Search

Persistent organic pollutants reach aquatic ecosystems during application and can bioconcentrate/biomagnify because of their lipophilic nature. Toxicological studies focus almost exclusively on the active ingredients of pesticides, instead of commercial formulations, whose toxicity can differ as a result of nonspecified ingredients. The intensive use of endosulfan as a wide-ranging insecticide over the last few decades makes it one of the most frequently detected contaminants in the aquatic environment, even after it has been restricted worldwide. The aim of the present study was to evaluate the bioaccumulation and organ distribution of waterborne endosulfan in the freshwater fish Cichlasoma dimerus, comparing the active ingredient and a commercial formulation. Males were exposed to 0.7 μg/L endosulfan for 2 wk, which was quantified (gas chromatography with an electron capture detector) in the liver, testes, gills, brain, and muscle. The results suggest rapid metabolism of α-endosulfan and β-endosulfan isomers to endosulfan sulfate (endosulfan-S) in tissues. Isomer levels were highest in gills, indicative of recent uptake. Levels of endosulfan-S were highest in liver and testes for the active ingredient and testes and brain for the commercial formulation. For the active ingredient, endosulfan-S levels showed a positive correlation with organ-lipid percentage. No correlation was evident for the commercial formulation, indicating that the presence of adjuvants alters endosulfan distribution because gills and liver showed a higher uptake and mobilization of β-endosulfan. These differences in organ distribution may alter tissue-specific toxicity; therefore, additives cannot be considered inactive even if nontoxic. Environ Toxicol Chem 2020;39:604-611. © 2019 SETAC., (© 2020 SETAC.)

Persistent organic pollutants (POPs) are of great concern for the environment. In this study we (a) determine levels and distribution of OCPs, PCBs, and PBDEs in sediments and two crab species (Neohelice granulata and Cyrtograpsus altimanus), (b) assess bioaccumulation in crabs, and (c) explore the occurrence of POPs in the Near Threatened Olrog's gull (Larus atlanticus) chicks and eggs in one of the most important salt marsh environments in the South West Atlantic. Sediments, crabs, and gull chicks and eggs showed POPs presence at low levels; being α-endosulfan, PCB-153, and BDE-47 the most represented compounds. In sediments, pollutant concentrations were lower than those reported in Canadian guidelines for the protection of the aquatic life. POP bioaccumulation was recorded in crabs, suggesting a risk to upper trophic level predators. Further studies are needed to understand the trophic effects of POPs in San Blas bay, particularly on the threatened Olrog's gull., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We investigated the effects of the insecticide endosulfan on energy metabolism and its possible accumulation in fruit bats. Adult male bats (Artibeus lituratus) were exposed for 35 days, when they were offered fruit treated with endosulfan (E) and adhesive spreader (AS) in the following concentrations (g/L): 0.0; 0.0 (Control), 0.0; 0.015 (AS), 1.05; 0.015 (E1), 2.1; 0.015 (E2). Concentrations used were those recommended by the manufacturer for fruit crop application (E1) or twice this value (E2). E1 bats showed decreased plasma glucose concentration. Carcass fatty acids were decreased in E1 and E2 bats. Endosulfan bioaccumulation was observed in both liver and adipose tissues from E1 and E2 bats. These results indicate that the chronic exposure of fruit bats to environmentally relevant concentrations of endosulfan can lead to significant bioaccumulation beyond control and also decreased fatty acid content, which may impair the health of this important seed disperser in neotropical forests.

