Use of genomic data in risk assessment case study: II. Evaluation of the dibutyl phthalate toxicogenomic data set

Euling, Susan Y.; White, L.; Kim, Andrea S.; Sen, Banalata; Wilson, Vickie S.; Keshava, Channa; Keshava, Nagalakshmi; Hester, Susan; Ovacik, Meric; Ierapetritou, Marianthi G.; Androulakis, Ioannis P.; Gaido, Kevin W.

doi:10.1016/j.taap.2011.06.014

Cited by 42 publications

(22 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most work on the effects of DBP on steroidogenesis has been done in males. Our observations are consistent with studies showing that in utero exposure to DBP results in decreased testicular expression of Star and Hsd3b1 among other genes that encode key steroidogenic enzymes [34–37]. …”

Section: Discussionsupporting

confidence: 92%

Short term exposure to di-n-butyl phthalate (DBP) disrupts ovarian function in young CD-1 mice

Sen

Liu

Craig

2015

Reproductive Toxicology

View full text Add to dashboard Cite

Di-n-butyl phthalate (DBP) is present in many beauty and medical products. Human exposure estimates range from 0.007–0.01 mg/kg/day in the general population and up to 0.233 mg/kg/day in patients taking DBP-coated medications. Levels of phthalates tend to be higher in women, thus, evaluating ovarian effects of DBP exposure is of great importance. Mice were given corn oil (vehicle) or DBP at 0.01, 0.1, and 1000 mg/kg/day (high dose) for 10 days to test whether DBP causes ovarian toxicity. Estrous cyclicity, steroidogenesis, ovarian morphology, and apoptosis and steroidogenesis gene expression were evaluated. DBP exposure decreased serum E2 at all doses, while 0.1DBP increased FSH, decreased antral follicle numbers, and increased mRNA encoding pro-apoptotic genes (Bax, Bad, Bid). Interestingly, mRNAs encoding the steroidogenic enzymes Hsd17b1, Cyp17a1 and Cyp19a1 were increased in all DBP-treated groups. These novel findings show that DBP can disrupt ovarian function in mice at doses relevant to humans.

show abstract

Section: Discussionsupporting

confidence: 92%

Short term exposure to di-n-butyl phthalate (DBP) disrupts ovarian function in young CD-1 mice

Sen

Liu

Craig

2015

Reproductive Toxicology

View full text Add to dashboard Cite

show abstract

“…One concerns the reanalysis of nine rat in vivo studies from the published literature that exposed rats to DBP during gestation and evaluated gene expression changes in testes or Wolffian ducts of male foetuses using microarrays (5) and/or qPCR (9) . A second study (Lehmann et al, 2004) corresponds to a rat in vivo study with DBP of which the qRT-PCR data were reanalysed by Euling et al (2011). In a third study the concentration-dependent effects of mono(2-ethylhexyl) phthalate (MEHP) and monomethyl phthalate (MMP, less toxic) on the transcriptome of rat whole embryo cultures (WECs) were analysed and examined in relation with dysmorphogenesis (Robinson et al, 2012).…”

Section: Hazardmentioning

confidence: 99%

A foresight study on emerging technologies: State of the art of Omics technologies and potential applications in food and feed safety

