Does diisocyanate exposure result in neurotoxicity?

Area of Science:

• Occupational Health
• Toxicology
• Epidemiology

Background:

• Diisocyanates are known sensitizers, with some reports suggesting potential neurotoxic effects.
• Limited evidence exists regarding the neurotoxicity of specific diisocyanates like TDI, HDI, and MDI.
• A systematic review evaluating the causal association between diisocyanate exposure and neurotoxicity in humans was lacking.

Purpose of the Study:

• To systematically review epidemiologic evidence on diisocyanate exposure and neurotoxicity.
• To assess the causal association using the Bradford Hill criteria.

Main Methods:

• Conducted a comprehensive literature search across multiple databases and internal industry reports.
• Included case reports, cross-sectional surveys, and cohort studies.
• An expert panel reviewed papers and applied the Hill criteria for causality assessment.

Main Results:

• Identified 12 papers (11 case reports, 1 cross-sectional study) on exposed populations with neurological symptoms.
• Studies were limited by poor exposure estimates, confounding factors, lack of objective measures, and inconsistent symptoms.
• A predictive model estimated a 21% probability of a causal association for neurotoxicity.

Conclusions:

• Insufficient evidence exists to establish a causal link between diisocyanate exposure and neurotoxic effects.
• The primary evidence supporting a link is the temporal association between reported symptoms and exposure.
• Future research needs improved exposure assessment and control for confounding variables.