Personal exposure assessment of pesticides in residents: The association between hand wipes and urinary biomarkers.

BACKGROUND: Residential exposure to pesticides may occur via inhalation of airborne pesticides, direct skin contacts with pesticide-contaminated surfaces, and consumption of food containing pesticide residues. The aim was to study the association of dermal exposure to pesticides between the use and non-use periods, between farmer and non-farmer families and between dermal exposure and the excretion of metabolites from urine in residents living close to treated agricultural fields. METHODS: In total, 112 hand wipes and 206 spot urine samples were collected from 16 farmer and 38 non-farmer participants living within 50 m from an agricultural field in the Netherlands. The study took place from May 2016 to December 2017 during the use as well as the non-use periods of pesticides. Hand wipes were analysed for the parent compound and urines samples for the corresponding urinary metabolite of five applied pesticides: asulam, carbendazim (applied as thiophanate-methyl), chlorpropham, prochloraz and tebuconazole. Questionnaire data was used to study potential determinants of occurrence and levels of pesticides in hand wipes according to univariate and multivariate analysis. RESULTS: Carbendazim and tebuconazole concentrations in hand wipes were statistically significantly higher in the pesticide-use period compared to the non-use period. In addition, especially during the use periods, concentrations were statistically significantly higher in farmer families compared to non-farmer families. For asulam, chlorpropham and prochloraz, the frequency of non-detects was too high (57-85%) to be included in this analysis. The carbendazim contents in urine samples and hand wipes were correlated on the first and second day after taking the hand wipe, whereas chlorpropham was only observed to be related on the second day following the spray event. CONCLUSIONS: Concentrations in hand wipes were overall higher in pesticide use periods compared to non-use periods and higher in farmer families compared to non-farmer families. Only for carbendazim a strong correlation between concentrations in hand wipes and its main metabolite in urine was observed, indicating dermal exposure via contaminated indoor surfaces. We expect this to be related to the lower vapour pressure and longer environmental lifetime of carbendazim compared to the other pesticides studies.

DNA adducts in skin biopsies and 1-hydroxypyrene in urine of psoriasis patients and healthy volunteers following treatment with coal tar.

Coal tar ointments (CTO) are frequently used in the treatment of psoriasis and eczema, but CTO contain carcinogenic polycyclic aromatic hydrocarbons (PAH). PAH are absorbed and metabolized in the skin. In psoriasis, the skin barrier is altered and therefore, absorption and metabolism of PAH may differ from healthy skin. In this study, levels of urinary 1-hydroxypyrene and PAH-DNA adducts in the skin were studied in psoriatic patients and healthy volunteers. Three punch biopsies were taken from the lower back of 10 male volunteers and from a psoriatic plaque in 10 male patients. A surface of 6.25 cm(2) was treated with CTO. After 96 h CTO was removed and another three skin biopsies were collected from the treated area. DNA was isolated from skin biopsies and urine was collected during and after the exposure period. After 24h, a twofold lower 1-hydroxypyrene urinary excretion was observed in patients compared to healthy volunteers and after 48 h, this difference reached statistical significance (p<0.05). Over 96 h the median level of the sum of PAH-DNA adducts, analyzed by (32)P-post-labeling, increased from 3.5 before CTO administration to 21.1 adducts per 10(8) nucleotides in volunteers, and from 1.0 to 3.6 adducts per 10(8) nucleotides in patients. At 96 h, PAH-DNA levels were higher in healthy volunteers than in patients (p<0.05). Biomarkers for uptake, bioavailability and bioactivation of PAH were lower in patients compared to volunteers. These data suggest a lower risk of carcinogenic effects of CTO in psoriatic skin compared to healthy skin.

Characterisation of exposure to total and hexavalent chromium of welders using biological monitoring.

Inhalation exposure to total and hexavalent chromium (TCr and HCr) was assessed by personal air sampling and biological monitoring in 53 welders and 20 references. Median inhalation exposure levels of TCr were 1.3, 6.0, and 5.4 microg/m(3) for welders of mild steel (MS, <5% alloys), high alloy steel (HAS, >5% alloys), and stainless steel (SS, >26% alloys), respectively. The median exposures to HCr compounds were 0.23, 0.20, and 0.08 microg/m(3), respectively. Median concentrations of TCr in urine, blood plasma and erythrocytes were elevated in all welders, compared with the corresponding median concentrations in the reference group (p<0.005). The TCr levels observed in plasma were two-fold higher in welders of SS and HAS than in welders of MS (p<0.01). Exposure to HCr as indicated by median total content of Cr in erythrocytes was 10 microg/L in welders of SS, MS and HAS. Uptake of TCr during the shift was confirmed for welders of SS by a median increase of urinary TCr from pre- to post-shift of 0.30 microg/g creatinine. For welders of MS and HAS as a group TCr was not increased.

