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Introduction: Diesel particulate matter (DPM) emitted from diesel engines is a major source of air pollutants. DPM is composed of elemental carbon, which adsorbs organic compounds including toxic polycyclic aromatic hydrocarbons (PAHs). The skin, as well as airways, is directly exposed to DPM, and association of atopic dermatitis, psoriasis flares, and premature skin aging with air pollutant levels has been documented. In skin, the permeation of DPM and DPM-adsorbed compounds is primarily blocked by the epidermal permeability barrier deployed in the stratum corneum. Depending upon the integrity of this barrier, certain amounts of DPM and DPM-adsorbed compounds can permeate into the skin. However, this permeation into human skin has not been completely elucidated., Methods: We assessed the permeation of PAHs (adsorbed to DPM) into skin using ex vivo normal (barrier-competent) organ-cultured human skin after application of DPM. Two major PAHs, 2-methylnaphthalene and triphenylene, and a carcinogenic PAH, benzo(a)pyrene, all found in DPM, were measured in the epidermis and dermis using liquid chromatography electrospray ionization tandem mass spectrometry. In addition, we investigated whether a topical formulation can attenuate the permeation of DPM into skin., Results: 2-Methylnaphthalene, triphenylene, and benzo(a)pyrene were recovered from the epidermis. Although these PAHs were also detected in the dermis after DPM application, these PAH levels were significantly lower than those found in the epidermis. We also demonstrated that a topical formulation that has the ability to form more uniform membrane structures can significantly suppress the permeation of PAHs adsorbed to DPM into the skin., Conclusion: Toxic compounds adsorbed by DPM can permeate even barrier-competent skin. Hence, barrier-compromised skin, such as in atopic dermatitis, psoriasis, and xerosis, is even more vulnerable to air pollutants. A properly formulated topical mixture that forms certain membrane structures on the skin surface can effectively prevent permeation of exogenous substances, including DPM, into skin., (© 2024 S. Karger AG, Basel.)

Particulate matter 2.5 (PM 2.5 ) exposure can increase the prevalence of allergic rhinitis (AR), the mechanism underlying which may include oxidative stress and inflammatory response. As a ROS quenching agent, N-acetylcysteine (NAC) can attenuate the accumulation of inflammatory cells and hyper-responsiveness in animal asthma models. To explore the effect of NAC on the oxidative stress and inflammatory reactions in AR rats exposed to PM 2.5 , we analyzed the components of PM 2.5 and examined the nasal symptoms, redox level in nasal mucosa, Th1/Th2-related serum cytokines, nasal mucosal histopathology and ultrastructure in AR rat models with NAC intervention after PM 2.5 exposure. The results showed that the high concentrations of metal cations and PAHs in PM 2.5 could aggravate Th2-dominant allergic inflammation in AR model and cause redox imbalance, accompanied by nasal epithelial cell stripping and eosinophil infiltration, while NAC intervention could alleviate the clinical symptoms of AR model after PM 2.5 exposure, correct the redox imbalance, reduce the Th2 cytokines, reduce eosinophil infiltration, and promote the moderate regeneration of epithelial cells. The mechanism of NAC reversing PM 2.5 -mediated action may be related to its anti-oxidant and anti-inflammatory effects, which may provide some new insights for the prevention of AR exacerbated by exposure to PM 2.5 ., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The research objective was to study the presence of DNA damages in haddock exposed to petrogenic or pyrogenic polyaromatic hydrocarbons (PAHs) from different sources: 1) extracts of oil produced water (PW), dominated by 2-ring PAHs; 2) distillation fractions of crude oil (representing oil-based drilling mud), dominated by 3-ring PAHs; 3) heavy pyrogenic PAHs, mixture of 4/5/6-ring PAHs. The biological effect of the different PAH sources was studied by feeding juvenile haddock with low doses of PAHs (0.3-0.7 mg PAH/kg fish/day) for two months, followed by a two-months recovery. In addition to the oral exposure, a group of fish was exposed to 12 single compounds of PAHs (4/5/6-ring) via intraperitoneal injection. The main endpoint was the analysis of hepatic and intestinal DNA adducts. In addition, PAH burden in liver, bile metabolites, gene and protein expression of CYP1A, GST activity, lipid peroxidation, skeletal deformities and histopathology of livers were evaluated. Juvenile haddock responded quickly to both intraperitoneal injection and oral exposure of 4/5/6-ring PAHs. High levels of DNA adducts were detected in livers three days after the dose of the single compound exposure. Fish had also high levels of DNA adducts in liver after being fed with extracts dominated by 2-ring PAHs (a PW exposure scenario) and 3-ring PAHs (simulating an oil exposure scenario). Elevated levels of DNA adducts were observed in the liver of all exposed groups after the 2 months of recovery. High levels of DNA adduct were found also in the intestines of individuals exposed to oil or heavy PAHs, but not in the PW or control groups. This suggests that the intestinal barrier is very important for detoxification of orally exposures of PAHs., Competing Interests: The authors have declared that no competing interests exist.

Air pollution, especially that initiated by particulate matter (PM), has been implicated as a risk factor for several inflammatory diseases. Previously, it was reported that PM enhances immune responses. PM includes the tar fraction that contains polycyclic aromatic hydrocarbons (PAHs), which produce adverse health effects in exposed individuals. However, the influence of the tar fraction (as a component of PM) on splenocytes is not fully understood. The aim of this study was to determine the effects of the tar fraction extracted from PM collected from the atmosphere in Fukuoka, Japan, on mouse splenocytes. ICR mice were administered tar (1 or 5 μg/mouse) intratracheally 4 times at 2-week intervals, and splenocytes from the tar-treated mice were extracted and examined. The parameters determined were proliferation, cytokine concentrations and transcription factors activation. Following tar treatment, splenocyte proliferation increased relative to controls. Concanavalin A (ConA)-induced interleukin (IL)-2 formation and ConA- or lipopolysaccharide (LPS)-induced interferon-γ production were elevated in splenocytes from tar-exposed mice. However, the production of tumor necrosis factor-α and IL-6 induced by LPS was not markedly changed following tar treatment. Further, nuclear factor of activated T cells, but not nuclear factor-κB, was enhanced in splenocytes of tar-exposed mice. Data indicate that tar-activated splenocytes and PM-bound PAHs might contribute to T cell activation in the spleen.

Background: Polycyclic aromatic hydrocarbons (PAHs) are of environmental and public health concerns and contribute to adverse skin attributes such as premature skin aging and pigmentary disorder. However, little information is available on the potential roles of chronic urban PAH pollutant exposure on the cutaneous microbiota. Given the roles of the skin microbiota have on healthy and undesirable skin phenotypes and the relationships between PAHs and skin properties, we hypothesize that exposure of PAHs may be associated with changes in the cutaneous microbiota. In this study, the skin microbiota of over two hundred Chinese individuals from two cities in China with varying exposure levels of PAHs were characterized by bacterial and fungal amplicon and shotgun metagenomics sequencing., Results: Skin site and city were strong parameters in changing microbial communities and their assembly processes. Reductions of bacterial-fungal microbial network structural integrity and stability were associated with skin conditions (acne and dandruff). Multivariate analysis revealed associations between abundances of Propionibacterium and Malassezia with host properties and pollutant exposure levels. Shannon diversity increase was correlated to exposure levels of PAHs in a dose-dependent manner. Shotgun metagenomics analysis of samples (n = 32) from individuals of the lowest and highest exposure levels of PAHs further highlighted associations between the PAHs quantified and decrease in abundances of skin commensals and increase in oral bacteria. Functional analysis identified associations between levels of PAHs and abundance of microbial genes of metabolic and other pathways with potential importance in host-microbe interactions as well as degradation of aromatic compounds., Conclusions: The results in this study demonstrated the changes in composition and functional capacities of the cutaneous microbiota associated with chronic exposure levels of PAHs. Findings from this study will aid the development of strategies to harness the microbiota in protecting the skin against pollutants. Video Abstract.

