ArticleDose-response : a publication of International Hormesis Society
Nonmonotonic Dose-Response Curves Occur in Dose Ranges That Are Relevant to Regulatory Decision-Making.
Article in Dose-response : a publication of International Hormesis Society. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis 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
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
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- Developmental Toxicity of Photolithography-Relevant Per- and Polyfluoroalkyl Substances (PFAS) Reveals Concerns for Less-Studied Functional Groups.Environmental science & technology · 2026Article
- Phytochemical profiling and pharmacological evaluation ofFrontiers in pharmacology · 2026Article
- Seasonal and geographic patterns of gastroschisis in Canada: protective effect of periconceptional sunlight exposure.Frontiers in endocrinology · 2026Article
- Low-level tetrabromobisphenol A (TBBPA) exposure disrupts early embryonic architecture: molecular impacts on dorsoventral patterning.Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · 2026Article
- Reproductive Impact of Natural, Synthetic and Emerging Chemicals on Wildlife and Domestic Animals.Advances in experimental medicine and biology · 2026Review
- Assessing the neuroendocrine and psychological effects of acute everolimus administration in healthy male participants.Brain, behavior, & immunity - health · 2025Article
- Prenatal Exposure to Imidacloprid Affects Cognition and Anxiety-Related Behaviors in Male and Female CD-1 Mice.Toxics · 2025Article
- Serotonergic and Cholinergic Imbalance in the Offspring of Rats Exposed to Bisphenol A and Bisphenol S During Pregnancy and Lactation: Short- and Long-Term Effects.International journal of molecular sciences · 2025Article
- Combined Effects of PFAS, Social, and Behavioral Factors on Liver Health.Medical sciences (Basel, Switzerland) · 2025Article
- Effects of organic and inorganic contaminants and their mixtures on metabolic health and gene expression in developmentally exposed zebrafish.Environmental toxicology and chemistry · 2025Article
- Prenatal exposure to persistent organic pollutants and associations with child behavior problems at 1-5 years.Environmental pollution (Barking, Essex : 1987) · 2025Article
- The Industrial Residue of Andiroba (Veterinary sciences · 2025Article
- Advancing the Spatiotemporal Dimension of Wildlife-Pollution Interactions.Environmental science & technology letters · 2025Review
- Effectiveness effects ofOpen veterinary journal · 2025Article
- Pesticides, an urgent challenge to global environmental health and planetary boundaries.Frontiers in toxicology · 2025Review
- The ENDOMIX perspective: how everyday chemical mixtures impact human health and reproduction by targeting the immune system†.Biology of reproduction · 2024Review
- DINCH Exposure Triggers Inflammatory, Oxidative, and Apoptotic Pathways in the Liver of Long-Evans Lactating Rats and Their Offspring.International journal of molecular sciences · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Non-monotonic dose response curves (NMDRCs) occur in cells, tissues, animals and human populations in response to nutrients, vitamins, pharmacological compounds, hormones and endocrine disrupting chemicals (EDCs). Yet, regulatory agencies have argued that NMDRCs are not common, are not found for adverse outcomes, and are not relevant for regulation of EDCs. Under the linear dose response model, high dose testing is used to extrapolate to lower doses that are anticipated to be 'safe' for human exposures. NMDRCs that occur below the toxicological no-observed-adverse-effect level (NOAEL) would falsify a fundamental assumption, that high dose hazards can be used to predict low dose safety. In this commentary, we provide examples of NMDRCs and discuss how their presence in different portions of the dose response curve might affect regulatory decisions. We provide evidence that NMDRCs do occur below the NOAEL dose, and even below the 'safe' reference dose, for chemicals such as resveratrol, permethrin, chlorothalonil, and phthalates such as DEHP. We also briefly discuss the recent CLARITY-BPA study, which reported mammary adenocarcinomas only in rats exposed to the lowest BPA dose. We conclude our commentary with suggestions for how NMDRCs should be acknowledged and utilized to improve regulatory toxicity testing and in the calculation of reference doses that are public health protective.
Indexed as
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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.