聚β-胡萝卜素聚合物的急性毒性试验、亚慢性毒性试验和致突变性试验

Acute Toxicity Test, Sub-Chronic Toxicity Test and Mutagenicity Test of Poly β-Carotene Polymer

本试验旨在通过小鼠急性毒性试验、大鼠亚慢性毒性试验和小鼠致突变性试验对聚β-胡萝卜素聚合物进行安全性评价。急性毒性试验:将50只昆明小鼠随机分为5组,每组10只。测定聚β-胡萝卜素聚合物的半数致死量(LD_(50))和95%置信区间。亚慢性毒性试验:将80只无特定病原体(SPF)级SD大鼠随机分为4组,每组20只。低、中高剂量组分别灌胃100、250和500 mg/kg BW的聚β-胡萝卜素聚合物,对照组灌胃等体积的植物油,连续灌服30 d。测定大鼠生长性能、血液生理指标、血清生化指标、脏器指数及组织病理学。致突变性试验:将50只昆明小鼠随机分为5组,每组10只。依据本试验得出聚β-胡萝卜素聚合物的LD50,低、中、高剂量组分别灌胃282.5、565.0和1130.0 mg/kg BW的聚β-胡萝卜素聚合物,阴性对照组灌胃等体积的植物油,阳性对照组腹腔注射0.4 mL/kg环磷酰胺。测定嗜多染红细胞/红细胞比值和嗜多染红细胞微核率。结果表明:1)急性毒性试验中,聚β-胡萝卜素聚合物的LD_(50)为2260 mg/kg BW,95%置信区间为2067~2470 mg/kg BW。2)亚慢性毒性试验中,试验期间内大鼠精神食欲等状况良好。与对照组相比,低、中、高剂量组的雄性大鼠和高剂量组的雌性大鼠末重、平均日增重、平均日采食量极显著升高(P<0.01),料重比极显著降低(P<0.01)。中剂量组的雄性大鼠红细胞压积显著低于低剂量组(P<0.05),各组之间大鼠的其他血液生理指标和血清生化指标均无显著差异(P>0.05)。中、高剂量组的雌性大鼠肾脏指数显著低于对照组和低剂量组(P<0.05),各组之间大鼠的脏器重和其他脏器指数均无显著差异(P>0.05)。组织病理学检查表明各组大鼠心脏、肝脏、脾脏、肾脏、肺脏无明显病理变化。3)致突变性试验中,与阴性对照组相比,阳性对照组的雄性、雌性小鼠的嗜多染红细胞微核率极显著增加(P<0.01),低、中、高剂量组的雄性、雌性小鼠的嗜多染红细胞微核率均差异不显著(P>0.05)。由此可见,聚β-胡萝卜素聚合物无明显急性毒性、亚慢性毒性和致突变性。聚β-胡萝卜素聚合物可以提高大鼠的生长性能,可作为一种安全的饲料添加剂进一步开发利用。

This study aimed to evaluate the safety of polyβ-carotene polymer through acute toxicity test in mice,sub-chronic toxicity test in rats and mutagenicity test in mice.Acute toxicity test:50 Kunming(KM)mice were randomly divided into 5 groups with 10 mice in each group.The median lethal dose(LD_(50))and 95%confidence interval of polyβ-carotene polymer were determined.Sub-chronic toxicity test:80 specific pathogen free(SPF)grade SD rats were randomly divided into 4 groups with 20 rats in each group.The low-,medium-and high-dose groups were gavaged with 100,250 and 500 mg/kg BW polyβ-carotene polymer,respectively,and the control group was gavaged with an equal volume of vegetable oil for 30 d.The growth performance,blood physiological indices,serum biochemical indices,organ indices and histopathology of the rats were determined.Mutagenicity test:50 KM mice were randomly divided into 5 groups with 10 mice in each group.Based on the LD_(50) of polyβ-carotene polymer derived from this test,the low-,middle-and high-dose groups were gavaged with 282.5,565.0 and 1130.0 mg/kg BW polyβ-carotene polymer,respectively;the negative control group was gavaged with an equal volume of vegetable oil,and the positive control group was injected intraperitoneally with 0.4 mL/kg cyclophosphamide.The polychromatic erythrocyte/erythrocyte ratio and polychromatic erythrocyte micronucleus rate were determined.The results showed as follows:1)in the acute toxicity test,the LD_(50) of polyβ-carotene polymer was 2260 mg/kg BW,with a 95%confidence interval of 2067 to 2470 mg/kg BW.2)In the sub-chronic toxicity test,the rat’s mental appetite and other conditions during the test period were good.Compared with the control group,the final weight,average daily gain,average daily feed intake of male rats in the low-,medium-and high-dose groups and female rats in the high dose group were significantly increased(P<0.01),and the feed to gain ratio was significantly decreased(P<0.01).The hematocrit of male rats in the medium-dose group was significantly lower than that in the low-dose group(P<0.05),and there were no significant differences in other blood physiological and serum biochemical indices of rats among all groups(P>0.05).The kidney index of female rats in middle-and high-dose groups was significantly lower than that in control and low-dose groups(P<0.05),and there was no significant difference in organ weight and other organ indices of rats among all groups(P>0.05).Histopathological examination showed that there were no obvious pathological changes in the heart,liver,spleen,kidney and lungs of rats among all groups.3)In the mutagenicity test,compared with the negative control group,the polychromatic erythrocyte micronucleus rate of male and female rats in the positive control group was significant increased(P<0.01),and the polychromatic erythrocyte micronucleus rate of male and female rats in low-,medium-and high-dose groups were no significant difference(P>0.05).In conclusion,the polyβ-carotene polymer has no obvious acute toxicity,sub-chronic toxicity and mutagenicity.The polyβ-carotene polymer can improve the growth performance of rats,and can be further developed and utilized as a safe feed additive.