National Toxicology Program

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. ¹

Names (NTP)

• Endosulfan
• ENDOSULFAN (ENDOCRINE DISRUPTER)
• 6,9-METHANO-2,4,3-BENZODIOXATHIEPIN,6,7,8,9,10,10-HEXACHLORO-1,5,5A,6,9,9A-HEXAHYDRO-, 3-OXIDE (9CI)
• Endocrine disrupter (Endosulfan)
• 6,9-METHANO-2,4,3-BENZODIOXATHIEPIN,6,7,8,9,10,10-HEXACHLORO-1,5,5A,6,9,9A-HEXAHYDRO-, 3-OXIDE (9CI)

Human Toxicity Excerpts

• SYSTEMIC POISONING CAUSES NERVOUSNESS, AGITATION, TREMORS, & CONVULSIONS. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-286]**PEER REVIEWED**
  
• A 70 YR OLD WOMAN DIED ABOUT 3 HR AFTER SHE HAD TAKEN ONLY "DROPS" OF AN ENDOSULFAN FORMULATION FOR STOMACH PAINS ... THE CLINICAL PICTURE ... INVOLVED GAGGING, VOMITING, DIARRHEA, AGITATION, TONIC CLONIC CONVULSIONS, FOAMING AT THE MOUTH, DYSPNEA, APNEA, CYANOSIS, & LOSS OF CONSCIOUSNESS. [Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 253]**PEER REVIEWED**
  
• NINE WORKERS SUFFERED ONE OR MORE CONVULSIONS FOLLOWING EXPOSURE TO ENDOSULFAN MAINLY IN CONNECTION WITH BAGGING 50% WATER WETTABLE POWDER. FIVE OF THE MEN WERE SAID TO HAVE USED A RESPIRATOR & PROTECTIVE CLOTHING; TWO DID NOT USE A RESPIRATOR, & THE PRACTICES OF THE OTHERS WERE UNKNOWN. SIX OF THE MEN HAD NO HISTORY OF A PREVIOUS SEIZURE, & NO HISTORY OF ANY SORT WAS AVAILABLE FOR THE OTHERS. IN THE ONLY THREE OF THESE CASES DESCRIBED ... PRODROMAL SYMPTOMS (MALAISE, VOMITING, DIZZINESS, WEAKNESS, OR CONFUSION) BEGAN WHILE THE MAN WAS AT WORK & SEVERAL HR BEFORE THE FIRST SEIZURE, WHICH SOMETIMES OCCURRED AT HOME OR ON THE STREET. AT LEAST IN ONE INSTANCE, A CONVULSION WAS FOLLOWED BY UNCONSCIOUSNESS LASTING AN HR; THE SEIZURE WAS SO VIOLENT, THAT IT RESULTED IN FRACTURES OF THE FOURTH & FIFTH DORSAL VERTEBRAE. ONE PATIENT REMAINED CONFUSED FOR ABOUT 24 HR & THEN RECOVERED RAPIDLY. [Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 253]**PEER REVIEWED**
  
• IN: THREE CASES ... ASSOCIATED WITH FILLING BAGS WITH FRESHLY GROUND ENDOSULFAN POWDER ... THE OUTSTANDING PRODROMAL SYMPTOM WAS HEADACHE, & THE INITIAL SIGN WAS FAINTING. THE FAINTING WAS ASSOCIATED WITH OR FOLLOWED BY EPILEPTOID TWITCHING & FOAM AT THE MOUTH. ONE MAN BIT HIS TONGUE, BUT APPARENTLY A FULL CONVULSION DID NOT DEVELOP. EEG CHANGES THAT PROMPTLY REVERTED TO NORMAL ACCOMPANIED THE ILLNESS. [Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 253]**PEER REVIEWED**
  
• A MAN WAS EMPLOYED BY A CHEMICAL PLANT WHERE HIS MAIN ASSIGNMENT WAS CLEANING VATS CONTAINING RESIDUES OF ENDOSULFAN. ... HE FAINTED SEVERAL TIMES ... CONVULSION /NOTED/ DURING SLEEP. HIS CONSCIOUSNESS WAS CLOUDED BUT VITAL SIGNS NORMAL. THE PATIENT RECEIVED DIAZEPAM & APPEARED TO RECOVER RAPIDLY ... AT HOME HIS FAMILY FOUND HIM DISORIENTED & OCCASIONALLY AGITATED OR ABUSIVE. THE AGITATION WAS ESSENTIALLY ELIMINATED BY PHENOTHIAZINE TRANQUILIZERS, BUT /HE/ ... COULD NOT CONVERSE EXCEPT FOR ANSWERING SIMPLE QUESTIONS. ... HE WAS OCCASIONALLY INCONTINENT OF URINE. [Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 253]**PEER REVIEWED**
  
• HUMAN LYMPHOID CELLS OF LAZ-007 CELL LINE, INCUBATED WITH 1X10-4 TO 1X10-6 MOLAR OF 8 DIFFERENT ORGANOCHLORINE PESTICIDES HAD DOSE RELATED CYTOTOXICITY, MITOTIC DEPRESSION AND CELL CYCLE TRAVERSE INHIBITION. THE FREQUENCY OF M3 METAPHASES IN CULTURES INCUBATED WITH 1X10-6 MOLAR CONCN WERE 15% FOR ENDOSULFAN COMPARED TO 17% IN CONTROL CULTURES. STATISTICALLY SIGNIFICANT INCR IN SISTER CHROMATID EXCHANGE FREQUENCY WAS SEEN IN CELLS EXPOSED TO ENDOSULFAN. [SOBTI RC ET AL; ARCH TOXICOL 52 (3): 221-31 (1983)]**PEER REVIEWED**
  
