Dose-Response Modeling of Occupational Exposure to Polycyclic Aromatic Hydrocarbons with Biomarkers of Exposure and Effect

Abstract

In regulatory toxicology, the dose-response relationship between occupational exposure and biomarkers is of importance in setting threshold values. We analyzed the relationships between occupational exposure to polycyclic aromatic hydrocarbons (PAH) and various biomarkers of internal exposure and DNA damage with data from 284 highly exposed male workers. Personal exposure to phenanthrene and other PAHs was measured during shift and correlated with the sum of 1À, 2+9À, 3À, and 4-hydroxyphenanthrenes in post-shift urine. PAHs and hydroxyphenanthrenes were associated with DNA damage assessed in WBC as 8-oxo-7,8-dihydro-2 ¶-deoxyguanosine/10 6 dGuo and strand breaks by Comet assay as Olive tail moment. Hydroxyphenanthrenes correlated with phenanthrene (Spearman r s = 0.70; P < 0.0001). No correlations could be found between strand breaks and exposure (r s = 0.01, P < 0.0001 for PAHs; r s = À0.03, P = 0.68 for hydroxyphenanthrenes). Correlations with 8-oxo-7,8-dihydro-2 ¶-deoxyguanosine/10 6 dGuo were weakly negative (r s = À0.22, P = 0.004 for PAHs) or flat (r s = À0.08, P = 0.31 for hydroxyphenanthrenes). Linear splines were applied to assess the relationships between the log-transformed variables. All regression models were adjusted for smoking and type of industry. For hydroxyphenanthrenes, 51.7% of the variance could be explained by phenanthrene and other predictors. Up to 0.77 Mg/m 3 phenanthrene, no association could be found with hydroxyphenanthrenes. Above that point, hydroxyphenanthrenes increased by a factor of 1.47 under a doubling of phenanthrene exposure (slope, 0.56; 95% confidence interval, 0.47-0.64). Hydroxyphenanthrenes may be recommended as biomarker of occupational PAH exposure, whereas biomarkers of DNA damage in blood did not show a dose-response relation to PAH exposure. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1863 -73)

Exposure and Emissions Monitoring during Carbon Nanofiber Production—Part II: Polycyclic Aromatic Hydrocarbons

“…1,2) of target PAHs having established exposure limits were well below those limits (Table 1). By comparison, the mean phenanthrene concentration reported for a study population of 284 workers 'highly exposed' to PAHs during the manufacture of refractory products (graphite electrode production, coke oven operation, tar distillation, and steel production) was 4.81 μg m −3 (Pesch et al, 2007), while it ranged from ~5 to 9 μg m −3 in this study. In another cross-industry study (Unwin et al, 2006), 8-h time-weighted average (TWA) concentrations of BaP ranged from <0.01 to 6.21 μg m −3 , with a geometric mean of 0.036 μg m −3 .…”

Urinary 1‐hydroxypyrene and 8‐hydroxydeoxyguanosine Levels among Coke‐oven Workers for 2 Consecutive Days

“…We found a tendency for positive correlation between urinary 1-OHP and 8-OH-dG after adjusting for gender, age, BMI, smoking status and drinking habit (p=0.070). However, some studies reported that there was no relationship between urinary 1-OHP and 8-OH-dG 19,34) . The first possible reason for these conflicting results is the different levels of internal exposure to PAHs.…”

DNA repair capacity marks susceptibility in pediatric asthma patients following low levels of polycyclic aromatic hydrocarbon exposure

“…The relationship between PAH exposure and DNA damage measured by Comet assay was not consistent among studies. In some studies 19,20 , there was no correlation between PAH exposure and DNA damage by Comet assay. However, in a paper by Gamboa and colleagues, a significant difference in tail length which measured by Comet assay to detect DNA damage between children exposed to high levels of PAH and children exposed to low levels of PAH was reported 21 .…”