Developmental toxicity study of dimethylpiperidone.
The potential maternal and developmental toxicity of dimethylpiperidone (DMPD) was assessed in rats. Groups of 25 mated female Crl:CD (SD)IGS BR rats were exposed by inhalation (whole-body exposures) for approximately six hours per day over days 7-21 of gestation (G); day 1G was the day of copulation plug detection. The exposure levels were 0, 52, 260, or 340 (vapor plus aerosol) mg/m3 DMPD. During the in-life portion, body weights, food consumption, and clinical observation data were collected. On day 22G, the dams were euthanized and examined for gross external and internal alterations. The uterine contents were described and the fetuses were weighed and examined for external, visceral, and skeletal alterations. Maternal toxicity was seen at both 260 and 340 mg/m3. At 340 mg/m3, evidence of maternal toxicity included mortality, increased clinical observations, and decreased body weight and food consumption. At 260 mg/m3, maternal toxicity was limited to increased clinical observations and decreased food consumption. Developmental toxicity was also produced at 260 and 340 mg/m3. At 340 mg/m3, evidence of developmental toxicity included decreased fetal weight, increased embryofetal lethality with concomitant reductions in litter size, and increased fetal malformations and variations. At 260 mg/m3, effects in fetuses were limited to slightly decreased fetal weight and increased fetal variations; additionally, one litter from this level consisted entirely of resorptions. There were no compound-related effects in either dams or fetuses at 52 mg/m3. It was, therefore, concluded that DMPD was not selectively toxic to the rat conceptus.
Munley
Susan M
SM
Haskell Laboratory for Health and Environmental Sciences, E. I. duPont de Nemours and Company, Inc., 1090 Elkton Road, Newark, DE 19714, USA. susan.m.munley@usa.dupont.com
O'Neill
Arthur J
AJ
Tyler
Deborah L
DL
Hurtt
Mark E
ME
Kennedy
Gerald L
GL
D000014:Abnormalities, Drug-Induced / Q000209:etiology* / Q000473:pathology; D000280:Administration, Inhalation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005328:Fetal Viability / Q000187:drug effects; D020567:Fetal Weight / Q000187:drug effects; D019570:Inhalation Exposure; D008098:Litter Size / Q000187:drug effects; D008136:Longevity / Q000187:drug effects; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D010881:Piperidones / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity*
D010881:Piperidones; D012997:Solvents; C491664:dimethylpiperidone