Trends in occupational exposure to styrene in the European glass fibre-reinforced plastics industry.

AIM: This study presents temporal trends of styrene exposure for workers in the European glass fibre-reinforced plastics (GRP) industry during the period 1966-2002. METHODS: Data of personal styrene exposure measurements were retrieved from reports, databases and peer-reviewed papers. Only sources with descriptive statistics of personal measurements were accepted. The styrene exposure data cover personal air samples and biological monitoring data, that is, urinary styrene metabolites (mandelic acid and/or phenylglyoxylic acid) and styrene in blood. Means of series of measurements were categorized by year, country, production process, job and sampling strategy. Linear mixed models were used to identify temporal trends and factors affecting exposure levels. RESULTS: Personal exposure measurements were available from 60 reports providing data on 24145 1-8-h time-weighted average shift personal air samples. Available data of biological exposure indicators included measurements of mandelic acid in post-shift urine (6361 urine samples being analysed). Trend analyses of the available styrene exposure data showed that the average styrene concentration in the breathing zone of open-mould workers in the European GRP industry has decreased on average by 5.3% per year during the period 1966-1990 and by only 0.4% annually in the period after 1990. The highest exposures were measured in Southern Europe and the lowest exposures in Northern Europe with Central Europe in between. Biological indicators of styrene (mandelic acid in post-shift urine) showed a somewhat steeper decline (8.9%), most likely because urine samples were collected in companies that showed a stronger decrease of styrene exposure in air than GRP companies where no biological measurements were carried out.

Personal exposure of workers to atmospheric PAHs on gasworks sites--The SOLEX study.

The aim of the SOLEX study was to estimate the personal exposure of workers to atmospheric polycyclic aromatic hydrocarbons (PAHs) on former gasworks sites in the Paris metropolitan area. Devices to sample gas and particulate phases for 9 PAHs were carried during one working day of a study week in November 1997 by 24 workers and in June 1998 by 19 workers with contrasted job profiles involving different opportunities for contact with the soil; among these volunteers, some were active in the process of contaminated soil remediation during the November study period. PAH concentrations were measured by high-performance liquid chromatography. Subjects working on the site under remediation were clearly more exposed (684.1 ng/m3 for total PAHs in November 1997) than workers, without close contact with soil, whose PAH exposure was similar to that measured by fixed monitors in the ambient air in Paris. The contrasts were weaker in June 1998, when soil remediation had nearly been completed. Only subjects involved in activities with close contact with the ground were found with exposures exceeding background levels. Further investigations are needed to improve our understanding of the influence of the pollutants present in the soil.

Benchmark guideline for urinary 1-hydroxypyrene as biomarker of occupational exposure to polycyclic aromatic hydrocarbons.

Many individual polycyclic aromatic hydrocarbons (PAH) are genotoxic carcinogens. One of the parent PAH, pyrene, undergoes simple metabolism to 1-hydroxypyrene. 1-Hydroxypyrene and its glucuronide are excreted in urine. Biological monitoring of exposure to PAH has rapidly been expanded since urinary 1-hydroxypyrene was suggested as a biological index of dose of pyrene. Since pyrene is always present in PAH mixtures, the biological indicator is not only an indicator of uptake of pyrene, but also an indirect indicator of all PAH. At present, several hundreds of papers reporting on urinary concentrations of 1-hydroxypyrene in workers' urine are available. It appeared that urinary 1-hydroxypyrene is a sound biomarker and that the analytical method is robust and non-laborious. Since epidemiological studies of cancer mortality related to long-term average urinary 1-hydroxypyrene concentration are lacking, a sound health-based limit value of 1-hydroxypyrene in urine cannot be set as yet. Since PAH exposure is widespread and the dermal uptake is substantial among exposed workers, an attempt was made to propose a three-level benchmark guideline for urinary 1-hydroxypyrene. The reference value as a 95th percentile in non-occupational exposed controls is 0.24 micromol mol(-1) creatinine and 0.76 micromol mol(-1) creatinine for non-smokers and smokers, respectively. This is the first level of the benchmark guideline. A no-biological-effect-level of 1-hydroxypyrene in urine of exposed workers was found at 1.4 micromol mol(-1) creatinine. It is the lowest reported level at which no genotoxic effects were found and therefore the estimate for the second level of the benchmark guideline. In two types of industry, coke ovens and primary aluminium production, the regression of airborne PAH concentrations and urinary 1-hydroxypyrene concentrations in exposed workers has been studied. The correlation of airborne concentrations and urinary 1-hydroxypyrene in urine of workers from coke ovens and in the primary aluminium industry was used to estimate the level of urinary 1-hydroxypyrene equal to the present occupational exposure limit (OEL) of PAH. The concentration of 1-hydroxypyrene in urine equal to the OEL is 2.3 micromol mol(-1) creatinine and 4.9 micromol mol(-1) creatinine, respectively, in these two industries. These latter values present the third level of the benchmark guideline.

