Metabolic Interactions of Pesticides - Pesticide Biotransformation and Disposition - page 168

CONCLUSIONS
Knowledge of the metabolism of pesticides is essential and further knowledge is still
needed for several reasons, including the development of more selective insecticides
and for providing, in part, the fundamental basis for science-based risk assessments for
human and environmental health. Since multiple exposures tend to be the rule rather
than the exception, knowledge of metabolic interactions is a vital adjunct to the risk
analysis process, one that is still inadequately understood or considered. Until relatively
recently, and as a matter of necessity, this research was carried out almost exclusively
on experimental animals, and the results, particularly in the case of human health risk
assessments, were extrapolated to humans. Although much essential background will
continue to be obtained from experimental animals, because of the new techniques of
molecular biology and the availability of human cells, human cell fractions, and recom-
binant human enzymes, it is now possible to work directly on human biotransforma-
tions and metabolic interactions. Molecular techniques also permit the study of genetic
polymorphisms that will enable us to identify populations at increased risk and enable
studies to be carried out at the level of specific isoforms of the XMEs involved. The
interaction of pesticides and clinical drugs, although long a subject for speculation, has
been the subject of little investigation. The work of Di Consiglio et al. (2005) on the
interaction between imipramine and organophosphorothionates makes it clear that
much more work is needed on this problem.
Thus the study of pesticide metabolism and metabolic interactions of pesticides has
entered a new molecular era that will be fascinating as well as useful.
REFERENCES
Abernathy, C. O., Hodgson, E., & Guthrie, F. E. (1971a). Structure-activity relationships on the induction of
hepatic microsomal enzymes in the mouse by 1,1,1-trichloro-2,2-bis( p -chlorophenyl)ethane (DDT)
analogs. Biochem. Pharmacol. , 20 , 2385-2393.
Abernathy, C. O., Philpot, R. M., Guthrie, F. E., & Hodgson, E. (1971b). Inductive effects of 1,1,1-tri-
chloro-2,2-bis( p -chlorophenyl)ethane (DDT), phenobarbital and benzpyrene on microsomal cyto-
chrome P-450, ethyl isocyanide spectra and metabolism in vivo of zoxazolamine and hexobarbital in
the mouse. Biochem. Pharmacol. , 20 , 2395-2400.
Adams, N. H., Levi, P. E., & Hodgson, E. (1993a). Differences in induction of three P450 isozymes by
piperonyl butoxide, sesamex, safrole, and isosafrole. Pestic. Biochem. Physiol. , 46 , 15-26.
Adams, N. H., Levi, P. E., & Hodgson, E. (1993b). Regulation of cytochrome P450 isozymes by methyl-
enedioxyphenyl compounds. Chem. Biol. Interact. , 86 , 225-274.
Adams, N. H., Levi, P. E., & Hodgson, E. (1995). Regulation of cytochrome P450 isozymes by methylene-
dioxyphenyl compounds—an updated review of the literature. Rev. Biochem. Toxicol. , 11 , 205-222.
Aggeler, P. M., & O'Reilly, R. A. (1969). Effect of heptabarbital on the response to bishydroxycoumarin in
man. J. Lab. Clin. Med. , 74 , 229-238.
Agyeman, A. A., & Sultatos, L. G. (1998). The actions of the H2-blocker cimetidine on the toxicity of the
phosphorothionate insecticide parathion. Toxicology , 128 , 207-218.
Allen, J. W., Wolf, D. C., George, M. H., Hester, S. D., Sun, G. B., Thai, S. F., et al. (2006). Toxicity profiles
in mice treated with hepatotumorigenic and non-hepatotumorigenic triazole conazole fungicides:
Propiconazole, triadimefon and myclobutanil. Toxicol. Pathol. , 34 , 853-862.