over- may give rise to leaching. Arbin [71] found that
wrapping the infusion bags w i t h polyethylene polypropylene releases many volatile low-mol-
(PE) or laminate foils [63]. It is advisable to over- ecular-weight oligomers, whilst polyethylene re-
wrap PVC infusion bags before autoclaving (al- leases more high-molecular weight oligomers.
though special, more expensive overwrap ma- In sum, it can be stated that the number of
terials are then needed), because of increased 'suspect' drugs and the clinical relevance of the
safety (leakage and easier detection of pinholes incompatibilities found are small [70]. If, how-
which could give rise to non-sterility), or when ever, an incompatibility is to be expected, vari-
bags with a sterile outer side are needed (e.g. in ous alternatives are open to the pharmacist to
operating theatres). circumvent this problem, like titration of the
When overwraps are used, the water evapor- patient, decreasing the drug concentration, in-
ation rate can be reduced to a level of approxi- creasing the rate of administration, or a change
mately 1% per annum at ambient room tempera- of formulation or of plastic material. The choice
ture, which leads to an acceptable stability of the alternative should be based upon a c o st-
period of 3 years. If necessary, concentrations benefit analysis [70].
can be slightly adapted during manufacture.
Sterilization
Compatibilities If PVC bags are to be steam-sterilized without
Since the classic studies by Moorhatch and containing fluid, the use of internally ribbed or
Chiou [64-67] the possibility of drug-plastic embossed films is required to prevent sticking of
interactions has been generally acknowledged the surface. After steam sterilization of filled in-
and summarized in many good survey articles fusion bags, the pH of the aqueous solution is de-
[68-70]. The pharmacist should be aware of the creased. The acidic impurities were found to be
following possible complications. formic acid and acetic acid, very likely decompo-
- Migration of drugs into plastic (sorption) may sition products from PVC oxidation during auto-
lead to subtherapeutic drug concentrations. claving [74].
Well-known examples are insulin, vitamin A PVC is rather sensitive to gamma irridiation.
acetate, diazepam and nitroglycerin. A tabu- It becomes light or dark brown in colour due to
lation of 'suspect' drugs is given by Wang and the formation of a chain of conjugated double
Chien [69]. Influencing factors are drug con- bonds initiated by free radicals formed by oxi-
centration, partition coefficient and lipophil- dation, also leading to the release of hydrochloric
icity, pH, excipients, temperature, structure of acid. Care has to be taken to control the radi-
the plastic, the volume/surface area ratio, ation dose. Special gamma-resistant PVC com-
storage time and, possibly, the rate of admin- pounds are commercially available.
istration [70]. Sterilization of medical disposables by ethyl-
- L e a k a g e of plastic components into the sol- ene oxide is a common procedure, although it
ution sometimes leads to undesirable reac- should be remembered that ethylene oxide is not
tions. Leakage of PVC plasticizer into a sol- only toxic to micro-organisms, but also to
ution is a well-known example, as mentioned mammals [75]. 5% Of all patients react allergi-
above. Apart from the composition of the cally to ethylene oxide, therefore the concen-
plastic, influencing factors are storage time, tration of ethylene oxide in the vicinity of the
pH, temperature, contact area and nature of sterilizator is bound to strict limits (5 ppm/
the stored solution. It appears that different 15 rain) [76].
supplies of PVC material give rise to different PVC, once gamma-irradiated, should not be
leachates, as was shown by Arbin [71]. resterilized with ethylene oxide. The hydro-
- B y means of various analytical techniques, chloric acid released during ionization may react

13(3) 1991 Pharmaceutisch Weekblad Scientific edition 113

 with ethylene oxide to form ethylene chlor-
hydrin, a toxic substance which is very difficult
to remove [19].

