Oral exposure to commercially available coal tar‐based pavement sealcoat induces murine genetic damage and mutations

Abstract

Coal tar (CT) is a thick black liquid produced as a by‐product of coal carbonization to produce coke or manufactured gas. It is comprised a complex mixture of polycyclic aromatic compounds, including a wide range of polycyclic aromatic hydrocarbons (PAHs), many of which are genotoxic and carcinogenic. CT is used in some pavement sealants (also known as sealcoat), which are applied to pavement in order to seal and beautify the surface. Human exposure is known to occur not only during application, but also as a result of the weathering process, as elevated levels of PAHs have been found in settled house dust in residences adjacent to CT‐sealed surfaces. In this study we examined the genotoxicity of an extract of a commercially available CT‐based sealcoat in the transgenic Muta™Mouse model. Mice were orally exposed to 3 doses of sealcoat extract daily for 28 days. We evaluated genotoxicity by examining: (1) stable DNA adducts and (2) lacZ mutations in bone marrow, liver, lung, small intestine, and glandular stomach, as well as (3) micronucleated red blood cells. Significant increases were seen for each endpoint and in all tissues. The potency of the response differed across tissues, with the highest frequency of adducts occurring in liver and lung, and the highest frequency of mutations occurring in small intestine. The results of this study are the first demonstration of mammalian genotoxicity following exposure to CT‐containing pavement sealcoat. This work provides in vivo evidence to support the contention that there may be adverse health effects in mammals, and potentially in humans, from exposure to coal tar. Environ. Mol. Mutagen. 57:535–545, 2016. © 2016 Her Majesty the Queen in Right of Canada

Hepatic DNA damage in harbour porpoises (Phocoena phocoena) stranded along the English and Welsh coastlines

“…An external benzo[ a ]pyrene‐7,8‐dihydrodiol‐9,10‐epoxide‐(BPDE)‐modified DNA standard was used as a positive control. As in prior studies, total DNA adduct levels were measured in the diagonal radioactive zone (DRZ) area of the TLC plates and were considered representative of PAH‐DNA and other aromatic/hydrophobic adducts resistant to nuclease P 1 digestion [Tang et al ; Kim et al ; Long et al ]. The method provides a summary measure of a complex mixture of adducts present in the postlabeling chromatograms.…”

Genetic Toxicity of Complex Mixtures of Polycyclic Aromatic Hydrocarbons: Evaluating Dose-Additivity in a Transgenic Mouse Model

“…CT-2, provided by the Canadian National Research Council, is from a Canadian coke production facility. Each CT sample was thoroughly mixed until homogeneous, and an aliquot was removed and extracted in an identical manner as the CT-seal, 21 according to a method adapted from Wise et al 22 An aliquot of the extract was set aside for chemical analysis, and the remainder was used to prepare dosing solutions by first sonicating the eluate and then diluting it in highly refined olive oil (Sigma-Aldrich Canada, Oakville, ON). Dosing solutions, in mg equivalent (eq) weight of crude CT per mL, were prepared weekly and stored in amber glass vials.…”

“…Mice were euthanized and necropsied as previously described, 20 and glandular stomach (GS), small intestine (SI), liver, (Lv), bone marrow (BM), and lung (Lg) were immediately harvested and stored at −80 °C. 20,21 GS was used instead of forestomach as we were unable to obtain sufficient high-quality DNA from the latter. Mice were bred, maintained, and treated according to the Canadian Council for Animal Care Guidelines (available online at: http://www.ccac.…”

“…16 The difference in the deviations from additivity between the bacterial and mammalian cell studies is presumably related to metabolic limitations, and this is discussed in more detail in Lemieux et al 16 In the current study, our aim was to expand on our earlier works by examining PAH mixture dose-additivity across several tissues using an in vivo model. Recently, we determined the in vivo MPs of the eight CCME carcinogenic PAHs, 20 as well as the MP of a purified CT-based driveway sealcoat (CT-seal) 21 following subchronic MutaMouse oral exposures. The data presented in these studies, plus new in vivo assessments of two CT preparations (i.e., CT-1 and CT-2), form the basis of the current follow-up study that employs in vivo genetic toxicity data to complete our evaluations of the dose-additivity assumption for PAHs.…”

Microsatellite mutation frequencies in river otters (Lontra Canadensis) from the Athabasca Oil Sands region are correlated to polycyclic aromatic compound tissue burden

“…Certain PACs are known to be genotoxic (i.e., can cause mutations) and carcinogenic (e.g., benzo[ a ]pyrene (B[ a ]P) (IARC, 2005)), and exposure to PAC mixtures has been shown to elicit genotoxic consequences in both laboratory animals and in wildlife. For instance, laboratory exposure to coal tar has been shown to induce DNA damage (i.e., cause DNA adducts) and mutations in mice (Long et al, 2016) as well as promote murine skin tumor formation when mixed with diesel particulate and cigarette smoke condensate (Siddens et al, 2012). In the Great lakes, herring gulls and cormorants had elevated mutation rates that were associated with PACs released from industrial operations (King et al, 2014; Yauk et al, 2000).…”