BIOTRANSFORMATION OF ORGANOPHOSPHORUS COMPOUNDS BY RAINBOW-TROUT (ONCORHYNCHUS-MYKISS) LIVER IN RELATION TO BIOCONCENTRATION

Biotransformation of a series of organophosphorus compounds by the 9,000-g supernatant of rainbow trout (Oncorhynchus mykiss) liver was tested in an in vitro system fortified either with NADPH-generating cofactors or with reduced glutathione (GSH). Elimination rate constants for both systems were calculated from linear decay curves when substrate concentrations were used that were considerably lower than the K(m) values of the concerned enzymatic reactions. The results reveal a large variation in both the oxidative and the glutathione-mediated biotransformation rate of the organophosphorus compounds. Half-lives ranged from 25 to 1,216 min in the NADPH system and from 18 to 381 min in the GSH system. Elimination rate constants in the GSH system were related to Hammett sigma constants or reactivity toward 4-nitrobenzylpyridine, which substantiates the assumption that electrophilicity is the controlling variable for the reaction with GSH within this particular class of compounds. A remarkable analogy was observed between compounds that were metabolized relatively quickly by glutathione S-transferases and compounds that showed a reduced bioconcentration factor in guppies. A significant improvement of the relationship between the bioconcentration factor in guppies and the octanol/water partition coefficient was obtained when the rate constant with GSH was introduced in this relationship. Such an improvement was not obtained with the rate constants from the oxidative system. These observations are discussed in view of the differences in the activities of the involved enzyme systems in the test species and in view of the possible relevance of the different biotransformation pathways for the in vivo situation.