Risk assessment conclusions for a site may differ when using site-specific versus default values for the relative bioavailability factor (RBAF) and dermal absorption fraction (ABS.d), because these inputs affect both surface soil screening levels and risk/hazard estimates. Indeed, our case study demonstrates that different conclusions may be reached as to regulatory need for remedial action to protect human health when evaluating soil sampling data for seven carcinogenic polycyclic aromatic hydrocarbons (PAHs) using site-specific versus default TCEQ and USEPA residential soil screening levels. Use of site-specific RBAF and ABS.d values increased carcinogenicity-based TCEQ and USEPA surface soil screening levels for PAHs by 4.4- and 6-fold on average, respectively. Soil screening levels for PAHs were more sensitive to changes in ingestion exposure route parameters than to changes in dermal exposure route parameters. Accordingly, site-specific RBAF and ABS.d information has important implications for screening chemicals at PAH-impacted sites, and in addition provides more realistic estimates of risks/hazards posed by PAHs in soil with reduced uncertainty compared to estimates based on default RBAF and ABS.d values. Although default values are generally deemed acceptable by regulatory agencies, use of risk/hazard estimates based on these default values may compel insufficiently justified remedial action in some instances., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants in aquatic ecosystems, which may have potentially toxic effects on organisms. In this study occurrence of DNA strand breaks, oxidative stress, and cytotoxicity were investigated in rainbow trout hepatocytes following in vitro exposure for 24 h to four PAHs (0.01-10 µM): naphthalene, fluoranthene, pyrene, and benzo[a]pyrene (B[a]P). The exposed hepatocytes were analyzed for DNA strand breaks using the comet assay and for antioxidant status by measuring intracellular glutathione (GSH) content using the fluorescent probe mBCl. The cytotoxicity of PAHs was assessed using the fluorescent probe CFDA-AM. The results showed that fluoranthene, pyrene, and B[a]P were genotoxic at all exposure concentrations, whereas naphthalene was genotoxic at concentrations ≥0.1 µM. All treatments reduced the intracellular concentrations of GSH for all four PAHs, except 10 µM of B[a]P, suggesting that some level of oxidative stress was present. The cytotoxic effect was observed for naphthalene at concentrations ≥0.1 µM and pyrene at all exposure concentrations, whereas fluoranthene and B[a]P were not cytotoxic at the tested concentrations. The study shows that low-molecular-weight PAHs may cause DNA strand breaks as high-molecular-weight PAHs do in fish tissue. In addition, two- to five-ring PAHs can induce oxidative stress and cytotoxicity.

Combined exposure to complex mixtures of polycyclic aromatic hydrocarbons (PAHs) and ultraviolet radiation (UVR) is suspected to enhance PAH skin permeability and skin cancer risk depending on PAH bioactivation. The impact of PAH mixtures (exposure dose, composition, and complexity) and UVR was assessed for PAH cutaneous absorption and metabolism using realistic exposure conditions and human skin explants. PAH complex mixtures were extracted from the industrial products coal tar pitch (CTP-I) and petroleum coke (PC-I). The synthetic mixture (CTP-S) was identically reconstituted using PAH standards. The applied dose was adjusted to 1 (PC-I, CTP-I) or 10 nmol (CTP-I, CTP-S) of benzo[a]pyrene (B[a]P). Unmetabolized PAHs were recovered from the skin surface, skin and medium, and then quantified by HPLC-fluorescence detection. PAH metabolites were collected from the medium and analyzed by GC-MS/MS. B[a]P and PAH penetration was lower for the highest B[a]P dose, industrial mixtures, and CTP-I compared to PC-I. Skin irradiation increased PAH penetration only for CTP-I. PAH uptake was poorly influenced by the different experimental conditions. PAH metabolism markedly decreased in the application of mixtures, leading to unmetabolized PAH accumulation in human skin. PAH metabolism was similar between CTP-I and PC-I, but was lower for the highest dose and the industrial mixtures, suggesting a saturation of xenobiotic metabolizing enzymes, as confirmed in a time-course study. UVR strongly inhibited all PAH metabolism. Altogether, these results underline the necessity to consider the reality of human exposure (PAH complex mixtures and UVR) during in vitro experiments to properly estimate skin absorption and metabolism.

As a robust radioanalytical method for tracking carbonaceous particulates in vivo, polycyclic aromatic hydrocarbons from diesel exhaust were labeled with a radioactive-iodine-tagged pyrene analogue. Single-photon emission computed tomography and biodistribution studies showed high uptake and slow clearance of this matter in the respiratory system, which may underlie its severe toxicity.

Alongside the analysis of urinary metabolites which are traditional biomarkers of polycyclic aromatic hydrocarbons (PAH) exposure, the possibility of detecting PAH as well as their metabolites in hair has also recently been demonstrated. As the concentration of pollutants detected in hair is not impacted by short-term variations in exposure as can be observed with urine, it accurately represents an individual's average level of exposure, which is the most relevant information when investigating possible linkages with biological effects. In the current study, based on a rat model exposed to a mixture of PAHs for a 90-day period, the linkage between the PAH exposure level and the resulting concentration of their metabolites in hair was then investigated. The linkage between exposure levels and the concentrations of OH-PAH in hair collected at the end of the experiment were compared to those obtained using urinary concentration of OH-PAH collected from the same animals. Linear relationship between levels of exposure and the concentration of OH-PAH in the rats' hair (R 2 0.722-0.965, p < 0.001) was observed for 28 OH-PAH out of the 54 investigated. The difference in PAH concentration between the different groups of exposure and the possibility to back determine the animals' level of exposure on the basis of PAH-metabolite concentrations in both hair and urine was also demonstrated. In addition to the strong linear relation observed between the doses of exposure and the levels of concentration of hydroxylated metabolites in hair (p < 0.001), the analysis of a subset of animals demonstrated a linkage between 3-OH-benzo[a]pyrene concentration levels in hair and the levels of B[a]P-DNA adduct formed (p < 0.05), thereby suggesting the potential of their analysis to predict genetic alteration.

Introduction: In Italy only a small fraction of cancer is reported to the supervisory body and recognised as professional by the insurance institution. Among the causes of this sub-notification, especially for lowgrade etiologic fractional cancers such as bladder cancers are the lack of knowledge of carcinogenicity in the occupational field and the consequent incomplete medical history collections., Objectives: Diagnosis of occupational bladder neoplasms and activation of systematic surveillance of tumors of professional origin through an "active research" program., Methods: From July 2010 to July 2017, all patients diagnosed with Bladder Cancer in the departments of Urology of Area Vasta 3 ASUR Marche underwent a first interview and a further anamnestic study in selected cases.When an occupational exposure was recognised, more information for preventive, social security and criminal justice has been acquired., Results: The study highlighted 18 cases of bladder tumors due to occupational exposure to aromatic amines and polycyclic aromatic hydrocarbons, which are the most important risk factor for BC after tobacco smoking., Conclusions: Our study confirmed that active research is an useful tool both for the activation of epidemiological surveillance and for the regional registration of professional tumors. In addition active research of occupational exposure allow obtaining information that can be used for preventive purposes, for criminal justice and for the initiation of medico-legal actions and improvement of working conditions aimed at guaranteeing workers' rights.

Background: Ultraviolet radiation (UVR) and crude coal tar (CCT) containing PAHs can accelerate the skin-aging process (SAP). However, UVR induces the formation of an important protective factor in SAP (vitamin D)., Objective: To determine the relation of SAP to selected risks and benefits of combined dermal exposure to UVR and coal tar (PAHs)., Methods: The study group consisted of patients with chronic stable plaque psoriasis and treated by Goeckerman therapy (GT; daily dermal application of UVR and 5% CCT ointment). The levels of urinary 1-hydroxypyrene (1-OHP), oxidative stress (DNA and RNA damage), genotoxic damage (chromosomal aberration in peripheral lymphocytes; ABC), 25-hydroxy-vitamin D [25(OH)D] and the PASI score were evaluated before and after GT., Results: Intensive dermal absorption of PAHs was confirmed by increased levels of 1-OHP (p<0.01). After the therapy, we found an increased level of oxidative stress (p<0.05), an increased level of genotoxic damage (ABC; p<0.001), a high efficiency of the treatment (p<0.001) and an elevated production of 25(OH)D (p<0.01). We also found a relationship between the duration of UVR and the genotoxic damage (p<0.01), vitD (p<0.05) and the PASI score (p<0.05). Furthermore, we found a relationship between oxidative stress and 25(OH)D (p<0.05) and between genotoxic damage and the PASI score (p<0.05)., Conclusion: Dermal exposure to UVR and coal tar (PAHs) enhances the level of oxidative stress and genotoxic damage and thus contributes to SAP. However, the exposure is very effective as a treatment and elevates the production of 25(OH)D, the protective factor in SAP. According to our results, UVR is probably a more hazardous factor in SAP., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

This article reviews the state of the science regarding oral bioavailability, bioaccessibility, and dermal absorption of carcinogenic polycyclic aromatic hydrocarbons (cPAHs) in soil by humans, and discusses how chemical interactions may control the extent of absorption. Derived from natural and anthropomorphic origins, PAHs occur in a limited number of solid and fluid matrices (i.e., PAH sources) with defined physical characteristics and PAH compositions. Existing studies provide a strong basis for establishing that oral bioavailability of cPAHs from soil is less than from diet, and an assumption of 100% relative bioavailability likely overestimates exposure to cPAHs upon ingestion of PAH-contaminated soil. For both the oral bioavailability and dermal absorption studies, the aggregate data do not provide a broad understanding of how different PAH source materials, PAH concentrations, or soil chemistries influence the absorption of cPAHs from soil. This article summarizes the existing studies, identifies data gaps, and provides recommendations for the direction of future research to support new default or site-specific bioavailability adjustments for use in human health risk assessment.

