Analysis of dermal exposure assessment in the US Environmental Protection Agency Toxic Substances Control Act risk evaluations of chemical manufacturing.

The United States Environmental Protection Agency (EPA) regulates chemical manufacture, import, processing, distribution, use, and disposal under the 2016 amended Toxic Substances Control Act (TSCA) for the purposes of protecting the public and sensitive populations-including workers-from chemical exposure risk. The publication of several TSCA risk evaluations provided a unique opportunity to evaluate the evolving regulatory approach for assessing the dermal exposure pathway in occupational settings. In this analysis, the occupational dermal exposure assessment methods employed in several TSCA risk evaluations were assessed. Specifically, a methodology review was conducted for the occupational dermal scenarios of manufacturing and feedstock use in the risk evaluations of three chlorinated organic chemicals: trichloroethylene, carbon tetrachloride, and perchloroethylene. Additionally, alternative exposure estimates were generated using the exposure model IH SkinPermTM. The review and alternative exposure analyses indicate that the current TSCA modeling approach may generate total dermal absorbed doses for chlorinated chemical manufacturing and feedstock use scenarios that are 2- to 20-fold higher than those generated by IH SkinPerm. Best-practice recommendations developed in the methodology review support a tiered, integrated approach to dermal exposure assessment that emphasizes collecting qualitative data; employing validated, peer-reviewed models that align with current industrial practices; and gathering empirical sampling data where needed. Collaboration among industry, EPA, and other stakeholders to share information and develop a standard approach to exposure assessment under TSCA would improve the methodological rigor of, and increase confidence in, the risk evaluation results.

PBPK modeling characterization of potential acute impairment effects from inhalation of ethanol during e-cigarette use.

Objective: Ethanol is used as a solvent for flavoring chemicals in some electronic cigarette (e-cigarette) liquids (e-liquids). However, there are limited data available regarding the effects of inhalation of ethanol on blood alcohol concentration (BAC) during e-cigarette use. In this study, a modified physiologically based pharmacokinetic (PBPK) model for inhalation of ethanol was used to estimate the BAC time-profile of e-cigarette users who puffed an e-liquid containing 23.5% ethanol. Materials and Methods: A modified PBPK model for inhalation of ethanol was developed. Use characteristics were estimated based on first-generation and second-generation e-cigarette topography parameters. Three representative use-case puffing profiles were modeled: a user that took many, short puffs; a typical user with intermediate puff counts and puff durations; and a user that took fewer, long puffs. Results and Discussion: The estimated peak BACs for these three user profiles were 0.22, 0.22, and 0.30 mg/L for first-generation devices, respectively, and 0.85, 0.58, and 0.34 mg/L for second-generation devices, respectively. Additionally, peak BACs for individual first-generation users with directly measured puffing parameters were estimated to range from 0.06 to 0.67 mg/L. None of the scenarios modeled predicted a peak BAC result that approached toxicological or regulatory thresholds that would be associated with physiological impairment (roughly 0.01% or 100 mg/L). Conclusions: The approach used in this study, combining a validated PBPK model for a toxicant with peer-reviewed topographical parameters, can serve as a screening-level exposure assessment useful for evaluation of the safety of e-liquid formulations. Abbreviations: BAC: blood alcohol concentration; e-cigarette: electronic cigarette; e-liquid: e-cigarette liquid or propylene glycol and/or vegetable glycerin-based liquid; HS-GC-FID: headspace gas chromatography with flame-ionization detection; HS-GC-MS: headspace gas chromatography-mass spectrometry; PBPK: physiologically based pharmacokinetic; Cair: puff concentration expressed as ppm; Cair,mass: ethanol air concentration expressed on a mass basis; Cv: ethanol concentration in the venous blood; ρ: density; EC: ethanol concentration in the liquid; PLC: liquid consumption per puff; PAV: air volume of the puff; Cair,mass: puff concentration expressed as ppm; MW: molecular weight; P: pressure; T: temperature; PK: pharmacokinetic.

Occupational survey of airborne metal exposures to welders, metalworkers, and bystanders in small fabrication shops.

