Chloroprene and isoprene: cytogenetic studies in mice.
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)
Tice
R R
RR
Medical Department, Brookhaven National Laboratory, Upton, NY 11973.
Boucher
R
R
Luke
C A
CA
Paquette
D E
DE
Melnick
R L
RL
Shelby
M D
MD
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002070:Butadienes / Q000633:toxicity*; D002737:Chloroprene / Q000633:toxicity*; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D045782:Hemiterpenes; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens; D010420:Pentanes; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D002070:Butadienes; D045782:Hemiterpenes; D009153:Mutagens; D010420:Pentanes; C005059:isoprene; D002737:Chloroprene