Last data update: Apr 18, 2025. (Total: 49119 publications since 2009)
Records 1-30 (of 43 Records) |
Query Trace: Snawder J[original query] |
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Correlation between graphitic carbon and elemental carbon in diesel particulate matter in workplace atmospheres
Zheng L , Birch ME , Johnson B , Breitenstein M , Snawder J , Kulkarni P . Anal Chem 2023 95 (6) 3283-3290 We investigated the suitability of the graphitic carbon (GC) content of diesel particulate matter (DPM), measured using Raman spectroscopy, as a surrogate measure of elemental carbon (EC) determined by thermal optical analysis. The Raman spectra in the range of 800-1800 cm(-1) (including the D mode at ∼1322 cm(-1) and the G mode at ∼1595 cm(-1)) were used for GC identification and quantification. Comparison of the Raman spectra for two certified DPM standards (NIST SRM 1650 and SRM 2975), two types of diesel engine exhaust soot, and three types of DPM-enriched workplace aerosols show that the uncertainty of GC quantification based on the D peak height, G peak height, and the total peak area below D and G peaks was about 6.0, 6.7, and 6.9%, respectively. The low uncertainty for different aerosol types suggested possible use of GC as a surrogate measure of EC in workplace atmospheres. A calibration curve was constructed using two laboratory-aerosolized DPM standards to describe the relationship between GC measured by a portable Raman spectrometer and the EC concentration determined by NIOSH Method 5040. The calibration curve was then applied to determine GC-based estimates of the EC contents of diesel engine exhaust samples from two vehicles and seven air samples collected at a hydraulic fracturing worksite. The GC-EC estimates obtained through Raman measurements agreed well with those found by NIOSH Method 5040 for the same samples at EC filter loadings below 2.86 μg/cm(2). The study shows that using an appropriate sample collection method that avoids high filter mass loadings, onsite measurement of GC by a portable or hand-held Raman spectrometer can provide a useful indicator of EC in workplace aerosol. |
Exposure monitoring strategies for applying low-cost pm sensors to assess flour dust in industrial bakeries
Ruiter S , Bard D , Ben Jeddi H , Saunders J , Snawder J , Warren N , Gorce JP , Cauda E , Kuijpers E , Pronk A . Ann Work Expo Health 2023 67 (3) 379-391 Low-cost particulate matter (PM) sensors provide new methods for monitoring occupational exposure to hazardous substances, such as flour dust. These devices have many possible benefits, but much remains unknown about their performance for different exposure monitoring strategies in the workplace. We explored the performance of PM sensors for four different monitoring strategies (time-weighted average and high time resolution, each quantitative and semi-quantitative) for assessing occupational exposure using low-cost PM sensors in a field study in the industrial bakery sector. Measurements were collected using four types of sensor (PATS+, Isensit, Airbeam2, and Munisense) and two reference devices (respirable gravimetric samplers and an established time-resolved device) at two large-scale bakeries, spread over 11 participants and 6 measurement days. Average PM2.5 concentrations of the low-cost sensors were compared with gravimetric respirable concentrations for 8-h shift periods and 1-min PM2.5 concentrations of the low-cost sensors were compared with time-resolved PM2.5 data from the reference device (quantitative monitoring strategy). Low-cost sensors were also ranked in terms of exposure for 8-h shifts and for 15-min periods with a shift (semi-quantitative monitoring strategy). Environmental factors and methodological variables, which can affect sensor performance, were investigated. Semi-quantitative monitoring strategies only showed more accurate results compared with quantitative strategies when these were based on shift-average exposures. The main factors that influenced sensor performance were the type of placement (positioning the devices stationary versus personal) and the company or workstation where measurements were collected. Together, these findings provide an overview of common strengths and drawbacks of low-cost sensors and different ways these can be applied in the workplace. This can be used as a starting point for further investigations and the development of guidance documents and data analysis methods. |
The Challenge for industrial hygiene 4.0: A NIOSH perspective on direct-reading methodologies and real-time monitoring in occupational environments
Cauda E , Snawder J , Spinazz , Cattaneo A , Howard J , Cavallo D . Synergist 2022 33 (2) 32-35 ![]() Direct-reading methodologies and real-time monitors will play a crucial role in workers' health and safety in the context of the Fourth Industrial Revolution. This article proposes that these technologies and other advancements will lead to a new stage of industrial hygiene, which may be called IH4.0. The Fourth Industrial Revolution is a way of describing the blurring of boundaries between the physical, digital, and biological worlds. There are several definitions for this revolution, but they all recognize the critical importance of data. Everyday life is already affected by data generated in different environments, some occupational and some not. The impact of data will become even more significant in the future, considering the characteristics of what is known as "Big Data." These characteristics are the high volume of data; the elevated velocity with which the data is generated; the variety of data of different natures; and the usefulness or value of collecting and modeling data. Even as IH4.0, industrial hygiene will continue to be organized according to the principles of anticipation, recognition, evaluation, and control (AREC). But like many other workplace activities, such as production, management, and quality control, industrial hygiene will be revolutionized by data. The profession has an opportunity and a responsibility to evolve because of a new understanding of data. |
Self-reported exposure to hazards and mitigation strategies among oil and gas extraction workers in 3U.S. states
Wingate KC , Scott KA , Pratt S , King B , Esswein EJ , Ramirez-Cardenas A , Snawder J , Hagan-Haynes K . J Occup Environ Hyg 2022 19 1-22 Numerous health and safety hazards exist at U.S. onshore oil and gas extraction worksites. Higher fatal injury rates have been reported among drilling and servicing companies, which are more likely to employ workers in construction and extraction occupations, compared to operators that employ more workers in management and office and administrative support roles. However, there is little information describing the extent to which workers encounter these hazards, are provided hazard mitigation strategies by their employers, or use personal protective equipment (PPE). A cross-sectional survey of 472 U.S. oil and gas extraction workers was conducted to identify and characterize factors related to on-the-job fatalities, injuries, and illnesses and determine the health and safety concerns of workers. Workers were employed by servicing companies (271/472, 57.4%), drilling contractors (106/472, 22.5%), and operators (95/472, 20.1%). The likelihood of contact with hazardous substances varied by substance and company type. Drilling and servicing employees had significantly higher odds of self-reported contact with pipe dope (OR(drilling)=10.07, 95% CI: 1.74-63.64; OR(servicing)=5.95, 95% CI: 2.18-18.34), diesel exhaust (OR(drilling)=2.28, 95% CI: 1.15-5.05; OR(servicing)=4.93, 95% CI: 2.73-10.32), and drilling mud (OR(drilling)=24.36, 95% CI: 4.45-144.69; OR(servicing)=3.48, 95% CI: 1.24-12.20), compared to operators. Safety policies, programs, and trainings were commonly reported by workers, although substance-specific training (e.g., respirable crystalline silica hazards) was less common. Differences in self-reported employer PPE requirements and worker use of PPE when needed or required for safety highlight a need for novel strategies to improve use of PPE. Overall, this study highlights differences in work conditions by company type and uncovers gaps in employer administrative controls and PPE use. |
