Seventy-six male volunteers, who were not occupationally exposed to polycyclic aromatic hydrocarbons (PAHs), participated in a study on the effect of tobacco smoking, alcohol consumption, dietary PAH intake, age, and body fat content on the baseline excretion of 1-hydroxypyrene in urine. Major determinants of urinary 1-hydroxypyrene excretion were smoking, dietary PAH intake, and age. The mean 1-hydroxypyrene concentrations in the urine of the volunteers in this study ranged between 0.05 and 0.79 mumol/mol creatinine. Smokers excreted on average 0.25 mumol/mol creatinine (range: 0.10-0.79 mumol/mol creatinine), and nonsmokers on average 0.12 mumol/mol creatinine (range: 0.04-0.29 mumol/mol creatinine). The average number of cigarettes smoked per day correlated well with urinary 1-hydroxypyrene concentrations (rs = 0.67, P < 0.001). The consumption of PAH-containing food products and active smoking account for 99% of total pyrene intake. The effect of age on 1-hydroxypyrene excretion is probably caused by a lower creatinine excretion in the elderly. Passive smoking and fat content had a statistically significant, but negligible effect on urinary 1-hydroxypyrene excretion. Passive smoking and the inhalation of ambient air are relatively in important for total pyrene intake (both account for less than 1%). Neither the consumption of alcohol nor the inhalation of ambient air significantly affected urinary 1-hydroxypyrene excretion. It is concluded that when urinary 1-OH-pyrene excretion is used in the assessment of PAH exposure, one should particularly be aware of the interindividual variability of the baseline excretion of PAH metabolites due to tobacco smoking and dietary PAH intake.

Twelve workers from a coke plant in The Netherlands participated in an intensive skin monitoring programme combined with personal air sampling and biological monitoring during five consecutive eight hour workshifts. The purpose of the study was to make a quantitative assessment of both the dermal and respiratory intake of polycyclic aromatic hydrocarbons (PAHs). Pyrene was used as a marker compound for both dermal and respiratory exposure to PAHs. The biological measure for the internal exposure to PAHs was urinary 1-OH-pyrene concentration.Measurements on exposure pads at six skin sites showed that mean total skin contamination of the 12 workers ranged between 21 and 166 ug pyrene a day. The dermal uptake of pyrene ranged between 4 and 34 4uglday, which was about 200/o of the pyrene contamination on skin. The mean concentration of total pyrene in the breathing zone air of the 12 coke oven workers ranged from 0.1 to 5-4 4ug/m3. The mean respiratory uptake of pyrene varied between 0*5 and 32*2 ug/day. Based on the estimates of the dermal and respiratory pyrene uptake it is concluded that an average 75% (range 2$%/o-95%, n = 12) of the total absorbed amount of pyrene enters the body through the skin. Because of the difference in the pyrene:benzo(a)pyrene ratio between the air samples and the skin contamination samples, the dermal uptake of benzo(a)pyrene was also estimated. This was about 51% of the total absorbed amount (range 80%o-92%, n = 12).The total excreted amount of urinary 1-OHpyrene as a result of exposure to PAHs during the five consecutive workshifts varied between 36 and 239 nmol. A multiple regression model of the mass balance between pyrene dose (both dermal and respiratory) and 1-OH-pyrene excretion confirmed the relevance of the dermal exposure route. The variation in urinary 1-OH-pyrene excretion was determined more by the dermal pyrene dose than by the respiratory dose. The model showed an estimate of the percentage of the absorbed amount of pyrene that is metabolised and excreted as 1-OH-pyrene in urine. For the 12 workers this percentage varied between 13% and 490/o depending on smoking habits and consumption of alcohol. The results of this study indicate that among coke oven workers, the skin is the main route of uptake of PAHs. Preventive measures to reduce exposure to PAHs should be focused more on the reduction of dermal contamination by PAHs than on the reduction of inhaled dose.

In order to determine differences in absorption of polycyclic aromatic hydrocarbons (PAH) between anatomical sites and individuals, coal-tar ointment was applied to skin of volunteers at various sites. The surface disappearance of PAH and the excretion of urinary 1-OH-pyrene after skin application of coal-tar ointment were used as parameters for dermal PAH absorption. The surface disappearance was determined by the measurement of the fluorescence of PAH on skin. Surface disappearance measurements show low but significant differences in dermal PAH absorption between anatomical sites: shoulder > forehead, forearm, groin, > ankle, hand (palmar site). The average PAH absorption rate constant at different skin sites ranges from 0.036/h to 0.135/h (overall mean: 0.066/h). This indicates that after 6 h of exposure, 20-56% of a low dermal dose of PAH (e.g., about 1.0 ng pyrene/cm2) will be absorbed. The interindividual differences in PAH absorption are small (7%) in comparison with differences between anatomical sites (69%). Results based on the urinary excretion of 1-OH-pyrene are less clear. The site of application of the coal-tar ointment (dose: 2.5 mg/cm2 during 6 h) has no significant effect on the excreted amount of 1-OH-pyrene in urine. It is estimated that after coal-tar ointment application on skin, 0.3-1.4% of the pyrene dose (about 2 micrograms pyrene/cm2) becomes systemically available. For the accurate estimation of PAH uptake through skin of workers, it seems relevant to distinguish different body regions, not only because of the regional variation in percutaneous PAH absorption, but also because of the high dispersal of PAH contamination on skin of workers.

No abstract

Urinary 1-OH-pyrene, a metabolite of pyrene, is a sensitive biological marker for dermal absorption of pyrene in man. In order to determine whether this metabolite is a reliable biomarker of cutaneous absorption of other polycyclic aromatic hydrocarbons (PAHs), the blood-perfused pig ear model was used to compare the dermal absorption flux of pyrene with nine other PAHs after coal tar application. Cumulative absorption of PAHs into the perfusion blood, 200 min after application of an overdose of coal tar, ranged between 830 pmol cm-2 for phenanthrene to less than 4 pmol cm-2 for benzo[b]fluoroanthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenzo[ah]anthracene and indeno[123-cd]pyrene. The results of this study show that when pyrene is used as a marker compound for PAH absorption through pig skin, the cumulative absorption of PAHs with a lower molecular weight will be underestimated: fluorene, tenfold; phenanthrene, 12-fold; anthracene and fluoranthene, ca. twofold. The percutaneous absorption of PAHs with a higher molecular weight than pyrene will be overestimated: e.g. benzo[a]pyrene, sevenfold; indeno [123-cd]pyrene, ca. 100-fold. It is likely that this conclusion is also valid for dermal PAH absorption in man.