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DOI10.1016/j.aquatox.2018.03.013
Effects of multiple life stage exposure to the fungicide prochloraz in Xenopus laevis: Manifestations of antiandrogenic and other modes of toxicity
Haselman, Jonathan T.1; Kosian, Patricia A.1; Korte, Joseph J.1; Olmstead, Allen W.1,2; Degitz, Sigmund J.1
发表日期2018-06-01
ISSN0166-445X
卷号199页码:240-251
英文摘要

The Larval Amphibian Growth and Development Assay (LAGDA) is an internationally harmonized testing guideline for evaluating effects of chronic chemical exposure in amphibians. In order to evaluate the effects of chronic exposure to an antiandrogenic chemical in an amphibian model, prochloraz was tested using a variation of the LAGDA design. Exposure was initiated with < 1d post-fertilization embryos at nominal concentrations of 0, 6.7, 20, 60 and 180 g/L (0, 18, 53, 159, 478 nM) and continued in flow-through conditions until two months following the median time that controls completed metamorphosis. Growth, developmental rate, circulating thyroid hormone and thyroid gland histopathology were evaluated in a subsample at completion of metamorphosis. There were no effects on growth or development at this stage, but circulating thyroid hormone was elevated in the 20, 60 and 180 mu g/L treatments and minimal to mild thyroid follicular cell hypertrophy was observed histologically in the 180 mu g/L treatment. Growth, overt toxicity, and reproductive development were evaluated at test termination. There were no effects on growth in either gender, but livers and kidneys exhibited treatment-related pathologies consistent with organ toxicity related to metabolism and presumably impaired excretion of prochloraz metabolites. Histological assessments of female ovaries resulted in minimal pathologies only in the 180 g/L treatment while male testes exhibited numerous treatment-related pathologies that are consistent with previously reported antiandrogenic effects of prochloraz in other species. The most severe testis pathologies occurred in the 180 g/L treatment; however, incidences of treatment-related pathologies occurred in all prochloraz treatments. Mullerian duct regression in males was inhibited by prochloraz exposure while MiiHenan duct maturation in females was accelerated, characteristic of a feminizing effect. Gene expression levels of potential biomarkers of testis function were also measured. Relative abundance of cyp17a1 transcripts was generally unaffected by prochloraz exposure whereas the Ins13 orthologue, rficff, was elevated by 3 and > 5 fold in the 60 and 180 mu g/L treatments, respectively, indicating impaired Leydig cell maturation and testosterone signaling. Overall, prochloraz exposure caused effects characteristic of an antiandrogenic mode of action, which is consistent with previously reported results in other species and supports the utility of the LAGDA design for chemical testing.


英文关键词Xenopus laevis;Prochloraz;LAGDA;Endocrine disruption;InsI3;Rflcii;Cyp17
语种英语
WOS记录号WOS:000433271600022
来源期刊AQUATIC TOXICOLOGY
来源机构美国环保署
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/58795
作者单位1.US EPA, Mid Continent Ecol Div, 6201 Congdon Blvd, Duluth, MN 55804 USA;
2.Bayer CropSci LP, Environm Toxicol & Risk Assessment, Dev North Amer, Res Triangle Pk, NC 27709 USA
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Haselman, Jonathan T.,Kosian, Patricia A.,Korte, Joseph J.,et al. Effects of multiple life stage exposure to the fungicide prochloraz in Xenopus laevis: Manifestations of antiandrogenic and other modes of toxicity[J]. 美国环保署,2018,199:240-251.
APA Haselman, Jonathan T.,Kosian, Patricia A.,Korte, Joseph J.,Olmstead, Allen W.,&Degitz, Sigmund J..(2018).Effects of multiple life stage exposure to the fungicide prochloraz in Xenopus laevis: Manifestations of antiandrogenic and other modes of toxicity.AQUATIC TOXICOLOGY,199,240-251.
MLA Haselman, Jonathan T.,et al."Effects of multiple life stage exposure to the fungicide prochloraz in Xenopus laevis: Manifestations of antiandrogenic and other modes of toxicity".AQUATIC TOXICOLOGY 199(2018):240-251.
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