Endrin toxicity

Studies in humans demonstrate that the nervous system is a primary target for endrin toxicity. 

Persons with a history of convulsive disorders would be expected to be at increased risk from exposure to endrin. Children may be more sensitive than adults to the acute toxic effects of endrin. In an endrin poisoning episode in Pakistan, children 1-9 years old represented about 70% of the cases of convulsions (Rowley et al. 1987). The causative factor responsible for the outbreak was not identified, however, and the age distribution of cases could be explained by age-specific exposure situations. In general, following oral administration, female animals appear to be more susceptible to endrin toxicity than males (Gaines 1960 Treon et al. 1955). The difference may be due to the more rapid excretion of endrin by male versus female rats (Hutson et al. 1975 Klevay 1971 Korte et al. 1970). A sex-related difference in toxicity was not apparent following dermal exposure (Gaines 1960, 1969). No sex-based differences in endrin-related... 

Grant, B.F. Endrin toxicity and distribution in freshwater a review. Bull Environ. Contam. Toxicol, 15 (3) 283-290, 1976. Grathwohl, P. Influence of organic matter from soils and sediments from various origins on the sorption of some chlorinated aliphatic hydrocarbons implications on Koc correlations. Environ. Sci. Technol, 24(11) 1687-1693, 1990. 

The development of strains resistant to insecticides is an extremely widespread phenomenon that is known to have occurred in more than 200 species of insects and mites, and resistance of up to several 100-fold has been noted. The different biochemical and genetic factors involved have been studied extensively and well characterized. Relatively few vertebrate species are known to have developed pesticide resistance and the level of resistance in vertebrates is low compared to that often found in insects. Susceptible and resistant strains of pine voles exhibit a 7.4-fold difference in endrin toxicity. Similarly pine mice of a strain resistant to endrin were reported to be 12-fold more tolerant than a susceptible strain. Other examples include the occurrence of organochlorine insecticide-resistant and susceptible strains of mosquito fish, and resistance to Belladonna in certain rabbit strains. 

Endrin [72-20-8] is l,2,3,4,10,10-hexachloro-l,4,4t ,5,8,8t -hexahydro-6,7-epoxy-l,4- <7o, <7o-5,8-dimethanonaphthalene (35) (mp 245 dec, vp 0.022 mPa at 25°C) and is soluble in water to 23 / g/L. It is produced by a Diels-Alder reaction of hexachloronorbomadiene with cyclopentadiene, followed by epoxidation. This reaction produces the endo,endo isomer of dieldrin, which is less stable and more toxic with rat LD q values of 17.8 and 7.5 (oral) and 15 (dermal) mg/kg. It is used as a cotton insecticide but because of its high toxicity to fish it has been restricted. 

The variation in toxicity of common organophosphate insecticides is exemplified in Table 5.37. The range of chlorinated hydrocarbon insecticides (Table 5.38) have, with the exception of Endrin and Isodrin, somewhat lower oral and dermal toxicities. The toxicities of a range of oilier insecticides, fungicides, herbicides and rodenticides are summarized in Table 5.39. 

The cyclodiene insecticides aldrin, dieldrin, endrin, heptachlor, endosulfan, and others were introduced in the early 1950s. They were used to control a variety of pests, parasites, and, in developing countries, certain vectors of disease such as the tsetse fly. However, some of them (e.g., dieldrin) combined high toxicity to vertebrates with marked persistence and were soon found to have serious side effects in the field, notably in Western European countries where they were extensively used. During the 1960s, severe restrictions were placed on cyclodienes so that few uses remained by the 1980s. 

As Muller had prophesied and indeed hoped, DDT stimulated the discovery of more synthetic insecticides. DDT relatives included chlordane, toxaphene, aldrin, dieldrin, endrin, and heptachlor. Popular substitutes for DDT s family included organophosphates such as parathion, which is a powerful neurotoxin, and carbamates, which are also highly toxic to people. Unlike DDT, parathion and aldicarb have killed and injured many farm workers. Malathion was later developed to be several hundred times less toxic than parathion. 

Toxic organic compounds commonly found in groundwater are presented in Table 18.4. Other toxic organic compounds (representing 1% of cases) include PCBs (polychlorinated biphenyls), 2,4-D, 2,4,5-TP (silvex), toxaphene, methoxychlor, lindane, and endrin, of which 2,4-D and silvex are commonly used for killing aquatic and land weeds. Inorganic toxic substances commonly found in... 

A waste is toxic under 40 CFR Part 261 if the extract from a sample of the waste exceeds specified limits for any one of eight elements and five pesticides (arsenic, barium, cadmium, chromium, lead, mercury, selenium, silver, endrin, methoxychlor, toxaphene, 2,4-D and 2,4,5-TP Silvex using extraction procedure (EP) toxicity test methods. Note that this narrow definition of toxicity relates to whether a waste is defined as hazardous for regulatory purposes in the context of this chapter, toxicity has a broader meaning because most deep-well-injected wastes have properties that can be toxic to living organisms. 