In this paper, we investigated the potential of lipid nanocapsules (LNCs) as a delivery system of small hydrophobic molecules, polycyclic aromatic hydrocarbons (PAHs) - pyrene, fluoranthene, phenanthrene, in the copepod Acartia tonsa. The LNCs were produced by a phase inversion process with a nominal size of 50 nm. These nanocapsules were obtained without organic solvent and with pharmaceutically acceptable excipients. The PAHs-LNCs displayed a stable monodisperse size distribution and a good stability in sea water for 7 days. By using fluorescent LNCs, it was possible to evidence LNCs ingestion by the copepods using confocal laser scanning microscopy. While blank LNCs are not toxic to copepods at tested concentrations, PAH-loaded LNCs were found to be very toxic on A. tonsa with a high mortality rate reaching 95% after 72 h exposure to 200 nM pyrene-loaded LNCs. On the other hand, when acetone is used to dissolve an equivalent concentration of PAHs in sea water, the copepod mortality is 10 times lower than using LNCs as nano-delivery system. This confirms the efficiency of using LNCs to deliver molecules directly in the gut or copepod carapace. The small size and non toxicity of these delivery nano-systems make them suitable for drug delivery to copepods., (Copyright © 2015 Elsevier B.V. All rights reserved.)

DNA methylation in promoter region can be a new chemopreventive marker against polycyclic aromatic hydrocarbons (PAHs). We performed a randomized, double blind and cross-over trial (N=12 healthy females) to evaluate chlorella (Chlorella vulgaris)-induced epigenetic modulation on exposure to PAHs. The subjects consumed 4 tablets of placebo or chlorella supplement (total chlorophyll ≈ 8.3mg/tablet) three times a day before meals for 2 weeks. When the subjects consumed chlorella, status of global hypermethylation (5-methylcytosine) was reduced, compared to placebo (p=0.04). However, DNA methylation at the DNMT1 or NQO1 was not modified by chlorella. We observed the reduced levels of urinary 1-hydroxypyrene (1-OHP), a typical metabolite of PAHs, by chlorella intake (p<0.1) and a positive association between chlorella-induced changes in global hypermethylation and urinary 1-OHP (p<0.01). Therefore, our study suggests chlorella works for PAH-detoxification through the epigenetic modulation, the interference of ADME of PAHs and the interaction of mechanisms., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Studying the effects of hydrophobic chemicals using in vitro cell based methods is hindered by the difficulty in bringing and keeping these chemicals in solution. Their effective concentrations are often lower than their nominal concentrations. Passive dosing is one approach that provides defined and stable dissolved concentrations during in vitro testing, and was applied to control and maintain freely dissolved concentrations of polycyclic aromatic hydrocarbons (PAHs) at levels up to their aqueous solubility limit. The immunomodulatory effects of 9 different PAHs at aqueous solubility on human bronchial epithelial cells were determined by analysing the cytokine promoter expression of 4 different inflammatory cytokines using stably transfected recombinant A549 cell lines. Diverse immunomodulatory responses were found with the highest induction observed for the most hydrophobic PAHs chrysene, benzo(a)antracene and benzo(a)pyrene. Cytokine promoter expression was then studied in dose response experiments with acenaphthene, phenanthrene and benzo(a)anthracene. The strongest induction was observed for benzo(a)anthracene. Cell viability analysis was performed and showed that none of the PAHs induced cytotoxicity at any of the concentrations tested. Overall, this study shows that (1) immunomodulatory effects of PAHs can be studied in vitro at controlled freely dissolved concentrations, (2) the most hydrophobic PAHs were the strongest inducers and (3) induction was often higher at lower exposure levels and decreased then with concentration despite the apparent absence of cytotoxicity., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: Coal tar ointments are used as treatment of various skin diseases, especially psoriasis and eczema. These ointments contain several carcinogenic polycyclic aromatic hydrocarbons. Metabolites of these polycyclic aromatic hydrocarbons are excreted in the urine and therefore, dermatological use of coal tar may be associated with an increased risk of bladder cancer. The objective of this study was to evaluate the association between dermatological use of coal tar ointments and bladder cancer., Material and Methods: A population-based case-control study was conducted including 1,387 cases diagnosed with bladder cancer and 5,182 population controls. Information on the use of coal tar, history of skin disease, and known risk factors for bladder cancer was obtained through postal questionnaires. Logistic regression analyses were performed to estimate the risk of bladder cancer after coal tar treatment, adjusted for age, gender, smoking status, duration of smoking, and intensity of smoking., Results: The use of coal tar ointments was approximately equal among cases and controls (3.8% vs. 3.0%, respectively). Dermatological application of coal tar was not significantly associated with bladder cancer (adjusted odds ratio = 1.37, 95% CI: 0.93-2.01). An inverse association between bladder cancer and a history of skin disease was observed (adjusted odds ratio = 0.74, 95% CI: 0.61-0.90)., Conclusion: This is the first study with a specific aim to study the association between the use of coal tar preparations and bladder cancer. The results suggest that there is no reason for safety concerns with respect to the risk of bladder cancer after the use of coal tar preparations in dermatological practice., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In a market basket study made at the National Food Agency in Sweden, in which the most common consumed foodstuffs are sampled, the content of polycyclic aromatic hydrocarbons (PAH), benzo(a)pyrene (B(a)P) and PAH4 (B(a)P, chrysene, benzo(b)fluoranthene, and benz(a)anthracene) were analysed. To this data, results on B(a)P and PAH4 levels originating from a home-barbecue-study on sausages and loin of pork were added. The calculated total mean intake of B(a)P and PAH4 was 50 ng/person and day 276 ng/person and day, respectively. Sugar and sweets, cereal products, meat, and dairy products contributed most to the total intake. In case of PAH concentrations below LOD, 0.03 µg/kg, ½ LOD was used in the intake calculations. The highest mean level of B(a)P and PAH4 were found in the barbecued products, but since the estimated consumption in Sweden is low, the contribution to the total food intake is almost negligible, about 2%. The calculated B(a)P levels in food has decreased during the last 10 years and indicates a low cancer risk for the Swedish population., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The concentrations and profiles of polycyclic aromatic hydrocarbons (PAHs) in commercially available infant formulae and follow-up formulae in Nigeria were determined with a view to providing information on the health risks to children from the consumption of these infant foods. The concentrations of PAHs were measured by means of gas chromatography-mass spectrometry (GC-MS) after extraction by ultrasonication with acetone/dichloromethane and clean-up. The concentrations of the Σ16 PAHs in these infant formulae ranged from 0.102 to 1.98 μg kg(-1), 0.054-1.98 μg kg(-1), 0.081-2.54 μg kg(-1) and 0.51-0.70 μg kg(-1) for infants of ages 0-6 months, 6-12 months, 1-3 years and 0-12 months respectively. The concentrations of benzo(a)pyrene (BaP) in all samples investigated were below the 1 μg kg(-1) European Commission permissible limit for BaP in foods meant for infants. The estimated daily intake of PAHs based on the European Food Safety Authority (EFSA) suggested indicators of occurrence and effects of PAHs in foods were not detected (nd) to 2.67 ng BaP kg(-1) bw day(-1), nd-5.29 ng PAH2 kg(-1) bw day(-1), nd-11.20 ngPAH4 kg(-1) bw day(-1) and nd-34.96 ng PAH8 kg(-1) bw day(-1). The estimated margin of exposure (MOE) values: BaP-MOE, PAH2-MOE, PAH4-MOE and PAH8-MOE values were greater than 10,000 which indicates that there are no health risks from the consumption of these products by infants. The concentrations and dietary exposure to PAHs from these products were similar to values reported in the literature for European Communities., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Petroleum (commonly called crude oil) is a complex substance primarily composed of hydrocarbon constituents. Based on the results of previous toxicological studies as well as occupational experience, the principal acute toxicological hazards are those associated with exposure by inhalation to volatile hydrocarbon constituents and hydrogen sulfide, and chronic hazards are associated with inhalation exposure to benzene and dermal exposure to polycyclic aromatic compounds. The current assessment was an attempt to characterize the potential for repeated dose and/or developmental effects of crude oils following dermal exposures and to generalize the conclusions across a broad range of crude oils from different sources. Statistical models were used to predict the potential for repeated dose and developmental toxicity from compositional information. The model predictions indicated that the empirical data from previously tested crude oils approximated a "worst case" situation, and that the data from previously tested crude oils could be used as a reasonable basis for characterizing the repeated dose and developmental toxicological hazards of crude oils in general.

