Ambient water quality criteria derived using probabilistic risk assessment.

National recommendations for numeric human health ambient water quality criteria (AWQC) for toxic substances are derived by the US Environmental Protection Agency (USEPA) using a deterministic approach that combines point estimates for exposure, toxicity, and acceptable risk. In accordance with the Clean Water Act, states, territories, and authorized tribes must either adopt these recommendations or modify and replace them with criteria using an alternative, scientifically defensible method. Recent reports have criticized the deterministic approach, stating that it suffers from compounded conservatism by selecting upper percentiles or maximum values for multiple inputs and that it cannot directly determine what portion of the population a given criterion protects. As an alternative, probabilistic risk assessment (PRA) has been promoted as a more transparent and robust method for deriving AWQC. Probabilistic risk assessment offers several advantages over the deterministic approach. For example, PRA uses entire data distributions rather than upper-percentile point estimates to specify exposures, thereby reducing compounded conservatism. Additionally, because it links acceptable risk targets with specific segments of the exposed population, PRA-based AWQC demonstrably protects multiple subsets of the population. To date, no study has quantitatively compared deterministic and PRA approaches and resulting AWQC using national inputs consistent with USEPA guidance. This study introduces a PRA method for deriving AWQC and presents case studies to compare probabilistically derived AWQC with USEPA's 2015 recommendations. The methods and results of this work will help federal and state regulators, water quality managers, and stakeholders better understand available approaches to deriving AWQC and provide context to assumption- and method-specific differences between criteria. Integr Environ Assess Manag 2023;19:501-512. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Opioid-Related Overdose Fatality Cases in Two Florida Counties.

Introduction: This study evaluates trends in drug-related death cases within both Pasco and Pinellas County, Florida, from the calendar years 2011 to 2016. Specifically, it focuses on opioids and the role of fentanyl in overdose-related mortality in rural versus suburban populations. Methods: Two sets of data from each calendar year were obtained from a Medical Examiner's Office. These data were compared by year to assess differences using the nonparametric ANOVA test with the statistical software SAS, University Edition. Binary logistic regression was performed to assess which drugs occurred most frequently in the presence or absence of fentanyl. Results: There was not a significant difference in the month of the year or the day of the week that drug-related fatalities occurred. More drug-related mortalities occurred during daylight hours (e.g., 8:00 AM-4:00 PM) and more fentanyl-related mortalities occurred in Pinellas County compared to Pasco County. Fentanyl and heroin tended to co-occur in mortalities, while ethanol, hydrocodone, morphine, oxycodone, and methadone were negatively associated with fentanyl-related overdose cases. Conclusion: The characteristics of drug-related mortalities identified here may be used to better target interventions against drug abuse and overdose.

Deriving Human Health and Aquatic Life Water Quality Criteria in the United States for Bioaccumulative Substances: A Historical Review and Future Perspective.

Methods used to derive water quality regulations for persistent, bioaccumulative, and toxic substances (PBTs) in the United States have evolved substantially over the past 50 yr, leveraging current understandings and assumptions about the nature and magnitude of partitioning and accumulation of substances in water, sediments, and organisms. In the United States and across the world, environmental regulations continue to evolve into more refined water quality criteria protective of aquatic life and human health. The present review provides historical context on the establishment of aquatic life and human health water quality criteria in the United States by compiling information from regulatory agencies and peer-reviewed literature on methods used to characterize and quantify bioaccumulation of substances in aquatic organisms and humans. Primary data needs and assumptions for various methods, as well as their application in setting criteria by the US Environmental Protection Agency over the past half century, are highlighted. Our review offers an important retrospective on the data and methods used to derive water quality criteria for PBTs and provides commentary on the future of US criteria development. Environ Toxicol Chem 2021;40:2394-2405. © 2021 SETAC.

Assessment of lead exposure controls on bridge painting projects using worker blood lead levels.

