Recent findings concerning dose response relationship in mutagenicity testing of chemicals.

Abstract

1. The results of experiments with graduated doses of alkylating agents, antimetabolites and cytotoxic environmental substances in mammalian test systems so far indicate that mutagenic effects like other toxic reactions are dose dependent. 2. In the dominant lethal test system and in in vivo cytogenetic investigations the optimal time of investigation, with regard to the last application, depends on the animal species involved, the type of cell system examined and the substances tested. The mutagenic effect varies according to the sensitivity of the cell system, the cell cycle and the pharmacokinetic behaviour of the substance. 3. The current results of comparative experiments with single administration of large or several applications of smaller doses of mutagenic substances do not answer the question, whether long term studies are necessary in mutagenicity testing.