Pielaat

Barker

Hendriksen

et al. 2013

EFSA Supporting Publications

View full text Add to dashboard Cite

Suggested citation: Pielaat A, Barker GC, Hendriksen P, Peijnenburg A and Kuile BH, 2013. A foresight study on emerging technologies: State of the art of omics technologies and potential applications in food and feed safety. REPORT 1: Review on the state of art of omics technologies in risk assessment related to food and feed safety. EFSA supporting publication 2013:EN-495, 126 pp. ABSTRACTThis report consists of a review of the available scientific evidence on the state of art of omics technologies with a particular focus on applications in the area of food and feed safety. The report gives a description of the different types of omics technologies with respect to recent progresses made on the application of these techniques in chemical and microbiological risk assessment. Hereto, case studies were selected in order to cover different areas under the remit of EFSA. In this review each case study has been investigated with respect to its hazard, experimental methodologies, (statistical) data analysis and its link to food/feed safety risk assessment. Finally, the added value of omics technologies as compared to classical risk assessment and current limitations of omics technologies for their application in chemical and microbiological food safety risk assessment has been discussed. This investigation shows that most of the studies on chemical agents focus on mode of action identification and a search for biomarkers using transcriptomics. As for microbial food safety, omics have not yet been successfully applied often. When applied, they never target the host, but focus on aspects of the pathogen, e.g. in detection or source attribution.

show abstract

“…Presence of various pollutants including PAEs and PAHs in NJS and NJT might be responsible for the lipid metabolic disturbance, which is confirmed by previous studies demonstrating that PAEs had a significant impact on rat lipid metabolism (Dai et al 2006;Xu et al 2006). PAEs are considered as an important group of environmental endocrine disruptors (Wong and Gill 2002;Lee and Koo 2007), which can also induce down-regulation of genes in the steroidogenesis pathway and lipid/sterol/cholesterol transport pathway (Euling et al 2011). Additionally, in vivo (Kawano et al 2010) and in vitro (Podechard et al 2012) studies have indicated that PAHs exposure can induced lipid accumulation or steatosis in animal cells.…”

Section: Alteration Of Biological Pathways and Related Gene Expressionmentioning

confidence: 99%

A transcriptomics study on hepatic lipid metabolism in mice exposed to contaminated drinking water

Yin

Zhao

Zhang

et al. 2013

Int. J. Environ. Sci. Technol.

View full text Add to dashboard Cite

DNA microarray was used to analyze hepatic transcriptional profile of male mice (Mus musculus) after the mice were fed with Yangtze River (China) source water (NJS) and tap water (NJT) for 90 days. Chemical analysis demonstrated that NJS and NJT contained various tracelevel pollutants including polycyclic aromatic hydrocarbons, phthalate ethers and inorganic contaminants. DNA microarray revealed occurrence of 5,042 differentially expressed genes (DEGs) in the mice fed with NJS and 828 DEGs in the mice fed with NJT, indicating that NJS posed greater influence on liver transcriptome. Annotation against Kyoto Encyclopedia of Genes and Genomes pathway database showed that the DEGs in NJS group were mostly involved in lipid metabolism (51 DEGs), followed by neurodegenerative diseases (47 DEGs), energy metabolism (41 DEGs) and endocrine system (38 DEGs). NJT exposure was found to affect lipid metabolism (14 DEGs), xenobiotics biodegradation and metabolism (6 DEGs), and cofactors and vitamins metabolism (5 DEGs). Annotation against Gene Ontology database confirmed that lipid metabolism among the altered pathways was most susceptible to both NJS and NJT exposure. The DEGs were involved in 6 lipid metabolic pathways including fatty acid metabolism, glycerophospholipid metabolism, unsaturated fatty acid biosynthesis, steroid biosynthesis, primary bile acid biosynthesis and steroid hormone biosynthesis. Although both NJS and NJT might cause no obvious liver tissue damages, the lipid metabolic disturbance induced by trace-level pollutants still deserves public health concern.

show abstract

Use of genomic data in risk assessment case study: II. Evaluation of the dibutyl phthalate toxicogenomic data set

Cited by 42 publications

References 32 publications

Short term exposure to di-n-butyl phthalate (DBP) disrupts ovarian function in young CD-1 mice

Short term exposure to di-n-butyl phthalate (DBP) disrupts ovarian function in young CD-1 mice

A foresight study on emerging technologies: State of the art of Omics technologies and potential applications in food and feed safety

A transcriptomics study on hepatic lipid metabolism in mice exposed to contaminated drinking water

Contact Info

Product

Resources

About