On the road again: A cross-sectional survey examining work schedules, commuting time, and driving-related outcomes among U.S. oil and gas extraction workers
Hagan-Haynes K , Ramirez-Cardenas A , Wingate KC , Pratt S , Ridl S , Schmick E , Snawder J , Dalsey E , Hale C . Am J Ind Med 2022 65 (9) 749-761 BACKGROUND: Oil and gas extraction (OGE) workers in the United States experience high fatality rates, with motor vehicle crashes the leading cause of death. Land-based OGE workers drive frequently to remote and temporary worksites. Limited information is available on factors that may influence crash risk for this workforce. METHODS: A cross-sectional survey of 500 land-based OGE workers examined work schedules and hours, commuting, sleep, employer policies, and their relationship to potentially harmful events while driving. RESULTS: Over 60% of participants worked 12 or more hours per day. The mean daily roundtrip commuting time was 1.82 h. Longer daily commutes, nonstandard work schedules, less sleep on workdays, and lack of employer policies were associated with one or more risky driving-related outcomes. CONCLUSIONS: Implementation and evaluation of OGE employer policies and programs to limit long work hours, reduce long daily commutes, promote sufficient sleep, and reduce drowsy driving among U.S. OGE workers are needed. |
Impact of ergonomic posture on the chemical exposure of workers in the petroleum and chemical industry
Whitehead C , Maier MA , Rao MB , Eturki M , Snawder JE , Davis KG . Ann Work Expo Health 2022 66 (8) 1022-1032 OBJECTIVES: Despite a rise in automation, workers in the petroleum refining and petrochemical manufacturing industry are potentially exposed to various chemicals through inhalation while performing routine job duties. Many factors contribute to the degree of exposure experienced in this setting. The study objective was to characterize the impact of workplace conditions, anthropometric variability, and task orientation on exposure for a simulated routine operations task. METHODS: A chemical exposure laboratory simulation study was designed to evaluate the dependent variable of chemical exposure level in the breathing zone for methane and sulfur hexafluoride. The independent variables were (i) posture of the worker, (ii) worker anthropometry, (iii) process configuration, and (iv) gas density. RESULTS: Pipe height was a significant predictor of gas concentration measured in the breathing zone when located in a position that encouraged the gas to enter the breathing zone of the worker. Worker anthropometry had a major impact; tall worker's (male) chemical concentrations exceeded those of the short worker (female) for methane simulations but the opposite resulted for sulfur hexafluoride. Also, worker posture had a significant impact on gas exposure where nonneutral postures were found to have higher levels of chemical concentration. CONCLUSIONS: The study findings indicate that the breathing zone location is altered by posture and worker height, which changes the exposures relative to the emission source depending on the gas density of the chemicals that are present. As a result, qualitative risk assessment cannot be performed accurately without accounting for these factors. Practically, controls may need to account for worker size differences and posture adaptations. |
Exposure assessment of polycyclic aromatic hydrocarbons in refined coal tar sealant applications
McCormick S , Snawder JE , Chen IC , Slone J , Calafat AM , Wang Y , Meng L , Alexander-Scott M , Breitenstein M , Johnson B , Meadows J , Fairfield Estill C . Int J Hyg Environ Health 2022 242 113971 BACKGROUND: Refined coal tar sealant (RCTS) emulsions are used to seal the surface of asphalt pavement. Nine of the 22 polycyclic aromatic hydrocarbons (PAHs) evaluated in this study are classified as known, probable, or possible human carcinogens. Exposure assessment research for RCTS workers has not been published previously. OBJECTIVES: The overall objective of this study was to develop a representative occupational exposure assessment of PAH exposure for RCTS workers based on worksite surveys. The specific aims were to: 1) quantify full-shift airborne occupational exposures to PAHs among RCTS workers; 2) quantify workers' dermal exposures to PAHs; 3) quantify biomarkers of PAH exposure in workers' urine; 4) identify specific job titles associated with RCTS exposure; and 5) apply these results to a biological exposure index to assess risk of potential genotoxicity from occupational exposures. METHODS: A total of twenty-one RCTS workers were recruited from three companies. Personal and area air samples were collected using a modification of NIOSH Method 5515. Dermal exposure was assessed by hand and neck wipes before and after shifts. Twenty-two PAHs were quantified via gas chromatography-mass spectrometry selected ion monitoring. Internal dose was estimated by quantifying select PAH metabolites in pre- and post-shift urine samples using on-line solid phase extraction-high performance liquid chromatography-tandem mass spectrometry. RESULTS: PAH levels in the worker breathing zones were highest for naphthalene, acenaphthene, and phenanthrene, with geometric means of 52.1, 11.4, and 9.8 μg/m(3), respectively. Hand wipe levels of phenanthrene, fluoranthene and pyrene were the highest among the 22 PAHs with geometric means of 7.9, 7.7, and 5.5 μg/cm(2), respectively. Urinary PAH biomarkers for naphthalene, fluorene, phenanthrene, and pyrene were detected in all workers and were higher for post-shift samples than those collected pre-shift. Urinary concentrations of the metabolite 1-hydroxypyrene were greater than the American Conference of Governmental Industrial Hygienists (ACGIH) Biological Exposure Index (BEI) for this metabolite in 89 percent of post-shift samples collected on the final day of the work week or field survey. Statistically significances were found between concentrations of fluorene, naphthalene, and phenanthrene in the breathing zone of workers and their corresponding urinary PAH biomarkers. Workers were placed in two work place exposure groups: applicators and non-applicators. Applicators had higher total PAH concentrations in personal breathing zone (PBZ) air samples than non-applicators and were more likely to have post-shift hand wipe concentrations significantly higher than pre-shift concentrations. Concentrations of post-shift urinary biomarkers were higher, albeit not significantly, for applicators than non-applicators. CONCLUSIONS: The exposure results from RCTS worker samples cannot be explained by proximal factors such as nearby restaurants or construction. Air and skin concentration levels were substantially higher for RCTS workers than previously published levels among asphalt workers for all PAHs. PAH profiles on skin wipes were more consistent with RCTS sealant product than air samples. Last day post-shift urinary concentrations of 1-hydroxypyrene greatly exceeded the ACGIH BEI benchmark of 2.5 μg/L in 25 of 26 samples, which suggests occupational exposure and risk of genotoxicity. When pyrene and benzo[a]pyrene were both detected, concentration ratios from personal exposure samples were used to calculate the adjusted BEI. Concentrations of 1-hydroxypyrene exceeded the adjusted BEIs for air, hand wipes, and neck wipes in most cases. These results indicate the need to increase safety controls and exposure mitigation for RCTS workers. |
