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目的研究四乙酰基六氮杂异伍兹烷(TAIW)的大鼠经口亚慢毒性,为六硝基六氮杂异伍兹烷(CL-20)的职业人员健康防护提供实验资料。方法将80只SPF级成年SD大鼠随机分为4组,每组20只,雌雄各半。采用饲喂法染毒,将TAIW混入饲料,低、中、高剂量组剂量分别为111、333、1 000 mg/kg,对照组给予常规饲料喂养。连续90 d后,采集尿液、血液,进行常规及生化分析;同时观察脏器指数和组织病理。结果 3个染毒组中,雄性大鼠血小板分布宽度(PDW)、大血小板比率(P-LCR)、平均血小板体积(MPV)、红细胞分布宽度-变异系数(RDW-CV)、平均红细胞体积(MCV)、胆碱脂酶(CHE)及雌性大鼠血小板压积(PCT)、PDW、P-LCR、MPV、尿酸(UA)、胆固醇(CHOL)均明显低于对照组(P<0.05);雄性大鼠平均红细胞血红蛋白浓度(MCHC)、肌酸激酶(CK)、乳酸脱氢酶(LDH)均明显高于对照组(P<0.05)。其余指标各组间差异不明显(P>0.05)。病理组织学检查结果显示,染毒剂量达到333mg/kg时,雌、雄性大鼠多个脏器均出现不同程度炎细胞浸润、充血水肿等病变。结论 TAIW大鼠亚慢性经口毒性试验的最大无作用剂量为111 mg/kg。
Objective To study the oral sub-chronic toxicity of tetraacetylhexaazaisowurtzitane (TAIW) in rats, and provide experimental data for the health protection of occupational personnel of hexanitrohexaazaisowurtzitane (CL-20). Methods Eighty adult Sprague-Dawley (SD) adult Sprague-Dawley rats were randomly divided into 4 groups with 20 rats in each group. TAIW was mixed with feed by feeding method. The doses of low, middle and high dose group were 111, 333, and 1000 mg / kg, respectively. The control group was fed with conventional feed. After 90 consecutive days, urine and blood were collected for routine and biochemical analysis; meanwhile, organ index and histopathology were observed. Results The PDW, P-LCR, MPV, RDW-CV, and mean erythrocyte volume MCV, CHE and PCT, PDW, P - LCR, MPV, UA and CHOL of female rats were significantly lower than those of the control group (P <0.05). The mean RBC hemoglobin concentration (MCHC), creatine kinase (CK) and lactate dehydrogenase (LDH) of male rats were significantly higher than those of the control group (P <0.05). The remaining indicators of the differences between groups was not significant (P> 0.05). Histopathological examination showed that the number of inflammatory cells infiltration, congestion and edema and other pathological changes were observed in multiple organs of female and male rats when the dose reached 333mg / kg. Conclusions The maximum non-acting dose of sub-chronic oral toxicity test in TAIW rats is 111 mg / kg.