Waste disposal
Finally, all plastics end up in the solid-waste
stream. However, they form only a minor part of Figure 1
this stream. In the Netherlands, total plastic Structures of dibenzodioxin (left) and dibenzofurane
waste amounts to 663,000 tons per annum, of (right)
which 13% (86,000 tons) consist of PVC [77]. The
amount of Dutch hospital waste is estimated to
be 115,000 tons, of which 15% (16,500 tons/ reuse the NaC1 formed by scrubbing [81] but in
annum) are plastics. The percentage of PVC in theory the chlorine cycle is completely closed, as
hospital waste is unknown [77]. is shown in the German Iserlohn incineration
Municipal waste, including hospital waste, is plant [82].
disposed of via different methods: Dioxin formation. Since 10 July 1976, the day
- landfill disposal; of the Seveso disaster, the word 'dioxin' has been
- incineration; added to the general vocabulary as a symbol of
- recycling. terror and catastrophy. Dioxin is a collective
term for as many as 210 different substances,
Landfill disposal with structures based on dibenzodioxin and di-
In the Netherlands, approximately 68% of mu- benzofurane moieties (Fig. 1). The toxicity of
nicipal waste is still disposed of via landfill [77]. these substances varies greatly, the most toxic
Landfill disposal of municipal waste is generally isomer being 2,3,7,8-tetrachlorodibenzopara-
not dangerous, but the formation of landfill gas dioxin (TCDD) (Fig. 2).
and the leaking of degradation products into The substance in Figure 2 is extremely toxic,
ground water should be considered. It is known but the acute toxicity is species-specific. The
that under certain conditions plasticizers may most sensitive animal is the guinea-pig (oral
leak out of deposited PVC material, and LD50 0.6-2.9 /xg/kg). The oral LD50 for the
although these are in principle easily degradable monkey is 70/~g/kg [83]. In humans acute skin
by micro-organisms it is not yet fully understood irritation (chloracne) and eye irritation were re-
whether bacterial degradation actually takes ported after the Seveso disaster [83]. Dioxins are
place under the conditions of decomposition. not metabolized appreciably by bio-organisms,
A relationship between PVC and VCM traces (except maybe by the cow) [83]; they appear to ac-
in landfill gas has not been established (the main cumulate in adipose tissues and can be excreted
source of VCM is thought to be chlorine- through breastmilk.
cOntaining solvents) [78]. Both dibenzodioxins and dibenzofuranes are
The main problem of landfill disposal is the in- teratogenic, but they appear to have no signifi-
creasing shortage of landfill sites. Thus, it is un- cant mutagenic activity in vitro [83]. In rats,
derstandable that governments are striving to TCDD is carcinogenic at doses of 0.1 ng-kg -1. d -1
decrease waste disposal by this means [79]. Land- It is a tumour promotor rather than a tumour in-
fill deposition is not the method of choice for the itiator. The no-observed-adverse-effect level
disposal of hospital waste. (NOAEL) is 0.001 ~ g . k g - l . d -~ and using a
safety margin of 100-250 when extrapolating
Waste incineration animal data to humans, a virtually safe dosis of
Two major problems are attributed to inciner- 1-10 pg. kg -1- d -1 for humans is reached [83].
ation of PVC: emission of hydrochloric acid and Dioxins are regarded to be side products of in-
dioxine formation. complete combustion [84]. Phenolic non-chlori-
Emission of hydrochloric acid. Upon inciner- nated precursors can be formed by pyrolysis from
ation, PVC releases hydrochloric acid which is a e.g. lignin [85]. Chlorination of these precursors
component of acid rain, attributing to the well- may follow in the cooling phase (400-200~
known forest death. HC1 formation due to incin- after their adsorption to fly-ash particles, in the
eration of waste contributes for only a minor part presence of heavy metals, like copper [80 86].
(0.35%) to the total acid emission responsible for For this so-called "de novo synthesis' the pres-
acid rain formation. 50-70% Of the HC1 emission ence of oxygen is essential; water has an antag-
caused by incineration of waste is due to PVC onistic effect [84]. Clearly, PVC may act as a
[79], the remainder being caused by burning source of chlorine necessary for the de novo syn-
paper (bleached with HC1), vegetables and other
so-called natural material (wood, NaC1 in
kitchen waste). Total HC1 emissions in offgases
from incinerators are in the region of 800-
900 mg/m 3 [80]. Without any PVC this amount
would drop to 300-450 mg/m 8. The future (1995)
Dutch norm for maximum HC1 emission is
50 mg/m ~ [80]. Thus, it should be concluded that
wet scrubbing of offgas to remove HC1 is necess-
ary with or without any PVC in the waste. Figure 2
A debate is still going on whether it is useful to Structure of 2,3, 7,8-tetrachlorodibenzoparadioxin

114 Pharmaceutisch Weekblad Scientific edition 13(3) 1991

 thesis. An assessment of the available literature less t h a n t h a t of the virgin material. Pharmaco-
on the influence of the PVC content of waste on poeial standards currently prevent the use of
dioxin formation during incineration leads to the PVC regenerates for pharmaceutical purposes.
