Isoprene, an endogenous hydrocarbon and industrial chemical, induces multiple organ neoplasia in rodents after 26 weeks of inhalation exposure.
Isoprene, the 2-methyl analogue of 1,3-butadiene, is a high production chemical used largely in the manufacture of synthetic rubber and is the major endogenous hydrocarbon exhaled in human breath. Thirteen-week inhalation toxicology studies of isoprene were conducted in male and female F344 rats and B6C3F1 mice at exposure concentrations of 0, 70, 220, 700, 2200, and 7000 ppm (6 h/day; 5 days/week). In addition, 26-week inhalation studies at the same exposure levels, followed by a 26-week recovery period, were conducted in male rats and mice. The 13-week exposures produced no discernible exposure-related toxic effects in rats. Interstitial cell hyperplasia of the testis was observed in all male rats in the 7000 ppm group after 26 weeks of exposure; following the 26-week recovery period the only effect in rats was a marginal increase in benign testicular interstitial cell tumors. In mice, isoprene induced toxic and carcinogenic effects at multiple organ sites. Following the 26-week exposure and 26-week recovery periods, incidences of neoplastic lesions in the liver, lung, forestomach, and harderian gland were significantly increased. Neoplastic effects were observed at 700 ppm and higher exposures. Non-neoplastic lesions in mice exposed to isoprene included spinal cord degeneration, testicular atrophy, degeneration of the olfactory epithelium, and epithelial hyperplasia of the forestomach. A partial hindlimb paralysis and a nonresponsive macrocytic anemia were also seen in mice. Most of the toxic and carcinogenic effects caused by isoprene, as well as the species' difference in response, had been observed after inhalation exposures to 1,3-butadiene.
Melnick
R L
RL
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Sills
R C
RC
Roycroft
J H
JH
Chou
B J
BJ
Ragan
H A
HA
Miller
R A
RA
D000236:Adenoma / Q000139:chemically induced* / Q000473:pathology; D000280:Administration, Inhalation; D000818:Animals; D002070:Butadienes / Q000008:administration & dosage / Q000633:toxicity*; D002277:Carcinoma / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D006243:Harderian Gland / Q000187:drug effects; D045782:Hemiterpenes; D006965:Hyperplasia / Q000139:chemically induced; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008175:Lung Neoplasms / Q000139:chemically induced; D008297:Male; D051379:Mice; D009378:Neoplasms, Multiple Primary / Q000139:chemically induced* / Q000473:pathology; D010420:Pentanes; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000139:chemically induced; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
D002070:Butadienes; D045782:Hemiterpenes; D010420:Pentanes; C005059:isoprene