Mammals pesticide metabolism

Hodgson, E., and Philpot, R. M. Interaction of methylenedioxyphenyl (1,3-benzodioxole) compounds with enzymes and their effects on mammals. Drug Metab. Rev. 3, 231,1974. Hodgson, E. Induction and inhibition of pesticide-metabolizing enzymes Roles in synergism of pesticides and pesticide action. Toxicol. Ind. Health 15, 6,1999. 

We must always recognize that pesticide metabolism studies cannot be considered as an end in themselves but rather, they are a means toward an end. For the ultimate value of a metabolism study, be it in microorganisms, plants, birds, laboratory mammals, or v atever, is its yield of data valuable toward further assessment of the toxicological significance of the pesticide in question to lower organisms (i.e., its environmental impact) or, more importantly, to assess toxicological significance to man himself. 

Chadwick, R.W., Copeland, M.R. and Chadwick, C.J. (1978). Enhanced pesticide metabolism - A previously unreported effect of dietary fibre in mammals. Food Cosmet. Toxicol. 16, 217-225. 

So far, metabolic studies of about 30 synthetic pyrethroids, including their chiral and geometrical isomers, have been carried out in mammals [1], However, detailed metabolism data have not necessarily all been published in scientific journals. In some cases, the reports of joint World Health Organization-Food and Agricultural Organization (WHO/FAO) expert meetings on pesticide residues and the... 

Hodgson E, Kulkarni AP, Fabacher DL, et al. 1980. Induction of hepatic drug metabolizing enzymes in mammals by pesticides A review. J Environ Sci Health B 15(6) 723-754. 

More than 130 years ago, Keller (1 ) reported the isolation of hippuric acid (benzoylglycine) from the urine of horses fed pure benzoic acid and so ushered in our modern era of metabolism investigations on xenobiotics (foreign substances in the environment). In addition to the valuable basic knowledge of the biological processes of terrestrial animals provided by such studies, the advent of regulations controlling the use of pesticides stimulated research on the disposition of these chemicals by both mammals and insects (2). 

Chlordane was introduced as an insecticide in 1945 and was the first cyclodiene insecticide that was used in agriculture (Eisler, 1990). It was the second most important organochlorine pesticide after toxaphene from 1976 to 1977 (Stansley Roscoe, 1999). It has been used on agricultural crops and extensively in the control of termites (Smith, 1991). Chlordane and heptachlor can be metabolized into two persistent (oxygenated) epoxides—oxychlordane and heptachlor epoxide—in mammals (Nomeir Hajjar, 1987) such that the two compounds are always measured together with chlordane and heptachlor. 

There are occasions in which death is undoubtedly due to a pesticide, and yet the chemical analysis fails to reveal its presence or shows only insignificant traces. This may be due to the rapid metabolic conversion of the particular pesticide. This is the case with parathion which is rapidly converted to para-nitrophenol due to in vivo hydrolysis. Pesticides, especially those that are comparatively less toxic to mammals, such as dichlorovos, etc, may be excreted rapidly and, therefore, may perhaps be found in the urine, though not in the tissues. 

Because oceans serve as a sink for chlorinated pesticides and CACs, marine mammals and piscivorous birds are consuming relatively high amounts of these compounds, whereas they have a relatively low capacity for metabolism. As a result, they may constitute the most vulnerable organisms with regard to longterm toxicity.14 Over 90% of the whole body burden of marine mammals may be present in their blubber.14... 

Figure 8.26 Metabolic pathways of diazinon in mammals and insects. (Redrawn from Aizawa, H., Metabolic Maps of Pesticides, Academic Press, New York, 1982.)...

Figure 9.11 Metabolism of malathion in insects and mammals. Source Hassal, K.A., The Biochemistry and Uses of Pesticides, 2nd ed., VCH Publisher, New York, 1990. With permission.

Dimethoate is rapidly absorbed after any route of administration in mammals. It is rapidly metabolized in the liver. Like other phosphorothionate pesticides, the parent compound is activated by cyp450 to... 

Pharmaca designed to be resistant to metabolic and especially oxidative attack could be potential persistent environmental pollutants. Since, however, the biological degrading capacity of the water and soil microflora is highly differentiated, compounds stable enough to avoid biotoxification in mammals and other animals may still be sufficiently vulnerable to microbiological attack. Moreover, in the case of therapeutics, food additives and selective, e.g. pheromone-derived pesticides only relatively small quantities of substance are involved. 

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... 

---