Advanced sensor technologies and the future of work
Howard J , Murashov V , Cauda E , Snawder J . Am J Ind Med 2021 65 (1) 3-11 Exposure science is fundamental to the field of occupational safety and health. The measurement of worker exposures to hazardous agents informs effective workplace risk mitigation strategies. The modern era of occupational exposure measurement began with the invention of the personal sampling device, which is still widely used today in the practice of occupational hygiene. Newer direct-reading sensor devices are incorporating recent advances in transducers, nanomaterials, electronics miniaturization, portability, batteries with high-power density, wireless communication, energy-efficient microprocessing, and display technology to usher in a new era in exposure science. Commercial applications of new sensor technologies have led to a variety of health and lifestyle management devices for everyday life. These applications are also being investigated as tools to measure occupational and environmental exposures. As the next-generation placeable, wearable, and implantable sensor technologies move from the research laboratory to the workplace, their role in the future of work will be of increasing importance to employers, workers, and occupational safety and health researchers and practitioners. This commentary discusses some of the benefits and challenges of placeable, wearable, and implantable sensor technologies in the future of work. |
Aerosol analysis using handheld raman spectrometer: On-site quantification of trace crystalline silica in workplace atmospheres
Wei S , Johnson B , Breitenstein M , Zheng L , Snawder J , Kulkarni P . Ann Work Expo Health 2021 66 (5) 656-670 A method for aerosol chemical analysis using handheld Raman spectrometer has been developed and its application to measurement of crystalline silica concentration in workplace atmosphere is described. The approach involves collecting aerosol as a spot sample using a wearable optical aerosol monitor, followed by direct-on-filter quantitative analysis of the spot sample for crystalline silica using handheld Raman spectrometer. The filter cassette of a commercially available optical aerosol monitor (designed to collect aerosol for post-shift analysis) was modified to collect 1.5-mm-diameter spot sample, which provided adequate detection limits for short-term measurements over a few tens of minutes or hours. The method was calibrated using aerosolized α-quartz standard reference material in the laboratory. Two Raman spectrometers were evaluated, one a handheld unit (weighing less than 410 g) and the other a larger probe-based field-portable unit (weighing about 5 kg). The lowest limit of quantification for α-quartz of 16.6 μg m-3 was obtained using the handheld Raman unit at a sample collection time of 1 h at 0.4 l min-1. Short-term measurement capability and sensitivity of the Raman method were demonstrated using a transient simulated workplace aerosol. Workplace air and personal breathing zone concentrations of crystalline silica of workers at a hydraulic fracturing worksite were measured using the Raman method. The measurements showed good agreement with the co-located samples analyzed using the standard X-ray powder diffraction (XRD) method, agreeing within 0.15-23.2% of each other. This magnitude of difference was comparable to the inter- and intra-laboratory analytical precision of established XRD and infrared methods. The pilot study shows that for silica-containing materials studied in this work it is possible to obtain quantitative measurements with good analytical figures of merit using handheld or portable Raman spectrometers. Further studies will be needed to assess matrix interferences and measurement uncertainty for several other types of particle matrices to assess the broader applicability of the method. |
Occupational safety and health and illicit opioids: State of the research on protecting against the threat of occupational exposure
Alexander-Scott M , Greenawald L , Chiu S , Broadwater K , Hirst D , Snawder J , Roberts J , Weber A , Knuth M . New Solut 2021 31 (3) 315-329 The nationwide opioid crisis continues to affect not only people who use opioids but also communities at large by increasing the risk of accidental occupational exposure to illicit opioids. In addition, the emergence of highly potent synthetic opioids such as fentanyl and carfentanil increases the need to protect workers who may encounter unknown drug substances during job activities. To support the National Institute for Occupational Safety and Health Opioids Research Gaps Working Group, we examined the state of the literature concerning methods to protect workers against accidental occupational exposure to illicit opioids, and have identified unmet research needs concerning personal protective equipment, decontamination methods, and engineering controls. Additional studies are needed to overcome gaps in technical knowledge about personal protective equipment, decontamination, and control methods, and gaps in understanding how these measures are utilized by workers. Increasing our knowledge of how to protect against exposure to illicit opioids has the potential to improve occupational health across communities. |
An optimized method for sample collection, extraction, and analysis of fentanyl and fentanyl analogs from a non-porous surface
Ciesielski AL , Wagner JR , Alexander-Scott M , Snawder J . Talanta 2021 228 122210 Illicit use of the potent opioid fentanyl and its analogs (fentanyls) are on the rise in the United States. As use increases, drug production tends to also increase, leading to more locations being contaminated with the potentially lethal substance. Because fentanyl-contaminated locations may present a risk to the general public, a method for sampling, identifying, and quantitating these fentanyls from surfaces is in need. This research developed and optimized a surface-wipe collection and extraction method for 17 fentanyls and 10 common fentanyl adulterants from a non-porous surface and quantitated the amount of each compound collected with liquid chromatography tandem mass spectrometry. The final, optimized surface-wipe method resulted in an average collection and extraction efficiency (±SD) of 62.0 (±14.0)%, with a range of 34.1 (±2.6) – 82.5 (±9.6)%. While legislation has yet to be implemented regarding remediation levels for fentanyl-contaminated locations, when such legislation is drafted, this method can be implemented to determine the safety of these locations prior to and after decontamination has occurred. |
Surface contamination generated by "one-pot" methamphetamine production
