Mammals cyclodiene toxicity

Some data on cyclodiene toxicity is presented in Table 5.9. Aldrin and dieldrin have similar levels of acute toxicity indeed, the toxicity of aldrin has been largely attributed to its stable metabolite, dieldrin. Dieldrin is highly toxic to fish, mammals. 

In the mid-1960s we showed firstly that the natural tolerance of houseflies to cyclodienes resulted mainly from oxidative detoxication (33 55) and secondly that another enzyme system, epoxide hydrase, converted certain dieldrin analogues into the corresponding trans-diols, (56,57) Interspecific differences in ability to attack enzymatically the unchlorinated ring systems of various analogues, either oxidatively and/or hydratively (if appropriate) can confer selective toxicity between insect species and also between insects and mammals (58) ... 

The major inhibitory neurotransmitter in invertebrates is Y-aminobutyric acid (GABA). Inhibitory neurones are found both in the CNS and at the neuromuscular junction in invertebrates (1), whereas they are not found at the neuromuscular junction in mammals. The widespread distribution of GABA-ergic neurones in insects is probably partly responsible for the selective toxicity towards insects of certain commercial insecticides, e.g., cyclodienes (2-41. avermectin (5), and perhaps some pyrethroids ( ). 

One important group of insecticides, the avermectins, works differently by being agonists and not antagonists as the other, acting on the chloride channels. The avermectins are produced by Streptomyces avermitilies. The binding site is different, and cross-resistance to fipronil, the cyclodienes, and lindane does not seem to occur. The toxic symptoms in insects and mammals are different. Mammals poisoned with avermectins exhibit hyperexcitability, incoordination, and tremor followed by ataxia and paralysis. In insects and nematodes, the hyperexcitation phase is absent. Their symptoms are... 

DDT was first synthesized in 1874 and its insecticidal properties discovered in 1939. Technical DDT is a stable, white, amorphous powder composed of up to 14 analogs and isomers. In 1942, hexachlorocyclohexane (benzene hexachloride) was discovered to be an effective and simple insecticide. Of its isomers, y-HCH has the greatest insecticidal activity and is marketed as lindane, whereas a-HCH and )3-HCH are more toxic to mammals. Chlordane, a mixture of terpenoid compounds, was discovered in 1945 to be a highly effective residual insecticide. In 1948, the most active principle of chlordane, termed heptachlor, was developed, along with two other cyclodiene derivatives, aldrin and dieldrin. It has been subsequently shown that microbial conversion of heptachlor in the environment yields heptachlor epoxide, which exhibits toxicity equal to or greater than that of the parent compound whereas photochemical conversion yields the equally toxic photoheptachlor. Also during 1948, a product obtained by the chlorination of turpentine and containing a considerable number of chlorinated camphenes was sold as toxaphene. 

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