Non-carcinogenic Polycyclic Aromatic Hydrocarbons Research Articles

Assessment of polycyclic aromatic hydrocarbon (PAH) profiles in heat-processed meat and fish: a study on health risk evaluation

The profiles of polycyclic aromatic hydrocarbons (PAHs) in selected heat-processed meat and fish were evaluated to determine the potential health risk associated with consumption. The samples were analysed using a gas Chromatography-Mass spectrometer. Different concentrations of individual PAHs were detected in the samples, with the smoked samples having the highest concentrations. The total PAHs (mg/kg) in smoked samples were 2.763 ± 0.185 (game meat), 1.618 ± 0.102 (mackerel fish), and 1.718 ± 0.129 (catfish), whereas levels (mg/kg) in grilled samples were 0.771 ± 0.049 (chicken) and 0.911 ± 0.053 (fish). The total carcinogenic PAH (PAH7) concentrations (mg/kg) in grilled chicken and fish and smoked (game meat, mackerel fish, and catfish) samples were 0.231, 0.294, 0.440, 0.309, and 0.332, while their total PAH8 concentrations were 0.356, 0.371, 0.537, 0.465, and 0.476 respectively. The non-carcinogenic PAH risk estimations, both individually (hazard quotient) and cumulatively (hazard index), were below 1 in all the samples. The mean concentrations of PAH markers B[a]P and the PAH4 were above the EU limits in both the smoked and the grilled samples tested. This implies that exposure to high levels of these PAHs through regular consumption of these products may increase the risk of developing certain types of cancer and other health issues. The smoked fishes has the lowest MOE values for the PAH8 compared to the other samples. The margin of exposures (MOEs), carcinogenic toxic equivalent (TEQ), and excess cancer risk (ECR) also indicated that frequent consumption of smoked fish (mackerel or catfish) by an adult of 70 kg body weight above the reported intake rate of 0.0019 kg/AME/day for a prolonged period may have higher cancer risks than in other samples. Smoked game meat had the highest PAH16 level, but indicated a relatively lower risk level, possibly because of its relatively low intake rate (0.0004 kg/AME/day).

Polycyclic aromatic hydrocarbon in community drinking water, Nsisioken, Nigeria: Source and health risk assessment.

In 2011, the United Nations Environment Programme discovered high levels of hydrocarbon pollution in drinking water wells in Nsisioken Agbi Ogale Rivers State, Nigeria. However, the level of polycyclic aromatic hydrocarbons (PAHs) in the same community's water supply was unknown. A comprehensive study of PAHs in three household dug wells and three boreholes was conducted using Agilent 7890B gas chromatography and 5975A mass spectrometry. The detected PAHs were mainly 4 - 5 ringed PAHs, such as Chrysene, Fluoranthene, Pyrene, Benzo[a]anthracene, and Benzo[b]fluoranthene. The total mean concentration was 5.8 ± 2.3 μg/L, with values ranging from not detected in borehole 3 to 8.0 μg/L at well 2. Source identification analysis suggested that the PAHs originated from fuel and biomass combustion. The incremental lifetime cancer risk for children and adults due to groundwater ingestion and skin contact ranged from ND to 7.448 × 10-3 and ND to 1.83 × 10-3 respectively. The Risk index (RI) values from ingestion and dermal routes were 1.5 ×10-2 and 2.4 × 10-2, indicating high risk of cancer. The hazard quotient for the two non-carcinogenic PAHs was greater than 1, indicating high toxicity. The PAH concentrations exceeded the maximum contamination limits set by the World Health Organization and the U.S. environmental Protection Agency, highlighting potential health risks associated with water use in the community. Authorities should provide a safe alternative water source for the community.

The overlooked toxicity of non-carcinogenic polycyclic aromatic hydrocarbons

The overlooked toxicity of non-carcinogenic polycyclic aromatic hydrocarbons

Occurrence and concentrations of organic micropollutants (OMPs) in highway stormwater: a comparative field study in Sweden