Background . Many individuals have been exposed to organochlorinated pesticides (OCPs) through food, water, air, dermal exposure, and/or vertical transmission. Due to enterohepatic reabsorption and affinity to adipose tissue, OCPs are not efficiently eliminated from the human body and may accrue in tissues. Many epidemiological studies demonstrate significant exposure-disease relationships suggesting OCPs can alter metabolic function and potentially lead to illness. There is limited study of interventions to facilitate OCP elimination from the human body. This study explored the efficacy of induced perspiration as a means to eliminate OCPs. Methods . Blood, urine, and sweat (BUS) were collected from 20 individuals. Analysis of 23 OCPs was performed using dual-column gas chromatography with electron-capture detectors. Results . Various OCPs and metabolites, including DDT, DDE, methoxychlor, endrin, and endosulfan sulfate, were excreted into perspiration. Generally, sweat samples showed more frequent OCP detection than serum or urine analysis. Many OCPs were not readily detected in blood testing while still being excreted and identified in sweat. No direct correlation was found among OCP concentrations in the blood, urine, or sweat compartments. Conclusions . Sweat analysis may be useful in detecting some accrued OCPs not found in regular serum testing. Induced perspiration may be a viable clinical tool for eliminating some OCPs.

The carry-over of dietary endosulfan to the fillet of farmed Atlantic salmon was studied. The uptake and elimination rate constants of the alpha and beta isoform of endosulfan were determined in seawater adapted Atlantic salmon (initial weigh 173+/-25 g) fed on endosulfan enriched diets (724 and 315 microg kg(-1) for alpha- and beta-endosulfan, respectively) for 92 days, followed by a 56 days depuration period with feeding on control diets (<0.3 microg kg(-1) endosulfan). The accumulation of the toxic metabolite endosulfan sulphate, which was not detected (<0.5 microg kg(-1)) in the experimental feeds, was also determined. Dietary beta-endosulfan was more persistent than alpha-endosulfan as demonstrated by a higher uptake (41+/-8% vs. 21+/-2%) and lower elimination (26+/-2 x 10(-3) day(-1) vs. 40+/-1 x 10(-3) day(-1)) rate constants, and a higher biomagnification factor (0.10+/-0.026 vs. 0.05+/-0.003, p<0.05). Based on the decrease in diastereometric factor over time, biotransformation was estimated to account for at least 50% of the endosulfan elimination. The formation of the metabolite endosulfan sulphate comprised a maximum 1.2% of the total accumulation of endosulfan. Using a simple one-compartmental model and the experimentally-determined rate constants, it was predicted that only dietary concentration higher than 7.5 mg kg(-1) would cause the estimated maximum residue level (MRL) in fillet of 0.47 mg kg(-1) to be exceeded. Model estimations also predict that current EU maximum permitted levels in fish feeds (0.005 mg kg(-1)) would give fillet concentrations that are under the detection limit (0.3 microg kg(-1)), which is in agreement with the general absence of endosulfan in monitored farmed Atlantic salmon.

The incorporation of plant-based ingredients, and the possible carry-over of pesticides such as endosulfan, in fish feeds may present new toxicological challenges to aquacultural species. Biological responses of Atlantic salmon (Salmo salar) to a 35-day dietary endosulfan exposure at levels ranging from 4 to 710 microgkg(-1) were assessed using tissue histology and biochemistry. Liver 7-ethoxyresorufin-O-deacetylase (EROD) activity was significantly elevated in the highest exposure group (710 microgkg(-1)) by day 35. Other hepatic indicators of stress impacts and responses (glutathione-S-transferase and glutathione peroxidase activities and hepatic alpha-tocopherol content) remained unchanged. Branchial Na(+), K(+)-ATPase activity was significantly reduced at day 14 in the highest exposure group, but returned to control levels by day 35. Conversely, intestinal Na(+), K(+)-ATPase activity was significantly inhibited at day 35, but again only at the highest exposure level. In contrast to the biochemical results, hepatic and intestinal histology revealed effects of exposure even at the lowest dose tested (4 microgkg(-1)). In the posterior intestine, pathology was characterised by vacuolation and fusion of villi, and in the most severe cases, loss of epithelial integrity in villi tips. In the liver the primary effects were glycogen depletion and lipidosis. These changes were typical of a generalised stress response. While histology endpoints may prove to be the most sensitive indicators of dietary endosulfan exposure, the organismal relevance of these structural changes must be considered in the absence of effects in other biomarkers at dietary levels less than 710 microgkg(-1).