The objective of this study was to characterize worker exposure to airborne metal and particulate matter in shops where multiple types of metalworking tasks were performed. The sampling strategy included full-shift and task-based personal samples on workers who performed flux-cored arc welding, personal samples on workers performing non-welding metalworking tasks, and area samples near welders, representing bystanders to welding. Size-fractionated particulate matter adjacent to welding activities was measured using real-time monitoring devices. Samples were analyzed for 21 individual metals, of which 8 were frequently detected. Exceedance fractions were calculated based on the distribution of results for each frequently detected metal. Exceedance fractions were <5% for all metals, except manganese (6% of the REL, 55% of the inhalable TLV-TWA and 91% of the respirable TLV-TWA) and iron oxide (10% of the REL and TLV-TWA) for Shop 1 bystander samples, manganese (68% for the inhalable TLV-TWA and 98% of the respirable TLV-TWA) for welder samples, and manganese (35% for the inhalable TLV-TWA and 80% of the respirable TLV-TWA) and iron oxide (12% for the PEL and 23% for the REL and TLV-TWA) for metalworker samples. Particulate matter concentrations measured at distances of 0.9-1.5 m and 2.1-2.7 m from the welder were within the same order of magnitude. The results of this study allow for comparison to health-based exposure limits for select individual components of welding fume with a low to medium degree of censorship.

Evaluation of take-home exposure to asbestos from handling asbestos-contaminated worker clothing following the abrasive sawing of cement pipe.

Although industrial uses of asbestos have declined since the 1970s, in recent years there has been a renewed interest in para-occupational ("take-home") exposure to these fibers. The aim of this study was to quantify the release of asbestos fibers, if any, during the shaking out of crocidolite- and chrysotile-contaminated clothing in a simulated at-home setting. An exposure study was conducted in which personal and area air samples were collected during the handling (i.e. shake-out) of work clothing (shirt and pants) previously worn by an operator who had cut asbestos-containing cement pipe. During eight "loading" events, the operator cut a historically representative asbestos-containing cement pipe (10% crocidolite and 25% chrysotile) using a powered abrasive saw. Subsequently, 30-minute air samples were collected during four "shake-out" events, each of which consisted of the handling of two complete sets of contaminated work clothes. Samples were analyzed in accordance with NIOSH methods 7400 and 7402. The mean phase contrast microscopy equivalent (PCME) airborne concentrations were 0.52 f/cc (SD = 0.34 f/cc) for total asbestos fibers, 0.36 f/cc (SD = 0.26 f/cc) for chrysotile and 0.17 f/cc (SD = 0.096 f/cc) for crocidolite. Based on likely estimates of the frequency of laundering activities, and assuming that the dusty clothing (1) is not blown off in the occupational setting using compressed air and (2) is not shaken out before entering the home, a family member handling the clothing could potentially have a lifetime cumulative exposure to chrysotile and crocidolite of approximately 0.20 f/cc-year and 0.096 f/cc-year, respectively.

Best-practices approach to determination of blood alcohol concentration (BAC) at specific time points: Combination of ante-mortem alcohol pharmacokinetic modeling and post-mortem alcohol generation and transport considerations.

Alcohol concentrations in biological matrices offer information regarding an individual's intoxication level at a given time. In forensic cases, the alcohol concentration in the blood (BAC) at the time of death is sometimes used interchangeably with the BAC measured post-mortem, without consideration for alcohol concentration changes in the body after death. However, post-mortem factors must be taken into account for accurate forensic determination of BAC prior to death to avoid incorrect conclusions. The main objective of this work was to describe best practices for relating ante-mortem and post-mortem alcohol concentrations, using a combination of modeling, empirical data and other qualitative considerations. The Widmark modeling approach is a best practices method for superimposing multiple alcohol doses ingested at various times with alcohol elimination rate adjustments based on individual body factors. We combined the selected ante-mortem model with a suggestion for an approach used to roughly estimate changes in BAC post-mortem, and then analyzed the available data on post-mortem alcohol production in human bodies and potential markers for alcohol production through decomposition and putrefaction. Hypothetical cases provide best practice approaches as an example for determining alcohol concentration in biological matrices ante-mortem, as well as potential issues encountered with quantitative post-mortem approaches. This study provides information for standardizing BAC determination in forensic toxicology, while minimizing real world case uncertainties.

Air monitoring of volatile organic compounds at relevant receptors during hydraulic fracturing operations in Washington County, Pennsylvania.