Chlordane interacts with other chemicals to produce additive or more-than-additive toxicity. For example, chlordane increased hepatotoxic effects of carbon tetrachloride in the rat (USEPA 1980 WHO 1984), and in combination with dimethylnitrosamine acts more than additively in producing liver neoplasms in mice (Williams and Numoto 1984). Chlordane in combination with either endrin, methoxychlor, or aldrin is additive or more-than-additive in toxicity to mice (Klaassen et al. 1986). Protein deficiency doubles the acute toxicity of chlordane to rats (WHO 1984). In contrast, chlordane exerts a protective effect against several organophosphorus and carbamate insecticides (WHO 1984), protects mouse embryos against influenza virus infection, and mouse newborns against oxazolone delayed hypersensitivity response (Barnett et al. 1985). More research seems warranted on interactions of chlordane with other agricultural chemicals. 

Jarvinen, A.W., D.K. Tanner, and E.R. Kline. 1988. Toxicity of chlorpyrifos, endrin, or fenvalerate to fathead minnows following episodic or continuous exposure. Ecotoxicol. Environ. Safety 15 78-95. 

Hall, R.J. and D. Swineford. 1980. Toxic effects of endrin and toxaphene on the southern leopard frog Rana sphenocephala. Environ. Pollut. 23A 53-65. 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective of the toxicology of endrin, endrin ketone and endrin aldehydex. It contains descriptions and evaluations of toxicological studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. 

Deaths as the result of acute exposure by ingestion of endrin have been observed in humans in a variety of incidents. In 1967, in Doha, Qatar, and Hofuf in Saudi Arabia, 874 people were hospitalized after an acute exposure to endrin-contaminated flour which resulted in 26 known deaths (Weeks 1967). Deaths occurred within 12 hours of the onset of symptoms of toxicity (convulsions, loss of consciousness, headache, nausea, vomiting) however, recovery of survivors was rapid. Concentrations of endrin in bread eaten by victims ranged from 48 to 1,807 ppm (Curley et al. 1970). The contaminated flour used to make the bread contained 2,153-3,367 ppm endrin. 

An outbreak of acute human endrin poisoning associated with central nervous system toxicity and 19 deaths in 194 known cases occurred in Pakistan in 1984 (Rowley et al. 1987). The vector for exposure was not identified, but contamination of a food item was the likely cause of poisoning. 

Ingestion of 12 g of endrin (dissolved in aromatic hydrocarbons) by a 49-year-old man in a suicide attempt caused convulsions persisting for 4 days death occurred after 11 days (Runhaar et al. 1985). Death occurred in 11 other cases following ingestion of endrin the time from administration to death ranged from 1 to 6 hours. In cases where endrin ingestion occurred with milk or alcohol, death occurred more rapidly (within 1-2 hours) presumably as the result of enhanced absorption that increased toxicity (Tewari and Sharma 1978). 

Poisoning episodes in humans show that the central nervous system is the primary target system of orally administered endrin. Acute human poisonings by endrin-contaminated food caused symptoms of central nervous system toxicity such as jerking of arms and legs, tonic-clonic contractions, convulsions, and sudden collapse and death (Carbajal-Rodriquez et al. 1990 Coble et al. 1967 Davies and Lewis 1956 Rowley etal. 1987 Waller et al. 1992 Weeks 1967). 

Results of developmental toxicity studies (see Section 2.22.6) in rodents suggest endrin can adversely affect pregnancy outcomes. There was reduced survival of pups in hamsters exposed to a single dose of 5 mg/kg (38% mortality, 3% in untreated controls) during the eighth gestation day (Ottolenghi et al. 

Dermal exposure of rats and rabbits to endrin resulted in toxicity and death (Gaines 1960 Treon et al. 1955), indicating that percutaneous absorption of endrin occurs. It is likely that occupational poisonings reported by Hoogendam et al. (1962, 1965) also involved dermal absorption, but the extent and relative contribution of dermal exposure cannot be determined. Data describing the rate or extent of dermal absorption were not located. 

Anti- and syn-12-hydroxyendrin and 12-ketoendrin are more toxic in the rat than endrin itself. The hydroxyendrins ard rapidly converted to the more toxic 12-ketoendrin, and this latter metabolite is most likely the toxic entity of endrin (Bedford et al. 1975a Hutson et al. 1975). 

A heritable resistance in pine mice to endrin raises the LD50 from 3 mg/kg in sensitive voles to 40 mg/kg in resistant animals (Webb et al. 1973). This trait is correlated with the greater excretion of endrin as the anti-12-hydroxy metabolite in the resistant mice. Associations between lethality and concentration of 12-ketoendrin residues has been made for rats (Hutson et al. 1975), rat fetuses (Kavlock et al. 1981), and hamster fetuses (Chemoff et al. 1979a). Toxicity also occurs when endrin itself appears in the tissues. 

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