Acute and repeated dose inhalation studies of alpha-methylstyrene (AMS) were completed. Unlike styrene, AMS did not cause hepatotoxicity in mice at similar (and higher) exposure concentrations. In addition, AMS caused hyaline droplet nephropathy in male rats, whereas this lesion was not caused by styrene. Further characterization of nephropathy was investigated in male and female F344 and male NBR rats exposed to concentrations of AMS up to 500 ppm. Hyaline droplet nephropathy is associated with the presence of 2u-globulin in the kidney; this protein is absent in female F344 and NBR rats. Immunostaining for the protein was positive only in the male F344 rats exposed to AMS. Acute and repeated dose inhalation studies of divinylbenzene (DBV) were conducted in B6C3F1 mice. The nasal cavity and liver were found to be the target organs for DVB in mice and DVB appeared to be more hepatotoxic than styrene. Based upon these results, protocols for 90d and 2 year chronic studies of DVB are being prepared. The genotoxicity of DVB was studied in collaboration with the USEPA. DVB induced dose-dependent increases in sister chromatid exchange that were statistically significant at 50 and 75 ppm. Pharmacokinetic studies will be conducted to evaluate the uptake, distri- bution, and metabolism of DVB in mice and rats during nose-only inhalation exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021136-07
Application #
2574269
Study Section
Special Emphasis Panel (TB)
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1996
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code