Higher susceptibility of newborn than young rats to 3-methylphenol.
To determine susceptibility of infants to 3-methylphenol, a repeated dose toxicity study was conducted with oral administration to newborn and young rats. In an 18-day newborn study from postnatal days 4 to 21 at doses of 30, 100 and 300 mg/kg/day, various clinical signs including deep respiration, hypersensitivity on handling and tremors under contact stimulus, and depressed body weight gain were observed at 300 mg/kg. At 100 mg/kg, hypersensitivity and tremors were also noted in a small number of males only on single days during the dosing period. No adverse effects were observed in the 30 mg/kg group. There were no abnormalities of physical development, sexual maturation and reflex ontogeny. The no observed adverse effect level (NOAEL) for newborn rats was considered to be 30 mg/kg/day and the unequivocally toxic level 300 mg/kg/day. In a 28-day study starting at 5 weeks of age, clinical signs and depression of body weight gain, as observed in the newborn rats, appeared in both sexes at 1000 mg/kg but not 300 mg/kg. The NOAEL and the unequivocally toxic level were 300 mg/kg/day and 1,000 mg/kg/day, respectively. From these results, newborn rats were concluded to be 3 to 10 times more susceptible to 3-methylphenol than young rats. However, the realistic no adverse effect dose for the newborn must be slightly lower than 100 mg/kg/day, at which the toxicity incidence was very low, rather than 30 mg/kg/day. Based on this speculation and the equal toxicity at unequivocally toxic levels, the differences in the susceptibility to 3-methylphenol could be concluded to be 3 to 4 times. This is consistent with the results of our previous comparative studies on 4-nitrophenol, 2,4-dinitrophenol and 3-aminophenol, which showed 2 to 4 times differences in the susceptibility between newborn and young rats.
Koizumi
Mutsuko
M
National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Noda
Atsushi
A
Ito
Yoshihiko
Y
Furukawa
Masatoshi
M
Fujii
Sakiko
S
Kamata
Eiichi
E
Ema
Makoto
M
Hasegawa
Ryuichi
R
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D003408:Cresols / Q000633:toxicity*; D005260:Female; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
D003408:Cresols; C042041:3-cresol