Results from new chromosome studies in laboratory animals, comparative investigations of styrene metabolism and pharmacokinetics in humans and animals, and several recent cytogenetic surveys of styrene-exposed workers have necessitated a comprehensive re-evaluation of the chromosome-damaging effects of this chemical. Both styrene and its genotoxic metabolite, styrene oxide, can induce chromosome aberrations (CA) and sister chromatid exchanges (SCE) in vitro, but the chromosome-damaging ability of styrene is only manifested if test conditions favour its metabolic activation over inactivation. There is no convincing evidence of styrene clastogenicity in experimental animals. Styrene oxide is clastogenic only at lethal concentrations via i.p. injection in Chinese hamsters (but not via inhalation) or after oral treatment of mice, a route considered inappropriate for investigating the chromosome-damaging potential of inhaled styrene in man. Styrene and styrene oxide can induce SCE in animals at very high concentrations. Eighteen of 52 cytogenetic studies (CA, micronuclei, SCE) on peripheral blood lymphocytes of styrene workers have reported increases in chromosome damage. The positive findings are not compatible with the conclusion that styrene is responsible for the cytogenetic effects for the following reasons. (a) The positive or negative outcome of the various investigations bears no relationship to the degree of exposure of the workers. (b) There is no convincing evidence of a positive dose response relationship. (c) The relative induction of CA and SCE in worker studies are the opposite of observations of styrene effects in cultured lymphocytes and in laboratory animals. (d) The reports of chromosome-type exchanges in some studies of styrene workers is inconsistent with observations of styrene clastogenicity in cultured lymphocytes. (e) Reports of SCE induction in workers exposed to low concentrations of styrene are not compatible with results of animal inhalation studies, particularly in view of the differences in styrene metabolism and pharmacokinetics between humans and rodents. The increases in cytogenetic effects reported in some studies on styrene workers are probably attributable to the presence of other chromosome-damaging agents in the workplace and/or to inadequate investigations.
