In Vitro Mammalian Mutagenicity of Complex Polycyclic Aromatic Hydrocarbon Mixtures in Contaminated Soils
- DOI
- Language of the publication
- English
- Date
- 2014-11-24
- Type
- Article
- Author(s)
- Lemieux, Christine L.
- Long, Alexandra S.
- Lambert, Iain B.
- Lundstedt, Staffan
- Tysklind, Mats
- White, Paul A.
- Publisher
- American Chemical Society
Abstract
This study employed an in vitro version of the lacZ transgenic rodent mutation assay to assess the mutagenicity of nonpolar neutral and semipolar aromatic soil fractions from 10 PAH-contaminated sites, and evaluated the assumption of dose additivity that is routinely employed to calculate the risk posed by PAH mixtures. Significant mutagenic activity was detected in all nonpolar neutral fractions, and 8 of 10 semipolar aromatic fractions (nonpolar > semipolar). Mutagenic activity of synthetic PAH mixtures that mimic the PAH content of the soils (i.e., 5-PAH or 16-PAH mix) were greater than that of the PAH-containing soil fractions, with 5-PAH mix >16-PAH-mix. Predictions of mutagenic activity, calculated as the sum of the contributions from the mutagenic mixture components, were all within 2-fold of the observed activity of the nonpolar neutral fractions, with one exception. Observed differences in mutagenic activity are likely the result of dynamic metabolic processes, involving a complex interplay of AhR agonsim and saturation of metabolic machinery by competitive inhibition of mixture components. The presence of hitherto unidentified polar compounds present in PAH-contaminated soils may also contribute to overall hazard; however, these compounds are generally not included in current contaminated site risk assessment protocols.
Plain language summary
Under the Federal Contaminated Sites Action Plan, Health Canada is an Expert Support Department, which means that it provides expert advice, guidance, training and tools on best practices and innovative methods for human health risk assessment to other federal departments. Toxicological evaluations of contaminated sites involve quantification of priority pollutant contamination, and subsequent human health risk assessment. Sites that pose the highest risk of adverse health effects are prioritised for remediation, rehabilitation or access restriction. Sites with a history of coke production, petrochemical processing, metal refining and founding, or coal gas production are often contaminated with high levels of polycyclic aromatic hydrocarbons (PAHs), several of which have the ability to induce genetic mutations and/or cancer. Assessments of lifetime cancer risk posed by complex mixtures of PAHs at contaminated sites generally employ an assumption of "additivity", whereby the total hazard/risk attributable to the PAH mixture is equal to the sum of the incremental contributions of a targeted subset of PAHs with known biological activity. This study employed cultured mouse cells to assess the ability of targeted PAHs, defined mixtures of targeted PAHs, and complex PAH-containing mixtures from contaminated soils to induce mutations and, moreover, used the results to evaluate the assumption of response additivity. The results showed that the ability of complex PAH-containing mixtures to induce mutations is generally within two-fold of that predicted based on the sum of the expected contributions from a small number of targeted PAHs. This indicates that although the mutagenic activity of a PAH-contaminated soil can be influenced by the levels of both targeted and non-targeted PAHs and polar aromatic compounds, the total activity appears to be dominated by a small number of PAHs that have already been identified and characterised. Thus, regulatory decisions based on an assumption of response additivity of targeted PAHs appear scientifically sound. These findings will support human health risk assessment advice given to federal departments managing contaminated sites.
Subject
- Health,
- Health and safety