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.
"Mild alkaline hydrolysis released the parent amines or their acetyl derivatives from aryl aminederived (TDA, MDA) adducts . Strong acid hydrolysis was needed to hydrolyse the TDI-or MDI-derived adducts . The amines released from globin adducts after mild alkaline hydrolysis or strong acid hydrolysis were analysed as perfluoro-acetylated derivatives, by use of deuterated diamines as internal standards . "
[Show abstract][Hide abstract] ABSTRACT: Toluene diisocyanate (TDI) and 4,4'-methylenediphenyl diisocyanate (MDI), used in the production of polyurethane foam, are well known for their irritating and sensitizing properties. Contradictory results have been obtained on their genotoxicity. We investigated the genotoxicity and protein binding of inhaled TDI and MDI in mice by examining micronucleated polychromatic erythrocytes (PCEs) in bone marrow and peripheral blood and TDI- and MDI-derived adducts in hemoglobin. Male C57Bl/6J mice (8 per group) were exposed head-only to TDI vapour (mean concentrations 1.1, 1.5, and 2.4mg/m(3); the mixture of isomers contained, on the average, 63% 2,4-TDI and 37% 2,6-TDI) or MDI aerosol (mean concentrations 10.7, 20.9 and 23.3mg/m(3)), during 1h/day for 5 consecutive days. Bone marrow and peripheral blood were collected 24h after the last exposure. Inhalation of TDI caused sensory irritation (SI) in the upper respiratory tract, and cumulative effects were observed at the highest exposure level. Inhalation of MDI produced SI and airflow limitation, and influx of inflammatory cells into the lungs. Hemoglobin adducts detected in the exposed mice resulted from direct binding to globin of 2,4- and 2,6-TDI and MDI, and dose-dependent increases were observed especially for 2,4-TDI-derived adducts. Adducts originating from the diamines of TDI (toluene diamine) or MDI (methylene dianiline) were not observed. No significant increase in the frequency of micronucleated PCEs was detected in the bone marrow or peripheral blood of the mice exposed to TDI or MDI. The ratio of PCEs and normochromatic erythrocytes (NCEs) was reduced at the highest concentration of MDI, and a slight reduction of the PCE/NCE ratio, dependent on cumulative inhaled dose, was also seen with TDI. Our results indicate that inhalation of TDI or MDI (1h/day for 5 days), at levels that induce toxic effects and formation of TDI- or MDI-specific adducts in hemoglobin, does not have detectable genotoxic effects in mice, as studied with the micronucleus assay.
"Quantification of amines in biological samples requires highly sensitive and selective methods. Such methods for HDA (Tinnerberg et al., 1995; Rosenberg et al., 2002; Creely et al., 2006), TDA (Lind et al., 1997b) and MDA (Sepai et al., 1995b) typically involve acid hydrolysis of samples and derivatization of the liberated amines with subsequent gas chromatography–mass spectrometry (GC–MS) analysis. Therefore, the total HDA concentration measured in hydrolyzed plasma represents the sum of covalently bound HDI monomer and HDA/AcHDA oxidation products, as well as non-covalently bound HDA and its metabolites (e.g. "
[Show abstract][Hide abstract] ABSTRACT: Quantification of amines in biological samples is important for evaluating occupational exposure to diisocyanates. In this study, we describe the quantification of 1,6-hexamethylene diamine (HDA) levels in hydrolyzed plasma of 46 spray painters applying 1,6-hexamethylene diisocyanate (HDI)-containing paint in vehicle repair shops collected during repeated visits to their workplace and their relationship with dermal and inhalation exposure to HDI monomer. HDA was detected in 76% of plasma samples, as heptafluorobutyryl derivatives, and the range of HDA concentrations was < or =0.02-0.92 microg l(-1). After log-transformation of the data, the correlation between plasma HDA levels and HDI inhalation exposure measured on the same workday was low (N = 108, r = 0.22, P = 0.026) compared with the correlation between plasma HDA levels and inhalation exposure occurring approximately 20 to 60 days before blood collection (N = 29, r = 0.57, P = 0.0014). The correlation between plasma HDA levels and HDI dermal exposure measured on the same workday, although statistically significant, was low (N = 108, r = 0.22, P = 0.040) while the correlation between HDA and dermal exposure occurring approximately 20 to 60 days before blood collection was slightly improved (N = 29, r = 0.36, P = 0.053). We evaluated various workplace factors and controls (i.e. location, personal protective equipment use and paint booth type) as modifiers of plasma HDA levels. Workers using a downdraft-ventilated booth had significantly lower plasma HDA levels relative to semi-downdraft and crossdraft booth types (P = 0.0108); this trend was comparable to HDI inhalation and dermal exposure levels stratified by booth type. These findings indicate that HDA concentration in hydrolyzed plasma may be used as a biomarker of cumulative inhalation and dermal exposure to HDI and for investigating the effectiveness of exposure controls in the workplace.
"Biomarkers of exposure have also been used for workers in continuous foaming plants (Maitre et al., 1993; Persson et al., 1993; Carbonelle et al., 1996; Tinnerberg et al., 1997; Kääria et al., 2001). Biomarkers in urine have a short half-life, about 2–8 h (Lind et al., 1997) reflecting the exposure during the sampling day. The half-life in plasma is $20 days (Lind et al., 1996) and reflects the exposure during the last month. "
[Show abstract][Hide abstract] ABSTRACT: Exposure to isocyanates is known to have respiratory effects in workers and therefore it is essential to monitor the occupational exposure. An earlier study of a continuous foaming plant using toluene diisocyanate (TDI) showed that the exposure to isocyanates can be high. Since then several preventive actions were implemented at the plant. The aim of this study was to observe the effect of these actions measured by air and biological monitoring. Four workers were monitored in the year 2000 and six in 2005, with air measurements during the continuous foaming process, and with measurements of biomarkers in one plasma sample each year and with two urinary samples being collected in the year 2000 and one in 2005. The median TDI air concentrations in 2005 were approximately 20% of the 2000 levels and the median levels of biomarkers in 2005 were approximately 10% of the 2000 levels. According to our measurements the preventive action had a real effect to decrease the exposure to TDI. As the workers both before and after the preventive actions used personal protective equipment, the use of biomarkers was necessary to assess the real gain in the preventive actions.
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