Exposure to carcinogenic polycyclic aromatic compounds and health risk assessment for diesel-exhaust exposed workers.

OBJECTIVES: Workers' exposure to diesel exhaust in a bus depot, a truck repair workshop and an underground tunnel was determined by the measuring of elemental carbon (EC) and 15 carcinogenic polycyclic aromatic compounds (PACs) proposed by the US Department of Health and Human Services/National Toxicology Program (NTP). Based on these concentration data, the genotoxic PAC contribution to the diesel-exhaust particle (DEP) lung-cancer risk was calculated. METHOD: Respirable particulate matter was collected during the summer and winter of 2001 (except for in the underground situation) and analysed by coulometry for EC and by GC-MS methods for PACs. The use of potency equivalence factors (PEFs) allowed the studied PAC concentrations to be expressed as benzo[a]pyrene equivalents (B[a]P(eq)). We then calculated the lung-cancer risk due to PACs and DEPs by multiplying the B[a]P(eq) and EC concentrations by the corresponding unit risk factor. The ratio of these two risks values has been considered as an estimate of the genotoxic contribution to the DEP cancer risk. RESULTS: For the bus depot and truck repair workshop, exposure to EC and PACs has been shown to increase by three to six times and ten times, respectively, during winter compared to summer. This increase has been attributed mainly to a decrease in ventilation during the cold. With the PEF approach, the B[a]P(eq) concentration is five-times higher than if only benzo[ a]pyrene (B[a]P) is considered. Dibenzopyrenes contribute an important part to this increase. A simple calculation based on unit risk factors indicates that the studied PAC contribution to the total lung-cancer risk attributed to DEPs is in the range of 3-13%. CONCLUSIONS: The 15 NTP PACs represent a small but non-negligible part of lung-cancer risk with regard to diesel exposure. From this point of view, the dibenzopyrene family are important compounds to be considered.

Development and validation of a new bitumen fume generation system which generates polycyclic aromatic hydrocarbon concentrations proportional to fume concentrations.

Bitumen fumes emitted during road paving and roofing contain polycyclic aromatic compounds (PACs) of potential health concern. Little information is available for an experimental device devoted to inhalation experiments with animals exposed to bitumen fumes, and in all studies the systems were never validated for a range of fume concentrations, which prohibited their use for toxicological concentration-effect studies. Therefore, the purpose of this study was to validate a new experimental device able to generate bitumen fumes at different total particulate matter (TPM) concentrations with a linear correlation between TPM and the concentrations of different PACs, thus allowing toxicological dose-response studies with fumes representative of those in the field. Atmosphere samples collected from an animal exposure chamber allowed the determination of TPM, toluene soluble matter, polycyclic aromatic hydrocarbons (PAHs) and semi-volatiles. The particulate size distributions were determined in order to assess the deposition pattern in the respiratory tract. The temperature of 170 degrees C was chosen by analogy with the upper range of the temperature used during paving operations. The temperature of the air passing over the fume emission area was regulated to 20 degrees C and stirring of the heated bitumen was restricted to 90 r.p.m. The data show that the objective of developing a static fume generation system that reproducibly produces fumes in the inhalation chamber for specified target concentrations (TPM) were successful. The within-day variation coefficients for TPM were between 2.5 and 6.1%. The day-to-day variations for TPM concentration were between 4.1 and 5.8%. The concentrations of the 4-5 ring PAHs and the polycyclic aromatic sulphur heterocycles were proportional to the TPM concentration. The 2 and 3 ring PAH concentrations showed a deviation from proportionality with the TPM, probably due to their re-evaporation during sampling. The mass median aerodynamic diameter of airborne particles varied from 1.4 micro m at a fume concentration of 5 mg/m(3) to 3.2 micro m at 100 mg/m(3). In conclusion, this equipment was suitable for nose-only inhalation studies in the 5-100 mg/m(3) range of TPM. Bitumen fumes were generated with a good reproducibility under well-controlled conditions. Finally, the PAH profiles from atmospheric samples were in good agreement with those measured during road paving.

A spectrophotometric method for the determination of organic soluble matter in bitumen fumes.

A UV spectrophotometric procedure was validated for the determination of organic soluble matter in bitumen fumes collected by filtration technique. Ultrasonic extraction was carried out with toluene, an efficient extraction solvent for polycyclic aromatic hydrocarbons, followed by UV absorbance measurements at 320 nm. A calibration curve is plotted from the same set of samples determined by classical weighing method. Further determinations can also be made using the slope factor of the calibration curve. The procedure presents obvious simplicity and rapidity advantages and is less prone to losses than the measurements of weight. Inter-method comparisons of samples collected from experimental laboratory-generated penetration bitumen fumes commonly used in road paving showed that the three available procedures-weighing, infrared, and UV--described for the determination of organic soluble matter yield equivalent results.