• SYMPTOMATOLOGY: (Onset of symptoms between 20 min and 12 hr after ingestion): 1. Malaise, headache, nausea, vomiting, dizziness, and tremors. 2. Clonic and tonic convulsions, sometimes without premonitory symptoms. 3. Convulsive episodes may alternate with periods of severe central nervous depression. Death from respiratory arrest may occur during coma, which commonly outlasts the convulsive phase and may persist for a few days. 4. During the acute phase, leukocytosis, rise in blood pressure, tachycardia, arrhythmias, metabolic acidosis, and fever have been described. Presumably they represent the consequences of hyperactivity of the sympathetic nervous system. 5. Disturbances of sleep, memory and behavior may persist for several days or weeks after the acute phase of ... poisoning. 6. Generalized cerebral dysrhythmia persisting for months, and both hematuria and albuminuria of about 2 weeks duration have been described in one aldrin poisoning in man. Transient hematuria occurred on the second day of an acute dieldrin poisoning. /Dieldrin/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-144]**PEER REVIEWED**
  
• IN ITS ACUTE TOXIC ACTION ENDOSULFAN IS SIMILAR TO DIELDRIN BUT POSSIBLY LESS TOXIC THAN ENDRIN. [Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 143]**PEER REVIEWED**
  
• AS DUST ... IS PROBABLY ONLY MODERATELY TOXIC BY INHALATION, BUT IN SOLN, ESP IN ALCOHOL OR AROMATIC SOLVENTS LIKE XYLENE, IT IS CONSIDERED TOXIC BY INGESTION & BY PERCUTANEOUS ABSORPTION ... [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-286]**PEER REVIEWED**
  
• STOMACH, SMALL INTESTINE CONTENTS, BLOOD, LIVER, KIDNEY & URINE OF A 28 YR OLD MAN, WERE ANALYZED FOR RESIDUES OF ENDOSULFAN. THE ANALYSIS RESULTS SHOWED THE PRESENCE OF HIGH CONCN OF THE TWO ENDOSULFAN ISOMERS IN ALL SAMPLES. SINCE ALCOHOL WAS ALSO PRESENT IN ALL THE TISSUES ANALYZED, IT WAS CONCLUDED THAT THE VICTIM DIED OF A COMBINED ENDOSULFAN-ALCOHOL POISONING. [DEMETER J ET AL; BULL ENVIRON CONTAM TOXICOL 18 (1): 110 (1977)]**PEER REVIEWED**
  
• Ten patients ingested 50-500 ml of the 35% concentrate (17.5-175 g endosulfan). Patients experienced vomiting within half an hour, hypotension, tonic-clonic seizures, fever, metabolic acidosis, and elevation in liver function enzymes. ... Five out of 10 patients died in 4 to 60 hours. [Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1626]**PEER REVIEWED**
  
• The usual symptoms include headache, giddiness, nervousness, blurred vision, weakness, nausea, cramps, diarrhea, and discomfort in the chest. Signs include sweating, miosis, tearing, salivation and other excessive respiratory tract secretion, vomiting, cyanosis, papilledema, uncontrollable muscle twitches followed by muscular weakness, convulsions, coma, loss of reflexes, and loss of sphincter control. The last four signs are seen only in severe cases but do not preclude a favorable outcome if treatment is prompt and energetic. Cardiac arrhythmias, various degrees of heart block, and cardiac arrest may occur ... /Organic phosphorus pesticides/ [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 938]**PEER REVIEWED**
  

Back to Top

Non-Human Toxicity Excerpts

• ... DOGS SHOWED SIGNS OF CMPD EFFECT AT 200 & 500 MG/KG /ACUTE ORAL/. LEVELS INCLUDE SALIVATION, EMESIS & GENERALIZED TONIC & CLONIC CONVULSIONS. DOGS WHICH VOMITED RECOVERED. NO CONSISTENT CMPD RELATED RESPONSES WERE SEEN AT ANY OF THE LOWER LEVELS. [Spencer, E. Y. Guide to the Chemicals Used in Crop Protection. 7th ed. Publication 1093. Research Institute, Agriculture Canada, Ottawa, Canada: Information Canada, 1982., p. 254]**PEER REVIEWED**
  
• CHRONIC /EXPOSURE/ ... ORAL RAT UP TO 30 PPM /IN THE DIET/ FOR 2 YR NO SYMPTOMS. [Spencer, E. Y. Guide to the Chemicals Used in Crop Protection. 7th ed. Publication 1093. Research Institute, Agriculture Canada, Ottawa, Canada: Information Canada, 1982., p. 254]**PEER REVIEWED**
  
• ABOUT 8 G OF /ENDOSULFAN/ KILLED CATTLE WITHIN 15 HR AND A DOSE OF 8 MG/KG DAILY FOR 2 DAYS HAS PRODUCED SIGNS OF POISONING IN A SHEEP. ... CATTLE ACCIDENTALLY SPRAYED WITH 0.1% EMULSION ... SHOWED LISTLESSNESS, STAGGERING, HYPEREXCITABILITY, EXAGGERATED GAIT & CONVULSIONS, AND 20% OF THE AFFECTED ANIMALS DIED. IN SOME CASES THERE WAS A 48 HR DELAY BEFORE THE ONSET OF CLINICAL SIGNS. [Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988., p. 151]**PEER REVIEWED**
  
