Food Contaminants
chlorpyrifos causes developmental neurotoxicity
In plain terms: Is chlorpyrifos dangerous to developing brains?
Contested Food Contaminants 🔬 Includes disconfirming
Part of: 🔍 pesticides in food
RefutedContestedStrong support
consensus score 0.04
Enough that US regulators pulled it from food use in 2021, and animal studies support harm at surprisingly low doses. But the human studies looking at ordinary food-level exposure came back null, so the risk is about high exposure, not groceries.
📅 Last reviewed: 2026-07-29 ⓘ
Evidence ladder
How far up the ladder this claim has climbed. A high consensus on a low rung means "consistent so far," not "proven in people."
Top evidence so far: Population patterns (Observational)
MechanismIn-vitroAnimalObservationalRCTMeta-analysis
How the studies fall
7 support 1 contradict 0 tested null 20 mixed · 28 sources, 8 independent groups
What the evidence shows
This is the finding that drove revocation of US food-use registrations in 2021, and the animal evidence is genuinely concerning: studies specifically designed to probe the low-dose question found lasting behavioural effects at doses near or below the level producing the classic cholinesterase inhibition, which is the contested scientific crux.
The evidence (28)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| Zwartsen A et al 2026 · study_type: in-vitro | in-vitro | mixed | moderate | [MECHANISM/in-vitro + regulatory] A human neuronal-progenitor-cell viability assay plus a pregnancy PBK model derived an in-vitro health-based threshold value (HBTV) for chlorpyrifos/chlorpyrifos-oxon DNT that was HIGHER than the maternal e TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Kendricks DR et al 2025 · study_type: animal | animal | mixed | moderate | [ANIMAL DNT, PRENATAL, 0.5 vs 5 mg/kg/day oral GD6.5-17.5, mice — KEY DOSE-RESPONSE STUDY, explicitly designed 'near the threshold to produce cholinesterase inhibition'] The high dose (5 mg/kg) impaired learning and disrupted brain oxidativ TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Normann SS et al 2024 · Neurotoxicology and teratology | observational | mixed | moderate | [HUMAN, DIETARY/background, prospective cohort n=812, Odense Child Cohort] Maternal urinary TCPy (median 1.67 μg/L) at GW28 vs child IQ (WISC-V) at 7y: a significant association appeared only at 'mid-level' exposure, not as a clean monotoni |
| Peterson BS et al 2025 · study_type: observational | observational | supports | moderate | [HUMAN, PRENATAL, n=270 (of 512 with CPF measured at delivery, from a 727-woman cohort), Columbia CCCEH Manhattan/Bronx cohort] Progressively higher prenatal CPF was associated with thicker fronto-temporal/posteroinferior cortex, reduced wh |
| Sherif MA et al 2025 · study_type: mechanism | mechanism | mixed | moderate | [MECHANISM/in-vitro] Chlorpyrifos directly potentiates and activates NMDA receptors in Xenopus oocytes (EC50 ≈40-55 nM for GluN2A/GluN2B) and mediates excitotoxicity in human fetal cortical neuronal stem cells (ReNcell CX) at 10 μM — nanomo TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Fage-Larsen B et al 2024 · Environmental research | observational | contradicts | moderate | [HUMAN, DIETARY/background, Odense Child Cohort, n=814-1114] Maternal (GW28) and child (age 5) urinary TCPy (medians 1.62 and 1.16 μg/L): 'No statistically significant associations were observed' between chlorpyrifos exposure and ADHD-sympt |
