Analysis of rodent chemical toxicity and reproduction in the nematode Caenorhabditis elegans
Toxicity assessment of chemicals is crucial in determining safe levels for human exposure.Current in vivo rodent models of toxicity can no longer meet the increasing requirements of proper toxicological evaluation,and there is a critical need to develop more efficient techniques of toxicity screening.In vivo studies in non-rodent model organisms provide a novel platform for screening a large number of chemicals for reproductive toxicity.We performed a brood size assay after chemical exposure in the nematode Caenorhabditis elegans (C.elegans) to determine potential toxic effects of these chemicals on reproduction.Sixteen hydrosoluble chemicals were selected from different Globally Harmonized System of Classification and Labeling of Chemicals (GHS) toxicity categories based on our previously published studies on acute and sub-acute toxicity in C.elegans.L4 stage nematodes were synchronized,and a single animal was cultivated on nematode growth medium (NGM) agar plates containing various concentrations of chemicals for 7 days.The nematodes were transferred to a fresh NGM plate every 24 h,and the total number of offspring produced per viable worm was determined.The no-observed-effect level (NOEL) and lowest-observed-effect level (LOEL) for reproductive toxicity were calculated,and the statistical differences were determined using a one-way ANOVA and the Dunnett”s test for multiple comparisons of the test compounds relative to controls.Our results indicate that 11 of the 16 chemicals tested caused a significant decrease in brood size (p<0.05).In addition,we found that the pH of the tested chemicals (2.76-9.30),which are in a physiologically tolerable range,could affect the brood size.Furthermore,there were positive correlations between the NOELs of C.elegans and the LC50s of C.elegans (r=0.90,p<0.01),and between the LOELs and LC50s of C.elegans (r=0.77,p<0.01).The NOELs of C.elegans also demonstrate a positive correlation with the rodent oral LD50s (r=0.674,p<0.01).Taken together,our studies indicate that C.elegans is a useful screening tool to complement other model systems in reproductive toxicological research.
Nan Zhang Zhuangsheng Tan Guojun Li Hongcai Yang Shan Zheng Liwei He Haiming Jing Shan Gao Yu Li Ling Ma Junyu Ning
Institute for Toxicology,Beijing Center for Disease Prevention and Control/Beijing Research Center f Institute for Toxicology,Beijing Center for Disease Prevention and Control/Beijing Research Center f Xinjiang Center for Disease Prevention and Contro,Urumqi.830000,China
国内会议
北京
英文
25-36
2014-12-01（万方平台首次上网日期，不代表论文的发表时间）