Takahashi Mika, Hirata-Koizumi Mutsuko, Nishimura Nobuo, Ito Yoshihiko, Sunaga Masao, Fujii Sakiko, Kamata Eiichi, Hasegawa Ryuichi, Ema Makoto
National Institute of Health Sciences, Kamiyoga, Tokyo, Japan.
Congenit Anom (Kyoto). 2006 Mar;46(1):26-33. doi: 10.1111/j.1741-4520.2006.00098.x.
Newborn rat studies were conducted with oral administration of 3-ethylphenol (3EP) and 4-ethylphenol (4EP) on postnatal days (PND) 4-21 to allow comparison of no observed adverse effect level (NOAEL) and unequivocally toxic level (UETL) with those from 28-day studies of young rats starting at 5-6 weeks of age. In the newborn rat studies, slightly lowered body weight was observed after 3EP treatment, and deaths, hypoactivity, Straub tail, deep respiration and delayed righting reflex were clearly observed after 4EP treatment. In the young rat studies, salivation, staggering gait, changes in the liver including high values of liver weight and alanine aminotransferase or total cholesterol and the lesions in the forestomach were clearly observed after 3EP and 4EP treatments. NOAELs of 3EP and 4EP in the newborn rat studies appeared to be almost 3 times lower than those in the young rat studies. As a clear toxicity of 3EP was not observed in newborn rats, UETLs were not established for 3EP. Regarding 4EP, UETL of young rats was 4-5 times higher than that of newborn rats. In conclusion, newborn rats were 3-5 times more susceptible to 3EP and 4EP than young rats.
在新生大鼠研究中,于出生后第4至21天经口给予3 - 乙基苯酚(3EP)和4 - 乙基苯酚(4EP),以便将未观察到有害作用水平(NOAEL)和明确毒性水平(UETL)与从5至6周龄开始的幼鼠28天研究中的相应水平进行比较。在新生大鼠研究中,3EP处理后观察到体重略有下降,而4EP处理后明显观察到死亡、活动减退、施特劳布尾、深呼吸和翻正反射延迟。在幼鼠研究中,3EP和4EP处理后均明显观察到流涎、步态蹒跚、肝脏变化(包括肝脏重量、丙氨酸转氨酶或总胆固醇值升高)以及前胃病变。新生大鼠研究中3EP和4EP的NOAEL似乎比幼鼠研究中的低近3倍。由于在新生大鼠中未观察到3EP的明显毒性,因此未确定3EP的UETL。关于4EP,幼鼠的UETL比新生大鼠高4至5倍。总之,新生大鼠对3EP和4EP的易感性比幼鼠高3至5倍。