Development of an analytical method for the simultaneous determination of 15 carcinogenic polycyclic aromatic hydrocarbons and polycyclic aromatic nitrogen heterocyclic compounds. application to diesel particulates.

A new method enabling the determination of 15 priority carcinogenic polyaromatic compounds (PAC) proposed by the US National Toxicology Program (NTP) has been developed and applied to diesel exhaust particulates (DEP). The clean-up procedure consists of solid-phase extraction (SPE) and HPLC fractionation on silica phases followed by liquid-liquid extraction and chromatography on a polyvinylbenzene copolymer column. The method gives good recoveries for all PAC studied except dibenzo[a,j]acridine and dibenzo[a,h]pyrene, for which recovery values are below 80%. The use of GC-MS ion trap and its capacity to achieve single-ion storage enhanced the sensitivity of the method, enabling the detection of high-molecular-weight PAH in the low ng g(-1) concentration range. Intermediate polarity GC columns, e.g. BPX-50 or equivalent, enabled better separation, when applied to DEP analysis, than the generally used DB-5 apolar phase. This is observed mainly for separation of isomeric compounds belonging to the benzofluoranthene and dibenzopyrene families. The application of this method to DEP sampled from the exhaust of a diesel engine and in confined locations such as a tunnel has shown that all PAH of the NTP list could be detected, except dibenzo[a,h]pyrene. No dibenzacridine or dibenzocarbazole could be detected in such matrices. The method is sufficiently sensitive to be applicable to environmental exposure measurements in occupational health surveys.

Saliva cotinine levels in smokers and nonsmokers.

The authors collected by mail self-reported data on smoking habits and saliva samples that were analyzed for cotinine concentration in 222 smokers and 97 nonsmokers. Participants were members of the University of Geneva (Switzerland) in 1995. The 207 cigarette-only smokers smoked on average 10.7 cigarettes/day and had a median concentration of cotinine of 113 ng/ml. The cotinine concentration was moderately associated with the number of cigarettes smoked per day (+14 ng/ml per additional cigarette, p < 0.001, R2 = 0.45) and was 54 ng/ml higher in men than in women after adjustment for cigarettes per day and for the Fagerström Test for Nicotine Dependence. The cotinine level was not associated with the nicotine yield of cigarettes (r= 0.08). In nonsmokers, the median concentration of cotinine was 2.4 ng/ml. The cotinine concentration was 1.5 times higher in nonsmokers whose close friends/spouses were smokers than in nonsmokers whose close friends/spouses were nonsmokers (p = 0.05). A cutoff of 7 ng/ml of cotinine distinguished smokers from nonsmokers with a sensitivity of 92.3% and a specificity of 89.7%; a cutoff of 13 ng/ml provided equally satisfactory results (sensitivity, 86.5%; specificity, 95.9%). This study provides evidence for the construct validity of both questionnaires and saliva cotinine for the assessment of active and passive exposure to tobacco smoke.

Switzerland: the status of silicosis from the past to the end of the 20th century. Control and prevention.

The silicosis issue in Switzerland is reviewed on the basis of data provided by Suva, the Swiss National Insurance Fund, in charge of law enforcement and of prevention. Pictures of the past period and nowadays consecutively to the occupational medicine surveillance and industrial hygiene practice showed that major improvements have been realized. In the 30's, a constant rise of new cases of silicosis has been observed every year. From 1940 to end of the 60's, a plateau was reached with about 200 to 300 cases per year. Since 1974, a significant decrease is observed, the annual number of new cases being about 100. Since 1989, the new cases level off at 30-50 per year due to drastic control measures and present announced cases are residuals of previous exposures. The number of annual deaths ranges at the unit level with a patient's life expectancy nearly equal to that of the general population. Prevention efforts however should be continued since the activities of concern have changed. Small enterprises with a limited number of personnel dispersed throughout the country, working in the sectors of stone cutting and grinding, civil engineering and cleaning of building surfaces make prevention difficult and may lower its efficiency. In addition, information should also reach categories of individual workers like professional pottery crafstmen or leisure-exposed persons.

[Do the isocyanate monomer standards still protect against attacks of occupational asthma? Should a standard including polyisocyanates be evolved?]. / Les normes sur les monomères d'isocyanates protègent-elles encore contre les atteintes d'asthme professionnel? Faut-il évoluer vers une norme incluant les polyisocyanates?

Field surveys of diisocyanates at the workplaces in Switzerland and particularly in car repair shops, where HDI was the most used, showed that the monomer levels comply with the Swiss permissible exposure limit (PEL) in the great number of situations. Cases of medical surveillance associated with industrial hygiene measurements demonstrate that occupational asthma was also observed in situations where the monomer concentrations are low although high peaks of prepolymers are often recorded. From the statistical data on compensations, the annual incidence of occupational asthma over the period 1988 to 1992 remains around 54 cases with a mean cost of 21,000 sFr. per case per year. It is suggested that a PEL on the prepolymers should be introduced in the Swiss PEL list to enhance the efficiency of prevention policy.

