Hemoglobin adducts and plasma Metabolites as biomarkers of exposure to 1,6-hexamethylene diisocyanate.
Flack-SL; Gaines-LG; Fent-KW; Thomasen-JM; Whittaker-SG; Ball-LM; Nylander French-LA
Toxicologist 2010 Mar; 114(1):283
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.
Airborne-particles; Biological-effects; Cell-biology; Cellular-reactions; Chemical-hypersensitivity; Chemical-reactions; Environmental-exposure; Exposure-assessment; Exposure-levels; Exposure-methods; Inhalation-studies; Microbiology; Microscopic-analysis; Occupational-diseases; Occupational-exposure; Occupational-health; Particle-aerodynamics; Particulate-dust; Particulates; Respiratory-hypersensitivity; Respiratory-system-disorders; Statistical-analysis; Toxic-effects; Toxins
Grant; Cooperative Agreement
Grant-Number-R01-OH-007598; Cooperative-Agreement-Number-T42-CCT-422952; Grant-Number-T42-OH-008673
The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah
University of North Carolina, Chapel Hill, North Carolina