Ciesielski AL , Wagner JR , Alexander-Scott M , Smith J , Snawder J . J Chem Health Saf 2021 28 (1) 49-54 Methamphetamine production is the most common form of illicit drug manufacture in the United States. The "one-pot"method is the most prevalent methamphetamine synthesis method and is a modified Birch reduction, reducing pseudoephedrine with lithium and ammonia gas generated in situ. This research examined the amount of methamphetamine surface contamination generated by one-pot syntheses or "cooks", as well as the effectiveness of hosing with water as a simplified decontamination technique, to assess associated public health and environmental consequences. Concentrations of methamphetamine contamination were examined prior to production, after production, and after decontamination with water. Contamination was qualitatively field screened using lateral flow immunoassays and quantitatively assessed using a fluorescence covalent microbead immunosorbent assay. Following screening, 0 of 23 pre-cook samples, 29 of 41 post-cook samples, and 5 of 27 post-decontamination samples were positive. Quantitatively, one pre-cook sample had a methamphetamine concentration of 1.36 ng/100 cm2. Post-cook and post-decontamination samples had average methamphetamine concentrations of 26.50 ± 63.83 and 6.22 ± 12.17 ng/100 cm2, respectively. While all one-pot methamphetamine laboratories generate different amounts of waste, depending on the amount of precursors used and whether the reaction vessel remained uncompromised, this study examined the surface contamination generated by a popular one-pot method known to law enforcement. By understanding the amount of surface contamination generated by common methods of one-pot methamphetamine production and the effectiveness of decontamination techniques used to remediate them, health risks associated with these production sites can be better understood and environmental contamination can be mitigated. |
Exploring evaluation variables for low-cost particulate matter monitors to assess occupational exposure
Ruiter S , Kuijpers E , Saunders J , Snawder J , Warren N , Gorce JP , Blom M , Krone T , Bard D , Pronk A , Cauda E . Int J Environ Res Public Health 2020 17 (22) Background: Small, lightweight, low-cost optical particulate matter (PM) monitors are becoming popular in the field of occupational exposure monitoring, because these devices allow for real-time static measurements to be collected at multiple locations throughout a work site as well as being used as wearables providing personal exposure estimates. Prior to deployment, devices should be evaluated to optimize and quantify measurement accuracy. However, this can turn out to be difficult, as no standardized methods are yet available and different deployments may require different evaluation procedures. To gain insight in the relevance of different variables that may affect the monitor readings, six PM monitors were selected based on current availability and evaluated in the laboratory; (2) Methods: Existing strategies that were judged appropriate for the evaluation of PM monitors were reviewed and seven evaluation variables were selected, namely the type of dust, within- and between-device variations, nature of the power supply, temperature, relative humidity, and exposure pattern (peak and constant). Each variable was tested and analyzed individually and, if found to affect the readings significantly, included in a final correction model specific to each monitor. Finally, the accuracy for each monitor after correction was calculated; (3) Results: The reference materials and exposure patterns were found to be main factors needing correction for most monitors. One PM monitor was found to be sufficiently accurate at concentrations up to 2000 µg/m(3) PM(2.5), with other monitors appropriate at lower concentrations. The average accuracy increased by up to three-fold compared to when the correction model did not include evaluation variables; (4) Conclusions: Laboratory evaluation and readings correction can greatly increase the accuracy of PM monitors and set boundaries for appropriate use. However, this requires identifying the relevant evaluation variables, which are heavily reliant on how the monitors are used in the workplace. This, together with the lack of current consensus on standardized procedures, shows the need for harmonized PM monitor evaluation methods for occupational exposure monitoring. |
Biological effects of inhaled hydraulic fracturing sand dust. IX. Summary and significance
Anderson SE , Barger M , Batchelor TP , Bowers LN , Coyle J , Cumpston A , Cumpston JL , Cumpston JB , Dey RD , Dozier AK , Fedan JS , Friend S , Hubbs AF , Jackson M , Jefferson A , Joseph P , Kan H , Kashon ML , Knepp AK , Kodali V , Krajnak K , Leonard SS , Lin G , Long C , Lukomska E , Marrocco A , Marshall N , Mc Kinney W , Morris AM , Olgun NS , Park JH , Reynolds JS , Roberts JR , Russ KA , Sager TM , Shane H , Snawder JE , Sriram K , Thompson JA , Umbright CM , Waugh S , Zheng W . Toxicol Appl Pharmacol 2020 409 115330 An investigation into the potential toxicological effects of fracking sand dust (FSD), collected from unconventional gas drilling sites, has been undertaken, along with characterization of their chemical and biophysical properties. Using intratracheal instillation of nine FSDs in rats and a whole body 4-d inhalation model for one of the FSDs, i.e., FSD 8, and related in vivo and in vitro experiments, the effects of nine FSDs on the respiratory, cardiovascular and immune systems, brain and blood were reported in the preceding eight tandem papers. Here, a summary is given of the key observations made in the organ systems reported in the individual studies. The major finding that inhaled FSD 8 elicits responses in extra-pulmonary organ systems is unexpected, as is the observation that the pulmonary effects of inhaled FSD 8 are attenuated relative to forms of crystalline silica more frequently used in animal studies, i.e., MIN-U-SIL®. An attempt is made to understand the basis for the extra-pulmonary toxicity and comparatively attenuated pulmonary toxicity of FSD 8. |
Biological effects of inhaled hydraulic fracturing sand dust. II. Particle characterization and pulmonary effects 30 d following intratracheal instillation
Fedan JS , Hubbs AF , Barger M , Schwegler-Berry D , Friend SA , Leonard SS , Thompson JA , Jackson MC , Snawder JE , Dozier AK , Coyle J , Kashon ML , Park JH , McKinney W , Roberts JR . Toxicol Appl Pharmacol 2020 409 115282 Hydraulic fracturing ("fracking") is used in unconventional gas drilling to allow for the free flow of natural gas from rock. Sand in fracking fluid is pumped into the well bore under high pressure to enter and stabilize fissures in the rock. In the process of manipulating the sand on site, respirable dust (fracking sand dust, FSD) is generated. Inhalation of FSD is a potential hazard to workers inasmuch as respirable crystalline silica causes silicosis, and levels of FSD at drilling work sites have exceeded occupational exposure limits set by OSHA. In the absence of any information about its potential toxicity, a comprehensive rat animal model was designed to investigate the bioactivities of several FSDs in comparison to MIN-U-SIL® 5, a respirable α-quartz reference dust used in previous animal models of silicosis, in several organ systems (Fedan, J.S., Toxicol Appl Pharmacol. 00, 000-000, 2020). The present report, part of the larger investigation, describes: 1) a comparison of the physico-chemical properties of nine FSDs, collected at drilling sites, and MIN-U-SIL® 5, a reference silica dust, and 2) a comparison of the pulmonary inflammatory responses to intratracheal instillation of the nine FSDs and MIN-U-SIL® 5. Our findings indicate that, in many respects, the physico-chemical characteristics, and the biological effects of the FSDs and MIN-U-SIL® 5 after intratracheal instillation, have distinct differences. |
Health effects from unintentional occupational exposure to opioids among law enforcement officers: Two case investigations
