DNA adducts and strand breaks in workers exposed to vapours and aerosols of bitumen: associations between exposure and effect.

To study the associations between exposure to vapours and aerosols of bitumen and genotoxic effects, a cross-sectional and cross-shift study was conducted in 320 exposed workers and 118 non-exposed construction workers. Ambient air measurements were carried out to assess external exposure to vapours and aerosols of bitumen. Hydroxylated metabolites of naphthalene, phenanthrene and pyrene were measured in urine, whereas (+)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide ((+)-anti-BPDE), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodGuo) and DNA strand breaks were determined in blood. Significantly higher levels of 8-oxodGuo adducts and DNA strand breaks were found in both pre- and post-shift blood samples of exposed workers compared to those of the referents. No differences between exposed workers and referents were observed for (+)-anti-BPDE. Moreover, no positive associations between DNA damage and magnitude of airborne exposure to vapours and aerosols of bitumen could be observed in our study. Additionally, no relevant association between the urinary metabolites of PAH and the DNA damage in blood was observed. Overall, our results indicate increased oxidative DNA damage in workers exposed to vapours and aerosols of bitumen compared to non-exposed referents at the group level. However, increased DNA strand breaks in bitumen workers were still within the range of those found in non-exposed and healthy persons as reported earlier. Due to the lack of an association between oxidative DNA damage and exposure levels at the workplaces under study, the observed increase in genotoxic effects in bitumen workers cannot be attributed to vapours and aerosols of bitumen.

Albumin and hemoglobin adducts of benzo[a]pyrene in humans--analytical methods, exposure assessment, and recommendations for future directions.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in our environment and can cause cancer. Exposure to PAHs can be assessed by protein adduct dosimetry using benzo[a]pyrene (B[a]P) as a model compound. We present an overview of analytical methods to detect B[a]P- derived protein adducts in humans, their uses in exposure assessment, and recommendations for future research. Two major methodologies, enzyme-linked immunosorbent assay (ELISA) and chemical-specific assays, could be traced in the literature but there remains limitations with both assays. ELISA is nonspecific due to cross-reactivity of the antibody with other PAHs and results are better interpreted in terms of PAH exposure. ELISA is unable to distinguish between exposed and nonexposed persons in the majority of studies. Adduct concentrations are higher by several orders of magnitude compared to those determined by chemical-specific methods. The latter methods mostly analyzed protein adducts derived by (+)-anti-B[a]P-diol epoxide. For this purpose, gas or liquid chromatography in combination with mass spectrometry or fluorescence detection were used. However, the prevalence of positive samples remained low when chemical- specific assays were used mainly due to the lack of sensitivity. Overall, data on B[a]P-derived protein adducts in humans remain inconclusive. Future research should focus on the development and standardization of a sensitive and specific method for B[a]P-derived protein adducts prior to its use in field studies. Finally, exposures of B[a]P at the workplace and via diet, a major route of exposure of the general population, can be studied. The results will contribute to the understanding of B[a]P-induced cancer and will allow for health preventive measures.

Assessment of DNA damage in WBCs of workers occupationally exposed to fumes and aerosols of bitumen.

We conducted a cross-shift study with 66 bitumen-exposed mastic asphalt workers and 49 construction workers without exposure to bitumen. Exposure was assessed using personal monitoring of airborne bitumen exposure, urinary 1-hydroxypyrene (1-OHP), and the sum of 1-, 2 + 9-,3-,4-hydroxyphenanthrene (OHPH). Genotoxic effects in WBC were determined with nonspecific DNA adduct levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and the formation of DNA strand breaks and alkali-labile sites. Concentration of fumes and aerosols of bitumen correlated significantly with the concentrations of 1-OHP and OHPH after shift (r(s) = 0.27; P = 0.03 and r(s) = 0.55; P < 0.0001, respectively). Bitumen-exposed workers had more DNA strand breaks than the reference group (P < 0.0001) at both time points and a significant correlation with 1-OHP and OHPH in the postshift urines (r(s) = 0.32; P = 0.001 and r(s) = 0.27; P = 0.004, respectively). Paradoxically, we measured higher levels of DNA strand breaks, although not significant, in both study groups before shift. 8-OxodGuo adduct levels did not correlate with DNA strand breaks. Further, 8-oxodGuo levels were associated neither with personal exposure to bitumen nor with urinary metabolite concentrations. Significantly more DNA adducts were observed after shift not only in bitumen-exposed workers but also in the reference group. Only low-exposed workers had significantly elevated 8-oxodGuo adduct levels before as well as after shift (P = 0.0002 and P = 0.02, respectively). Our results show that exposure to fumes and aerosols of bitumen may contribute to an increased DNA damage assessed with strand breaks.

DNA adduct formation of benzo[a]pyrene in white blood cells of workers exposed to polycyclic aromatic hydrocarbons.

