Quantitative Plasma Biomarker Analysis in HDI Exposure Assessment

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.

Hemoglobin adducts in workers exposed to 1,6-hexamethylene diisocyanate

“…Fifteen spray painters (4 from North Carolina and 11 from Washington State) were randomly selected from our HDI study population (Flack et al 2010a). Blood samples were collected during each sampling visit when workers consented ( N = 35).…”

“…1, 6-Hexamethylene diamine (HDA) in biological media (e.g., urine, plasma) has been utilized as a biological marker for occupational exposure to 1,6-hexamethylene diisocyanate (HDI) (Maître et al 1996, Williams et al 1999, Rosenberg et al 2002, Pronk et al 2006, Flack et al 2010a). During automotive spray painting, workers may be exposed to HDI present in paint formulations via skin or inhalation routes.…”

“…HDA in acid-hydrolyzed urine and plasma are the only validated biomarkers to date for short-term (Tinnerberg et al 1995, Maître et al 1996, Gaines et al 2010) and cumulative exposure to HDI monomer (Flack et al 2010a). Once in the body, the isocyanato moiety (NCO) may be hydrolyzed to an amine (e.g., HDA), catalyzed by bicarbonate in the blood (Berode et al 1991), or may react with proteins, such as albumin and hemoglobin (Hb), to form protein adducts.…”

“…The stronger correlation between HDA in acid-hydrolyzed plasma and dermal or inhalation exposure to HDI monomer occurring ~0.5–2 months before blood collection compared with the same day exposure among 46 spray painters demonstrated the presence of longer-lived albumin adducts (Flack et al 2010a). Moreover, a biphasic elimination pattern has been described for diisocyanate-derived amines, thought to result from the rapid urinary excretion of short-term metabolites within a few hours (Brorson et al 1990b, Tinnerberg et al 1995), followed by the excretion of long-lived protein adducts days later (Lind et al 1997).…”

“…Additionally, different levels of Hb adducts and urinary MDA corresponding to MDI or MDA exposure and varying MDA-Hb levels by exposure route (i.e., dermal or inhalation) have been observed (Pauluhn & Lewalter, 2002). In our previous study, plasma HDA levels were modified by coverall use and type of ventilated paint booth that the workers used during spray painting (Flack et al 2010a). Therefore, exposure route, stability of metabolic intermediates, and exposure to the diisocyanate versus the diamine (e.g., HDI vs. HDA) may drive specific metabolic pathways of HDI and, consequently, the types and yields of products formed.…”