Acute Toxicity

patients with advanced primary squamous cell carcinoma (SCC) of cervix (FIG0 Stages RIB, IVA or extensive nodal involvement) and 8 with recurrent disease were treated using a pilot regimen of combination chemotherapy (CT): Mitomycin C (MIT), 5 Fluorouracil (5 FU), and radiation therapy (RT). CT and RT doses on this Phase I-II Study were escalated to the current regimen. A split course of RT was used, either pelvic RT alone (4560 Gy in 28 fractions) or the same pelvic RT plus para-aortic RT (3600 Gy in 24 fractions). CT was given: MIT 6 mg/M* IV push day 1, and 5 FU 1.0 g/M* (maximum daily 1.5 g) by continuous IV infusion days 1 through 4 of each half-course of RT. This was followed by one application of intrauterine "'Cs when possible. Three of the 8 patients with recurrence in the pelvis or para-aortic nodes had a complete response (CR) to CT-RT and are alive without disease at 19, 19 and 22 months after treatment, respectively. Twenty of the 27 (74%) primary patients had a CR. With a median duration of follow-up of 6 months 4/20 have relapsed, 1 in RT field, 2 at distant sites, and 1 in both. Pelvic disease remains controlled in 19/27 (70%) including one patient salvaged with surgery. The acute toxicity of this regimen was tolerable: 2/35 developed transient leukopenia with one febrile episode, 9/35 developed transient thrombocytopenia without bleeding. Symp tomatic sigmoid strictures developed in two patients, one requiring surgical intervention.

This article reports the 6-year results of a controlled adjuvant trial carried out in 140 postmenopausal women aged 65 years or less having resectable breast cancer and positive axillary nodes. Within 4 weeks after surgery, patients were started on cyclophosphamide, methotrexate, and fluorouracil and prednisone (CMFP) for 6 cycles foilowed by Adriamycin | plus vincristine (AV) for 4 cycles. Chemotherapy was delivered with minimal dose reduction schedule. Patients were randomized to receive standard dose regimen for both combinations (treatment A) or progressive dose intensification (treatment B). There was no significant difference in the relapse-free (RFS) and overall survival (OS) rates between the 2 treatment groups. Treatment results were inversely related to the number of involved axillary nodes. In the subset with 1 to 3 positive nodes, present findings are superior (RFS 75.2%, OS 84.2 %) when retrospectively compared to the 6-year results achieved with adjuvant CMF in the same postmenopausal subset (12 cycles: RFS 55.4%, OS 67.3%; 6 cycles: RFS 47.5%, OS 65.5%). Acute toxicity was moderate and reversible, and no patient showed signs of cardiomyopathy. The results of this trial indicate that sequential noncrossresistant combinations administered with minimal dose reductions can favorably affect the postoperative course of postmenopausal women with limited nodal involvement. The study design does not allow for quantitating the relative contribution of CMFP versus AV chemotherapy.

Twenty-four-hour IC50 values (50% immobilization concentration) for phenol, o-cresol, mcresol, p-cresol, six xylenols, and three trimethylphenols were determined for Daphnia magna under static conditions. Our results show that cresols are more toxic than phenol, that xylenols do not exhibit significantly higher toxicity than cresols, and that trimethylphenols are less toxic than cresols. Thus, no direct relationship can be found between the number and position of methyl groups on the phenol nucleus and their acute toxicity to the water flea.

This study aims to elucidate the processes underlying neuroprotection of kaempferol in models of rotenone-induced acute toxicity. We demonstrate that kaempferol, but not quercetin, myricetin or resveratrol, protects SH-SY5Y cells and primary neurons from rotenone toxicity, as a reduction of caspases cleavage and apoptotic nuclei are observed. Reactive oxygen species (ROS) levels and mitochondrial carbonyls decrease significantly. Mitochondrial network, transmembrane potential and oxygen consumption are also deeply preserved. We demonstrate that the main event responsible for the kaempferol-mediated antiapoptotic and antioxidant effects is the enhancement of mitochondrial turnover by autophagy. Indeed, fluorescence and electron microscopy analyses show an increase of the mitochondrial fission rate and mitochondria-containing autophagosomes. Moreover, the autophagosome-bound microtubule-associated protein light chain-3 (LC3-II) increases during kaempferol treatment and chemical/genetic inhibitors of autophagy abolish kaempferol protective effects. Autophagy affords protection also toward other mitochondrial toxins (1-methyl-4-phenyilpiridinium, paraquat) used to reproduce the typical features of Parkinson's disease (PD), but is inefficient against apoptotic stimuli not directly affecting mitochondria (H 2 O 2 , 6-hydroxydopamine, staurosporine). Striatal glutamatergic response of rat brain slices is also preserved by kaempferol, suggesting a more general protection of kaempferol in Parkinson's disease. Overall, the data provide further evidence for kaempferol to be identified as an autophagic enhancer with potential therapeutic capacity.

Teas of Vernonia condensata Baker (Asteraceae) are widely used in Brazil for gastro-intestinal disorders and to treat several other diseases. In this study, we evaluated the acute toxicity, embryotoxicity and mutagenicity of a lyophilized aqueous extract (LAE) from V. condensata leaves. Single doses of LAE, up to 5000 mg/kg body weight, were given orally or intraperitoneally to male and female Swiss albino mice. No toxicity was observed after oral administration. The "Approximate Lethal Dose" after intraperitoneal injections was 3400 mg/kg for males and 5000 mg/kg for females. Embryotoxicity was investigated in Han:NMRI mice. LAE (0, 500 and 2000 mg/kg/day) was given by gavage on days 10, 11 and 12, and dams were submitted to caesarean sections on day 18 of pregnancy. Fetuses were weighed, examined for externally visible malformations, and evaluated for skeletal anomalies. Except for a slight reduction of fetal body weight accompanied by signs of delayed ossification at the highest dose, no other embryotoxic effect was noted in the exposed offspring. LAE-induced mutagenicity was evaluated in the Salmonella/microsome assay without and with S9 mixture. LAE, tested up to 5000 microg/plate, was not mutagenic to tester strains TA97a, TA98 and TA100. Results therefore suggest that V. condensata aqueous extracts present low acute toxicity and pose neither teratogenic nor mutagenic risks.

