A web tool for the identification of potential interactive effects of chemical mixtures.

This project was undertaken to develop a toxicological database allowing the identification of possible additive or other interactive effects of mixtures present in the work environment. In the first phase of the project, whose findings have already been published, critical toxicological data were compiled for each of the 695 chemical substances in the Quebec Occupational Health Regulation, allowing the prediction of potential additivity among components of a mixture. In the second phase of this project, the types of interactions for mixtures most likely to be found in workplaces and for which primary literature data are available were specified. The toxicological data were evaluated only for realistic exposure concentrations up to the short-term exposure limit or ceiling value or five times the 8-hr time-weighted average (TWA) permissible exposure limit (PEL) for human data and up to 100 times the 8-hr TWA PEL or ceiling value for animal studies. In total, 675 studies were evaluated covering 209 binary mixtures of substances. For the majority of cases where potential additivity was identified in Phase 1, there is a lack of toxicological data in the primary literature. In these cases, the results of the first phase will be useful as the default hypothesis. The resulting database integrates the results from both phases of the project. A web-based computer tool allows the user to determine whether there is potential additivity or interaction among components of a mixture.

Performance of small evacuated canisters equipped with a novel flow controller for the collection of personal air samples.

Small evacuated canisters have become more common in industrial hygiene personal sampling in recent years. The smaller canisters necessitate a low flow rate to ensure a full-shift air sample can be collected. Evaluation of small evacuated canisters compared to sorbent sampling methods is essential to ensure that the canisters accurately monitor airborne contamination. This data, in a controlled environment, will provide practitioners with valuable reference information when considering air-sampling campaigns. Six 300-mL evacuated canisters were used to collect 6-hour breathing zone samples of styrene on volunteers in a large exposure chamber. The canisters were specially designed with a capillary flow controller developed at McGill University in the mid-1990s. Based on the geometry of the capillary the airflow into the canisters was controlled to a low flow rate, approximately 0.3 mL/min. This low sampling flow rate allowed for the use of small-volume canisters as personal samplers to collect styrene vapors. Charcoal tubes and diffusive badges were simultaneously used to collect side-by-side samples for comparison. In addition, an online gas chromatograph (GC) documented the concentration in the chamber throughout the duration of the exposure. The three methods did not disclose any significant statistical difference when compared to the online GC values and to each other. In addition, linear regression analysis between the charcoal tubes and the canisters resulted in a correlation (R(2) > 0.95). An evaluation of the bias and precision (overall uncertainty) of the capillary-canister method, charcoal tubes, and diffusive badges found them to be within criteria established by European Committee for Standardization 482. The results indicate that the capillary-canister sampling device can be an acceptable alternative to sorbent samplers as a personal sampler providing reliable results that are representative of exposures.

Risk assessment of lung cancer related to environmental PAH pollution sources.

We assessed the lung cancer risk in six localities with aluminium smelting activities and five with other polycyclic aromatic hydrocarbon (PAH) pollution sources, using two quantitative risk assessment (QRA) approaches for PAH mixtures and compared their risk predictions against actual cancer incidence. In the first approach, carcinogen exposure was estimated from animal-derived BaP toxic equivalents (BaPeq) of individual PAHs. The upper bound lifetime risk estimates ranged between 0.012-4.7 x 10(-5) and 0.019-0.94 x 10(-5) in the aluminium and other localities, respectively. The second approach assumed that the potency of PAH mixtures was linked to their BaP content and lifetime lung cancer unit risk gradients were estimated from epidemiological studies based on BaP exposure measurements. Lifetime risks ranged between 0.02-89 x 10(-5) and 0.06-6.8 x 10(-5) in the aluminium and other localities, respectively. Predicted risks were generally higher in smelter towns, and higher when based on epidemiological studies than on BaPeq. In smelting communities, there was a linear relationship (R2 approximately 0.8) between female lung cancer rates and PAH exposure estimates. To conclude, animal/BaPeq-based QRAs predicted lower risks than occupational/BaP-based QRAs. Epidemiological validation of the QRA could be performed for elevated past exposure to PAHs, but not for currently lower concentrations.

Database for the toxicological evaluation of mixtures in occupational atmospheres.

Workers are regularly simultaneously exposed to multiple chemical substances. As in the ACGIH (American Conference of Governmental Industrial Hygienists) approach, the Québec Regulation prescribes that when two or more hazardous substances are present in workplaces and have similar effects on the same organs of the human body, their effects should be considered additive, unless established otherwise. This project was undertaken to develop a user-friendly toxicological database aid in identification of possible interactive effects of mixtures present in the work environment. In the first phase of the project, standard general literature references were used to compile critical data, such as target organs, effects on the target organs, mechanisms of action, and toxicokinetic characteristics of each of the 668 chemical substances appearing in the regulation. Each substance was assigned to one or more of 32 classes of biological effects retained by a group of toxicologists. The resulting database allows the user to find if there is potential additivity among components of a mixture.

Is 1-hydroxypyrene a reliable bioindicator of measured dietary polycyclic aromatic hydrocarbon under normal conditions?

Five healthy volunteers consumed similar amounts of identical foods for 5 consecutive days. The concentration of pyrene and of benzo(a)pyrene was determined in each of the 15 meals by a short analytical method that included sample saponification, solvent extraction, and HPLC analysis. The volunteers also provided three daily total volume 8-h urine samples for the duration of the study for the assessment of 1-hydroxypyrene, a biomarker of pyrene and polycyclic aromatic hydrocarbon (PAH) exposure. Mean recoveries were 83 and 75%, respectively, for pyrene and benzo(a)pyrene in food. Daily dietary pyrene doses varied from 0.7 to 3 microg. Excluding two outliers consisting of meals containing charbroiled pork and beef, pyrene content in the meals estimated from the published literature data was correlated to the measured pyrene, but overestimated the actual concentration by ca. 70%. Despite the identical ingested doses of pyrene, there was a 50-76% (coefficient of variation) interindividual variability in the daily-excreted amount of 1-hydroxypyrene. Urinary excretion of this metabolite was not correlated with ingested dose of pyrene under the normal feeding conditions used in this study. Bioavailability, enzymatic polymorphism, and differences in enterohepatic cycling of the metabolite may contribute to the observed variability. It was calculated that dietary pyrene intake accounts for between 87.5 and 99.8% of the sum of dietary and inhalation intake. From the presented data, unless the above-mentioned factors are taken into account, 1-hydroxypyrene might not be a reliable bioindicator of ingested pyrene (PAHs) under normal feeding conditions.