This study details the occurrence and concentrations of organic micropollutants (OMPs) in stormwater collected from a highway bridge catchment in Sweden. The prioritized OMPs were bisphenol-A (BPA), eight alkylphenols, sixteen polycyclic aromatic hydrocarbons (PAHs), and four fractions of petroleum hydrocarbons (PHCs), along with other global parameters, namely, total organic carbon (TOC), total suspended solids (TSS), turbidity, and conductivity (EC). A Monte Carlo (MC) simulation was applied to estimate the event mean concentrations (EMC) of OMPs based on intra-event subsamples during eight rain events, and analyze the associated uncertainties. Assessing the occurrence of all OMPs in the catchment and comparing the EMC values with corresponding environmental quality standards (EQSs) revealed that BPA, octylphenol (OP), nonylphenol (NP), five carcinogenic and four non-carcinogenic PAHs, and C16-C40 fractions of PHCs can be problematic for freshwater. On the other hand, alkylphenol ethoxylates (OPnEO and NPnEO), six low molecule weight PAHs, and lighter fractions of PHCs (C10-C16) do not occur at levels that are expected to pose an environmental risk. Our data analysis revealed that turbidity has a strong correlation with PAHs, PHCs, and TSS; and TOC and EC highly associated with BPA concentrations. Furthermore, the EMC error analysis showed that high uncertainty in OMP data can influence the final interpretation of EMC values. As such, some of the challenges that were experienced in the presented research yielded suggestions for future monitoring programs to obtain more reliable data acquisition and analysis.

Occurrence and probabilistic risk assessment of polycyclic aromatic hydrocarbons in blood and urine of auto-mechanics in Akure Metro, Nigeria

This study provides baseline data on the concentration of polycyclic aromatic hydrocarbons (PAHs) in blood and urine samples of auto-mechanics, using Nigeria as a case study. Eighteen auto-mechanics participated in the study excluding two controls. The concentrations for the ΣPAHs across all participants (excluding control) ranged from 1.67 to 3.30 (2.17 ± 0.58) in blood with a significantly higher (P < 0.05) range of 7.61 to 10.76 (8.69 ± 1.00) in urine. The high molecular weight PAHs (4-6 rings) dominated the PAH profile in both blood (≥ 92%) and urine (≥ 87%) across all locations. Dibenz(a)anthracene was the most distributed PAH, while acenaphthene and indeno(1,2,3-cd)pyrene were the least distributed. The dermal route constituted approximately 99% of the total chronic exposure, followed by ingestion, and the least via inhalation. The hazard index (HI) was below the safe thresholds (HI = 1), suggesting non-carcinogenic PAH effects. However, all the participants including control samples had carcinogenic risk (CR) values above the acceptable level of 10-6 in both blood and urine samples. The carcinogenic and mutagenic potencies were higher in urine than in blood. The results suggest less acute toxicity and more potential chronic effects. The computed elimination ratio (> 1) suggests low excretion in urine and a potentially harmful trend. Molecular diagnostic ratios and principal component analysis suggest mixed PAH sources. The study revealed biomonitoring solely dependent on blood analysis may greatly underestimate health risks due to PAH exposure. To the best of our knowledge, this study is the first to provide levels of PAHs in the blood and urine of Nigerian mechanics. Findings herein will support policymakers at all levels in re-focusing attention to the less prioritized professions that pre-disposes people to PAHs and other emerging pollutants in society.

Association of smoking and dietary polycyclic aromatic hydrocarbon exposure on the prevalence of metabolic syndrome in Korean adults.

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that are potentially hazardous to human health. Dietary exposure is recognized as one of the major pathways of exposure to PAHs among humans. While some PAH exposures have been associated with metabolic syndrome (MetS) in the general population, most epidemiological studies are based on urinary metabolites of a few noncarcinogenic PAHs. To investigate the association between estimates of dietary exposure to major carcinogenic PAHs and MetS in Korean adults. Multi-cycle Korean National Health and Nutrition Examination Survey (KNHANES) database (n = 16,015) and PAH measurement data from the total diet survey were employed to estimate daily PAH intake for each participating adult. After adjusting for potential confounders, multinomial logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) between PAHs and MetS of the participating adults. Benzo(a)pyrene exposure was associated with an increased risk of MetS in men (OR = 1.30; 95% Cl: 1.03-1.63; P-trend = 0.03). In women, however, only chrysene and low high-density lipoprotein (HDL-c) were positively associated with an increased risk of MetS (OR = 1.24; 95% CI: 1.03-1.48; P-trend = 0.0172). Among men, smokers were at an increased risk for MetS, regardless of whether they were exposed to low or high total PAHs and benzo(a)pyrene levels. Our findings suggested that PAHs are associated with the risk of MetS and MetS components in Korean adults. In particular, it was confirmed that smoking may influence the relationship between PAH exposure and MetS.Further prospective cohort studies are required to confirm the causal relationship between PAHs and MetS. Epidemiological studies on PAH exposure are often hampered by a lack of reliable exposure estimates, as biomonitoring of urine does not capture exposure to more toxic PAHs. Using multi-cycle KNHANES data and the measurement data from a total diet survey of Korea, we could develop a personalized PAH intake estimate for each participating adult and assessed the association with MetS.

