title: Inhalation developmental toxicity and reproduction studies with cyclohexane.
abstract: The reproductive and developmental toxicity of cyclohexane was assessed in a two-generation reproduction study with Crl:CD BR rats and in developmental toxicity studies with Crl:CD BR rats and Hra:(NZW)SPF rabbits. The animals were exposed whole-body to atmospheric concentrations of 0, 500, 2000, or 7000 ppm cyclohexane. In the two-generation reproduction study, parental effects included statistically significantly lower mean body weight, overall mean body weight gain, and overall mean food efficiency for P1 and F1 females of the 7000 ppm level and statistically significantly lower mean body weight for F1 males of that level. Adult rats exposed to 2000 ppm cyclohexane and above exhibited a transient diminished or absent response to a sound stimulus while in the chambers during exposure. Mean pup weight was statistically significantly lower than control from lactation day 7 throughout the remainder of the 25-day lactation period for both F1 and F2 7000 ppm litters. Changes observed at 500 ppm were either considered not to be compound related or not adverse. Therefore, the systemic-toxicity no-observed-effect level (NOEL) was 500 ppm and the reproductive NOEL was 2000 ppm. The reproductive NOEL was based solely on the decreased pup weights in both the F1 and F2 generations observed at 7000 ppm. In the developmental toxicity studies, only the rats showed evidence of maternal toxicity. For rats in the 7000 ppm group, statistically significant reductions were observed in overall maternal body weight gain and overall maternal food consumption for the treatment period. Rats exposed to 2000 ppm cyclohexane and above again exhibited a transient diminished or absent response to a sound stimulus while in the chambers during exposure. Therefore, for rats, the maternal no-observed-effect level (NOEL) was 500 ppm. In the rabbit developmental toxicity study, no compound-related maternal effects were observed at concentration levels of 7000 ppm and below. Therefore, the maternal NOEL for rabbits was 7000 ppm. No compound-related evidence of developmental toxicity was observed at any test concentration in either species. Therefore, the developmental NOEL for both species was 7000 ppm, the highest concentration tested.
authors.affiliation: The DuPont Company, Haskell Laboratory for Toxicology and Industrial Medicine, Newark, DE 19714, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Kreckmann
authors.forename: J K
authors.initials: JK
authors.lastname: Baldwin
authors.forename: L G
authors.initials: LG
authors.lastname: Roberts
authors.forename: R J
authors.initials: RJ
authors.lastname: Staab
authors.forename: D P
authors.initials: DP
authors.lastname: Kelly
authors.forename: J E
authors.initials: JE
authors.lastname: Saik
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects*; D003510:Cyclohexanes / Q000633:toxicity*; D005260:Female; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D018811:Maternal Exposure; D019055:No-Observed-Adverse-Effect Level; D018812:Paternal Exposure; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D014481:United States; D014484:United States Environmental Protection Agency
chemical_list: D003510:Cyclohexanes