Evaluating Neutral PFAS for Potential Dermal Absorption from the Gas Phase.

Exposures to per- and polyfluoroalkyl substances (PFAS) are of increasing concern. Assessments typically focus only on ingestion and inhalation exposure due to a lack of generally accepted approaches for estimating dermal absorption. Prior work indicates limited dermal absorption of ionic PFAS, but absorption of neutral PFAS has not been examined from the liquid vehicle or from vapor. Partitioning of semivolatile organic compounds from the gas phase to the skin surface (i.e., stratum corneum) is well known, but the potential for partitioning of neutral PFAS from the gas phase to the stratum corneum has yet to be estimated. The SPARC-estimated physicochemical properties were used to calculate transdermal permeability coefficients (kp_g) and dermal-to-inhalation (D/I) exposure ratios for two groups of neutral PFAS, including those on a U.S. Environmental Protection Agency PFAS list. 11 neutral PFAS gave calculated D/I ratios >5, indicating that direct transdermal absorption may be an important exposure pathway compared to inhalation. Data on consumer products or indoor air is needed for the 11 neutral PFAS, followed by possible biomonitoring to experimentally verify dermal absorption from air. Additional PFAS should be estimated by the protocol used here as they are identified in commercial products.

Disposition of Fluorine on New Firefighter Turnout Gear.

Firefighter turnout gear is essential for reducing occupational exposure to hazardous chemicals during training and fire events. Per-and polyfluoroalkyl substances (PFASs) are observed in firefighter serum, and possible occupational sources include the air and dust of fires, aqueous film-forming foam, and turnout gear. Limited data exist for nonvolatile and volatile PFASs on firefighter turnout gear and the disposition of fluorine on the individual layers of turnout gear. Further implications for exposure to fluorine on turnout gear are not well understood. Three unused turnout garments purchased in 2019 and one purchased in 2008, were analyzed for 50 nonvolatile and 15 volatile PFASs by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-qTOF-MS) and gas chromatography-mass spectrometry (GC-MS), respectively. Particle-induced gamma ray emission (PIGE), a surface technique, and instrumental neutron activation analysis (INAA), a bulk technique, were used to measure total fluorine. Bulk characterization of the layers by pyrolysis-GC/MS (py-GC/MS) was used to differentiate fluoropolymer (e.g., PTFE) films from textile layers finished with side-chain polymers. The outer layer, moisture barrier, and thermal layers of the turnout gear all yielded measured concentrations of volatile PFASs that exceeded nonvolatile PFAS concentrations, but the summed molar concentrations made up only a small fraction of total fluorine (0.0016-6.7%). Moisture barrier layers comprised a PTFE film, as determined by py-GC-MS, and gave the highest individual nonvolatile (0.159 mg F/kg) and volatile PFAS (20.7 mg F/kg) as well as total fluorine (122,000 mg F/kg) concentrations. Outer and thermal layers comprised aromatic polyamide-based fibers (aramid) treated with side-chain fluoropolymers and had lower levels of individual nonvolatile and volatile PFASs. Equal concentrations of total fluorine by both PIGE and INAA on the outer and thermal layers is consistent with treatment with a side-chain fluoropolymer coating. New turnout gear should be examined as a potential source of firefighter occupational exposure to nonvolatile and volatile PFASs in future assessments.

Comparative Probabilistic Assessment of Occupational Pesticide Exposures Based on Regulatory Assessments.

Implementation of probabilistic analyses in exposure assessment can provide valuable insight into the risks of those at the extremes of population distributions, including more vulnerable or sensitive subgroups. Incorporation of these analyses into current regulatory methods for occupational pesticide exposure is enabled by the exposure data sets and associated data currently used in the risk assessment approach of the Environmental Protection Agency (EPA). Monte Carlo simulations were performed on exposure measurements from the Agricultural Handler Exposure Database and the Pesticide Handler Exposure Database along with data from the Exposure Factors Handbook and other sources to calculate exposure rates for three different neurotoxic compounds (azinphos methyl, acetamiprid, emamectin benzoate) across four pesticide-handling scenarios. Probabilistic estimates of doses were compared with the no observable effect levels used in the EPA occupational risk assessments. Some percentage of workers were predicted to exceed the level of concern for all three compounds: 54% for azinphos methyl, 5% for acetamiprid, and 20% for emamectin benzoate. This finding has implications for pesticide risk assessment and offers an alternative procedure that may be more protective of those at the extremes of exposure than the current approach.

