Subchronic inhalation toxicity of ethylbenzene in mice, rats, and rabbits

Mice, rats, and rabbits (five/sex/group) were exposed by inhalation to ethylbenzene (EB) vapors for 6 hr/day, 5 days/week for 4 weeks (20 exposures). Rats and mice received 0, 99, 382, or 782 ppm EB while rabbits received 0, 382, 782, or 1610 ppm. No changes were evident in mortality patterns, clinical chemistries, urinalyses, or treatment-related gross/microscopic (including ophthalmologic) lesions. Rats exhibited sporadic lacrimation and salivation, as well as significantly increased liver weights at 382 and 782 ppm, and small increases in leukocyte counts at 782 ppm. Males at this exposure level also showed marginal elevations in platelet counts. In mice, females showed statistically increased absolute and relative liver weights at 382 and 782 ppm, while males had statistically increased relative liver-to-brain weight ratios only at 782 ppm. Female rabbits at the high exposure level of 1610 ppm gained weight more slowly than controls (not statistically significant); males showed a similar transient downward trend after 1 week, but showed no differences from controls at study's end. A no observed adverse effect level (NOAEL) of 382 ppm appears appropriate for rats and mice with a lowest observed adverse effect level (LOAEL) of 782 ppm. A NOAEL of 782 ppm and LOAEL of 1610 ppm are appropriate for rabbits.