Residual fate and dissipation pattern of endosulfan (50 WDG) in soil and plant was studied by gas liquid chromatography following twice applications (at 350 g and 700 g a.i. ha(-1)) in chick-pea, Bengal gram (Cicer arietinum) at vegetative and flowering stages of the crop. The initial residues of Endosulfan (alpha + beta + endosulfan sulfate) in plant following second application was 23.40-57.91 microg g(-1) and its maximum deposit in soil was 1.00-2.45 microg g(-1) after 1 day. Dissipation followed first order reaction kinetics and the half-life values were 2.6-2.9 days in green foliage and 4.4-5.0 days in soil. A pre-harvest interval of 14-19 days was recommended for green foliage. No residues were detected in harvested seeds. Maximum concentration of the metabolite endosulfan sulfate was 0.152-0.473 microg g(-1) in soil and 5.42-9.40 microg g(-1) in plant on third day. Endosulfan-beta was more persistent than alpha-isomer attributable to higher conversion of the later to endosulfan sulfate in soil and plant.

Endosulfan-alpha is metabolized to a single metabolite, endosulfan sulfate, in pooled human liver microsomes (Km = 9.8 microM, Vmax = 178.5 pmol/mg/min). With the use of recombinant cytochrome P450 (P450) isoforms, we identified CYP2B6 (Km = 16.2 microM, Vmax = 11.4 nmol/nmol P450/min) and CYP3A4 (Km = 14.4 microM, Vmax = 1.3 nmol/nmol P450/min) as the primary enzymes catalyzing the metabolism of endosulfan-alpha, although CYP2B6 had an 8-fold higher intrinsic clearance rate (CL(int) = 0.70 microl/min/pmol P450) than CYP3A4 (CL(int) = 0.09 microl/min/pmol P450). Using 16 individual human liver microsomes (HLMs), a strong correlation was observed with endosulfan sulfate formation and S-mephenytoin N-demethylase activity of CYP2B6 (r(2) = 0.79), whereas a moderate correlation with testosterone 6 beta-hydroxylase activity of CYP3A4 (r(2) = 0.54) was observed. Ticlopidine (5 microM), a potent CYP2B6 inhibitor, and ketoconazole (10 microM), a selective CYP3A4 inhibitor, together inhibited approximately 90% of endosulfan-alpha metabolism in HLMs. Using six HLM samples, the percentage total normalized rate (% TNR) was calculated to estimate the contribution of each P450 in the total metabolism of endosulfan-alpha. In five of the six HLMs used, the percentage inhibition with ticlopidine and ketoconazole in the same incubation correlated with the combined % TNRs for CYP2B6 and CYP3A4. This study shows that endosulfan-alpha is metabolized by HLMs to a single metabolite, endosulfan sulfate, and that it has potential use, in combination with inhibitors, as an in vitro probe for CYP2B6 and 3A4 catalytic activities.

Endosulfan, an organochlorine (OC) insecticide belonging to the cyclodiene group, is one of the most commonly used pesticides to control pests in vegetables, cotton, and fruits. To date, no physiologically based pharmacokinetic (PBPK) model has been located for endosulfan in animal species and humans. The estimation by a mathematical model is essential since information on humans can scarcely be obtained experimentally. The PBPK model was constructed based on the pharmacokinetic data of our experiment following single oral administration of (14)C-Endosulfan to male Sprague-Dawley rats. The model was parameterized by using reference physiological parameter values and partition coefficients that were determined in the experiment and optimized by manual adjustment until the best visual fit of the simulations with the experimental data were observed. The model was verified by simulating the disposition of (14)C-Endosulfan in vivo after single and multiple oral dosages and comparing simulated results with experimental results. The model was further verified by using experimental data retrieved from the literature. The present model could reasonably predict target tissue dosimetries in rats. Simulation with three-time repeated administration of (14)C-Endosulfan and experimental data retrieved from the literature by the constructed model fitted fairly well with the experimental results; thus suggesting that the newly developed PBPK model was developed. Sensitivity analyses were used to determine those input parameters with the greatest influence on endosulfan tissue concentrations.