Exposure to dust and particle-associated 1-nitropyrene of drivers of diesel-powered equipment in underground mining.

A field study was conducted in two mines in order to determine the most suitable strategy for ambient exposure assessment in the framework of a European study aimed at validation of biological monitoring approaches for diesel exhaust (BIOMODEM). Exposure to dust and particle-associated 1-nitropyrene (1-NP) was studied in 20 miners of black coal by the long wall method (Czech Republic) and in 20 workers in oil shale mining by the room and pillar method (Estonia). The study in the oil shale mine was extended to include 100 workers in a second phase (main study). In each mine half of the study population worked underground as drivers of diesel-powered trains (black coal) and excavators (oil shale). The other half consisted of workers occupied in various non-diesel production assignments. Exposure to diesel exhaust was studied by measurement of inhalable and respirable dust at fixed locations and by personal air sampling of respirable dust. The ratio of geometric mean inhalable to respirable dust concentration was approximately two to one. The underground/surface ratio of respirable dust concentrations measured at fixed locations and in the breathing zones of the workers was 2-fold or greater. Respirable dust was 2- to 3-fold higher in the breathing zone than at fixed sampling locations. The 1-NP content in these dust fractions was determined by gas chromatography-mass spectrometry/mass spectrometry and ranged from 0.003 to 42.2 ng/m(3) in the breathing zones of the workers. In mine dust no 1-NP was detected. In both mines 1-NP was observed to be primarily associated with respirable particles. The 1-NP concentrations were also higher underground than on the surface (2- to 3-fold in the coal mine and 10-fold or more in the oil shale mine). Concentrations of 1-NP in the breathing zones were also higher than at fixed sites (2.5-fold in the coal mine and 10-fold in the oil shale mine). For individual exposure assessment personal air sampling is preferred over air sampling at fixed sites. This study also suggests that particle-associated 1-NP much better reflects the ambient exposure to diesel exhaust particles than dust concentrations. Therefore, measurement of particle-associated 1-NP is preferred over measurement of dust concentrations by gravimetry, when linking ambient exposure to biomonitoring outcomes such as protein and DNA adducts and excretion of urinary metabolites of genotoxic substances.

BIOMarkers for occupational diesel exhaust exposure monitoring (BIOMODEM)--a study in underground mining.

Methods for the assessment of exposures to diesel exhaust were evaluated, including various biomarkers of internal exposure and early biological effects. The impact of possible biomarkers of susceptibility was also explored. Underground workers (drivers of diesel-powered excavators) at an oil shale mine in Estonia were compared with surface workers. Personal exposures to particle-associated 1-nitropyrene (NP) were some eight times higher underground than on the surface. Underground miners were also occupationally exposed to benzene and polycyclic aromatic hydrocarbons, as indicated by excretion of urinary metabolites of benzene and pyrene. In addition, increased O(6)-alkylguanine DNA adducts were detected in the white blood cells of underground workers, suggesting higher exposure to nitroso-compounds. However, no differences between underground and surface workers were observed in the levels of other bulky DNA adducts determined by 32P-postlabelling, or in DNA damage. The study indicated that smoking, diet and residential indoor air pollution are important non-occupational factors to consider when interpreting biomonitoring results.

Assessment of genotoxic damage in nurses occupationally exposed to antineoplastics by the analysis of chromosomal aberrations.

