Michel Lafontaine

Bitumen fumes: review of work on the potential risk to workers and the present knowledge on its origin

Bitumens fumes contain polycyclic aromatic compounds (PAC). There is a possibility of long-term health effects following chronic exposure by inhalation or skin contamination in asphalt road pavers and highway maintenance workers. Epidemiological and experimental studies on this topic are reviewed and the possible causes of cancer discussed with a primary focus on heterocyclic polyaromatic compounds. In 2001, the results of the IARC epidemiological study confirmed an excess of lung cancer despite a lower cancer mortality. In vitro genotoxicity and mechanistic studies demonstrated a mutagenic effect of bitumen fume condensates (BFC) and some data suggested that the polycyclic aromatic hydrocarbons (PAH) analysed were not the major genotoxic compounds in bitumen fume condensates. Other compounds such as nitrogen-, sulfur- and/or oxygen-containing PAH or their alkyl substituted analogues, mutagenic in the Ames mutation assay, may be involved in the genotoxic effect of BFC. After skin painting with BFC, DNA adducts were found in skin, lung and lymphocytes of all the treated animals. Differences in the adduct patterns were also observed, but a more polar adduct was common to the three tissues and not observed in those from rats treated with coal-tar fume condensates (CTFC). Rat inhalation experiments with bitumen fumes confirmed the presence of a DNA-adduct in the lungs with the same Rf as the previous polar adduct. This adduct therefore merits further investigation as a potential biomarker in lymphocyte DNA to follow exposed workers. All the analytical data and the mechanistic data are complementary and suggest the potential role of thiophenes in the genotoxicity of bitumen fumes. Some thiophenes have lower mutagenic activity than their isosteric PAH, whereas others are very potent carcinogens. Generally, the sulfur analogues of PAH (SPAH) in bitumen fumes have a higher concentration than the PAH of similar molecular weight, whereas the SPAH in coal-tar fumes have a much lower concentration than the corresponding PAH. This may explain why the more polar adducts have been detected only in animals exposed to bitumen fume. In a skin carcinogenicity study of condensed asphalt roofing fumes, it has been demonstrated that the most active fractions were those containing a variety of aromatic SPAH. In conclusion to this review, there is an interest in determining the chemical identity of the major DNA adducts induced by BFC. This would allow experimental studies on the carcinogenic potency of these compounds and their validation as potential biomarkers. These compounds could thus merit further analytical investigation in preference to the PAH included in the list of the US Environmental Protection Agency that are currently being analysed by the industry in field studies.

Inhalation study on exposure to bitumen fumes. Part 2: Analytical results at two exposure levels

During the hot application of bitumen-containing materials, e.g. in road paving or roofing, fumes are emitted that contain traces of polycyclic aromatic compounds (PACs). Although workers exposure to these fumes is low, it might lead to health problems. For studying DNA adduct formation as a consequence of inhalation of bitumen fumes we developed and validated an inhalation system (a dynamic fume generator plus a nose only inhalation chamber). This paper presents and discusses the analytical results from the different laboratories involved in this study on the fumes sampled in the inhalation chamber during three series of experiments where the animals were exposed to fumes at the 5 mg/m3 and 50 mg/m3 level, coming from bitumen heated at 200 degrees C and, as a positive control, fumes from coal tar, heated to 110 degrees C at the 5 mg/m3 level. The following parameters were controlled: temperatures at different key places in the generator; humidity of the chamber; the bitumen or coal tar flow rate; and Total Particulate Matter (TPM). Analyses were performed for Benzene Soluble Matter (BSM), the EPA polycyclic aromatic hydrocarbon (PAH) mixture and for a number of heteroatom-containing PACs. The data show that the coal tar fumes produced at 110 degrees C were very volatile and that most of the differences in particulate matter found between the laboratories can be attributed to evaporative losses. The bitumen fumes boil 25-50 degrees C higher and contain higher boiling compounds. A comparison is made between the PAC exposure profiles for bitumen experiments aimed at 5 and 50 mg/m3. Although the same molecules are found in both fumes their proportion is dramatically different. This effect is largest with the 2- and 3-ring PACs, the ratio of the concentrations found in the 50 mg/m3 TPM concentration to that in the 5 mg/m3 experiment gradually declines from 5500 for acenaphthene to 500 for pyrene, for the 5-ring PACs this ratio is 20-30. As function of their vapour pressure, the ratios of the concentrations of the hetero PACs follow the same trend as that of the 16 EPA PAHs and are of the same order of magnitude. In conclusion, for the compounds investigated, the equipment delivers a fume atmosphere in a reproducible manner. The 50 mg/m3 bitumen fumes are not representatives of field fumes. The reason for these quantitative differences is unclear and further work would be needed to clarify this. Nevertheless it was felt that these fumes at 50 mg/m3 might be a useful tool for qualitative detection of DNA adducts in an animal exposure study.

