ArticleEnvironmental health perspectives2009
A clash of old and new scientific concepts in toxicity, with important implications for public health.
Article in Environmental health perspectives, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
60 citing papers in PubMed, 3 syntheses or guidelines pooled it, 182 citations in OpenAlex.
- Updated Intrinsic Role of Phytochemicals against Glyphosate-induced Neurotoxicity: Systematic Review.Current medicinal chemistry · 2025Pooled it
- A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals.Environmental health : a global access science source · 2016Pooled it
- Using systematic reviews for hazard and risk assessment of endocrine disrupting chemicals.Reviews in endocrine & metabolic disorders · 2015Pooled it
- Impact of glyphosate and its mixture with 2,4-D and dicamba on gut biochemical function, intestinal barrier integrity and microbiome composition in adult rats with prenatal commencement of exposure.Archives of toxicology · 2026Article
- Epigenetic dysregulation of H19/IGF2 in hepatic cells exposed to toxic metal mixtures in vitro.Scientific reports · 2024Article
- Urinary Concentrations of Bisphenol Mixtures during Pregnancy and Birth Outcomes: The MAKE Study.International journal of environmental research and public health · 2021Article
- Noscapine Acts as a Protease Inhibitor of In Vitro Elastase-Induced Collagen Deposition in Equine Endometrium.International journal of molecular sciences · 2021Article
- Multi-omics phenotyping of the gut-liver axis reveals metabolic perturbations from a low-dose pesticide mixture in rats.Communications biology · 2021Article
- Agrochemicals with estrogenic endocrine disrupting properties: Lessons Learned?Molecular and cellular endocrinology · 2020Review
- The Use and Misuse of Historical Controls in Regulatory Toxicology: Lessons from the CLARITY-BPA Study.Endocrinology · 2020Article
- Impacts of food contact chemicals on human health: a consensus statement.Environmental health : a global access science source · 2020Article
- Untangling the association between environmental endocrine disruptive chemicals and the etiology of male genitourinary cancers.Biochemical pharmacology · 2020Review
- Diet as a Source of Exposure to Environmental Contaminants for Pregnant Women and Children from Six European Countries.Environmental health perspectives · 2019Article
- CLARITY-BPA academic laboratory studies identify consistent low-dose Bisphenol A effects on multiple organ systems.Basic & clinical pharmacology & toxicology · 2019Review
- Endocrine disruptors and the future of toxicology testing - lessons from CLARITY-BPA.Nature reviews. Endocrinology · 2019Review
- Adaptive responses to low doses of radiation or chemicals: their cellular and molecular mechanisms.Cellular and molecular life sciences : CMLS · 2019Review
- 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
- Preconception exposure to dietary levels of genistein affects female reproductive outcomes.Reproductive toxicology (Elmsford, N.Y.) · 2017Article
- The mouse mammary gland as a sentinel organ: distinguishing 'control' populations with diverse environmental histories.Environmental health : a global access science source · 2017Article
- Metabolism disrupting chemicals and metabolic disorders.Reproductive toxicology (Elmsford, N.Y.) · 2017Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA core assumption of current toxicologic procedures used to establish health standards for chemical exposures is that testing the safety of chemicals at high doses can be used to predict the effects of low-dose exposures, such as those common in the general population. This assumption is based on the precept that "the dose makes the poison": higher doses will cause greater effects.
objectivesWe challenge the validity of assuming that high-dose testing can be used to predict low-dose effects for contaminants that behave like hormones. We review data from endocrinology and toxicology that falsify this assumption and summarize current mechanistic understanding of how low doses can lead to effects unpredictable from high-dose experiments. DISCUSSION: Falsification of this assumption raises profound issues for regulatory toxicology. Many exposure standards are based on this assumption. Rejecting the assumption will require that these standards be reevaluated and that procedures employed to set health standards be changed. The consequences of these changes may be significant for public health because of the range of health conditions now plausibly linked to exposure to endocrine-disrupting contaminants.
conclusionsWe recommend that procedures to establish acceptable exposure levels for endocrine-disrupting compounds incorporate the inability for high-dose tests to predict low-dose results. Setting acceptable levels of exposure must include testing for health consequences at prevalent levels of human exposure, not extrapolations from the effects observed in high-dose experiments. Scientists trained in endocrinology must be engaged systematically in standard setting for endocrine-disrupting compounds.
Indexed as
Identifiers
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.