Acute Exposure Guideline Levels Research Articles

Estimating specific acute exposure guideline levels for emergency response at the scene of chemical accidents: A case study of acrylic acid

Acute Exposure Guideline Levels (AEGLs) proposed by the United States Environmental Protection Agency (USEPA) are reference values for disaster management during scenarios involving chemical accidents. We attempted to specify the present AEGLs of acrylic acid that are provided with only five intervals (10, 30 min, 1, 4, and 8 h) as a brief case study. The AEGL-1, 2, 3 values for acrylic acid were estimated at 96 intervals (5 min–8 h) in detail using the revised Haber's formula (k = Cn × t) and applying a regression model. The AEGL-1 value was constant for the entire exposure duration of 1.5 ppm since it caused only slight irritation without irreversible health effects. The AEGL-2 value was obtained with fixed values (n = 1.8, uncertainty factor of 3, and each 5 min interval), with that for the initial 5 min being derived as 183 ppm, which decreased to 43 ppm after 8 h of exposure. The AEGL-3 values fluctuated because of the risk to human health. The AEGL-3 for the initial 5 min exposure was derived as 696 ppm, which decreased to 58 ppm after 8 h exposure applied to the regression model. Specific AEGL values for acrylic acid were derived using toxicity data and the revised Haber's formula. By applying the methodology described in this study, the reference values for chemical substances that have no AEGL values can be calculated to potentially enhance emergency response in the event of chemical accidents.

Application of Meta-Analysis to Derivation of Points-of-Departure for Short-Term Inhalation Exposure Levels of Hazardous Chemicals

BACKGROUND AND AIM: For short-term chemical inhalation exposures to hazardous chemicals, the incidence of a health effect usually conforms to a generalized linear model with a bivariate probit link function dependent on inhalant concentration ({C}) and the duration of exposure ({t}). The National Academy’s Acute Exposure Guideline Levels (AEGLs) Committee relies on this model when deriving AEGLs. Threshold concentrations at AEGL durations are established by the toxic load equation, {C}^{n} x {t} = {constant}, which Toxic Load Exponent {n} (TLE or {n}-value) directly follows from the probit model. When multiple probit datasets are available, often they cannot be directly pooled together because of disparities in experimental design. METHODS: Recently, we reported both a meta-analytical framework for multiple studies and an application of the new methodology to dimethyl sulfide. The new methodology allows accurate TLE estimation even if multiple datasets are heterogenous. The utilized techniques include categorical regression, common-effect and random-effects models. The proposed framework was applied to multiple-study datasets from AEGL technical support documents. RESULTS:Using the framework, both new TLEs and confidence intervals on them were derived. The recalculated TLEs and points-of-departure include ammonia ({n} = 2.13, 95% CI: 1.98–2.27), allyl alcohol ({n} = 0.95, 95% CI: 0.76–1.15), 1,1,1-trichloroethane ({n} = 3.46, 95% CI: 2.85–4.07 ), carbon tetrachloride ({n} = 2.51, 95% CI: 2.27–2.76), and oxygen difluoride ({n} = 1.29, 95% CI: 0.26–2.32). CONCLUSIONS:The new TLEs and their confidence intervals were applied in calculations of short-term inhalation points of departure at five reference AEGL durations. Disclaimer: The findings and conclusions in this presentation have not been formally disseminated by the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry and should not be construed to represent any agency determination or policy. KEYWORDS: Risk Assessment, Meta-analysis, Toxic Load Exponent (TLE), n-value, Probit, Categorical Regression

Propellant Off-Gassing and Implications for Triage and Rescue.

INTRODUCTION: Hypergolic propellants can be released in large amounts during space launch contingencies. Whether propellant-contaminated suit fabric poses a significant risk to rescue crews, due to off-gassing, has not been explored in detail. In this study, we addressed this issue experimentally, exposing space suit fabric to propellants (dinitrogen tetroxide [N₂O₄] and monomethyl hydrazine [MMH]).METHODS: The NASA Space Shuttle Program Advanced Crew Escape System II (ACES II) is similar to the NASA Orion Crew Survival System (OCSS) and was utilized here. Suit fabric was placed and sealed into permeation cells. Fabric exterior surface was exposed to constant concentrated hypergolics, simulating permeation and leakage. Fabric was rinsed, and permeation and off-gassing kinetics were measured. Experimental parameters were selected, simulating suited flight crewmembers during an evacuation transport without cabin air flow.RESULTS: The fabric allows for immediate permeation of liquid or vaporized MMH and N₂O₄. NO₂ off-gassing never exceeded the AEGL-1 8-h level (acute exposure guideline level). In contrast, MMH off-gassing levels culminated in peak levels, approaching AEGL-2 10-min levels, paralleling the drying process of the fabric layers. DISCUSSION: Our findings demonstrate that MMH off-gassing is promoted by the drying of suit material in a delayed fashion, resulting in MMH concentrations having the potential for adverse health effects for flight and rescue crews. This indicates that shorter decontamination times could be implemented, provided that suit material is either kept moist to prevent off-gassing or removed prior to medical evacuation. Additional studies using OCSS or commercial crew suits might be needed in the future.Schwertz H, Roth LA, Woodard D. Propellant off-gassing and implications for triage and rescue. Aerosp Med Hum Perform. 2020; 91(12):956961.