Comparison of Risk Predicted by Multiple Norovirus Dose-Response Models and Implications for Quantitative Microbial Risk Assessment.

The application of quantitative microbial risk assessments (QMRAs) to understand and mitigate risks associated with norovirus is increasingly common as there is a high frequency of outbreaks worldwide. A key component of QMRA is the dose-response analysis, which is the mathematical characterization of the association between dose and outcome. For Norovirus, multiple dose-response models are available that assume either a disaggregated or an aggregated intake dose. This work reviewed the dose-response models currently used in QMRA, and compared predicted risks from waterborne exposures (recreational and drinking) using all available dose-response models. The results found that the majority of published QMRAs of norovirus use the 1 F1 hypergeometric dose-response model with α = 0.04, ß = 0.055. This dose-response model predicted relatively high risk estimates compared to other dose-response models for doses in the range of 1-1,000 genomic equivalent copies. The difference in predicted risk among dose-response models was largest for small doses, which has implications for drinking water QMRAs where the concentration of norovirus is low. Based on the review, a set of best practices was proposed to encourage the careful consideration and reporting of important assumptions in the selection and use of dose-response models in QMRA of norovirus. Finally, in the absence of one best norovirus dose-response model, multiple models should be used to provide a range of predicted outcomes for probability of infection.

Dermal absorption of benzo[a]pyrene into human skin from soil: Effect of artificial weathering, concentration, and exposure duration.

In vitro assessments of 14C-benzo[a]pyrene (BaP) absorption through human epidermis were conducted with the sub-63-µm fraction of four test soils containing different amounts of organic and black carbon. Soils were artificially weathered for eight weeks and applied to epidermis at nominal BaP concentrations of 3 and 10 mg/kg for 8 or 24 h. Experiments were also conducted at 24 h with unweathered soils and with BaP deposited onto skin from acetone at a comparable chemical load. For the weathered soils, absorption was independent of the amount of organic or black carbon, the mass in the receptor fluid was proportional to exposure duration but independent of concentration, and the mass recovered in the skin after washing was proportional to concentration and independent of exposure time. Results from the weathered and unweathered soils were similar except for the mass recovered in the washed skin, which was lower for the weathered soil only at the higher concentration. We hypothesize that chemical concentrations exceeded the BaP sorption capacity accessible within the artificial weathering timeframe for all soils tested, and that BaP mass in the washed skin was dominated by particles that were not removed by washing. Fluxes into and through skin from soils were lower by an order of magnitude than from acetone-deposited BaP.

Oral Bioavailability, Bioaccessibility, and Dermal Absorption of PAHs from Soil-State of the Science.

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.

Analysis of finite dose dermal absorption data: implications for dermal exposure assessment.

A common dermal exposure assessment strategy estimates the systemic uptake of chemical in contact with skin using the fixed fractional absorption approach: the dermal absorbed dose is estimated as the product of exposure and the fraction of applied chemical that is absorbed, assumed constant for a given chemical. Despite the prominence of this approach there is little guidance regarding the evaluation of experiments from which fractional absorption data are measured. An analysis of these experiments is presented herein, and limitations to the fixed fractional absorption approach are discussed. The analysis provides a set of simple algebraic expressions that may be used in the evaluation of finite dose dermal absorption experiments, affording a more data-driven approach to dermal exposure assessment. Case studies are presented that demonstrate the application of these tools to the assessment of dermal absorption data.

The mismeasure of dermal absorption.

The results of dermal absorption experiments are routinely and often exclusively reported in terms of fractional absorption. However, fractional absorption is not generally independent of skin loading conditions. As a consequence, experimental outcomes are commonly misinterpreted. This can lead in turn to poor estimation of exposures under field conditions and inadequate threat assessment. To aid interpretation of dermal absorption-related phenomena, a dimensionless group representing the ratio of mass delivery to plausible absorptive flux under experimental or environmental conditions is proposed. High values of the dimensionless dermal number (N(DERM)) connote surplus supply (i.e., flux-limited) conditions. Under such conditions, fractional absorption will generally depend on load and should not be assumed transferable to other conditions. At low values of N(DERM), dermal absorption will be delivery-limited. Under those conditions, high fractional absorption is feasible barring maldistribution or depletion due to volatilization, washing, mechanical abrasion or other means. Similar logic also applies to skin sampling and dermal toxicity testing. Skin surface sampling at low N(DERM) is unlikely to provide an appropriate measure of potential dermal dose due to depletion, whereas dermal toxicity testing at high N(DERM) is unlikely to show dose dependence due to saturation.