• ACUTE /ORAL/ SYMPTOMS /FOR MALE MALLARDS 3-4 MONTHS OLD/: ... HIGH CARRIAGE, WINGS CROSSED HIGH OVER BACK, TAIL POINTED DOWN ... TREMORS (POSSIBLY SHIVERING) ... FALLING ... SYMPTOMS OCCURRED AS SOON AS 10 MIN AFTER TREATMENT & PERSISTED UP TO A MONTH IN A FEW ANIMALS. [U. S. Department of the Interior, Fish & Wildlife Service, Bureau of Sport Fisheries & Wildlife. Handbook of Toxicity of Pesticides to Wildlife. Washington, D. C.: U. S. Government Printing Office, 1970., p. 114]**PEER REVIEWED**
  
• ENDOSULFAN WAS ADMIN ORALLY TO MALE ALBINO RATS AT 0, 11, 22, 36, OR 55 MG/KG DAILY FOR 5 DAYS. THE HIGHEST DOSES WERE ASSOCIATED WITH CLINICAL SIGNS OF INSECTICIDE POISONING & DEATH. CYTOGENETIC ANALYSIS OF BONE MARROW CELLS & SPERMATOGONIAL CELLS DID NOT REVEAL ANY SIGNIFICANT EFFECT ON CHROMOSOMES. THE MITOTIC INDEX & FREQUENCY OF CHROMATID BREAK IN THE TWO CELL TYPES HAD NO CORRELATION WITH THE DOSES TESTED & WERE NOT DIFFERENT FROM THOSE OF THE CONTROL GROUP. [DIKSHITH TS, DATTA KK; BULL ENVIRON CONTAM TOXICOL 20 (6): 826 (1978)]**PEER REVIEWED**
  
• A SUDDEN FISH KILL IN THE UITHOORNSE POLDER WAS ATTRIBUTED TO A DISCHARGE OF ENDOSULFAN INTO THE WATER. THE ENDOSULFAN CONTENT IN THE WATER FELL FROM 30.9 TO 0.01-6.5 UG/L IN 4 DAYS OWING TO ABSORPTION ONTO MUD. THE ENDOSULFAN CONTENT OF THE DEAD FISH WAS GREATER THAN 200 MG/KG ON A FAT BASIS. [KERKHOFF M, DE BOER J; VISSERIJ 30 (3): 136 (1977)]**PEER REVIEWED**
  
• ENDOSULFAN INTERFERES WITH ENERGY METABOLISM IN VIVO OF THE FRESH WATER TELEOST FISH, CHANA GACHUA, FOLLOWING CHRONIC EXPOSURE TO VARIOUS SUBLETHAL CONCENTRATIONS. THE MARKED SENSITIVITY OF MITOCHONDRIAL MAGNESIUM(2+) ATPASE TO ENDOSULFAN IS SUGGESTIVE OF THE POTENTIAL FOR ENDOSULFAN TO INTERFERE MARKEDLY WITH VARIOUS ENERGY REQUIRING PROCESSES IN THE FISH BODY. [DALELIA RC ET AL; TOXICOLOGY 11 (4): 361 (1978)]**PEER REVIEWED**
  
• ... GIVEN ORALLY ON DAYS 6 THROUGH 14 IN DOSES OF 5 & 10 MG/KG TO RATS ... NO SOFT TISSUE DEFECTS WERE FOUND. SOME DELAYED OSSIFICATION OCCURRED WITH TREATMENT. [Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986., p. 231]**PEER REVIEWED**
  
• ... ATAXIA ... /WHICH/ PROGRESSED TO COMPLETE INABILITY TO STAND BUT NEVER INVOLVED OBSERVED CONVULSIONS WAS REPORTED IN PIGS & LAMBS THAT GRAZED IN A FIELD THAT HAD BEEN SPRAYED WITH ENDOSULFAN. ... BLINDNESS ... WAS OBSERVED IN SHEEP ... ONSET OF BLINDNESS WAS DELAYED 1 WK AFTER FIRST EXPOSURE TO PASTURE SPRAYED WITH ENDOSULFAN; SOME RECOVERY WAS NOTED AFTER AN ADDITIONAL 2 WK, WITH FULL RECOVERY AT THE END OF THE MONTH. [Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 252]**PEER REVIEWED**
  
• TECHNICAL GRADE ENDOSULFAN WAS ADMIN IN THE FEED: 952 AND 408 PPM FOR 50 MALE RATS, 445 AND 223 PPM FOR 50 FEMALE RATS, 6.9 AND 3.5 PPM FOR 50 MALE MICE, & 3.9 AND 2.0 PPM FOR 50 FEMALE MICE. THE CMPD WAS ADMIN FOR 74 WK (HIGH DOSE MALE RATS), 82 WK (LOW DOSE MALE RATS), OR 78 WK (FEMALE RATS & ALL MICE). AFTER AN ADDNL OBSERVATION PERIOD OF 33 WK (FEMALE RATS) OR 14 WK (MICE), THE ANIMALS WERE SACRIFICED. CARCINOGENICITY COULD NOT BE EVALUATED IN MALE RATS & MICE BECAUSE OF THE HIGH MORTALITY RATE EARLY IN THE STUDY. ENDOSULFAN WAS NOT CARCINOGENIC IN FEMALE RATS OR MICE UNDER CONDITIONS OF THE BIOASSAY. [CARCINOGENESIS TESTING PROGRAM; NATL CANCER INST CARCINOG TECH REP SER 62: 54 PAGES (1978)]**PEER REVIEWED**
  
• THE MUTAGENICITIES OF VARIOUS PESTICIDES WERE TESTED IN MICE VIA THE MICRONUCLEUS TEST WITH 1/3 LD50 DOSES OF EACH CMPD. WHEN MICE WERE ADMIN ENDOSULFAN (43.3 MG/KG) IN STERILE DISTILLED WATER IN 2 DOSES SEPARATED BY A 24 HR INTERVAL, NO SIGNIFICANT EFFECT ON THE FREQUENCY OF MICRONUCLEI OCCURRED. [USHA RANI MV ET AL; BULL ENVIRON CONTAM TOXICOL 25 (2): 277-82 (1980)]**PEER REVIEWED**
  