A 3-month air monitoring study was conducted in Washington County, Pennsylvania, at the request of local community members regarding the potential risks resulting from air emissions of pollutants related to hydraulic fracturing operations. Continuous air monitoring for total volatile organic compounds was performed at two sampling sites, including a school and a residence, located within 900 m of a hydraulic fracturing well pad that had been drilled prior to the study. Intermittent 24-hour air samples for 62 individual volatile organic compounds were also collected. The ambient air at both sites was monitored during four distinct periods of unconventional natural gas extraction activity: an inactive period prior to fracturing operations, during fracturing operations, during flaring operations, and during another inactive period after operations. The results of the continuous monitoring during fracturing and flaring sampling periods for total volatile organic compounds were similar to the results obtained during inactive periods. Total volatile organic compound 24-hour average concentrations ranged between 0.16 and 80 ppb during all sampling periods. Several individual volatile compounds were detected in the 24-hour samples, but they were consistent with background atmospheric levels measured previously at nearby sampling sites and in other areas in Washington County. Furthermore, a basic yet conservative screening level evaluation demonstrated that the detected volatile organic compounds were well below health-protective levels. The primary finding of this study was that the operation of a hydraulic fracturing well pad in Washington County did not substantially affect local air concentrations of total and individual volatile organic compounds.

Survey of 24-h personal formaldehyde exposures in geographically distributed urban office workers in the USA.

An air sampling study was conducted to evaluate personal formaldehyde exposures in a group of office workers spread across five geographical locations in the USA. Passive badge samples for formaldehyde were collected on three participants in each location, as well as in the office and home indoor microenvironments of each participant over 3 individual days. Median personal 24-h formaldehyde concentrations ranged from 9.9 to 18 µg/m3. Personal 24-h formaldehyde concentrations in one location were significantly higher than concentrations measured in the other four locations; no significant differences existed between any of the other locations. The participants in this study spent an average of 53% of their daily time in their homes, 36% at their office, and 11% in other indoor and outdoor locations. A comparison of measured 24-h personal formaldehyde concentrations and a model of average exposure based upon measured concentrations in the indoor microenvironments suggested that both the home and office formaldehyde concentrations were a strong predictor (R2 = 0.88) of overall personal exposure. The data from this study are representative of office workers in urban environments and can be used as background formaldehyde exposure levels (in the absence of specific sources) for both occupational and nonoccupational exposure assessments.

Characterization of airborne BTEX exposures during use of lawnmowers and trimmers.

Few studies have evaluated airborne exposures to benzene, toluene, ethylbenzene, and xylenes (BTEX) during operation of two-stroke and four-stroke small engines, such as those in lawn maintenance equipment. Full-shift, 8-hour personal samples were collected during a simulation study to characterize yard maintenance activities including mowing, trimming, and fueling. Short-term, 15-minute personal samples were collected to separately evaluate mowing and trimming exposures. Mean 8-hour time weighted average (TWA) BTEX concentrations were 2.3, 5.8, 0.91, and 4.6 ppb, respectively (n = 2). Mean 15-minute TWA BTEX concentrations were 1.6, 1.8, 0.22, and 1.3 ppb, respectively, during mowing and 1.2, 3.6, 0.68, and 3.3 ppb, respectively, during trimming (n = 3 per task). Measured BTEX concentrations during fueling were 20-110, 61-310, 8-41, and 40-203 ppb, respectively (n = 2, duration 2-3 minutes). These exposure concentrations were well below applicable US occupational exposure limits.

Evaluation of Personal Exposure to Surgical Smoke Generated from Electrocautery Instruments: A Pilot Study.

Hospital technician surgical smoke exposures during several types of electrocautery-based procedures were evaluated. Personal and area air sampling was performed for 106 individual analytes including ultrafine particulate matter (UFP), volatile organic compounds, polycyclic aromatic hydrocarbons, phenol, aldehydes, carbon monoxide, hydrogen sulfide, and hydrogen cyanide. Acetone, d-limonene, ethanol, ethyl acetate, and fluorene were measured in surgical suites at concentrations 1.1- to 3.7-fold higher than those observed in background. Benzene, α-pinene, methylene chloride, and n-hexane were measured in the absence of a detectable background concentration. All analytes were measured at concentrations that were <1% of the corresponding US federal and state 8-h permissible exposure limits (PELs), if PELs existed. Full-shift average UFP concentrations ranged from 773 to 2257 particles/cm3, approximately one order of magnitude higher than surgical suite background concentrations. A comparison of two breast reduction procedures suggested that the use of smoke evacuators reduced UFP exposure by 6-fold. We concluded that selection and evaluation of key hazards, particularly UFP, under a variety of experimental conditions would be beneficial to elucidate potential health effects and causes osf employee complaints. Recommendations for successful sampling campaigns in future surgical smoke occupational exposure studies are provided. We also recommend the continued use of engineering controls, local exhaust ventilation, and surgical N95 respirators to reduce personal exposures to UFP in surgical smoke.