| Koenig JA et al 2025 · study_type: animal | animal | mixed | moderate | [ANIMAL DNT, PRENATAL/gestational, 5 mg/kg SC GD18-21, rat] Acetylcholinesterase was only 'modestly inhibited' and returned to baseline by postnatal day 12, with no overt acute toxicity — yet offspring showed persistent synaptic-plasticity TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Jiang Y et al 2026 · study_type: animal | animal | mixed | moderate | [ANIMAL DNT, larval, 0.01-100 μg/L water] Concentration-dependent effects: 100 μg/L reduced swimming activity ~49-58%; a low 1 μg/L dose modestly increased distance (+7%, p=.003), altered neurotransmitters (↑dopamine/GABA/acetylcholine), an TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Biosca-Brull J et al 2026 · study_type: animal | animal | mixed | moderate | [ANIMAL DNT, PRENATAL, 1 mg/kg/day oral GD12-18] In C57BL/6J and humanized APOE3/APOE4 mice, prenatal chlorpyrifos produced genotype- and sex-specific anxiety-like behavior and impaired long-term memory retention in APOE4 carriers of both s TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Koenig JA et al 2025 · bioRxiv | animal | mixed | moderate | [ANIMAL DNT — DUPLICATE/preprint version of PMID 40345837: same lab, same 5 mg/kg SC GD18-21 rat somatosensory-cortex design] Do not double-count against the published version; reports the same modest/transient AChE inhibition alongside per TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Biosca-Brull J et al 2021 · International journal of environmental research and public health | observational | supports | moderate | [HUMAN+ANIMAL SR] Systematic review of 45 human + 16 preclinical pesticide-ASD studies; chlorpyrifos is the most-studied OP preclinically, where gestational exposure raised ASD-like behaviors, while human studies of prenatal OP/OC exposure |
| Miglioranza E et al 2025 · study_type: animal | animal | mixed | moderate | [ANIMAL DNT, perinatal, 5 mg/kg/day oral to dams mating-to-weaning, mice; offspring not directly dosed] Adult offspring showed increased sighs/apneas during sleep, upregulated hippocampal pro-inflammatory cytokines, and downregulated PPAR g TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Valle EMA et al 2026 · Preprints.org | animal | mixed | low | [ANIMAL DNT, embryonic, 0.7-700 μg/L] Zebrafish embryos exposed to chlorpyrifos alone or with PFHxS for 5 days showed concentration-dependent reduced survival, increased malformations, decreased locomotor activity, and upregulated neurotoxi TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Rimawi I et al 2026 · study_type: animal | animal | mixed | low | [ANIMAL DNT, paternal preconception exposure, chicken] Paternal (pre-conception) chlorpyrifos exposure altered protein expression (GDNF, DCX, FOS, MAP2) in offspring learning-related brain regions and completely abolished cholinergic-mediat TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Mikó Z et al 2025 · study_type: animal | animal | mixed | moderate | [ANIMAL DNT, developmental (tadpole), 0.5 vs 5 μg/L] At the environmentally-relevant LOW concentration (0.5 μg/L), chronic or acute exposure had NO significant effect on survival, brain morphology, or behavior; only the higher 5 μg/L dose r |
| Lopez V et al 2026 · bioRxiv | animal | mixed | low | [ANIMAL DNT, developmental (tadpole stage 42-49), 1 μM] Xenopus laevis tadpoles exposed to chlorpyrifos during synaptogenesis showed abnormal schooling/body-axis alignment, reduced looping and increased seizure-like swimming, plus reduced i TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Mitzel KM et al 2025 · study_type: observational | observational | supports | low | [MECHANISM, narrative review] Reviews evidence that chlorpyrifos disrupts oxytocin/vasopressin ('nonapeptide') circuit organization during neurodevelopment, altering adult social behavior in non-traditional mammal models; no primary data, d |
| Grandjean P et al 2014 · The Lancet. Neurology | observational | supports | low | [HUMAN, narrative review — Grandjean & Landrigan, Lancet Neurology 2014] Names chlorpyrifos as one of six developmental neurotoxicants newly identified 2006-2014 (with manganese, fluoride, DDT, PCE, PBDEs) based on epidemiological studies; |
| Torres-Ruiz M et al 2026 · preprint | animal | mixed | low | [ANIMAL DNT/NAM, larval zebrafish] A new visual-acoustic thigmotaxis assay validated against caffeine/diazepam controls tested several neuroactive compounds including chlorpyrifos, reporting only that it produced 'stimulus-dependent respons |
