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Endosulfan Health Effects Studies

OverviewChemical Structure of Endosulfan

The U.S. EPA classifies endosulfan as highly acutely toxic (Toxicity Category I) by oral exposure, based on oral LD50 values in rats of 82 mg/kg (males) and 30 mg/kg (females). The World Health Organization classifies it "Moderately Hazardous" (Category II) based on an oral LD50 of 80 mg/kg.

A growing body of evidence suggests that endosulfan has estrogenic activity and can disrupt hormonally mediated processes. The U.S. EPA considers it to be a potential human endocrine disruptor, and in 2000 Agency for Toxics and Disease Registry (ATSDR) concluded that “endosulfan may potentially cause reproductive toxicity in humans.” Since then, studies of popluations exposed to endosulfan have been published suggesting that endosulfan can increase the risk of autism, delay puberty in boys, and cause birth defects of the male reproductive system.

Endosulfan is not considered to be a known or possible carcinogen by the EPA, the International Agency for Research on Cancer (IARC), or the State of Cailfornia. There is, however, some evidence from laboratory tests that endosulfan could contribute to cancer, particularly of the breast.

Below are links to risk assessments, monographs, and scientific articles that discuss in greater detail what is known about the health effects of endosulfan. This compilation of articles will be updated periodically and it is by no means comprehensive.

Monographs and Risk Assessments

Government Sources:

Non-Governmental Sources:

Individual Studies of Endosulfan's Effects on Humans

Endosulfan and Autism

Abstract:
Background: Ambient levels of pesticides ("pesticide drift") are detectable at residences near agricultural field sites.

Objective: Our goal was to evaluate the hypothesis that maternal residence near agricultural pesticide applications during key periods of gestation could be associated with the development of autism spectrum disorders (ASD) in children.

Methods: We identified 465 children with ASD born during 1996–1998 using the California Department of Developmental Services electronic files, and matched them by maternal date of last menstrual period to 6,975 live-born, normal-birth-weight, term infants as controls. We determined proximity to pesticide applications using California Department of Pesticide Regulation records refined using Department of Water Resources land use polygons. A staged analytic design applying a priori criteria to the results of conditional logistic regressions was employed to exclude associations likely due to multiple testing error.

Results: Of 249 unique hypotheses, four that described organochlorine pesticide applications—specifically those of dicofol and endosulfan—occurring during the period immediately before and concurrent with central nervous system embryogenesis (clinical weeks 1 through 8) met a priori criteria and were unlikely to be a result of multiple testing. Multivariate a posteriori models comparing children of mothers living within 500 m of field sites with the highest nonzero quartile of organochlorine poundage to those with mothers not living near field sites suggested an odds ratio for ASD of 6.1 (95% confidence interval, 2.4–15.3) . ASD risk increased with the poundage of organochlorine applied and decreased with distance from field sites.

Conclusions: The association between residential proximity to organochlorine pesticide applications during gestation and ASD among children should be further studied.

Related to this study: "Pesicide Link to Autism Suspected" by Marla Cone, The Los Angeles Times, 07/30/07.

Follow-up correspondence in EHP: "The Interaction of Agricultural Pesticides and Marginal Iodine Nutrition Status as a Cause of Autism Spectrum Disorders", Sullivan KM, Environ. Health Perspect. 116(4): A155, 2008.

Human Reproductive Toxicity

Abstract:
There is experimental evidence of adverse effects of endosulfan on the male reproductive system, but there are no human data. Therefore, we undertook a study to examine the relationship between environmental endosulfan exposure and reproductive development in male children and adolescents. The study population was composed of 117 male schoolchildren (10-19 years of age) of a village situated at the foothills of cashew plantations, where endosulfan had been aerially sprayed for more than 20 years, and 90 comparable controls with no such exposure history. The study parameters included recording of clinical history, physical examination, sexual maturity rating (SMR) according to Tanner stages, and estimation of serum levels of testosterone, luteinizing hormone (LH) , follicle-stimulating hormone, and endosulfan residues (70 study and 47 control subjects) . Mean ± SE serum endosulfan levels in the study group (7.47 ± 1.19 ppb) were significantly higher (p < 0.001) than in controls (1.37 ± 0.40 ppb) . Multiple regression analysis showed that SMR scoring for development of pubic hair, testes, penis, and serum testosterone level was positively related to age and negatively related to aerial exposure to endosulfan (AEE ; p < 0.01) . Serum LH levels were significantly positively related to AEE after controlling for age (p < 0.01) . The prevalence of congenital abnormalities related to testicular descent (congenital hydrocele, undescended testis, and congenital inguinal hernia) among study and controls subjects was 5.1% and 1.1%, respectively, but the differences were statistically nonsignificant. Our study results suggest that endosulfan exposure in male children may delay sexual maturity and interfere with sex hormone synthesis. Our study is limited by small sample size and nonparticipation.
Related to this study: Follow-up correspondence in Environmental Health Perspectives.