A retrospective analysis of worker blood lead levels (BLL) was conducted using blood lead data collected by four bridge painting contractors before and after lead exposure. The objective of the study was to evaluate the effectiveness of exposure controls in preventing elevated blood lead levels (>25 µg/dl) during bridge painting projects. The contractors selected for the study submitted BLL data for 289 workers representing ten work tasks and 11 bridge painting projects. In total, 713 blood lead levels results were evaluated. The mean blood lead level for all work classifications combined was 10.9 µg/dl at baseline compared with 14.9 µg/dl after two months of exposure and 15.0 µg/dl after four months of exposure. Two months after initial exposure, 29% of the painters and 35% of the laborers had a 10 µg/dl incremental increase or greater in blood lead level. Likewise, 18% of the painters and 26% of the laborers had a blood lead level greater than 25 µg/dl during the same time. The blood lead levels that exceeded the 25 µg/dL threshold ranged from 30µg/dL-63 µg/dL for painters and 26 µg-56 µg/dL for laborers. All work tasks with high-intensity exposure (abrasive blaster/painter, abrasive blaster, painter & laborer) experienced an average blood lead level increase that ranged from 0.2 µg/dl to 8.9 µg/dl two months after initial exposure. Blood lead testing conducted after modified exposure controls (two months after the initial follow-up blood testing) were implemented showed a decrease in average blood lead levels (range -0.14 µg/dl to -2.7 µg/dl) for two high-intensity exposure work tasks. In comparison, the other two high-intensity work tasks had moderate increases (range 1 µg/dl to 2.4 µg/dl). The modified exposure controls included an increase in the air velocity inside of the work containment and an administrative control in the form of additional worker training on lead exposure prevention. The reduction in the 95th percentile (point estimate) BLL exposure profile for each exposure group at the 4-month follow-up blood testing period is associated with modified exposure controls. Ineffective exposure controls were identified through the analysis of worker BLLs. We found two exposure groups (laborer and painter) whose 95th percentile (point estimate) exposure profile was greater than the OSHA construction lead standard's targeted BLL goal (25 µg/dl) during the first two months of exposure. Our research findings provide support for monthly blood lead testing after baseline until blood lead levels are controlled to an acceptable concentration.

Evaluation of airborne asbestos exposure from routine handling of asbestos-containing wire gauze pads in the research laboratory.

Three independently conducted asbestos exposure evaluations were conducted using wire gauze pads similar to standard practice in the laboratory setting. All testing occurred in a controlled atmosphere inside an enclosed chamber simulating a laboratory setting. Separate teams consisting of a laboratory technician, or technician and assistant simulated common tasks involving wire gauze pads, including heating and direct wire gauze manipulation. Area and personal air samples were collected and evaluated for asbestos consistent with the National Institute of Occupational Safety Health method 7400 and 7402, and the Asbestos Hazard Emergency Response Act (AHERA) method. Bulk gauze pad samples were analyzed by Polarized Light Microscopy and Transmission Electron Microscopy to determine asbestos content. Among air samples, chrysotile asbestos was the only fiber found in the first and third experiments, and tremolite asbestos for the second experiment. None of the air samples contained asbestos in concentrations above the current permissible regulatory levels promulgated by OSHA. These findings indicate that the level of asbestos exposure when working with wire gauze pads in the laboratory setting is much lower than levels associated with asbestosis or asbestos-related lung cancer and mesothelioma.

Reduced oxygen tension culturing conditionally alters toxicogenic response of differentiated H9c2 cardiomyoblasts to acrolein.

Acrolein is a reactive electrophilic aldehyde known to cause mitochondrial dysfunction, oxidative stress, and dysregulation of signaling transduction in vitro. Most in vitro systems employ standard cell culture maintenance conditions of 95% air/5% CO2, translating to a culture oxygen tension of approximately 20%, far above most physiological tissues. The purpose of this investigation was to examine whether low-serum, retinoic acid differentiated H9c2 cells were less sensitive to acrolein insult when cultured under reduced oxygen tension. H9c2 cells were maintained separately in 20% and 5% oxygen, differentiated for 5 d, and then exposed to acrolein for 30 min in media containing varying concentrations of tricarboxylic acid and glycolytic substrates, followed by fresh medium replacement. Cells were then assessed for MTT reduction at 2 h and 24 h after acrolein insult. We showed that pyruvate supplementation in combination with lowered oxygen culturing significantly attenuated acrolein-induced viability loss at 24 h. Poly(ADP-ribose) polymerase inhibition and EGTA preferentially provided partial rescue to low oxygen cultures, but not for standard cultures. Collectively, these results offer evidence supporting altered toxicogenic response of H9c2 during physiologically relevant oxygen tension culturing.