To estimate the genotoxic risk of occupational exposure to antineoplastic drugs, chromosomal aberration (CAs) frequencies in peripheral lymphocytes were determined for 20 nurses handling antineoplastics and 18 referents matched for age and sex. Urinary cyclophosphamide (CP) excretion rates, which are used as a marker for drug handling, were also measured on these nurses. We have observed significant frequencies of CAs (about 2.5-fold increase) including chromatid breaks, gaps, and acentric fragments for nurses handling antineoplastics as compared to control subjects (p < 0.05, p < 0.01, excluding and including gaps, respectively). The mean value of CP excretion rate for 12 nurses was 1.63 microg/24 h, suggesting that when the nurses handled CP (and other antineoplastic drugs) this particular compound was absorbed. Our study has shown that increased genetic damage was evident in nurses, at population level, due to occupational exposure to antineoplastics. Until the effects of handling antineoplastics from low-level exposure are known, it will be important to keep the exposure to a minimum.

Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys.

Dermal exposure to anti-neoplastic drugs has been suggested as a potentially important route of exposure of hospital workers. Three small-scale workplace surveys were carried out in several hospitals focusing on contamination by leakage from IV infusion systems; contamination by spilled urine of patients treated with anti-neoplastic drugs and particulate phase anti-neoplastic drugs in the air of outpatient and nursing clinics. A new visual scoring technique using a fluorescent tracer was developed. The method showed a very low limit of detection (0.02 microl of contamination) and a very high inter-observer agreement (ICC=0.99). Evaluation of IV systems and connectors showed distinct differences between the systems. It was estimated that 0.5-250 microg of a drug can become available for contamination during each infusion. Differences in average contamination between nurses were negligible in the experimental set-up. Widespread and frequent contamination due to spillage of contaminated urine was revealed and appeared not to be restricted to the patient's room. Airborne particulate concentrations went undetected for 80% of the measurements. However, in a few cases concentrations up to 2 ng/m(3) of cyclophosphamide were measured predominantly in a room of a patient treated with this anti-neoplastic drug. Based on these results and a recently proposed conceptual model for dermal exposure a most likely exposure scenario was postulated both for nurses involved in administering drugs and nurses caring for treated patients. Estimation of all relevant mass transport rates will be a challenge for the near future.

Urinary cyclophosphamide excretion and micronuclei frequencies in peripheral lymphocytes and in exfoliated buccal epithelial cells of nurses handling antineoplastics.

In this study, urinary cyclophosphamide (CP) excretion rate, as well as micronuclei (MN) in peripheral lymphocytes and in buccal epithelial cells were determined for 26 nurses handling antineoplastics and 14 referents matched for age and sex. In urine samples of 20 out of 25 exposed nurses CP excretion rate was found in a range of 0.02-9.14 microg CP/24 h. Our results of the analyses of CP in urine demonstrates that when the nurses were handling CP (and other antineoplastic drugs) this particular compound was observed in urine. The mean values (+/-SD) of MN frequencies (%) in peripheral lymphocytes from the nurses and controls were 0.61 (+/-0. 32) and 0.28 (+/-0.16), respectively (p<0.01). The mean value (+/-SD) of MN frequency (%) in buccal epithelial cells of nurses was 0.16 (+/-0.19) and also mean MN frequency in buccal epithelial cells for controls was found to be as 0.08 (+/-0.08), (p>0.05). Age, sex and smoking habits have not influenced the parameters analyzed in this study. Handling time of antineoplastics, use of protective equipment and handling frequency of drugs have no effect on urinary and cytogenetic parameters analyzed. No correlation was found between the urinary CP excretion and the cytogenetic findings in nurses. Neither could we find any relationship between two cytogenetic endpoints. Our results have identified the possible genotoxic damage of oncology nurses related to occupational exposure to at least one antineoplastic agent, which is used as a marker for drug handling. As a whole, there is concern that the present handling practices of antineoplastic drugs used in the several hospitals in Ankara will not be sufficient to prevent exposure.

Exposure of pharmacy technicians to antineoplastic agents: reevaluation after additional protective measures.

In the past, special guidelines and protective measures have been introduced to protect hospital workers during the handling of antineoplastic agents; nevertheless, it was found that they did not prevent the uptake of these toxic compounds. In response, additional protective measures were introduced, including adaptations of the laminar downflow hood, use of special masks, use of double pairs of gloves, and replacement of ampules with vials. In the current study, the authors compared the effects in these additional measures with results of a previous study. Cyclophosphamide, 5-fluorouracil, and methotrexate constituted 81% of the antineoplastic agents prepared; therefore, the investigators monitored these compounds again by personal air sampling and by determining the levels of contamination on masks and gloves. Cyclophosphamide in the urine of workers was also measured. During preparation, investigators concluded that there were lower concentrations of cyclophosphamide in the air than had occurred in the previous study. Replacement of ampules with vials (i.e., 5-fluorouracil) resulted in a significantly diminished contamination of latex gloves. Cyclophosphamide was detected in urine samples provided by six of nine technicians; the maximum amount excreted over 5 d was 2.6 microg. The mean cyclophosphamide excretion/d was not significantly lower than that found in the previous study (0.16 microg and 1.44 microg, respectively). Despite an intensified hygienic regimen, exposure to antineoplastic agents cannot be reduced if the reasons for exposure remain unknown.