• THE PORPHYRINOGENIC ABILITY OF 4 PESTICIDES WAS INVESTIGATED IN 17 DAY OLD CHICK EMBRYO LIVER IN OVO. ENDOSULFAN PROMOTED REMARKABLE INCR IN HEPATIC PORPHYRIN ACCUMULATION. WHEN DELTA-AMINOLEVULINIC ACID SYNTHETASE ACTIVITY WAS ANALYZED IN THE CHICK EMBRYOS NO ALTERATION COULD BE FOUND IN SPITE OF PRODUCING NOTICEABLE ACCUM OF PORPHYRINS. [VILA MC ET AL; TOXICOL 25 (4): 323-32 (1982)]**PEER REVIEWED**
  
• THE RELATIVE TOXICITY /SRP: LC50 IN A CONTINUOUS-FLOW SYSTEM/ OF TECH ENDOSULFAN, ITS ISOMERS ENDOSULFAN A AND B, AND 2 FORMULATED PRODUCTS (35% EC AND 4% DUST) TO LABEO ROHITA DECR IN THE ORDER: ENDOSULFAN A GREATER THAN EC GREATER THAN ENDOSULFAN GREATER THAN DUST GREATER THAN ENDOSUFAN B IN A 96 HR EXPOSURE. ENDOSULFAN A WAS APPROX 20 TIMES MORE TOXIC THAN ENDOSULFAN B. /ENDOSULFAN A AND B/ [RAO DM R ET AL; J TOXICOL ENVIRON HEALTH 6 (4): 825-34 (1980)]**PEER REVIEWED**
  
• ENDOSULFAN WAS TESTED FOR ITS ABILITY TO INDUCE MUTATION, MITOTIC CROSSING OVER, AND GENE CONVERSION IN THE YEAST SACCHAROMYCES CEREVISIAE. TREATMENT OF CELLS WITH 1.0% DID NOT INDUCE MITOTIC CROSSOVERS BUT REDUCED SURVIVAL AND INCR THE % OF ABERRANT COLONIES AS WELL AS THE FREQUENCY OF GENE CONVERTANTS AND REVERTANTS OVER CONTROLS TREATED WITH 10% ACETONE. ENDOSULFAN WAS NOT ONLY TOXIC TO YEAST CELLS BUT ALSO GENETICALLY EFFECTIVE WITHOUT ACTIVATION. THE GENOTOXIC EFFECTS WERE MORE PRONOUNCED WITH INCR DURATION OF CELL EXPOSURE. [YADAV AS ET AL; MUTAT RES 105 (6): 403-7 (1982)]**PEER REVIEWED**
  
• 228 PESTICIDES INCL ENDOSULFAN WERE TESTED FOR MUTAGENICITY IN BACTERIAL REVERSION-ASSAY SYSTEMS WITH 5 STRAINS (TA100, TA98, TA1535, TA1537 AND TA1538) OF SALMONELLA TYPHIMURIUM AND A STRAIN (WP2 HCR) OF ESCHERICHIA COLI. ENDOSULFAN TESTED NEGATIVE IN EACH SYSTEM. [MORIYA M ET AL; MUTAT RES 116 (3-4): 185-216 (1983)]**PEER REVIEWED**
  
• ... Concentrations of 0.035 to 0.14% were phytotoxic to all but one species of Cucurbitae. Phytotoxicity was estimated by necrotic spots on the leaves. [Morey RJ, Singh Z; Haryana Agric Univ J Res 10: 509-16 (1980) as cited in WHO; Environ Health Criteria: Endosulfan p.37 (1984)]**PEER REVIEWED**
  
• Endosulfan reduced the germination of cucumber pollen to 54.6% of control levels at a concn of 1000 mg active ingredient/l, half of the recommended concn for field use. At the same concn pollen tube length was 8.1% of controls. [Gentile AG et al; Environ Entomol 7: 689-91 (1978) as cited in WHO; Environ Health Criteria: Endosulfan p.37 (1984)]**PEER REVIEWED**
  
• ... Exposure of germinating Cicerarietinum seeds to endosulfan resulted in a fall in pectin, hemicellulose, and cellulose contents of cell walls at all stages of germination compared with untreated controls. [Agarwal S, Beg MU; Ind J Exp Biol 20: 319-23 (1982) as cited in WHO; Environ Health Criteria: Endosulfan p.40 (1984)]**PEER REVIEWED**
  
• Vingna radiata (green gram) was exposed to four concentrations of endosulfan between 0.35 g/kg and 3 g/kg. Toxic effects were dose dependent. At 0.35 g/kg and 0.7 g/kg, no adverse effects were observed in any of the parameters studied. ... At higher concentrations of 1.5 g/kg and 3 g/kg, symptoms of toxicity ... included coiling of radical, inhibition of root growth, stunting of shoots, burning of root growth, and burning of the tips and margins of the leaves. Plants were dwarfed and chlorotic, having damaged pollen grains and low productivity. [Gupta PK, Gupta RC, Toxicol 8: 283-8 (1977) as cited in WHO; Environ Health Criteria: Endosulfan p.37 (1984)]**PEER REVIEWED**
  
• The harbor seal population in the Dutch Wadden Sea decreased significantly and its pup production was low compared to the more stable population in Schleswig-Holstein, Germany, and a correlation was made associating an assumed inverse trend of contaminant residue levels in seal tissues. Dead stranded animals are collected in both areas and blubber, liver, brain and kidney are analyzed for ... endosulfan. ... High levels of all contaminants /including endosulfan were found/. [Reijnders PJH; J Sea Res 14 (1): 30-65 (1980)]**PEER REVIEWED**
  
