Vertebrates, pesticide metabolism

Many pesticides cause endocrine disruption in vertebrate and invertebrate species at concentrations that are not overtly metabolically toxic. The insect growth inhibitor diflubenzuron can affect the reproduction, development and behaviour of estuarine crustaceans at concentrations of just lOmgP (reviewed... 

Walker, C.H. (1981). The correlation between in vivo and in vitro metabolism of pesticides in vertebrates. Progress in Pesticide Biochemistry 1, 247-286. 

Modification of the Toxicity of Pesticides with Formulation Additives. Potentially the use of additives to modulate the toxicity of pesticides could lead to a considerable increase in their safety to non-target species, man included. This concept has been well explored and exploited in adding safeners to certain herbicides such as the thiocarbamates. These compounds stimulate defensive metabolic reactions in the crop species but not in weeds This principle has also been applied to vertebrates, but only to a very limited degree. Under some circumstances the thiocarbamate rice herbicide, molinate, may show toxicity to carp in nearby ponds. Based on a knowledge of the safeners that are active in plants, a compound was discovered that, when applied with molinate, acted as an antidote/safener for the carp (20). Little effort, either theoretical or empirical, seems to have gone into developing other such examples. 

The extreme difference in toxicity toward mammals for equally potent pesticidal carbamates is striking. The difference is at least partly due to the difference in cholinesterase sensitivity, but in some cases, metabolism is important. Carbosulfan must be transformed to carbofuran in order to become an active cholinesterase inhibitor — a conversion that does not occur in vertebrates. Aldicarb is extremely poisonous and stable. It can be activated... 

Once OPs enter the body, they are mainly metabolized in the liver, gastrointestinal tract, malpighian tubulc.s, and body fat by mixed function oxida.ses, which further increase their toxicity. Oxidative desulfuration of OPs leads to maximum anticholincstera,se activity. To consider the possible toxic effect of OPs, it is necessary to take into account the type of chemical and the species in question because there are wide differences. For example, in vertebrates, after one. single exposure to OP pesticides the recovery time from the amicholincsicrase effecl-s ranges from I to 3 weeks, whereas only approximately 1 day is necessary to recover from exposure to a CM pesticide. Birds and mammals have similar metabolic responses to anticholinesterase pesticides. However, birds tend to be more sensitive to their toxic action, probably due to lower levels of metabolizing enzymes. 

In fact, the differences in metabolism and physiological conditions between different species may result in some chemicals being harmless to certain vertebrates, but toxic or highly toxic to others (this made possible the development of selective pesticides, which can kill chosen pests selectively while being relatively harmless to the operator and to other animals likely to be in contact with them, e.g., norbormide, a heterocyclic nitrogen compound which is extremely poisonous to rats but has negligibly low toxicity to humans and domestic animals). 

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