Urinary cyclophosphamide excretion and chromosomal aberrations in peripheral blood lymphocytes after occupational exposure to antineoplastic agents.

In this study we have compared the results of a method for the detection of cyclophosphamide in urine and the results of analysis of chromosomal aberrations in peripheral blood lymphocytes of four groups of subjects with various exposure statuses. These groups are 17 Dutch and 11 Czech exposed workers (mainly hospital nurses and pharmacy technicians) handling antineoplastic agents and 35 Dutch and 23 Czech controls (nurses, medical doctors, pharmacy and lab technicians) not handling these drugs. The groups were subdivided into smokers and non-smokers because of a confounding effect of smoking. Within the Dutch groups, the percentage of aberrant cells and the number of breaks per cell were increased for smokers compared to non-smokers. The percentage of aberrant cells was increased in Dutch exposed workers in comparison with Dutch control workers. Within the Czech groups the percentage of aberrant cells and the number of breaks per cell were increased in exposed workers in comparison with control workers. However, both Dutch and Czech smokers mainly contributed to the increase. The results suggest an additive effect of exposure and smoking in the Dutch subjects and a more than additive effect in the Czech subjects. In urine samples of three out of 11 Dutch exposed workers cyclophosphamide was found in a range of 0.1-0.5 micrograms/24 h. Higher levels were detected in the urine of eight out of 11 Czech exposed workers, a range of 0.1-2.9 micrograms/24 h. No correlation was observed between the amounts of cyclophosphamide excreted in urine on the one hand and the percentage of aberrant cells and the number of breaks per cell on the other hand. The present study is the first study showing that hospital workers having an increase in chromosome aberrations related to their work are exposed to at least one antineoplastic agent.

Environmental contamination and assessment of exposure to antineoplastic agents by determination of cyclophosphamide in urine of exposed pharmacy technicians: is skin absorption an important exposure route?

In the Netherlands, special guidelines and safety precautions were introduced about 10 y ago for preparation and administration of antineoplastic agents. However, little is known about the effectiveness of these measures. In this study, occupational exposure to antineoplastic agents of nine pharmacy technicians who were involved in drug preparation was investigated. Cyclophosphamide, 5-fluorouracil, and methotrexate accounted for 95% of the antineoplastic agents prepared; therefore, the presence of these compounds was monitored. During preparation, cyclophosphamide was detected in the air of the work environment (< 0.04-10.1 micrograms/m3). Contamination of and permeation through latex gloves were found for each of the three compounds. The uptake of cyclophosphamide was assessed by the determination of cyclophosphamide in urine. The drug was found in urine samples of six pharmacy technicians, including three persons who were not directly involved in the preparation of cyclophosphamide. The amounts excreted ranged from 0.2 to 19.4 micrograms/24 h. The results strongly suggest that inhalation is of minor importance for internal exposure, compared with other, presumably dermal, routes.

Biological and environmental monitoring of occupational exposure of pharmaceutical plant workers to methotrexate.

The exposure of 11 pharmaceutical plant workers to methotrexate (MTX) was studied. Personal air samples were taken during the different manufacturing processes: drug compounding, vial filling, and tablet preparation. The uptake of MTX was established by the determination of MTX in urine. MTX was analyzed using the fluorescence polarization immunoassay (FPIA), a method that is frequently used for monitoring serum levels in patients treated with MTX. The FPIA method was modified in such a way that MTX could be measured quickly and efficiently in air and urine samples. MTX was detected in air samples of all workers except for those involved in the vial filling process (range: 0.8-182 micrograms/m3; median: 10 micrograms/m3). The highest concentrations were observed for workers weighing MTX (118 and 182 micrograms/m3). MTX was detected in urine samples of all workers. The mean cumulative MTX excretion over 72-96 h was 13.4 micrograms MTX-equivalents (range: 6.1-24 micrograms MTX-equivalents). A significantly lower background level of 10.2 micrograms MTX-equivalents was measured in urine of 30 control persons (range: 4.9-21 micrograms MTX-equivalents).

