Dose-response modeling of occupational exposure to polycyclic aromatic hydrocarbons with biomarkers of exposure and effect.
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 1-, 2+9-, 3-, 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) = -0.03, P = 0.68 for hydroxyphenanthrenes). Correlations with 8-oxo-7,8-dihydro-2'-deoxyguanosine/10(6) dGuo were weakly negative (r(s) = -0.22, P = 0.004 for PAHs) or flat (r(s) = -0.08, 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 microg/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.
Pesch
Beate
B
BGFA Forschungsinstitut für Arbeitsmedizin der Deatschen Gesetzlichen Unfallversicherung, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. pesch@bgfa.de
Kappler
Martin
M
Straif
Kurt
K
Marczynski
Boleslaw
B
Preuss
Ralf
R
Rossbach
Bernd
B
Rihs
Hans-Peter
HP
Weiss
Tobias
T
Rabstein
Sylvia
S
Pierl
Christiane
C
Scherenberg
Michael
M
Adams
Ansgar
A
Käfferlein
Heiko Udo
HU
Angerer
Jürgen
J
Wilhelm
Michael
M
Seidel
Albrecht
A
Brüning
Thomas
T
D015415:Biomarkers; D002274:Carcinogens, Environmental / Q000633:toxicity*; D020552:Comet Assay; D003198:Computer Simulation; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007221:Industry; D008297:Male; D015233:Models, Statistical; D016273:Occupational Exposure; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*
D015415:Biomarkers; D002274:Carcinogens, Environmental; D011084:Polycyclic Aromatic Hydrocarbons