A 7-day mixture toxicity experiment with the terrestrial springtail Folsomia candida was conducted, and the effects were linked to three different mixture exposure parameters. Passive dosing from silicone was applied to tightly control exposure levels and compositions of 12 mixture treatments, containing the polycyclic aromatic hydrocarbons (PAHs) naphthalene, phenanthrene, and pyrene. Springtail lethality was then linked to sum chemical activities (∑a), sum equilibrium lipid concentrations (∑C(lipid eq.)), and sum toxic units (∑TU). In each case, the effects of all 12 mixture treatments could be fitted to one sigmoidal exposure-response relationship. The effective lethal chemical activity (La50) of 0.027 was well within the expected range for baseline toxicity of 0.01-0.1. Linking the effects to the lipid-based exposure parameter yielded an effective lethal concentration (LC(lipid eq 50)) of 133 mmol kg(-1) lipid in good correspondence with the lethal membrane burden for baseline toxicity (40-160 mmol kg(-1) lipid). Finally, the effective lethal toxic unit (LTU50) of 1.20 was rather close to the expected value of 1. Altogether, passive dosing provided tightly controlled mixture exposure in terms of both level and composition, while ∑a, ∑C(lipid eq.), and ∑TU allowed baseline toxicity to be linked to mixture exposure.

In this study, laboratory experiments were carried out in order to come to a better understanding of the fate of polycyclic aromatic hydrocarbons (PAHs) in the marine environment and especially on their bioaccumulation, biotransformation and genotoxic effects in fish. Juveniles of turbot (Scophthalmus maximus) were exposed to PAHs through different routes via (1) a mixture of dissolved PAHs, (2) a PAH-polluted sediment and (3) an oil fuel elutriate. Fish were exposed 4 days followed by a 6-day depuration period. In each experiment, PAH concentrations in the seawater of the tanks were analysed regularly by gas chromatography coupled with mass spectrometry. Muscle and liver samples were also analysed for parent PAH levels and PAH bioconcentration factors were calculated. Biotransformation was evaluated by measuring the levels of PAH metabolites in fish bile. Genotoxicity was assessed by the alkaline comet assay. Regardless of exposure route, the parent PAH concentrations in the liver and muscle showed a peak level 1 day after the beginning of the exposure, followed by a decrease up to the background level towards the end of the experiment, except for the exposure to dissolved PAHs for which levels were relatively low throughout the study. As a consequence, no bioaccumulation was observed in fish tissues at the end of the experiment. In contrast, regardless of exposure routes, a rapid production of biliary metabolites was observed throughout the whole exposure experiment. This was especially true for 1-hydroxypyrene, the major metabolite of pyrene. After 6 days of recovery in clean water, a significant decrease in the total metabolite concentrations occurred in bile. Fish exposed through either route displayed a significant increase in DNA strand breaks after 4 days of exposure, and significant correlations were observed between the level of biliary PAH metabolites and the level of DNA lesions in fish erythrocytes. Overall results indicate that exposure to either a mixture of dissolved PAHs, a PAH-contaminated sediment or a dispersed oil fuel elutriate leads to biotransformation and increase in DNA damage in fish. The quantification of PAH metabolites in bile and DNA damage in erythrocytes appear to be suitable for environmental monitoring of marine pollution either in the case of accidental oil spills or sediment contamination.

Formation of mutagenic heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) is one pathway believed to drive the association of colon cancer with meat consumption. Limited data exist on the associations of individual HCAs and PAHs in red or white meat with colon cancer. Analyzing data from a validated meat preparation questionnaire completed by 1062 incident colon cancer cases and 1645 population controls from an ongoing case-control study, risks of colon cancer were estimated using unconditional logistic regression models, comparing the fourth to the first quartile of mutagen estimates derived from a CHARRED based food frequency questionnaire. Total dietary intake of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) [adjusted odds ratio (aOR) = 1.87, 95% confidence interval (CI) = 1.44-2.44, P(trend) < 0.0001], 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) (aOR = 1.68, 95% CI = 1.29-2.17, P(trend) = 0.001) and meat-derived mutagenic activity (aOR = 1.77, 95% CI = 1.36-2.30, P(trend) < 0.0001) were statistically significantly associated with colon cancer risk. Meat type specific analyses revealed statistically significant associations for red meat-derived MeIQx, DiMeIQx, and mutagenic activity but not for the same mutagens derived from white meat. Our study adds evidence supporting red meat-derived, but not white-meat derived HCAs and PAHs, as an important pathway for environmental colon cancer carcinogenesis.

This study is part of a broader initiative to characterize, quantify and assess the human health risk associated with exposure to polycyclic aromatic hydrocarbons (PAHs) in street dust along the Trans-ECOWAS highway in West Africa. In the first part, PAHs were characterized and quantified in low- and high-traffic zones. In this study, cancer and noncancer human health risks from exposure to (PAHs) in street dust in the Tamale metropolis, Ghana were assessed in accordance with the USEPA risk assessment guidelines. The results of the study as obtained from inhalation of benzo [a] anthracene (BaA), benzo [a] pyrene (BaP), benzo [k] fluoranthene (BkF) and chrysene via central tendency exposure parameters (CTE) by trespassers (street hawkers including children and adults) in street dust within low traffic zones in the Tamale metropolis are 1.6E-02, 4.7E-02, 1.8E-03, and 1.6E-04 respectively. For reasonable maximum exposure parameters (RME), risk values of 1.2E-01, 3.5E-01, 1.3E-02 and 1.2E-03 respectively were obtained for benzo [a] anthracene, benzo [a] pyrene, benzo [k] fluoranthene and chrysene. Hazard index for acenaphthene, anthracene, fluoranthene, fluorine, naphthalene and pyrene in the CTE and RME scenarios were 2.2, 3.E-01, 2.6, 2.6, 100, 38 and 12, 1.7,15, 14, 550, 210 respectively. Generally, the cancer health risk associated with inhalation of benzo [a] anthracene, benzo [a] pyrene, benzo [k] fluoranthene and chrysene revealed that resident adults and children in the Tamale metropolis are at risk from exposure to these chemicals. The results of this preliminary assessment that quantified PAH related health risks along this part of the Trans-ECOWAS highway revealed that, there is the need for regulatory agencies to put in comprehensive measures to mitigate the risks posed to these categories of human receptors.

Context: Electronic cigarettes (e-cigarettes) have earned considerable attention recently as an alternative to smoking tobacco, but uncertainties about their impact on health and indoor air quality have resulted in proposals for bans on indoor e-cigarette use., Objective: To assess potential health impacts relating to the use of e-cigarettes, a series of studies were conducted using e-cigarettes and standard tobacco cigarettes., Methods and Materials: Four different high nicotine e-liquids were vaporized in two sets of experiments by generic 2-piece e-cigarettes to collect emissions and assess indoor air concentrations of common tobacco smoke by products. Tobacco cigarette smoke tests were conducted for comparison., Results: Comparisons of pollutant concentrations were made between e-cigarette vapor and tobacco smoke samples. Pollutants included VOCs, carbonyls, PAHs, nicotine, TSNAs, and glycols. From these results, risk analyses were conducted based on dilution into a 40 m³ room and standard toxicological data. Non-cancer risk analysis revealed "No Significant Risk" of harm to human health for vapor samples from e-liquids (A-D). In contrast, for tobacco smoke most findings markedly exceeded risk limits indicating a condition of "Significant Risk" of harm to human health. With regard to cancer risk analysis, no vapor sample from e-liquids A-D exceeded the risk limit for either children or adults. The tobacco smoke sample approached the risk limits for adult exposure., Conclusions: For all byproducts measured, electronic cigarettes produce very small exposures relative to tobacco cigarettes. The study indicates no apparent risk to human health from e-cigarette emissions based on the compounds analyzed.