Urinary 1-hydroxypyrene as a biomarker of polycyclic aromatic hydrocarbons exposure of workers on a contaminated site: influence of exposure conditions.

The aim of the study was to determine the exposure levels of workers to polycyclic aromatic hydrocarbons on gasworks sites by the measurement of urinary 1-hydroxypyrene. Start-shift and end-shift urine samples were taken every day during an entire week (Monday to Friday), once in November and a second time in June. Four groups of workers were selected according to their activity. Increased exposure was only found among volunteers involved in the remediation of a site, 0.16 to 2.31 mumol/mol creatinine in non-smokers. The median of the non-smoker referent group was 0.02 mumol/mol creatinine (95% confidence interval, 0.01 to 0.04). Smokers had greater exposure levels than non-smokers in every group. Within and between variability was around 200%. Assessment of the exposure of persons on contaminated soil is possible, with the condition that the exposed subjects come in direct contact with the soil.

Feasibility of assessing dermal exposure to PAHs of workers on gaswork sites--the SOLEX study.

Population exposure to pollutants in soil is an important public health concern. Difficult to measure, it is usually estimated using multimedia models. Modeling data predict that the skin surface is a predominant exposure route in roughly 15% of the US Superfund sites. Nonetheless, no study has confirmed these predictions. The SOLEX study was an opportunity to study the feasibility of estimating the cutaneous polycyclic aromatic hydrocarbons (PAHs: all 16 of the United States Environmental Protection Agency list) load of workers at three former manufactured gas sites, one of those being under remediation. Over two measurement periods (November 1997 and June 1998), 30 and 28 volunteers, respectively, were equipped for a single day work with five pads that collected soil particles and were placed at the neck, shoulder, wrist, groin, and ankle. Pad contamination was observed for six of the nine workers on the site being remediated but not on other sites. The wrist pad was most often affected, followed by the neck pad, these are, the exposed regions of the body. The PAHs most frequently identified were anthracene, fluoranthene, naphthalene, phenanthrene, and pyrene, at concentrations relatively high. In conclusion, this study showed that estimating skin exposure to soil pollutants is feasible. Secondly, it suggested that only subjects in close contact with the soil had a detectable exposure to PAHs. Extension of this approach to other exposure settings is warranted, especially among children playing in polluted public or private gardens, because their games lead to frequent contact with the soil.

Methods for routine biological monitoring of carcinogenic PAH-mixtures.

