Subchronic Oral Toxicity Evaluation of Lanthanum： A 90-day, Repeated Dose Study in Rats

Objective The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level（NOAEL）,which is a critical factor in the establishment of an acceptable dietary intake（ADI）.Methods In accordance with the Organization for Economic Co-operation and Development（OECD） testing guidelines,lanthanum nitrate was administered once daily by gavage to Sprague-Dawley（SD） rats at dose levels of 0,1.5,6.0,24.0,and 144.0 mg/kg body weight（BW） per day for 90 days,followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control groups.Outcome parameters were mortality,clinical symptoms,body and organ weights,serum chemistry,and food consumption,as well as ophthalmic,urinary,hematologic,and histopathologic indicators.The benchmark dose（BMD） approach was applied to estimate a point of departure for the hazard risk assessment of lanthanum.Results Significant decreases were found in the 144.0 mg/kg BW group in the growth index,including body weight,organ weights,and food consumption.This study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per day.Importantly,the 95% lower confidence value of the benchmark dose（BMDL） was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in males.Conclusion The present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements（REEs）.

Subchronic Oral Toxicity Evaluation of Sodium Dehydroacetate: A 90-day Repeated Dose Study in Rats

Objective The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate(DHA-Na)and to determine the point of departure(POD),which is a critical factor in the establishment of an acceptable dietary intake.Methods DHA-Na was administered once daily by gavage to Sprague–Dawley rats at dose levels of 0.0,31.0,62.0,and 124.0 mg/kg BW per day for 90 days,followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups.The outcome parameters were mortality,clinical observations,body weights,food consumption,hematology and clinical biochemistry,endocrine hormone levels,and ophthalmic,urinary,and histopathologic indicators.The benchmark dose(BMD)approach was applied to estimate the POD.Results Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate,whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group.Importantly,the 95%lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight.Conclusion The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels(62.0 and 124.0 mg/kg BW)after a 90-day oral exposure.

DL-丙氨酸的急性经口毒性和28天经口毒性研究

目的通过DL-丙氨酸的急性经口毒性和28 d经口毒性试验研究,初步判断DL-丙氨酸作为食品添加剂的安全性。方法分别按照国标的GB 15193.3-2014和GB 15193.22-2014方法来进行急性经口毒性试验和28 d经口毒性试验,然后将大鼠的各项数据进行对比分析。结果急性经口毒性试验中无毒作用表现,雌雄大鼠的经口LD50>10000 mg/(kg BW)。28 d经口试验中大鼠一般状况正常,期末体重增长、进食量、食物利用率等指标未发现明显的改变;血常规、凝血、血生化及尿常规等指标均未发现有意义的异常改变;雄性高剂量组肾脏系数与对照组相比差异有统计学意义(P<0.05),各剂量组间具有剂量-反应关系,其他未见异常情况;病理学检查未见与受试物有关的病理性改变。结论 DL-丙氨酸在本研究中未见毒性作用,但长期食用的安全性尚需进一步研究。

Acute and 28-day repeated oral toxicological evaluation of Kuruthi Azhal Chooranam-a Siddha preparation on rodents

Objective:To determine the effect of phytochemicals in acute and repeated dose of 28-day oral toxicity of Kuruthi Azhal Chooranam(KAC)in Sprague Dawley rats of both sexes.Methods:Acute oral toxicity was conducted with 2000 mg/kg body weight of KAC orally and the treated animals were observed for signs of toxicity at 30 min,1,2,4 and 24 h and for up to 14 days.In repeated 28-day oral toxicity study,the KAC formulation was administered orally with 600,900 and 1200 mg/kg body weight/day to all the three groups of rats.The animals were observed for clinical signs of toxicity,mortality and morbidity throughout the study.Also body weight,feed consumption,haematological,plasma biochemistry and serum electrolytes,gross pathology,weights of the organ and histology were studied for no-observed-adverse-effect level.High dose of KAC formulation and control reversal groups were also included for delayed toxic effects determination.Results:In the acute toxicity study of KAC formulation,2000 mg/kg body weight dose exhibited no toxic signs and mortality during study.In sub-acute 28-day repeated dose toxicity study,there was no significant difference found between control and KAC treated groups(body weight,haematology,biochemistry and serum electrolytes).No abnormalities was found in gross pathology,organs weight and histological observation after KAC treatment.Conclusions:The current study suggests that LD_(50)of KAC was>2000 mg/kg and no-observed-adverse-effect level was>1200 mg/kg/day in rats.KAC could be used as Siddha drug for various indications.

苦荞醋饮的安全性初步研究

目的:研究药食两用物质苦荞发酵而成的苦荞醋饮有无急性经口毒性和亚急性经口毒性,为安全的食品提供动物实验依据。方法:在急性经口毒性试验中,剂量组灌胃人体推荐摄入量100倍的苦荞醋饮,对照组灌胃蒸馏水,灌胃体积为20 mL/kg,灌胃后连续观察14 d,记录小鼠的一般情况、体重变化、大体解剖检查结果及脏器系数等数据;在28 d经口毒性试验中,高、中、低剂量组分别灌胃人体推荐摄入量100倍、50倍、25倍的苦荞醋饮,对照组给予蒸馏水,连续灌胃28 d,灌胃体积为10 mL/kg,试验期间记录大鼠的一般情况、体重变化、摄食量和食物利用率等数据,试验结束时进行血液学检查、血生化检查、大体解剖检查及脏器系数的测定、组织病理学观察。结果:小鼠未出现中毒症状,也未出现死亡。与对照组相比,剂量组小鼠的体重、主要器官的脏器系数差异均无统计学意义(P>0.05);大鼠未出现中毒表现,也未出现死亡,低剂量组雌性大鼠的白细胞计数、中剂量组雄性大鼠的脾脏绝对重量与对照组比较差异有统计学意义(P<0.05),但均在正常范围内,无临床意义,其余指标与对照组比较差异均无统计学意义(P>0.05)。结论:苦荞醋饮无急性经口毒性和亚急性经口毒性,是安全、无毒的食品。

