O(6)-methylguanine DNA adducts associated with occupational nitrosamine exposure.

Occupational nitrosamine exposures from a rubber vehicle seal (VS) curing operation were compared with the peripheral blood lymphocyte concentrations of two nitrosamine-related DNA adducts, N(7)-methylguanine (N(7)mdG) and O(6)-methylguanine (O(6)mdG), and with the activity of the enzyme that repairs O(6)mdG adducts, O(6)-alkylguanine-DNA alkyltransferase (AGT). The occupational personal breathing zone (PBZ) nitrosamine exposures ranged from 0.4 to 9.3 microg/m(3) in the VS area, from 0.1-2 microg/m(3) in an area remote from the VS and were not detected at a nearby rubber plant. Workers from all three of these locations had detectable concentrations of N(7)mdG adducts, ranging from 0.1 to 133.2 adducts/10(7) deoxyguanosine nucleosides. Although N(7)mdG concentrations were elevated for those who worked in the VS area (median 3.60 compared with 1.44), the difference was not statistically significant after controlling for confounding factors. The O(6)mdG adduct concentrations were much lower than those of N(7)mdG, ranging from non-detectable to 12.7 O(6)mdG adducts/10(7) deoxyguanosine nucleosides and many of the participants (40/78 successfully analyzed) did not have detectable amounts of these adducts (limit of detection 0.03 O(6)mdG adducts/10(7) deoxyguanosine nucleosides). Analysis of the ordinal exposure categories (high, medium/high, medium/low, low and no exposure) yielded a statistically significant association with having detectable O(6)mdG adducts (Kendall's taub = -0.253, asymptotic SE = 0.096). There was no significant association between AGT activity and nitrosamine exposure or exposure category (P > 0.30). Although no association was found between PBZ exposure and either the N(7)mdG adduct concentrations or AGT activity, the significant positive association between working in and near the VS department and the presence of O(6)mdG adducts, which have mutagenic potential, provides evidence to link nitrosamine exposure one step closer to human cancer by demonstrating an association between external nitrosamine exposures and cancer-related biological effects.

Worker exposures to nitrosamines in a rubber vehicle sealing plant.

Occupational nitrosamine exposures were measured during a National Institute for Occupational Safety and Health (NIOSH) health hazard evaluation at a rubber vehicle sealing plant. All of the 28 personal breathing zone samples had detectable concentrations of nitrosodimethylamine (NDMA), nitrosodiethylamine, nitrosopiperidine (NPIP), and nitrosomorpholine; and 27 of the 28 samples had detectable concentrations of nitrosopyrrolidine. The NDMA exposures were the highest, ranging from 0.47 to 11.44 micrograms/m3. The next highest exposures were to NPIP, ranging from 0.20 to 4.39 micrograms/m3. Several general area air samples were also collected, which revealed concentrations of NDMA ranging from 2.29 to 88.47 micrograms/m3 at the drills along the salt bath lines. The salt bath curing process appears to be the primary source of nitrosamine formation, and personal exposures were highest for the salt bath line operators and assistant operators. Although there are no numerical occupational nitrosamine standards in the United States to reference, the exposures in this plant were much higher than the German standard of 1 micrograms/m3 total nitrosamines for general industry and 2.5 micrograms/m3 total nitrosamines for certain processes such as vulcanization. NIOSH investigators recommended that the ventilation systems be improved to reduce the exposures to the lowest feasible concentrations until the process can be redesigned so that nitrosamines are not formed.