A series of experiments were conducted to determine the toxicity, behavior, blood glucose stress response, and disease susceptibility in Nile tilapia Oreochromis niloticus following un-ionized ammonia (UIA) exposure. The acute toxicity of un-ionized ammonia to Nile tilapia was measured in a 96-h static test. The median lethal concentration (LC50) was 1.46 mg/L UIA at 24 and 48 h postexposure, 1.33 mg/ L at 72 h postexposure, and 0.98 mg/L at 96 h postexposure. No mortalities were noted in unexposed (0 mg/ L) control fish or fish exposed to 0.5 mg/L UIA. However, 93-100% mortalities were observed within 24 h among fish exposed to 2.0, 3.0, or 4.0 mg/L UIA. In additional UIA exposure experiments, Nile tilapia were exposed to sublethal concentrations (0.32-0.37 mg/L UIA) for 24 h and then administered an intraperitoneal injection with 750 colony-forming units (CFU) of Streptococcus agalactiae per fish. Mortalities of UIAexposed and control fish were not significantly different 21 d postchallenge. Blood glucose levels were not significantly different between exposed and control fish 24 h after the beginning of UIA exposure or between preexposure fish and 24-h postexposure fish. Glucose levels in both groups increased significantly after UIA exposure and subsequent bacterial challenge, suggesting that Nile tilapia experienced handling or infection stress and not necessarily UIA exposure stress alone. During a time course study with 24-h UIA exposure, sequential blood glucose samples indicated acute stress responses 1-4 h postexposure that decreased by 24 h postexposure. The results of this study indicate that exposure to increased UIA concentrations alone had acute, transient effects on stress responses in Nile tilapia and that 24-h exposure to sublethal UIA concentrations up to 0.37 mg/L did not increase susceptibility to S. agalactiae.

Sida cordifolia L. (Malvaceae) is used in folk medicine for the treatment of inflammation of the oral mucosa, blenorrhea, asthmatic bronchitis and nasal congestion. The anti-inflammatory, analgesic effects and acute toxicity of an aqueous extract of S. cordifolia were evaluated in animal models. The extract was prepared using leaves collected before the flowering period. The aqueous extract (AE) showed a significant inhibition of carrageenin-induced rat paw edema at a dose of 400 mg/kg administered orally, but did not block the edema induced by arachidonic acid. The AE also increased the latency period for mice in the hot plate test, and inhibited the number of writhes produced by acetic acid at the oral dose of 400 mg/kg. The aqueous extract of S. cordifolia showed low acute toxicity in mice.

After the definitive ban on tin-based antifouling substances, new organic compounds have recently been introduced in antifouling paint formulations, as either principal or booster biocides. In most cases, previous risk assessment of these biocides has been inadequate so that their possible effects on aquatic ecosystems is a matter of great concern. We studied the effects of two new organic biocides often associated in paint formulations, Sea-Nine 211 TM (4,5 dichloro-2-n-octyl-4-isothiazoline-3-one) and chlorothalonil (2,4,5,6-tetrachloroisophthalonitrile), on haemocytes of the compound ascidian Botryllus schlosseri exposed for 60 min to various concentrations (from 0.1 to 10 M) of the xenobiotics. This species had previously proved to be a good bioindicator of organotin compounds. Both compounds, at concentrations of 1 and 10 M, altered the morphology of phagocytes, and these changes were closely related to disrupting effects on cytoskeletal components. At the same concentrations, phagocytosis, which requires cytoskeletal modifications for pseudopod formation, was severely hindered. Both compounds were able to induce apoptosis of Botryllus blood cells, probably as a consequence of severe oxidative stress related to the reported decrease of intracellular reduced glutathione (GSH) content. In the case of Sea-Nine 211 TM , a substantial increase in intracellular Ca 2+ and a negative effect on Ca 2+-ATPase activity may also be involved in the activation of the cell death machinery. Cytochrome-c-oxidase was also significantly inhibited by the two biocides, indicating perturbation of the mitochondrial respiratory chain. Isodynamic mixtures of Sea-Nine 211 TM and chlorothalonil were used to evaluate the occurrence of interactions between the two compounds. Results suggest the combined action of partial additivity when cell-spreading and cytochrome-c-oxidase activity were considered, and were indicative of antagonism in the case of the GSH depletion. On the whole, our results indicate that short-term in vitro exposure of haemocytes to high concentrations of Sea-Nine 211 TM and chlorothalonil provokes a marked reduction in haemocyte functionality, higher than or comparable to that of TBT. These assays of acute toxicity stress the immunosuppressive potential of these compounds, which, although counterbalanced by their short half-life in the marine environment, can lead to biocoenosis dismantling through rapid bioaccumulation by filter-feeding non-target benthic organisms.

