{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T08:24:31Z","timestamp":1794385471643,"version":"4.9.0"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Dutch Research Council","doi-asserted-by":"publisher","award":["NWA-ORC 1292.19.272"],"award-info":[{"award-number":["NWA-ORC 1292.19.272"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007192","name":"Rijksinstituut voor Volksgezondheid en Milieu","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007192","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology"],"published-print":{"date-parts":[[2026,11]]},"DOI":"10.1016\/j.tox.2026.154526","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:27:06Z","timestamp":1781105226000},"page":"154526","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Exposure matters: The impact of exposure characteristics on In Vitro neurotoxicity of pesticides and implications for regulatory testing"],"prefix":"10.1016","volume":"526","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6487-1655","authenticated-orcid":false,"given":"Julia J.","family":"Meerman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo L.","family":"Sinnige","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1971-2385","authenticated-orcid":false,"given":"Walther","family":"Klerx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Tuominen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Legler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldert H.","family":"Piersma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3269-5586","authenticated-orcid":false,"given":"Harm J.","family":"Heusinkveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4948-2007","authenticated-orcid":false,"given":"Remco H.S.","family":"Westerink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.tox.2026.154526_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2024.172838","article-title":"Literature review and meta-analysis of environmental toxins associated with increased risk of Parkinson's disease","volume":"931","author":"Aravindan","year":"2024","journal-title":"Sci. Total. Environ."},{"issue":"1","key":"10.1016\/j.tox.2026.154526_bib2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1471-2210-8-8","article-title":"Comparison of four different colorimetric and fluorometric cytotoxicity assays in a zebrafish liver cell line","volume":"8","author":"Bopp","year":"2008","journal-title":"BMC Pharmacol."},{"issue":"1","key":"10.1016\/j.tox.2026.154526_bib3","doi-asserted-by":"crossref","DOI":"10.1186\/1750-1326-3-21","article-title":"Chronic, low-dose rotenone reproduces lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells","volume":"3","author":"Borland","year":"2008","journal-title":"Mol. Neurodegener."},{"issue":"1","key":"10.1016\/j.tox.2026.154526_bib4","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41420-023-01790-7","article-title":"A new advanced cellular model of functional cholinergic-like neurons developed by reprogramming the human SH-SY5Y neuroblastoma cell line","volume":"10","author":"D'Aloia","year":"2024","journal-title":"Cell. Death Discov."},{"key":"10.1016\/j.tox.2026.154526_bib5","unstructured":"Dinoseb2011. ILO-WH) International Chemical Safety Cards (ICSCs). \u3008https:\/\/chemicalsafety.ilo.org\/dyn\/icsc\/showcard.display?p_card_id=0149\u3009."},{"issue":"6","key":"10.1016\/j.tox.2026.154526_bib6","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.neuro.2007.04.008","article-title":"Reactive oxygen species generation by the ethylene-bis-dithiocarbamate (EBDC) fungicide mancozeb and its contribution to neuronal toxicity in mesencephalic cells","volume":"28","author":"Domico","year":"2007","journal-title":"NeuroToxicology"},{"issue":"8","key":"10.1016\/j.tox.2026.154526_bib7","doi-asserted-by":"crossref","first-page":"618","DOI":"10.2174\/1871527319666200708132716","article-title":"Quantitative characterization of phenotypical markers after differentiation of SH-SY5Y cells","volume":"19","author":"Ducray","year":"2020","journal-title":"CNS Neurol. Disord. - Drug. Targets"},{"key":"10.1016\/j.tox.2026.154526_bib8","unstructured":"Endosulfan (mixed isomers)1998. ILO-WHO International Chemical Safety Cards (ICSCs). \u3008https:\/\/chemicalsafety.ilo.org\/dyn\/icsc\/showcard.display?p_lang=en&p_card_id=0742&p_version=2\u3009."},{"key":"10.1016\/j.tox.2026.154526_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.envpol.2022.119024","article-title":"Pesticides in doormat and floor dust from homes close to treated fields: spatio-temporal variance and determinants of occurrence and concentrations","volume":"301","author":"Figueiredo","year":"2022","journal-title":"Environ. Pollut."