ArticleToxicological sciences : an official journal of the Society of Toxicology2018
Mixed "Antiandrogenic" Chemicals at Low Individual Doses Produce Reproductive Tract Malformations in the Male Rat.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Organizing mechanism-related information on chemical interactions using a framework based on the aggregate exposure and adverse outcome pathways.Environment international · 2020Pooled it
- Mixture Effects Investigation of a Thyroid Hormone System-Specific Interaction with Azole Fungicides.Toxics · 2026Article
- Dose-response assessment of dipentyl phthalate effects on testosterone production and morphogenesis of late-gestation fetal rat testis.Environment international · 2025Article
- Evaluation of the endocrine disrupting potential of Di-isononyl phthalate.Current research in toxicology · 2025Article
- Evaluation of the endocrine disrupting potential of Di-isodecyl phthalate.Current research in toxicology · 2025Article
- Pesticide Exposures during Pregnancy and Health Outcomes in Latin America and the Caribbean: A Scoping Review of Human Observational Studies.Journal of health & pollution · 2024Review
- Article
- 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
- Science evolves but outdated testing and static risk management in the US delay protection to human health.Frontiers in toxicology · 2024Article
- Application of AOPs to assist regulatory assessment of chemical risks - Case studies, needs and recommendations.Environmental research · 2023Review
- Cumulative maternal and neonatal effects of combined exposure to a mixture of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) during pregnancy in the Sprague-Dawley rat.Environment international · 2022Article
- In Utero Exposure to a Mixture of the Perfluoroalkyl-Isopropyl Pesticide Pyrifluquinazon With Dibutyl Phthalate Cumulatively Disrupts Male Rat Reproductive Development via Different Mechanisms of Action.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Critical review and analysis of literature on low dose exposure to chemical mixtures in mammalianCritical reviews in toxicology · 2022Review
- Developmental toxicity of Nafion byproduct 2 (NBP2) in the Sprague-Dawley rat with comparisons to hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX) and perfluorooctane sulfonate (PFOS).Environment international · 2022Article
- Prenatal exposure to phenols and benzophenones in relation to markers of male reproductive function in adulthood.Frontiers in endocrinology · 2022Article
- AOP key event relationship report: Linking androgen receptor antagonism with nipple retention.Current research in toxicology · 2022Review
- Interaction between mono-(2-ethylhexyl) phthalate and retinoic acid alters Sertoli cell development during fetal mouse testis cord morphogenesis.Current research in toxicology · 2022Article
- A mixture of 15 phthalates and pesticides below individual chemical no observed adverse effect levels (NOAELs) produces reproductive tract malformations in the male rat.Environment international · 2021Article
- REPRODUCTIVE TOXICOLOGY: Environmental exposures, fetal testis development and function: phthalates and beyond.Reproduction (Cambridge, England) · 2021Review
- Genomic and Hormonal Biomarkers of Phthalate-Induced Male Rat Reproductive Developmental Toxicity Part II: A Targeted RT-qPCR Array Approach That Defines a Unique Adverse Outcome Pathway.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Biomonitoring efforts have clearly shown that all humans are exposed to chemical mixtures. Of concern is whether or not exposure to mixtures during pregnancy contributes to congenital abnormalities in children even when each chemical is at an individual dose that does not affect the fetus. Here, we hypothesized that in utero exposure to a mixture of chemicals covering multiple "antiandrogenic" mechanisms of action at doses that individually have no adverse effect would result in permanent reproductive tract alterations in the male rat after birth. Pregnant dams were exposed to a range of dilutions (100%, 50%, 25%, 12.5%, 6.25%, or vehicle control) of a mixture containing pesticides, phthalates, and drugs (p, p'-DDE, linuron, prochloraz, procymidone, pyrifluquinazon, vinclozolin, finasteride, flutamide, simvastatin, and 9 phthalates [dipentyl, dicyclohexyl, di-2-ethylhexyl, dibutyl, benzyl butyl, diisobutyl, diisoheptyl, dihexyl, and diheptyl]). The top dose contained each chemical at 20% of its lowest observed adverse effect level (LOAEL) for the most sensitive male reproductive alteration following in utero exposure. We found that male rat offspring displayed a variety of neonatal, pubertal, and permanent adult effects across all dose levels. Even at the lowest dose (each chemical approximately 80-fold below lowest observed adverse effect level) there were permanent reductions in several reproductive tract tissue weights. In the top dose group, 100% of male offspring displayed permanent severe birth defects including genital malformations. Despite acting via 5 different molecular initiating events, a mixture of 18 chemicals can combine to produce additive effects even when each compound is at is at a relatively low dose.
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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.