The ability of a biomarker to provide an assessment of the integrated individual dose following uptake through multiple routes is especially valuable for mixtures of polycyclic aromatic hydrocarbons (PAH), due to methodological and practical difficulties of collecting and analysing samples from the various environmental compartments like air, water and soil and various media such as diet, cigarette smoke and workroom air. Since 1980, a large variety of novel approaches and techniques have been suggested and tested, e.g. urinary thioethers, mutagenicity in urine, levels of PAH or PAH-metabolites in blood and urine and methods for determination of adducts in DNA and proteins. Two approaches are more frequently reported: PAH-DNA-adduct monitoring in blood cells and urinary 1-hydroxypyrene monitoring. A large research effort has been made to use the extent of binding of PAH to DNA as a biomarker of exposure. The 32P-post-labeling assay detects the total of aromatic DNA-adducts and the adduct level in white blood cells is claimed to be an indicator of the biological effect of the PAH-mixture. However, the levels of aromatic DNA-adducts may be subject to appreciable analytical and biological variation. The present technical complexity of the method makes it more convenient for research applications than for routine application in occupational health practice. Pyrene is a dominant compound in the PAH mixture and is mainly metabolised to the intermediary 1-hydroxypyrene to form 1-hydroxypyrene-glucuronide, which is excreted in urine. Since the introduction of the determination of 1-hydroxypyrene in urine as a biomarker for human exposure assessment in 1985, many reports from different countries from Europe, Asia and America confirmed the potential of this novel approach. The conclusion of the first international workshop on 1-hydroxypyrene in 1993 was that urinary 1-hydroxypyrene is a solid biological exposure indicator of PAH. Studies with a comparison of several biomarkers confirmed that 1-hydroxypyrene in urine is a valid and sensitive indicator of exposure. Periodical monitoring of 1-hydroxypyrene appears to be a powerful method in controlling occupational PAH-exposure in industries. The reference level and the biological exposure limit of 1-hydroxypyrene in urine are discussed.

Uptake of polycyclic aromatic hydrocarbons among trainers in a fire-fighting training facility.

The exposure of fire-fighting trainers to polycyclic aromatic hydrocarbons (PAH) was assessed by personal air sampling. Uptake of PAH was determined by biological monitoring, measuring a metabolite of pyrene, 1-hydroxypyrene, in urine. Eight-hour time-weighted average concentrations benzo(a)pyrene of 0.029 microgram/m3 (instructor), 0.045 microgram/m3 (safety officer), and 0.16 microgram/m3 (fire assistant) were found. Both tobacco smoking and exposure to smoke from fire appeared to be significant sources of increased 1-hydroxypyrene concentrations in fire-fighting trainers. There was evidence of exposure and uptake of PAH among fire-fighting instructors despite the short time of effective exposure and the routine use of protective respirators and protective clothing. Though the uptake of PAH was much lower than found in coke-oven workers, who are known to have an increased relative risk of cancer, a long-term health risk for fire-fighting trainers cannot be excluded. Biological monitoring with urinary 1-hydroxypyrene may be useful in tracing highly exposed persons and in monitoring the effectiveness of control measures.

Dermal absorption of polycyclic aromatic hydrocarbons in the blood-perfused pig ear.

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.

Polycyclic aromatic hydrocarbon-DNA adducts in white blood cell DNA and 1-hydroxypyrene in the urine from aluminum workers: relation with job category and synergistic effect of smoking.

We examined a group of 105 workers from a primary aluminum plant for the presence of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in their WBC and 1-hydroxypyrene in their urine. Workers were recruited from five job categories with different PAH exposure: the anode factory; the bake oven; and the electrolysis and the pot-relining departments. Unexposed workers from the foundry department served as the control group. The exposure to PAH was measured by personal monitoring, and the average PAH concentrations in the work atmosphere ranged from 0.4 micrograms/m3 in the foundry to 150 micrograms/m3 in the pot-relining department. The average exposure to benzo(a)pyrene was under the Swedish exposure limit of 5 micrograms/m3. The internal dose of pyrene was measured utilizing the 1-hydroxypyrene concentration in pre- and postshift urine samples. Higher exposure to PAH in the work atmosphere was associated with increased concentrations of 1-hydroxypyrene in the urine. The average increase in concentration of 1-hydroxypyrene ranged from 0.2 mumol/mol creatinine in the control group to 5.9 mumol/mol creatinine in the pot-relining department; an accumulation of 1-hydroxypyrene over a 5-day working period was observed. A good correlation was found between PAH exposure and the concentration of 1-hydroxypyrene in the urine on a group level (rs = 0.90; P = 0.02). PAH-DNA adducts were determined by 32P-postlabeling analysis (nuclease P1 enrichment procedure).(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of urinary 1-hydroxypyrene excretion in coke-oven workers exposed to polycyclic aromatic hydrocarbons due to improved hygienic skin protective measures.