Assessment of occupational exposure of pharmaceutical plant workers to 5-fluorouracil. Determination of alpha-fluoro-beta-alanine in urine.

The exposure of pharmaceutical plant workers, involved in drug compounding and drug production, to 5-fluorouracil (5FU) was studied. 5FU was found by the analysis of air and wipe samples. During weighing, 5FU was detected in the air (75 micrograms/m3). 5FU was also present on the filter of the mask of the weigher (120 micrograms). Before drug compounding 5FU was found on the floor (range, < 1 to 8 ng/cm2; median, 2 ng/cm2). After routine cleaning significant higher amounts of 5FU were measured (range, 70 to 630 ng/cm2; median, 150 micrograms/cm2; P = .02). The amounts of 5FU present on several objects were lower when compared to the amounts on the floor. The gloves used were always contaminated (range, 22 to 720 micrograms/pair of gloves; median, 141 micrograms/pair of gloves). The uptake of 5FU was established by the determination of alpha-fluoro-beta-alanine, the main metabolite of 5FU, in the urine of the workers. Fifty micrograms of alpha-fluoro-beta-alanine were found in urine of the weigher.

Determination of cyclophosphamide in urine by gas chromatography-mass spectrometry.

A sensitive gas chromatographic method for the determination of cyclophosphamide in urine is presented. After liquid-liquid extraction with diethyl ether and derivatization with trifluoroacetic anhydride, cyclophosphamide was identified and quantified with mass spectrometry. The method is suitable for the determination of cyclophosphamide at concentrations of more than 0.25 ng/ml, which enables the uptake of cyclophosphamide during occupational activities, such as the preparation and administration of antineoplastic agents in hospitals, to be measured. Simple preparation makes the method appropriate for routine analysis.

Excretion of benzo[a]pyrene and metabolites in urine and feces of rats: influence of route of administration, sex and long-term ethanol treatment.

The urinary and fecal excretion of benzo[a]pyrene (B[a]P) and its main metabolites were studied after oral and intraperitoneal administration of B[a]P to male and female ethanol-treated and non-ethanol-treated rats. After oral administration of B[a]P more mutagenic compounds as well as B[a]P metabolites were found in feces than after intraperitoneal administration. The excretion of B[a]P metabolites in urine and feces after oral administration were maximal at days 1 and 2 whereas after intraperitoneal administration excretion was maximal at days 2 and 3. In males, the amounts of excreted phenolic metabolites in urine and feces were generally higher than in females. The amounts of mutagenic products in urine and feces of males were also higher than in females after intraperitoneal and oral administration of B[a]P. In urine of female rats that received B[a]P intraperitoneally, a decreased excretion of phenolic metabolites was found after ethanol treatment. In feces of both male and female rats, a decreased excretion of 3-OH-B[a]P was found after ethanol treatment. In this study, the influence of sex and administration route on the excretion of B[a]P metabolites was more pronounced than the effect of ethanol treatment.

Occupational exposure of animal caretakers to cyclophosphamide.

Little is known about the exposure of animal caretakers to toxic agents during the administration of such chemicals to laboratory animals. In this study, we have investigated the environmental contamination with cyclophosphamide (CP) in an animal laboratory where mice were housed and injected with this compound. Also the contamination of gloves, sleeve protectors, and masks used for personal protection was studied. The uptake of CP by the animal caretakers was determined by the analysis of unmetabolized CP in urine. For the estimation of CP in the air, air samples were taken and filters of the air-circulation system were analyzed. On the filters, amounts of CP were detected corresponding with < 0.1-1.0 microgram/day. Environmental contamination was also measured by analysis of wipe samples taken from different spots (objects and surfaces). The presence of CP was not only observed in the room where the mice were housed and treated with CP but also in adjacent rooms (< 0.02-44 ng/cm2). The gloves used during the injection of CP were always contaminated (2-199 micrograms/pair). No penetration of the gloves was established. The sleeve protectors were incidentally contaminated (< 0.3-10 micrograms) and on the masks no CP was found (< 0.2 microgram). Eighty seven urine samples from four animal caretakers were analyzed for unmetabolized CP. In one sample, CP was detected (0.7 microgram). The results show that in this particular study animal caretakers are exposed to CP during their work.