Alpinia galanga is an important ingredient in various herbal formulations has reached extensive acceptability as therapeutic agents for several diseases. The investigation of authentic analytical methods, which can reliably profile the phytochemical composition and studies on toxicity profile, including hematological and biochemical parameters is an important initial step for the establishment of standardization to screen further in search of consistent biological activity. Aim: To screen ethanolic extract of Alpinia galanga for its phytochemical constituents and acute toxicity profile. Methods: Acute toxicity studies done in rodent by OECD guideline 423 and phytochemical analysis by standard laboratory grade reagents. Results The present study revealed the presence of complex phytochemical constituents including phenols and flavanoids. The acute toxicity results has classified the test material to fall under the hazard category 2000mg/kg<LD50<5000mg/kg according to globally harmonized classification system. Conclusion The present study concludes the safety of ethnobotanical use of Alpinia galanga from acute toxicity results and the presence of various phytochemical constituents in Alpinia galanga may be responsible for its various pharmacological actions documented in traditional medicine.

Cladocerans have long been used for toxicological assessments of a diverse range of substances. The use of cladocerans in toxicity tests has many advantages, such as their short life cycle, parthenogenetic reproduction (clones), and high sensitivity to toxicants, as well as the easy laboratory maintenance of cultures. The most commonly used cladoceran in ecotoxicological studies of aquatic environments is undoubtedly Daphnia magna. Standard methods using cladocerans as test organisms have been documented and adopted by major international organizations and regulatory agencies of many countries. However, today there is a growing need for improving test organisms and protocols to better reflect local species sensitivity or site-specific conditions. The present study aimed to assess the tropical species Pseudosida ramosa as a potential test organism for ecotoxicological purposes, by carrying out standard acute tests with six reference compounds. Based on the results obtained in the present study and in comparison with other cladocerans, it was found that P. ramosa was more sensitive than Daphnia magna, had a sensitivity similar to that of Daphnia similis, and was less sensitive compared to Ceriodaphnia dubia and C. silvestrii (Neotropical species), except for the salts, sodium chloride and potassium chloride. Also, when P. ramosa was compared with test organisms of other taxonomic groups, we observed that it was more sensitive than most of the others, from simple coelenterates to complex fish. Considering these results and the wide distribution of the cladoceran P. ramosa in tropical and subtropical regions, we suggest that this species can be adopted as a test organism, being a good substitute for the exotic daphnid D. magna, for monitoring of toxicants in freshwaters.

In 1997, the National Cancer Institute (NCI) led an effort to revise and expand the Common Toxicity Criteria (CTC) with the goal of integrating systemic agent, radiation, and surgical criteria into a comprehensive and standardized system. Representatives from the Radiation Therapy Oncology Group (RTOG) participated in this process in an effort to improve acute radiation related criteria and to achieve better clarity and consistency among modalities. CTC v. 2.0 replaces the previous NCI CTC and the RTOG Acute Radiation Morbidity Scoring Criteria and includes more than 260 individual adverse events with more than 100 of these applicable to acute radiation effects. One of the advantages of the revised criteria for radiation oncology is the opportunity to grade acute radiation effects not adequately captured under the previous RTOG system. A pilot study conducted by the RTOG indicated the new criteria are indeed more comprehensive and were preferred by research associates. CTC v. 2.0 represents an improvement in the evaluation and grading of acute toxicity for all modalities.

Labisia pumila (Myrsinaceae), is a popular herb among the women in Malaysia known locally as ''Kacip Fatimah". Recently many nutraceutical products containing the powdered or extracted parts of the plant have become available for women's health care. However no evaluation of the effect of the repeated dosing of any herbal product of this plant had been undertaken prior to a 28-day sub-acute study presented in this report. The results showed that a dose of 50 mg/kg of an aqueous extract of L. pumila corresponded to no-adverse-effect-level (NOAEL), whereas higher doses were associated with some toxicity concerns.

Background and purpose:Evidence indicates that the endocannabinoid, 2-arachidonoylglycerol (2-AG), increases food intake when injected into the nucleus accumbens shell (NAcS), thereby potentially activating hypothalamic nuclei involved in food intake regulation. We aimed to evaluate potential orexigenic effects of the endocannabinoid anandamide and of AA5HT, a fatty acid amide hydrolase (FAAH) inhibitor, and OMDM-1, an inhibitor of anandamide uptake, injected in the NAcS, as well as the effect of these treatments on activation of hypothalamic nuclei.Evidence indicates that the endocannabinoid, 2-arachidonoylglycerol (2-AG), increases food intake when injected into the nucleus accumbens shell (NAcS), thereby potentially activating hypothalamic nuclei involved in food intake regulation. We aimed to evaluate potential orexigenic effects of the endocannabinoid anandamide and of AA5HT, a fatty acid amide hydrolase (FAAH) inhibitor, and OMDM-1, an inhibitor of anandamide uptake, injected in the NAcS, as well as the effect of these treatments on activation of hypothalamic nuclei.Experimental approach:Drugs were given into the NAcS of rats and food intake quantified during the next 4 h. In other groups, after the same treatments the brains were processed for c-Fos immunohistochemistry with focus on hypothalamic nuclei. Additional groups were used to quantify endocannabinoid levels in the nucleus accumbens and the hypothalamus after AA5HT and OMDM-1 intra-NAcS injections.Drugs were given into the NAcS of rats and food intake quantified during the next 4 h. In other groups, after the same treatments the brains were processed for c-Fos immunohistochemistry with focus on hypothalamic nuclei. Additional groups were used to quantify endocannabinoid levels in the nucleus accumbens and the hypothalamus after AA5HT and OMDM-1 intra-NAcS injections.Key resultsOur results indicate that the above treatments stimulate food intake during 4 h post-injection. They also increase c-Fos immunoreactivity in hypothalamic nuclei. The CB1 antagonist, AM251, blocked these effects. Finally, we found elevated levels of 2-AG, but not anandamide, after intra-NAcS injections of AA5HT.Our results indicate that the above treatments stimulate food intake during 4 h post-injection. They also increase c-Fos immunoreactivity in hypothalamic nuclei. The CB1 antagonist, AM251, blocked these effects. Finally, we found elevated levels of 2-AG, but not anandamide, after intra-NAcS injections of AA5HT.Conclusions and implications:These data support the involvement of the endocannabinoid system in feeding behavior at the level of the NAcS and hypothalamus. In addition, this is the first experimental demonstration that the pharmacological inhibition of endocannabinoid inactivation in the NAcS stimulates food intake, suggesting that the endocannabinoid degrading proteins can be a target for treating eating disorders.British Journal of Pharmacology (2007) 151, 1109–1116; doi:10.1038/sj.bjp.0707313These data support the involvement of the endocannabinoid system in feeding behavior at the level of the NAcS and hypothalamus. In addition, this is the first experimental demonstration that the pharmacological inhibition of endocannabinoid inactivation in the NAcS stimulates food intake, suggesting that the endocannabinoid degrading proteins can be a target for treating eating disorders.British Journal of Pharmacology (2007) 151, 1109–1116; doi:10.1038/sj.bjp.0707313

