Dataset Information

Database of pharmacokinetic time-series data and parameters for 144 environmental chemicals.

ABSTRACT: Time courses of compound concentrations in plasma are used in chemical safety analysis to evaluate the relationship between external administered doses and internal tissue exposures. This type of experimental data is rarely available for the thousands of non-pharmaceutical chemicals to which people may potentially be unknowingly exposed but is necessary to properly assess the risk of such exposures. In vitro assays and in silico models are often used to craft an understanding of a chemical's pharmacokinetics; however, the certainty of the quantitative application of these estimates for chemical safety evaluations cannot be determined without in vivo data for external validation. To address this need, we present a public database of chemical time-series concentration data from 567 studies in humans or test animals for 144 environmentally-relevant chemicals and their metabolites (187 analytes total). All major administration routes are incorporated, with concentrations measured in blood/plasma, tissues, and excreta. We also include calculated pharmacokinetic parameters for some studies, and a bibliography of additional source documents to support future extraction of time-series. In addition to pharmacokinetic model calibration and validation, these data may be used for analyses of differential chemical distribution across chemicals, species, doses, or routes, and for meta-analyses on pharmacokinetic studies.

SUBMITTER: Sayre RR

PROVIDER: S-EPMC7170868 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Database of pharmacokinetic time-series data and parameters for 144 environmental chemicals.

Sayre Risa R RR Wambaugh John F JF Grulke Christopher M CM

Scientific data 20200420 1

Time courses of compound concentrations in plasma are used in chemical safety analysis to evaluate the relationship between external administered doses and internal tissue exposures. This type of experimental data is rarely available for the thousands of non-pharmaceutical chemicals to which people may potentially be unknowingly exposed but is necessary to properly assess the risk of such exposures. In vitro assays and in silico models are often used to craft an understanding of a chemical's pha ...[more]

PMID: 32313097

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Project description:BackgroundMiscarriage is a prevalent public health issue and many events occur before women are aware of their pregnancy, complicating research design. Thus, risk factors for miscarriage are critically understudied. Our goal was to identify environmental chemicals with a high number of interactions with miscarriage genes, based on known toxicogenomic responses.MethodsWe used miscarriage (MeSH: D000022) and chemical gene lists from the Comparative Toxicogenomics Database in human, mouse, and rat. We assessed enrichment for gene ontology biological processes among the miscarriage genes. We prioritized chemicals (n = 25) found at Superfund sites or in the blood or urine pregnant women. For chemical-disease gene sets of sufficient size (n = 13 chemicals, n = 20 comparisons), chi-squared enrichment tests and proportional reporting ratios (PRR) were calculated. We cross-validated enrichment results.ResultsMiscarriage was annotated with 121 genes and overrepresented in inflammatory response (q = 0.001), collagen metabolic process (q = 1 × 10-13), cell death (q = 0.02), and vasculature development (q = 0.005) pathways. The number of unique genes annotated to a chemical ranged from 2 (bromacil) to 5607 (atrazine). In humans, all chemicals tested were highly enriched for miscarriage gene overlap (all p < 0.001; parathion PRR = 7, cadmium PRR = 6.5, lead PRR = 3.9, arsenic PRR = 3.5, atrazine PRR = 2.8). In mice, highest enrichment (p < 0.001) was observed for naphthalene (PRR = 16.1), cadmium (PRR = 12.8), arsenic (PRR = 11.6), and carbon tetrachloride (PRR = 7.7). In rats, we observed highest enrichment (p < 0.001) for cadmium (PRR = 8.7), carbon tetrachloride (PRR = 8.3), and dieldrin (PRR = 5.3). Our findings were robust to 1000 permutations each of variable gene set sizes.ConclusionWe observed chemical gene sets (parathion, cadmium, naphthalene, carbon tetrachloride, arsenic, lead, dieldrin, and atrazine) were highly enriched for miscarriage genes. Exposures to chemicals linked to miscarriage, and thus linked to decreased probability of live birth, may limit the inclusion of fetuses susceptible to adverse birth outcomes in epidemiology studies. Our findings have critical public health implications for successful pregnancies and the interpretation of adverse impacts of environmental chemical exposures on pregnancy.

Dataset Information

Database of pharmacokinetic time-series data and parameters for 144 environmental chemicals.

Publications

Database of pharmacokinetic time-series data and parameters for 144 environmental chemicals.

Similar Datasets

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