| Kalenik S et al 2026 · study_type: observational | observational | supports | low | [MECHANISM, narrative review] Asserts chlorpyrifos and its oxon metabolite disrupt neurodevelopment via oxidative stress, neuroinflammation, and epigenetic alteration, alongside effects on endocrine, gut, hepatic, musculoskeletal and carcin |
| Koenig JA et al 2026 · study_type: animal | animal | mixed | moderate | [ANIMAL DNT, PRENATAL/gestational, rat] Gestational chlorpyrifos exposure increased spontaneously-firing fast-spiking parvalbumin interneurons and c-Fos activity in somatosensory cortex of juvenile/adult offspring, plus altered 5-HT1B recep TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Song S et al 2026 · Environmental pollution (Barking, Essex : 1987) | animal | mixed | low | [ANIMAL DNT, pregnancy+lactation exposure, mice] Chlorpyrifos during pregnancy and lactation produced ASD- and depression-like behaviors (repetitive/stereotypic behavior, social deficits) in offspring, rescued by trehalose via mTOR-autophag TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Coppola L et al 2025 · study_type: animal | animal | mixed | moderate | [ANIMAL/mixed SR] Systematic review of 70 papers (human, rodent, avian, fish) on 21st-century developmental-toxicity NAM data for chlorpyrifos: animal models show memory/learning/cognitive impairment via AChE inhibition, glutamate-receptor TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Juntarawijit Y et al 2021 · preprint | observational | supports | low | [HUMAN, RESIDENTIAL/maternal pesticide-use route] Case-control study (442 developmental-delay cases vs 413 controls), Thailand: maternal chlorpyrifos use in pregnancy associated with developmental delay, OR 3.71 (95% CI 1.03-13.36, ever-use |
| Kebieche N et al 2026 · study_type: in-vitro | in-vitro | mixed | moderate | [MECHANISM/in-vitro] Mouse cortical neurosphere NAM used chlorpyrifos as the 'DNT-positive reference compound': biphasic response with early neurosphere enlargement then growth arrest and impaired radial migration, with overt cytotoxicity o TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Sami SA et al 2025 · study_type: observational | observational | supports | low | [MECHANISM, narrative review] States chlorpyrifos, an AChE inhibitor, 'at low levels causes cognitive deficits, developmental delays, and behaviour problems' — asserted as a summary claim without citing specific studies, doses, or effect si |
| Diaz L et al 2025 · preprint | animal | mixed | low | [ANIMAL DNT, embryonic, zebrafish] Embryonic chlorpyrifos exposure caused lasting social-behavior deficits and suppressed neuronal/ASD-risk genes (RNA-seq) in brain, rescued by the gut metabolite butyrate via HDAC1 inhibition; links CPF-ind TEMPERED: preclinical (animal/in-vitro) evidence, retained in the ledger but not carrying a human-outcome headline; dosing is typically far above human exposure. |
| Guardia-Escote L et al 2025 · study_type: animal | animal | mixed | moderate | [ANIMAL DNT, postnatal (PND10-15), oral, mice] Postnatal chlorpyrifos affected spatial-learning performance only in 'certain groups' when later combined with a high-fat diet, with sex- and APOE-genotype-dependent direction (apoE4-TR females |
Disagree, or know a study we missed?
We grade by evidence, not opinions. The way to weigh in is to point us to a study we haven't cited (check the evidence table above first), or to flag a problem with one we have. Every submission is reviewed; if it holds up, the grade updates and shows in Science Changes Its Mind.
Opens a short form. You'll sign in with Google so submissions are tied to a real account — we don't display your identity, and we only accept a link we can verify (PubMed, DOI, ClinicalTrials.gov).
Educational only, not medical advice. Grades and scores reflect published evidence weighted by study design and quality; see the methodology.