Acute Toxicity

Abstract:
Introduction: Organochloride insecticides are chlorinated cyclic hydrocarbons having molecular weights in the range of 300-550 Da. Case series of endosulfan poisoning are extremely rare in the literature. We report 23 cases of endosulfan poisoning.
Methods: This retrospective study enrolled patients with endosulfan poisoning presenting to our emergency department from January to December 2005. The data were collected from clinical records and laboratory files.
Results: On admission, initial symptoms were nausea and vomiting in 17 patients (73.9 percent), seizures in five patients (21.7 percent), and dizziness in one patient (4.3 percent). Symptoms began within one hour after ingestion in 12 patients (52.2 percent), in the second hour in nine patients (39.1 percent), and in the third hour in two patients (8.7 percent). Seizure types were generalised tonic-clonic in 16 patients (84.2 percent), and focal seizures in three patients (15.8 percent). 19 patients were observed for one day, two patients were observed for two days, and one patient was followed-up for ten days in the emergency department. One patient was transferred for liver transplantation on the fifth day to another centre. All patients were treated symptomatically by intravenous diazepam for controlling seizures.
Conclusions: Endosulfan poisoning can be suspected in the presence of primary central nervous system manifestations including seizures, with or without clinical or laboratory evidence of other organ dysfunction such as liver failure.
Abstract:
The author describes a case of acute poisoning by endosulfan (a chlorinated hydrocarbon insecticide) in an industrial worker, with residual psychiatric syndrome. The acute phase was manifested by repeated convulsions and impaired consciousness. After recovery the patient became disoriented and agitated. The residual phase, 2 years after initial hospitalization, was manifested by cognitive and emotional deterioration, severe impairment of memory and inability to perform any but the simplest tasks. Psychological tests revealed gross impairment of visual-motor coordination. The differential diagnosis of chronic brain syndrome requires accurate history and milder cases of endosulfan poisoning may easily be overlooked or misdiagnosed.

Non-human Studies

Reproductive and Developmental Toxicity Studies in Rats and Mice

Abstract:
The possible neurotoxic effects of the organochlorine pesticide endosulfan have been evaluated on male offspring rats exposed in utero and during lactation. Dams were treated with 0.61mg or 6.12mg endosulfan/kg/day from the gestation beginning until the weaning. Male offspring rats were sacrificed at post-natal days (PND) 15, 30 and 60, and possible alterations in the content and metabolism of biogenic amines and amino acids were determined in prefrontal cortex using high-performance liquid chromatography (HPLC). Globally, endosulfan induced an increase in amino acid content in prefrontal cortex at PND 15 and PND 30. However, the levels of GABA at PND 15 and those of glutamine at PND 30 were not modified. At PND 60, a significant reduction in the content of GABA and taurine was observed, while the concentration of glutamate, aspartate and glutamine remained constant. Endosulfan did not modify norepinephrine and dopamine content, but serotonin concentration was increased at PND 30 and PND 60 and serotoninergic and dopaminergic metabolism was also modified. These results suggest that pre- and post-natal exposure to endosulfan affects biogenic amines and amino acids in prefrontal cortex, and those variations could be related to several alterations in the functions in which the prefrontal cortex is involved.
Abstract:
Dietary exposures to food pollutants such as mycotoxin(s) or pesticide(s) are most significant due to their adverse effects on the production and reproduction in animals and the human population. The present investigation was conducted to evaluate the teratogenic potential of citrinin (CIT) and endosulfan either alone or in combination in pregnant rats during gestational days 6-20. Endosulfan (1 mg kg(-1) body weight, by oral intubation) and CIT (10 mg kg(-1) feed, through diet) when administered either alone or in combination in pregnant rats caused significant teratogenic effects in the developing fetuses. There was no maternal mortality, however, reduced maternal weight gain and number of live fetuses and increased fetal resorptions were recorded in all the treated groups. The fetal body weights and crown to rump lengths were significantly decreased and the percent gross, visceral and skeletal anomalies were significantly increased in the fetuses of dams of all the treated groups. The internal hydrocephalus, cerebellar hypoplasia, microphthalmia, contracted and notched kidneys, multilobulated liver, dilated renal pelvis, incomplete ossification of skull bones, rib anomalies and sacral and caudal vertebrae agenesis were the important fetal malformations. The occurrence of fetal gross, skeletal and visceral malformations was more severe in the combination group, suggesting an additive interaction of CIT and endosulfan in inducing developmental toxicity in Wistar rats.
Related to this study: "Experimentally induced citrinin and endosulfan toxicity in pregnant Wistar rats: histopathological alterations in liver and kidneys of fetuses." Singh ND, Sharma AK, Dwivedi P, Patil RD, Kumar M. J Appl Toxicol. Published ahead of print online 2008 May 20.

Possible Carcinogenic Effects

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