ArticleToxicology in vitro : an international journal published in association with BIBRA2020
Application of a combined aggregate exposure pathway and adverse outcome pathway (AEP-AOP) approach to inform a cumulative risk assessment: A case study with phthalates.
Article in Toxicology in vitro : an international journal published in association with BIBRA, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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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.
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Who cites it
10 citing papers in PubMed, 35 citations in OpenAlex.
- Epigenetic vulnerability in endocrine disruption: bridging mechanisms, models, and environmental inequities.Clinical epigenetics · 2026Review
- Evaluation of the endocrine disrupting potential of Di-isononyl phthalate.Current research in toxicology · 2025Article
- Adverse Outcome Pathways Mechanistically Describing Hepatotoxicity.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Advancing human health risk assessment: the role of new approach methodologies.Frontiers in toxicology · 2025Review
- The Role of "Physiologically Based Pharmacokinetic Model (PBPK)" New Approach Methodology (NAM) in Pharmaceuticals and Environmental Chemical Risk Assessment.International journal of environmental research and public health · 2023Review
- Linking freshwater ecotoxicity to damage on ecosystem services in life cycle assessment.Environment international · 2023Review
- A Framework that Considers the Impacts of Time, Cost, and Uncertainty in the Determination of the Cost Effectiveness of Toxicity-Testing Methodologies.Risk analysis : an official publication of the Society for Risk Analysis · 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
- REPRODUCTIVE TOXICOLOGY: Environmental exposures, fetal testis development and function: phthalates and beyond.Reproduction (Cambridge, England) · 2021Review
- Development of a putative adverse outcome pathway network for male rat reproductive tract abnormalities with specific considerations for the androgen sensitive window of development.Current research in toxicology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Advancements in measurement and modeling capabilities are providing unprecedented access to estimates of chemical exposure and bioactivity. With this influx of new data, there is a need for frameworks that help organize and disseminate information on chemical hazard and exposure in a manner that is accessible and transparent. A case study approach was used to demonstrate integration of the Adverse Outcome Pathway (AOP) and Aggregate Exposure Pathway (AEP) frameworks to support cumulative risk assessment of co-exposure to two phthalate esters that are ubiquitous in the environment and that are associated with disruption of male sexual development in the rat: di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DnBP). A putative AOP was developed to guide selection of an in vitro assay for derivation of bioactivity values for DEHP and DnBP and their metabolites. AEPs for DEHP and DnBP were used to extract key exposure data as inputs for a physiologically based pharmacokinetic (PBPK) model to predict internal metabolite concentrations. These metabolite concentrations were then combined using in vitro-based relative potency factors for comparison with an internal dose metric, resulting in an estimated margin of safety of ~13,000. This case study provides an adaptable workflow for integrating exposure and toxicity data by coupling AEP and AOP frameworks and using in vitro and in silico methodologies for cumulative risk assessment.
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What OpenQuestion holds
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.