EXPOSURE TO POLYCYCLIC AROMATIC HYDROCARBONS AND EXCRETION OF URINARY 3-HYDROXYBENZO[A]PYRENE: ASSESSMENT OF AN APPROPRIATE SAMPLING TIME

Biomonitoring of workers was carried out in seven workplaces—two aluminium plants, an electrometallurgy plant, two carbon brake disk factories, a creosoting workshop, and an artificial target factory—to assess exposure to polycyclic aromatic hydrocarbons (PAHs). At least all the 48 h voided urine samples were collected, the first urine before the preshift at the beginning of the week and the last one after the preshift of the third day. The 3-hydroxybenzo[a]pyrene (3-OHBaP) and 1-hydroxypyrene (1-OHPy) in each urine sample were then analyzed separately by methods developed by INRS. Concentration profiles were determined. They indicate a considerable lag between the maximum excretion of the two metabolites. Including the previously published data obtained with workers exposed to PAHs, this varies from 3 to 24 h (mean lag = 15 h, n = 42). In order to determine the most appropriate sampling time for 3-OHBaP, the time of the 3-OHBaP maximum concentration is compared with the preshift.

URINARY 3-HYDROXYBENZO[A]PYRENE AS A BIOMARKER OF EXPOSURE TO POLYCYCLIC AROMATIC HYDROCARBONS: AN APPROACH FOR DETERMINING A BIOLOGICAL LIMIT VALUE

Atmospheric and biological monitoring was carried out on 38 people exposed to polycyclic aromatic hydrocarbons in different workplaces. The relationship between the atmospheric BaP and the 3-OHBaP urinary concentration peaks was determined. To avoid misinterpretation due to dermal exposure, only people with mainly respiratory exposure were chosen. The selection was carried out from observation of working conditions and from urinary data. For the limit value determination, BaP concentrations higher than 5,000 ng/m3 were discarded and the 3-OHBaP values were adjusted to a 8 h exposure time. A close relationship was observed between the two variables: n = 17, r = 0.89, p < .0001 (C 3-OHBaP = 0.001835*C BaP + 0.1729). To estimate the 3-OHBaP limit concentration, the French recommended value of 150 ng/m3 for atmospheric BaP was used. The corresponding 3-OHBaP was 0.45 nmol/mol creatinine. This value could be used as a sound basic element for determining a biological exposure index.

Excretion of Urinary 1-Hydroxypyrene in Relation to the Penetration Routes of Polycyclic Aromatic Hydrocarbons

In order to determine the respective contribution of cutaneous and respiratory exposure to urinary PyOH excretion, some experimental follow-ups were carried out during cathode relining in the aluminum industry, leading to qualitative (excretion profiles) and quantitative assessments (excreted PyOH/inhaled pyrene). The procedure was as follows: no exposure on Monday, Wednesday, and Friday; polluting operations on Tuesday and Thursday without or with different protections. For workers with cutaneous protection only, a significant peak of PyOH concentration is observed at the postshift, which is followed by a fast decrease to the background level. For workers with respiratory protection, the maximum is in the shape of a plateau which extends for several hours after the postshift and then decreases slowly. For people with contaminated working clothes, a significant amount of PyOH is excreted on the days with no exposition. The mean ratio of urinary excreted PyOH to inhaled pyrene dose is 15.3% for workers with cutaneous protection and 24.5% for workers with no protection.

Automated column-switching high-performance liquid chromatography for the determination of aflatoxin M1

An extractionless method for determining aflatoxin M1 (AFM1), a major metabolite of aflatoxin B1 (AFB1), in human urine was developed. The biological fluid is injected directly into the chromatographic system after simple dilution and centrifugation. A pre-column, packed with a cation-exchange phase and coupled on-line to a column-switching liquid chromatography (LC) system, is used for sample pre-treatment and concentration. The analytes are non-selectively desorbed with the LC eluent and cleaned by means of a column-switching procedure. Pre-treatment and analysis were performed within 40 min. Average AFMI recovery reached 97% in the 10-100 ng/l range of urine. The detection limit of AFM1 in urine and milk was 2.5 ng/l for 1 ml of injected sample. A comparison with an immunoaffinity column clean-up and LC method was performed. The method was applied to determine AFM1 in the urine of AFB1 gavaged rats, and in the urine of both potentially exposed and supposedly unexposed workers. The method was also extended to milk.