following considerations. F u r t h e r problems in recycling include [88]:
- Waste incineration contributes for about 25% - cleanliness of the material and possibilities of
of total air dioxin concentration [80]. In the demixing various waste components, without
vicinity of incinerators, this percentage is leading to pollution of the environment;
probably higher. Other sources, like cigarette - regenerates should lead to products acceptably
burning, traffic offgases, household open fires fit for use;
and barbecueing, may also lead to dioxin - at the moment, recycling is still only rarely
emission. economical. It can be expected t h a t this will
- There is a non-quantifiable probability t h a t a change rapidly in the near future [77].
decrease of chlorine-containing sources in the Approximately 90-95% of scrap in the medical
waste would lead to a decrease of dioxin for- plastic processing industry is already recycled in-
mation. house or by specialized recycling companies,
- Addition of PVC to the waste does not decrease although not for medical purposes [88].
the incineration temperature. Possibilities to recycle empty infusion bags,
- Under experimental conditions, the burning of tablet strips or sets are still hampered by dif-
pure PVC does not lead to dioxin formation, ficulties in separating, e.g., metal or rubber com-
not even at low temperatures. For the de novo ponents and in disinfecting and drying the prod-
synthesis m o r e factors should be present. ucts to make t h e m suitable for processing, but as
- Normal dioxin emissions are in the nanogram soon as these problems have been overcome it
range. Even without any PVC the chlorine can well be envisaged t h a t such articles could be
content of waste (approximately 0.7%) pre- charged with mandatory deposit money to en-
sents an enormous excess to the amounts of sure separate collection [77]. Research is on its
chlorine needed for dioxin formation [77 87 way into new techniques to separate waste com-
88]. ponents and to recycling processes, such as py-
- The analysis of dioxins, especially the step of rolysis (heating at 600-900~ without oxygen),
sample preparation, is difficult. Analytical re- hydrogenation (with hydrogen gas under elev-
sults should be viewed with caution, taking ated pressure at temperatures of 300-500 ~C) and
into account accuracy and confidentiality in- fuelling of plastics for energy recycling [88].
tervals [89]. Studies on the relationship be-
tween PVC content of waste and dioxin C o n c l u s i o n s

emission present conflicting results. In vari- Since the beginning of the seventies, PVC has
ous studies, both under experimental and had to face various severe threats shaking the
practical conditions, no relationship could be roots of its existence: firstly, the vinylchloride
established [86 90-93], but a recent Dutch carcinogenicity, secondly, plasticizer leakage
study showed a positive relation [80]. This and toxicity and nowadays, the environmental
latter test was carried out in a relatively old issues. Close scrutiny of the available literature
incinerator and the conditions were not opti- leads to the conclusion t h a t there is no scientific
mal [77]. justification for any complete or partial ban of
In conclusion, it must be stated t h a t the avail- PVC. The problems of VCM exposure for workers
able literature data is contradictory and t h a t in polymerization plants and for patients have
further research is necessary. A general consen- been largely solved by processing measurements
sus in the literature can be found in the desig- and strict standards for m a x i m u m levels in medi-
nation of priority steps to be t a k e n in order to de- cal grade PVC. Furthermore, there is no proof
crease dioxin emissions by waste incineration, t h a t the plasticizer D E H P is toxic or carcino-
which pertain to improvement of combustion genic to humans, whilst its beneficial effects on
conditions [77]: red blood cell survival is a valued property. The
- incineration under homogeneous, undisturbed total PVC content of solid waste is only a minor
process conditions; fraction, although PVC does account for the
- m i n i m u m furnace t e m p e r a t u r e 800-850~ main part of the hydrochloric acid formation
- avoidance of overload (slow addition of waste after incineration of municipal waste. However,
to maintain combustion temperature); without PVC in the waste this HC1 emission is
- offgas scrubbing to scavenge dioxins; still above acceptable m a x i m u m levels, and
- recombustion or removal of fly-ash [87]. sequestering HC1 by means of wet scrubbing is a
more logical step towards diminishing its
Recycling emission t h a n a ban of PVC. Neither has it been
Recycling of waste will become one of the great proven t h a t PVC would have any effect on the
challenges of the coming era. The Dutch govern- formation of dioxins during incineration. The
ment aims at an increase of the recycling per- existing literature is conflicting, but it can gen-
centage of plastic waste from 10% (in 1986) to erally be agreed t h a t good incineration cir-
37% (in the year 2000) [79]. cumstances have a better effect on the decrease
Recycling is a means of reducing waste of dioxin emissions t h a n the removal of PVC
streams: it leads to an effective reuse of ma- from the waste.