• Eight insecticides were identified from 43 samples of honey bees (Apis mellifera) obtained from 35 beekeepers in 1981 and 1982. A total of 268 colonies were documented to have been contaminated from May through early October. Insecticides detected in honey bees included endosulfan, chlordane, malathion, diazinon, and acephate. [Anderson JF, Glowa W; Environ Entomol 13 (1): 70-4 (1984)]**PEER REVIEWED**
  
• Two studies have been undertaken on the toxicity and carcinogenicity of endosulfan, a chlorinated cyclodiene - the NCI Endosulfan Rat Study and the NCI Endosulfan Mouse Study. Histological sections have been examined and the results of this review are based on diagnosis. Endosulfan is highly toxic for male and female Osborne-Mendel rats, particularly for male rats. The chemical causes interstitial fibrosis or acute tubular necrosis of the kidney and death. These lesions, as well as atrophy of the testes, polyarteritis, parathyroid hyperplasia, osteitis fibrosis of bone, and abscesses of the lung, interfere with health of the animals. [Reuber MD, Columbia MD; Sci Total Environ 20 (1): 23-47 (1981)]**PEER REVIEWED**
  
• FORTY-EIGHT HR LC50 VALUES FOR ENDOSULFAN & ITS METABOLITES, INCLUDING ENDOSULFAN SULFATE, WERE DETERMINED IN 11 MARINE FISH, INSECTS, MOLLUSKS, CRUSTACEANS, & TUBIFEX TUBIFEX. THE ESPECIALLY HIGH TOXICITY TO FISH WAS DECREASED BY METABOLIC REMOVAL OF SULFUR FROM THE MOLECULE TO A LEVEL IN THE SAME RANGE AS FOR THE INVERTEBRATES (LC50 1-10 PPM). [KNAUF W, SCHULZE EF; MEDED FAC LANDBOUWWETENSCH RIJKSUNIV GENT 38 (3): 717-32 (1973)]**PEER REVIEWED**
  
• Fish were 1x10+4 times more sensitive to endosulfan and its metabolites than worms and snails. The increasing order of sensitivity was worms
• Histopathological lesions were produced by endosulfan (0.001 ppm, for 20 days) in the hypothalamo-hypophysial complex-ovarian axis of the fish, Sarotherodon mossambicus. The aquatic medium in which the fish lives when it is contaminated with endosulfan may result in changes in oxygen content and pH. [Shukla L, Pandey AK; Bull Environ Contam Toxicol 36 (1): 122-31 (1986)]**PEER REVIEWED**
  
• Single exposure of endosulfan (5 mg/kg) to pigeons (Columba livia) caused neuronal hyperexcitability as evidence by spike discharges of 200-500 muV in the electroencephalograms from the telencephalon and hyperstriatum, but there was no effect on the ectostriatal area. Cholinergic (muscarinic) receptor binding study using (3)H-quinuclidinyl benzilate as a specific ligand indicated that a single exposure to 5 mg endolsulfan/kg caused a significant increase in (3)H-quinuclidinyl benzilate binding to the striatal membrane. Behavioral study further indicated that a single dose of 200 ug/kg oxotremorine produced a significant induction in the tremor in endosulfan pretreated pigeons. [Anand M et al; Environ Res 40 (2): 421-6 (1986)]**PEER REVIEWED**
  
• Endosulfan, a chlorinated pesticide, is widely used to control various insect pests. Rats exposed to 1 mg and 3 mg endosulfan/kg for periods of 10, 30, and 60 days showed significant (p< 0.05) inhibition of (3)H5-hydroxytryptamine uptake by platelet rich plasma. Rats treated with endosulfan (1 and 3 mg/kg) up to 60 days elucidated a marked inhibition of ADP induced aggregatory responses of the platelets. Incubation of platelet rich plasma with 10 uM and 100 uM endosulfan for 15 min at 37 deg C also resulted in significant (p< 0.05) inhibition of platelet aggregation in vitro. [Anand M et al; Toxicol Lett 32 (3): 203-8 (1986)]**PEER REVIEWED**
  
• Relative toxicity of technical and commercial formulations of malathion and endosulfan were evaluated by determining LC50 values and their 95% confidence interval end points for 24, 48, 72, and 96 hr exposure to Channa punctatus using the "trimmed Spearman-Karber method". The commercial formulation of malathion and endosulfan were 1.176 and 1.88 times more toxic than their technical materials, respectively. 96 hr LC50 values (0% trimming) of technical and commerical formulations of malathion and endosulfan (95% confidence interval in parentheses) were 4.51 (4.11-4.96) and 3.89 (3.46-4.38) mg/liter, and 5.78 (4.49-7.44) and 3.07 (2.43-3.84) ug/liter, respectively. [Haider S, Inbaraj RM; Ecotoxicol Environ Saf 11 (3): 347-51 (1986)]**PEER REVIEWED**
  
• AFTER A SINGLE ORAL DOSE OF ENDOSULFAN (40 MG/KG) A SIGNIFICANT INCR IN BLOOD GLUCOSE, BLOOD ASCORBIC ACID, AND BLOOD AND BRAIN GLUTATHIONE WAS OBSERVED IN 12 HR FASTED MALE RATS. REPEATED ORAL ADMIN OF ENDOSULFAN (0.625 TO 20 MG/KG) FOR 7 WK SIGNIFICANTLY DECR PLASMA CALCIUM, THE MAX FALL (35%) BEING OBSERVED AT 4 HR. AT 20 MG/KG, BLOOD GLUCOSE WAS SLIGHTLY INCR (16%). [GARG A ET AL; TOXICOL LETT 5 (2): 119-23 (1980)]**PEER REVIEWED**
  