Carcinogenic Potentials of Toxic Metals and Polycyclic Aromatic Hydrocarbons in Telfairia occidentalis and Talinum triangulare Impacted by Wastewater, Southern Nigeria

Health risks of toxic metals and polycyclic aromatic hydrocarbons (PAHs) associated with the consumption of Telfairia occidentalis and Talinum triangulare impacted by wastewater from water treatment plants within Uyo Metropolis, Southern Nigeria, were investigated using standard methods. The level of toxic metals and PAHs was higher in vegetables impacted by wastewater from food processing industries than in the other investigated sources. The levels of cadmium (Cd), lead (Pb), arsenic (As), and chromium (Cr) in the vegetables exceeded their recommended limits by the Food and Agriculture Organization (FAO) and the World Health Organization (WHO). Wastewater was confirmed as the major source of toxic metals in the vegetables. The estimated chronic daily intake of toxic metals through vegetables for both child and adult populations was lower than their tolerable daily intake. The hazard quotients of noncarcinogenic PAHs indicated higher values for children than adults. The vegetables contained all the priority PAHs except dibenz[a,h]anthracene. The estimated daily intake of PAHs was higher in children than in adults, except for phenanthrene. The threshold screening values for PAHs indicated lower non-carcinogenic health risks for consumers. The carcinogenic health risks of metals and PAHs via vegetables indicated a moderately high risk for both populations. The consumption of vegetables impacted by wastewater could result in serious health problems for both child and adult populations. This study has exposed the environmental and human health problems related to the use of wastewater for the irrigation of vegetable gardens, which hitherto were unavailable in the study area.

Interaction of Polycyclic Aromatic Hydrocarbon compounds in fish primary hepatocytes: From molecular mechanisms to genotoxic effects

Polycyclic Aromatic Hydrocarbons (PAHs) are persistent pollutants normally found in the environment as complex mixtures. Although several individual PAHs are classified as mutagenic and carcinogenic pollutants, the interaction effects between compounds in a mixture may trigger different toxicological mechanisms and, consequently, yield different effects to organisms which are not accounted for in risk assessment guidelines. Given the ubiquity of PAHs, understanding the mechanistic features of their mixtures is a pressing research need. Therefore, the present work aimed to disclose the interaction effects of three PAHs with different carcinogenic potential and chemical structure, in primary hepatocyte cells of gilt-headed seabreams (Sparus aurata). Hepatocytes were exposed to Phenanthrene (Phe), Benzo[a]pyrene (B[a]P) and Benzo[b]fluoranthene (B[b]F) and their mixtures at different proportions and several cellular responses were analyzed: cellular viability, CYP1A1 activity (EROD assay) and protein expression level (Western blot); transcript (mRNA) levels of CYP1A1, EPXH1 and GST-3 (qRT-PCR); genotoxic effects (DNA strand breakage) by the Comet assay. Results show that B[a]P induced CYP1A1 gene and protein expression increasing its activity and, therefore, increasing the production of metabolites that trigger genotoxic DNA damage (%). Most importantly, mixtures containing Phe and B[a]P increased even further CYP1A1 mRNA levels and DNA damage (up to 70 %) which suggests that, although Phe is considered a non-carcinogenic PAH, it potentiates CYP1A1 synthesis induced by B[a]P, increasing its genotoxicity. These findings indicate that the upregulation of CYP1A1 by carcinogenic PAHs will not weaken even when in mixtures with non-carcinogenic PAHs. On contrary, non-carcinogenic PAHs may potentiate the genotoxic effect of carcinogenic PAH and therefore mixture composition should be taken in account when assessing PAH toxicity. In fact, our results point to the need of redefining Environmental Risk Assessment protocols for mixtures of carcinogenic pollutants.