terials and it can save natural resources [77]. All It might even be contended t h a t in the long
thermoplastics including PVC can be recycled, term, after the problem of acid scrubbing and
although the quality of the regenerates is always preventing the 'de novo synthesis' of dioxins has

13(3) 1991 Pharmaceutisch Weekblad Scientific edition 115

 b e e n solved, P V C h a s a m o r e positive effect on 17 Estep TN, Pedersen RA, Miller TJ, Stupar KR.
e n v i r o n m e n t a l e m i s s i o n s t h a n polyolefins, since Characterization of erythrocyte quality during the re-
it n o t o n l y r e l e a s e s less c a r b o n m o n o x i d e a n d frigerated storage of whole blood containing di(2-ethyl-
hexyl)phthalate. Blood 1984;64:1270-6.
n i t r o g e n oxide, b u t also less c a r b o n dioxide. 18 Aubuchon JP, Estep TN, Davey RJ. The effect of plasti-
T h u s , P V C h a s less i n f l u e n c e o n t h e causes of t h e cizer di-2-ethylhexylphthalate on the survival of stored
' g r e e n h o u s e ' effect! RBC's. Blood 1988;71:448-52.
W e b e l i e v e t h a t PVC will r e m a i n a cheap, ver- 19 Lemm W, Bficherl ES. Was ist medizinisches no-DOP-
PVC? Kardiotechnik 1986;9:39-42.
s a t i l e a n d w e l l - s t u d i e d p l a s t i c w h i c h will keep its 20 Warner WL, Nelson EJ. Container for platelet storage.
place i n p h a r m a c y as a disposable p a c k a g i n g ma- US Patent 4280497, 1981.
t e r i a l . T h a t does n o t m e a n t h a t r e s e a r c h on n e w 21 Wallvik J, Akerblom O. Platelet concentrates stored at
plastic materials should not continue, although 22~ need oxygen. Vox Sang 1983;45:303-11.
22 Holme S, Heaton A, Momoda G. Evaluation of a new,
it will t a k e a long t i m e before t h e a d v a n t a g e s more oxygen-permeable polyvinylchloride container.
a n d d i s a d v a n t a g e s of such n e w c o m p o u n d s will Transfusion 1989;29:159-63.
be k n o w n to t h e s a m e e x t e n t t h a t a t p r e s e n t is 23 Autian J. Toxicity and health threats of phthalate
esters: review of the literature. Environm Health
k n o w n of PVC [94-96]. I n t h e n e a r f u t u r e , u s e of Perspect 1973;4:3-26.
n e w plastics will r e m a i n l i m i t e d to c e r t a i n 24 Peakall DB. Phthalate esters: occurrence and bio-
h i g h l y specialized a r e a s [3]. O n t h e o t h e r h a n d , logical effects. Residue Rev 1975;54:1-41.
b o t h t h e p h a r m a c e u t i c a l i n d u s t r y a n d t h e com- 25 Thomas JA, Darby ThD, Wallin RF, Garven PJ,
Martis L. A review of the biological effects of di-
m u n i t y a n d h o s p i t a l p h a r m a c i s t s will become (-2-ethylhexyl)phthalate. Toxicol Appl Pharmacol
more a n d more i n v o l v e d i n t h e logistics of recyc- 1978;45:1-27.
l i n g waste, i n c l u d i n g w a s t e - P V C . P h a r m a c i s t s 26 Kluwe WM. Overview of phthalate ester pharmaco-
will h a v e to face a n e w t a s k : t h e collection of kinetics in mammalian species. Environm Health
Perspect 1982;45:3-10.
w a s t e i n c l u d i n g PVC disposables, p r o b a b l y 27 Kemper FH, Lfipke NP, Bitter M. Zum Thema Weich-
a g a i n s t deposit m o n e y , i n order to i m p r o v e recyc- macher. Phthals~iuredialkylester. Pharmakologische
l i n g logistics. und Toxikologische Aspekte. Frankfurt: Verband
Kunststofferzeugende Industrie, 1983.