Detection of contamination with antineoplastic agents in a hospital pharmacy department.

The contamination with fluorouracil, cyclophosphamide and methotrexate was studied in a hospital pharmacy department where these drugs were prepared. In the preparation room, air samples were taken before and during preparation of the drugs. Methotrexate was detected in one sample which was collected during preparation (0.3 micrograms/m3). Spot samples were taken in the vertical laminar airflow safety hood before and after preparation of the drugs and after cleaning of the hood. Contamination of the laminar airflow hood was: cyclophosphamide: 1-160 ng/cm2; fluorouracil: 10-62 ng/cm2 and methotrexate: 2-633 ng/cm2. Spot samples from the floor in front of and beneath the laminar airflow hood showed contamination with especially fluorouracil (48-236 micrograms/m2). The gloves used during preparation of the drugs were contaminated mainly with fluorouracil (5-980 ng/cm2). Urine samples from two workers involved in the preparation of the drugs were analysed for unmetabolized cyclophosphamide; it was not detected. Although no uptake of cyclophosphamide was established, it is shown that the methods for measurement of cyclophosphamide, fluorouracil and methotrexate in the preparation room are applicable for the control of occupational exposure to these drugs.

Occupational exposure to antineoplastic agents at several departments in a hospital. Environmental contamination and excretion of cyclophosphamide and ifosfamide in urine of exposed workers.

The occupational exposure to cyclophosphamide (CP), ifosfamide (IF), 5-fluorouracil (5FU), and methotrexate (MTX) of 25 pharmacy technicians and nurses from four departments of a hospital was investigated. Previously developed methods for the detection of exposure to some antineoplastic agents were validated. Exposure to CP, IF, 5FU, and MTX was measured by the analysis of these compounds in the environment (air samples and wipe samples from possible contaminated surfaces and objects). Contamination of the work environment was found not only on the working trays of the hoods and on the floors of the different rooms but also on other objects like tables, the sink unit, cleaned urinals and chamber pots, and drug vials and ampules used for preparation and packing of drugs. The gloves used during preparation of the drugs and during cleaning of the hoods were always contaminated. The uptake of CP or IF was determined by the analysis of both compounds in urine. CP or IF was detected in the urine of eight pharmacy technicians and nurses. The amounts ranged from less than 0.01 to 0.5 micrograms (median: 0.1 microgram). CP and IF were found not only in the urine of pharmacy technicians and nurses actively handling these compounds (n = 2) but also in the urine of pharmacy technicians and nurses not directly involved in the preparation and administration of these two drugs (n = 6). CP and IF were excreted during different periods ranging from 1.40 to 24.15h after the beginning of the working day, suggesting different times of exposure, different exposure routes, and/or interindividual differences in biotransformation and excretion rate for these compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambient and biological monitoring of cokeoven workers: determinants of the internal dose of polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAH) were measured in the breathing zone air of 56 battery workers at two cokeovens during three consecutive days. The concentration of total PAH ranged up to 186 micrograms/m3. Preshift and end of shift urine samples were collected to determine 1-hydroxypyrene, a metabolite of pyrene. Control urine samples were available from 44 workers in the shipping yard of a hot rolling mill. The median values of 1-hydroxypyrene in urine of smoking and non-smoking controls were 0.51 and 0.17 mumol/mol creatinine, respectively. Concentrations of 1-hydroxypyrene up to 11.2 mumol/mol were found in the urine of the cokeoven workers. At the start of the three day working period after 32 hours off work, the 1-hydroxypyrene concentrations were four times higher and at the end of the working period 10 times higher compared with control concentrations. Excretion of 1-hydroxypyrene occurred with a half life of 6-35 hours. Both the ambient air monitoring data and the biological monitoring data showed that the topside workers were the heaviest exposed workers. The relation between air monitoring data and biological monitoring data was not strong. Multiple regression analysis was performed to identify determinants of the internal dose. The combination of exposure and smoking amplify each other and the use of a protective airstream helmet decreases the internal dose. An effect of alcohol consumption and the use of medication on the toxicokinetics of pyrene was not found.