Relationship Between Urinary Levels of 1-Hydroxypyrene and 3-Hydroxybenzo[ a ]pyrene for Workers Exposed to Polycyclic Aromatic Hydrocarbons

Biomonitoring of workers was carried out in three working areas--an artificial target factory, an aluminum plant, and an electrometallurgy plant--to assess exposure to PAHs. All the 48 hr-voided urine samples of the exposed workers were collected and the 3-hydroxybenzo[ a ]pyrene (3-OHB a P) and 1-hydroxypyrene (1-OHPy) analyzed according to procedures using automated column-switching high-performance liquid chromatography. The exposure profiles indicate an important lag between the excretion of the two metabolites: the maximum of 3-OHB a P urinary excretion is observed 10 to 17 hr after the 1-OHPy maximum, with a much closer correlation ( r = 0.81) than that obtained with both metabolites in real time ( r = 0.21). This delayed excretion agrees with data from animal intoxication studies (intravenous administration or inhalation). Mean ratios of 1-OHPy to 3-OHB a P were studied without lag (varying from 2,230 to 15,330) and with a lag of 16 hr (varying from 940 to 8,390).

Inhalation Study on Exposure to Bitumen Fumes: Formation of DNA Adducts in Various Rat Tissues Following Nose-only Inhalation

Abstract During the hot application of bitumen containing materials, e.g., in hot paving or roofing, fumes are emitted that contain traces of polycyclic aromatic compounds (PACs) including heterocyclic and/or substituted PACs. Previous studies of DNA adduct formation by bitumen and coal-tar fume condensates (BFCs and CTFCs, respectively) indicated that the genotoxic compounds responsible for DNA adduct formation in BFCs and CTFCs were of different nature. Moreover, it was suggested that the major adduct found in the lungs and also in skin and lymphocytes of BFC-treated rats might be usable as a marker of exposure to bitumen fumes.

Use of physiologically-based pharmacokinetic modeling to simulate the profiles of 3-hydroxybenzo(a)pyrene in workers exposed to polycyclic aromatic hydrocarbons.

Biomathematical modeling has become an important tool to assess xenobiotic exposure in humans. In the present study, we have used a human physiologically-based pharmacokinetic (PBPK) model and an simple compartmental toxicokinetic model of benzo(a)pyrene (BaP) kinetics and its 3-hydroxybenzo(a)pyrene (3-OHBaP) metabolite to reproduce the time-course of this biomarker of exposure in the urine of industrially exposed workers and in turn predict the most plausible exposure scenarios. The models were constructed from in vivo experimental data in rats and then extrapolated from animals to humans after assessing and adjusting the most sensitive model parameters as well as species specific physiological parameters. Repeated urinary voids from workers exposed to polycyclic aromatic hydrocarbons (PAHs) have been collected over the course of a typical workweek and during subsequent days off work; urinary concentrations of 3-OHBaP were then determined. Based on the information obtained for each worker (BaP air concentration, daily shift hours, tasks, protective equipment), the time courses of 3-OHBaP in the urine of the different workers have been simulated using the PBPK and toxicokinetic models, considering the various possible exposure routes, oral, dermal and inhalation. Both models were equally able to closely reproduce the observed time course of 3-OHBaP in the urine of workers and predicted similar exposure scenarios. Simulations of various scenarios suggest that the workers under study were exposed mainly by the dermal route. Comparison of measured air concentration levels of BaP with simulated values needed to obtain a good approximation of observed time course further pointed out that inhalation was not the main route of exposure for most of the studied workers. Both kinetic models appear as a useful tool to interpret biomonitoring data of PAH exposure on the basis of 3-OHBaP levels.

Aerosols Deposits on the Inner Cassette Walls During Pah Sampling : Underestimation of the Inhaled Fraction and of the Occupational Risk

Abstract The inhalable fraction of PAHs is generally collected using a 37 mm glass-fiber filter for particulate matter, followed by a XAD-2 adsorbent tube for gas phase and semi-volatiles. The glass-fiber filter is placed in a closed polystyrene cassette. Under these conditions, a significant part of the sampled fraction is not collected on the filter, but is retained on the inner walls. In order to determine the amount of PAH deposits, 158 samplings were performed in various situations (especially workplaces). For BaP, the deposits represent on average 29% of the whole sampled fraction (44% during cathode relining in an aluminium plant). For pyrene, they represent on average 33% of the sampled fraction (41% at the restoration of soils contaminated by creosote). As deposits on the inner cassette walls are rarely taken into consideration by the occupational hygienists, this may result in a significant risk underestimation when using atmospheric values. Accordingly, percutaneous penetration may be overestim...