Sorption - desorption of HCH (1,2,3,4,5,6 - Hexachlorocyclohexane) and Endosulfan (1,2,3,4,7,7 - Hexachlorobicyclo [2,2,1] -2 - heptene - 5,6 - bisoxy methylene sulfite) on soil was studied using the batch equilibration technique with initial concentrations for the two chemicals ranging from 0.03 to 340 microg ml(-1), which corresponds to a field application rate of 0.1 2.0 kg m(-2). Calculated slopes of the Freundlich sorption isotherms were near to 1. The Kf, Kd, and Koc values determined for endosulfan were at least an order of magnitude greater than that determined for HCH. Kf values were 209 and 8035 for HCH and Endosulfan respectively. Hysteresis was observed for desorption of both the chemicals. Studies showed that Endosulfan and HCH binding to soil was strong and desorption cannot be predicted from adsorption isotherms only.

This paper assesses the uptake of persistent organic pollutants (POP's) into plants. In particular, uptake of alpha-endosulfan, beta-endosulfan and endosulfan sulfate from lettuce. The lettuce plants were grown on compost that had previously been contaminated at 10 and 50 microg g(-1) per POP. The soil was slurry spiked by adding the appropriate amount of POP in acetone in an approximate ratio of 1 ratio 2, w/v soil ratio solvent. The solvent was left to evaporate at ambient temperature for 24 hours. Lettuce plants were grown under artificial daylight for 12 hours a day. The influence of soil ageing on the recovery of POP's from spiked soil samples was also assessed. The average recovery of endosulfan compounds from slurry spiked soil (10, 20 and 40 microg g(-1)) was consistent (92.9 +/- 4.4% for n= 9). However, ageing of endosulfan compounds on the slurry spiked soil resulted in lower recoveries (average losses were 12.5% after 14 days ageing of slurry spiked soil). The uptake of POP's was assessed by measuring the amount of endosulfan compounds in roots and leaves from lettuce plants after 10, 20 and 33 days. In addition, control plants grown in uncontaminated soil were monitored and analysed. It was found that endosulfan compounds were present in the roots of all lettuce plants irrespective of soil spike level or age of plant. In the 33 day lettuce plants where the soil was spiked at the highest level (50 microg g(-1)) endosulfan compounds were determined in the leaves. The root to leaf ratio was found to be 3.1 for alpha-endosulfan, 46.0 for beta-endosulfan, and 24.3 for endosulfan sulfate. Spiked lettuce samples were subjected to in vitro gastrointestinal extraction to assess the bioavailability of endosulfan compounds. No detectable endosulfan compounds were determined in the gastric extracts while small quantities (range 0.06-0.12 microg g(-1)) were found in the intestinal extraction. All samples (soil and lettuce) were extracted using pressurised fluid extraction and analysed using gas chromatography with mass selective detection.

Endosulfan (ES), an organochlorine (OC) insecticide that belongs to the cyclodiene group, is one of the most commonly used pesticides to control pests in vegetables, cotton, and fruits. The toxicokinetics of 14C-endosulfan following oral administration of a single dose of 5 mg/kg body weight was investigated in male Sprague-Dawley rats. Three rats were sacrificed 30 min, 1 h, 2 h, 4 h, and 8 h after dosing. 14C-endosulfan radioactivity was detected in all tissues at each time point. In a separate experiment urine and feces were collected for 96 h. The total radioactivity recovered in the excreta for 4 days was 106.8% +/- 26.2%, with fecal elimination the major route of elimination route (94.4% +/- 21.4%). The cumulative excretion in the urine for 4 days was 12.4% +/- 4.8%. Radioactivity 8 h after administration was highest in gastrointestinal (GI) tract tissue (20.28 +/- 16.35 mg ES eq./L) and lowest in muscle (0.18 +/- 0.06 mg ES eq./L). The toxicokinetic parameters obtained from 14C-endosulfan-derived radioactivity in blood were distribution half-life (T1/2 x) = 31 min and terminal elimination half-life (T1/2 y) = 193 h. Blood concentration reached its maximum (Cmax) of 0.36 +/- 0.08 mg ES eq./L 2 h after the oral dose. Endosulfan was rapidly absorbed into the GI tract in rats, with an absorption rate constant (ka) of 3.07 h(-1)., ((c) 2005 Wiley Periodicals, Inc.)

