ArticleEnvironmental health perspectives2013
Contrasting theories of interaction in epidemiology and toxicology.
Article in Environmental health perspectives, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Using simulations to explore the conditions under which "true" dose-response relationships are detectable for environmental exposures: polychlorinated biphenyls and birthweight: a case study.American journal of epidemiology · 2026Article
- Joint Association of Cholesterol, High-Density Lipoprotein and Glucose Index, and Circadian Syndrome With Incidence of Cardiovascular Disease: Results From National Longitudinal Prospective Studies.Cardiovascular therapeutics · 2026Article
- Combined Exposures and Mixtures Research: An Enduring NIEHS Priority.Environmental health perspectives · 2024Article
- Nutritional Modulation of Associations between Prenatal Exposure to Persistent Organic Pollutants and Childhood Obesity: A Prospective Cohort Study.Environmental health perspectives · 2023Article
- Bayesian Weighted Sums: A Flexible Approach to Estimate Summed Mixture Effects.International journal of environmental research and public health · 2021Article
- Joint and interactive effects between health comorbidities and environmental exposures in predicting amyotrophic lateral sclerosis.International journal of hygiene and environmental health · 2021Article
- Quantile g-Computation: A New Method for Analyzing Mixtures of Environmental Exposures.Environmental health perspectives · 2020Article
- Chemical mixtures and neurobehavior: a review of epidemiologic findings and future directions.Reviews on environmental health · 2020Review
- A family of partial-linear single-index models for analyzing complex environmental exposures with continuous, categorical, time-to-event, and longitudinal health outcomes.Environmental health : a global access science source · 2020Article
- A Cumulative Risk Perspective for Occupational Health and Safety (OHS) Professionals.International journal of environmental research and public health · 2020Article
- The use of Logic regression in epidemiologic studies to investigate multiple binary exposures: an example of occupation history and amyotrophic lateral sclerosis.Epidemiologic methods · 2020Article
- Statistical Methodology in Studies of Prenatal Exposure to Mixtures of Endocrine-Disrupting Chemicals: A Review of Existing Approaches and New Alternatives.Environmental health perspectives · 2019Review
- Environmental exposure mixtures: questions and methods to address them.Current epidemiology reports · 2018Article
- Exploring associations between prenatal solvent exposures and teenage drug and alcohol use: a retrospective cohort study.Environmental health : a global access science source · 2017Article
- Article
- Statistical Approaches for Assessing Health Effects of Environmental Chemical Mixtures in Epidemiology: Lessons from an Innovative Workshop.Environmental health perspectives · 2016Article
- What Can Epidemiological Studies Tell Us about the Impact of Chemical Mixtures on Human Health?Environmental health perspectives · 2016Article
- The identification of complex interactions in epidemiology and toxicology: a simulation study of boosted regression trees.Environmental health : a global access science source · 2014Article
- Chemical mixtures and children's health.Current opinion in pediatrics · 2014Review
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2 authors.
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Abstract
backgroundEpidemiologists and toxicologists face similar problems when assessing interactions between exposures, yet they approach the question very differently. The epidemiologic definition of "interaction" leads to the additivity of risk differences (RDA) as the fundamental criterion for causal inference about biological interactions. Toxicologists define "interaction" as departure from a model based on mode of action: concentration addition (CA; for similarly acting compounds) or independent action (IA; for compounds that act differently).
objectivesWe compared and contrasted theoretical frameworks for interaction in the two fields.
methodsThe same simple thought experiment has been used in both both epidemiology and toxicology to develop the definition of "noninteraction," with nearly opposite interpretations. In epidemiology, the "sham combination" leads to a requirement that noninteractive dose-response curves be linear, whereas in toxicology, it results in the model of CA. We applied epidemiologic tools to mathematical models of concentration-additive combinations to evaluate their utility.
resultsRDA is equivalent to CA only for linear dose-response curves. Simple models demonstrate that concentration-additive combinations can result in strong synergy or antagonism in the epidemiologic framework at even the lowest exposure levels. For combinations acting through nonsimilar pathways, RDA approximates IA at low effect levels.
conclusionsEpidemiologists have argued for a single logically consistent definition of interaction, but the toxicologic perspective would consider this approach less biologically informative than a comparison with CA or IA. We suggest methods for analysis of concentration-additive epidemiologic data. The two fields can learn a great deal about interaction from each other.
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