Acrolein measurement and degradation in Dulbecco's Modified Eagle Medium: an examination of in-vitro exposure metrics.

Acrolein is a reactive α,ß-unsaturated aldehyde known for its adduction to endogenous biomolecules, resulting in initiation or exacerbation of several disease pathways. In-vitro systems are routinely used to elucidate the cytotoxic or mechanistic role(s) of acrolein in pathogenesis. Nevertheless, the half-life of acrolein in biological or in-vitro systems, e.g. blood or culture media, has not been well characterized. Since in-vitro cytotoxic and mechanistic investigations routinely expose cultures to acrolein from 1 hour to 72 hours, we aimed to characterize the half-life of acrolein in culture medium to ascertain the plausible exposure window. Half-life determinations were conducted in low-serum DMEM at room temperature and 37 °C, both with and without H9c2 cells. For quantitative assessment, acrolein was derivatized to a fluorescent 7-hydroxyquinoline method validated in-house and assessed via fluorescent spectroscopy. In closed vessel experiments at room temperature, acrolein in DMEM was reduced by more than 40% at 24 hours, irrespective of the initial concentration. Expectedly, open vessel experiments demonstrated accelerated depletion over time at room temperature, and faster still at 37 °C. The presence of cells tended to further accelerate degradation by an additional 15-30%, depending on temperature. These results undermine described experimental exposure conditions stated in most in-vitro experiments. Recognition of this discrepancy between stated and actual exposure metrics warrant examination of novel alternative objective and representative exposure characterization for in-vitro studies to facilitate translation to in-vivo and in-silico methods.

Acrolein Can Cause Cardiovascular Disease: A Review.

Acrolein is a highly reactive unsaturated aldehyde that is formed during the burning of gasoline and diesel fuels, cigarettes, woods and plastics. In addition, acrolein is generated during the cooking or frying of food with fats or oils. Acrolein is also used in the synthesis of many organic chemicals and as a biocide in agricultural and industrial water supply systems. The total emissions of acrolein in the United States from all sources are estimated to be 62,660 tons/year. Acrolein is classified by the Environmental Protection Agency as a high-priority air and water toxicant. Acrolein can exert toxic effects following inhalation, ingestion, and dermal exposures that are dose dependent. Cardiovascular tissues are particularly sensitive to the toxic effects of acrolein based primarily on in vitro and in vivo studies. Acrolein can generate free oxygen radical stress in the heart, decrease endothelial nitric oxide synthase phosphorylation and nitric oxide formation, form cytoplasmic and nuclear protein adducts with myocyte and vascular endothelial cell proteins and cause vasospasm. In this manner, chronic exposure to acrolein can cause myocyte dysfunction, myocyte necrosis and apoptosis and ultimately lead to cardiomyopathy and cardiac failure. Epidemiological studies of acrolein exposure and toxicity should be developed and treatment strategies devised that prevent or significantly limit acrolein cardiovascular toxicity.

"Pressured to prescribe" The impact of economic and regulatory factors on South-Eastern ED physicians when managing the drug seeking patient.

OBJECTIVE: The purpose of this study was to elicit the opinions of Emergency Department (ED) physicians, currently practicing in the United States, regarding the impact of economic and regulatory factors on their management of patients exhibiting "drug seeking" behavior. METHODS: A descriptive, cross-sectional study, utilizing a convenience sample of ED physicians located in Florida and Georgia was conducted for a period of 2 months. The inclusion criteria specified that any ED physician, currently practicing within the United States, could participate. RESULTS: Of the ED physicians surveyed (n = 141), 71% reported a perceived pressure to prescribe opioid analgesics to avoid administrative and regulatory criticism and 98% related patient satisfaction scores as being too highly emphasized by reimbursement entities as a means of evaluating their patient management. Rising patient volumes and changes in the healthcare climate were cited by ED physicians as impacting their management of patients exhibiting "drug seeking" behavior. CONCLUSIONS: The ED physician faces unique challenges in changing healthcare and economic climates. Requirements to address pain as the "fifth vital sign," patient satisfaction based reimbursement metrics and an economically driven rise in ED patient volume, may have inadvertently created an environment conducive to exploitation by prescription opioid abusers. There is an identified need for the development of continuing medical education and standardized regulatory and legislative protocols to assist ED physicians in the appropriate management of patients exhibiting "drug seeking" behavior.

