HIGHER SUSCEPTIBILITY OF NEWBORN THAN YOUNG RATS TO 3-METHYLPHENOL

• Published in: Journal of toxicological sciences 2003, Vol.28(2), pp.59-70
• Main Authors: KOIZUMI, Mutsuko, NODA, Atsushi, ITO, Yoshihiko, FURUKAWA, Masatoshi, FUJII, Sakiko, KAMATA, Eiichi, EMA, Makoto, HASEGAWA, Ryuichi
• Format: Article
• Language: English
• Subjects: 3-Methylphenol; Aging - physiology; Animals; Animals, Newborn - physiology; Blood Chemical Analysis; Body Weight - drug effects; Cresols - toxicity; Female; Male; No-Observed-Adverse-Effect Level; Organ Size - drug effects; Pregnancy; Rats; Rats, Sprague-Dawley; Sex Characteristics; Toxicity in newborn rats
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.28.59

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.