Endrin is an organochlorine insecticide which has been used since the 1950s against a wide range of agricultural pests, mostly on cotton but also on rice, sugar-cane, maize, and other crops. It is also used as a rodenticide. It is available commercially as dusts, granules, pastes, and an emulsiFIable concentrate. Endrin enters the air mainly by volatilization and aerial drift. In general, volatilization takes place after application to soils and crops and depends on many factors, such as the organic matter and moisture content of the soil, humidity, air flow, and the surface area of plants. The most important route of contamination of surface water is run-off from soil. Contamination from precipitation in the form of snow or rain is negligible. Local contamination of the environment may occur from industrial effluents and careless application practices. The major source of endrin in soil is from direct application to soil and crops. Endrin can be retained, transported, or degraded in soil, depending on a number of Factors. The greatest retention occurs in soils with a high content of organic matter. The persistence of endrin is highly dependent upon local conditions; its half-life in soil can range up to 12 years. Volatilization and photodecomposition are the primary factors in the disappearance of endrin from soil surfaces . Under the influence of sunlight (ultraviolet light), the isomer delta-ketoendrin is formed. In intense summer sun, about 50% of endrin was isomerized to this ketoendrin within 7 days. Microbial transformation (in fungi and bacteria) takes place, especially under anaerobic conditions, to give the same product. Aquatic invertebrates and fish take up endrin rapidly from water, but exposed fish transferred to uncontaminated water lose the pesticide rapidly Bioconcentration factors of 14-18 000 have been recorded after continuous exposure (log Pow = 5.34). Soil invertebrates may also take up endrin readily. The occasional presence of low levels of endrin in air and in surface and drinking-water in agricultural areas is of little significance from the point of view of public health. The only exposure that may be relevant is dietary intake. In general, however, the reported intake levels are far below the acceptable daily intake of 0.0002 mg/kg body weight established in 1970 (FAO/WHO, 1971). Effects on organisms in the environment: The effect of endrin on soil bacteria and fungi is minimal. Dose levels of 10-1000 mg/kg of soil had no effect on decomposition of organic matter, denitrification, or generation of methane. Endrin is very toxic to fish, aquatic invertebrates, and phytoplankton: the 96-h LC50 values are mostly below 1.0 ug/litre. The 48-h LC50 value for Daphnia magna was 4.2 mg/l. The lowest observed adverse effect level in a life cycle test on the mysid shrimp, Mysidopsis bahia, was established at 30 ng/litre. The reported tests on the acute toxicity of endrin in aquatic organisms were conducted in aquaria without sediment; the presence of sediment would be expected to attenuate the effect of endrin. Heavily contaminated sediment had little effect on species living in open water, suggesting that sediment-bound endrin has low bioavailability. Tests have not been conducted on aquatic animals living in sediment. The LD50 for terrestrial mammals and birds is in the order of 1.0-10.0 mg/kg body weight. Mallard ducks fed up to 3.0 mg/kg body weight for 12 weeks showed no effect on egg production, fertility, or hatchability. The LD50 for bees after contact was 0.65 ug/bee, and the acute oral LD50 was 0.46 ug/bee. Certain species of aquatic invertebrates, fish, and small mammals have been reported to be resistant to the toxicity of endrin, and exposure to several different organochlorine pesticides led to selection of strains resistant to endrin. Fish kills were observed in areas of agricultural run-off and industrial discharge; and declining populations of brown pelicans (in Louisiana, USA) and of sandwich terns (in the Netherlands) have been attributed to exposure to endrin in combination with other halogenated chemicals. Effects on experimental animals and in vitro: Endrin is a highly toxic pesticide, the signs of intoxication being neurotOxic. The oral LD50,of technical-grade endrin for laboratory animals is m the range of 3-43 mg/kg body weight; the dermal LD50 for rats is 520 mg/kg body weight. No substantial difference in acute oral or dermal toxicity was found