ArticleToxicological sciences : an official journal of the Society of Toxicology2015
Dose Addition Models Based on Biologically Relevant Reductions in Fetal Testosterone Accurately Predict Postnatal Reproductive Tract Alterations by a Phthalate Mixture in Rats.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
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Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 67 citations in OpenAlex.
- Systematic evidence map on the association between exposure to personal care products and fetal growth.Environment international · 2026Pooled it
- Systematic reviews and meta-analyses of human and animal evidence of prenatal diethylhexyl phthalate exposure and changes in male anogenital distance.Journal of toxicology and environmental health. Part B, Critical reviews · 2018Pooled it
- Prenatal PFAS exposure and offspring health: evidence review and implications for intergenerational risk assessment.Frontiers in public health · 2026Review
- Dose-response assessment of dipentyl phthalate effects on testosterone production and morphogenesis of late-gestation fetal rat testis.Environment international · 2025Article
- Evaluation of a hypothesized Sertoli cell-based adverse outcome pathway for effects of diisononyl phthalate on the developing testis.Current research in toxicology · 2025Article
- Evaluation of the endocrine disrupting potential of Di-isononyl phthalate.Current research in toxicology · 2025Article
- Mechanistic screening of reproductive toxicity in a novel 3D testicular co-culture model shows significant impairments following exposure to low-dibutyl phthalate concentrations.Archives of toxicology · 2024Article
- Elucidating the mechanisms and mitigation strategies for six-phthalate-induced toxicity in male germ cells.Frontiers in cell and developmental biology · 2024Article
- Adolescent endocrine disrupting chemical exposure and academic achievement.Environmental research · 2023Article
- Complex Mixtures and Multiple Stressors: Evaluating Combined Chemical Exposures and Cumulative Toxicity.Toxics · 2023Article
- Racial disparities affect the association between gestational urinary phthalate mixtures and infant genital measures.Frontiers in reproductive health · 2023Article
- Mixture Risk Assessment of Complex Real-Life Mixtures-The PANORAMIX Project.International journal of environmental research and public health · 2022Article
- 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
- Pilot-scale expanded assessment of inorganic and organic tapwater exposures and predicted effects in Puerto Rico, USA.The Science of the total environment · 2021Article
- 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
- Gonadal sex steroid hormone secretion after exposure of male rats to estrogenic chemicals and their combinations.Molecular and cellular endocrinology · 2021Article
- A prospective whole-mixture approach to assess risk of the food and chemical exposome.Nature food · 2021Review
- Associations of prenatal exposure to phthalates with measures of cognition in 7.5-month-old infants.Neurotoxicology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Challenges in cumulative risk assessment of anti-androgenic phthalate mixtures include a lack of data on all the individual phthalates and difficulty determining the biological relevance of reduction in fetal testosterone (T) on postnatal development. The objectives of the current study were 2-fold: (1) to test whether a mixture model of dose addition based on the fetal T production data of individual phthalates would predict the effects of a 5 phthalate mixture on androgen-sensitive postnatal male reproductive tract development, and (2) to determine the biological relevance of the reductions in fetal T to induce abnormal postnatal reproductive tract development using data from the mixture study. We administered a dose range of the mixture (60, 40, 20, 10, and 5% of the top dose used in the previous fetal T production study consisting of 300 mg/kg per chemical of benzyl butyl (BBP), di(n)butyl (DBP), diethyl hexyl phthalate (DEHP), di-isobutyl phthalate (DiBP), and 100 mg dipentyl (DPP) phthalate/kg; the individual phthalates were present in equipotent doses based on their ability to reduce fetal T production) via gavage to Sprague Dawley rat dams on GD8-postnatal day 3. We compared observed mixture responses to predictions of dose addition based on the previously published potencies of the individual phthalates to reduce fetal T production relative to a reference chemical and published postnatal data for the reference chemical (called DAref). In addition, we predicted DA (called DAall) and response addition (RA) based on logistic regression analysis of all 5 individual phthalates when complete data were available. DA ref and DA all accurately predicted the observed mixture effect for 11 of 14 endpoints. Furthermore, reproductive tract malformations were seen in 17-100% of F1 males when fetal T production was reduced by about 25-72%, respectively.
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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.