28 Timoney RF. Plastic materials and containers for
pharmaceutical use: progress in the development of in-
References ternational standards. Pharm Int 1984;5:178-81.
1 Tolsma H. Kunststof klem tussen succes en milieu- 29 Belegaud PJ. Di(2-ethylhexyl)phthalate. Di(2-ethyl-
beweging [Plastics trapped between success and en- hexyl) adipate. Toxicological aspects. Evaluation of the
vironmentalists]. Ingenieurskrant 1990;(14 juli):8-10. risks. Brussels: Association of Plastic Manufacturers
2 Klatte F. Verfahren zur Herstellung einer auf Horner- in Europe, 1986.
satz, Filme, Kunstf~iden, Lacke und dergleichen 30 Woodward KN. Phthalate esters: toxicity and metab-
verarbeitbaren plastischen Masse. Deutsches Reich olism. Vol. I and II. Boca Raton: CRC Press, 1988.
Patent 281877, 1913. 31 Rubin RJ, Ness PM. What price progress? An update
3 Blais P. Vinyl in medicine - a special case. J Vinyl on vinyl plastic bloodbags. Transfusion 1989;29:
Techn 1989;11:71-80. 358-61.
4 Anonymous. Polyvinylchlorid (PVC). Kunststoffe 32 Jaeger RJ, Rubin RJ. Extraction localization and
1986;76:835-7. metabolism of di-2-ethylhexyl phthalate from PVC
5 Kremers G, Van Ooijen R. Groei kunststoffen boven plastic medical devices. Environm Health Perspect
Europees gemiddelde [Growth of polymers above Euro- 1973;3:95-102.
pean average]. Kunststof en Rubber 1990;12:56-63. 33 Thomas JA, Thomas MJ. Biological effects of di(2-
6 Anonymous. Materials 90. Western Europe. Mod Plast ethylhexyl)phthalate and other phthalic acid esters.
Int 1991;(Jan):51-65. CRC Crit Rev Toxicol 1984;13:283-317.
7 Viola PL, Bigotti A, Caputo A. Oncogenic response of 34 Jaeger RJ, Rubin RJ. Plasticizers from plastic devices:
rat skin, lungs and bones to vinylchloride. Cancer Res extraction, metabolism and accumulation by biological
1971;31:516-22. systems. Science 1970;170:460-1.
8 Maltoni C, Lefemine G, Ciliberti A, Cotti D, Carretti 35 Jaeger RJ, Rubin RJ. Phthalate ester metabolism in
D. Experimental research on vinyl chloride carcino- the isolated perfused rat liver system. Environm
genesis. In: Maltoni C, Mehlman MA, eds. Archives of Health Perspect 1973;3:49-51.
research on industrial carcinogenesis. Vol II. 36 Jaeger RJ, Rubin RJ. Migration of a phthalate ester
Princeton: Princeton Scientific Publishers, 1984. plasticizer from polyvinyl chloride blood bags into
9 Creech JL Jr, Johnson MN. Angiosarcoma of liver in stored human blood and its localization in human tis-
the manufacture of polivinyl chloride. J Occup Med sues. N Engl J Med 1972;287:1114-8.
1974;16:150-1. 37 Peck CC, Albro PW. Toxic potential of the plasticizer
10 Anonymous. Technical Report No. 31. The mutagen- di(2-ethyl-hexyl)phthalate in the context of its dis-
icity and carcinogenicity of vinyl chloride: a historical position and metabolism in primates and man.
reviewand assessment. Brussels: European Chemical Environm Health Perspect 1982;45:11-7.
Industry Ecology and Toxicology Centre, 1988. 38 Marcel YL~ Determination of di-2-ethylhexylphthalate
11 Bartsch H, Malaveille C, Barbin A, Planche G. Muta- levels in human blood plasma and cryoprecipitates.
genic and alkylating metabolites of halo-ethylenes, Environm Health Perspect 1973;3:119-21.
chlorobutadiens and dichlorobutenes produced by 39 Rock G, Tocchi M, Ganz PR, Tackaberry ES. Incor-
rodent or human liver tissues. Arch Toxicol 1979;41: poration of plasticizer into red cells during storage.