In order to evaluate the toxicity of TiO 2 particles, the acute toxicity of nano-sized TiO 2 particles (25 and 80 nm) on adult mice was investigated compared with fine TiO 2 particles (155 nm). Due to the low toxicity, a fixed large dose of 5 g/kg body weight of TiO 2 suspensions was administrated by a single oral gavage according to the OECD procedure. In 2 weeks, TiO 2 particles showed no obvious acute toxicity. However, the female mice showed high coefficients of liver in the nano-sized (25 and 80 nm) groups. The changes of serum biochemical parameters (ALT/AST, LDH) and pathology (hydropic degeneration around the central vein and the spotty necrosis of hepatocytes) of liver indicated that the hepatic injury was induced after exposure to mass different-sized TiO 2 particles. In addition, the nephrotoxicity like increased BUN level and pathology change of kidneys was also observed in the experimental groups. The significant change of serum LDH and alpha-HBDH in 25 and 80 nm groups showed the myocardial damage compared with the control group. However, there are no abnormal pathology changes in the heart, lung, testicle (ovary), and spleen tissues. Biodistribution experiment showed that TiO 2 mainly retained in the liver, spleen, kidneys, and lung tissues, which indicated that TiO 2 particles could be transported to other tissues and organs after uptake by gastrointestinal tract.

The environmental fate of many of the additives in the deicing agents used at airports is poorly understood. One and two years after deicing activities ceased, soil and groundwater samples were taken at an abandoned airport. Benzotriazole (BT), a corrosion and flame inhibitor, was found in low concentrations in soils along runways (mean 0.33 mg/kg), at a snow disposal site (0.66 mg/kg), as well as in sediments of a drainage ditch (13 mg/kg). Locally, high BT concentrations were found in the groundwater below the deicing pad, the regeneration plant and the snow disposal site (1.2 to 1100 µg/l). Methyl substituted triazoles or tolytriazoles (MeBT) were found in concentrations less than 10% of the BT concentration. Propylene glycol was not detected in soil samples and in only one of the groundwater samples. Microtox tests of the water samples revealed no acute toxic response, however a reduction in nitrification rate was observed (14-43%). The nitrification response could not be related directly to the BT concentration in the samples, although samples with a high BT concentration showed the largest reduction in nitrification rate. BT showed very little sorption in various soil matrices, only peat and compost with a high organic carbon content showed significant sorption. Sorption could be best described using a Freundlich isotherm. These results indicate a high mobility and possibly long persistence of BT in soil and groundwater, which may be attributed to the absence of microbial degradation of BT.

Context: Pithecellobium dulce (PD) is an annual herbaceous plant commonly used in African traditional medicine as a purgative, antipyretic, anti-ulcer and wound dressing agent. Aims: To evaluate the acute and sub-acute toxicity of P. dulce stem bark hydroethanolic extract in Wistar rats. Methods: In the acute test, a single dose of 5 g/kg body weight was administered to Wistar rats afterwards they were observed individually 4 hours post-dosing, and at least once daily for 14 consecutive days. The sub-acute toxicity was evaluated by daily oral administration of 0.5 and 1 g/kg extract, for 28 days. Biochemical and hematological parameters assessment as well as body and organ weights of the rats were carried out. Results: The limit dose of 5 g/kg did not cause any mortality or signs of acute toxicity on the rats during the experimentation period. In the sub-acute test, uterus-ovary-trompe (UOT) weight decreased dose-dependently: Control group (0.82 ± 0.03 g); Extract 0.5 g/kg (0.57 ± 0.06 g); Extract 1g/kg (0.48 ± 0.01 g) (p ˂ 0.01). Extract lowered urea values in female group treated with 1 g/kg (p < 0.01). Lymphocytes percentage was dose dependently increased in treated male groups: Control group (53.00 ± 0.58%); extract 0.5 g/kg (58.67 ± 0.67%) and extract 1 g/kg (60.67 ± 2.41%). Conclusions: These findings suggest that PD is relatively safe when administered orally in rats but is slightly atrophic for female reproductive organs.

Reducing environmental impacts and getting economic benefits, based on by-product recovery, and on reduction of both water consumption and organic load, was the aim of the implementation of an eco-efficiency process in a crispy chips industry. Separations at the source were implemented resulting in increase of business productivity, due to the added value achieved through by-product valorisation. Improvement changes were monitored through physico-chemical and ecotoxicological evaluations of the wastewater, which has favourably evolved from acutely toxic to minor acutely toxic. Evidence is provided about the formulation of cleaner production opportunities enabling the downsizing of the wastewater treatment plant (WWTP) with a subsequent decrease of energy, water and chemicals input and a decrease in sludge generation.