• Chemical test results cytogenetic for effects in Chinese Hamster ovary cells in FY 1987 were negative. [NTP; Fiscal Year 1988 Annual Plan p.87 (1988) NTP-87-200]**PEER REVIEWED**
  
• THE EFFECT OF ENDOSULFAN (0.5, 1.0, OR 2 MG/KG IV) WAS STUDIED IN PENTOBARBITAL ANESTHETIZED AND PARALYZED CATS. THE PESTICIDE CAUSED HYPERTENSION, PUPILLARY DILATATION & AN INCR IN CARDIAC OUTPUT & PERIPHERAL RESISTANCE. SINCE THESE CHANGES COINCIDED WITH SPIKE DISCHARGES IN THE EEG, & SINCE THERE WAS ALSO A PROFUSE SALIVATION INDICATING AUGMENTATION OF PARASYMPATHETIC ACTIVITY AS WELL, ENDOSULFAN WAS APPARENTLY ACTING WITHIN THE BRAIN TO INCR AUTONOMIC ACTIVITY. THE MICROSPHERE TECHNIQUE REVEALED THAT THE CARDIAC OUTPUT WAS PREFERENTIALLY REDISTRIBUTED TO THE HEART & THE BRAIN @ THE COST OF THE FRACTION GOING TO THE KIDNEYS, LUNGS, MUSCLES & LARGE INTESTINE. THERE WAS AN INCR IN CEREBRAL BLOOD FLOW WHICH WAS MORE MARKED IN DIENCEPHALON & CEREBRAL HEMISPHERES. [ANAND M ET AL; VET HUM TOXICOL 23 (4): 252-8 (1981)]**PEER REVIEWED**
  
• Dose dependent increased activities of aminopyrine-N-demethylase and aniline hydroxylase in endosulfan treated rats suggest that endosulfan is an inducer of the mixed function oxidase system. [Aganval DK et al; Environ Saf Health C13: 49 (1978) as cited in USEPA; Health Effects Assessment for Alpha- Beta- Endosulfan p.11 (1987) EPA 600/8-88-34]**PEER REVIEWED**
  
• The toxicity to mice of ip administered polychlorocycloalkane insecticides is generally correlated with their potency as in vitro inhibitors of the brain specific (35)S-t-butylbicyclophosphorothionate binding site with correction for metabolic activation and detoxification. These findings from our earlier studies are extended here to in vivo investigations relating convulsant action to inhibition of the (35)S-t-butylbicyclophosophorothionate binding site in poisoned mice. Radioligand binding assays involved brain P2 membranes washed three times with 1 mM EDTA to remove endogenous gamma-aminobutyric acid or other modulator(s) which otherwise serves as a noncompetitive inhibitor of (35)S-t-butylbicyclophosophorothionate binding at the gamma-aminobutyric acid regulated chloride ionophore. Examination of lindane, technical toxaphene, toxaphene toxicant A, and 10 polychlorocyclodiene insecticides revealed 62 + or - 4% binding site inhibition 30 min after their LD50 doses with 32 + or - 3% inhibition at one-half and 6 + or - 3% inhibition at one-quarter of their LD50 doses. This correlation between binding site inhibition and convulsant action is also evident in dose and time dependency studies with endosulfan sulfate. The brain P2 membranes of treated mice contain the parent compound with each of the polychlorcycloalkanes plus activation products of some of the cyclodienes: endosulfan sulfate from alpha- and beta-endosulfan and 12-ketoendrin from isodrin and endrin. [Cole LM, Casida JE; Life Sci 39 (20): 1855-62 (1986)]**PEER REVIEWED**
  

Back to Top

Human Toxicity Values

• None found

Back to Top

Non-Human Toxicity Values

• LD50 Rat oral 18 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1463]**PEER REVIEWED**
  
• LC50 Rat ihl 80 mg/cu m/4 hr [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1463]**PEER REVIEWED**
  
• LD50 Rat skin 34 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1463]**PEER REVIEWED**
  
• LD50 Rat ip 8 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1463]**PEER REVIEWED**
  
• LD50 Mouse oral 7360 ug/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1463]**PEER REVIEWED**
  
• LD50 Mouse ip 7 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1463]**PEER REVIEWED**
  
• LD50 Dog oral 76,700 ug/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1463]**PEER REVIEWED**
  
• LD50 Cat oral 2 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1463]**PEER REVIEWED**
  
• LD50 Rabbit oral 28 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1463]**PEER REVIEWED**
  
• LD50 Rabbit skin 90 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1463]**PEER REVIEWED**
  
• LD50 Rabbit sc 360 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1463]**PEER REVIEWED**
  
• LD50 Hamster oral 118 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1463]**PEER REVIEWED**
  
• LD50 Hamster ip 80 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1463]**PEER REVIEWED**
  

Back to Top

Absorption, Distribution and Excretion

• IT IS RAPIDLY ABSORBED FROM GI TRACT ... [Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 143]**PEER REVIEWED**
  
• ENDOSULFAN WAS DIFFERENTIALLY DISTRIBUTED IN CNS OF THE CAT BRAIN WITH CONCN PATTERN CHANGING WITH TIME. WHITE MATTER HAD SLOWER UPTAKE & RELEASE WITH LOWER MAX CONCN OF ENDOSULFAN THAN DID GRAY MATTER. [KHANNA RN ET AL; BULL ENVIRON CONTAM TOXICOL 22 (1-2): 72 (1979)]**PEER REVIEWED**
  
