Hemoglobin Adducts and Plasma Metabolites as Biomarkers of Exposure to 1,6-Hexamethylene Diisocyanate

Details

• Personal Author:
  Ball LM ; Fent, Kenneth W. ; Flack SL ; Gaines LG ; Nylander French LA ; Thomasen JM ; Whittaker SG
• Description:
  Diisocyanates (dNCO) are considered a major cause of occupational asthma. The mechanisms of toxic reactions, type and yield of various dNCO metabolites, and their relationship with exposure have not been adequately addressed in exposure assessment. We investigated the utility of 1,6-hexamethylene diamine (HDA) hemoglobin adducts and plasma HDA as internal dosimeters of exposure to 1,6-hexamethylene diisocyanate (HDI). We quantified levels of HDA hemoglobin (Hb) adducts, as well as HDA in hydrolyzed plasma among 15 spray painters (N=36) applying HDI-containing paint and investigated their relationship with HDI air exposure or urinary HDA levels. HDA-Hb adducts were detected by GC-MS as heptafluorobutyryl derivatives (1.2-37.2 ng/g Hb). The correlation between HDA-Hb adducts and HDI air exposure was strongest when exposures were measured 2-5 months before blood collection (r2=0.40, P=0.019). However, the correlation between plasma HDA and HDI air exposure was strongest when exposures were measured 0.5-2 months before blood collection (r2=0.28, P=0.010). Urinary HDA was most strongly associated with plasma HDA collected on the same day or within the previous 2 months (r2=0.12-0.86, P<0.10), whereas urinary HDA was most strongly correlated with Hb-HDA adducts in blood collected 2-5 months prior (r2=0.16, P=0.11). These findings indicate different elimination kinetics of plasma and Hb-adduct metabolites, and their application as biomarkers of cumulative exposure to HDI monomer. Such information on the type and yield of different metabolites and their relationship with cumulative HDI air exposure levels may be used in retrospective studies and to promote further research into susceptibility factors related to disease development. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Chemistry Environmental Exposure Environmental Monitoring Hazardous Substances Hypersensitivity Microbiology Occupational Diseases Occupational Exposure Occupational Health Particulate Matter Respiratory Hypersensitivity Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Airborne-particles Biological-effects Cell-biology Cellular-reactions Chemical-hypersensitivity Chemical-reactions Environmental-exposure Exposure-assessment Exposure-levels Exposure-methods Inhalation-studies Microscopic-analysis Occupational-diseases Occupational-exposure Occupational-health Particle-aerodynamics Particulate-dust Particulates Respiratory-hypersensitivity Respiratory-system-disorders Statistical-analysis Toxic-effects Toxins

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  North Carolina ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 8 ; Utah ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  114
• Issue:
  1
• NIOSHTIC Number:
  nn:20036662
• Citation:
  Toxicologist 2010 Mar; 114(1):283
• Federal Fiscal Year:
  2010
• Performing Organization:
  University of North Carolina, Chapel Hill, North Carolina
• Peer Reviewed:
  False
• Start Date:
  20030801
• Source Full Name:
  The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah
• End Date:
  20070731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8efff8ba29688cbb699c30541d00be970a34b4473a3b8ab93f28be2decc16be5cf1b539d03fa7d6547ea94f5bbca428720a4f22e417c9f9d4c9ff1836e136ce8
• Download URL:
  https://stacks.cdc.gov/view/cdc/187992/cdc_187992_DS1.pdf
• File Type:
  [PDF - 725.73 KB ]