To evaluate the toxicity of environmental chemicals to invertebrates, a static bioassay was developed in the laboratory using the Caenorhabditis elegans (C. elegans). First, reproducibility of this aquatic acute toxicity test system was confirmed. In order to estimate chemical toxicities in C. elegans, worms were subsequently exposed to eleven different xenobiotics. Mortality after 24 hr was adopted as the endpoint of toxicity. We found that benzo[a]pyrene, nonylphenol, benzophenone, bisphenol A and cadmium chloride affected viability of C. elegans. These data suggest that C. elegans is a suitable toxicity test organism for environmental xenobiotic chemicals, and that lethality can be used as a testing endpoint.

Atlantic salmon (Salmo salar) parr were exposed to aluminium under both steady state and non-steady state chemical conditions in 21 2 alkaline water. Under alkaline (pH 9.5) steady state conditions, |350 mg Al l (predominantly aluminate, Al(OH)) had no acute toxic 4 effect on the salmon. The fish, however, showed a physiological response after 3 weeks of exposure (|300% increase in blood glucose 2 concentration, about 30% increase in blood haematocrit, and about 15% decrease in plasma Cl concentration). No increase in toxicity was evident under non-steady state conditions, i.e. lowering Al solubility as pH was lowered from 9.5 to 7.5. The results indicate that the 2 toxicity of the aluminate ion (Al(OH)) is low, and particularly lower than the corresponding toxicity of cationic Al hydroxides. The 4 effects observed in fish exposed to Al-rich water at pH 9.5 were counteracted as Al solubility was decreased by lowering pH to 7.5. This is contrary to previous observations where Al solubility has been lowered by increasing pH from 5.0 to 6.5.

Light exposure of aqueous suspensions of prednisolone and dexamethasone causes their partial phototransformation. The photoproducts, isolated by chromatographic techniques, have been identified by spectroscopic means. Prednisolone, dexamethasone and their photoproducts have been tested to evaluate their acute and chronic toxic effects on some freshwater chain organisms. The rotifer Brachionus calyciflorus and the crustaceans Thamnocephalus platyurus and Daphnia magna were chosen to perform acute toxicity tests, while the alga Pseudokircheneriella subcapitata (formerly known as Selenastrum capricornutum) and the crustacean Ceriodaphnia dubia to perform chronic tests. The photochemical derivatives are more toxic than the parent compounds. Generally low acute toxicity was found. Chronic exposure to this class of pharmaceuticals caused inhibition of growth population on the freshwater crustacean C. dubia while the alga P. subcapitata seems to be less affected by the presence of these drugs.

Chronic toxicity studies were performed with commercial phthalate esters and Duphniu mugnu (14 phthalates) and rainbow trout (Oncorhynchus mykiss) (six phthalates). For the lower-molecular-weight phthalate esters-dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), and butylbenzyl phthalate (BBP)-the results of the studies indicated a general trend in which toxicity for both species increased as water solubility decreased. The geometric mean maximum acceptable toxicant concentration (GM-MATC) for D. mugnu ranged from 0.63 to 34.8 mg/L. For the higher-molecular-weight phthalate esters-dihexyl phthalate (DHP), butyl2-ethylhexyl phthalate (BOP), di-(n-hexyl, n-octyl, n-decyl) phthalate (610P), di-(Zethylhexyl) phthalate (DEHP), diisooctyl phthalate (DIOP), diisononyl phthalate (DINP), di-(heptyl, nonyl, undecyl) phthalate (71 lP), diisodecyl phthalate (DIDP), diundecyl phthalate (DUP), and ditridecyl phthalate (DTDP)-the GM-MATC values ranged from 0.042 to 0.15 mg/L. Survival was equally sensitive and sometimes more sensitive than reproduction. The observed toxicity to daphnids with most of the higher-molecular-weight phthalate esters appeared to be due to surface entrapment or a mode of toxicity that is not due to exposure to dissolved aqueous-phase chemical. Early life-stage toxicity studies with rainbow trout indicated that survival (DMP) and growth (DBP) were affected at 24 and 0.19 mgiL, respectively. This pattern of observed toxicity with the lower-molecular-weight phthalate esters and not the higher-molecular-weight phthalate esters is consistent with previously reported acute toxicity studies for several aquatic species.

Deoxynivalenol (DON), a trichothecene, is prevalent worldwide in crops used for food and feed production. The presence of mycotoxins in poultry feeds is a significant factor for financial losses to animal industries. Although DON is one of the least acutely toxic trichothecenes, it should be treated as an important food safety issue because it is a common contaminant of grains. Special care must be taken in so-called "Fusarium years". As poultry is regarded to be less sensitive to DON compared to other species it is suspected to divert the infected cereal batches to poultry feeding. This review focuses on the ability of DON to induce toxicologic and immunotoxic effects in chickens. Chickens and laying hens respond to increasing dietary DON concentrations with a reduction in productivity only at high levels above 5mg/kg but there is no clear evidence of a dose-response relationship. The main effect at low dietary concentrations appears to be a reduction in food consumption (anorexia), while higher doses induce severe reduction in weight and impaired resistance to infection, particularly bacterial infection. One important aspect of DON toxicity is injury to the gastrointestinal tract. DON has an influence intestinal morphology of chickens, especially in the duodenum and jejunum, as evidenced by shorter and thinner villi. Additionally, DON decreased the intestinal nutrients absorption (glucose and amino acid) in the chicken small intestine in vivo and In vitro. The capacity of DON to alter normal immune function has been of particular interest. There is extensive evidence that DON impairs the immune function in broiler and Leghorn chicks. DON induced changes in the haematopoietic system of chicks and altered the mitogen-induced proliferation of lymphocytes. The feeding of DON contaminated grains decreases serum antibody titers against Newcastle disease virus (NDV) and infectious bronchitis virus (IBV) in laying hens and broilers. Other effects include superinduction of cytokine production by T helper cells (In vitro) and activation of T cells to produce a proinflammatory cytokine. To what extent the elevation of cytokines contributes to metabolic effects such as decreased feed intake remains to be established. Further toxicological studies on the impact of DON in the immune system and gastrointestinal tract of poultry are warranted.

