Dose-response of promotion by polychlorinated biphenyls and chloroform in rat liver foci bioassay

Using the rat liver foci bioassay a dose-response relationship was evaluated for the promoting activity of the ubiquitous and persistent environmental pollutants polychlorinated biphenyls (PCBs) and chloroform. Initiation of liver foci was performed by oral administration of a single dose of 8 mg/kg body wt of diethylnitrosamine to weanling female Sprague-Dawley rats. For polychlorinated biphenyls (PCBs) and chloroform a dose-dependent promoting effect was found. The lowest effective dose of PCBs was 1 mg/kg body wt, given three times a week for 11 concecutive weeks. That of chloroform was 100 mg/kg body wt, administered twice a week for 11 consecutive weeks. The livers were screened for preneoplastic foci 12 weeks after starting the experiments. The amounts of PCBs as well as chloroform normally taken up by humans are greater than a factor of 1000 lower than the effective experimental doses. Thus the risk of human exposure to these chemicals is estimated to be very low. In the case of heavy pollution with PCBs, however, as happened in the Yusho accident (Japan, 1968), the daily intake of PCBs was in the range of the effective doses used in the experiment.Dedicated to Professor Dr. med. Herbert Remmer on the occasion of his 65th birthdaySupported by Grant UBA 106 04 017 from the Umweltbundesamt, Berlin