The effect of hygienic skin protective measures on the internal exposure to polycyclic aromatic hydrocarbons (PAHs) was studied in 13 coke-oven workers. The study took place over 2 consecutive weeks. In 1 week the subjects worked under the normal circumstances, in the other week extra hygienic skin protective measures were instituted: laundered working clothes and a new pair of gloves before each 8-h work shift, and the washing both of the hands and of the face before each break. Biological monitoring was undertaken to measure the effect of the extra hygienic measures on the urinary 1-hydroxypyrene excretion, which is a measure of the internal PAH exposure. The increase of the urinary 1-hydroxypyrene concentration over the 4-day workweek was on average 37% lower when extra hygienic measures were taken, being 1.3 instead of 2.3 mumole 1-hydroxypyrene per mole creatinine (P = 0.03, N = 13). This study demonstrates that simple hygienic skin protective measures result in a significant reduction of the internal PAH exposure.

Biological monitoring of environmental exposure to polycyclic aromatic hydrocarbons; 1-hydroxypyrene in urine of people.

A biomarker of human exposure to chemical agents provides a valuable parameter for assessing the extent and significance of the uptake by giving a measurement that is direct and integrated over time and exposure routes. Urinary 1-hydroxypyrene is currently tested as a biomarker for the assessment of low level environmental exposure of people to polycyclic aromatic hydrocarbons (PAH). Five examples of the application of urinary 1-hydroxypyrene methodology in the assessment of environmental exposure to PAH are presented: inhalation of tobacco smoke; inhalation of urban outdoor air; windsurfers sailing on polluted water; absorption of contaminated food; exposure in an urban area with many heavy industries. The examples illustrate that the urinary 1-hydroxypyrene test is sufficiently sensitive. Urinary 1-hydroxypyrene is an effective biomarker for the assessment of human environmental exposure to PAH.

Smoking and dietary intake of polycyclic aromatic hydrocarbons as sources of interindividual variability in the baseline excretion of 1-hydroxypyrene in urine.

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.

Estimation of individual dermal and respiratory uptake of polycyclic aromatic hydrocarbons in 12 coke oven workers.

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 micrograms pyrene a day. The dermal uptake of pyrene ranged between 4 and 34 micrograms/day, which was about 20% 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 micrograms/m3. The mean respiratory uptake of pyrene varied between 0.5 and 32.2 micrograms/day. Based on the estimates of the dermal and respiratory pyrene uptake it is concluded that an average 75% (range 28%-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 8%-92%, n = 12). The total excreted amount of urinary 1-OH-pyrene 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 49% 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.

Effect of the reduction of skin contamination on the internal dose of creosote workers exposed to polycyclic aromatic hydrocarbons.

Ten creosote-exposed workers of a wood impregnation plant participated in this study, which took place in two consecutive weeks on a Monday, after a weekend off. On one of the two days each worker wore Tyvek coveralls underneath his normal workclothes. Dermal contamination measurements (pyrene on exposure pads) and biological monitoring (urinary 1-OH-pyrene) were performed to measure the reduction of both the skin contamination and the internal dose. The total pyrene skin contamination of workers not wearing coveralls ranged between 47 and 1510 micrograms.d-1 (0.2-7.5 mumol.d-1). On the average, the coveralls reduced the pyrene contamination on the workers' skin by about 35 (SD 63)%. The excreted amount of 1-OH-pyrene in urine decreased significantly from 6.6 to 3.2 micrograms (30.2 to 14.7 nmol). Multiple regression analysis showed that skin contamination by polycyclic aromatic hydrocarbons is the main determinant of the internal exposure dose of creosote workers.