[Occupational asthma due to isocyanates: current research orientation in occupational hygiene]. / Asthme professionnel dû aux isocyanates: nouvelles orientations des recherches en hygiène du travail.

The replacement of the HDI monomer by less volatile prepolymers is not accompanied by a decrease of the incidence of occupational asthma in Switzerland. Field measurements show that the prepolymer concentration levels may be high although the monomer is hardly detectable or complies with the norm. Our researches are focused on the improvement of generation and measurement techniques (international quality control), on the characterization of the prepolymers to study their transformation in biological media. Field surveys will be conducted to establish the prepolymer concentration profiles. We recommend for the introduction in Switzerland of threshold limit values for HDI-biuret and isocyanurate.

Design and evaluation of a solid sampler for the monitoring of airborne 1,6-hexamethylene diisocyanate (HDI) and its prepolymers in two-component spray painting.

An active, solvent-free solid sampler was developed for the collection of 1,6-hexamethylene diisocyanate (HDI) aerosol and prepolymers. The sampler was made of a filter impregnated with 1-(2-methoxyphenyl)piperazine contained in a filter holder. Interferences with HDI were observed when a set of cellulose acetate filters and a polystyrene filter holder were used; a glass fiber filter and polypropylene filter cassette gave better results. The applicability of the sampling and analytical procedure was validated with a test chamber, constructed for the dynamic generation of HDI aerosol and prepolymers in commercial two-component spray paints (Desmodur N75) used in car refinishing. The particle size distribution, temporal stability, and spatial uniformity of the simulated aerosol were established in order to test the sampler. The monitoring of aerosol concentrations was conducted with the solid sampler paired to the reference impinger technique (impinger flasks contained 10 mL of 0.5 mg/mL 1-(2-methoxyphenyl)piperazine in toluene) under a controlled atmosphere in the test chamber. Analyses of derivatized HDI and prepolymers were carried out by using high-performance liquid chromatography and ultraviolet detection. The correlation between the solvent-free and the impinger techniques appeared fairly good (Y = 0.979X-0.161; R = 0.978), when the tests were conducted in the range of 0.1 to 10 times the threshold limit value (TLV) for HDI monomer and up to 60 micrograms/m3 (3 U.K. TLVs) for total -N=C=O groups.

A safer methylation procedure with boron trifluoride-methanol reagent for gas chromatographic analysis of ritalinic acid in urine.

Ritalinic acid (RITA), the major metabolite of methylphenidate (Ritaline) is extracted with a solid-phase C8 column. Following elution, methylation of the carboxylic group is performed with boron trifluoride-methanol as a reagent. The methyl ester of RITA which structurally corresponds to the parent compound methylphenidate is reextracted at pH 9-11. Each step of the analytical method has been systematically studied, particularly the parameters governing the esterification reaction with BF3-methanol. The recovery from the overall method is 96%. The limit of detection is 0.05 micrograms ml-1 with GC-NPD for a 10-ml urine sample. The method has been successfully applied to the detection and quantitation of RITA in urine specimens. The specificity of the methylated RITA peak has been verified by GC-MS in scan mode. Use of diazomethane or sulphuric acid is thus replaced by the use of a less hazardous reagent.

Occupational exposure of truck drivers to dust and polynuclear aromatic hydrocarbons: a pilot study in Geneva, Switzerland.

The exposure to dust and polynuclear aromatic hydrocarbons (PAH) of 15 truck drivers from Geneva, Switzerland, was measured. The drivers were divided between "long-distance" drivers and "local" drivers and between smokers and nonsmokers and were compared with a control group of 6 office workers who were also divided into smokers and nonsmokers. Dust was measured on 1 workday both by a direct-reading instrument and by sampling. The local drivers showed higher exposure to dust (0.3 mg/m3) and PAH than the long-distance drivers (0.1 mg/m3), who showed no difference with the control group. This observation may be due to the fact that the local drivers spend more time in more polluted areas, such as streets with heavy traffic and construction sites, than do the long-distance drivers. Smoking does not influence exposure to dust and PAH of professional truck drivers, as measured in this study, probably because the ventilation rate of the truck cabins is relatively high even during cold days (11-15 r/h). The distribution of dust concentrations was shown in some cases to be quite different from the expected log-normal distribution. The contribution of diesel exhaust to these exposures could not be estimated since no specific tracer was used. However, the relatively low level of dust exposure dose not support the hypothesis that present day levels of diesel exhaust particulates play a significant role in the excess occurrence of lung cancer observed in professional truck drivers.