between technical-grade and formulated (emulsifiable concentrate and wettable powder) products. Short-term experiments for oral toxicity have been carried out using mice, rats, rabbits, dogs, and domestic animals. In mice and rats, the maximum tolerated doses for 6 weeks were 5 and 15 mg/kg diet(equivalent to O.7 mg/kg body weight), respectively. Rats survived a 16-week exposure to 1 mg/kg diet (equivalent to 0.05 mg/kg body weight); rabbits died after receiving repeated doses of 1 mg/kg body weight. In dogs, a dose of 1 mg/kg of diet (approximately equivalent to 0.025 mg/kg body weight), given over 2 years, was without effect. The neurological basis of the observed signs of intoxication is inhibition of gamma-arninobutyric acid (GABA) function at low doses. Like other chlorinated hydrocarbon insecticides, endrin also affects the liver, and stimulation of enzyme systems involved in the metabolism of other chemicals is evident, as shown by, for instance, decreased hexobarbital sleeping time in mice. Doses of 75-150 mg/kg applied dermally as a dry powder for 2 h daily caused convulsions and death in rabbits but did not result in skin irritation. Production of systemic toxicity without irritation at the site of contact is noteworthy. Long-term studies of toxicity and carcinogenicity have been performed in mice and rats. No carcinogenic effect was found, but these studies had shortcomings, including poor survival of the animals. The no observed effect level for toxicity in a two-year study in rats was 1 mg/kg of diet (equivalent to about 0.05 mg/kg body weight). Tumour promoting effects were not demonstrated when endrin was tested in combination with subminimal quantities of chemicals known to be carcinogenic to animals. The Task Group concluded that the data are insufficient to indicate that endrin is a carcinogenic hazard to humans. Endrin was found to be nonmutagenic in several studies. In most studies, it was not teratogenic to mice, rats, or hamsters, even at doses that caused maternal or fetotoxicity. The no-observed-adverse effect level was 0.5 mg/kg body weight in mice and rats and 0.75 mg/kg body weight in hamsters. Endrin did not induce reproductive effects in rats over three generations when given at a dose of 2 mg/kg of diet (about 0.1 mg/kg body weight). A number of the metabolites of endrin have similar or higher acute toxicities than the parent compound. The transformation product, deltaketoendrin, is less toxic than endrin, but 12-ketoendrin is considered to be the most toxic metabolite of endrin in mammals, with an oral LD50 in rats of 0.8-1.1 mg/kg body weight. Effects on human beings: Several episodes of fatal and non-fatal accidental and suicidal poisoning have occurred. Cases of acute non-fatal intoxication due to accidental overexposure were observed in workers in an endrin manufacturing plant. The oral dose that causes death has been estimated to be approximately 10 mg/kg body weight; the single oral dose that causes convulsions was estimated to be 0.25-1.0 mg/kg body weight. The primary site of action of endrin is the central nervous system. Exposure of humans to a toxic dose may lead within a few hours to such signs and symptoms of intoxication as excitability and convulsions, and death may follow within 2-12 h after exposure if appropriate treatment is not administered immediately. Recovery from non-fatal poisoning is rapid and complete. Endrin does not accumulate in the human body to any significant degree. No long-term adverse effects were reported in 232 occupationally exposed workers (length of exposure, 4-27 years) under medical supervision (observation time, 4-29 years). The only effect observed was indirect evidence of a reversible stimulation of drug metabolizing enzymes. Endrin was detected in virtually none of a large number of samples of adipose tissue, blood, and breast milk analysed in many countries. The Task Group attributed the absence of endrin in human samples to the low exposure of the general population to this pesticide and to its rapid metabolism. Endrin was detected in blood (at up to 450 ug/litre) and in adipose tissue (at 89.5 mg/kg) in cases of fatal accidental poisoning. No endrin was found in workers under normal circumstances. The threshold level of endrin in blood, below which no sign or symptom of intoxication occurs, has been estimated to be 50-100 ug/litre. The half-life of endrin in blood may be in the order of 24 h. (Shortened)