The relationship between polycyclic aromatic hydrocarbons in air and in urine of workers in a Söderberg potroom.

The relationships between increase of urinary 1-hydroxypyrene over the workweek and the airborne concentrations of benzo(a)pyrene and coal tar pitch volatiles (CTPVs) were studied among groups of workers in a vertical-stud Söderberg potroom of an aluminum smelter. There was a strong correlation between the natural logarithm of the pyrene concentration and the natural logarithm of the total polycyclic aromatic hydrocarbon (PAHs) concentration in personal air samples (r = 0.94). 1-Hydroxypyrene as the major metabolite of pyrene, a polycyclic aromatic hydrocarbon, was used as a marker for exposure to PAHs. A strong positive correlation was found between the natural logarithm of increase of urinary 1-hydroxypyrene and the natural logarithm of the estimated airborne PAH exposure (R2 = 0.84 with CTPV) when the use of facial protective clothing was taken into account. The relationship between increase of urinary 1-hydroxypyrene and PAHs differed for workers who used facial protective clothing under their respirators compared to those who did not. A contradictory fact was found: the use of facial protection seemed to lead to an elevated increase of 1-hydroxypyrene over the workweek. The regression model for the relationship between increase of urinary 1-hydroxypyrene over the workweek and airborne CTPV was: LN(change in 1-hydroxypyrene) = -4.7 + 1.2 LN(CTPV) -0.44 LN(CTPV)*(use of facial protection) + 3.5 (use of facial protection).

Effects of the peroxisome proliferator mono(2-ethylhexyl)phthalate in primary hepatocyte cultures derived from rat, guinea pig, rabbit and monkey. Relationship between interspecies differences in biotransformation and peroxisome proliferating potencies.

Primary hepatocyte cultures derived from rat, rabbit, guinea pig and monkey have been treated in vitro with metabolites of di(2-ethylhexyl)phthalate, i.e. mono(2-ethylhexyl)phthalate (MEHP), mono(5-carboxy-2-ethylpentyl)phthalate (metabolite V) and mono(2-ethyl-5-oxohexyl)phthalate (metabolite VI). In rat hepatocyte cultures MEHP and metabolite VI were equally potent in inducing peroxisome proliferation, while metabolite V was much less potent. In rat hepatocytes a 50% increase in both peroxisomal palmitoyl-CoA oxidase activity and microsomal lauric acid omega-hydroxylation activity was found after treatment with 5-15 microM MEHP. In guinea pig, rabbit and monkey hepatocyte cultures, a 50% increase in peroxisomal palmitoyl-CoA oxidase activity was found after treatment with 408-485 microM MEHP. No induction of lauric acid omega-hydroxylation activity was found. These results indicate that peroxisome proliferation can be induced by MEHP in rabbit, guinea pig and monkey hepatocytes, but that these species are at least 30-fold less sensitive to peroxisome proliferation induction than rats. The proposed mechanistic inter-relationship between induction of lauric acid omega-hydroxylation activity and peroxisome proliferation is found in rat hepatocytes, but not in hepatocytes of the other three species. Treatment of guinea pig hepatocyte cultures with MEHP resulted in an increase in triglyceride concentrations in the hepatocytes. In rat and rabbit hepatocyte cultures, triglyceride concentrations were much less altered by MEHP. In monkey hepatocytes a decrease in hepatic triglyceride concentration was found after treatment with MEHP. These effects are in agreement with in vivo effects observed before. After treatment of primary hepatocyte cultures with MEHP, high concentrations of omega- and (omega-1)-hydroxylated metabolites of MEHP were found in media from rat, rabbit and guinea pig cultures. The formation of these metabolites did not decline in time. During treatment the metabolite profile in media from rat hepatocyte cultures moved towards omega-hydroxy metabolites of MEHP. In media from monkey hepatocyte cultures the lowest concentrations of hydroxylated metabolites were determined. No major species differences were found in the potency to form oxidized MEHP metabolites, and thus no unique metabolite differences were found, which could explain the species differences in sensitivity for peroxisome proliferation.