Polycyclic Aromatic Hydrocarbons (PAHs) constitute a family of over one hundred compounds and can generally be found in complex mixtures. PAHs metabolites cause DNA damage which can lead to the development of carcinogenesis. Toxicity assessment of PAH complex mixtures is currently expressed in terms of toxic equivalents, based on Toxicity Equivalent Factors (TEFs). However, the definition of new TEFs for a large number of PAH could overcome some limitations of the current method and improve cancer risk assessment. The current investigation aimed at deriving the relative potency factors of PAHs, based on their genotoxic effect measured in vitro and analyzed with mathematical models. For this purpose, we used a new genotoxic assay (γH2AX) with two human cell lines (HepG2 and LS-174T) to analyze the genotoxic properties of 13 selected PAHs at low doses after 24h treatment. The dose-response for genotoxic effects was modeled with a Hill model; equivalency between PAHs at low dose was assessed by applying constraints to the model parameters. In the two cell lines tested, we observed a clear dose-response for genotoxic effects for 11 tested compounds. LS-174T was on average ten times more sensitive than HepG2 towards PAHs regarding genotoxicity. We developed new TEFs, which we named Genotoxic Equivalent Factor (GEF). Calculated GEF for the tested PAHs were generally higher than the TEF usually used. Our study proposed a new in vitro based method for the establishment of relevant TEFs for PAHs to improve cancer risk assessment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAH) are toxic compounds that have been classified by the International Agency for Research on Cancer as probable or possible human carcinogens. Human exposure to PAH is usually assessed by considering data from a single air monitoring station as being representative of a large region; however, air pollution levels change on small spatial scales and thus also affect environmental exposure. The use of environmental biomonitors is a useful tool to assess the levels of PAH with high spatial resolution. The aims of this study were to (1) assess human exposure to PAH in a petrochemical region in Portugal, integrating data from environmental biomonitors (lichens), air, and soil in a regional area, and (2) determine the health risks associated with exposure to PAH with high spatial resolution. Bearing this in mind, benzo[a]pyrene (BaP) equivalent concentrations in samples of soil, air, and lichens collected in the study region were used to assess human exposure through different pathways, including inhalation of air and soil particles, ingestion of soil, and dermal contact with soil. Human health risk was calculated through the Incremental Lifetime Cancer Risk (ILCR). BaP equivalent concentrations found in the region ranged from 6.9 to 46.05 ng BaPeq/g in lichens, from 16.45 to 162.02 ng BaPeq/g in soils, and from 0.02 to 0.16 ng BaPeq/m³ in air, indicative of high variability in this regional area. Human exposure to PAH varied between 976 and 42,877 ng BaPeq/d. When considering all exposure pathways, ILCR values were between 10⁻⁴ and 10⁻³. Considering only inhalation, ILCR values were between 10⁻⁶ and 10⁻⁵. The main risk seemed to arise from soil (either ingestion or inhalation of resuspended soil particles). The high spatial resolution of our environmental data allowed for detection of critical exposure levels at unexpected sites. Our results identified important areas where health studies on local populations need to be focused, and where environmental levels of PAH need to be monitored over time in order to protect human health.

A total of 175 samples of 18 types of food were collected from markets in Shanghai, China, and the concentrations and bioaccessibility of 15 priority-controlled polycyclic aromatic hydrocarbons (PAHs) in these samples were determined. The mean concentrations of PAHs varied between 2.4 and 47.1 ng g(-1) wet weight, with the highest being observed in snail and lowest in chicken. The concentrations were lower than the maximum levels of PAH allowed for food per EU regulations. Among the PAHs measured, phenanthrene was the predominant one. Most of the PAHs originated from pyrogenic sources, analysed using molecular indices. The mean bioaccessibility of PAHs varied from 29.0% to 61.2% as measured by simulating the human gastrointestinal digestion process. Linear relationships between the bioaccessibility and lipid contents were observed for most PAH congeners. The daily intake of PAHs by an average Shanghai resident was 848 ng day(-1) and decreased to 297 ng day(-1) when the bioaccessibility of PAHs were considered, demonstrating that most intake might have been overestimated. According to the potency equivalent concentrations and screening values of PAHs, consumption of snail and clam, especially snail, should be limited.

Eurasian perch (Perca fluviatilis) was exposed trophically to phenanthrene, pyrene and benzo[a]pyrene. Accumulation kinetics in the muscle tissue of parent PAHs and hydroxylated metabolites were established for 56 days at 3 levels of exposure (0, 100 and 500 μg/kg BW). Benzo[a]pyrene and 3-hydroxy-benzo[a]pyrene were not detected in the muscles. During exposure, there was an increase in phenanthrene, pyrene and their hydroxylated metabolites in the muscle tissue. Low transfer to muscle tissue was observed at equilibrium for phenanthrene (4.4±0.6% and 2.7±0.8%) and pyrene (1.0±0.2% and 0.33±0.09%), depending on the concentrations in the spiked feed., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Juvenile rainbow trout were fed a diet containing an environmentally relevant mixture of 10 high molecular weight polycyclic aromatic hydrocarbons (PAHs) at a dose of 0.66 or 7.82 µg PAH · g fish(-1) · d(-1). At 3, 7, 14, and 28 d, biomarkers of aryl hydrocarbon receptor activation (AHR), hepatic microsomal ethoxyresorufin-O-deethylase (EROD) activity, and cytochrome P4501A (CYP1A)-associated staining increased 14- to 26-fold and 6- to 14-fold, respectively, in fish fed 7.82 µg PAH · g fish (-1) · d(-1). Cytochrome P4501A-associated staining increased 2- to 9-fold on days 3, 7, and 28 in fish fed 0.66 µg PAH · g fish(-1) · d(-1). Bile fluorescent aromatic compounds served as a biomarker of exposure and confirmed that PAH exposure was consistent over 50 d. DNA damage in blood cells, protein oxidation, and lipid peroxidation in the kidney were biomarkers of oxidative stress and all increased in fish fed 7.82 µg PAH · g fish(-1) · d(-1). Fish fed 0.66 µg PAH · g fish(-1) · d(-1) had elevated DNA damage in blood cells but increased protein oxidation or lipid peroxidation in the kidney were not observed. Challenge with Aeromonas salmonicida, at lethal concentration (LC) 20, decreased survival in fish previously fed either 0.66 µg PAH · g fish(-1) · d(-1) or 7.82 µg PAH · g fish(-1) · d(-1) relative to fish fed the control diet. In general, biomarkers of both AHR activation and oxidative stress peaked at 3 to 14 d then declined at 28 to 50 d of PAH exposure and an increase in susceptibility to disease was observed at 50 d. These results link PAH exposure to biomarker responses that may be useful as early indicators of population level responses, such as mortality resulting from an increase in disease susceptibility., (Copyright © 2011 SETAC.)