Time Course Of Dermal Anthracene Absorption Utilizing Intradermal Microdialysis

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants encountered through daily exposures, including smoking, vehicular exhaust, industry sources, and occupational settings, such as firefighting. Inhalation has received greatest attention as a major exposure route, with limited data regarding dermal absorption. PURPOSE: Utilizing the non-carcinogenic PAH, anthracene (ANT), we aimed to assess 1) time course of dermal ANT absorption and 2) effects of local skin temperature on the magnitude of dermal absorption. METHODS: Two intradermal microdialysis (MD) fibers were inserted in the ventral forearm of 6 healthy participants (32 ± 5 yrs, 5 male, 1 female). MD fibers were perfused with 10% 2-hydroxypropyl-β-cyclodextrin with lactated Ringer’s at 1 μl/min. A 2% ANT solution was applied to skin over each MD site with overlying local heaters (LH) housing laser Doppler flowmeters for assessment of skin blood flow (SkBf). LH were clamped at 33 °C during baseline dialysate sampling. Following baseline, LH were set to 1) 43 °C (Hot, HT) and 2) 33 °C as thermoneutral (TN) for the duration of the protocol. Dialysate samples were collected intermittently over 4 hours and 15 minutes, and SkBf, blood pressure and HR were recorded throughout the protocol. Atmospheric pressure chemical ionization tandem mass spectrometry was used to quantify ANT dialysate concentrations. RESULTS: Preliminary data indicate that no ANT was detected in any baseline samples. From 1 h30 to 1 h 45 min, ANT was detected in 3 of 6 and 0 of 6 samples for the HT and TN sites, respectively. One HT sample was quantifiable at 317.5 ppb. Sampling from 4 h to 4 h 15 min, ANT was detected in all samples at the HT site and quantified in one (344.9 ppb). ANT was detected in only 1 of 6 samples at the TN site during this sampling period. SkBf was significantly higher at HT versus TN at both 1 h 45 min (8.7 ± 5.7 and 29.2 ± 20.5 CVC%max, P < 0.05) and 4 h 15 min (12.8 ± 8.3 and 42.8 ± 22.3 CVC%max, P < 0.05). CONCLUSIONS: Preliminary data indicate that dermal absorption and recovery of the PAH anthracene is increased when skin is heated versus thermoneutral, increasing over time. This has potential implications for dermal absorption of contaminants in individuals working in the heat. These data also suggest that microdialysis may be an effective method of assessing dermal absorption of PAHs.

Screening of Carcinogenic and Non-carcinogenic Polycyclic Aromatic Hydrocarbon in a Typical Urban City Center, Owerri, Nigeria

The study screened the carcinogenic and non-carcinogenic PAH in urban city center Owerri, Imo State. Soxhlet extraction-gas chromatography-flame ionization detector (SE-GC-FID) method was used to analyze PAH concentrations in the different environmental component to determine its impact. Result of the physicochemical properties of the spent engine oil polluted soil sample showed that exchangeable base (4.67g/kg), exchangeable acidity (1.25g/kg), organic carbon (6.32g/kg), organic matter (6.45g/kg), percentage nitrogen (0.46%), were higher in the polluted soil when compared to soil collected from a non-polluted agricultural farm. However, the effective cation exchange capacity (9.27g/kg), was lower in the polluted soil sample although, the pH value of the polluted soil was acidic. Result of the water sample collected from urban city center, showed that water sample properties of turbidity and magnesium, had mean values of 9.6±1.10mg/l and 26.7±0.08mg/l, respectively. Five carcinogenic PAH were detected in soil, water and sediment of the study area. The concentration of PAHs detected were within the range of 0.55±0.1 and 0.87±0.11 for sediment and water samples while, spent engine oil polluted sample and Abattoir soil sample were found in the range of 2.25±0.11 and 0.50±0.01 respectively. However, the detection of these carcinogenic PAH obtained from the different sampling point suggest the toxicity propensity of these pollutant.

