Project description:This SuperSeries is composed of the following subset Series: GSE21008: Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: atrazine GSE21010: Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: cadmium GSE21011: Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: fluoranthene Refer to individual Series
Project description:Triclocarban (TCC) is a widely used antimicrobial agent that is routinely detected in surface waters. The present study was designed to examine TCC’s efficacy and mode of action as a reproductive toxicant in fish. Reproductively mature Pimephales promelas were continuously exposed to either 1 or 5 μg TCC/L, 0.5 μg 17β-trenbolone (TRB)/L or a mixture (MIX) of 5 μg TCC and 0.5 μg TRB/L for 22 d and a variety of reproductive and endocrine-related endpoints were examined. The data were evaluated to answer several key questions: first, whether exposure to TCC could be linked with an ecologically-relevant adverse outcome, i.e., impaired reproduction; second, whether the present study provided additional support for augmentation of androgen action as an endocrine-disrupting mode of action for TCC; and third, whether there were any novel and/or plausible linkages between changes in the ovarian transcriptome and the apical responses observed in females that could support adverse outcome pathway development and/or further hypothesis-driven testing.
Project description:Di(2-ethylhexyl) phthalate (DEHP; CAS No. 117-81-7) belongs to the phthalate class of chemicals, and is commonly added to plastics for flexibility. DEHP has been identified as an index compound for group-TDI calculations owing to its extensive toxicological dataset. Humans are exposed to this ubiquitous environmental contaminant through multiple routes. DEHP has been designated as probably and possibly carcinogenic to humans based on its ability to induce rodent carcinogenicity, although the relevance of its mode of action (MoA) in humans remains unclear. The aim of this study was to investigate the carcinogenic potential of DEHP using an alternative method and explore the possible mode and mechanisms of action at the molecular level. Special attention has been paid to DEHP dissolution in cell media, leading to the use of a final concentration of 0.5% DMSO. Transcriptomics were conducted on cells treated with a cytotoxic concentration of DEHP (19.7 µg/mL) for 24 h. The aim of the microarray experiment was to analyze the molecular effects of the substance under the specific conditions of the Cell Transformation Assay protocol (BALB c/ 3T3 clone A31-1-1 CTA, according to the method validated by ECVAM, Sasaki et al., 2012), in order to provide mechanistic explanations of the test results derived from the CTA.