Although industrialized nations have restricted or banned many organochlorine pesticides, some of these chemicals (e.g., endosulfans) are still used, on the assumption that they pose little threat to the environment, wildlife, or human health. According to available information, Spain is the main consumer of endosulfans within the European Union, accounting for almost half of the total consumption. Reports on human exposure in Southern Spain to persistent bioacumulable organochlorine pesticides have indicated considerable exposure to endosulfans. The present study investigated the presence of endosulfan I, endosulfan II, and endosulfan metabolites in fatty and non-fatty tissues and fluids from women of reproductive age and children in Southern Spain. The highest concentration of commercial endosulfan I and endosulfan II was found in adipose tissue, with a mean value (I+II) of 17.72 ng/g lipid, followed by human milk, with a mean value (I+II) of 11.38 ng/mL milk. These findings support the lipophilicity of these chemicals and their elimination by milk secretion. The concentration in the placenta homogenate was similar to that in the blood from the umbilical cord (7.74 and 6.11 ng/mL, respectively) and reflected their lower fat content. Endosulfan diol and endosulfan sulfate were more frequently found in placenta homogenate, with a mean concentration of 12.56 and 3.57 ng/mL, respectively, and in blood from umbilical cord, at 13.23 and 2.82 ng/mL, respectively. Therefore, women of reproductive age in Southern Spain appear to be currently exposed to endosulfans. Because these chemicals can be mobilized during pregnancy and lactation, further research is warranted to investigate the health consequence in children resulting from exposure to chemicals suspected of immunotoxic, neurotoxic, or endocrine-disrupting effects.

Background: Organochlorine insecticides are highly toxic compounds that are responsible for a number of severe intoxications worldwide with several deaths. Despite their widespread use in agriculture during the 1940s to 1960s and the well-known signs and symptoms of intoxication, the clinical picture in case of poisoning varies. We report two cases of acute intentional endosulfan intoxication with cerebral edema and cardiac failure., Case Reports: Both cases developed life-threatening signs like epileptic state, respiratory insufficiency and hemodynamic instability soon after ingestion. The survivor developed severe myocardial insufficiency and pulmonary edema documented by echocardiography and x-ray of the chest. The deceased patient developed severe cerebral edema and multiorgan failure ten days after ingestion of Thiodan 35. The peak serum concentration of endosulfan in the survivor was 0.12 mg/L approximately 23 hours after ingestion, whereas the peak blood concentration in the fatal case was 0.86 mg/L approximately 25 hours post-ingestion. Post-mortem endosulfan levels in different organs were determined., Conclusion: Endosulfan is a highly toxic organochlorine insecticide that produces well-known neurological symptoms of tonic-clonic convulsions, headache, dizziness and ataxia but also can cause gastrointestinal symptoms and metabolic disturbances. Life-threatening cerebral edema and hemodynamic instability may occur. Treatment is symptomatic and supportive.

