Does Diisocyanate Exposure Result in Neurotoxicity?

Details

• Personal Author:
  Carson, M. ; Collins, M. A. ; Hughes, M. A. ; Jolly, A. T. ; Molenaar, D. M. ; Steffens, W. ; Swaen, G. M. H.
• Description:
  Context. Diisocyanates have been associated with respiratory and dermal sensitization. Limited number of case reports, and a few case studies, media, and other references suggest potential neurotoxic effects from exposures to toluene diisocyanate (TDI), 1,6 hexamethylene diisocyanate (HDI), and methylene diisocyanate (MDI). However, a systematic review of the literature evaluating the causal association on humans does not exist to support this alleged association. Objective. To perform systematic review examining the body of epidemiologic evidence and provide assessment of causal association based on principles of the Sir Austin Bradford Hill criteria or considerations for causal analysis. Methods. A comprehensive search of public databases for published abstracts, case reports, cross-sectional surveys, and cohort studies using key search terms was conducted. Additional searches included regulatory reviews, EU IUCLID and EU Risk Assessment databases, and unpublished reports in the International Isocyanate Institute database. An expert panel consisting of physicians, toxicologists, and an epidemiologist critically reviewed accepted papers, providing examination of epidemiologic evidence of each report. Finally, the Hill criteria for causation were applied to the summative analysis of identified reports to estimate probability of causal association. Results. Twelve papers reporting exposed populations with a variety of neurological symptoms or findings suitable for analysis were identified, including eleven case or case series reports, and one cross-sectional study. Three papers reported on the same population. Each of the papers was limited by paucity of diisocyanate exposure estimates, the presence of confounding exposures to known or suspected neurotoxicants, a lack of objective biological measures of exposure or neurotoxic effects, and lack of relative strength of association measures. Additionally, reported health symptoms and syndromes lacked consistency or specificity. No plausible mechanism of toxicity was found. Application of a predictive mathematical model for determining probability of causal association for neurotoxicity was calculated to be 21%. Conclusion. There is insufficient evidence for a causal association of neurotoxic effects and diisocyanate exposure based on lack of evidence in all categories of the Hill criteria for causality except for temporal association of reported symptoms and alleged exposure. Future reports should attempt to address more rigorous exposure assessment and control for confounding exposures. [Description provided by NIOSH]
• Subjects:
  Isocyanates Nervous System Occupational Health Safety Toluene
• Keywords:
  4,4'methylenebisphenyl Isocyanate Author Keywords: Diisocyanate Central Nervous System Diisocyanates HDI Hexamethylene Diisocyanate MDI Neurological Reactions Neurotoxic Effects Neurotoxicity Neurotoxicology Peripheral Nervous System Sir Bradford Hill Criteria Systematic Reviews TDI

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• ISSN:
  1556-3650
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Michigan ; Minnesota ; OSHA Region 3 ; OSHA Region 5 ; OSHA Region 8 ; Pennsylvania ; Utah
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  17 pdf pages
• Volume:
  52
• Issue:
  4
• NIOSHTIC Number:
  nn:20067384
• Citation:
  Clin Toxicol 2014 Apr; 52(4):242-257
• Contact Point Address:
  Dr Matthew A. Hughes, MD, MPH, University of Utah School of Medicine, Rocky Mountain Center for Occupational and Environmental Health, 391 Chipeta Way, Salt Lake City, UT 84108, USA
• Email:
  matthew.hughes@hsc.utah.edu
• Federal Fiscal Year:
  2014
• Performing Organization:
  University of Utah
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Clinical Toxicology
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:786426b567aa0c7f3855a28eb170b54131507a7f3b0e280ee135087f9d48eba8e1218ac0c6addb3859cb9365962cfb7df519255350e330ad18f075a1bf1e24af
• Download URL:
  https://stacks.cdc.gov/view/cdc/230790/cdc_230790_DS1.pdf
• File Type:
  [PDF - 480.43 KB ]