The proposed research centers about the metabolism and disposition of xenobiotic chemicals in fish. The major goals are to determine the pathways of biotransformation of chlorinated benzenes, pyrethroid insecticides and petroleum hydrocarbons in fish and to determine the extent to which metabolism influences the toxicity and persistence of these chemicals. If biotransformation of these compounds in fish leads to less toxic compounds and the reactions proceed at significant rates, inhibition of their metabolism would be expected to increase toxicity as well as alter residue patterns of the parent compound and metabolites. On the other hand stimulation of metabolism by inducers such as polychlorinated biphenyls and polycyclic aromatic hydrocarbons may decrease toxicity and increase residues of metabolites. The information gleaned from these biotransformation studies may lead to the mechanims of species selectivity of many water borne pollutants in addition to providing data necessary for residue analysis of metabolites of foreign compounds as well as the parent molecule. In general, the experimental approach involves determination of the acute toxicity (LC50) of the above compounds in trout, studying the metabolism of each compound and determining if the toxicity is altered by known inhibitors and inducers of microsomal drug metabolizing enzymes. Special attention will be given to the possibility of alteration of these metabolic processes by inducers and inhibitors which may be present in the aqueous environment.
NIH ExPorter
NIH ExPorter