The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated methyl styrene [25013‐15‐4] considering all toxicological endpoints and revised the maximum concentration at the workplace (MAK value). Publications are described in detail.
In long‐term inhalation studies with methyl styrene, inflammation and hyperplasia were observed in nasal tissue of rats and mice with LOAECs of 100 ml/m3 and 10 ml/m3, respectively. As was shown with styrene, the reason for mice being more susceptible than rats is differences in the rates of phase I and phase II metabolism. While the rate of oxidation to the epoxide is almost the same in rats and mice, the detoxification via epoxide hydrolase and GSH‐transferase is about 10‐fold faster in rats than in mice. In human nasal tissue in vitro, oxidation of styrene is minimal but metabolization via epoxide hydrolase and GSH‐transferase occurs at almost the same rate as in rat nasal tissue. Therefore, humans are much less sensitive to nasal effects of styrene and this species difference is assumed to be the same for the similarly metabolized methyl styrene. The MAK value is derived from the LOAEC in rats and set at 20 ml methyl styrene/m3. Due to the local effect being critical, the substance is assigned to Peak Limitation Category I. As there was no sensory irritation in volunteers with methyl styrene at 50 ml/m3, the excursion factor is 2.
Methyl styrene has a limited genotoxic potential only at systemically toxic doses, and 2‐year carcinogenicity studies were negative.
Dermal absorption does not contribute significantly to the systemic toxicity and investigations in humans and animals do not indicate a significant sensitizing effect.
Because 3 studies on the developmental toxicity of methyl styrene are only available as summaries and the reason for the differing effects cannot be evaluated, methyl styrene is assigned to Pregnancy Risk Group D.