Dermal absorption of environmental contaminants from soil and sediment: a critical review.

Risk assessment of hazardous wastes sites may require characterization of the dermal availability of chemical contaminants in soil and/or sediment. Current U.S. Environmental Protection Agency guidance for assessment of dermal exposures to contaminants in water and soil was finalized in 2004 as a supplement (Part E) to the Risk Assessment Guidance for Superfund (RAGS). The soil protocol presented in RAGS Part E is less sophisticated than the water protocol and is supported by less empirical data. Investigations of dermal absorption of soil and sediment-borne contaminants that have been conducted to date include in vitro and in vivo experiments using both human and surrogate skin. A review of that literature was conducted with attention to relevant criteria including consideration of layering effects, degree of chemical saturation of soil, appropriateness of particle size distribution employed, soil-chemical contact time, and continuity of soil-skin contact (in in vivo studies). Most studies published to date are deficient by virtue of execution or reporting on one or more of the selected criteria. In addition the lack of methodological standardization evident in the literature hinders systematic evaluation of results. Since additional experimental work is needed, general agreement on acceptable approaches would be useful. Recommendations for good practice are presented.

Para niños saludables: a community intervention trial to reduce organophosphate pesticide exposure in children of farmworkers.

BACKGROUND: Exposure to organophosphate (OP) pesticides is an occupational hazard for farmworkers and affects their children through the take-home pathway. OBJECTIVES: We examined the effectiveness of a randomized community intervention to reduce pesticide exposure among farmworkers and their children. METHODS: We conducted a baseline survey of a cross-sectional sample of farmworkers (year 1) in 24 participating communities. Communities were randomized to intervention or control. After 2 years of intervention, a new cross-sectional survey of farmworkers was conducted (year 4). Farmworkers with a child 2-6 years of age were asked to participate in a substudy in which urine was collected from the farmworker and child, and dust was collected from the home and the vehicle driven to work. RESULTS: The median concentration of urinary metabolites was higher in year 4 than in year 1 for dimethylthiophosphate (DMTP) and dimethyldithiophosphate in adults and for DMTP for children. There were significant increases within both the intervention and control communities between year 1 and year 4 (p < 0.005); however, the differences were not significant between study communities after adjusting for year (p = 0.21). The dust residue data showed azinphos-methyl having the highest percentage of detects in vehicles (86% and 84% in years 1 and 4, respectively) and in house dust (85% and 83% in years 1 and 4, respectively). There were no significant differences between intervention and control communities after adjusting for year (p = 0.49). CONCLUSIONS: We found no significant decreases in urinary pesticide metabolite concentrations or in pesticide residue concentrations in house and vehicle dust from intervention community households compared with control community households after adjusting for baseline. These negative findings may have implications for future community-wide interventions.

Effect of PBPK model structure on interpretation of in vivo human aqueous dermal exposure trials.

Multiple research teams have reported data from in vivo human trials in which breath was monitored during and after whole-body or partial immersion in aqueous solutions of volatile organic compounds. Estimation of total dermal absorption from exhaled breath measurements requires modeling, a task to which physiologically based pharmacokinetic (PBPK) models have often been applied. In the context of PBPK models, the exposed skin compartment can be modeled in many different ways. To demonstrate potential effects of alternative skin models on overall PBPK model performance, alternative models of skin have been incorporated in a PBPK model used to predict chloroform in breath during and after immersion in aqueous solution. The models investigated include treatment of skin as both a homogeneous phase and as a membrane in which concentration varies with depth. Model predictions are compared with in vivo human experimental results reported in the prior literature. In the example chosen, the common practice of modeling skin as a homogenous phase leads to prediction of more rapid initial uptake and lower cumulative uptake than does modeling skin as a membrane. Numerical estimates of the permeability coefficient are shown to be dependent upon skin model form and temperature of the aqueous solution.

