ArticleToxicological sciences : an official journal of the Society of Toxicology2016
A Demonstration of the Uncertainty in Predicting the Estrogenic Activity of Individual Chemicals and Mixtures From an In Vitro Estrogen Receptor Transcriptional Activation Assay (T47D-KBluc) to the In Vivo Uterotrophic Assay Using Oral Exposure.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 53 citations in OpenAlex.
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- Lessons learned from evaluating defined chemical mixtures in a high-throughput estrogen receptor assay system.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Dose Addition Models Accurately Predict the Subacute Effects of a Mixture of Perfluorooctane Sulfonate and Perfluorooctanoic Acid on Japanese Quail (Coturnix japonica) Chick Mortality.Environmental toxicology and chemistry · 2024Article
- Invisible Hand behind Female Reproductive Disorders: Bisphenols, Recent Evidence and Future Perspectives.Toxics · 2023Review
- Review
- The mixture effect of propyl paraben and bisphenol A on the uterotrophic response in the ovariectomized rats after oral administration.Environmental analysis, health and toxicology · 2023Article
- In vitro activity of a panel of per- and polyfluoroalkyl substances (PFAS), fatty acids, and pharmaceuticals in peroxisome proliferator-activated receptor (PPAR) alpha, PPAR gamma, and estrogen receptor assays.Toxicology and applied pharmacology · 2022Article
- IVIVE: Facilitating the Use ofToxics · 2022Review
- Endocrine disruptors of sex hormone activities.Molecular and cellular endocrinology · 2022Review
- Public and private tapwater: Comparative analysis of contaminant exposure and potential risk, Cape Cod, Massachusetts, USA.Environment international · 2021Article
- In vitro effects-based method and water quality screening model for use in pre- and post-distribution treated waters.The Science of the total environment · 2021Article
- De Facto Water Reuse: Bioassay suite approach delivers depth and breadth in endocrine active compound detection.The Science of the total environment · 2020Article
- Differential activity of BPA, BPAF and BPC on zebrafish estrogen receptors in vitro and in vivo.Toxicology and applied pharmacology · 2019Article
- Oral Systemic Bioavailability of Bisphenol A and Bisphenol S in Pigs.Environmental health perspectives · 2019Article
- Toxicokinetics and bioavailability of bisphenol AF following oral administration in rodents: A dose, species, and sex comparison.Toxicology and applied pharmacology · 2019Article
- A Conflicted Tale of Two Novel AR Antagonists In Vitro and In Vivo: Pyrifluquinazon Versus Bisphenol C.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Generalized Concentration Addition Model Predicts Glucocorticoid Activity Bioassay Responses to Environmentally Detected Receptor-Ligand Mixtures.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Screening Estrogen Receptor Modulators in a Paper-Based Breast Cancer Model.Analytical chemistry · 2018Article
- DifferentialEnvironmental health perspectives · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In vitro estrogen receptor assays are valuable tools for identifying environmental samples and chemicals that display estrogenic activity. However, in vitro potency cannot necessarily be extrapolated to estimates of in vivo potency because in vitro assays are currently unable to fully account for absorption, distribution, metabolism, and excretion. To explore this issue, we calculated relative potency factors (RPF), using 17α-ethinyl estradiol (EE2) as the reference compound, for several chemicals and mixtures in the T47D-KBluc estrogen receptor transactivation assay. In vitro RPFs were used to predict rat oral uterotrophic assay responses for these chemicals and mixtures. EE2, 17β-estradiol (E2), benzyl-butyl phthalate (BBP), bisphenol-A (BPA), bisphenol-AF (BPAF), bisphenol-C (BPC), bisphenol-S (BPS), and methoxychlor (MET) were tested individually, while BPS + MET, BPAF + MET, and BPAF + BPC + BPS + EE2 + MET were tested as equipotent mixtures. In vivo ED50 values for BPA, BPAF, and BPC were accurately predicted using in vitro data; however, E2 was less potent than predicted, BBP was a false positive, and BPS and MET were 76.6 and 368.3-fold more active in vivo than predicted from the in vitro potency, respectively. Further, mixture ED50 values were more accurately predicted by the dose addition model using individual chemical in vivo uterotrophic data (0.7-1.5-fold difference from observed) than in vitro data (1.4-86.8-fold). Overall, these data illustrate the potential for both underestimating and overestimating in vivo potency from predictions made with in vitro data for compounds that undergo substantial disposition following oral administration. Accounting for aspects of toxicokinetics, notably metabolism, in in vitro models will be necessary for accurate in vitro-to-in vivo extrapolations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.