Chloroprene and isoprene: cytogenetic studies in mice

Abstract

Groups of male B6C3F1 mice (n = 15) were exposed for 6 h per day to ambient air, to chloroprene (12, 32, 80, 200 p.p.m.) or to isoprene (438, 1750 and 7000 p.p.m.) on 12 days. These compounds are the 2-chloro and the 2-methyl analogues, respectively, of 1,3-butadiene, a genotoxic and carcinogenic chemical in B6C3F1 mice. Exposure to chloroprene resulted in a 100% incidence of mortality among the mice exposed to 200 p.p.m. At concentrations of 80 p.p.m. and below, chloroprene neither induced a significant increase in chromosomal aberrations (CA), sister chromatid exchanges (SCE) or micronucleated erythrocytes, nor significantly altered the rate of erythropoiesis or of bone marrow cellular proliferation kinetics. However, the mitotic index (MI) in the bone marrow of chloroprene-exposed mice was significantly increased. Under similar conditions, exposure to isoprene induced significant increases at all concentrations in the frequency of SCE in bone marrow cells and in the levels of micronucleated polychromatic erythrocytes (PCE) and of micronucleated normochromatic erythrocytes in peripheral blood. In addition, a significant lengthening of the bone marrow average generation time and a significant decrease in the percentage of circulating PCE was detected. However, exposure to isoprene did not induce in bone marrow a significant increase in the frequency of CA nor did the exposure significantly alter the MI. The dose-response curves for SCE and micronuclei induction were non-linear, appearing to saturate at 438 and 1750 p.p.m., respectively. These results suggest that, similarly to butadiene, inhaled isoprene can be expected to induce tumors at multiple sites in B6C3F1 mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Results of NTP-Sponsored Mouse Cytogenetic Studies on 1,3-Butadiene, Isoprene, and Chloroprene

“…Isoprene was investigated in a 12-day exposure regimen using the same end points, route of exposure and species, strain, and sex of animals (9). Concentrations tested were 0, 438, 1750, and 7000 ppm.…”

“…The other cytogenetic end point scored, MN-PCE, was not elevated at 70 or 220 ppm but at 700 ppm they gave a value that was intermediate between the 438-and 1750-ppm Chloroprene was investigated in similar experiments (9). Twelve-day exposures at 0, 12, 32, 80, and 200 ppm were administered to male B6C3F1 male mice; 200 ppm was lethal to all exposed animals.…”

“…Results of these NTP-sponsored studies have been published (7)(8)(9), and the present paper summarizes those study results.…”

Inhalation Toxicology of Isoprene in F344 Rats and B6C3F 1 Mice Following Two-Week Exposures

“…Both compounds induce increases in the frequency of sister chromatid exchanges in bone marrow cells and in the levels of micronucleated erythrocytes in peripheral blood of mice (7,18); both compounds can be metabolized to monoepoxide and diepoxide intermediates by liver microsomal monooxygenases (8,9,19,20), the diepoxide intermediates of both compounds are mutagenic in Salmonella (10,21); both compounds cause reductions in red blood cell counts, hemoglobin concentrations, and volume of packed red cells in mice; and both compounds produced olfactory epithelial changes, testicular atrophy, and forestomach epithelial hyperplasia in mice. Due to these similarities, 13- exposure studies of isoprene at concentrations ranging from 70 to 7000 ppm have been initiated in F344 rats and B6C3F1 mice to determine whether isoprene acts similar to 1,3-butadiene after longer exposure durations.…”

Micronucleus Test from Free Living Rodents as a Biomarker for Environmental Stressin Situ

“…The in vivo micronucleus (MN) has been widely used as a cytogenetic test to detect environmental mutagens and has been utilized on wild rodents since 1978 (6,7,8,19,24). Significant correlations between heavy metal contamination and MN have been detected in wild rodents leaving in polluted areas (14,15,22,26).…”