Biomarkers in hydrolysed urine, plasma and erythrocytes among workers exposed to thermal degradation products from toluene diisocyanate foam.
ABSTRACT Blood and urine samples were collected from six workers and two volunteers exposed to thermal degradation products from toluene diisocyanate (TDI)-based polyurethane (PUR) before and during the summer vacation. Air samples were collected on filters impregnated with 9-(N-methylaminomethyl)anthracene. The concentrations of the amines corresponding to 2,4- and 2,6-TDI, i.e., 2,4- and 2,6-toluenediamine (TDA), were determined in urine (U-TDA), plasma (P-TDA) and erythrocytes (E-TDA) after acid hydrolysis as pentafluoropropionic anhydride derivatives by GC-MS. Among the workers urinary elimination phases were seen. The estimated medians of the urinary half-lives were for the slow phase 18 d for 2,4-TDA and 19 d for 2,6-TDA. P-2,4-TDA ranged between 2.5 and 19 ng ml-1 and P-2,6-TDA between 4.4 and 30 ng ml-1. The estimated median of the half-lives in plasma were 7.8 d for 2,4-TDA and 9.6 d for 2,6-TDA. E-2,4-TDA ranged between 0.5 and 6.6 ng g-1 and E-2,6-TDA between 1.2 and 14 ng g-1. A significant linear relationship was found between the mean P-TDA and the mean E-TDA. Linear relationships were observed between the mean daily U-TDA and P-TDA and E-TDA. Virtually linear relationships were obtained for P-TDA and E-TDA and the TDI air levels. Proteins from lysed erythrocytes were separated and fractionated by gel filtration. 'TDI'-modified proteins were found in six out of a total of 80 fractions (fractions 51-56). These co-eluted completely with the haemoglobin (UV, 415 nm). Fractions 51-56 contained 89% of the applied amounts of 2,4-TDA and 81% of 2,6-TDA.
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ABSTRACT: Abstract Humans are exposed to toluene diisocyanate (TDI) primarily through inhalation in workplaces where TDI is produced or used. It is classified as a possible human carcinogen, based primarily on increased tumor incidences in rodents treated with TDI by oral gavage. We used the hypothesis-based weight-of-evidence (HBWoE) method to evaluate whether the available data support the hypothesis that TDI is a human carcinogen. The epidemiology data are not sufficiently robust to support TDI as a human carcinogen; the few positive associations are more likely attributable to alternative explanations than causation. The experimental animal studies indicate that inhalation exposure to TDI does not induce tumors in rats or mice. Tumors observed after oral gavage exposure are most likely due to the conversion of approximately 5% of the administered TDI to toluene diamine (TDA), a known rodent tumorigen. This contention is supported by the observations that TDA is rapidly formed from TDI during in vitro genotoxicity assays, the spectra of responses to TDA and TDI in these assays and in oral bioassays are essentially the same, and TDI is not genotoxic in rodents or humans in vivo after inhalation exposure, when TDA is not formed to a biologically significant degree. We conclude that the weight of the evidence indicates that the conversion of TDI to TDA does not occur in mammalian species under physiological exposure conditions (i.e. inhalation), but is necessary for carcinogenesis to occur. Thus, a causal association between TDI exposure and carcinogenic effects is not plausible in humans.Critical Reviews in Toxicology 05/2013; · 6.25 Impact Factor
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ABSTRACT: PURPOSE: Exposure to diisocyanates is a known occupational hazard. One method for monitoring occupational exposure is by analyzing biomarkers in hydrolyzed urine and plasma. The half-life of the biomarkers in plasma is about 3 weeks, and the urinary elimination is divided into one fast (hours) and one slow phases (weeks). Polymorphism in glutathione S-transferase enzymes (GST) is earlier shown to modify the metabolism. The aim of the study was to assess whether biomarkers of exposure in urine collected after two non-exposed days correlate with levels in plasma and whether they can be used as a measure for long-term exposure to aromatic diisocyanates and further whether polymorphisms in GST influenced the correlations. METHODS: Biomarkers of exposure was analyzed in urine and blood samples collected from 24 workers, exposed to at least one of toluene-, methylenediphenyl- or naphthalene diisocyanate, on a Monday morning after at least two unexposed days. Moreover, genotype was determined for 19 of the workers. RESULTS: The corresponding specific gravity-adjusted biomarkers in urine and plasma levels for the different diisocyanates correlated well (r between 0.689 and 0.988). When taking all samples together, the correlation coefficient was 0.926. Polymorphism in the GSTM1 genotype seemed to modify the association. CONCLUSION: Urine collected after two unexposed days can possibly be used as long-term biomarker of exposure for aromatic diisocyanates.International Archives of Occupational and Environmental Health 04/2013; · 2.10 Impact Factor