Investigations on the in vitro and in vivo genotoxic potential of 5-vinyl-2-norbornene.

Abstract

5-Vinyl-2-norbornene (VNB: CAS no. 3048-64-4), an industrial chemical that produces hyaline droplet nephropathy in the male rat with associated alpha2u-globulin increases, was investigated in vitro and in vivo for its genotoxic potential. A Salmonella typhimurium reverse mutation assay (strains TA98, 100, 1535, 1537, 1538) was negative both without (dose range 0.003-0.3 mg per plate) and with (0.003-0.3 mg per plate) metabolic activation. A forward gene mutation test in Chinese Hamster Ovary (CHO) cells (HGPRT locus) did not show any significant concentration-related increases in mutation frequencies in the absence (0.01-0.1 mg ml[-1]) or presence (0.005-0.1 mg ml[-1]) of metabolic activation. In a sister chromatid exchange (SCE) test, VNB did not produce statistically significant or dose-related increases in the incidence of SCEs in the absence (0.02-0.06 mg ml[-1]) or presence (0.005-0.03 mg ml[-1]) of metabolic activation. A bone marrow chromosome aberration test was conducted in groups of 10 male and 10 female Sprague-Dawley rats exposed for 6 hr/day for 5 consecutive days to mean (+/- SD) VNB vapor concentrations of 0 (air control), 48.1 +/- 1.29, 146 +/- 9.2, or 336 +/- 8.5 ppm. Marrow was collected 6 and 24 hr after the final exposure. No statistically significant or dose-related increases in chromosomal aberrations occurred in the VNB-exposed animals. 5-Vinyl-2-norbornene did not show any potential for genotoxic activity with this in vitro-in vivo battery of tests.