[Detection of lysergic acid diethylamide in human urine: elimination, screening and analytical confirmation]. / Détection de l'acide lysergique diéthylamide (LSD) dans l'urine humaine: élimination, dépistage et confirmation analytique.

The Coat-A-Count DPC and Roche Abuscreen RIA for LSD were used to search for LSD in urines containing various drugs commonly found in specimens from addicted groups. Elimination of LSD in urine of a volunteer after ingestion of 50 micrograms confirmed that LSD can be detected after 3 days at 0.1 ng/ml cut-off level. Chromatographic conditions were restudied and the full spectrum of trimethylsilyl LSD at 0.125 ng with ion trap GC-MS (ITS40) was shown.

Simultaneous detection and quantitation of O6-monoacetylmorphine, morphine and codeine in urine by gas chromatography with nitrogen specific and/or flame ionization detection.

It is of importance to differentiate heroin intake from the absorption of opiate-containing pharmaceuticals or opiates from other sources. A method for the routine determination of O6-monoacetylmorphine (6-MAM), the specific metabolite of heroin in human urine, by gas chromatography and classical detectors without having recourse to gas chromatography/mass spectrometry-selected ion mode (GC/MS-SIM) is described. With dual detection by nitrogen selective and flame ionization detectors, the limits of detection for 6-MAM were determined to be 2 ng/mL and 4 ng/mL urine for a 10 mL sample. When applied to urines preliminarily screened for opiates, the results appeared consistent in comparison with those obtained by GC/MS-SIM. The method was also developed for the simultaneous quantitative analysis of morphine and codeine. The linearity was tested up to 600 ng/mL for the three compounds of interest 6-MAM, morphine and codeine and their absolute recoveries were 76%, 78%, 75% respectively.

Deposition rates of sidestream tobacco smoke particles in an experimental chamber.

The natural dissipation rates of sidestream smoke (SS) particles dispersed in a chamber were studied from the standpoint of a static atmosphere and were expressed as half-lives of residence in the air. The half-lives for particles less than 0.3 micron, 0.3-0.5 micron and 0.5-1 micron were found to be 25.5, 12.8 and 4.9 h, respectively. Total particulate matter (TPM) decreases by half after 6.2 h. Other data on diluted SS in the indoor air were also reported.

[Is it necessary to confirm the results of drug screening with a 2d analytical method?]. / Faut-il confirmer les résultats du dépistage des drogues par une deuxième méthode d'analyse?

Systematic analyses of positives from urine drug screening with immunochemical techniques have shown the importance of the confirmation of results by a chromatographic procedure. 15 to 30% of false positives can be encountered for opiates. The confirmation technique should have better sensitivity (and specificity) in order to discard divergence from differences between detection limits. Potential false negatives or falsification of positives are discussed. Propositions for a coherent behavior in the Swiss situation are given.

[Exposure to involuntary smoking in local indoor air. Problems linked to the measurement of exposure to tobacco smoke]. / Exposition au fumage involontaire dans l'air intérieur des locaux. Problèmes liés aux mesures de l'exposition à la fumée de tabac.

A brief and critical review of the physical and chemical markers of ETS was made as well as the techniques which were used to measure their concentrations in indoor air. Despite the existing data, more investigations and measurements are needed to characterize the exposure to ETS and their health effects.

[Validation of a method for detecting benzodiazepines in the urine by acid extraction of their benzophenones and thin layer chromatography]. / Validation d'un procédé de détection des benzodiazépines dans l'urine par extraction acide de leurs benzophénones et chromatographie sur couche mince.

The authors confirm the validity of a method of detection for 18 benzodiazepines. Its original feature consists of the extraction in an acid medium. Between 70 and 100 per cent of the drug is recovered, except for the benzophenones which are strongly basic. The yield of hydrolysis is between 70 and 95 per cent, except for diazepam and lormetazepam, for which the yield is about 50 per cent. Depending on the nature of the benzodiazepines, the limit of detection of the process described is between 5 and 20 micrograms/l of urine. Following a single therapeutic dose in non-dependent volunteers, the benzodiazepines were detectable for at least 36 to 48 hours.

[Excretion of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in experimental smokers. Duration of detection in urine]. / Excrétion de l'acide 11-nor-delta 9-tétrahydrocannabinol-9-carboxylique chez les fumeurs expérimentaux. Durée de détection dans l'urine.

Cannabis cigarettes of comparable potency were smoked by experimental smokers. Peak excretion occurs between 2 to 7 hours and falls rapidly in the first 30 hours period. Elimination then goes on slowly over 5 days. Individual and interindividual variations are observed. The test can detect occasional use of cannabis no longer than 36 h to 48 h with good probability. Negative detected user can suddenly excrete metabolites to positive levels. This has a consequence on the use of the test to screen exposed group for epidemiologic studies.