A novel method for deriving thresholds of toxicological concern for vaccine constituents.

Safety assessment evaluating the presence of impurities, residual materials, and contaminants in vaccines is a focus of current research. Thresholds of toxicological concern (TTCs) are mathematically modeled levels used for assessing the safety of many food and medication constituents. In this study, six algorithms are selected from the open-access ToxTree software program to derive a method for calculating TTCs for vaccine constituents: In Vivo Rodent Micronucleus assay/LD50, Benigni-Bossa/LD50, Cramer Extended/LD50, In Vivo Rodent Micronucleus assay/TDLo, Benigni-Bossa/TDLo, and the Cramer Extended/TDLo. Using an initial dataset (n = 197) taken from INCHEM, RepDose, RTECS, and TOXNET, the chemicals were divided into two families: "positive" - based on the presence of structures associated with adverse outcomes, or "negative" - no such structures or having structures that appear to be protective of health. The final validation indicated that the Benigni-Bossa/LD50 method is the most appropriate for calculating TTCs for vaccine constituents. Final TTCs were designated as 18.06 µg/person and 20.61 µg/person for the Benigni-Bossa/LD50 positive and negative structural families, respectively.

Human health risk characterization of petroleum coke calcining facility emissions.

Calcining processes including handling and storage of raw petroleum coke may result in Particulate Matter (PM) and gaseous emissions. Concerns have been raised over the potential association between particulate and aerosol pollution and adverse respiratory health effects including decrements in lung function. This risk characterization evaluated the exposure concentrations of ambient air pollutants including PM10 and gaseous pollutants from a petroleum coke calciner facility. The ambient air pollutant levels were collected through monitors installed at multiple locations in the vicinity of the facility. The measured and modeled particulate levels in ambient air from the calciner facility were compared to standards protective of public health. The results indicated that exposure levels were, on occasions at sites farther from the facility, higher than the public health limit of 150 µg/m(3) 24-h average for PM10. However, the carbon fraction demonstrated that the contribution from the calciner facility was de minimis. Exposure levels of the modeled SO2, CO, NOx and PM10 concentrations were also below public health air quality standards. These results demonstrate that emissions from calcining processes involving petroleum coke, at facilities that are well controlled, are below regulatory standards and are not expected to produce a public health risk.

Occupational health surveillance: Pulmonary function testing in emergency responders.

Emergency responders may be exposed to a variety of fumes, gases, and particulates during the course of their job that can affect pulmonary function (PF) and require the use of respiratory protection. This investigation used occupational health monitoring examination data to characterize PF in a population currently employed as emergency responders. PF tests for workers who required health examinations to ensure fitness for continued respirator use were compared to the National Health and Nutrition Examination Survey (NHANES) III Raw Spirometry database to determine if decreased PF was associated with employment as an emergency responder. The results of this research indicated that the emergency responders experienced a modest, but statistically significant, increase in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) mean values over the NHANES III population in both total and stratified analyses, including stratification by age, gender, height, and smoking history. Results are likely due to a combination of effectively controlled exposures in the workplace, and the healthy worker effect among long-term workers. PF testing required by the Occupational and Safety Health Administration (OSHA) has substantial utility for conducting occupational surveillance at the population level. In this investigation, we were able to quickly evaluate if abnormal PF existed in an industrial sector known to have exposures that, when uncontrolled, can lead to PF impairment.

Isocyanate and VOC exposure analysis using Flexane®.

Flexane® 80 is a trowelable urethane product used in combination with cleaners and primers to effect rubber conveyor belt repairs. These products are of concern due to the potential for worker exposure to isocyanates and volatile organic compounds (VOCs). Small chamber experiments were used to identify chemicals liberated to the ambient air from each of the Flexane®-related products. A new sample collection method using treated cotton sleeves as a surrogate skin surface to assess potential dermal exposure to isocyanates during mixing and application of the Flexane® product was validated. Six simulations of a worst case scenario were performed by an experienced belt repair technician in a walk-in laboratory exposure chamber. Analysis of air samples from the large chamber simulations did not detect airborne isocyanates. The average airborne VOC concentrations were below established occupational exposure levels. Dermal sleeve samples detected intermittent and low levels of isocyanates from self-application while wearing gloves having surface residues of uncured Flexane®. The data strongly suggest that the normal and intended use of Flexane® putty, and its associated products under worst case or typical working conditions is not likely to result in worker VOC or isocyanate exposure levels sufficient to produce adverse health effects.