Chiu SK , Hornsby-Myers JL , de Perio MA , Snawder JE , Wiegand DM , Trout D , Howard J . Am J Ind Med 2019 62 (5) 439-447 Recent increases in the rate of drug overdose-related deaths, the emergence of potent opioids such as carfentanil, and media reports of incidents have raised concerns about the potential for work-related exposure to a variety of illicit drugs among law enforcement officers (LEOs), other emergency responders, and other workers in the United States. To characterize the risk associated with unintentional occupational exposure to drugs, we retrospectively investigated two incidents that occurred in 2017 and 2018 where LEOs were exposed to opioid and stimulant drugs and experienced health effects. We interviewed five affected LEOs and others. We reviewed records, including emergency department documentation, incident reports, forensic laboratory results, and when available, body camera footage. Multiple drug types, including opioids and nonopioids, were present at each incident. Potential routes of exposure varied among LEOs and were difficult to characterize with certainty. Health effects were not consistent with severe, life-threatening opioid toxicity, but temporarily precluded affected LEOs from performing their essential job duties. While health risks from occupational exposure to drugs during law enforcement activities cannot currently be fully characterized with certainty, steps to prevent such exposures should be implemented now. The creation and implementation of appropriate controls plus education and training are both important to protecting first responders from these hazardous agents. To more fully characterize potential exposures, timely prospective toxicological evaluation of affected responders is recommended. |
(1 3) beta-Glucan induces multimodal toxicity responses in parallel exposures of model human lung epithelial cells and immature macrophage
Turner J , McCabe K , Snawder J , Hernandez M . Air Qual Atmos Health 2018 12 (4) 379-387 Many epidemiological studies have associated bioaerosol exposures with a variety of adverse health effects; however, the role of bioaerosol components in the development and manifestation of hypersensitivity and non-infectious respiratory diseases remains unclear. Despite many studies which have examined allergic responses to bioaerosols, less is known about non-allergenic effects. In order to elucidate the mechanisms by which bioaerosols can exert non-atopic stresses on a cellular level, there is a need for improving existing in vitro approaches. In response, a cohort of toxicology assays were optimized to create a robust analytical suite for studying the effects that biogenic atmospheric pollutants generate on two model human lung cell lines (A549 epithelial line and GDM-1 immature macrophage line). To demonstrate the utility for studying the cellular responses to select bioaerosols, cells exposed to curdlan (a linear (1 3)--glucan) were examined in a composite cytometry platform. Results suggest that curdlan has the potential to elicit significant responses in A549 and GDM-1 in two or more toxicological modes associated with exposure to airborne particulate matter. As designed, this suite provided a more powerful tool for characterizing curdlan-induced toxicological potential than any individual assay. Responses to curdlan were distinctly modal and cell line dependent, suggesting that the use of a suite of toxicological assays, in a common platform on different cell lines, can help provide important insights into the formative toxigenic responses that primary bioaerosols can induce in respiratory cells. |
Field evaluation of onsite near real-time monitors for surface contamination by 5-fluorouracil
Smith JP , Sammons D , Robertson S , Krieg E , Snawder J . J Oncol Pharm Pract 2018 25 (5) 1152-1159 Objectives In order to produce near real-time onsite results to detect surface contamination by antineoplastic drugs, the National Institute for Occupational Safety and Health developed monitors for 5-fluorouracil, which use surface wiping and lateral flow immunoassay for measurement. The monitors were tested in the laboratory to assess the sensitivity of detection on laboratory-produced contaminated surfaces. A field evaluation to assess the capability of the monitors to make measurements in healthcare workplaces was carried out in collaboration with a medical device company and the results are presented in this report. Methods The 5-fluorouracil monitor was evaluated in areas where oncology drugs were prepared and administered to patients at five different hospitals. The levels of contamination measured with the monitors were compared to levels measured with liquid chromatography-tandem mass spectrometry. Results The 5-fluorouracil values measured with the liquid chromatography-tandem mass spectrometry ranged from 0 to over 200,000 ng/100 cm(2). Measurements by the 5-fluorouracil monitors in the range 10-100 ng/100 cm(2) correlated with the liquid chromatography-tandem mass spectrometry. Receiver operating characteristic curves developed for the data indicated that a positive limit of 22 ng/100 cm(2) would give an acceptable level of false-positives while retaining most true-positive samples. If the liquid chromatography-tandem mass spectrometry measured greater than 100 ng/100 cm(2), then the monitors also measured levels greater than 100 ng/100 cm(2) for the majority of samples. Conclusion The data indicate that there are many areas in hospitals that are contaminated with 5-fluorouracil and the monitors will be useful in identifying this contamination. |
Measurement of area and personal breathing zone concentrations of diesel particulate matter (DPM) during oil and gas extraction operations, including hydraulic fracturing
Esswein EJ , Alexander-Scott M , Snawder J , Breitenstein M . J Occup Environ Hyg 2017 15 (1) 0 Diesel engines serve many purposes in modern oil and gas extraction activities. Diesel particulate matter (DPM) emitted from diesel engines is a complex aerosol that may cause adverse health effects depending on exposure dose and duration. This study reports on personal breathing zone (PBZ) and area measurements for DPM (expressed as elemental carbon) during oil and gas extraction operations including drilling, completions (which includes hydraulic fracturing) and servicing work. Researchers at the National Institute for Occupational Safety and Health (NIOSH) collected 104 full-shift air samples (49 PBZ and 55 area) in Colorado, North Dakota, Texas, and New Mexico during a four year period from 2008-2012 The arithmetic mean (AM) of the full shift TWA PBZ samples was 10 microg/m3; measurements ranged from 0.1 to 52 microg/m3. The geometric mean (GM) for the PBZ samples was 7 microg/m3. The AM of the TWA area measurements was 17 microg/m3 and ranged from 0.1 to 68 microg/m3. The GM for the area measurements was 9.5 microg/m3. Differences between the GMs of the PBZ samples and area samples were not statistically different (P>0.05). Neither the Occupational Safety and Health Administration (OSHA), NIOSH, nor the American Conference of Governmental Industrial Hygienists (ACGIH) have established occupational exposure limits (OEL) for DPM. However, the State of California, Department of Health Services lists a time-weighted average (TWA) OEL for DPM as elemental carbon (EC) exposure of 20 microg/m3. Five of 49 (10.2%) PBZ TWA measurements exceeded the 20 microg/m3 EC criterion. These measurements were collected on Sandmover and Transfer Belt (T-belt) Operators, Blender and Chemical Truck Operators, and Water Transfer Operators during hydraulic fracturing operations. Recommendations to minimize DPM exposures include elimination (locating diesel-driven pumps away from well sites), substitution, (use of alternative fuels), engineering controls using advanced emissions controls technologies, administrative controls (configuration of well sites), hazard communication and worker training. |
Enhanced performance of methamphetamine lateral flow cassettes using an electronic lateral flow reader