Exposure to polycyclic aromatic hydrocarbons (PAHs) always involves complex mixtures that may induce synergistic or antagonistic effects on the genotoxic properties and make risk assessment more difficult. In this study, we evaluated how particulate PAHs modulated the formation of DNA damage induced by carcinogenic benzo[a]pyrene (B[a]P). Single strand breaks and alkali labile sites, as well as BPDE-N²-dGuo DNA adducts were measured in the competent HepG2 cells by Comet assay and HPLC-tandem mass spectrometry, respectively. B[a]P, alone or in binary mixture with other PAHs (1 μM each), led to low amounts of strand breaks. In contrast, formation of BPDE-N²-dGuo adducts was significant and found to be enhanced in HepG2 co-treated for 14 h by B[a]P in the presence of either benzo[b]fluoranthene (B[b]F), dibenz[a,h]anthracene (DB[a,h]A) or indeno[1,2,3-cd]pyrene (IP). Opposite results were obtained with benzo[k]fluoranthene (B[k]F). The same observations were made when cells were pre-incubated with PAH before incubation with B[a]P. These results show that the interactions between PAHs are not direct competition reactions. Emphasis was then placed on the modulation of B[a]P-induced DNA damage by B[b]F and B[k]F. No difference in the time-course formation of DNA damage was observed. However, dose-response relationship differed between these two PAHs with a concentration-dependent inhibition of BPDE-N²-dGuo DNA by B[k]F whereas a constant level of potentiation for B[b]F was observed for concentrations higher than 1 μM. Altogether, these results show that the genotoxicity of B[a]P in binary mixtures with other carcinogenic PAH may be modulated. In such cases, a potentiation of BPDE-N²-dGuo adduct formation is most often observed with exception of B[k]F. Several biological mechanisms may account for these observations, including binding of PAHs to the Ah receptor (AhR), their affinity toward CYP450 and competition for metabolism. These different interactions have to be considered when addressing the intricate issue of the toxicity of mixtures., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: To estimate the dietary intake of total polycyclic aromatic hydrocarbons (PAH) and benzo(a)pyrene (BaP), and to characterise factors associated with higher intake during pregnancy. Recent studies suggest that prenatal exposure to PAH is associated with adverse reproductive outcomes. Other than tobacco smoke and occupational exposures, diet is the main source of human PAH exposure., Design: Prospective birth cohort study. Dietary exposure to total PAH and BaP was calculated combining food consumption data and estimated PAH concentrations in foods. One-way ANOVA was used to assess differences in intake among non-smokers, passive or active smokers. Linear regression was used to assess factors related to higher intake, and associations between dietary PAH and birth weight., Setting: Sabadell, Spain, 2004-2006., Subjects: Women (n 657) recruited during the first trimester of pregnancy., Results: The mean dietary intake of BaP and total PAH was significantly higher among active (0·199 and 10·207 μg/d, respectively) and passive smokers (0·196 and 9·458 μg/d) than among non-smokers (0·181 and 8·757 μg/d; P value < 0·005). Maternal age, educational level and region of origin were also associated with higher BaP intake. In all women, major contributors to PAH intake were processed/cured meats, cereals/potatoes and shellfish. Elevated first trimester dietary BaP was associated with a significant reduction in birth weight (fourth v. first quartile: β = -142·73 g, P value < 0·05)., Conclusions: Active and passive smokers had higher dietary PAH exposure during pregnancy because of higher intake of processed meats and shellfish. As tobacco smoke is an additional route of PAH exposure, the added dietary burden in these women is of concern.

The authors have previously demonstrated that wildfire-derived coarse or fine particulate matter (PM) intratracheally instilled into lungs of mice induce a strong inflammatory response. In the current study, the authors demonstrate that wildfire PM simultaneously cause major increases in oxidative stress in the mouse lungs as measured by decreased antioxidant content of the lung lavage supernatant fluid 6 and 24 h after PM administration. Concentrations of neutrophil chemokines/cytokines and of tumor necrosis factor (TNF)-alpha were elevated in the lung lavage fluid obtained 6 and 24 h after PM instillation, consistent with the strong neutrophilic inflammatory response observed in the lungs 24 h after PM administration, suggesting a relationship between the proinflammatory activity of the PM and the measured level of antioxidant capacity in the lung lavage fluid. Chemical analysis shows relatively low levels of polycyclic aromatic hydrocarbons compared to published results from typical urban PM. Coarse PM fraction is more active (proinflammatory activity and oxidative stress) on an equal-dose basis than the fine PM despite its lower content of polycyclic aromatic hydrocarbons. There does not seem to be any correlation between the content of any specific polycyclic aromatic hydrocarbon (or of total polycyclic aromatic hydrocarbon content) in the PM fraction and its toxicity. However, the concentrations of the oxidation products of phenanthrene and anthracene, phenanthraquinone and anthraquinone, were several-fold higher in the coarse PM than the fine fraction, suggesting a significant role for atmospheric photochemistry in the formation of secondary pollutants in the wildfire PM and the possibility that such secondary pollutants could be significant sources of toxicity in the wildfire PM.

An increasing literature associates high intake of meat, especially red meat and processed meat with an increased risk of cancers, especially colorectal cancer. There is evidence that this risk may not be a function of meat per se, but may reflect high-fat intake, and/or carcinogens generated through various cooking and processing methods. The cancer risk may be modulated by certain genotypes. Cancers associated with high meat consumption may be reduced by the addition of anticarcinogens in the diet, especially at the same time as meat preparation or meat consumption, or modification of food preparation methods. Meat contains potential anticarcinogens, including omega-3 polyunsaturated fatty acids, and conjugated linoleic acid (CLA). Red meat, in particular, is an important source of micronutrients with anticancer properties, including selenium, vitamin B6 and B12, and vitamin D. Adjusting the balance between meat and other dietary components may be critical to protecting against potential cancer risks.

Concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) were measured in 26 types of seafood commonly consumed by the general Korean population. The concentrations of total and carcinogenic PAHs ranged from 12.3 to 243 ng/g dry weight and from 0.21 to 18.4 ng/g dry weight, respectively, similar to those reported in other countries. The lower-molecular-weight aromatics, such as naphthalene, phenanthrene, and fluorine, predominated in the seafood samples. Estimated intakes of PAHs by seafood consumption for the general population, for men, and for women were 15.3, 16.7, and 13.8 ng/kg body weight/d, respectively. Squid, mackerel, and yellow croaker contributed to the highest intakes of PAHs. Among the 8 age groups investigated, children age <2 years and 3 to 6 years had high intakes of PAHs compared with adult groups. Dioxin toxic equivalents (TEQs) of PAHs were calculated using a TEQ proposed in the literature, and the intake was estimated to be 0.91 pg TEQ/kg body weight/d, which indicates that PAHs contributed the most (43%) to total TEQ intake. The estimated excess cancer risk values from seafood consumption for the general population (2.85 x 10(-6)), for men (2.93 x 10(-6)), and for women (2.68 x 10(-6)) slightly exceeded the guideline value (1.0 x 10(-6)) for potential cancer risk.

Binding of polycyclic aromatic hydrocarbons (PAHs) with DNA is one of the key steps in their mutagenic process. In this work, a previously established electrochemical displacement method was utilized to measure the binding constants (K(b)) of 26 hydroxylated PAHs (OH-PAHs) with DNA. Eighteen OH-PAHs induced more than 50% signal reduction in the displacement measurement with calf thymus DNA, and K(b) calculated from the EC(50) value is between 8.3 x 10(4) and 3.0 x 10(5)M(-1). Other eight OH-PAHs induced less than 50% signal reduction. For the latter compounds, EC(50) values were obtained by fitting the displacement curve with a bi-exponential decay function and extrapolating it to 50% signal. K(b) was then calculated, and was found to be in the range of 4.5 x 10(4) and 7.6 x 10(4)M(-1). Measurements with polydG.polydC (pdGC) and polydA.polydT (pdAT) demonstrate that the OH-PAHs have no obvious selectivity toward DNA base pairs. In atomic force microscopy, a clear morphological change of calf thymus DNA from linear type to condensation form was observed after binding with 9-hydroxyfluorene. The change is similar to the one observed with the DNA-intercalating electrochemical indicator, suggesting that 9-hydroxyfluorene binds with DNA also by intercalation. An examination of the relationship between the molecular structure characteristics of the 26 OH-PAHs and their DNA-binding affinity revealed that the most positive net atomic charge on a hydrogen atom (q(+)(H)) correlated significantly with K(b) at 0.05 level, with sig. (2-tailed) of 0.015. The correlation suggests that hydrogen bonding may play an important role in DNA/OH-PAH binding interaction. It was further revealed that Connolly accessible area (CAA), Connolly molecular area (CMA), and Connolly solvent-excluded volume (CSEV) of the nine hydroxybenzo[a]pyrenes correlated significantly with K(b) at 0.01 or 0.05 level, with sig. (2-tailed) 0.019, 0.012 and 0.009, implying that steric effect might be an important factor in the binding of differently substituted OH-PAH with DNA.

Primary Objective: To develop of a quantitative food frequency questionnaire (QFFQ) to assess intake of specific foods, nutrients and heterocyclic aromatic amines (HAAs) in a case-control study of colorectal adenoma., Methods and Procedures: A cross-sectional survey conducted in a hospital in Sao Paulo, Brazil. A trained dietitian collected 24-h recalls from 60 Japanese Brazilian outpatients (29 men and 31 women; mean age 58 years and 57 years, respectively)., Main Outcomes and Results: Fruit, vegetable and legume intake was high, with mean daily servings consumed in men and women of 8.2 and 6.9, respectively. The QFFQ contains 161 food items presented in 15 food groupings, with particular emphasis paid to the HAA content of meat, fish and chicken items., Conclusions: We have developed a QFFQ appropriate for Japanese Brazilians that will allow us to estimate HAA intake and will be used to examine our hypotheses related to foods, nutrients and HAAs, and diet-gene interactions in colorectal neoplasia in this population.

