Exposure related mutagens in urine of rubber workers associated with inhalable particulate and dermal exposure

Abstract

Aims: To determine the relation of the inhalation and dermal exposure routes and mutagenic activity in the urine of rubber workers (n = 105). Methods: Mutagenic activity of ambient total suspended particulate matter (TSPM), surface contamination wipes, and Sunday and weekday urine samples was assessed with S typhimurium YG1041 in the presence of a metabolic activation system. Each subject was grouped into one of two exposure categories for dermal exposure (high (>25 revertants/cm 2 ), low (<25 revertants/cm 2 )) based on the mutagenic activity detected on likely skin contact surfaces and into two airborne mutagenic exposure categories (high (>210 revertants/m 3 ), low (<210 revertants/m 3 )). The potential influence of skin aberrations and acetylation status (NAT2) on urinary mutagenicity levels was also evaluated. Results: A non-significant increase of +1605 revertants/g creatinine in urinary mutagenicity during the workweek relative to levels observed on Sunday was observed for the total population. Subsequent multivariate regression analyses, with the subjects' weekday urinary mutagenicity levels as the dependent variable, revealed associations with environmental and mainstream tobacco smoke exposure, with the level of mutagenic contamination on surfaces with which the subjects had likely contact, with the subjects' inhalable particulate exposure level, with observed mild skin aberrations, and when the subjects had a slow acetylation phenotype. Similar associations, although weaker were observed with Sunday urinary mutagenicity levels as well, except for the association with slow acetylation phenotype. Based on measured exposure levels it could be estimated that a high potential for exposure to surface contamination with mutagenic activity increased weekday urinary mutagenicity by about 62% when compared to low exposed workers, while high inhalable particulate exposure levels increased weekday urinary mutagenicity levels by about 21%. Subjects with mild skin aberrations had an additional, non-significant, increase in weekday urinary mutagenic activity compared to subjects without any skin aberrations. Discussion: Results suggest that the dermal exposure route may contribute more to the level of genotoxic compounds in urine of rubber workers than the inhalation route. Although the study was limited in size, the results warrant further investigation in the importance of and ways to effectively control the dermal exposure route in the rubber industry.

Urinary Mutagenicity in Chemical Laboratory Workers Exposed to Solvents

“…The increase in mutagenicity, however, was limited to assays conducted with the O-acetyltransferase-overproducing strain, YG1024, in the presence of S9 mix. Although this finding is in general agreement with previous observations 30,38,39) , it is difficult to rationalize with the presumed exposure to solvents for the exposed population in this study. Our results with strain YG1024 (+S9) suggest that the workers are exposed to indirect mutagens and the mutagenicity in these chemical workers may have been due to exposure to solvents.…”

“…Urinary mutagenic activity has been used in occupational and epidemiological studies for decades as a cost effective, general biomarker of exposure to genotoxic compounds, e.g., occupational exposures in the rubber, coke oven, ink, pharmaceutical, and textile industries [28][29][30] . The data from bacterial mutagenicity assays, particularly the Ames test, and the results of exposure to ethanol have generally been negative [31][32][33] .…”

Dermal exposure assessment in occupational epidemiologic research

“…Adverse skin conditions (eg, hydration, dryness, skin diseases) have been shown to affect percutaneous absorption under both laboratory and field circumstances (67)(68)(69)(70)(71). Of the adverse skin conditions, skin abrasions (eg, dermatitis, cuts, burns) have been shown to have a potentially dramatic effect on percutaneous absorption.…”

Polycyclic Aromatic Hydrocarbon Exposure, Urinary Mutagenicity, and DNA Adducts in Rubber Manufacturing Workers

“…DNA was extracted from the PBMCs using the chloroform -isoamyl alcohol method (18). DNA samples were analyzed using the (19). DNA was hydrolyzed by incubation for 3 h at 37jC using 2.5 units of micrococcal endonuclease (Sigma Chemical Co.) and 0.25 Ag (4 milliunits) of calf spleen phosphodiesterase (Sigma).…”

“…Acetylation status was previously found to influence urinary mutagenicity and urothelial cell DNA adducts levels (7,19). Acetylation status was determined by measuring caffeine and its metabolites as described by Grant et al (20).…”