{"v":1,"ledgerId":"mit","generatedAt":"2026-11-05T21:27:14.479Z","query":"(TITLE:(\"Methylisothiazolinone\" OR \"METHYLISOTHIAZOLINONE\" OR \"METHYLCHLOROISOTHIAZOLINONE\" OR \"KATHON CG\" OR \"2682-20-4\") OR ABSTRACT:(\"Methylisothiazolinone\" OR \"METHYLISOTHIAZOLINONE\" OR \"METHYLCHLOROISOTHIAZOLINONE\" OR \"KATHON CG\" OR \"2682-20-4\")) AND (TOXICITY OR EXPOSURE OR \"ENDOCRINE\" OR \"REPRODUCTIVE\" OR CARCINOGEN* OR \"BIOMONITORING\" OR \"SYSTEMATIC REVIEW\") AND SRC:MED AND LANG:eng","totalPapers":287,"lastYearPapers":26,"analysed":35,"byFunding":{"independent":15,"industry":1,"mixed":1,"none_declared":1,"unclear":17},"byDesign":{"human":12,"animal":5,"in_vitro":6,"review":4,"other":8},"byFinding":{"concern":29,"no_effect":5,"mixed":1},"gap":{"independent":{"concern":10,"total":15},"industry":{"concern":1,"total":1}},"fundingSources":{"full_text":9,"grant_metadata":16,"abstract":0,"none":10},"newestPublished":"2026-10-23","papers":[{"id":"pmid:42919945","pmid":"42919945","pmcid":"","doi":"10.1007/s00204-026-04592-9","title":"Mechanistic pathways of cosmetic ingredient toxicity: a critical review of in vitro and in vivo evidence.","journal":"Archives of toxicology","published":"2026-10-23","design":"systematic_review","finding":"concern","summary":"A scoping review maps cosmetic ingredient toxicology, noting evidence linking benzophenone-3 to estrogen receptor activation, lower testosterone, and altered pubertal timing.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:42702274","pmid":"42702274","pmcid":"","doi":"10.1016/j.tiv.2026.106298","title":"Comparative toxicoproteomics reveals distinct proteostasis and ribosomal stress signatures of CMIT and PHMG.","journal":"Toxicology in vitro : an international journal published in association with BIBRA","published":"2026-09-06","design":"in_vitro","finding":"concern","summary":"Subcytotoxic exposure to CMIT altered 73 proteins in human alveolar epithelial A549 cells, preferentially affecting proteostasis, oxidative stress, and protein quality control pathways.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42708931","pmid":"42708931","pmcid":"","doi":"10.1021/acs.est.6c05943","title":"Divergent Evolutionary Trajectories of Pseudomonas aeruginosa PAO1 under Trace versus Preservative-Level Antimicrobial Methylisothiazolinone Exposure.","journal":"Environmental science & technology","published":"2026-09-01","design":"in_vitro","finding":"concern","summary":"Methylisothiazolinone exposure enhanced horizontal gene transfer capacity at trace levels and drove antibiotic resistance mutations and hypervirulence at preservative levels in Pseudomonas aeruginosa.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"National Natural Science Foundation of China\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42438158","pmid":"42438158","pmcid":"PMC13555111","doi":"10.1111/1346-8138.70378","title":"Hand Eczema Referred for Patch Testing: Retrospective Study in Shanghai, China From 2018 to 2023.","journal":"The Journal of dermatology","published":"2026-07-12","design":"human_cohort","finding":"concern","summary":"A retrospective cohort study identified methylisothiazolinone and methylisothiazolinone/methylchloroisothiazolinone among the top five allergens associated with hand eczema in patch-tested patients.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"National Natural Science Foundation of China\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42419525","pmid":"42419525","pmcid":"","doi":"10.1016/j.tiv.2026.106277","title":"Integrating multi-organ cytokine responses with CTD and AOP-based knowledge to identify disease-relevant hazard signals: A case study of CMIT/MIT.","journal":"Toxicology in vitro : an international journal published in association with BIBRA","published":"2026-07-08","design":"in_vitro","finding":"concern","summary":"CMIT/MIT exposure induced dose-dependent ROS elevation and cell type-specific cytokine perturbations across four human cell lines, indicating multi-organ disease hazard signals.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"Horizon 2020\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42324175","pmid":"42324175","pmcid":"PMC13551383","doi":"10.1111/cod.70207","title":"Fragrance and Preservative Contact Allergens in Cosmetic and Household Cleaning Products in Turkey: Variation by Target Population, Product Type and Manufacturing Origin.","journal":"Contact dermatitis","published":"2026-06-21","design":"other","finding":"concern","summary":"An evaluation of 245 cosmetic and cleaning products in Turkey found methylisothiazolinone and methylchloroisothiazolinone were among the most frequent preservative allergens detected on product labels.