Smith JP , Sammons DL , Robertson SA , Snawder JE . J Occup Environ Hyg 2015 12 (1) 45-50 Surface contamination from methamphetamine in meth labs continues to be a problem. We had previously developed a lateral flow assay cassette for field detection of methamphetamine contamination that is commercially available and has been used by a number of groups to assess contamination. This cassette uses the complete disappearance of the test line as an end point for detection of 50 ng/100 cm2 of methamphetamine contamination for surface sampling with cotton swabs. In the present study, we further evaluate the response of the cassettes using an electronic lateral flow reader to measure the intensities of the test and control lines. The cassettes were capable of detecting 0.25 ng/ml for calibration solutions. For 100 cm2 ceramic tiles that were spiked with methamphetamine and wiped with cotton-tipped wooden swabs wetted in assay/sampling buffer, 1 ng/tile was detected using the reader. Semi-quantitative results can be produced over the range 0-10 ng/ml for calibration solutions and 0-25 ng/tile for spiked tiles using either a 4-parameter logistic fit of test line intensity versus concentration or spiked mass or the ratio of the control line to the test line intensity fit to concentration or spiked mass. Recovery from the tiles was determined to be about 30% using the fitted curves. Comparison of the control line to the test line was also examined as a possible visual detection end point and it was found that the control line became more intense than the test line at 0.5 to 1 ng/ml for calibration solutions or 1 to 2 ng/tile for spiked tiles. Thus the lateral flow cassettes for methamphetamine have the potential to produce more sensitive semi-quantitative results if an electronic lateral flow reader is used and can be more sensitive for detection if the comparison of the control line to the test line is used as the visual end point. |
A toxicology suite adapted for comparing parallel toxicity responses of model human lung cells to diesel exhaust particles and their extracts
Turner J , Hernandez M , Snawder JE , Handorean A , McCabe KM . Aerosol Sci Technol 2015 49 (8) 599-610 Epidemiological studies have shown that exposure to airborne particulate matter (PM) can be an important risk factor for some common respiratory diseases. While many studies have shown that PM exposures are associated with inflammatory reactions, the role of specific cellular responses in the manifestation of primary hypersensitivities and the progression of respiratory diseases remains unclear. In order to better understand mechanisms by which PM can exert adverse health effects, more robust approaches to support in vitro studies are warranted. In response to this need, a group of accepted toxicology assays was adapted to create an analytical suite for screening and evaluating the effects of important, ubiquitous atmospheric pollutants on two model human lung cell lines (epithelial and immature macrophage). To demonstrate the utility of this suite, responses to intact diesel exhaust particles (DEP) and mass-based equivalent doses of their organic extracts were examined. Results suggest that extracts have the potential to induce greater biological responses than those associated with their colloidal counterpart. Additionally, macrophage cells appear to be more susceptible to the cytotoxic effects of both intact DEP and their organic extract, than epithelial cells tested in parallel. As designed, the suite provided a more robust basis for characterizing toxicity mechanisms than the analysis of any individual assay. Findings suggest that cellular responses to PM are cell line dependent, and show that the collection and preparation of PM and/or their extracts have the potential to impact cellular responses relevant to screening fundamental elements of respiratory toxicity. |
Detection of 5-fluorouracil surface contamination in near real time
Smith JP , Sammons DL , Pretty JR , Kurtz KS , Robertson SA , DeBord DG , Connor TH , Snawder JE . J Oncol Pharm Pract 2015 22 (3) 396-408 OBJECTIVES: Contamination of workplace surfaces by antineoplastic drugs presents an exposure risk for healthcare workers. Traditional instrumental methods to detect contamination such as gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS) are sensitive and accurate but expensive and incapable of producing results in real time. This limits their utility in preventing worker exposure. We are currently developing monitors based on lateral flow immunoassay that can detect drug contamination in near real time. In this report, we describe the laboratory performance of a 5-fluorouracil (5-FU) monitor. METHODS: The monitor was evaluated by spiking ceramic, vinyl, composite, stainless steel, and glass surfaces of 100 cm2 area with 5-FU masses of 0, 5, 10, 25, 50, and 100 ng. The surface was sampled with a wetted cotton swab, the swab was extracted with buffer, and the resulting solution was applied to a lateral flow monitor. Two ways of evaluating the response of these monitors were used: an electronic method where a lateral flow reader was used for measuring line intensities, and a visual method where the intensity of the test line was visually compared to the control line. RESULTS: The 5-FU monitor is capable of detecting 10 ng/100 cm2 (0.1 ng/cm2) using the electronic reader and 25 ng/100 cm2 (0.25 ng/cm2) using the visual comparison method for the surfaces studied. The response of the monitors was compared to LC-MS/MS results for the same samples for validation and there was good correlation of the two methods but some differences in absolute response, especially at higher spiking levels for the surface samples. |
Detection and measurement of surface contamination by multiple antineoplastic drugs using multiplex bead assay
Smith JP , Sammons DL , Robertson SA , Pretty JR , DeBord DG , Connor TH , Snawder JE . J Oncol Pharm Pract 2014 22 (1) 60-7 OBJECTIVES: Contamination of workplace surfaces by antineoplastic drugs presents an exposure risk for healthcare workers. Traditional instrumental methods to detect contamination such as liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) are sensitive and accurate but expensive. Since immunochemical methods may be cheaper and faster than instrumental methods, we wanted to explore their use for routine drug residue detection for preventing worker exposure. METHODS: In this study we examined the feasibility of using fluorescence covalent microbead immunosorbent assay (FCMIA) for simultaneous detection and semi-quantitative measurement of three antineoplastic drugs (5-fluorouracil, paclitaxel, and doxorubicin). The concentration ranges for the assay were 0-1000 ng/ml for 5-fluorouracil, 0-100 ng/ml for paclitaxel, and 0-2 ng/ml for doxorubicin. The surface sampling technique involved wiping a loaded surface with a swab wetted with wash buffer, extracting the swab in storage/blocking buffer, and measuring drugs in the extract using FCMIA. RESULTS: There was no significant cross-reactivity between these drugs at the ranges studied indicated by a lack of response in the assay to cross analytes. The limit of detection (LOD) for 5-fluorouracil on the surface studied was 0.93 ng/cm2 with a limit of quantitation (LOQ) of 2.8 ng/cm2, the LOD for paclitaxel was 0.57 ng/cm2 with an LOQ of 2.06 ng/cm2, and the LOD for doxorubicin was 0.0036 ng/cm2 with an LOQ of 0.013 ng/cm2. CONCLUSION: The use of FCMIA with a simple sampling technique has potential for low cost simultaneous detection and semi-quantitative measurement of surface contamination from multiple antineoplastic drugs. |
