Add time:07/26/2019         Source:sciencedirect.com

4-N-Pyrrolidinylazobenzene (4N) has been described sequentially as a potential rat hepatocarcinogen, a non-hepatocarcinogen to the rat, a possible pure initiating agent to the rat liver and as unlikely to be either a rat hepatocarcinogen or a cancer initiating agent. Given the importance of defining a pure initiating agent to the rodent liver we have conducted experiments to evaluate the status of 4N in this respect. By histopathological criteria 4N is non-hepatotoxic to the rat liver following daily oral gavage for 6 weeks, but it can be detected unbound in the rat liver following a single exposure via oral gavage and methaemoglobin is evident in peripheral blood. In addition, it fails to bind covalently to hepato-proteins or to initiate unscheduled DNA synthesis in the rat liver following oral dosing. Under similar conditions of bioassay, the rat liver carcinogen 3′-methyl-4-dimethylaminoazobenzene (3′M) gave a positive response on each count. Further, no evidence of histopathological change was observed in the rat liver following daily intraperitoneal injection of 4N for 2 weeks. It is concluded that 4N is both non-toxic and non-genotoxic to the rodent liver in vivo in all respects studied, and that it is therefore very unlikely to possess cancer initiating activity in this tissue.

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