Polycyclic aromatic hydrocarbons (PAHs) enter the aquatic environment by various routes and are usually found as mixtures in the water. Many studies have shown that solar ultraviolet (UV) radiation can greatly enhance the toxicity of some PAHs to a variety of marine species. In the present study, we tested the phototoxicity of four PAHs with simple structures, both alone and in binary combinations, to a species of marine diatom, Phaeodactylum tricornutum, in the laboratory. The results indicated that simulated solar UV radiation not only enhanced the toxicity of the different PAHs to this alga, but also changed their relative toxic strengths. The photo-induced toxicity of PAHs to this alga might be a synergistic effect of photo-modification and photosensitization reactions, causing the microalgal cells to suffer oxidative stress. Four binary mixtures of these PAHs were found to have a synergistic joint action mode, while two binary mixtures displayed an antagonistic reaction, revealing a complex pattern of possible interactions of PAHs with marine diatoms.

The toxicity of sublethal polycyclic aromatic hydrocarbons (PAHs) levels in soils was assessed by testing their impact on expression of annetocin, a reproduction regulating gene, and translationally controlled tumor protein (TCTP), a tumorigenic response gene, in the earthworm Eisenia fetida cultured in artificial soil spiked with, phenanthrene (Phe), pyrene (Pyr), fluoranthene (Flu), or benzo(a)pyrene (Bap). Annetocin and TCTP were both up-regulated by 0.1 and 1.0 mg kg(-1) benzo(a)pyrene and TCTP was down-regulated by 10.0 mg kg(-1) phenanthrene. Weight loss and cocoon production of the worms were also analyzed. Only 10.0 mg kg(-1) phenanthrene impacted earthworm weight loss significantly and no significant differences on cocoon production were observed. Our study indicated that the potential ecotoxicity of sublethal PAHs in soil should not be neglected and mRNA transcription level in earthworms was a more sensitive indicator of PAHs exposure than traditional indexes using cocoon production as endpoints and/or using the whole-organism as the test materials.

The partitioning of organic soil pollutants into soil organisms is driven by their chemical activity, which normally does not exceed that of the pure pollutant. Passive dosing with the silicone poly(dimethylsiloxane) (PDMS) was used to initiate and maintain the maximum chemical activity of 10 polycyclic aromatic hydrocarbons (PAHs) in toxicity tests with the springtail Folsomia candida. The test animals could move freely on the PDMS saturated with PAHs, resulting in direct contact and exposure to saturated air. After 7 days, springtail lethality correlated neither with the octanol-water partition coefficients of the PAHs nor with their molecular size, but with their melting point All low-melting PAHs (T(M) < or = 110 degrees C) caused 100% lethality, whereas all high-melting PAHs (TM > or = 180 degrees C) caused no significant lethality. The lethality was successfully fitted to one chemical activity response curve for all PAHs tested, with effective chemical activity causing 50% lethality (Ea-50) of 0.058. It was also fitted to the PAH concentration in the PDMS, resulting in an EC(PDMS)-50 of 8.7 mM. Finally, the combined exposure to anthracene and pyrene was described by the sum of chemical activities causing lethality, in good agreement with the chemical activity-response curve obtained.

The in vitro effects of polycyclic aromatic hydrocarbons (PAHs) on haemocyte and haemolymphatic parameters of the Pacific oyster, Crassostrea gigas, were tested using field concentrations (10(-7) and 10(-9) mg mL(-1)) observed in the Marennes-Oleron Basin (Charente-Maritime, France) and high concentrations (10(-3) and 10(-5) mg mL(-1)) observed during oil spills. As a first step, the effects of pollutants, after a 24 h contamination period, were monitored on individual and pooled haemolymph samples and similar results were observed for both sample types. In a second step, haemolymphs from 45 oysters were withdrawn and pooled. Eighteen pollutants were tested in vitro after a 4 and 24h contamination period and 10 of them showed significant modulations of the five haemocyte parameters tested. Seven pollutants (fluorene, pyrene, anthracene, phenanthrene, chrysene, indeno[1,2,3-c,d]pyrene and heavy fuel oil (HFO)) induced a decrease in haemocyte mortality. Fluorene, pyrene and HFO significantly decreased phagocytosis activity. Percentage of non-specific esterase positive cells, phenoloxidase activity and lysosome presence were increased by naphthalene, benzo[b]fluoranthene and dibenz[a,h]anthracene, respectively. Modulation of immune parameters in the Pacific oyster by PAHs suggested that PAH pollution may be related to enhanced susceptibility to diseases.

Objectives: This study was conducted to assess external and internal exposure of workers to polycyclic aromatic hydrocarbons (PAHs). In this context, the analytical and diagnostical reliability of 3-hydroxybenzo[a]pyrene (3OH-BaP) as a biomarker of internal exposure to PAHs was established., Methods: Ambient and biological monitoring was carried out of 225 PAH-exposed employees of different industries. External exposure was determined by personal air sampling and analysis of 16 EPA-PAH. Internal exposure was examined by the urinary metabolites 3OH-BaP, 1-hydroxypyrene (OH-Pyr) and monohydroxylated phenanthrenes (OH-Phens)., Results: Benzo[a]pyrene (BaP) was detected at all workplaces. Concentrations in the breathing zone of the workers ranged from below the limit of detection up to 44.3 mug/m(3). In biological monitoring, urinary 3OH-BaP was found in median concentrations of 0.8 ng/g creatinine (crea) and the 95th percentile of 6.7 ng/g crea. The results ranged from the limit of detection up to 19.5 ng/g crea. Only 1% of the analysed samples showed concentrations below the limit of detection (0.05 ng/l). Regarding median concentrations, workers in coking plants showed lower 3OH-BaP concentrations (0.5 ng/g crea) than those employed in the production of fireproof material in refractories (1.1 ng/g crea), converter infeed (1.2 ng/g crea) and graphite electrode production (1.3 ng/g crea). Strong correlations of 3OH-BaP with OH-Pyr and the sum of OH-Phens were found for the workplaces converter infeed, coking plants and graphite electrode production (r(Pearson) ranging from 0.618 to 0.867, p<0.001). The poor correlation of BaP in the air and 3OH-BaP in urine is most probably caused by routes of uptake other than via air-for example, dermal uptake., Conclusion: 3OH-BaP as a metabolite of the carcinogenic BaP could be shown to be a diagnostically specific and sensitive biomarker for determining the internal exposure of workers in different industries. Using this method, the estimation of health risks for workers can be fundamentally improved, because the 3OH-BaP represents the group of carcinogenic PAHs. The procedure for analysing 3OH-BaP is complex, but it is robust and produces reliable results.

The yellowtail trumpeter (Amniataba caudavittata) is an estuarine-dependent omnivorous fish found in the Swan-Canning Estuary, Western Australia. Thirty five fish were injected with either the polycyclic aromatic hydrocarbon, benzo[a]pyrene (B[a]P), the synthetic flavenoid beta-naphthoflavone (BNF), or used as controls. The fish were then sampled at 3 and 7 days postinjection. Induction of the enzyme ethoxyresorufin O-deethylase (EROD) activity was nonsignificant while ethoxycoumarin O-deethylase (ECOD) activity induction differed amongst treatments. A high interindividual variability in the EROD activity was observed. The measurement of sorbitol dehydrogenase in the serum (s-SDH) was elevated (BNF 2.2 times and B[a]P 3.2 times the control fish) demonstrating that liver cell damage had occurred. Increases in biliary metabolites of both B[a]P-type and pyrene-type (19 times and 3.4 times the controls respectively) indicated that detoxification of pyrene-type compounds had taken place. Fish of the Terapontidae family, such as the yellowtail trumpeter, were found to be suitable for biomonitoring the health of the Swan-Canning Estuary. A combination of ECOD activity, s-SDH, and the measurement of biliary metabolites represents a suitable suite of biomarkers for environmental monitoring of the sublethal effects of PAH pollution in these fish.

