Difference between species in response to a 3,5‐dichloropyridyloxyphenoxy compound: Induction of cytochrome P‐450 and/or peroxisome proliferation†

In toxicological studies, the test compound FOE 3440 A, a [(3,5‐dichloro‐2‐pyridyl)oxy]phenoxypropanoate with herbicidal properties, produced a severe increase in weight and an intensive induction of monooxygenases activity in the mouse, but not in the rat. Comparative subacute studies were performed with oral administration of 0, 5, 20 and, in some instances, 80 mg kg−1 body weight to mice, rats, hamsters, dogs and rhesus monkeys. Liver enzyme activities were measured. The evaluation of the enzyme activity results showed an unusually severe dose‐related induction of the monooxygenases [7‐ethoxycoumarin‐O‐deethylase (EOD), 7‐ethoxyresorufin‐O‐deethylase (EOR) and aldrin epoxidase (ALD)] in the mouse and a much weaker reaction in the other species tested. This exceptional position of the mouse was also demonstrated in vitro by a cytochrome P‐450 interaction (inhibition of ALD). The primary metabolite of FOE 3440 A produced a distinct inhibition of the ALD in mice liver microsomes. There were no interaction...