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The screen‐and‐bin approach for interpretation of genotoxicity data is predicated on three false assumptions: that genotoxicants are rare, that genotoxicity dose–response functions do not contain a low‐dose region mechanistically characterized by zero‐order kinetics, and that genotoxicity is not a bona fide toxicological endpoint. Consequently, there is a need to develop and implement quantitative methods to interpret genotoxicity dose–response data for risk assessment and regulatory decision‐making. Standardized methods to analyze dose–response data, and determine point‐of‐departure (PoD) metrics, have been established; the most robust PoD is the benchmark dose (BMD). However, there are no standards for regulatory interpretation of mutagenicity BMDs. Although 5–10% is often used as a critical effect size (CES) for BMD determination, values for genotoxicity endpoints have not been established. The use of BMDs to determine health‐based guidance values (HBGVs) requires assessment factors (AFs) to account for interspecies differences and variability in human sensitivity. Default AFs used for other endpoints may not be appropriate for interpretation of in vivo mutagenicity BMDs. Analyses of published dose–response data showing the effects of compensatory pathway deficiency indicate that AFs for sensitivity differences should be in the range of 2–20. Additional analyses indicate that the AF to compensate for short treatment durations should be in the range of 5–15. Future work should use available data to empirically determine endpoint‐specific CES values; similarly, to determine AF values for BMD adjustment. Future work should also evaluate the ability to use in vitro dose–response data for risk assessment, and the utility of probabilistic methods for determination of mutagenicity HBGVs. Environ. Mol. Mutagen. 61:66–83, 2020. © 2019 Her Majesty the Queen in Right of Canada [ABSTRACT FROM AUTHOR]

Background The Alberta oil sands are an important economic resource in Canada, but there is growing concern over the environmental and health effects as a result of contaminant releases and exposures. Recent studies have shown a temporal and spatial trend of increased polycyclic aromatic hydrocarbon (PAH) concentrations in sediments and snowpack near the Athabasca oil sands operations (i.e., open pit mines), but thus far similar studies have not been done for the Cold Lake region where steam assisted gravity drainage ( in situ) extraction is performed. Methods Many PAHs are known mutagenic carcinogens, and this study measured soil and atmospheric concentrations of PAHs in the Cold Lake region to assess the excess lifetime cancer risk posed to the First Nations' inhabitants of the region. Using both deterministic and probabilistic risk assessment methods, excess lifetime cancer risks were calculated for exposures from inhalation or inadvertent soil ingestion. Results The mean excess cancer risk for First Nations' people through ingestion who engage in traditional wilderness activities in the Cold Lake region was 0.02 new cases per 100,000 with an upper 95% risk level of 0.07 cases per 100,000. Exposure to PAHs via inhalation revealed a maximum excess lifetime cancer risk of less than 0.1 cases per 100,000. Conclusions Excess lifetime risk values below 1 case per 100,000 is generally considered negligible, thus our analyses did not demonstrate any significant increases in cancer risks associated with PAH exposures for First Nations people inhabiting the Cold Lake region. [ABSTRACT FROM AUTHOR]

There is currently limited knowledge regarding the impact of different cigarette designs on the toxicological properties of cigarette smoke condensate (CSC). This study used the Salmonella Mutagenicity Assay to examine the mutagenic activity of mainstream CSCs from 11 commercial Canadian cigarette brands with different design features or tobacco blend. The brands were selected to include design features that are common for cigarettes sold in the Canadian market, as well as cigarettes with alternate filters (charcoal or MicroBlue™), the super slim design, and cigarettes containing mixed blends of different tobacco types. CSCs were obtained using the International Organization for Standardization (ISO) and Health Canada Intense (HCI) smoking regimes, and mutagenic activity was assessed using Salmonella strains TA98, YG1041 and YG5185. Comparisons of the commercial brands to the Kentucky 3R4F, the Canadian Monitor 8 reference and a Canadian best seller revealed no significant reduction in CSC mutagenicity for cigarettes with alternate filters. However, the super slim design did afford some reduction in mutagenic potency. Nevertheless, since the study did not attempt to evaluate the impact of the cigarette designs on human health at the individual or population level, the super slim cigarettes cannot be considered ‘reduced-harm’ cigarettes. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are a group of compounds formed during the incomplete combustion of organic matter. Several are mutagenic carcinogens; the magnitude of exposure can be assessed by examining urinary levels of PAH metabolites. Data from biomonitoring studies that record urinary PAH metabolite levels, as well as demographic and lifestyle information, can be used to investigate relationships between PAH exposure and variables, such as smoking status, workplace smoking restrictions, age, sex, household income, home age, and occupation. This study analysed creatinine-adjusted urinary PAH metabolite concentrations and questionnaire data from ~1200 individuals aged 16 years and older surveyed in Cycle 2 of the Canadian Health Measures Survey (CHMS). Statistical analyses revealed that smoking status, age, and sex are associated with urinary concentrations of a pyrene metabolite (1-OHP), phenanthrene metabolites (ΣOH-Phen), fluorene metabolites (ΣOH-Flu) and naphthalene metabolites (ΣOH-Nap). More specifically, smoking status, age and sex can collectively account for 30, 24, 52, and 34% of the observed variations in 1-OHP, ΣOH-Phen, ΣOH-Flu and ΣOH-Nap metabolites, respectively (p < 0.001). Analyses of non-smokers revealed weak but significant effects of age, sex, home age, and occupation on urinary levels of selected PAH metabolites (i.e., <7% of observed variation, p < 0.05). The unexplained variation in PAH metabolite levels is most likely related to diet, which was not examined. Although the results revealed significant relationships between urinary PAH metabolite levels and several lifestyle and/or demographic variables, robust examinations of selected effects (e.g., sex, home age, occupation) will require datasets that are balanced with respect to the other highlighted variables. The results can be used to identify remedial measures to reduce exposure and concomitant risk, and/or design follow-up studies to test hypotheses regarding the causes of exposure differences empirically related to sex, age, home age, and occupation.

Cigarette smoking leads to various detrimental health outcomes. Tobacco companies produce different brands of cigarettes that are marketed as reduced harm tobacco products. Early examples included "light" cigarettes, which differ from regular cigarettes due to filter ventilation and/or differences in chemical constituents. In order to establish baseline similarities and differences among different tobacco brands available in Canada, the present study examined the cytotoxicity, mutagenicity, clastogenicity, and gene expression profiles of cigarette smoke condensate (CSC) from three tobacco products, encompassing a full-flavor, blonde, and "light" variety. Using the Salmonella mutagenicity assay, we confirmed that the three CSCs are mutagenic, and that the potency is related to the presence of aromatic amines. Using the Muta™Mouse FE1 cell line we determined that the CSCs were clastogenic and cytotoxic, but nonmutagenic, and the results showed few differences in potencies among the three brands. There were no clear brand-specific changes in gene expression; each brand yielded highly similar expression profiles within a time point and concentration. The molecular pathways and biological functions affected by exposure included xenobiotic metabolism, oxidative stress, DNA damage response, cell cycle arrest and apoptosis, as well as inflammation. Thus, there was no appreciable difference in toxicity or gene expression profiles between regular brands and products marketed as "light," and hence no evidence of reduced harm. The work establishes baseline CSC cytotoxicity, mutagenicity, and expression profiles that can be used as a point of reference for comparison with data generated for products marketed as reduced harm and/or modified risk tobacco products., (Copyright © 2012 Wiley Periodicals, Inc.)