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:42300206","pmid":"42300206","pmcid":"PMC13551410","doi":"10.1111/cod.70202","title":"Methylchloroisothiazolinone and Methylisothiazolinone 10 Years After Regulation: A Case Story of Liquid Soaps and Shampoos.","journal":"Contact dermatitis","published":"2026-06-16","design":"other","finding":"concern","summary":"Analysis of Danish cosmetic products found two of 25 labelled products exceeded the 15 ppm limit for MCI/MI, suggesting the regulatory limit may not sufficiently protect against contact allergy.","funding":"mixed","conflictOfInterest":false,"fundingEvidence":["industry: \"unrestricted grant\"","public: \"European Union\""],"fundingSource":"full_text","verified":false},{"id":"pmid:42159740","pmid":"42159740","pmcid":"","doi":"10.1007/s00204-026-04452-6","title":"Translating human biomonitoring data into quantitative exposure and risk estimates for chloromethylisothiazolinone and methylisothiazolinone using a population pharmacokinetic model.","journal":"Archives of toxicology","published":"2026-05-20","design":"other","finding":"no_effect","summary":"A population pharmacokinetic model using biomonitoring data showed that CMIT/MIT exposures in general populations yield margins of exposure above 1, indicating unlikely health concerns under typical conditions.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"Institute of\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42144692","pmid":"42144692","pmcid":"PMC13441379","doi":"10.1111/cod.70186","title":"Patch Testing in Chronic Hand Eczema: A Multicentre Study in Portugal.","journal":"Contact dermatitis","published":"2026-05-17","design":"human_cross_sectional","finding":"concern","summary":"In a multicentre study of chronic hand eczema patients, methylisothiazolinone was confirmed as an emergent allergen, showing frequent relevance particularly in patients with atopic dermatitis.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:42097823","pmid":"42097823","pmcid":"PMC13441323","doi":"10.1111/cod.70181","title":"Contact Sensitisation Trends in Slovenian Children and Adolescents: A Retrospective Single-Centre Study.","journal":"Contact dermatitis","published":"2026-05-07","design":"human_cross_sectional","finding":"concern","summary":"In a retrospective study of Slovenian pediatric patients, methylisothiazolinone emerged as an important allergen with a 3.2% contact sensitisation rate in 2020–2024.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"full_text","verified":false},{"id":"pmid:42115796","pmid":"42115796","pmcid":"","doi":"10.15586/aei.v54i3.1621","title":"Forgotten Skin: What do our geriatric patch test findings reveal?","journal":"Allergologia et immunopathologia","published":"2026-05-01","design":"human_cross_sectional","finding":"concern","summary":"Methylchloroisothiazolinone/methylisothiazolinone and methylisothiazolinone were among the most frequent contact allergens identified in patch testing of patients aged 75 years or older.","funding":"none_declared","conflictOfInterest":false,"fundingEvidence":["none: \"No funding\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:41889151","pmid":"41889151","pmcid":"PMC13238301","doi":"10.1111/cod.70147","title":"Development of a Generic Analysis Method for Isothiazolinones in Consumer Products Prompted by Increased Sensitisation to Benzisothiazolinone.","journal":"Contact dermatitis","published":"2026-03-26","design":"human_cross_sectional","finding":"concern","summary":"Patch testing of 803 dermatitis patients revealed a 5.2% sensitisation rate to CMIT/MIT, and chemical analysis detected CMIT and MIT in consumer products.