title: Enantioselectivity in zebrafish embryo toxicity of the insecticide acetofenate.
abstract: Enantioselectivity in separation and toxicology of chiral xenobiotics have become one of the frontier topics interfacing chemistry and toxicology. In this study, enantiomers of insecticide acetofenate (AF) were separated on selected chiral columns by HPLC, and enantioselectivity in developmental toxicity was evaluated using the zebrafish embryo-larval assays. The AF enantiomers were baseline separated on Chiralcel OD, Chiralpak AD, and Sumichiral OA-2500I columns under optimized conditions. Pure enantiomers were obtained on Chiralcel OD. Optical rotatory dispersion (ORD) and circular dichroism (CD) detectors were used to determine the elution order and CD spectra of the enantiomers. The absolute configuration of enantiomers was identified as S-(+)-AF and R-(-)-AF by the octant rule from force-field calculations and CD spectra. The individual enantiomers were used in 4-day zebrafish embryo-larval bioassays, and a series of developmental end points were measured and compared. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to investigate the expressions of estrogen receptor alpha (ERalpha) in zebrafish embryo exposed to varying enantiomers. While the enantiomers showed no difference in acute toxicity, significant enantioselectivity was observed in developmental toxicities such as yolk sac edema and pericardial edema. The data of qRT-PCR showed that there was about 3.2-fold induction in the mRNA levels of ERalpha between fish exposed to (+)-AF and (-)-AF. The results suggest that enantioselectivity may occur at the developmental level even in the absence of selective acute toxicity and should be considered when evaluating ecotoxicological effects of chiral contaminants.
authors.affiliation: Research Center of Green Chirality, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.forename: Meirong
authors.initials: M
authors.lastname: Zhao
authors.forename: Weiping
authors.initials: W
authors.lastname: Liu
authors.forename: Shengwen
authors.initials: S
authors.lastname: Chen
authors.forename: Jiangying
authors.initials: J
authors.lastname: Gan
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D004980:Ethane / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology* / Q000633:toxicity*; D007306:Insecticides / Q000737:chemistry* / Q000633:toxicity*; D008958:Models, Molecular; D008968:Molecular Conformation; D012333:RNA, Messenger / Q000235:genetics; D013237:Stereoisomerism; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
chemical_list: C530171:2,2,2,-trichloro-1-(3,4-dichlorophenyl)-ethylacetate; D047628:Estrogen Receptor alpha; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; D012333:RNA, Messenger; D004980:Ethane