The LD 50 of Z 7557 in mice was between 500 and 625 mg/kg after i.v. and around 2310 mg/kg after oral administration. The corresponding LD 10 was around 435 mg/kg (i.v.) or 1100-1250 mg/kg (p.o.), respectively. The LD 50 values in rats were in the range of 250-310 mg/kg after i.v. administration and around 1000-1250 mg/kg if given orally. With repeated daily i.v. injections only 70% of the daily dose contributed to lethality. A second administration of Z 7557 to rats after reversal of all toxic signs from the first administration induced the same symptoms and degree of toxicity as the initial injection. Reversible myelosuppression was the predominant feature of toxicity in mice and rats, but at equimolar doses this myelotoxicity was less than half that of cyclophosphamide (CP). First signs of immunosuppression were seen only at 100 mg/kg i.v.. No severe urotoxicity was observed in rats with single i.v. doses up to 192 mg/kg. This might be due to the fast and complete renal excretion of the thiol moiety of Z 7557, whereas the activated oxazaphosphorine component occurred in the urine only to a much smaller amount, as could be shown by a pilot pharmacokinetic study. In conclusion, Z 7557 appeared to have an overall tolerance in rats and mice similar to cyclophosphamide but was clearly less toxic with respect to the bone marrow, the immune system and the urinary tract.

is an organophosphorous compound still largely used in agriculture and fish hatcheries. This pesticide is not quite selective and is potentially toxic for both vertebrates and invertebrates. Its mechanism of acute toxicity is the inhibition of the enzyme acetylcholinesterase in nervous tissue. Binding of pesticides to plasma proteins is one of many factors that influence their distribution and elimination. The free concentration available for toxic action can be effectively reduced for pesticides with high binding to plasma proteins, although the affinity of pesticides to plasma proteins is often lower than for the enzyme targets. Several different transport proteins exist in blood plasma, but albumin only is able to bind a wide diversity of xenobiotics reversibly with high affinity. It was already known that parathion (ethyl parathion) exhibits a high affinity to human and bovine serum albumins. We studied interactions of methyl parathion with these albumins by using fluorescence quenching techniques. We selectively excited the fluorescence of tryptophan residues with a 290 nm wavelength light, and observed quenching by titrating human and bovine serum albumin solutions with methyl parathion. Stern-Volmer graphs were plotted and quenching constants were estimated. Our results pointed to the formation of complexes of methyl parathion with albumins. Association constants at 25 • C were 3.07 × 10 4 (1.2 × 10 3 ) M −1 for human serum albumin, and 1.96 × 10 4 (±4.5 × 10 2 ) M −1 for bovine serum albumin. At 37 • C, they were 1.08 × 10 4 (±2.0 × 10 2 ) M −1 for human serum albumin, and 8.16×10 3 (±1.9×10 2 ) M −1 for bovine serum albumin. Results also suggest that the primary binding site for methyl parathion on albumin is close to tryptophan residues 214 of human serum albumin and 212 of bovine serum albumin.

Potassium permanganate is a chemical compound widely used in aquaculture for the control and removal of parasites, and in the prevention of diseases caused by bacteria and fungi. However, this compound can be toxic to fish, being a strong oxidant. Moreover, there is no consistent information in the literature about its toxicity to non-target organisms. The purpose of this study was to evaluate the acute toxicity (LC50;96h) of potassium permanganate for tilapia, Oreochromis niloticus, and to determine its toxic effects on nontarget organisms using ecotoxicological assays performed with the microcrustacean Ceriodaphnia dubia and with the green microalgae Pseudokirchneriella subcapitata. The results showed that the concentration of 1.81 mg L − 1 of potassium permanganate caused acute toxic effect in tilapia fingerlings. The ecotoxicological assays demonstrated that concentrations above 0.12 mg L − 1 can cause chronic toxic effects on non-target organisms, indicating possible deleterious effects on the food chain of the aquatic ecosystem that may receive the discharge of effluents released by fish cultures treated with this chemotherapy. All toxic concentrations determined in this study were below those recommended in the literature for the use of this chemotherapy in fish cultures, demonstrating that this type of therapy should be more carefully considered in order to avoid damage to the treated fish and to the environment.

An acute toxicity study of three metals to Hydra species carried out using two different assessment methods, (i) determination of the LC50 and (ii) measurement of progressive morphological changes, demonstrated that relative toxicity decreased from copper to cadmium with zinc the least toxic for all species. The latter method revealed more details of the effect on Hydra in terms of physical damage to the polyp but both methods indicated that H. viridissima was more sensitive to copper and cadmium than H. vulgaris1 (Zurich strain, male clone), H. vulgaris2 (a dioecious strain reproducing sexually and asexually) and H. oligactis (dioecious, reproducing sexually and asexually). The responses to zinc were similar for all Hydra. The possible role of metabolic interactions between H. viridissima and its symbiotic green algae in contributing to the greater sensitivity of this polyp is discussed.

