ArticleEnvironmental health perspectives2019
Proposed Key Characteristics of Female Reproductive Toxicants as an Approach for Organizing and Evaluating Mechanistic Data in Hazard Assessment.
Article in Environmental health perspectives, 2019. 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, 70 citations in OpenAlex.
- Associations between Exposure to Organochlorine Chemicals and Endometriosis: A Systematic Review of Experimental Studies and Integration of Epidemiological Evidence.Environmental health perspectives · 2021Pooled it
- Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: An update of a systematic literature review.Mutation research. Reviews in mutation researchPooled it
- SynergisticiScience · 2026Article
- Unveiling toxicological adverse outcomes: toward construction and simulation of large-scale networks.Toxicological sciences : an official journal of the Society of Toxicology · 2026Review
- Identifying the known and unknown health hazard information for chemical disasters: a phased scoping review of the East Palestine, Ohio train derailment.Journal of exposure science & environmental epidemiology · 2025Article
- A workflow for human health hazard evaluation using transcriptomic data and Key Characteristics-based gene sets.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Consensus on the key characteristics of metabolism disruptors.Nature reviews. Endocrinology · 2025Review
- The key characteristics concept.Current opinion in toxicology · 2025Article
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- Pesticides, an urgent challenge to global environmental health and planetary boundaries.Frontiers in toxicology · 2025Review
- An advancement in developmental and reproductive toxicity (DART) risk assessment: evaluation of a bioactivity and exposure-based NAM toolbox.Frontiers in toxicology · 2025Article
- Advancing quantitative hazard banding using expanded probabilistic reference doses and high-throughput screening data for preliminary hazard assessment.NAM journal · 2025Article
- Multi-cellular engineered living systems to assess reproductive toxicology.Reproductive toxicology (Elmsford, N.Y.) · 2024Review
- Enabling novel paradigms: a biological questions-based approach to human chemical hazard and drug safety assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK-Nrf2-HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells.Open life sciences · 2024Article
- Potential mammary carcinogens used in food contact articles: implications for policy, enforcement, and prevention.Frontiers in toxicology · 2024Article
- Article
- Research Recommendations for Selected IARC-Classified Agents: Impact and Lessons Learned.Environmental health perspectives · 2023Review
- Issue analysis: key characteristics approach for identifying endocrine disruptors.Archives of toxicology · 2023Article
- A science-based agenda for health-protective chemical assessments and decisions: overview and consensus statement.Environmental health : a global access science source · 2023Article
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13 authors at 8 institutions in 3 countries.
Funding
Abstract
backgroundIdentification of female reproductive toxicants is currently based largely on integrated epidemiological and
objectiveWe sought to apply a key characteristics approach similar to that pioneered for carcinogen hazard identification to female reproductive toxicant hazard identification.
methodsA working group of international experts was convened to discuss mechanisms associated with chemical-induced female reproductive toxicity and identified 10 key characteristics of chemicals that cause female reproductive toxicity: 1) alters hormone receptor signaling; alters reproductive hormone production, secretion, or metabolism; 2) chemical or metabolite is genotoxic; 3) induces epigenetic alterations; 4) causes mitochondrial dysfunction; 5) induces oxidative stress; 6) alters immune function; 7) alters cell signal transduction; 8) alters direct cell–cell interactions; 9) alters survival, proliferation, cell death, or metabolic pathways; and 10) alters microtubules and associated structures. As proof of principle, cyclophosphamide and diethylstilbestrol (DES), for which both human and animal studies have demonstrated female reproductive toxicity, display at least 5 and 3 key characteristics, respectively. 2,3,7,8-Tetrachlorodibenzo- DISCUSSION: Future efforts should focus on evaluating the proposed key characteristics against additional known and suspected female reproductive toxicants. Chemicals that exhibit one or more of the key characteristics could be prioritized for additional evaluation and testing. A key characteristics approach has the potential to integrate with pathway-based toxicity testing to improve prediction of female reproductive toxicity in chemicals and potentially prevent some toxicants from entering common use. https://doi.org/10.1289/EHP4971.
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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.