Evaluation of some potential chemical exposure risks during flowback operations in unconventional oil and gas extraction: preliminary results
Esswein EJ , Snawder J , King B , Breitenstein M , Alexander-Scott M , Kiefer M . J Occup Environ Hyg 2014 11 (10) D174-84 Approximately 562,000 workers were employed in the U.S. oil and gas extraction industry in 2012; nearly half of those workers were employed by well servicing companies, which include companies that conduct hydraulic fracturing and flowback operations. To understand possible risks for chemical exposures in modern oil and gas extraction operations, the National Institute for Occupational Safety and Health (NIOSH) initiated the Field Effort to Assess Chemical Exposures in Oil and Gas Workers. Initial research identified exposure risks for respirable crystalline silica during hydraulic fracturing as an occupational health hazard. This report describes industrial hygiene sampling during flowback operations at six unconventional oil and gas extraction sites in Colorado and Wyoming during spring and summer 2013. The results are considered preliminary; additional exposure assessments are needed to better understand the range of possible exposures, risk factors, and controls during flowback operations. | |
Systemic exposure to PAHs and benzene in firefighters suppressing controlled structure fires
Fent KW , Eisenberg J , Snawder J , Sammons D , Pleil JD , Stiegel MA , Mueller C , Horn GP , Dalton J . Ann Occup Hyg 2014 58 (7) 830-45 Turnout gear provides protection against dermal exposure to contaminants during firefighting; however, the level of protection is unknown. We explored the dermal contribution to the systemic dose of polycyclic aromatic hydrocarbons (PAHs) and other aromatic hydrocarbons in firefighters during suppression and overhaul of controlled structure burns. The study was organized into two rounds, three controlled burns per round, and five firefighters per burn. The firefighters wore new or laundered turnout gear tested before each burn to ensure lack of PAH contamination. To ensure that any increase in systemic PAH levels after the burn was the result of dermal rather than inhalation exposure, the firefighters did not remove their self-contained breathing apparatus until overhaul was completed and they were >30 m upwind from the burn structure. Specimens were collected before and at intervals after the burn for biomarker analysis. Urine was analyzed for phenanthrene equivalents using enzyme-linked immunosorbent assay and a benzene metabolite (s-phenylmercapturic acid) using liquid chromatography/tandem mass spectrometry; both were adjusted by creatinine. Exhaled breath collected on thermal desorption tubes was analyzed for PAHs and other aromatic hydrocarbons using gas chromatography/mass spectrometry. We collected personal air samples during the burn and skin wipe samples (corn oil medium) on several body sites before and after the burn. The air and wipe samples were analyzed for PAHs using a liquid chromatography with photodiode array detection. We explored possible changes in external exposures or biomarkers over time and the relationships between these variables using non-parametric sign tests and Spearman tests, respectively. We found significantly elevated (P < 0.05) post-exposure breath concentrations of benzene compared with pre-exposure concentrations for both rounds. We also found significantly elevated post-exposure levels of PAHs on the neck compared with pre-exposure levels for round 1. We found statistically significant positive correlations between external exposures (i.e. personal air concentrations of PAHs) and biomarkers (i.e. change in urinary PAH metabolite levels in round 1 and change in breath concentrations of benzene in round 2). The results suggest that firefighters wearing full protective ensembles absorbed combustion products into their bodies. The PAHs most likely entered firefighters' bodies through their skin, with the neck being the primary site of exposure and absorption due to the lower level of dermal protection afforded by hoods. Aromatic hydrocarbons could have been absorbed dermally during firefighting or inhaled during the doffing of gear that was off-gassing contaminants. |
Is organic farming safer to farmers' health? A comparison between organic and traditional farming
Costa C , Garcia-Leston J , Costa S , Coelho P , Silva S , Pingarilho M , Valdiglesias V , Mattei F , Dall'armi V , Bonassi S , Laffon B , Snawder J , Teixeira JP . Toxicol Lett 2014 230 (2) 166-76 Exposure to pesticides is a major public health concern, because of the widespread distribution of these compounds and their possible long term effects. Recently, organic farming has been introduced as a consumer and environmental friendly agricultural system, although little is known about the effects on workers' health. The aim of this work was to evaluate genetic damage and immunological alterations in workers of both traditional and organic farming. Eighty-five farmers exposed to several pesticides, thirty-six organic farmers and sixty-one controls took part in the study. Biomarkers of exposure (pyrethroids, organophosphates, carbamates, and thioethers in urine and butyrylcholinesterase activity in plasma), early effect (micronuclei in lymphocytes and reticulocytes, T-cell receptor mutation assay, chromosomal aberrations, comet assay and lymphocytes subpopulations) and susceptibility (genetic polymorphisms related to metabolism - EPHX1, GSTM1, GSTT1 and GSTP1 - and DNA repair-XRCC1 and XRCC2) were evaluated. When compared to controls and organic farmers, pesticide farmers presented a significant increase of micronuclei in lymphocytes (frequency ratio, FR=2.80) and reticulocytes (FR=1.89), chromosomal aberrations (FR=2.19), DNA damage assessed by comet assay (mean ratio, MR=1.71), and a significant decrease in the proportion of B lymphocytes (MR=0.88). Results were not consistent for organic farmers when compared to controls, with a 48% increase of micronuclei in lumphocytes frequency (p=0.016) contrasted by the significant decreases of TCR-Mf (p=0.001) and %T (p=0.001). Our data confirm the increased presence of DNA damage in farmers exposed to pesticides, and show as exposure conditions may influence observed effects. These results must be interpreted with caution due to the small size of the sample and the unbalanced distribution of individuals in the three study groups. |
Personal breathing zone exposures among hot-mix asphalt paving workers; preliminary analysis for trends and analysis of work practices that resulted in the highest exposure concentrations