PCB and endosulfan concentrations in the chorioallantoic membrane (CAM) of white leghorn chickens (Gallus domesticus) were evaluated as indicators of hepatic cytochrome P450 isozyme activity in hens and chicks as well as toxicant concentrations in eggs and hens. Sixteen hens were randomly divided into four groups of four and dosed with a mixture of PCB105 (2,3,3',4,4'-pentachlorobiphenyl), PCB156(2,3,3',4,4',5-hexachlorobiphenyl), PCB189 (2,3,3',4,4',5,5'-heptachlorobiphenyl), and technical grade endosulfan (3:1 ratio of alpha and beta isomers) at three different dose groups. The first 10 fertile eggs laid by each hen were collected, the even-numbered eggs incubated until hatched, and the odd numbered eggs were analyzed for test chemicals. Strong (r2), significantly positive (p value) relationships were found between total PCB mass (ng) in CAMs and both total PCB concentrations (ng/g wet wt) in adults (r2 = 0.91, p = 0.0001) and eggs (r2 = 0.87, p = 0.0001). The relationship between total PCB mass in CAMs and hepatic cytochrome p450 isozyme activity in chicks (r2 = 0.49, p = 0.0001) and hens (r2 = 0.45, p = 0.014) was also significant but not as strong. This study shows that CAMs can be used to estimate avian exposure to PCBs and resultant biological response.

A multiresidue method based on normal-phase liquid chromatography (LC) cleanup and gas chromatography-electron capture detection-mass selective detection (GC-ECD-MSD) analysis has been developed for the determination of endosulfan and its main metabolic derivatives in human adipose tissues. Analytes were extracted by dissolving the fat samples in n-hexane, and the hexanic extracts were directly injected onto the silicagel column of the automated LC cleanup system. Purified LC extracts were analyzed by GC-ECD or GC-MSD, without any solvent exchanges or preconcentration steps. The high efficiency of the high-performance liquid chromatographic cleanup for the elimination of fats allowed to reach detection limits for all analytes at low nanograms-per-gram concentration levels. The optimized overall analytical procedure was applied to 18 selected human mammary adipose and abdominal fat tissue samples. p,p'-DDE, hexachlorobenzene, and beta-HCH were the most frequently detected compounds, and residues of endosulfan-sulfate and -ether were also found in several samples. All findings were confirmed by an additional GC-MS-MS analysis of the LC sample extracts.

Agricultural pesticide runoff in southeastern coastal regions of the United States is a critical issue. Bioconcentration of pesticides by phytoplankton and zooplankton at the base of the aquatic food web may increase the persistence of pesticides in aquatic ecosystems and cause effects at higher trophic levels. This study examined the toxicity of a widely used agricultural pesticide, endosulfan, to Pseudokirchneriella subcapitatum (freshwater green alga) and Daphnia magna (freshwater cladoceran). We then investigated the potential of both plankton species to sequester endosulfan from their surrounding media. We also assessed the degree to which endosulfan is accumulated by D. magna via food (endosulfan-contaminated P. subcapitatum). A 96-h growth rate EC50 of 427.80 microg/L endosulfan was determined for P. subcapitatum, whereas a 24-h immobilization EC50 of 366.33 microg/L endosulfan was determined for D. magna. The 5-h EC50s for filtration and ingestion in D. magna were 165.57 microg/L and 166.44 microg/L, respectively. An average bioconcentration factor (BCF) of 2,682 was determined for P. subcapitatum exposed to 100 microg/L endosulfan for 16 h. An average BCF of 3,278 was determined for D. magna in a 100 microg/L endosulfan water-only exposure. There was negligible uptake of endosulfan by D. magna feeding on contaminated algae in clean water (BCF approximately 0). Different proportions of parent isomers (endosulfan I and II) and the primary degradation product (endosulfan sulfate) were detected among treatments. Endosulfan was rapidly accumulated and concentrated from water by P. subcapitatum and D. magna neonates. Endosulfan contained in phytoplankton, however, was not bioaccumulated by zooplankton. These findings may prove useful in assessing ecosystem risk, because uptake from the water column appears to be the dominant route for bioconcentration of endosulfan by zooplankton.