249-77. Transfusion 1984;24:493-8.
12 Van Duuren BL. On the possible mechanism of car- 40 Horowitz BH, Stryker MH, Waldman AA, Woods KR,
cinogenic action of vinyl chloride. Ann NY Acad Sci Gass JD, Drago J. Stabilization of red blood cells by the
1975;246:258-67. plasticizer diethylhexylphthalate. Vox Sang 1985;48:
13 Anonymous. Documentation of the threshold limit 150-5.
values and biological exposure indices. 5th ed. 41 Aubuchon JP, Davey RJ, Estep T, Miripol J. Effect of
Cincinnati: American Conference of Governmental the plasticizer di-2-ethylhexylphthalate on survival of
and Industrial Hygienists, 1986. stored red cells [Abstract]. Transfusion 1982;24:422.
14 Anonymous. Ph.Neth. 9th ed. 1983. VI.1.2.1. Materials 42 Valeri CR, Contreras TJ, Feingold H, Stubley RH,
based on poly(vinyl-chloride). The Hague: Staatsuitge- Jaeger RJ. Accumulation of di-2-ethylhexylphthalate
verij, 1984. (DEHP) in whole blood, platelet concentrates, and
15 Mficke G. Wieviel kann nichts sein? Chem Ind 1984; placelet-poor plasma. I. Effect of DEHP on platelet sur-
XXXVI:215-8. vival and function. Environm Health Perspect 1973;3:
16 Anonymous. Ph.Neth. 9th ed. 1983. VI. 1.2.2. Polyole- 103-18.
fines. The Hague: Staatsuitgeverij, 1984. 43 Maxwell T, Milne GAW, Fales HM, Law N. Plasti-

116 P h a r m a c e u t i s c h W e e k b l a d Scientific e d i t i o n 13(3) 1991

 cizers in blood - real or artifactual? Environm Health chemicals from bags containing various solvent media.
Perspect 1973;3:139-40. Am J Hosp Pharm 1974;31:149-52.
44 Rubin RJ, Jaeger RJ. Some pharmacologic and toxi- 68 D'Arcy PF. Drug interactions with medical plastics.
cologic effects of di-2-ethylhexyl phthalate (DEHP) and Drug Intell Clin Pharm 1983;17:726-31.
other plasticizers. Environm Health Perspect 1973;3: 69 Wang YJ, Chien YW. Sterile pharmaceutical pack-
53-9. aging: compatibility and stability. Philadelphia:
45 Schulz CO, Rubin RJ. Distribution, metabolism and Parenteral Drug Association, 1984. (Technical Report
excretion of di-2-ethylhexyl phthalate in the rat. No. 5.)
Environm Health Perspect 1973;3:123-9. 70 Jongejan GAM, Smit JCA, Helling EAM, Hekster YA.
46 Albro PW, Thomas R, Fishbein L. Metabolism of di- De wisselwerking tussen geneesmiddelen en kunst-
ethylhexyl phthalate by rats. Isolation and character- stoffen voor medisch gebruik [Interaction of drugs with
ization of the urinary metabolites. J Chromategr polymers for medical purposes]. Pharm Weekbl 1989;
1973;76:321-30. 124:440-4.
47 Albro PW, Corbett JT, Schroeder JL, Jordan S, 71 Arbin A. Migration of chemicals from plastic packag-
Matthews HB. Pharmacokinetics, interactions with ing materials. In: Klason C, Skov HR, red. Proceedings
macromolecules and species differences in metabolism of the Conference on medical plastics, Copenhagen,
of DEHP. Environm Health Perspect 1982;45:19-25. Denmark, 15-17 September 1987. Copenhagen: Society
48 Gesler RM. Toxicology of di-2-ethylhexylphthalate and of Plastic Engineers, 1987.
other phthalic acid ester plasticizers. Environm 72 Jacobsson S. Analysis of volatile organic compounds in
Health Perspect 1973;3:73-9. polymers by dynamic headspace and gas chroma-
49 Lake BG, Gangolli SD, Grasso P, Lloyd AG. Studies on tography/mass spectrometry. J High Res Chrom
the hepatic effects of orally administered di(2-ethyl- Chrom Commun 1984;7:185-90.
hexyl)phthalate in the rat. Toxicol Appl Pharmacol 73 Martens HJM, De Goede PNFC, Kok RM, Stellaard F.