Osborn LV , Snawder JE , Kriech AJ , Cavallari JM , McClean MD , Herrick RF , Blackburn GR , Olsen LD . J Occup Environ Hyg 2013 10 (12) 663-73 An exposure assessment of hot-mix asphalt (HMA) paving workers was conducted to determine which of four exposure scenarios impacted worker exposure and dose. Goals of this report are to present the personal-breathing zone (PBZ) data, discuss the impact of substituting the releasing/cleaning agent, and discuss work practices that resulted in the highest exposure concentration for each analyte. One-hundred-seven PBZ samples were collected from HMA paving workers on days when diesel oil was used as a releasing/cleaning agent. An additional 36 PBZ samples were collected on days when B-100 (100% biodiesel, containing no petroleum-derived products) was used as a substitute releasing/cleaning agent. Twenty-four PBZ samples were collected from a reference group of concrete workers, who also worked in outdoor construction but had no exposure to asphalt emissions. Background and field blank samples were also collected daily. Total particulates and the benzene soluble fraction were determined gravimetrically. Total organic matter was determined using gas chromatography (GC) with flame ionization detection and provided qualitative information about other exposure sources contributing to worker exposure besides asphalt emissions. Thirty-three individual polycyclic aromatic compounds (PACs) were determined using GC with time-of-flight mass spectrometry; results were presented as either the concentration of an individual PAC or a summation of the individual PACs containing either 2- to 3-rings or 4- to 6-rings. Samples were also screened for PACs containing 4- to 6-rings using fluorescence spectroscopy. Arithmetic means, medians, and box plots of the PBZ data were used to evaluate trends in the data. Box plots illustrating the diesel oil results were more variable than the B-100. Also, the highest diesel oil results were much higher in concentration than the highest B-100 results. An analysis of the highest exposure results and field notes revealed a probable association between these exposures and the use of diesel oil, use of a diesel-powered screed, elevated HMA paving application temperatures, lubricating and working on broken-down equipment, and operation of a broom machine. |
Occupational exposures to respirable crystalline silica during hydraulic fracturing
Esswein EJ , Breitenstein M , Snawder J , Kiefer M , Sieber WK . J Occup Environ Hyg 2013 10 (7) 347-56 This report describes a previously uncharacterized occupational health hazard: work crew exposures to respirable crystalline silica during hydraulic fracturing. Hydraulic fracturing involves high pressure injection of large volumes of water and sand, and smaller quantities of well treatment chemicals, into a gas or oil well to fracture shale or other rock formations, allowing more efficient recovery of hydrocarbons from a petroleum-bearing reservoir. Crystalline silica ("frac sand") is commonly used as a proppant to hold open cracks and fissures created by hydraulic pressure. Each stage of the process requires hundreds of thousands of pounds of quartz-containing sand; millions of pounds may be needed for all zones of a well. Mechanical handling of frac sand creates respirable crystalline silica dust, a potential exposure hazard for workers. Researchers at the National Institute for Occupational Safety and Health collected 111 personal breathing zone samples at 11 sites in five states to evaluate worker exposures to respirable crystalline silica during hydraulic fracturing. At each of the 11 sites, full-shift samples exceeded occupational health criteria (e.g., the Occupational Safety and Health Administration calculated permissible exposure limit, the NIOSH recommended exposure limit, or the ACGIH threshold limit value), in some cases, by 10 or more times the occupational health criteria. Based on these evaluations, an occupational health hazard was determined to exist for workplace exposures to crystalline silica. Seven points of dust generation were identified, including sand handling machinery and dust generated from the work site itself. Recommendations to control exposures include product substitution (when feasible), engineering controls or modifications to sand handling machinery, administrative controls, and use of personal protective equipment. To our knowledge, this represents the first systematic study of work crew exposures to crystalline silica during hydraulic fracturing. Companies that conduct hydraulic fracturing using silica sand should evaluate their operations to determine the potential for worker exposure to respirable crystalline silica and implement controls as necessary to protect workers. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: a file containing controls and recommendations to limit worker exposures to respirable crystalline silica at hydraulic fracturing work sites.]. |
Recommendations for biomonitoring of emergency responders: focus on occupational health investigations and occupational health research
Decker JA , DeBord DG , Bernard B , Dotson GS , Halpin J , Hines CJ , Kiefer M , Myers K , Page E , Schulte P , Snawder J . Mil Med 2013 178 (1) 68-75 The disaster environment frequently presents rapidly evolving and unpredictable hazardous exposures to emergency responders. Improved estimates of exposure and effect from biomonitoring can be used to assess exposure-response relationships, potential health consequences, and effectiveness of control measures. Disaster settings, however, pose significant challenges for biomonitoring. A decision process for determining when to conduct biomonitoring during and following disasters was developed. Separate but overlapping decision processes were developed for biomonitoring performed as part of occupational health investigations that directly benefit emergency responders in the short term and for biomonitoring intended to support research studies. Two categories of factors critical to the decision process for biomonitoring were identified: Is biomonitoring appropriate for the intended purpose and is biomonitoring feasible under the circumstances of the emergency response? Factors within these categories include information needs, relevance, interpretability, ethics, methodology, and logistics. Biomonitoring of emergency responders can be a valuable tool for exposure and risk assessment. Information needs, relevance, and interpretability will largely determine if biomonitoring is appropriate; logistical factors will largely determine if biomonitoring is feasible. The decision process should be formalized and may benefit from advance planning. |
Application of an updated physiologically-based pharmacokinetic model for chloroform to evaluate CYP2E1-mediated renal toxicity in rats and mice
Sasso AF , Schlosser PM , Kedderis GL , Genter MB , Snawder J , Li Z , Rieth S , Lipscomb JC . Toxicol Sci 2012 131 (2) 360-74 Physiologically-based pharmacokinetic (PBPK) models are tools for interpreting toxicological data, and extrapolating observations across species and route of exposure. Chloroform (CHCl(3)) is a chemical for which there are PBPK models available in different species, and multiple sites of toxicity. Since chloroform induces toxic effects in the liver and kidneys via production of reactive metabolites, proper characterization of metabolism in these tissues is essential for risk assessment. While hepatic metabolism of chloroform is adequately described by these models, there is higher uncertainty for renal metabolism due to a lack of species-specific data and direct measurements of renal metabolism. Furthermore, models typically fail to account for regional differences in metabolic capacity within the kidney. Mischaracterization of renal metabolism may have a negligible effect on systemic chloroform levels, but it is anticipated to have a significant impact on the estimated site-specific production of reactive metabolites. In this paper, rate parameters for chloroform metabolism in the kidney are revised for rats, mice, and humans. New in vitro data were collected in mice and humans for this purpose and are presented here. The revised PBPK model is used to interpret data of chloroform-induced kidney toxicity in rats and mice exposed via inhalation and drinking water. Benchmark dose (BMD) modeling is used to characterize the dose-response relationship of kidney toxicity markers as a function of PBPK-derived internal kidney dose. Applying the PBPK model, it was also possible to characterize the dose-response for a recent dataset of rats exposed via multiple routes simultaneously. Consistent BMD modeling results were observed regardless of species or route of exposure. |
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