Does diisocyanate exposure result in neurotoxicity?

Abstract

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.ObjectiveTo 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.MethodsA 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 Additional searches included regulatory reviews, EU IUCLID and EU Risk Assessment databases, and unpublished reports in the International Isocyanate Institute database.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.ResultsTwelve 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%.ConclusionThere 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.

Causal assessment in evidence synthesis: A methodological review of reviews

“…Clearly defining viewpoints is important for transparent implementation of BH viewpoints, but fewer than half (16/46, 34.8%) of reviews [32][33][34][35][36]38,43,46,[53][54][55]57,58,70,72,76 did so explicitly and the definitions varied. For example, consistency was defined by Fenton and colleagues 43 as variation across different study designs while others [32][33][34][35]57 described consistency as variation across populations and settings.…”

“…Note: The review topics, in terms of exposures, varied: sixteen (16/53, 30.2%) reviews focused on occupational health [32][33][34][35][60][61][62][63][64][65]69,70,[73][74][75] ; eleven (11/53, 20.8%) on environmental health 40,44,46,47,49,59,68,71,78,79 ; nine (9/53, 17.0%) on nutritional health 43,[51][52][53][54][55]57,77,81 ; four (4/53, 7.5%) on smoking 42,45,66,72 ; four (4/53, 7.5%) on mental health 48,56,67,82 ; three (3/53, 5.7%) on alcohol consumption 36,38,39 ; two (2/53, 3.8%) on child health 50,58 ; two (2/53, 3.8%) on health inequalities 41,83 ; one (1/53, 1....…”

The role of isocyanates in fire toxicity

“…2) and 3) further decomposition of the materials to primary amines, secondary amines, vinyl esters and carbon dioxide. Adapted from Jiao et al (2013) (Jiao et al 2013) No (Nehez et al 1989) No (Nehez et al 1989 Severe (Vernot et al 1977) Severe (Vernot et al 1977) Toluene-2,4-diisocyanate (2,4-TDI) (Bolognesi et al 2001) No (Zocca et al 1990) Yes (Buschmann 1990) Insufficient evidence (Hughes et al 2014) Lungs (Hughes et al 2014) Irreversible decline in pulmonary function (Centers for Disease Cotrol and Prevention 2015e)…”

Ruik je dat niet? Reukstoornissen door blootstelling in het werk

“…Isocyanaten zijn geregeld oorzaak van beroepsastma, met name via de monomeren MDI (methyleendifenyldiisocyanaat) of TDI (tolueendiisocyanaat) die vrij kunnen komen voor uitharding van polyurethaan. Maar hoewel de studie van Hughes et al13 een subjectieve veranderde reuksensatie aantoonde na blootstelling aan TDI, was dit effect niet-significant. Op basis van de beperkte literatuur is er onvoldoende bewijs voor een causaal verband tussen isocyanaten en reukstoornissen of andere neurologische effecten.…”