Analysis of technological conditions for the formation and burnout of carcinogenic pahs in boiler flue gases

THE PURPOSE. The necessity of establishing emission standards for highly toxic substances with carcinogenic properties in the context of the implementation of new principles of state regulation of environmental protection activities at energy enterprises is substantiated and confirmed. The analysis of the features of the formation and burnout of carcinogenic polycyclic aromatic hydrocarbons in the flue gases of boilers during the combustion of coals in lowtemperature conditions of the furnace process is carried out. Based on the analysis, the total and partial indicators of the harmfulness of flue gases were calculated in order to assess and predict the overall toxicity of coal combustion products, taking into account the contribution of carcinogenic substances.METHODS. When calculating the overall toxicity of flue gases, a systematic analysis and generalization of experimental data on the content of carcinogenic and non-carcinogenic polycyclic aromatic hydrocarbons in the combustion products of low-power boilers was applied.RESULTS. As a result of the performed study, the contribution of carcinogenic and non-carcinogenic polycyclic hydrocarbons to the overall toxicity of boiler flue gases during the combustion of Azeysky, Mugunsky, Cheremkhovsky and Tugnuy coal was determined. It is shown that substances such as benz(a)pyrene, fluoranthene, pyrene and phenanthrene significantly affect the level of the total indicator of the harmfulness of combustion products from 38.8 to 53.6%.CONCLUSION. The obtained research results can be applied at energy enterprises at the stage of substantiating the introduction of regime-technological and environmental measures in order to develop measures to improve environmental efficiency through technological rationing of carcinogenic emissions.

Polycyclic Aromatic Hydrocarbons Activate the Aryl Hydrocarbon Receptor and the Constitutive Androstane Receptor to Regulate Xenobiotic Metabolism in Human Liver Cells.

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants produced by incomplete combustion of organic matter. They induce their own metabolism by upregulating xenobiotic-metabolizing enzymes such as cytochrome P450 monooxygenase 1A1 (CYP1A1) by activating the aryl hydrocarbon receptor (AHR). However, previous studies showed that individual PAHs may also interact with the constitutive androstane receptor (CAR). Here, we studied ten PAHs, different in carcinogenicity classification, for their potential to activate AHR- and CAR-dependent luciferase reporter genes in human liver cells. The majority of investigated PAHs activated AHR, while non-carcinogenic PAHs tended to activate CAR. We further characterized gene expression, protein abundancies and activities of the AHR targets CYP1A1 and 1A2, and the CAR target CYP2B6 in human HepaRG hepatoma cells. Enzyme induction patterns strongly resembled the profiles obtained at the receptor level, with AHR-activating PAHs inducing CYP1A1/1A2 and CAR-activating PAHs inducing CYP2B6. In summary, this study provides evidence that beside well-known activation of AHR, some PAHs also activate CAR, followed by subsequent expression of respective target genes. Furthermore, we found that an increased PAH ring number is associated with AHR activation as well as the induction of DNA double-strand breaks, whereas smaller PAHs activated CAR but showed no DNA-damaging potential.

Mixture effects of food-relevant polycyclic aromatic hydrocarbons on the activation of nuclear receptors and gene expression, benzo[a]pyrene metabolite profile and DNA damage in HepaRG cells

Carcinogenic benzo[a]pyrene (BP) and other non-carcinogenic polycyclic aromatic hydrocarbons (PAH) like fluoranthene (FA) and pyrene (PYR) occur as food contaminants. Molecular effects of BP, FA and PYR in human liver cells were investigated using mixtures occurring in grilled meat. Activation of aryl hydrocarbon receptor (AHR) and constitutive androstane receptor (CAR) was investigated along with target gene expression. Mixture effects on BP metabolite profile and DNA-damaging potential were studied as biological downstream effects.Compared to BP, FA and PYR activated the AHR only weakly. Mixtures were less efficient than BP. Analysis of CYP1A1 expression showed synergistic induction after co-exposure in HepaRG cells. FA and PYR were strong CAR agonists, whereas BP was less potent. Mixtures containing BP caused a strong decrease of CAR transactivation in line with lower CYP2B6 expression. The BP metabolite profile and BP-induced DNA damage were only weakly affected.PAH mixtures modulate AHR, CAR activation and their target genes. However, these mixture effects appear not to be reflected at the level of downstream events like BP metabolite formation or BP-induced DNA damage. Our study clearly shows that endpoints at all biological levels should be considered for mixture evaluation, instead of drawing conclusions exclusively based on early molecular events.