• The A and B-isomers of (14)C-endosulfan were administered to rats separately as single 2 mg/kg oral doses in corn oil. No appreciable differences were observed in the fecal (or urine) elimination of radioactivity of the two isomers. Approximately 11 and 13%, 55 and 62%, and 68 and 75% of the administered radioactivity was eliminated in the feces at 24, 48, and 120 hours after treatment with the alpha and beta-isomers, respectively. Analyses of bile collected for 48 hours showed that 47% of the alpha-endosulfan dose and 29% of the beta-endosulfan dose was eliminated by this route. [Dorough HW et al; Pestic Biochem Physiol 8: 241-52 (1978) as cited in USEPA; Health Effects Assessment for Alpha and Beta-Endosulfan p.3 (1987) EPA 600/8-88-034]**PEER REVIEWED**
  
• In studies with sheep receiving a single oral dose of radiolabeled endosulfan, 92 percent of the dose was eliminated in 22 days. The organ with the highest concentration of radiolabeled endosulfan after 40 days was the liver. Major metabolites did not persist in the fat or in the organs. [Gorbach SG et al; J Agric Food Chem 16: 950 (1968) as cited in USEPA; Health and Environmental Effects Profile for Endosulfan p.98-8 (1980)]**PEER REVIEWED**
  
• The principal route of excretion for endosulfan and endosulfan sulfate is in the feces. [USEPA; Health and Environmental Effects Profile for Endosulfan p.98-9 (1980)]**PEER REVIEWED**
  
• The beta-isomer is more readily absorbed than the alpha-isomer. [Maier-Bode H; Residue Rev 22: 2 (1968) as cited in USEPA; Health and Environmental Effects Profile for Endosulfan p.96-8 (1980)]**PEER REVIEWED**
  
• In mice, 24 hours after oral administration of (14)C-endosulfan, residues were detected in fat, liver, kidney, brain, and blood. [Deema P et al; Jour Econ Entomol 59: 546 (1966) as cited in USEPA; Health and Environmental Effects Profile for Endosulfan p.97-8 (1980)]**PEER REVIEWED**
  
• Data from autopsies of three suicides show levels of endosulfan in brain which were much lower than those in liver and kidney, which in turn, were lower than levels in blood. Data from another suicide indicate higher levels of endosulfan in liver and kidneys than in blood. [Demeter J et al; Bull Environ Contam Toxicol 18: 110 (1977) as cited in USEPA; Health and Environmental Effects Profile for Endosulfan p.97-8 (1980)]**PEER REVIEWED**
  
• Alcohols, oils, and emulsifiers accelerate the absorption of endosulfan by the skin. [Maier-Bode H; Residue Rev 22: 2 (1968) as cited in USEPA; Health and Environmental Effects Profile for Endosulfan p.96-8 (1980)]**PEER REVIEWED**
  
• Most of the radioactivity is excreted within the first 48 hrs. The amounts excreted are independent of dose level, number of dosages, and isomerism. There are indications of species-specificity. [Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994., p. 390]**PEER REVIEWED**
  

Back to Top

Metabolism/Metabolites

• IN TEMP STRESSED RATS ORALLY DOSED WITH ENDOSULFAN I OR II, ENDOSULFAN SULFATE WAS THE METABOLITE MOST COMMONLY RECOVERED FROM TISSUES, ORGANS & FECES REGARDLESS OF TEMP STRESS. THE DIOL, ALPHA-HYDROXY ETHER & LACTONE ... WERE FOUND IN MOST URINE & FECES SAMPLES. [Menzie, C.M. Metabolism of Pesticides, Update II. U.S. Department of the Interior, Fish Wildlife Service, Special Scientific Report - Wildlife No. 2l2. Washington, DC: U.S. Government Printing Office, 1978., p. 133]**PEER REVIEWED**
  
• ... WHITE MICE (BALB/C STRAIN) WERE FED (14)C-LABELED ENDOSULFAN. THE TWO ISOMERS WERE NOT COMPLETELY ABSORBED FROM GI TRACT BUT, ALONG WITH ENDOSULFAN SULFATE & DIOL, WERE EXCRETED IN FECES. ONLY A TRACE OF OXIDIZED ENDOSULFAN WAS FOUND IN KIDNEY & MUSCLE EXTRACTS BUT NEITHER OF THE TWO KNOWN METABOLITES NOR ENDOSULFAN WAS FOUND IN BLOOD OR BRAIN EXTRACTS. ... LARGE AMOUNTS OF ENDOSULFAN SULFATE WERE DETECTED IN THE LIVER & TRACES IN THE KIDNEY 24 HR AFTER /MICE/ ... RECEIVED SINGLE DOSES OF ENDOSULFAN. [Menzie, C.M. Metabolism of Pesticides. U.S. Department of the Interior, Bureau of Sport Fisheries and Wildlife, Publication 127. Washington, DC: U.S. Government Printing Office, 1969., p. 197]**PEER REVIEWED**
  
• ENDOSULFAN-(14)C WAS FED TO MILK SHEEP. ANALYSIS OF MILK SAMPLES SHOWED THAT UP TO 88% OF RADIOACTIVE MATERIALS REMAINED IN CREAM. GAS LIQUID CHROMATOGRAHPY & THIN LAYER CHROMATOGRAHY SHOWED THAT THE RADIOACTIVE MATERIAL WAS ALMOST ENTIRELY ENDOSULFAN SULFATE. ANALYSES OF URINE SAMPLES SHOWED THE PRESENCE OF ENDOSULFAN ALCOHOL & ALPHA-HYDROXYENDOSULFAN ETHER. OTHER METABOLITES PRESENT WERE NOT IDENTIFIED. [Menzie, C.M. Metabolism of Pesticides. U.S. Department of the Interior, Bureau of Sport Fisheries and Wildlife, Publication 127. Washington, DC: U.S. Government Printing Office, 1969., p. 197]**PEER REVIEWED**
  