},{"issue":"8","key":"10.1016\/j.tox.2026.154526_bib10","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1007\/s00204-018-2250-8","article-title":"Toxicity, recovery, and resilience in a 3D dopaminergic neuronal in vitro model exposed to rotenone","volume":"92","author":"Harris","year":"2018","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.tox.2026.154526_bib11","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.toxlet.2016.04.014","article-title":"Vitro neurotoxic hazard characterisation of dinitrophenolic herbicides","volume":"252","author":"Heusinkveld","year":"2016","journal-title":"Toxicol. Lett."},{"issue":"3","key":"10.1016\/j.tox.2026.154526_bib12","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s10654-017-0229-z","article-title":"Agricultural activities and the incidence of Parkinson's disease in the general French population","volume":"32","author":"Kab","year":"2017","journal-title":"Eur. J. Epidemiol."},{"key":"10.1016\/j.tox.2026.154526_bib13","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.3389\/ftox.2026.1790669","article-title":"Next generation validation for next generation risk assessment","volume":"8","author":"Kopa\u0144ska","year":"2026","journal-title":"Front. Toxicol."},{"issue":"10","key":"10.1016\/j.tox.2026.154526_bib14","doi-asserted-by":"crossref","first-page":"4355","DOI":"10.1038\/s41380-022-01663-y","article-title":"Transcriptomics analysis of human iPSC-derived dopaminergic neurons reveals a novel model for sporadic Parkinson\u2019s disease","volume":"27","author":"Krauskopf","year":"2022","journal-title":"Mol. Psychiatry"},{"issue":"2-4","key":"10.1016\/j.tox.2026.154526_bib15","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1080\/10937404.2010.483176","article-title":"Toxicity testing in the 21st century: a vision and a strategy","volume":"13","author":"Krewski","year":"2010","journal-title":"J. Toxicol. Environ. Health B Crit. Rev."},{"issue":"7378","key":"10.1016\/j.tox.2026.154526_bib16","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nature10648","article-title":"Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease","volume":"480","author":"Kriks","year":"2011","journal-title":"Nature"},{"issue":"5","key":"10.1016\/j.tox.2026.154526_bib17","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2025.9198","article-title":"Proximity to golf courses and risk of parkinson disease","volume":"8","author":"Krzyzanowski","year":"2025","journal-title":"JAMA Netw. Open."},{"key":"10.1016\/j.tox.2026.154526_bib18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mito.2018.06.003","article-title":"Mancozeb selectively induces mitochondrial-mediated apoptosis in human gastric carcinoma cells through ROS generation","volume":"48","author":"Kumar","year":"2019","journal-title":"Mitochondrion"},{"key":"10.1016\/j.tox.2026.154526_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2022.160851","article-title":"Proximity to residential and workplace pesticides application and the risk of progression of Parkinson's diseases in Central California","volume":"864","author":"Li","year":"2023","journal-title":"Sci. Total. Environ."},{"key":"10.1016\/j.tox.2026.154526_bib20","unstructured":"Mancozeb2003. ILO-WHO International Chemical Safety Cards (ICSCs). \u3008https:\/\/chemicalsafety.ilo.org\/dyn\/icsc\/showcard.display?p_lang=en&p_card_id=0754&p_version=2\u3009."},{"key":"10.1016\/j.tox.2026.154526_bib21","unstructured":"Mancozeb Hazardous Substances Data Bank (HSDB). \u3008https:\/\/pubchem.ncbi.nlm.nih.gov\/source\/hsdb\/6792\u3009."},{"key":"10.1016\/j.tox.2026.154526_bib22","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.neuro.2023.11.001","article-title":"An adverse outcome pathway for chemical-induced Parkinson\u2019s disease: Calcium is key","volume":"99","author":"Meerman","year":"2023","journal-title":"NeuroToxicology"},{"key":"10.1016\/j.tox.2026.154526_bib23","article-title":"Neurodegeneration in a regulatory context: The need for speed","volume":"33","author":"Meerman","year":"2023","journal-title":"Curr. Opin. Toxicol."},{"issue":"1","key":"10.1016\/j.tox.2026.154526_bib24","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/toxsci\/kfu110","article-title":"Inhibition of voltage-gated calcium channels as common mode of action for (mixtures of) distinct classes of insecticides","volume":"141","author":"Meijer","year":"2014","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.tox.2026.154526_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2023.167797","article-title":"Occurrence of pesticide residues in indoor dust of farmworker households across Europe and Argentina","volume":"905","author":"Navarro","year":"2023","journal-title":"Sci. Total. Environ."