Neurobehavioural effects of developmental toxicity
Open accessAbstract
Neurodevelopmental disabilities, including autism, attention-deficit hyperactivity disorder, dyslexia, and other cognitive impairments, affect millions of children worldwide, and some diagnoses seem to be increasing in frequency. Industrial chemicals that injure the developing brain are among the known causes for this rise in prevalence. In 2006, we did a systematic review and identified five industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls, arsenic, and toluene. Since 2006, epidemiological studies have documented six additional developmental neurotoxicants-manganese, fluoride, chlorpyrifos, dichlorodiphenyltrichloroethane, tetrachloroethylene, and the polybrominated diphenyl ethers. We postulate that even more neurotoxicants remain undiscovered. To control the pandemic of developmental neurotoxicity, we propose a global prevention strategy. Untested chemicals should not be presumed to be safe to brain development, and chemicals in existing use and all new chemicals must therefore be tested for developmental neurotoxicity. To coordinate these efforts and to accelerate translation of science into prevention, we propose the urgent formation of a new international clearinghouse.
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Direct evidence linking any specific EDC to a clearly defined clinical disorder involving the social brain is sparse, and no single chemical has yet been definitively implicated.
“Direct evidence linking any specific EDC to a clearly defined clinical disorder involving the social brain is sparse, and no single chemical has yet been definitively implicated (18, 21–25).”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [22]
In “Other suspected developmental neurotoxicants” (page unavailable), the paper links phthalates to impaired social interactions and says their effects could relate to endocrine disruption. In “Developmental neurotoxicity and clinical neurology” (page unavailable), it links phthalates to ADHD risk and autism-like behaviours. These are qualified associations, but the paper does not establish that direct evidence is sparse overall or state that no individual EDC has been definitively implicated in a clinical disorder involving the social brain. (LLM, conf=0.78)
Experimental — accuracy not yet measuredCPF has been linked to ADHD and other developmental neural disorders in children.
“CPF has been linked to ADHD and other developmental neural disorders in children, prompting the EPA to impose a ban on residential use in 2001 (22, 106, 107).”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [22]
In “Newly recognised developmental neurotoxicants” (page unavailable), the paper links prenatal chlorpyrifos exposure to neurobehavioural deficits and brain abnormalities in children. “Developmental neurotoxicity and clinical neurology” links ADHD risk to organophosphates as a group, but does not specifically link chlorpyrifos to an ADHD diagnosis. The cited passages also do not establish that these findings prompted a 2001 EPA residential-use ban. (LLM, conf=0.87)
Experimental — accuracy not yet measuredDevelopmental neurotoxicity (DNT) testing is particularly critical, as chemical-induced disruptions in neurogenesis, synaptogenesis, migration, or network formation during vulnerable developmental windows can cause lifelong neurological deficits.
“Developmental neurotoxicity (DNT) testing is particularly critical, as chemical-induced disruptions in neurogenesis, synaptogenesis, migration, or network formation during vulnerable developmental windows can cause lifelong neurological deficits (Rice and Barone, 2000; Grandjean and Landrigan, 2014).”
From Challenges and solutions in transitioning to animal-free standards: a comprehensive analysis of components in human cell-based developmental neurotoxicity assays (2026) · cites this paper as Grandjean and Landrigan, 2014
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredOrganophosphate pesticides can have endocrine disrupting properties, particularly at environmentally relevant doses below those causing systemic toxicity.
“Although their primary mechanism of action is inhibition of acetylcholinesterase, they can also have endocrine disrupting properties, particularly at dose levels which are more environmentally relevant and well below those which cause systemic toxicity (16, 22, 105).”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [22]
The Introduction’s ‘Newly recognised developmental neurotoxicants’ section links prenatal organophosphate exposure to neurodevelopmental effects, but does not describe endocrine disruption or specify doses below those causing systemic toxicity. The ‘Other suspected developmental neurotoxicants’ section discusses endocrine disruption in relation to phthalates instead. Searches for organophosphates, endocrine disruption, acetylcholinesterase and low-dose effects found no passage establishing the attributed claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredXenobiotic agents may act through diverse pathophysiological pathways in the immune, gut-brain and endocrine systems, interacting with genetic factors, thus altering neurodevelopment of neural circuitry and synapses, cell migration and connectivity.
“Xenobiotic agents may act through diverse pathophysiological pathways in the immune, gut–brain and endocrine systems, interacting with genetic factors, thus altering the neurodevelopment of neural circuitry and synapses, cell migration and connectivity [184].”
From The contribution of environmental exposure to the etiology of autism spectrum disorder (2019) · cites this paper as [184]
Of more than 80,000 chemicals, over 1,000 have laboratory evidence of neurotoxicity, but only a small fraction have been studied in humans during critical developmental windows.
“out of a chemical universe topping 80,000 agents, over 1000 have laboratory evidence of neurotoxicity, but only a small fraction have been studied in humans during critical windows of development.10,11”
From Environmental Chemical Exposures and Autism Spectrum Disorders: A Review of the Epidemiological Evidence (2014) · cites this paper as [11]
Arsenic, fluoride, and manganese are increasingly recognized as human neurodevelopmental toxicants.
“Other metals, including arsenic, fluoride, and manganese, are increasingly recognized as also being human neurodevelopmental toxicants.”
From Environmental Chemical Exposures and Autism Spectrum Disorders: A Review of the Epidemiological Evidence (2014) · cites this paper as [11]
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- Authors
- Grandjean, P., & Landrigan, P. J.
- Affiliations
- Harvard University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Grandjean, Philippe
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 13
- Issue
- 3
- Pages
- 330-338
- ISSN
- 1474-4422 (ISSN-L)
- PMC
- PMC4418502
- OpenAlex
- W2152739465
- Cited by
- 1,886
- References
- 113
- Citations by year
- 2026: 173 · 2025: 166 · 2024: 148 · 2023: 180 · 2022: 157 · 2021: 163 · 2020: 156 · 2019: 151 · 2018: 155 · 2017: 126 · 2016: 146 · 2015: 115 · 2014: 46
- FWCI
- 14.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences (ES09797, ES11687, ES09584, P01ES009584, U01ES009797, R01ES009797, R01ES011681)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Keywords
- developmental neurotoxicity, industrial chemicals, neurodevelopmental disorders, autism spectrum disorder, attention deficit hyperactivity disorder, dyslexia, lead, methylmercury, polychlorinated biphenyls, arsenic, toluene, manganese, fluoride, chlorpyrifos, DDT, tetrachloroethylene, polybrominated diphenyl ethers, neurotoxicity testing, prevention
- MeSH terms
- Animals, Brain, Developmental Disabilities, Environmental Exposure, Humans, Methylmercury Compounds, Polychlorinated Biphenyls, Neurotoxicity Syndromes
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