Suspended fine particulate matter (PM2.5), microplastics (MPs), and polycyclic aromatic hydrocarbons (PAHs) in air: Their possible relationships and health implications

Exposure to fine particulate matter (PM2.5) and their associated microcontaminants have been linked to increased harmful effects on the human health. In this study, the possible relationships between PM2.5, microplastics (MPs), and polycyclic aromatic hydrocarbons (PAHs) were analyzed in an urban area of Bushehr port, in the northern part of the Persian Gulf. Presence, sources, and health risks of MPs and PAHs in both normal and dusty days were also investigated. The median of PM2.5 and ƩPAHs were 52.8 μg/m3 and 14.1 ng/m3, respectively, indicating high pollution levels especially in dusty days. The mean level of MPs in urban suspended PM2.5 was 5.2 items/m3. Fragments were the most abundant shape of identified MPs and polyethylene terephthalate (PET) was the most plastic types in urban dust of Bushehr port. The results revealed that PM2.5 and MPs may possibly act as a carrier for airborne MPs and PAHs, respectively. In addition, the significant positive relationships between MPs, wind speed and wind direction, confirmed that the MPs transportation were highly controlled by atmospheric condition. Moreover, the source identification methods and trajectory analyses indicated that petrogenic sources from both proximal and distal origins play an important role in the level of PAHs. The results of chronic health risk evaluation via inhalation revealed that PM2.5-bound PAHs had high potential cancer risk in winter, while, the estimated risks for non-carcinogenic PAHs were not considerable. In the case of MPs, the assessment of human intake of MPs via inhalation highlighted the possible risks for habitants.

Classifying polycyclic aromatic hydrocarbons by carcinogenic potency using in vitro biosignatures

One of the most difficult challenges for risk assessment is evaluation of chemicals that predominately co-occur in mixtures like polycyclic aromatic hydrocarbons (PAHs). We previously developed a classification model in which systems biology data collected from mice short-term after chemical exposure accurately predict tumor outcome. The present study demonstrates translation of this approach into a human in vitro model in which chemical-specific bioactivity profiles from 3D human bronchial epithelial cells (HBEC) classify PAHs by carcinogenic potency. Gene expression profiles were analyzed from HBEC exposed to carcinogenic and non-carcinogenic PAHs and classification accuracies were identified for individual pathway-based gene sets. Posterior probabilities of best performing gene sets were combined via Bayesian integration resulting in a classifier with four gene sets, including aryl hydrocarbon receptor signaling, regulation of epithelial mesenchymal transition, regulation of angiogenesis, and cell cycle G2-M. In addition, transcriptional benchmark dose modeling of benzo[a]pyrene (BAP) showed that the most sensitive gene sets to BAP regulation were largely dissimilar from those that best classified PAH carcinogenicity challenging current assumptions that BAP carcinogenicity (and subsequent mode of action) is reflective of overall PAH carcinogenicity. These results illustrate utility of using systems toxicology approaches to analyze global gene expression towards carcinogenic hazard assessment.

Abstract A41: Assessing the effect of glucobrassicin-rich Brussels sprouts on the metabolism of deuterated phenanthrene: Developing food-based chemoprevention of tobacco-related lung cancer