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:41819607","pmid":"41819607","pmcid":"PMC13238334","doi":"10.1111/cod.70134","title":"Patch Test Results With the European Baseline Series, 2021/2022-Joint European Results of the ESSCA<sup>A</sup> and the EBS<sup>B</sup> Working Groups of the ESCD, and the GEIDAC<sup>C</sup>.","journal":"Contact dermatitis","published":"2026-03-12","design":"human_cross_sectional","finding":"concern","summary":"Patch testing of 18,832 European patients in 2021 and 2022 found sensitization rates of 5.52% for MCI/MI and 5.28% for MI.","funding":"industry","conflictOfInterest":true,"fundingEvidence":["industry: \"Sanofi\"","COI: \"advisory board\""],"fundingSource":"full_text","verified":false},{"id":"pmid:41804652","pmid":"41804652","pmcid":"PMC13139707","doi":"10.1111/cod.70124","title":"Prevalence of Contact Allergy to Isothiazolinones in Dermatitis Patients From 2000 to 2025: A Systematic Review and Meta-Analysis.","journal":"Contact dermatitis","published":"2026-03-10","design":"systematic_review","finding":"concern","summary":"A systematic review of 1,514,781 dermatitis patients found contact allergy prevalence of 4.58% for MCI/MI and 5.48% for MI.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"Environmental Protection Agency\""],"fundingSource":"full_text","verified":false},{"id":"pmid:41567001","pmid":"41567001","pmcid":"","doi":"10.1111/cod.70084","title":"Allergic Contact Dermatitis of the Hands: A Retrospective Cohort Study From Turkey Between 1996 and 2021.","journal":"Contact dermatitis","published":"2026-01-22","design":"human_cohort","finding":"concern","summary":"A retrospective study found that methylchloroisothiazolinone/methylisothiazolinone and methylisothiazolinone from cosmetics and personal care products were typically associated with non-occupational hand allergic contact dermatitis.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:41548371","pmid":"41548371","pmcid":"","doi":"10.1016/j.chemosphere.2026.144831","title":"Effects of chloromethylisothiazolinone/methylisothiazolinone on cytotoxicity and mitochondrial dysfunction in bronchial epithelial cells.","journal":"Chemosphere","published":"2026-01-17","design":"in_vitro","finding":"concern","summary":"CMIT/MIT exposure decreased cell viability, impaired mitochondrial function, elevated reactive oxygen species, and triggered apoptosis and autophagy in human bronchial epithelial BEAS-2B cells.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"Ministry of\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:41540775","pmid":"41540775","pmcid":"PMC12956421","doi":"10.1111/cod.70087","title":"Isothiazolinones in Disposable Rubber Gloves-Results of Chemical Analysis.","journal":"Contact dermatitis","published":"2026-01-15","design":"other","finding":"concern","summary":"Chemical analysis of disposable rubber gloves from occupational dermatology patients detected methylisothiazolinone in solitary gloves at small concentrations.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"full_text","verified":false},{"id":"pmid:41485758","pmid":"41485758","pmcid":"","doi":"10.1016/j.envres.2026.123679","title":"Translational toxicokinetics of chloromethylisothiazolinone/methylisothiazolinone: Radioactivity-associated materials-physiologically based toxicokinetic modeling and human dose extrapolation.","journal":"Environmental research","published":"2026-01-02","design":"other","finding":"no_effect","summary":"A physiologically based toxicokinetic model for CMIT/MIT was developed using rat biodistribution data and extrapolated to humans to estimate route-specific reference doses.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"Ministry of\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42686586","pmid":"42686586","pmcid":"","doi":"10.2131/jts.51.471","title":"Polypharmacological neurotoxic effects of methylisothiazolinone revealed by integrated in vitro and network-based chemoinformatics approaches.","journal":"The Journal of toxicological sciences","published":"2026-01-01","design":"in_vitro","finding":"concern","summary":"Methylisothiazolinone exposure in SH-SY5Y cells induced intrinsic apoptosis, oxidative stress, and neuroinflammatory responses, with an IC50 value of 115 µM.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:41429422","pmid":"41429422","pmcid":"PMC12956422","doi":"10.1111/cod.70070","title":"Skin Barrier Biomarkers in Patch-Induced and Clinical Allergic and Irritant Contact Dermatitis.","journal":"Contact dermatitis","published":"2025-12-22","design":"human_cross_sectional","finding":"concern","summary":"Methylisothiazolinone-induced allergic contact dermatitis reactions showed elevated stratum corneum biomarkers cholesterol sulphate and glucosylcholesterol, reflecting skin barrier impairment.