• AFTER PERORAL, CUTANEOUS, & SUBCUTANEOUS APPLICATION OF ENDOSULFAN TO MALE IMAGOS OF THE LOCUST (PACHYTILUS MIGRATORIUS MIGRATORIOIDES), FOUR METABOLITES WERE ... IDENTIFIED AS: ENDOSULFAN SULFATE; ENDOSULFAN ETHER; ENDOSULFAN HYDROXYETHER; & ENDOSULFAN LACTONE. [Menzie, C.M. Metabolism of Pesticides. U.S. Department of the Interior, Bureau of Sport Fisheries and Wildlife, Publication 127. Washington, DC: U.S. Government Printing Office, 1969., p. 198]**PEER REVIEWED**
  
• IN A HUMAN ENDOSULFAN POISONING: ... ENDOSULFAN SULFATE WAS FOUND IN THE LIVER AT A CONCN OF 3.4 PPM [Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 253]**PEER REVIEWED**
  
• Metabolism of topical endosulfan in the Indian honey bee, Apis cerana indica was studied. The two endosulfan isomers were found to be inconvertable in bees. The products were endosulfan sulfate, diol, ether, hydroxyether, and lactone and two unknown compounds. Endosulfan diol, hydroxyether and lactone were found to be conjugated in the excreta of the treated bees. [Nath A et al; Experientia 14 (11): 1411-12 (1985)]**PEER REVIEWED**
  
• THE TOXICITY & METABOLISM OF ENDOSULFAN TO 3 FRESHWATER CATFISHES WERE STUDIED. THE PRINCIPAL METABOLITE WAS ENDOSULFAN SULFATE & THE PRINCIPAL DETOXIFICATION PRODUCTS WERE ENDOSULFAN ALCOHOL & ENDOSULFAN ETHER. THE LIVER WAS THE PRINCIPAL SITE OF STORAGE & DEGRADATION OF ENDOSULFAN. [RAO DM R, MURTY AS; ENVIRON POLLUT SER A 27 (3): 223-31 (1982)]**PEER REVIEWED**
  
• EXPERIMENTS WERE CONDUCTED WITH THE FRESHWATER FISH MACROGNATHUS ACULEATUM TO STUDY THE TOXICITY & METABOLISM OF ENDOSULFAN & ITS EFFECT ON OXYGEN CONSUMPTION & TOTAL NITROGEN EXCRETION. THE 96-HR MEDIAN LETHAL CONCN VALUE WAS 3.5 PPB. IN BRAIN, GILLS, GUT, LIVER, & KIDNEY, ENDOSULFAN WAS METABOLIZED TO ENDOSULFAN SULFATE, BUT THIS APPEARS TO BE ONLY AN INTERMEDIARY STEP AS THE NONTOXIC ETHER WAS FOUND ONLY IN THE LIVER & KIDNEY. ENDOSULFAN, BOTH AT SUBLETHAL & LETHAL CONCN, DECREASED OXYGEN CONSUMPTION & TOTAL NITROGEN EXCRETION. [RAO DM R ET AL; PESTIC BIOCHEM PHYSIOL 15 (3): 282-7 (1981)]**PEER REVIEWED**
  
• FEMALE ALBINO RATS WERE GIVEN DAILY ORAL DOSES OF 0.5 AND 100 PPM ENDOSULFAN MIXED IN THE DIET. RATS WERE FED FOR 9 AND 18 WK ON POOR RICE DIETS (5% PROTEIN) OR FOR 18 WK ON A HIGH-PROTEIN DIET. IN BOTH LOW & HIGH PROTEIN DIET GROUPS, ENDOSULFAN CAUSED ACCUM OF PERIRENAL ADIPOSE TISSUE. ADIPOSE TISSUE WAS FOUND TO CONTAIN ALPHA-ENDOSULFAN, BETA-ENDOSULFAN, AND ENDOSULFAN SULFATE; TISSUE SAMPLES FROM LOW-PROTEIN RATS CONTAINED HIGHER CONCN OF THESE METABOLITES. [DAS N, GARG A; PESTIC BIOCHEM PHYSIOL 15 (1): 90-8 (1981)]**PEER REVIEWED**
  

Back to Top

TSCA Test Submissions

• Endosulfan (CAS # 115-29-7) was evaluated for developmental toxicity in the offspring of primigravida Charles River-CD rats (5/group) administered single dermal applications upon clipped backs at doses of 0 (DMSO vehicle control), 450, 670, 1000, 1500, and 2250 mg/kg bodyweight on gestation Day 1 (Day 11 in a few instances due to breeder error). All surviving animals were then sacrificed on gestation Day 20 (Day 31 in a few instances due to breeder error) for observation of acute maternal, embryo-, and fetotoxicity. One female rat each died following 1500 and 2250 mg/kg exposures. Gross examination of uteri, with evaluation of number of implantation sites, number of live fetuses, early and late resorptions, fetal weight, and fetal crown-rump length, revealed no significant treatment- related abnormalities relative to vehicle control. Upon examination of fetuses, 3 and 2 instances of exoencephaly were identified among those of mothers receiving 670 and 1000 mg/kg dermal applications. Results were summarized and no further information regarding method or results was provided.[E I Dupont de Nemours & Co; Maternal Toxicity, Embryotoxicity and Teratogenic Potential Study of Neoprene Accelerators Applied to Skin of Rats During Organogenesis; 06/29/73; EPA Document No. 86940000194; Fiche No. OTS0556789]**UNREVIEWED**
  

Back to Top

Footnotes

¹ Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.