Abstract Introduction: Indole-3-carbinol (I3C) and 3,3-´diindolylmethane (DIM), derived from the glucosinolate glucobrassicin, are found in cruciferous vegetables. I3C and DIM possess a potent chemopreventive effect against the development of tobacco carcinogen-induced lung tumors in mice. Polycyclic aromatic hydrocarbons (PAH) are potent lung carcinogens present in high levels in tobacco smoke. An individual’s ability to metabolically activate and/or detoxify PAH may be related to lung cancer risk from smoking. We hypothesize that I3C administered by eating a rational dose of Brussels sprouts, defined in terms of glucobrassicin concentration, can decrease the metabolic activation and/or increase detoxification of PAH, represented by the noncarcinogenic PAH [D10]Phenanthrene ([D10]Phe). Use of deuterated phenanthrene eliminates confounding by environmental phenanthrene. Metabolic activation of [D10]Phe is represented by [D10]Phenanthrene tetraol ([D10]PheT), and detoxification is represented by [D10]phenanthrol. We are conducting a clinical trial to determine whether glucobrassicin-rich Brussels sprouts can favorably modify the metabolism of the [D10]Phe. Study Design: This is a single-arm clinical trial. The primary objective is to determine the effect of a 7-day course of Brussels sprout consumption on [D10]PheT. Secondary objectives include analysis of [D10]phenanthrol and the [D10]PheT:[D10]phenanthrol ratio. Exploratory objectives include determining the correlation between 24 h urinary DIM with the reduction in [D10]PheT, and determining the effect of Brussels sprout consumption on circulating immune cell composition and activity. Forty-eight generally healthy, adult current smokers and former smokers will be enrolled. Subjects are given 1 microgram of [D10]phe, and all urine is collected for 6 hours (h) afterwards to quantify baseline levels of [D10]PheT and [D10]phenanthrol. Subjects then consume 200 micromol glucobrassicin in the form of raw Brussels sprouts (~200-300 g) once daily for 7 days. Urine is collected for 24 h after vegetable consumption on days 3 ± 1 and 6 of the feeding intervention for DIM quantification. On day 7 of the feeding intervention, a second dose of 1 microgram of [D10]phe is administered at the study center 60 minutes ± 10 minutes after vegetable consumption, followed by another 6 h urine collection. [D10]pheT and [D10]phenanthrol levels are quantified using a validated tandem mass spectrometry assay. Pre- and post-[D10]PheT levels are compared using a paired t-test after log transformation. The results will also be analyzed by GSTT1 and GSTM1 genotyping. Results: Twelve subjects have completed the study. Baseline [D10]PheT levels ranged from 48.34 to 331.05 pmol/6 h. Day 7 [D10]PheT levels ranged from 26.57 to 333.35 pmol/6 h. Percent change from baseline to Day 7 [D10]PheT ranged from a 33% decrease to an 86.5% increase (mean +/- SE of 12.8 +/- 11.6%). Conclusions: The study is ongoing and more subjects are necessary to make a definitive conclusion. Citation Format: Naomi Fujioka, Michelle To, Bruce R. Lindgren, Vincent A. Fritz, Charles Rohwer, Dorothy Hatsukami, Stephen S. Hecht. Assessing the effect of glucobrassicin-rich Brussels sprouts on the metabolism of deuterated phenanthrene: Developing food-based chemoprevention of tobacco-related lung cancer [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A41.

Effect Of Skin Temperature On Dermal Absorption Of Anthracene

Exposure to a variety of ubiquitous pollutants, including polycyclic aromatic hydrocarbons (PAHs), occurs during daily exposure to vehicular exhaust fumes, smoking, grilling, and in many occupations, including firefighting. Dermal absorption of potential carcinogens has received limited attention compared to respiratory routes due to the challenges with measurement in vivo. PURPOSE: Our aims were 1) establish the efficacy of microdialysis (MD) as a sampling technique for dermal absorption of PAHs and 2) determine the effect of skin temperature on dermal absorption of the non-carcinogenic PAH, anthracene (ANT). METHODS: Two MD fibers were inserted into the ventral forearm of 6 healthy participants (32 ± 5 yrs, 5 male, 1 female) and perfused with lactated Ringers and 10% 2-hyroxypropyl-β-cyclodextrin at a rate of 1 μl/min. 2% ANT cream was applied over each site, dialysate samples were collected and skin blood flow (SkBF) measured at a locally heated (HT, 43°C) and thermoneutral (TN, 33°C) site. The concentration of ANT from dialysate samples were measured via targeted tandem mass spectrometry. RESULTS: Dialysate ANT concentration was similar between the HT and TN sites (2.9 ± 0.4 vs. 3.5 ± 0.4 ppm, P=0.26). Absolute SkBF was significantly higher at the HT versus TN site (35.7 ± 11.8 and 7.2 ± 1.0 CVC, P=0.001). CONCLUSIONS: These data provide support for MD as a sampling technique for dermal absorption of PAHs. Despite similar ANT concentrations between sites, dermal absorption and sampling can be modulated by multiple factors. Further research is required to elucidate the influence of skin temperature versus clearance on dermal absorption of ANT and other PAHs. This has important implications for understanding dermal absorption of potentially carcinogenic compounds in occupational workers and the general poulation.

Mapping the Mitochondrial Regulation of Epigenetic Modifications in Association With Carcinogenic and Noncarcinogenic Polycyclic Aromatic Hydrocarbon Exposure.