},{"issue":"2","key":"10.1016\/j.tox.2026.154526_bib26","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1093\/toxsci\/kfx145","article-title":"From the cover: manganese and rotenone-induced oxidative stress signatures differ in iPSC-derived human dopamine neurons","volume":"159","author":"Neely","year":"2017","journal-title":"Toxicol. Sci."},{"issue":"1","key":"10.1016\/j.tox.2026.154526_bib27","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1038\/s41467-023-38215-z","article-title":"A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides","volume":"14","author":"Paul","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.tox.2026.154526_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.envres.2021.111161","article-title":"Pesticides expenditures by farming type and incidence of Parkinson disease in farmers: a French nationwide study","volume":"197","author":"Perrin","year":"2021","journal-title":"Environ. Res."},{"issue":"1","key":"10.1016\/j.tox.2026.154526_bib29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41531-024-00864-2","article-title":"Investigating Parkinson's disease risk across farming activities using data mining and large-scale administrative health data","volume":"11","author":"Petit","year":"2025","journal-title":"NPJ Park. Dis."},{"issue":"13","key":"10.1016\/j.tox.2026.154526_bib30","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25137439","article-title":"Exploring the regulation of cytochrome P450 in SH-SY5Y cells: implications for the onset of neurodegenerative diseases","volume":"25","author":"Pifferi","year":"2024","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.tox.2026.154526_bib31","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1093\/ije\/dyx225","article-title":"Pesticide use in agriculture and Parkinson's disease in the AGRICAN cohort study","volume":"47","author":"Pouchieu","year":"2018","journal-title":"Int. J. Epidemiol."},{"issue":"6","key":"10.1016\/j.tox.2026.154526_bib32","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0361-9230(97)00328-6","article-title":"Staurosporine Differentiated Human SH-SY5Y Neuroblastoma Cultures Exhibit Transient Apoptosis and Trophic Factor Independence","volume":"43","author":"Prince","year":"1997","journal-title":"Brain Res. Bull."},{"key":"10.1016\/j.tox.2026.154526_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.tiv.2021.105133","article-title":"Effective exposure of chemicals in in vitro cell systems: a review of chemical distribution models","volume":"73","author":"Proen\u00e7a","year":"2021","journal-title":"Toxicol. Vitr."},{"key":"10.1016\/j.tox.2026.154526_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2021.105587","article-title":"Brunner syndrome associated MAOA mutations result in NMDAR hyperfunction and increased network activity in human dopaminergic neurons","volume":"163","author":"van Rhijn","year":"2022","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.tox.2026.154526_bib35","unstructured":"Rotenone2000. ILO-WHO International Chemical Safety Cards (ICSCs). \u3008https:\/\/chemicalsafety.ilo.org\/dyn\/icsc\/showcard.display?p_lang=en&p_card_id=0944&p_version=2\u3009."},{"key":"10.1016\/j.tox.2026.154526_bib36","unstructured":"Rotenone Hazardous Substance Data Bank.\u3008https:\/\/pubchem.ncbi.nlm.nih.gov\/source\/hsdb\/1762\u3009."},{"key":"10.1016\/j.tox.2026.154526_bib37","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.taap.2017.06.013","article-title":"Distribution, lipid-bilayer affinity and kinetics of the metabolic effects of dinoseb in the liver","volume":"329","author":"Salla","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"issue":"2","key":"10.1016\/j.tox.2026.154526_bib38","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.toxlet.2014.02.001","article-title":"Immediate and delayed effects of subchronic Paraquat exposure during an early differentiation stage in 3D-rat brain cell cultures","volume":"230","author":"Sandstr\u00f6m von Tobel","year":"2014","journal-title":"Toxicol. Lett."},{"key":"10.1016\/j.tox.2026.154526_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.envint.2023.108082","article-title":"New approach methodologies in human regulatory toxicology \u2013 not if, but how and when!","volume":"178","author":"Schmeisser","year":"2023","journal-title":"Environ. Int."