We present herein a new herbal combination called Etana that is composed of five herbal extracts including Panax quinquelotius (Ginseng), Eurycoma longifolia (Tongkat Ali), Epimedium grandiflorum (Horny goat weed), Centella asiatica (Gotu Kola) and flower pollen extracts. Most of the above-mentioned extracts have a long historical and traditional use for erectile dysfunction (ED). On the basis of the mechanism of action of each of the above, a combination is introduced to overcome several physiological or induced factors of ED. This study was conducted to show an enhancement of erectile function in male rats. The animals were observed for 3 h after each administration for penile erection, genital grooming and copulation mounting, and the penile erection index (PEI) was calculated. The maximum response was observed at the concentration of 7.5 mg kg -1 of Etana. At a 7.5 mg kg -1 single dose, the percentage of responding rats was 53±7 with a PEI of 337±72 compared with 17±6 with a PEI of 30±10 for control animals. This PEI was significantly (Po0.001) higher than each single component and than the sum of any two herbal components of Etana. When compared with sildenafil citrate, Etana induced more pronounced PEI than 0.36 mg kg -1 , but similar to 0.71 mg kg -1 of sildenafil. Furthermore, full acute and sub-acute toxicity studies showed no toxic effects of Etana. In conclusion, this study describes a new and safe combination of herbal components that enhance erectile function in male rats. Clinical studies are warranted for evaluating Etana's significance in ED.

The current study was conducted to determine the LC 50 value of ammonia-N as well as the effects of acute exposure to elevated ammonia on the haemolymph osmolality, ionic composition, ammonia-N and pH levels of early juvenile mud crabs, Scylla serrata. The results show that early S. serrata juveniles have a high 96-h LC 50 value of 95.35 mg/L ammonia-N (6.81 mg/L NH 3 -N) or 6.80 mmol/L total ammonia-N (0.486 mmol/L NH 3 -N). Following a 96-h exposure, the haemolymph osmolality and K + levels of the surviving crabs remained unaltered (p N 0.05) at all ammonia-N concentrations, while the haemolymph Na + and Ca 2+ were significantly lower (p b 0.05) for the crabs exposed to 5.710 and 7.138 mmol/L ammonia-N. While the haemolymph ammonia-N levels of the crabs significantly increased (p b 0.01) with increasing external ammonia-N concentrations, the haemolymph ammonia-N of the crabs remained below the external ammonia-N concentrations. The haemolymph pH of the crabs significantly increased between 0.714 and 4.283 mmol/L total ammonia-N. However, at 5.710 mmol/L total ammonia-N the haemolymph pH dropped and was not significantly different (p N 0.05) from that of the control crabs which coincided with significantly lower (p b 0.05) haemolymph Na + and Ca 2+ levels. These physiological responses may explain the high ammonia tolerance of early S. serrata juveniles.

Coagulation and subsequent chlorination are typically used for surface water treatment in order to produce potable water. Chitosan, a linear cationic polymer of high molecular weight, has recently been proposed for application in drinking water treatment as potential alternative to metal species based coagulants. However, due to its nature some organic matter may be released during coagulation step, thus increasing the concentration of disinfection by-products as well as the toxicity of finished water. In the present paper the efficiency of chitosan and conventional coagulants (aluminium sulphate and ferric chloride) was compared in terms of turbidity and natural organic matter (NOM) removal, as well as acute toxicity on Daphnia magna of coagulated and coagulated/chlorinated surface water. The coagulation experiments were carried out by jar test using low TOC and high alkalinity surface water. Turbidity and NOM removal, as well as toxicity were investigated (i) under actual conditions, (ii) for different pH (5, 6, 7) and (iii) in humic acid (HA) spiked surface water samples. All coagulants decreased toxicity on D. magna from 100% to 0% immobilization. However, the addition of humic acids affected final toxicity in different ways according to coagulant type and dose. Moreover, the chlorination step after coagulation increased toxicity too according to the coagulant type as follows: chitosan > ferric chloride > aluminium sulphate.

We present herein a new herbal combination called Etana that is composed of five herbal extracts including Panax quinquelotius (Ginseng), Eurycoma longifolia (Tongkat Ali), Epimedium grandiflorum (Horny goat weed), Centella asiatica (Gotu Kola) and flower pollen extracts. Most of the above-mentioned extracts have a long historical and traditional use for erectile dysfunction (ED). On the basis of the mechanism of action of each of the above, a combination is introduced to overcome several physiological or induced factors of ED. This study was conducted to show an enhancement of erectile function in male rats. The animals were observed for 3 h after each administration for penile erection, genital grooming and copulation mounting, and the penile erection index (PEI) was calculated. The maximum response was observed at the concentration of 7.5 mg kg-1 of Etana. At a 7.5 mg kg-1 single dose, the percentage of responding rats was 53±7 with a PEI of 337±72 compared with 17±6 with a PEI of 30±10 for control animals. This PEI was significantly (Po0.001) higher than each single component and than the sum of any two herbal components of Etana. When compared with sildenafil citrate, Etana induced more pronounced PEI than 0.36 mg kg-1 , but similar to 0.71 mg kg-1 of sildenafil. Furthermore, full acute and sub-acute toxicity studies showed no toxic effects of Etana. In conclusion, this study describes a new and safe combination of herbal components that enhance erectile function in male rats. Clinical studies are warranted for evaluating Etana's significance in ED.