The major DNA adducts of anti-benzo[a]pyrene diolepoxide (BPDE) were determined by high performance liquid chromatography with fluorescence detection (HPLC-FLD) in white blood cells (WBC) of workers exposed to benzo[a]pyrene (B[a]P). In addition, ambient concentrations of B[a]P at the workplace were determined by personal air sampling. Workers in a refractory setting were examined before (n=26) and 3 months after (n = 33) changing the production material (binding pitch). Furthermore, 9 coke oven workers were examined. The change in the production process in the refractory setting led to a decrease in the median of ambient B[a]P concentrations (0.14 to <0.07 microg/m3). The median of BPDE-DNA adduct levels in WBC also decreased from 0.9 adducts/10(8) nucleotides before changing the production material to <0.5 adducts/10(8) nucleotides 3 months afterwards. The B[a]P concentrations at the workplace for the coke oven workers were found to be significantly higher than in the refractory setting. However, BPDE-DNA adduct concentrations in coke oven workers and refractory setting workers showed no significant difference, which was probably due to the low number of studied subjects in the coke-oven setting. No significant differences could be observed for BPDE-DNA adduct levels between current smokers (n=21) and non-smokers (n=14; p = 0.93) from both plants. In addition, no correlation between B[a]P concentrations in the air and DNA adduct levels in refractory workers and in coke oven workers could be found (r = -0.03, p = 0.87). Because of the missing correlation between personal air sampling and BPDE-DNA adduct levels in WBC, the results may indicate that their formation is either influenced by other routes of exposure to B[a]P (e.g., skin absorption, dietary habits) or interindividual differences in their formation and repair.

Airway responsiveness of rabbits after exposure to 2-octyl dodecanol.

Cooling lubricants are used in the metal industry during drilling or turning. Vapors and aerosols of these lubricants are suspected to induce airway hyperresponsiveness (AHR) in exposed workers. In a previous study the authors demonstrated that water-soluble lubricants induce AHR after acute exposure of rabbits to concentrations near the German MAK value (10 mg/m(3)). In the present investigation the influence of a fatty alcohol as special non-water-soluble cooling lubricant was examined to determine its influence on airway responsiveness (AR). The effects of an aerosolized non-water-soluble lubricant (40, 90, and 220 mg/m(3)) on AR to acetylcholine in a rabbit model were studied. Lubricant atmosphere analysis was performed with infrared spectroscopy. Before exposure, after 2 and 4 hours of application, AR to aerosols from 0.2 and 2% acetylcholine was tested. Basal airway and cardiovascular parameters as well as blood gases did not change during exposure. Lubricant aerosol concentration of 40 and 220 mg/m(3) for 4 hours did not significantly alter AR. Inhalation of 90 mg/m(3) lubricant increased contractile response to ACH significantly. In contrast to formerly investigated water-soluble cooling lubricants, the examined non-water-soluble lubricant did not increase AR in concentrations near the MAK; however, in higher concentrations a significant (p<.05) increase was obtained.

Renal toxicity after chronic inhalation exposure of rats to trichloroethylene.

Male Long-Evans rats were exposed to 0 (controls) or 500 ppm trichloroethylene (TRI) for 6 months, 6 h daily, and 5 days a week. The TRI metabolites trichloroethanol (TCE) in blood and trichloroacetic acid (TCA) in urine were measured. Specific parameters related to the renal damage were determined in urine [biomarker for glomerular damage: high molecular weight proteins (HMW), albumin (ALB); for proximal tubular damage: N-acetyl-beta-D-glucosaminidase (NAG), low-molecular-weight-proteins (LMW)]. Significantly increased concentrations of NAG and LMW in urine of exposed rats were detected. No DNA-strand breaks in kidney cells could be detected using the comet assay, and histological examinations were performed. Histological alterations were observed in glomeruli and tubuli of exposed rats. The release of biomarkers for nephrotoxicity suggested alterations preferably in the proximal tubules of the exposed rats.

Chronic exposure to trichloroethylene affects neuronal plasticity in rat hippocampal slices.

Inhalational exposure to organic solvents is known to exert neurotoxic effects. Using the new multielectrode dish system (Panasonic) the effects of chronic exposure to trichloroethylene (TCE) on neuronal plasticity were assessed in different regions of the adult rat brain. Two groups of Long-Evans rats were exposed to 0 ppm or 500 ppm TCE, respectively, 6 h/day, 5 days/week for 6 months. Long-term potentiation (LTP) as well as paired-pulse potentiation/inhibition were assessed in slices from the visual cortex and the hippocampus. In addition, several behavioral tests were performed. Trichloroethanol concentrations were measured in blood and trichloroacetic acid concentrations were determined in urine. While TCE exposure impaired LTP as well as paired-pulse potentiation in hippocampal slices, no effects were seen in cortical slices. Our data demonstrate brain region specific functional changes following TCE exposure with the hippocampus being more vulnerable than the visual cortex. The behavioral measurements revealed no TCE related effects.