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"full_text","verified":false},{"id":"pmid:41344074","pmid":"41344074","pmcid":"","doi":"10.1016/j.ecoenv.2025.119507","title":"Unveiling the role of Hedgehog signaling pathway in mitigating methylisothiazolinone-induced anxiety in zebrafish.","journal":"Ecotoxicology and environmental safety","published":"2025-12-03","design":"animal","finding":"concern","summary":"Methylisothiazolinone exposure in zebrafish induced anxiety-like behaviors, oxidative stress, and markers of ferroptosis, involving Hedgehog signaling pathway activation.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"Province\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:41338091","pmid":"41338091","pmcid":"","doi":"10.1016/j.ecoenv.2025.119508","title":"Evaluation of physiological changes in Mytilus galloprovincialis exposed to an isothiazolinone-based compound: A multi-marker approach.","journal":"Ecotoxicology and environmental safety","published":"2025-12-02","design":"animal","finding":"concern","summary":"Exposure of Mytilus galloprovincialis to methylchloroisothiazolinone for 14 days caused alterations in hemocyte function, osmoregulatory response, and oxidative stress markers.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"European Commission\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:41267567","pmid":"41267567","pmcid":"PMC12793816","doi":"10.1111/cod.70057","title":"A Cross-Sectional Study of Contact Allergens in Hotel Personal Care Products in Canada, the United States and Europe.","journal":"Contact dermatitis","published":"2025-11-21","design":"other","finding":"concern","summary":"MCI/MI was identified in 4.4% of hotel personal care products in Europe, significantly lower than in Canada (47.8%) and the United States (40.0%).","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"full_text","verified":false},{"id":"pmid:41273099","pmid":"41273099","pmcid":"","doi":"10.1111/pai.70245","title":"Contact sensitization in children and adolescents: Trends from a multicentre European study (2011-2022).","journal":"Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology","published":"2025-11-01","design":"human_cross_sectional","finding":"concern","summary":"A retrospective study of 6,961 European youth found methylisothiazolinone sensitization rates of 4.2% in children aged 1–5 years and 3.2% in adolescents aged 13–16 years.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:41187467","pmid":"41187467","pmcid":"","doi":"10.1016/j.aquatox.2025.107633","title":"Endocrine disruptive effects and mechanisms of isothiazolinone analogs in marine medaka (Oryzias melastigma) embryos and H295R cells.","journal":"Aquatic toxicology (Amsterdam, Netherlands)","published":"2025-11-01","design":"animal","finding":"mixed","summary":"Marine medaka embryos were exposed to isothiazolinones including MIT and MCI to evaluate developmental toxicity and endocrine disrupting effects.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"National Natural Science Foundation of China\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:41262804","pmid":"41262804","pmcid":"PMC12625795","doi":"10.7759/cureus.94906","title":"Virtual Reality Headset as a Cause of Allergic Contact Dermatitis in a Child.","journal":"Cureus","published":"2025-10-19","design":"other","finding":"concern","summary":"A 13-year-old boy with dermatitis from a virtual reality headset demonstrated positive patch test reactions to methylisothiazolinone and methylchloroisothiazolinone/methylisothiazolinone.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:40885155","pmid":"40885155","pmcid":"","doi":"10.1016/j.chroma.2025.466322","title":"Nontarget screening and identification of emerging preservatives and their metabolites in human urine.","journal":"Journal of chromatography. A","published":"2025-08-27","design":"human_cross_sectional","finding":"no_effect","summary":"A nontarget screening workflow identified a methylisothiazolinone metabolite in urine samples collected from a general population in Guangzhou, China.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"Provincial\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:40824751","pmid":"40824751","pmcid":"","doi":"10.1177/17103568251368314","title":"The Changing Spectrum of Pediatric Allergic Contact Dermatitis: A Prospective Multicentric Study in Spain.","journal":"Dermatitis : contact, atopic, occupational, drug","published":"2025-08-18","design":"human_cohort","finding":"concern","summary":"A prospective study of 508 pediatric patch-tested patients in Spain identified methylisothiazolinone as a top sensitizing allergen among children aged 6 to 16 years.