Five treatments including control and four concentrations of water soluble fraction (WSFs) crude oil (5 ppm, 6 ppm, 8 ppm and 10 ppm) were made. Triplicate and ten fish of red tilapia with an average weight of 8g ± 1.5 were incubated for 96 hours. The 96 hours LC 50 was determined (5.25ppm). Histopathological examination of the fish was made for liver, gills, kidney, male gonad and female gonad. Liver showed congestion of blood vessels and hepatic sinusoids with focal necrotic changes of hepatocytes. Gills showed congestion of blood vessels, hyperplasia and adhesion of secondary gill lamellae. Kidney showed congestion of blood vessels and degeneration of renal tubules. Male gonad showed degeneration and necrosis of some seminiferous tubules, edema and severe reduction in all spermatogenic stages and degeneration and Female gonad showed severe necrosis of developmental stages of oocytes along with degenerated mature ripped oocytes in WSFs treated fish compared to control group.

Alteration in behavioral patterns and histopathology of gill, kidney and liver were studied in Channa punctatus, after acute exposure to hexavalent chromium. The 96 h LC 50 of chromium salt, potassium dichromate was determined to be 41.75 mg/L. The exposed fish displayed erratic swimming and became lethargic. The changes in gills were characterized by epithelial hyperplasia, lamellar fusion, oedema, epithelial lifting, epithelial necrosis and desquamation, aneurism as well as curling of secondary lamellae. Hypertrophy of epithelial cells of renal tubules with reduced lumens, atrophy of the renal tubules, glomeruli contraction in the Bowman's capsules and necrosis of haematopoietic tissues were observed in the trunk kidney of exposed fish. The interrenal cells of the head kidney exhibited distinct hypertrophy and vacuolization. The liver hepatocytes showed cytoplasmic vacuolization with the lateral nuclei arrangement. Hepatocytes atrophy and increase in sinusoidal space were also observed. The result showed that acute chromium toxicity severely affects the vital organs and normal behavior which may be deleterious for fish populations.

AbstractÐSodium bromide can be used to convert hypochlorous acid into hypobromous acid. An alternative strategy to biofouling control uses the simultaneous addition of sodium bromide and chlorine to water used for power plant condenser cooling. This approach can signi®cantly reduce the total disinfectant and halogen application rates because the bromine oxidants that are generated are more eective for controlling biofouling than their chlorine counterparts, especially at higher pHs. Since such a change in biofouling control strategy could adversely impact the environment, the acute toxicity of bromine oxidants were evaluated in both continuous and intermittent exposure scenarios. Decay properties of bromine oxidants were compared to those of chlorine oxidants. In addition, two tests were conducted to investigate the relative toxicities of chloramines and bromamines. For the six species tested, bromine oxidants were two to ®ve times more toxic than chlorine oxidants. For continuous exposure to bromine oxidants, LC 50 values for daphnids (Dapnia magna) and amphipods (Hyalella azteca) could not be calculated because signi®cant mortality occurred at the oxidant quantitation limit. Both chlorine and bromine proved to be more toxic to daphnids and mysids (Mysidopsis bahia) in the presence of ammonia. While the toxicity data show that bromine oxidants are more toxic than chlorine oxidants, bromine oxidants decayed two to ®ve times faster than chlorine oxidants in freshwater and saltwater, respectively. With regard to potential environmental impact, it is important that one consider the more ecacious biocidal characteristics of bromine (i.e. higher pHs) in the context of more rapid decay relative to chlorine. The strategy of using simultaneous addition of sodium bromide and chlorine could reduce environmental impact potential, although insucient data exists to prove this. #

Propyl paraben (CAS no. 94-13-3) is a stable, non-volatile compound used as an antimicrobial preservative in foods, drugs and cosmetics for over 50 years. It is an ester of p-hydroxybenzoate. Propyl paraben is readily absorbed via the gastrointestinal tract and dermis. It is hydrolyzed to p-hydroxybenzoic acid, conjugated and the conjugates are rapidly excreted in the urine. There is no evidence of accumulation. Acute toxicity studies in animals indicate that propyl paraben is relatively non-toxic by both oral and parenteral routes, although it is mildly irritating to the skin. Following chronic administration, no-observed-eect levels (NOEL) as high as 1200±4000 mg/kg have been reported and a no-observed-adverse-eect level (NOAEL) in the rat of 5500 mg/kg is posited. Propyl paraben is not carcinogenic, mutagenic or clastogenic. It is not cytogenic in vitro in the absence of carboxyesterase inhibitors. The mechanism of propyl paraben may be linked to mitochondrial failure dependent on induction of membrane permeability transition accompanied by the mitochondrial depolarization and depletion of cellular ATP through uncoupling of oxidative phosphorylation. Sensitization has occurred when medications containing parabens have been applied to damaged or broken skin. Parabens have been implicated in numerous cases of contact sensitivity associated with cutaneous exposure, but high concentrations of 5±15% in patch testing are needed to elicit reaction in susceptible individuals. Allergic reactions to ingested parabens have been reported, although rigorous evidence of the allergenicity of ingested paraben is lacking.

The risks to non-target birds and other wildlife from the use of vertebrate pesticides, including anticoagulant rodenticides, are determined to a significant extent by species&#39; intrinsic susceptibility, and the toxicokinetics of the compounds used. Brodifacoum is highly toxic to birds and mammals. The acute toxicity of brodifacoum to birds in New Zealand varies from &lt;1 mg/kg in pukeko (Porphyrio p. melanotus), the native swamp hen, to &gt;20 mg/kg in the paradise shelduck (Tadorna variegata). Like other second-generation anticoagulants brodifacoum is strongly bound to vitamin K epoxide reductase and will persist, apparently for at least 6 months, in organs and tissue containing this enzyme, e.g., liver, kidney, and pancreas. The unique toxicokinetics of this class of compound exacerbates the risk of primary and secondary poisoning of non-target species. Vertebrate pest control programmes in New Zealand using bait containing brodifacoum have resulted in the primary and seconda...

Purpose: To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. Methods and Materials: A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. Results: The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. Conclusion: High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control. Ó