Oral and Dermal Bioavailability Studies of Polycyclic Aromatic Hydrocarbons from Soils Containing Weathered Fragments of Clay Shooting Targets.

The relative oral bioavailability and dermal absorption of chemical substances from environmental media are key factors that are needed to accurately estimate site-specific risks and manage human exposures. This study evaluated the in vivo relative oral bioavailability and in vitro dermal absorption of several polycyclic aromatic hydrocarbons (PAHs) found in soils collected from two formerly used Department of Defense sites impacted by weathered fragments of clay shooting targets. Concentrations of individual carcinogenic PAHs in the ≤250 µm fraction of soil ranged from approximately 0.1 to 100 mg/kg. A novel sample preparation method was developed to produce accurate and precise test diets for oral studies. The resulting test diets showed consistent concentrations of PAHs in soil- and soil-extract-amended diets and a consistent PAH concentration profile. Mean oral relative bioavailability factors (RBAFs) and dermal absorption fractions (ABSd) for benzo(a)pyrene ranged from 8 to 14% and 0.58 to 1.3%, respectively. Using the RBAF and ABSd values, measured here, for benzo(a)pyrene in USEPA's regional screening level equations yields concentrations for residential soils that are approximately eight times higher than those when default values are used (e.g., 9.6 vs 1.2 mg/kg at a target excess risk of 1 × 10-5).

Testing the validity of a proposed dermal cancer slope factor for Benzo[a]pyrene.

In 2014, the United States Environmental Protection Agency (EPA) proposed a Dermal Slope Factor (DSF) for benzo[a]pyrene (BaP) of 0.006 (µg/day)-1 (USEPA 2014a). It would make cancer risk estimates associated with soil contact 100 times greater than those from soil ingestion and would predict that a large fraction of skin Basal Cell Carcinomas (BCCs) and Squamous Cell Carcinomas (SCCs) worldwide are caused by low level dermal exposures to PAHs, such as BaP. This is not logical given that sunlight (ultraviolet radiation (UV)) exposure is the generally recognized cause of BCCs and SCCs. This paper critically evaluates the proposed DSF. First, a reality check is performed using EPA standard risk assessment methods and comparing the results to actual BCC and SCC rates in the U.S. population. Then, the biological plausibility of the mechanism by which PAHs might cause human skin cancer is evaluated by exploring the generally recognized etiology of human skin cancer and comparing the genetic mutation signatures of rodent skin tumors caused by PAH exposures to those of human skin cancers. It is concluded that scientific flaws resulted in a proposed DSF value that greatly overestimates the skin cancer risk for humans dermally exposed to BaP in soil.

Risk assessment implications of site-specific oral relative bioavailability factors and dermal absorption fractions for polycyclic aromatic hydrocarbons in surface soils impacted by clay skeet target fragments.

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.

Quantitative determination of hydroxy polycylic aromatic hydrocarbons as a biomarker of exposure to carcinogenic polycyclic aromatic hydrocarbons.

A high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS) method was developed for quantitative analysis of hydroxy polycyclic aromatic hydrocarbons (OH-PAHs). Four hydroxy metabolites of known and suspected carcinogenic PAHs (benzo[a]pyrene (B[a]P), benz[a]anthracene (B[a]A), and chrysene (CRY)) were selected as suitable biomarkers of PAH exposure and associated risks to human health. The analytical method included enzymatic deconjugation, liquid - liquid extraction, followed by derivatization with methyl-N-(trimethylsilyl) trifluoroacetamide and instrumental analysis. Photo-induced oxidation of target analytes - which has plagued previously published methods - was controlled by a combination of minimizing exposure to light, employing an antioxidant (2-mercaptoethanol) and utilizing a nitrogen atmosphere. Stability investigations also indicated that conjugated forms of the analytes are more stable than the non-conjugated forms. Accuracy and precision of the method were 77.4-101% (<4.9% RSD) in synthetic urine and 92.3-117% (<15% RSD) in human urine, respectively. Method detection limits, determined using eight replicates of low-level spiked human urine, ranged from 13 to 24pg/mL. The method was successfully applied for analysis of a pooled human urine sample and 78 mouse urine samples collected from mice fed with PAH-contaminated diets. In mouse urine, greater than 94% of each analyte was present in its conjugated form.

Dermal irritation assessment of three benzene sulfonate compounds.

Three benzene sulfonate compounds, benzene sulfonate, benzene meta-disulfonate, and para-phenol sulfonate, were reported to be present in groundwater sampled from residential wells near a former disposal site. Concentrations ranged from < 0.005 mg/L to 474 mg/L. Acute dermal irritation studies were performed on rabbits for each of the three sulfonate compounds to determine if they had the potential to cause irritation to the skin of persons using this groundwater for bathing, showering, or other uses where skin would be exposed. The studies were performed by Toxikon Corporation (Bedford, MA) in accordance with the United States Environmental Protection Agency (USEPA)'s 1998 Health Effects Test Guidelines. At the highest concentration tested (5000 mg/L), all three sulfonate compounds were considered to be slight irritants, producing very slight to mild erythema (Draize Score 1). In all cases, the reactions were reversible. At 2000 mg/L, benzene meta-disulfonate and para-phenol sulfonate caused no irritation and were considered not to be irritants. At 2000 mg/L, only benzene sulfonate was considered to be a slight irritant, producing a mild erythema that was completely reversible within 24 hours. Benzene sulfonate was not considered an irritant at 1000 mg/L or at 500 mg/L. It is important to note that all three sulfonate compounds produced only a slight irritation at the highest concentration tested. None of the compounds produced a moderate to severe irritation response (i.e., severe erythema, edema). Furthermore, any irritation response observed at the highest concentrations tested was reversible within 72 hours. The only irritation response observed at the second highest dose was also reversible within 24 hours.