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:40653073","pmid":"40653073","pmcid":"","doi":"10.1016/j.envres.2025.122339","title":"Isothiazolinone biocides as aromatase inhibitors: Hormonal disruption, and in silico docking and SAR/QSAR analysis.","journal":"Environmental research","published":"2025-07-11","design":"in_vitro","finding":"concern","summary":"Methylchloroisothiazolinone and methylisothiazolinone inhibited human and rat CYP19A1 aromatase activity and suppressed estradiol synthesis in BeWo cells.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"Science and Technology Bureau\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:40652745","pmid":"40652745","pmcid":"","doi":"10.1016/j.aquatox.2025.107487","title":"Effects of legacy and emerging antimicrobial compounds to early-life stages of rainbow trout (Oncorhynchus mykiss).","journal":"Aquatic toxicology (Amsterdam, Netherlands)","published":"2025-07-07","design":"animal","finding":"no_effect","summary":"Methylisothiazolinone exposure in early-life rainbow trout caused no observable effects on survival, development, or tissue histopathology, and induced minimal transcriptomic changes.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"Research Council\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:40555101","pmid":"40555101","pmcid":"PMC12226112","doi":"10.1016/j.abd.2025.501126","title":"Prevalence of reactive allergens in contact patch testing studies using the Brazilian standard battery: a systematic review.","journal":"Anais brasileiros de dermatologia","published":"2025-06-23","design":"systematic_review","finding":"concern","summary":"A systematic review in Brazil found that contact patch test positivity for Kathon CG increased every 5 years between 2000 and 2022.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"full_text","verified":false},{"id":"pmid:40559955","pmid":"40559955","pmcid":"PMC12197752","doi":"10.3390/toxics13060482","title":"Absence of Adverse Effects on Pulmonary Histopathology and Functions Following Inhalation Exposure to Chloromethylisothiazolinone/Methylisothiazolinone.","journal":"Toxics","published":"2025-06-06","design":"other","finding":"no_effect","summary":"Rodent inhalation studies showed that exposure to chloromethylisothiazolinone and methylisothiazolinone produced no significant histopathological alterations, pulmonary function changes, or pulmonary fibrosis.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"full_text","verified":false},{"id":"pmid:40443262","pmid":"40443262","pmcid":"PMC12318914","doi":"10.1111/cod.14818","title":"Trends in Contact Allergy to Preservatives From 2014 to 2023: Benzisothiazolinone on the Rise.","journal":"Contact dermatitis","published":"2025-05-30","design":"human_cross_sectional","finding":"concern","summary":"Contact allergy rates in patch-tested patients significantly decreased from 2014 to 2023 for MCI/MI (3.3% to 2.2%) and MI (3.9% to 2.5%).","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"Environmental Protection Agency\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:40280059","pmid":"40280059","pmcid":"","doi":"10.1016/j.jhazmat.2025.138392","title":"Nociceptive effects and gene alterations of CMIT/MIT mixture in zebrafish embryos and larvae.","journal":"Journal of hazardous materials","published":"2025-04-23","design":"animal","finding":"concern","summary":"Exposure of zebrafish embryos and larvae to CMIT/MIT heightened nociceptive behavioral responses, increased neuronal activity, and upregulated inflammatory and nociception-related markers.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"University\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:40008983","pmid":"40008983","pmcid":"PMC12304492","doi":"10.1177/12034754251322883","title":"Patterns of Pediatric Chronic Hand Eczema: A Systematic Review With Focus on Causes and Management.","journal":"Journal of cutaneous medicine and surgery","published":"2025-02-26","design":"systematic_review","finding":"concern","summary":"A systematic review of pediatric chronic hand eczema identified methylchloroisothiazolinone and/or methylisothiazolinone as the most common allergen, frequently associated with slime exposure.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false}],"model":"gemini-3.8-flash","run":{"aiCalls":37,"cachedPapers":1,"offTopic":3,"inputTokens":24442,"outputTokens":5283}}