1975;32:355-67. Onderzoek naar de identiteit van weekmakers in PVC
50 Lake BG, Rijcken WRP, Gray TJB, Foster JR, Gangolli infuuszakken [Identity of plasticizers in PVC bags for
SD. Comparative studies of the hepatic effects of di- injection fluids]. Ziekenhuisfarmacie 1988;4:16-8.
and mono-octyl phthalates, di(2-ethylhexyl) phthalate 74 Arbin A, Ostelius J, Callmer K, Sroka J, H~_nninen K,
and clofibrate in the rat. Acta Pharmacol Toxicol 1984; Axelsson S. Migration of chemicals from soft PVC bags
54:167-76. into intravenous solutions. Act Pharm Suec 1983;
51 Kevy SV, Jacobson MS. Hepatic effects of a phthalate 3(Suppl):20-33.
ester plasticizer leaked from poly (vinylchloride)blood- 75 Anonymous. Ethyleneoxide worker exposure limit
bags following transfusion. Environm Health Perspect should be 'considerably below' 5 ppm. MDDI reports.
1982;45:57-64. Gray Sheet 1983;9(30):5.
52 Warren JR, Lalwani ND, Reddy JK. Phthalate esters 76 Anonymous. Ethyleneoxide 5 parts per million excur-
as peroxisome proliferator carcinogens. Environm sion limit final standard. MDDI reports. Gray Sheet
Health Perspect 1982;45:35-40. 1988;14(15):3-4.
53 Kluwe WM, McConnell EE, Huff JE, et al. Carcino- 77 Nagelhout D, Sein AA, Duvoort GL. Concept-informa-
genicity testing of phthalate esters and related com- tie-document kunststofafval [Rapport] [Concept-infor-
pounds by the National Toxicology Program and the mation document on plastic waste (Report)]. Bilthoven:
National Cancer Institute. Environm Health Perspect Rijksinstituut voor Volksgezondheid en Milieu-
1982;45:129-33. hygiene, 1989.
54 Anonymous. Technical Report 217. Carcinogenesis bio- 78 Wendland F. Geologische und Okologische Aspekte
assay of di(2-ethylhexyl) phthalate in F 344 rats and des Verhaltens yon PVC in Deponien. Jiilich: Kern-
B6C3F1 mice (feed study). Washington: National Toxi- forschungsanlage Jfilich, 1988. (Interner Bericht KFA-
cology Research Center, 1982. STE-1B-8/88)
55 Tomita I, Nakamura Y, Aoki N, Inui N. Mutagenic/ 79 Anonymous. Nationaal Milieubeleidsplan: kiezen of
carcinogenic potential of DEHP and MEHP. Environm verliezen [(Dutch) National Plan on Environmental
Health Perspect 1982;45:119-25. Control: choose or loose]. Tweede Kamer, vergaderjaar
56 Peters~JW, Cook RM. Effect of phthalate esters on re- 1988-1989, 21137, nrs. 1-2.
production in rats. Environm Health Perspect 1973;3: 80 Sein AA, Sluijmers JJ, Verhagen EJH. Onderzoek
91-4. emissies afvalverbrandingsinstallaties [Eindrapport]
57 Dillingham EO, Autian J. Teratogenicity, mutagen- [Study into emissions by incinerators (Final report)].
icity and cellular toxicity of phthalate esters. Bilthoven: Rijksinstituut voor Volksgezondheid en
Environm Health Perspect 1973;3:81-9. Milieuhygi~ne, 1989.
58 Shiota K, Nishimura H. Teratogenicity of di(2-ethyl- 81 Vogg H. Von der Schadstoffquelle zur Schadstoffsenke-
hexyl)phthalate and di-n-butyl phthalate (DBP) in neue Konzepte der Mfillverbrennung. Chem Ing Techn
mice. Environm Health Perspect 1982;45:65-70. 1988;60:247-55.
59 Autian J. Antifertility effects and dominant lethal 82 Anonymous. Vollstfindiges Chlor-Recycling keine Uto-
assays for mutagenic effect of DEHP. Environm pie. Solvay Report. Rheinberg: Solvay, 1986:1.
