Occupational exposure to HDI: progress and challenges in biomarker analysis
Sheila L Flack1, Louise M Ball, Leena A Nylander-French
1Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, CB #7431, Rosenau Hall, Chapel Hill, NC 27599-7431, USA.
Summary
Occupational asthma linked to 1,6-hexamethylene diisocyanate (HDI) exposure is clarified by measuring urinary biomarkers. New methods quantify N-acetyl-1,6-hexamethylene diamine (monoacetyl-HDA) and N,N′-diacetyl-1,6-hexamethylene diamine (diacetyl-HDA), revealing HDI metabolism pathways.
Area of Science:
- Occupational Health and Toxicology
- Biomarker Discovery and Analysis
- Immunology and Respiratory Medicine
Background:
- 1,6-Hexamethylene diisocyanate (HDI) is a significant occupational hazard, particularly in the automotive repair sector, frequently causing occupational asthma.
- The precise pathological mechanisms underlying HDI-induced asthma remain incompletely understood, highlighting a critical need for better exposure assessment tools.
- Quantifying specific biomarkers of HDI exposure is essential for bridging knowledge gaps concerning susceptibility, immunological reactions, and sensitization pathways leading to asthma.
Purpose of the Study:
- To address challenges in analyzing N-acetyl-1,6-hexamethylene diamine (monoacetyl-HDA) and N,N′-diacetyl-1,6-hexamethylene diamine (diacetyl-HDA) in urine following 1,6-hexamethylene diisocyanate (HDI) exposure.
- To optimize reaction conditions for synthesizing monoacetyl-HDA and diacetyl-HDA standards.
- To quantify these key HDI metabolites in urine samples from occupationally exposed individuals.
Main Methods:
- Established methods for HDA analysis were adapted for the quantification of monoacetyl-HDA and diacetyl-HDA in human urine.
- Reaction conditions for the synthesis of monoacetyl-HDA and diacetyl-HDA were optimized to create reliable analytical standards.
- Urine samples from three occupationally HDI-exposed workers were analyzed using the developed methods, including base and acid hydrolysis treatments.
Main Results:
- Diacetyl-HDA was detected in untreated urine samples at concentrations ranging from 0.015–0.060 μg/l.
- Base hydrolysis significantly increased monoacetyl-HDA levels in urine, revealing concentrations 60-fold higher on average (0.19–2.2 μg/l) compared to untreated samples.
- Acid hydrolysis proved most effective for HDA detection, yielding concentrations of 0.36–10.1 μg/l, indicating distinct metabolic pathways and hydrolysis efficiencies for different metabolites.
Conclusions:
- The study confirms that occupational exposure to 1,6-hexamethylene diisocyanate (HDI) leads to its metabolism via an N-acetylation pathway.
- The findings demonstrate the formation of protein adducts, providing further insight into the immunological mechanisms underlying HDI-induced occupational asthma.
- Accurate quantification of urinary monoacetyl-HDA and diacetyl-HDA serves as a valuable tool for assessing HDI exposure and understanding its health implications.