The distributions of PCB 105, 156, 189, and endosulfan in incubating, maternally exposed, viable white leghorn chicken eggs (Gallus domesticus) were investigated. Hens were subcutaneously injected every 4 days with a mixture of the above chemicals. One group of five eggs was removed from the incubator at each of 9, 14, and 19 days of incubation; dissected into three compartments (embryo, chorioallantoic membrane, and yolk + albumin); weighed; frozen; and then later analyzed for the dosing chemicals. Through 19 days of development (90% of incubation), greater than 70% of the total chemical mass in the whole egg remained within the yolk + albumin, whereas, depending on the chemical, 17% to 30% was absorbed by the embryo and 0.2% to 9% was transported into the chorioallantoic membrane. As a percentage of total PCB mass within the respective compartment, PCB 105 composition in the embryo and chorioallantoic membrane decreased significantly throughout development while PCB 156 and 189 composition increased significantly throughout development. Though endosulfan composition within any of the compartments was highly variable, it did not change significantly during development. The results of this study indicate that the majority of avian chick exposure to contaminants occurs posthatch as the chick continues to utilize the residual yolk.

Reported avian maternal transfer rates of organochlorine contaminants range from 1% to as much as 20% of maternal body burdens. However, to our knowledge, no investigation of factors governing maternal transfer has been reported. Here, we report an investigation of maternal transfer of 2,3,3',4,4'-pentachlorinated biphenyl (PCB 105), 2,3,3',4,4',5-hexachlorinated biphenyl (PCB 156), 2,3,3',4,4',5,5'-heptachlorinated biphenyl (PCB 189), and technical-grade endosulfan into eggs by white leghorn chickens (Gallus domesticus). Two experiments were performed to evaluate individual chemical excretion into eggs when hens were injected with each chemical individually (experiment one) or with a mixture of all four chemicals (experiment two). Each hen was injected subcutaneously every 4 d during a 21-d period with 100 microliters of the dosing solution during both experiments. The mass of each chemical excreted into the egg was compared among eggs and with the mass injected into hens to determine the influence of chemical structure (experiment one) and interaction (experiment two) on maternal transfer of those chemicals into eggs. Maternal transfer of PCBs was inversely related to congener chlorination. The congener mass in eggs, as a percentage of the mass injected into hens, was 0.42% for PCB 189, 0.54% for PCB 156, and 0.61% for PCB 105. In experiment two, absolute excretion of only PCB 189 and alpha-endosulfan into eggs was affected by the presence of other chemicals. Excretion of PCB 189 (0.51%) and alpha-endosulfan (0.03%) increased and decreased, respectively, compared with when they were individually injected into hens during experiment one. Lastly, much less of the more metabolically susceptible endosulfan (0.04-0.12% of the mass injected) was excreted into the egg relative to PCBs, despite being injected into the hens at concentrations comparable with those of PCBs, suggesting, at least in avian species, lower maternal transfer of more metabolically susceptible chemicals.

Case Report: A case of nonaccidental endosulfan intoxication in a previously healthy 43-year-old male patient is reported. On admission, the patient had few symptoms, but refractory seizures began 1 hour after ingestion. The patient died on the fourth day after admission showing clinical signs of cerebral herniation confirmed at autopsy. Blood, urine, and tissue samples were analyzed for alpha-endosulfan, beta-endosulfan, and endosulfan sulfate by capillary gas chromatography with electron capture detection. Concentration versus time data for endosulfan were fitted using the program MW/Pharm, assuming complete bioavailability although it is recognized that the bioavailability of endosulfan after ingestion may have been low and the calculated clearance was primarily due to redistribution. Hemoperfusion was shown to be ineffective.