Absorption of polycyclic aromatic hydrocarbons through human skin: differences between anatomical sites and individuals.

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.

Metabolites of the plasticizer di(2-ethylhexyl)phthalate in urine samples of workers in polyvinylchloride processing industries.

Little is known about occupational exposure to the plasticizer di(2-ethylhexyl)phthalate (CAS number 117-81-7), a compound widely used in polyvinylchloride (PVC) plastics. We have studied the uptake of DEHP in workers by determining the concentrations of four metabolites of DEHP in urine samples, i.e., mono(2-ethylhexyl)phthalate (MEHP), mono(5-carboxy-2-ethylpentyl)phthalate, mono(2-ethyl-5-oxohexyl)phthalate, and mono(2-ethyl-5-hydroxyhexyl)phthalate. In addition DEHP concentrations in the air were determined by personal air sampling. Nine workers in a PVC boot factory exposed to a maximum of 1.2 mg/m3 DEHP showed an increase in the urinary concentrations of all four metabolites over the workshift. These results were obtained on both the first and the last day of the workweek. With the exception of MEHP, the increases in the concentrations of the metabolites during a workday were statistically significant. Six workers from a PVC cable factory exposed to a maximum of 1.2 mg/m3 DEHP showed a one- to fourfold increase in the concentrations of the four metabolites over the workshift, but these increases were not statistically significant. These results indicate that measurement of DEHP metabolites in urine samples may be of use for monitoring the occupational exposure to DEHP.

Determination of four metabolites of the plasticizer di(2-ethylhexyl)phthalate in human urine samples.

A method for biological monitoring of exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) is described. In this method the four main metabolites of DEHP [i.e., mono(2-ethylhexyl)phthalate (MEHP), mono(5-carboxy-2-ethylpentyl)phthalate, mono(2-ethyl-5-oxohexyl)phthalate, and mono(2-ethyl-5-hydroxyhexyl)-phthalate] are determined in urine samples. The procedure includes enzymatic hydrolysis, ether extraction, and derivatization with triethyloxonium tetrafluoroborate. Analysis is performed by gas chromatography-electron impact mass spectrometry. The detection limit for all four metabolites is less than 25 micrograms/l urine. The coefficient of variation based on duplicate determinations of urine samples of workers occupationally exposed to DEHP was 16% for MEHP (mean concentration 0.157 mg/l) and 6%-9% for the other three metabolites (mean concentrations 0.130-0.175 mg/l). The method described here was used to study DEHP metabolism in man. Most persons excrete mono(2-ethyl-5-oxohexyl)-phthalate and mono(2-ethyl-5-hydroxyhexyl)phthalate as a (glucuronide) conjugate. Mono(5-carboxy-2-ethylpentyl)phthalate is mainly excreted in free form, while for MEHP a large interindividual variation in conjugation status was observed. Of the four metabolites quantified, 52% are products of a (omega-1)-hydroxylation reaction of MEHP [i.e., mono(2-ethyl-5-oxohexyl)phthalate and mono(2-ethyl-5-hydroxylation reaction of MEHP [i.e., mono(5-carboxy-2-ethylpentyl)phthalate], and 26% is not oxidized further (i.e., MEHP). A good correlation is obtained when the amount of MEHP omega-hydroxylation products is compared with the amount of MEHP (omega-1)-hydroxylation products in urine samples. When the internal dose of DEHP has to be established we recommend that the levels of all four metabolites of DEHP be studied in urine samples.