Polycyclic aromatic hydrocarbons (PAHs) refer to a ubiquitous group of anthropogenic air pollutants that are generated through incomplete carbon combustion. Although the immunotoxic nature of PAHs has been previously reported, the underlying molecular mechanisms of this effect are not fully understood. In the present study, we investigated the mitochondrial-mediated epigenetic regulation of 2 PAHs, carcinogenic (benzo[a]pyrene; BaP) and noncarcinogenic (anthracene [ANT]), in peripheral lymphocytes. While ANT exposure triggered mitochondrial oxidative damage, no appreciable epigenetic modifications were observed. On the other hand, exposure to BaP perturbed the mitochondrial redox machinery and initiated cascade of epigenetic modifications. Cells exposed to BaP showed prominent changes in the expression of mitochondrial microRNAs (miR-24, miR-34a, miR-150, and miR-155) and their respective gene targets (NF-κβ, MYC, and p53). The exposure of BaP also caused significant alterations in the expression of epigenetic modifiers (DNMT1, HDAC1, HDAC7, KDM3a, EZH2, and P300) and hypomethylation within nuclear and mitochondrial DNA. This further induced methylation of histone tails, which play a crucial role in the regulation of chromatin structure. Overall, our study provides novel mechanistic insights into the mitochondrial regulation of epigenetic modifications in association with PAH-induced immunotoxicity.

Development of human health ambient water quality criteria of 12 polycyclic aromatic hydrocarbons (PAH) and risk assessment in China

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in various environmental media and have thus attracted extensive attention worldwide. To prevent and control PAH pollution in China, the study of ambient water quality criteria (AWQC), human health risks, and aquatic ecological risk is critical. There are no reports to date on the human health AWQC of PAHs in China. Therefore, this study first derived the human health AWQC values of 12 PAHs based on exposure data and bioaccumulation factor in China. We found that local exposure parameters and other relevant factors were key during the development of AWQC in different countries and regions, which led to differences with the reference value recommended by USEPA. Based on the incremental life time cancer risk (ILCR), hazard quotients (HQ) and potentially affected fraction (PAF) methods, the health and ecological risks of 16 PAHs were assessed subsequently. And the results are as follows: the non-carcinogenic PAHs’ health risks ranged from 1.01 × 10−10 to 1.60 × 10−9, and carcinogenic PAH health risks ranged from 5.03 × 10−7 to 4.74 × 10−5. The toxic effects of 8 PAHs on aquatic organisms exhibited the following order: benzo (a) pyrene (BaP) > anthracene (Ant) > pyrene (Pye) > phenanthrene (Phe) > fluoranthene (Flua) > acenaphthene (Ace) > fluorene (Flu) > naphthalene (Nap). Among these, the ecological risks posed by Ant and BaP were the highest, according to the HQ and PAF methods.

CONCENTRATION AND POTENTIAL HEALTH RISK ASSOCIATED WITH DIETARY INTAKE OF SMOKED FISH FROM LAGOS LAGOON

This study assessed the concentration and potential health risk associated with dietary exposure to polycyclic aromatic hydrocarbons (PAHs) in smoked fish products from four fishing communities along Lagos Lagoon, Nigeria. Sixty smoked fish samples obtained from two fish species (Chrysichthys nigrodigitatus and Elops lacerta) which were processed individually with three firewood (Cola nitida, Funtumia elastica and Alchornea cordifolia) were collected from fish processors between October and December, 2018. Samples were subjected to polycyclic aromatic hydrocarbons (PAHs) analysis using gas chromatography-mass spectrometry (GC-MS) and human health risk model analysis. The PAH congeners varied in smoked fish while Pyrene was the most dominant congener in all the fish samples, accounting for more than 70% of the total PAHs. The highest total PAHs levels (2431.85 mg kg-1) was observed in E. lacerta smoked with C. nitida. The Dietary Daily Intake (DDI) values for total and carcinogenic PAHs were higher in E. lacerta smoked with C. nitida and C. nigrodigitatus smoked with A. cordifolia, respectively. Carcinogenic Toxic Equivalent (TEQ) values were lower than the estimated Screening Value (SV) of 12.83 indicating low risk of developing cancer through consumption of assessed smoked fish products. Excess Cancer Risk estimated exceeded the permissible limit (1.0x10−6) set by USEPA. Positive correlations (P&lt;0.01) existed between TEQ and total PAHs, noncarcinogenic PAHs, PAH4, and DDI. This study provides insights into the variation in PAHs level and appropriateness of different fuelwood for smoking similar or dissimilar fish species.