Comparative susceptibility of newborn and young rats to six industrial chemicals.
To elucidate the comparative susceptibility of newborn rats to chemicals, newborn and young animals were administered six industrial chemicals by gavage from postnatal days (PND) 4 to 21, and for 28 days starting at 5-6 weeks of age respectively, under the same experimental conditions as far as possible. As two new toxicity endpoints specific to this comparative analysis, presumed no-observed-adverse-effect-levels (pNOAELs) were estimated based on results of both main and dose-finding studies, and presumed unequivocally toxic levels (pUETLs) were also decided. pNOAELs for newborn and young rats were 40 and 200 for 2-chlorophenol, 100 and 100 for 4-chlorophenol, 30 and 100 for p-(alpha,alpha-dimethylbenzyl) phenol, 100 and 40 for (hydroxyphenyl)methyl phenol, 60 and 12 for trityl chloride, and 100 and 300 mg/kg/day for 1,3,5-trihydroxybenezene, respectively. To determine pUETLs, dose ranges were adopted in several cases because of the limited results of experimental doses. Values for newborn and young rats were thus estimated as 200-250 and 1000 for 2-chlorophenol, 300 and 500 for 4-chlorophenol, 300 and 700-800 for p-(alpha,alpha-dimethylbenzyl) phenol, 140-160 and 1000 for (hydroxyphenyl)methyl phenol, 400-500 and 300 for trityl chloride, and 500 and 1000 mg/kg/day for 1,3,5-trihydroxybenzene, respectively. In most cases, newborn rats were 2-5 times more susceptible than young rats in terms of both the pNOAEL and the pUETL. An exception was that young rats were clearly more susceptible than their newborn counterparts for trityl chloride.
Hasegawa
Ryuichi
R
Division of Medicinal Safety Science, National Institute of Health Sciences, Kamiyoga, Tokyo, Japan. hasegawa@nihs.go.jp
Hirata-Koizumi
Mutsuko
M
Takahashi
Mika
M
Kamata
Eiichi
E
Ema
Makoto
M
D000818:Animals; D000831:Animals, Newborn; D001555:Benzene Derivatives / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002733:Chlorophenols / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D009596:Nitrophenols / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects; D014320:Triphenylmethyl Compounds / Q000633:toxicity
D001555:Benzene Derivatives; D002733:Chlorophenols; D009596:Nitrophenols; D010636:Phenols; D014320:Triphenylmethyl Compounds; C029107:4-chlorophenol; C003723:trityl chloride; C030683:2-chlorophenol