Hirata-Koizumi Mutsuko, Hamamura Masao, Furukawa Hiromi, Fukuda Naemi, Ito Yoshihiko, Wako Yumi, Yamashita Kotaro, Takahashi Mika, Kamata Eiichi, Ema Makoto, Hasegawa Ryuichi
Division of Medicinal Safety Science, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan.
Congenit Anom (Kyoto). 2005 Dec;45(4):146-53. doi: 10.1111/j.1741-4520.2005.00084.x.
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.
为了确定新生大鼠对2-叔丁基苯酚(2TBP)和2,4-二叔丁基苯酚(DTBP)毒性的易感性,研究人员在出生后第4天至第21天进行了口服给药实验,并将结果与5或6周龄幼鼠暴露28天的结果进行了比较。在新生大鼠中,未观察到对身体和性发育以及反射个体发育的特定影响。虽然新生大鼠和幼鼠的毒理学特征没有明显差异,但未观察到有害作用水平(NOAELs)却有显著差异。对于2TBP,观察到共济失调步态、运动活动减少等临床症状以及肝脏影响,如器官重量增加,新生大鼠和幼鼠的NOAELs分别为20和100毫克/千克/天。基于肝脏和肾脏毒性(组织病理学变化以及器官重量增加伴随血液生化变化),DTBP的相应NOAELs分别为5和20毫克/千克/天。因此,发现新生大鼠对2TBP和DTBP的易感性比幼鼠高4至5倍。