Elevated susceptibility of newborn as compared with young rats to 2-tert-butylphenol and 2,4-di-tert-butylphenol toxicity.
In order to determine the susceptibility of newborn rats to 2-tert-butylphenol (2TBP) and 2,4-di-tert-butylphenol (DTBP) toxicity, studies were conducted with oral administration from postnatal days (PND) 4 to 21 and the findings were compared with results for young rats exposed from 5 or 6 weeks of age for 28 days. In the newborn rats, specific effects on physical and sexual development and reflex ontogeny were not observed. While there were no clear differences in toxicological profiles between newborn and young rats, the no-observed-adverse-effect levels (NOAELs) differed markedly. For 2TBP, clinical signs such as ataxic gait, decrease in locomotor activity and effects on liver, such as increase in organ weight, were observed and the NOAELs were concluded to be 20 and 100 mg/kg/day in newborn and young rats, respectively. Based on hepatic and renal toxicity (histopathological changes and increase in organ weight with blood biochemical changes), the respective NOAELs for DTBP were concluded to be 5 and 20 mg/kg/day. Therefore, the susceptibility of newborn rats to 2TBP and DTBP was found to be 4-5 times higher than that of young rats.
Hirata-Koizumi
Mutsuko
M
Division of Medicinal Safety Science, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan. mkoizumi@nihs.go.jp
Hamamura
Masao
M
Furukawa
Hiromi
H
Fukuda
Naemi
N
Ito
Yoshihiko
Y
Wako
Yumi
Y
Yamashita
Kotaro
K
Takahashi
Mika
M
Kamata
Eiichi
E
Ema
Makoto
M
Hasegawa
Ryuichi
R
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010636:Phenols; C056559:2,4-di-tert-butylphenol; C035406:2-tert-butylphenol