GENOTOXICITY RESEARCH

Styrene is of low concern for potential genotoxic effects.

Genotoxicity studies reported since 1989 reinforce the findings from previous studies that styrene is not mutagenic (i.e. causing DNA mutations), or only very weakly so.

One published literature review concluded that increases in cytogenetic (i.e. cell) 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 (Scott, 1993, Scott and Preston, 1994). Human studies reporting increased chromosomal aberrations must be viewed cautiously, since controlled exposures in rodent studies at concentrations of up to 20 times higher than workplace exposure levels did not result in chromosomal aberrations.

Human Studies

Styrene-exposed workers have been studied extensively over two decades for induction of various types of genotoxic effects. The outcome of these studies have been conflicting. Variable results have been reported with regard to the association between exposure to styrene and chromosomal damage. Increased frequencies of chromosomal aberrations in human body were not reported in most studies and only weak evidence was reported for induction of sister chromatid exchange that reflects predominantly short-term exposure due to repair and cell turnover. A number of different assay types have been used to detect DNA damage. DNA adducts are used primarily as biomarkers of exposure rather than effect, although their levels will be related to individual metabolic processes and DNA repair as well as exposure levels. Although there is some evidence for DNA damage in styrene-exposed workers, the studies have not been consistent, those reported to be positive are not consistently related to exposure levels and the significance of any positive response is unclear. Generally, DNA adducts are indicative of more recent exposure due to DNA repair process and cell turnover. Overall, the evidence to date is that some of the DNA adducts induced by styrene in humans are potentially mutagenic, but it not known whether the level and the lack of accumulation of genotoxic damage over time are sufficient to result in mutations in styrene-exposed workers.

Animal Studies

Equivocal results were obtained from new genotoxicity tests in laboratory animals after exposure to very high doses of styrene causing lethality ( death). A recently published micronucleus test in bone marrow cells of mice conforming to the current OECD guideline clearly showed no effect. In contrast to generally negative clastogenicity data, a consistently small increase in sister chromatid exchanges is seen in animal studies of styrene, but both Scott and Preston (1994) and Bonassi et al.(1996) agreed there was no dose-response increase in sister chromatid exchanges in human studies. In their review, Scott and Preston concluded that there was no evidence to indicate that styrene is clastogenic in animal studies under condition relevant to human exposure (i.e., low inhalation concentrations). Mutagenic effects of styrene can only be expected under extreme exposure conditions if styrene oxide is not efficiently detoxified and primary DNA lesions are not completely repaired. However, there is no clear evidence that styrene induces mutagenic/clastogenic effects in animal studies when tested under appropriate test conditions.

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