Airborne asbestos exposures associated with work on asbestos fire sleeve materials.

Asbestos-containing fire sleeves have been used as a fire protection measure for aircraft fluid hoses. This investigation was conducted to determine the level of airborne asbestos fiber exposure experienced by mechanics who work with fire sleeve protected hoses. Duplicate testing was performed inside a small, enclosed workroom during the fabrication of hose assemblies. Personal air samples taken during this work showed detectable, but low airborne asbestos fiber exposures. Analysis of personal samples (n=9) using phrase contract microscopy (PCM) indicated task duration airborne fiber concentrations ranging from 0.017 to 0.063 fibers per milliliter (f/ml) for sampling durations of 167-198 min, and 0.022-0.14 f/ml for 30 min samples. Airborne chrysotile fibers were detected for four of these nine personal samples, and the resulting asbestos adjusted airborne fiber concentrations ranged from 0.014 to 0.025 f/ml. These results indicate that work with asbestos fire sleeve and fire sleeve protected hose assemblies, does not produce regulatory noncompliant levels of asbestos exposure for persons who handle, cut and fit these asbestos-containing materials.

Risk characterization of vapor intrusion in former manufactured gas plant sites.

Soil vapor intrusion (SVI) has recently garnered much interest as a potential exposure route for occupants of properties overlying and surrounding former Manufactured Gas Plants (MGPs). This investigation evaluates SVI at 10 commercial buildings and 26 single family and multi-family residential properties overlying and/or adjacent to three former MGPs. SVI was evaluated in three categories according to thickness of the vadose zones: no vadose zone; 0-6 feet thick, and 6-25 feet thick. Indoor and outdoor air, and soil vapor samples were analyzed for volatile organic compounds (VOCs). Comparative risks were evaluated based on maximum and mean concentrations for benzene, toluene, ethylbenzene, and xylenes relative to background levels. All calculated Hazard Indices were less than 1 or were comparable to mean and maximum background levels. Cancer risks for exposure to benzene ranged from 9.75×10(-6) to 4.52×10(-4). Comparative background cancer risk from benzene exposure not related to former MGP sites ranged from 9.9×10(-6) to 3.59×10(-3). The results did not identify evidence of MGP-related soil vapor intrusion from any of the 36 sites. No increased public health risks were associated with occupied residential or commercial properties overlying or surrounding MGPs.

Prognostic performance of metabolic indexes in predicting onset of type 1 diabetes.

OBJECTIVE: In this investigation we evaluated nine metabolic indexes from intravenous glucose tolerance tests (IVGTTs) and oral glucose tolerance tests (OGTTs) in an effort to determine their prognostic performance in predicting the development of type 1 diabetes in those with moderate risk, as defined by familial relation to a type 1 diabetic individual, a positive test for islet cell antibodies and insulin autoantibody, but normal glucose tolerance. RESEARCH DESIGN AND METHODS: Subjects (n = 186) who had a projected risk of 25-50% for developing type 1 diabetes within 5 years were followed until clinical diabetes onset or the end of the study as part of the Diabetes Prevention Trial-Type 1. Prognostic performance of the metabolic indexes was determined using receiver operating characteristic (ROC) curve and survival analyses. RESULTS: Two-hour glucose from an OGTT most accurately predicted progression to disease compared with all other metabolic indicators with an area under the ROC curve of 0.67 (95% CI 0.59-0.76), closely followed by the ratio of first-phase insulin response (FPIR) to homeostasis model assessment of insulin resistance (HOMA-IR) with an area under the curve value of 0.66. The optimal cutoff value for 2-h glucose (114 mg/dl) maintained sensitivity and specificity values >0.60. The hazard ratio for those with 2-h glucose ≥ 114 mg/dl compared with those with 2-h glucose <114 mg/dl was 2.96 (1.67-5.22). CONCLUSIONS: The ratio of FPIR to HOMA-IR from an IVGTT provided accuracy in predicting the development of type 1 diabetes similar to that of 2-h glucose from an OGTT, which, because of its lower cost, is preferred. The optimal cutoff value determined for 2-h glucose provides additional guidance for clinicians to identify subjects for potential prevention treatments before the onset of impaired glucose tolerance.