沙棘醋饮的安全性初步研究

目的:通过急性经口毒性试验和28 d经口毒性试验对沙棘醋饮的安全性进行初步研究,为护理人员将沙棘醋饮作为一种新型饮食干预形式进行饮食推荐提供安全性试验证据。方法:急性经口毒性试验选用美国癌症研究所(ICR)小鼠,随机分为对照组和剂量组,剂量组将人体推荐摄入量100倍剂量的沙棘醋饮以20 mL/kg分2次灌胃小鼠,间隔时间6 h;对照组给予等量蒸馏水灌胃。灌胃后观察14 d,观察指标包括一般临床表现、体重情况及脏器系数。28 d经口毒性试验选用Sprague-Dawley(SD)大鼠,随机分为高剂量组、中剂量组、低剂量组、对照组。高剂量组、中剂量组、低剂量组分别将人体推荐摄入量100倍、50倍、25倍剂量的沙棘醋饮以10 mL/kg灌胃大鼠,对照组给予等量蒸馏水灌胃,连续灌胃28 d,观察指标包括一般临床表现、体重及摄食情况、血液学指标、血生化指标及脏器系数。结果:急性经口毒性试验过程中,小鼠一般临床表现无异常,生长发育状况良好,剂量组体重与对照组比较,差异无统计学意义(P>0.05)。剂量组主要器官的脏器系数与对照组比较差异无统计学意义(P>0.05)。28 d经口毒性试验过程中,各组大鼠生长情况良好,其日常活动、自主活动及行为表现等未见异常。4组体重、摄食量、食物利用率、血液学指标、血生化指标和主要器官的脏器系数方差分析结果显示,差异均无统计学意义(P>0.05)。显微镜下观察对照组与高剂量组的心脏、肝脏、脾脏、肾脏及胃组织切片均未见异常,组织结构和形态完整。结论:沙棘醋饮无急性及短期毒性效应和毒作用特征,初步验证沙棘醋饮安全无毒。

经口喂养大鼠乳酸菌混合菌粉的毒性研究

目的通过研究一种复合混合菌粉的28 d经口毒性,为其作为保健品的开发和制备提供安全性依据。方法分别灌胃给予雌、雄大鼠不同剂量的乳酸菌R9639+Zhang+P9+V9+P-8+XLTG11混合菌粉,连续28 d,旨在观察不同组中动物基本情况、体质量、血液学检查、脏器指数和重要脏器病理学状态等。结果灌胃给予不同剂量的混合菌粉后,各组大鼠的体质量、摄食量、食物利用率、血液学检查及尿常规等指标未发现明显的改变;脏器指数、重要脏器的组织病理形态均无显著差异。结论28 d经口毒性研究结果表明,该混合菌粉对大鼠无显著毒性,具有良好的安全性。

桂花阿胶固体饮料基于动物毒理实验的安全性评价

目的评价桂花阿胶固体饮料的安全性。方法急性经口毒性试验,采用限量法,将大鼠禁食(不禁水)16h后,经口灌胃给予受试物,剂量为20.0g/kg·BW,给药后观察14d;细菌回复突变试验,设5个剂量组,及空白、溶剂、阳性对照组,采用平板参入法,对组氨酸缺陷型4株鼠伤寒沙门氏菌突变型菌株TA97a、TA98、TA100和TA102进行回变菌落计数;哺乳动物红细胞微核试验,设三个剂量组,及环磷酰胺组、阴性对照组,试验采用30h灌胃法,两次灌胃间隔24h进行试验,计数骨髓嗜多染红细胞在总红细胞的比例及微核嗜多染红细胞的比率;28d经口毒性试验,设三个剂量组及一个空白对照组,经口灌胃28d,观察体质量、食物利用率、血液学指标、血液生化指标及病理检测。结果该样品急性经口毒性试验结果为无毒性,细菌回复突变试验、哺乳动物红细胞微核试验结果均为阴性,28d经口毒性试验各项指标与空白对照组比较差异无显著性。结论各项试验表明桂花阿胶固体饮料在一定剂量范围内通过系统的体内和体外试验证明其具有食用安全性。

β-葡聚糖生物强化大米28天经口毒性研究

目的通过28 d经口毒性试验研究,对β-葡聚糖生物强化大米的安全性进行评价。方法将断乳SD大鼠随机分为对照组和低、中、高剂量组(2.5、5.0和10.0 g/kg BW),每组22只,雌雄各半。按照10 mL/kg BW经口灌胃,连续给予28 d,实验前后对大鼠进行眼部检查,处死动物后进行尿常规、血液学、血生化、脏器系数测定及组织病理学检查。结果与对照组相比,给药组动物外观、体质量、食物利用率、脏器系数、血生化和尿常规检测均没有明显差异;雄性中、高剂量组和雌性高剂量组在第4周的进食量与对照组相比具有统计学差异(P<0.05或P<0.01),但均无时间上的延续性,认为无毒理学意义;雄性中、高剂量组的血小板含量与对照组相比具有统计学差异(P<0.05),但无剂量-反应关系,仅限单个指标异常,且均在实验室参考值范围之内,认为不具有毒理学意义;高剂量组病理学检查未见与受试物有关的病理性改变。结论在本试验条件下,SD大鼠短期经口摄入β-葡聚糖生物强化大米未见毒性作用,但长期食用的安全性尚需进一步研究。