},{"issue":"5","key":"10.1016\/j.tox.2026.154526_bib40","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1007\/s00204-024-03703-8","article-title":"Recent advances and current challenges of new approach methodologies in developmental and adult neurotoxicity testing","volume":"98","author":"Serafini","year":"2024","journal-title":"Arch. Toxicol."},{"issue":"16","key":"10.1016\/j.tox.2026.154526_bib41","doi-asserted-by":"crossref","first-page":"7006","DOI":"10.1523\/JNEUROSCI.22-16-07006.2002","article-title":"An in vitro model of Parkinson's disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage","volume":"22","author":"Sherer","year":"2002","journal-title":"J. Neurosci."},{"key":"10.1016\/j.tox.2026.154526_bib42","doi-asserted-by":"crossref","unstructured":"Shilpa, T., Vaishnavi, A., Nair, A.R., 2025. Oxidative imbalance induced by dithiocarbamate fungicide, Mancozeb aborts Nrf2 anti-oxidant signaling pathway protection in Vero cell line. Pharmacological Research - Reports 3:100041 doi:https:\/\/doi.org\/10.1016\/j.prerep.2025.100041.","DOI":"10.1016\/j.prerep.2025.100041"},{"key":"10.1016\/j.tox.2026.154526_bib43","doi-asserted-by":"crossref","DOI":"10.1016\/j.envres.2020.110186","article-title":"Pesticide use and incident Parkinson's disease in a cohort of farmers and their spouses","volume":"191","author":"Shrestha","year":"2020","journal-title":"Environ. Res."},{"issue":"11","key":"10.1016\/j.tox.2026.154526_bib44","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1007\/s00204-015-1637-z","article-title":"A LUHMES 3D dopaminergic neuronal model for neurotoxicity testing allowing long-term exposure and cellular resilience analysis","volume":"90","author":"Smirnova","year":"2016","journal-title":"Arch. Toxicol."},{"issue":"11","key":"10.1016\/j.tox.2026.154526_bib45","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.3390\/antiox14111274","article-title":"Mechanistic insights into mancozeb-induced redox imbalance and structural remodelling affecting the function of human red blood cells","volume":"14","author":"Spinelli","year":"2025","journal-title":"Antioxidants"},{"key":"10.1016\/j.tox.2026.154526_bib46","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuro.2026.103393","article-title":"Prolonged duration induces divergent transcriptomic responses to manganese, distinct from concentration effects, in an SH-SY5Y neurotoxicity model","volume":"113","author":"Tang","year":"2026","journal-title":"NeuroToxicology"},{"issue":"6","key":"10.1016\/j.tox.2026.154526_bib47","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1289\/ehp.1002839","article-title":"Rotenone, paraquat, and Parkinson's disease","volume":"119","author":"Tanner","year":"2011","journal-title":"Environ. Health Perspect."},{"issue":"1","key":"10.1016\/j.tox.2026.154526_bib48","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00204-017-2133-4","article-title":"An adverse outcome pathway for parkinsonian motor deficits associated with mitochondrial complex I inhibition","volume":"92","author":"Terron","year":"2018","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.tox.2026.154526_bib49","unstructured":"Toxicological Profile for Endosulfan. Atlanta (GA): agency for toxic substances and disease registry (US); 2015 Aug. 4, CHEMICAL AND PHYSICAL INFORMATION. Available from: \u3008https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK592006\/\u3009."},{"issue":"2","key":"10.1016\/j.tox.2026.154526_bib50","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0306-4522(02)00875-8","article-title":"The organochlorine pesticides gamma-hexachlorocyclohexane (lindane), alpha-endosulfan and dieldrin differentially interact with GABA(A) and glycine-gated chloride channels in primary cultures of cerebellar granule cells","volume":"117","author":"Vale","year":"2003","journal-title":"Neuroscience"}],"container-title":["Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X26001332?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X26001332?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T07:35:27Z","timestamp":1794382527000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0300483X26001332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,11]]},"references-count":50,"alternative-id":["S0300483X26001332"],"URL":"https:\/\/doi.org\/10.1016\/j.tox.2026.154526","relation":{},"ISSN":["0300-483X"],"issn-type":[{"value":"0300-483X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Exposure matters: The impact of exposure characteristics on In Vitro neurotoxicity of pesticides and implications for regulatory testing","name":"articletitle","label":"Article Title"},{"value":"Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tox.2026.154526","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"154526"}}