of Work:
The aim of these studies is to characterize and compare the toxicokinetics and potential toxicity of inhaled styrene, alpha-methylstyrene (AMS) and divinylbenzene (DVB). Toxicokinetic data for DVB will be utilized to design chronic toxicity and carcinogenicity studies. The toxicokinetic data collected for these three chemicals will be used in developing a PBPK model. Short-term toxicity studies of these three related chemicals have been completed. Based upon these results, protocols for 90d and 2 year chronic studies of styrene DVB were prepared. In toxicity studies, the liver and nasal cavity were found to be the primary target organs for styrene and DVB; AMS was not toxic at comparable exposure concentrations. The liver and nasal cavity were the primary target organs for both DVB and styrene, although DVB was more toxic at considerably lower exposure concentrations. Toxicokinetic studies of styrene and AMs have been completed, and comparable studies of DVB are in progress. Data obtained for the uptake, distribution, and metabolism of DVB and styrene are needed to explain differences in the toxicity and potential carcinogenicity of these chemicals. A PBPK model for these chemicals is being developed and will be useful in helping to predict the toxicity of other epoxide-forming chemicals.
