The objective of this project is to characterize dose-response relationships and toxicity of isoprene (I), chloroprene (C), and 1,3- butadiene (B) administered by inhalation to rats and mice in 2-wk and 13-wk prechronic (C and I) 13-wk pre-chronic in rats only (B) and 104 wk chronic mouse studies (B). In each study, 10 animals/sex/species/treatment group and control group will be exposed 6 hrs/day, 5 day/wk for 2, 13 or 104 wks. At the end of each study, all animals will be given gross and microscopic evaluation. Hematology, clinical chemistry and urinalysis will be performed during each 2 wk study and 13 wk study with C and I. In addition, in vivo cytogenetics will be performed during each 2 wk study. SMVC athione measurements and neurobehaviorial tests will be made during each 13 wk study. Thirteen week rat and 104 wk mouse B studies will be conducted simultaneously. Hematology will be performed on rats at terminal sacrifice. During the mouse B chronic study groups of animals will be exposed for 2, 13, 26, 40, 65, and 104 wks. Interim sacrifices will be performed at 40 and 65 wks at which time hematology and organ weight measurements will be made. Animals whose exposure stops at 13, 26, and 40 wks will be left to continue until sacrificed at 104 wks. The results of the 13 wk studies will be used by NIP to establish doses to be used in chronic studies. The results of the 2-year study will be used by NTP to determine onset of carcinogenesis with exposure to 1,3-butadiene.
