COMPARISON OF THE PHARMACOKINETICS OF SEVERAL POLYCHLORINATED-BIPHENYLS IN MOUSE, RAT, DOG, AND MONKEY BY MEANS OF A PHYSIOLOGICAL PHARMACOKINETIC MODEL

  • 1 January 1984
    • journal article
    • research article
    • Vol. 12  (5) , 527-535
Abstract
Physiologic pharmacokinetic analysis of 4,4''-dichlorobiphenyl, 2,2'',3,3'',6,6''-hexachlorobiphenyl and 2,2'',4,4'',5,5''-hexachlorobiphenyl is presented for the dog and monkey, and the results are compared with previous similar analyses for the rat and mouse. The normalized clearances (ml/min per kg body wt) vary considerably between the dog and the monkey; the rat and the mouse show less species variation. The equilibrium tissue-to-blood distribution ratios for parent and metabolite are generally similar for all 4 species. The fat compartment has the highest parent distribution ratio for all 4 species, and the metabolite distribution ratios are much smaller than the parent distribution ratios. Metabolism appears to be a prerequisite to urinary and biliary excretion for all 3 compounds in each species. Elimination from the body occurs predominantly by the fecal route. The 2,2'',4,4'',5,5''-hexachlorobiphenyl is more slowly metabolized than the 2,2,3,3'',6,6''-isomer in all species, which supports the contention that 2 adjacent, unsubstituted carbon atoms on the biphenyl ring promote more rapid metabolism.