Biologic monitoring to characterize organophosphorus pesticide exposure among children and workers: an analysis of recent studies in Washington State.

We examined findings from five organophosphorus pesticide biomonitoring studies conducted in Washington State between 1994 and 1999. We compared urinary dimethylthiophosphate (DMTP) concentrations for all study groups and composite dimethyl alkylphosphate (DMAP) concentrations for selected groups. Children of pesticide applicators had substantially higher metabolite levels than did Seattle children and farmworker children (median DMTP, 25 microg/L; p < 0.0001). Metabolite levels of children living in agricultural communities were elevated during periods of crop spraying. Median DMTP concentrations for Seattle children and farmworker children did not differ significantly (6.1 and 5.8 microg/L DMTP, respectively; p = 0.73); however, the DMAP concentrations were higher for Seattle children than for farmworker children (117 and 87 nmol/L DMAP, respectively; p = 0.007). DMTP concentrations of U.S. children 6-11 years of age (1999-2000 National Health and Nutrition Examination Survey population) were higher than those of Seattle children and farmworker children at the 75th, 90th, and 95th percentiles. DMTP concentrations for workers actively engaged in apple thinning were 50 times higher than DMTP concentrations for farmworkers sampled outside of peak exposure periods. We conclude that workers who have direct contact with pesticides should continue to be the focus of public health interventions and that elevated child exposures in agricultural communities may occur during active crop-spraying periods and from living with a pesticide applicator. Timing of sample collection is critical for the proper interpretation of pesticide biomarkers excreted relatively soon after exposure. We surmise that differences in dietary exposure can explain the similar exposures observed among farmworker children, children living in the Seattle metropolitan area, and children sampled nationally.

Child dermal sediment loads following play in a tide flat.

Dermal contact with sediment is sometimes identified as a pathway of concern in risk assessments. Dermal exposure to sediment is poorly characterized and exposure assessors may rely on default soil adherence values. The purpose of this study was to obtain sediment adherence data for a genuine exposure scenario, child play in a tide flat. This study reports direct measurements of sediment loadings on five body parts (face, forearms, hands, lower legs and feet) after play in a tide flat. Each of nine subjects participated in two timed sessions and pre- and post-activity sediment loading data were collected. Geometric mean (geometric standard deviation) dermal loadings (mg/cm(2)) on the face, forearm, hands, lower legs and feet for the combined sessions were 0.04 (2.9), 0.17 (3.1), 0.49 (8.2), 0.70 (3.6) and 21 (1.9), respectively. Participants' parents completed questionnaires regarding their child's typical activity patterns during tide flat play, exposure frequency and duration, clothing choices, bathing practices and clothes laundering. Data presented in this paper supplement very limited prior adherence data for sediment contact scenarios. Results will be useful to risk assessors considering exposure scenarios involving child activities at a coastal shoreline or tide flat.

Comparison of organophosphorus pesticide metabolite levels in single and multiple daily urine samples collected from preschool children in Washington State.

A total organophosphorus pesticide exposure study was conducted in Washington State in 1998 in a sample population of 13 children aged 2.5-5.5 years. The children were roughly split between rural and suburban populations and had been previously identified as having potentially elevated organophosphorus pesticide exposures. One component of the study was urine collection and analysis. Urine samples were collected from each subject up to four times in 24 h in two different seasons. Samples were collected at specific time points: before bed, first morning void, after lunch, and before dinner. Urine samples were analyzed initially for the six nonspecific dialkylphosphate (DAP) metabolites and subsequently for eight specific metabolites including malathion dicarboxylic acid (MDA), 3,5,6-trichloro-2-pyridinol (TCPy), and paranitrophenol (PNP). Relatively large percentages of the urine samples contained quantifiable amounts of two of the nonspecific DAP metabolites (DMTP-97%; DETP-67%), and three of the specific metabolites (MDA (71%), TCPy (79%), and PNP (96%)). A percent deviation analysis was employed to determine which of the spot sample time points was the best predictor of the estimated volume-weighted daily average. Of the four spot samples collected, first morning void samples were consistently found to be the best predictors of weighted-average daily metabolite concentration. This finding also held when the data were creatinine-adjusted. The results of this analysis suggest that if spot sampling is to be conducted as part of a biological monitoring study, first morning void samples should be preferentially collected.