The impact of a sublethal concentration of an organochlorine pesticide endosulfan on the activity, specific activity, electrophoretic patterns and kinetic properties of crude and purified forms of cytoplasmic malate dehydrogenase (cMDH) and mitochondrial malate dehydrogenase (mMDH) was evaluated in the liver of the freshwater catfish, Clarias batrachus. The endosulfan reduced significantly the activity and the specific activity of cMDH and mMDH, but had no effect on total cytoplasmic and mitochondrial protein contents. The inhibition produced by endosulfan was of mixed non-competitive-uncompetitive type (KiE > KiES) and of mixed competitive-non-competitive type (KiE < KiES) for crude cMDH and mMDH, respectively. The PAGE shows five distinct isoforms (C1 to C5) of cMDH and two isoforms (M1 and M2) of mMDH. The C5-isoform of liver cMDH is predominant and it corresponds to M2-isoform of mMDH. There are no endosulfan-associated differences in the relative charges of crude cMDH and mMDH as well as their purified isoforms, C5-cMDH and M2-mMDH. The relative molecular weights of the purified isoforms are not affected by endosulfan. The purified C5-cMDH and M2-mMDH of endosulfan-treated liver in vivo showed simple non-competitive (KiE = KiES) type of inhibition; whereas in vitro it was of uncompetitive (KiES) and mixed competitive-non-competitive (Ki < KiES) type for the two respective isoforms. G-1-P acts as an uncompetitive (KiES) inhibitor of C5-cMDH and mixed competitive-non-competitive (KiE < KiES) inhibitor of M2-mMDH of the control fish. The inhibitory pattern of G-1-P is modulated by endosulfan in case of C5-cMDH; whereas there is no alteration in case of M2-mMDH. Summarizing, it can be stated that endosulfan exerts an inhibitory effect on crude cMDH and mMDH in vivo, and their purified isoforms (C5-cMDH and M2-mMDH) in vivo as well as in vitro. The impact of endosulfan is mediated through enzyme-substrate-endosulfan (ES-END) complexing for cMDH and enzyme-endosulfan (E-END) complexing for mMDH.

The sites of tissue accumulation in lactating goats of the organochlorine insecticide endosulfan were studied. Twelve lactating goats were dosed orally with endosulfan (1 mg/kg body weight per day) for 28 days. Groups of 3 animals were killed on days 1, 8, 15, and 21 after endosulfan treatment ended and their tissues examined for the presence of endosulfan. Total residues of alpha and beta endosulfan and endosulfan sulphate (mg/kg) were detected in kidney (0.29), gastro-intestinal tract (0.20), liver (0.12), brain (0.06), muscle and spleen (0.04), lung and heart (0.01) and milk (0.02) on the first sampling day but within 15 days, concentrations had fallen to < 0.01 mg/kg in all tissues except kidney (0.20). Endosulfan could not be detected in animals 21 days after dosing had ceased. The residue in milk could only be detected on day 1 of sampling. This study indicates that kidney rather than fatty tissue should be used to monitor the presence of endosulfan in animals intended for human consumption.

1. The acute toxicity of endosulfan was determined for the freshwater rotifer Brachionus calyciflorus. 2. The mean 24 hr LC50 value for endosulfan was 5.15 ppm with a coefficient of variation of 14.7%. 3. Rotifers were exposed at two sublethal concentrations (1.5-2.0 ppm) of endosulfan for bioaccumulation experiments, for an exposure time of 24, 48, 72 and 96 hr. The rotifers were fed with Nannochloris oculata (5 x 10(5) cell/ml). 4. The highest accumulation of endosulfan was found 24 hr after the start of the exposure to 1.5 ppm of the toxicant. A steady-state concentration in rotifer was reached between 24-48 hr, followed by a gradual decrease until 96 hr.

A one step extraction and cleanup procedure for determining endosulfan in fish was investigated. Minced Fish was mixed with trisodium citrate, disodium hydrogen orthophosphate and sodium sulphate into a dry powdery mixture, which was eluted through silicic acid and alumina with a mixture of dichloromethane and hexane. The eluate was concentrated and chromatographed on GLC using an EC detector without further cleanup. Three species of fresh water fish exposed to 0.7-16 micrograms/litre-1 technical grade endosulfan in tanks for various periods of time were found to concentrate both alpha and beta endosulfan and metabolise them to sulfate, diol, ether and lactone. Fish collected from Gwydir River in the cotton growing area in summer (Dec. 1986-Feb. 1987) were found to contain endosulfan residues suggesting endosulfan is quite stable in the environment and can cause residues.