Health Perspect 1982;45:115-8. 83 Burg RV. Toxicology update TCDD. J Appl Toxicol
60 Anonymous. Group of experts No. 16. DEHP in medi- 1988;8:145-8.
cal accessories made of PVC-plastic materials. 23 June 84 Anonymous. Dioxinen 1989. Chem Mag 1989;(Dec):
1989: PA/PH/Exp 16/T (89) 4. Brussels: European 735-40.
Pharmacopoeia Committee, 1989. 85 BrSker G. Massnahmen zur Verminderung der Dioxin
61 Labow RS, Card RT, Rock G. The effect of the plasti- Emissionen an Miillverbrennungsanlagen. In: VDI
cizer di(2-ethylhexyl) phthalate on red cell deform- Berichte 634: Dioxin, eine Technische, Analytische,
ability. Blood 1987;70:319-23. Okologische und Toxikologische Herausforderung.
62 Anonymous. United States Pharmacopeia XX. Bio- Dfisseldorf: VDI Verlag 1987:515-39.
logical tests, plastic containers. Easton: Mack 86 Carroll WF. PVC and incineration. J Vinyl Technol
Publishing Company, 1980. 1988;10:90-4.
63 Janknegt R, Oldenhof AGJ, Steenhoek A. Is her om- 87 De Leer EWB, Verbeek A. Milieu-aspecten van afval-
hullen van infuuszakken zinvol? [Effectiveness of verbranding - mogelijkheden tot verbetering [En-
wrapping PVC infusion bags]. Ziekenhuisfarmacie vironmental aspects of waste incineration - possi-
1988;4:44-6. bilities for improvement]. Toegepaste Wetensch TNO
64 Chiou WL, Moorhatch P. Interaction between vitamin Mag 1990;7:6-13.
A and plastic intravenous fluid bags. JAMA 1973;224: 88 Reimann DO. PVC als Abfallprodukt. Mfill Abfall
328. 1988;6:256-67.
65 Chiou WL, Moorhatch P. Leaching of chemicals from 89 Hagenmeier H, Brunner H, Haag R. Stand der Dioxin
plastic intravenous fluid bags. JAMA 1973;224:1298-9. Analytik. In: eine Berichte 634: Dioxin, eine Techni-
66 Moorhatch P, Chiou WL. Interactions between drugs sche, Analytische, Okologische und Toxikologische
and plastic intravenous fluid bags. Part I. Sorption Herausforderung. Dfisseldorf: VDI Verlag 1987:61-89.
studies on 17 drugs. Am J Hosp Pharm 1974;31:72-8. 90 Karasek FW, Viau AC, Guichon G, Gonnord MF. Gas
67 Moorhatch P, Chiou WL. Interactions between drugs chromatographic-mass spectrometric study on the
and plastic intravenous fluid bags. Part II. Leaching of formation of polychlorinated dibenzo-p-dioxins and

13(3) 1991 P h a r m a c e u t i s c h W e e k b l a d Scientific e d i t i o n 117

 polychlorobenzenes from polyvinyl chloride in a mu- of municipal solid wastes with high contents of organic
nicipal incinerator. J Chromatogr 1983;270:227-34. chlorine (PVC). Chemosphere 1989;19:407-11.
91 Neulicht R. Results of the combustion and emissions 94 Hekster YA. PVC: extruderen of excommuniceren?
research project at the Vicon Incinerator Facility in [PVC: extrusion or excommunication?]. Pharm Weekbl
Pittsfield, Massachusetts [Final report (vol. 1)]. Energy 1989;124:772.
Author Rep 1987;(June):87-16. 95 Bakker A, Boom FA, Tjoeng MM. PVC: eerst commu-
92 Martin JJE, Zahlten M. Betriebs- und Inputvariations- niceren, dan elimineren! [PVC: communication first,
versuche an einer Mfillverbrennungsanlage: Ergib- elimination later]. Pharm Weekbl 1989;124:1005-6.
nisse und Ausblick. Abfallwirtschaftsjournal 1989;1: 96 Hekster YA. PVC: elimineren of limiteren? [PVC:
41-54. elimination or limitation?] Pharm Weekbl 1989;124:
93 Giugliano M, Cernuschi S, Ghezzi U. The emission of 1006.
dioxins and related compounds from the incineration

118 P h a r m a c e u t i s c h W e e k b l a d Scientific e d i t i o n 13(3) 1991