Objective: To examine which exposure pathway, dietary or inhalation, contribute more to the exposure to, and/or internal dose of, polycyclic aromatic hydrocarbons (PAHs) of non-smoking Japanese., Methods: Duplicated diet, personal air samples and 24-h urine were collected from 14 non-smoking male university students without occupational exposure and the concentrations of PAHs in diet and air and that of 1-hydroxypyrene (1-OHP) in urine were measured with HPLC-fluorescence detector., Results: Daily dietary exposure contributed more than 90% of the total (diet + inhalation) daily exposure level for pyrene (diet/inhalation: 757/1.2 ng/day), benzo[k]fluoranthene (25/1.7 ng/day) and benzo[a]pyrene (91/2.1 ng/day). Urinary excretion of 1-OHP (median: 37 ng/day) was statistically significantly correlated only with dietary PAHs exposure level but not with inhalation., Conclusion: Countermeasures to lower PAHs levels in atmosphere has been successful in Japan and more attention should be directed to dietary exposure to PAHs for reducing cancer risk in general population.

Background: Polynuclear aromatic hydrocarbons (PAH), benzo[alpha]pyrene (B[alpha]P) and 7,12-dimethylbenz[alpha]anthracene (DMBA) are toxic environmental agents distributed widely. The relative deleterious effects of these agents on growth and blood vasculature of fetus and placental tissues of the rat were studied., Methods: Pregnant rats (Day 1 sperm positive) with implantation sites confirmed by laparotomy were treated intraperitoneally (i.p.) on Pregnancy Days 10, 12, and 14 with these agents dissolved in corn oil at cumulated total doses 50, 100, and 200 mg/kg/rat, and control with corn oil only (3-20 dams/group). Fetal growth, tissue hemorrhage, and placental pathology were evaluated by different parameters on Pregnancy Day (PD) 20 in treated and control rats., Results: DMBA was relatively more deleterious compared to B[alpha]P indicated by increased lethality and progressive reduction of body weight of the mother with increasing doses. At 200 mg/kg/rat doses of these agents, maternal survival was 45% and 100% and body weight reduced 24% and 52% of controls, respectively. The fetal survival rates in live mothers were similar to that of controls. They induced marked fetal growth retardation and necrosis of placental tissues. B[alpha]P and DMBA produced significant toxicity to differentiating fetal blood vascular system as exhibited by rupture of blood vessels and hemorrhage, especially in the skin, cranial, and brain tissues., Conclusions: Maternal PAH exposure induced placental toxicity and associated adverse fetal development and hemorrhage in different parts of the fetal body, in particular, marked intradermal and cranial hemorrhage, showing that developing fetal blood vasculature is a target of PAH toxicity.

Large quantities of petroleum products are released into the marine environment as result of tanker wrecks. Such catastrophic events have a dramatic impact on marine ecosystems, affecting a broad range of species. Seabirds are placed at the uppermost trophic level of the marine food chain. Therefore, important toxic effects are expected in these organisms. The recent Prestige oil spill gave the opportunity to test this. A previous study reported that yellow-legged gulls (Larus michahellis) breeding in the oiled area (17 months after the spill) showed differences both in plasma biochemistry and in the total circulating levels of polycyclic aromatic hydrocarbons (TPAHs) in blood regard to gulls sampled in clean areas. In the present study, wild yellow-legged gulls were fed with heavy fuel oil from the Prestige oil spill (P-gulls) and compared with control gulls (C-gulls) fed only with the vehicle (vegetable oil). Consistent with the cited previous findings, gulls fed with fuel oil showed reduced glucose and inorganic phosphorus levels in plasma, as well as a trend to significantly reduced creatinine values. In addition, glucose concentration was negatively related to TPAH levels. Males but not females fed with fuel oil showed higher plasma activity of asparatate aminotransferase (AST) than controls. With regard to plasma activity of gamma-glutamyl transferase (GGT), the results were opposite to the previous study. The GGT activity increased in C-females, apparently to meet with increased liver metabolism due to egg laying demands, but not in P-females. Differences to the previous study possibly reflect different adaptive responses of these enzymes to an acute short-term exposure to heavy fuel oil. Since the yellow-legged gull belongs to a complex of species widely distributed throughout the Northern hemisphere, the results as a whole might provide a tool for future evaluations of short- and long-term effects of oil spills on seabirds. Decreased glucose and inorganic phosphorus levels in plasma are expected in both short- and long-lasting exposures to fuel oil, whereas responses of AST and GGT enzymes would depend on both the sex of individuals and the temporal pattern of exposure.

In order to identify molecular targets of environmental polycyclic aromatic hydrocarbons (PAHs), we have analysed regulation of integrin (ITG) expression in PAH-exposed human macrophages. Among ITG subunits, beta7 ITG was found to be markedly up-regulated at both mRNA and protein levels in response to the prototypical PAH benzo(a)pyrene (BP). Knock-down of the transcription factor c-maf, known to control beta7 ITG expression, markedly impaired BP-mediated beta7 ITG induction. Moreover, chromatin immunoprecipitation and electrophoretic mobility shift assays showed BP-triggered binding of c-maf to a specific maf-responsive element found in beta7 ITG promoter. Such a binding, and also beta7 ITG induction, were however abolished in response to chemical inhibition of the aryl hydrocarbon receptor (AhR), to which PAHs bind. Taken together, these data establish beta7 ITG as a new molecular target of PAHs, whose up-regulation by these environmental contaminants most likely requires activation of co-operative pathways involving both AhR and c-maf.

Background: Monitoring biological responses that are mediated via the aryl-hydrocarbon receptor (AhR) in animals exposed to environmental contaminants can indicate both the presence of chemicals that act through this biochemical pathway and whether these chemicals are bioavailable., Objectives: The use of an ex-situ method that incorporated biological responsiveness monitoring in mice for determining the presence of 'biologically active' hydrocarbons in contaminated soils was investigated., Methods: The use of C57BL/6 as a test organism was validated by determining hepatic and immune responsiveness to two polyaromatic hydrocarbons (PAHs): 3,4 benz[a]pyrene (B[a]P) and 1,2 benz (a)anthracene (BA) administered via intraperitoneal (i.p.) injection. The responsiveness of mice exposed to soils spiked with hydrocarbons or ex situ exposures to soil removed from two contaminated sites was also investigated., Results and Discussion: Mice that were exposed to B[a]P via i.p. injections showed a 14-fold increase in liver microsomal ethoxyresorufin O-deethylase (EROD) activity compared to the control group. In contrast EROD activity following BA exposure at the same level was not significantly enhanced. Mouse immune response was significantly inhibited in a dose-dependent manner by i.p. injections of B[a]P. No significant inhibition occurred with the same doses of BA. Following i.p. exposure, the retention of B[a]P in mouse carcasses was greater than BA. Mice exposed to clean soils spiked with environmentally relevant concentrations of B[a]P and BA failed to show any significantly different hepatic or immune responses. Carcass residue data indicated a limited uptake of PAH from the soil. In contrast, EROD activity in mice exposed (ex situ) to hydrocarbon-contaminated soils removed from a fuel-loading depot and decommissioned gas works was significantly enhanced (4- and 2-fold respectively). However, this increase in EROD activity did not appear to correlate with either soil or carcass PAH concentrations., Conclusions and Outlook: These results support the assumption that B[a]P has a higher affinity for the aryl hydrocarbon receptor (AhR) compared to BA. Soil parameters such as organic carbon content, structure and particle size distribution can modulate the bioavailability of contaminants to biological receptors. These factors are implicated in the lack of responsiveness demonstrated in the spiked soil experiments. However the responsiveness of EROD activity in mice exposed (ex situ) to soil contaminated with complex mixtures of hydrocarbon compounds confirms the potential usefulness of this model to determine the presence of 'biologically active' compounds in aged soils removed from contaminated sites.

The concentrations of benzo[a]pyrene and 11 other polycyclic aromatic hydrocarbons (PAHs) were analysed from 322 commercial, cured meat products and 14 home-grilled meat samples as part of the Estonian food safety monitoring programme during 2001-2005. The maximum acceptable concentration of 5 microg kg(-1) for benzo[a]pyrene was exceeded in 3.4% of samples. The highest PAH concentrations were detected in home-grilled pork samples. Using of disposable grilling unit resulted in 1.6 times higher PAH concentrations compared to the traditional wood-burning grill. The average intake of benzo[a]pyrene and sum of 12 PAHs from meat products was estimated for children (age 1-16 years) on the basis of an individual food consumption questionnaire and, for the general population, based on national food consumption data. The highest total PAH concentrations detected were 16 microg kg(-1) in smoked meat and ham, 19 microg kg(-1) in smoked sausage and 6.5 microg kg(-1) in smoked chicken samples. Since smoking and grilling are prevalent meat-cooking methods in Estonia, the impact of meat products is assessed to be significant in overall PAH intake.