Snider Thomas H, McGarry Kevin G, Babin Michael C, Jett David A, Platoff Gennady E, Yeung David T
Battelle, 505 King Avenue, JM-7, Columbus, Ohio 43201-2693, USA.
National Institutes of Health/National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA.
Fundam Toxicol Sci. 2016;3(5):195-204. doi: 10.2131/fts.3.195.
The oral toxicity of phorate oxon (PHO), with emphasis on gender- and age-related effects, was characterized in the Sprague-Dawley rat. The oral LD (95% fiducial limits) for PHO in corn oil was 0.88 (0.79, 1.04) mg/kg in males and 0.55 (0.46, 0.63) mg/kg in females with a probit slope of 15. Females had higher baseline blood cholinesterase titers, but males were significantly more tolerant. Younger rats generally had lower absolute cholinesterase blood titers. However as PHO challenges increased, baseline-normalized cholinesterase inhibition was independent of age and gender. Butyrylcholinesterase (BChE) and especially acetylcholinesterase (AChE) in brains of younger females were affected more than that in either males or older females. In summary, while female rats, especially older females, had higher titers relative to males, female rats were more susceptible in terms of absolute cholinesterase inhibition and 24-hr lethality data, but the differences were not observed when titers were normalized to baseline levels.
在斯普拉格-道利大鼠中对氧乐果的急性经口毒性进行了研究，重点关注性别和年龄相关的影响。氧乐果在玉米油中的经口半数致死剂量（95%可信限），雄性为0.88（0.79，1.04）mg/kg，雌性为0.55（0.46，0.63）mg/kg，其概率单位斜率为15。雌性大鼠的基线血胆碱酯酶滴度较高，但雄性大鼠的耐受性明显更强。年幼大鼠的绝对血胆碱酯酶滴度通常较低。然而，随着氧乐果剂量的增加，以基线水平标准化后的胆碱酯酶抑制率与年龄和性别无关。年幼雌性大鼠脑内的丁酰胆碱酯酶（BChE），尤其是乙酰胆碱酯酶（AChE），比雄性或年长雌性大鼠受到的影响更大。总之，虽然雌性大鼠，尤其是年长雌性大鼠，相对于雄性大鼠具有更高的滴度，但在绝对胆碱酯酶抑制率和24小时致死率数据方面，雌性大鼠更易受到影响，不过当滴度以基线水平进行标准化后，差异并不明显。