Ammonia and hydrogen sulphide odour emissions from different areas of a landfill in Hangzhou, China

This study examined the release characteristics of malodorous ammonia (NH3) and hydrogen sulphide (H2S) gases in different areas of a full-capacity operational landfill in Hangzhou, China. Gas samples were collected using static boxes from exposed working areas (EWAs), temporarily covered areas (TCAs), and final closure areas (FCAs), and were analysed using spectrophotometric methods. Gas release increased in the following order: TCA > EWA > FCA. The average concentrations of released NH3 in these areas were 2763, 1171, and 27 mg m-3, respectively, and those of H2S were 2481, 631, and 10 mg m-3, respectively. The concentrations of gases released from holes in the film in the temporarily covered and EWAs were significantly higher than the AEGL-3 level values specified by the Acute Exposure Guideline Levels (AEGL) Advisory Committee. EWAs were identified as key for odour control, where the highest NH3 release was recorded at approximately 12:00. The diurnal variation in H2S release was insignificant (p > 0.05). Therefore, the study shows that working in EWAs should be avoided at approximately noon. Adverse impacts on human health can be reduced by standardising procedures, using higher-quality films, and improving film installation procedures. The results of this study serve as a valuable reference for odour control in operational landfills.

Meta-analysis of animal studies applied to short-term inhalation exposure levels of hazardous chemicals

For short-term chemical inhalation exposures to hazardous chemicals, the incidence of a health effect in biological testing usually conforms to a general linear model with a probit link function dependent on inhalant concentration C and the duration of exposure t. The National Academy's Acute Exposure Guideline Levels (AEGLs) Committee relies on these models when establishing AEGLs. Threshold concentrations at AEGL durations are established by the toxic load equation Cn x t = constant, which toxic load exponent n (TLE or n-value) directly follows from the bivariate probit model. When multiple probit datasets are available, the AEGL Committee routinely pools studies' incidence data. Such meta-analytical models are valid only when the pooled data are homogeneous, with similar sensitivities and equivalent responses to exposure concentrations and durations. In the present study, the homogeneity of datasets meta-analyzed by the AEGL Committee was examined, finding that 70% of datasets pooled by the AEGL Committee are heterogeneous. In these instances, data pooling leads to a statistically invalid model and TLE estimate, potentially resulting in under- or over-estimated inhalation guidance levels. When data pooling is inappropriate, other meta-analysis options include categorical regression, fixed-effect and random-effects models, or even designation of a key study based on scientific judgement. In the present work, options of TLE meta-analysis are summarized in a decision tree contingent on statistical testing.

Amplified Detection of Chemical Warfare Agents Using Two-Dimensional Chemical Potential Gradients.

Chemical warfare agents such as sarin are highly toxic, and detection of even trace levels is important. Using a hydrogel film containing a built-in two-dimensional chemical potential gradient, we demonstrate the detection of a sarin simulant under conditions potentially as low as a level 1 (6.90 × 10–9 mg/cm3 for 10 min) Acute Exposure Guideline Level sarin exposure. Specifically, the sarin simulant diisopropyl fluorophosphate (DFP) is aerosol-deposited on a hydrogel film containing a built-in ionic chemical gradient and the enzyme, diisopropyl fluorophosphatase (DFPase). DFPase degrades the DFP, releasing fluoride ions. The fluoride ions are then concentrated by the gradient to a miniature electrochemical sensor embedded in the hydrogel providing a 30-fold amplification of the fluoride ion signal, which is an indication of exposure to DFP, relative to a gradient-free system. This method is general for agents which hydrolyze into chemically detectable ionic species.

Fourier Transform Infrared Absorption Spectroscopy for Quantitative Analysis of Gas Mixtures at Low Temperatures for Homeland Security Applications.

Performance standard specifications for point chemical vapor detectors are established in ASTM E 2885-13 and ASTM E 2933-13. The performance evaluation of the detectors requires the accurate delivery of known concentrations of the chemical target to the system under test. Referee methods enable the analyte test concentration and associated uncertainties in the analyte test concentration to be validated by independent analysis, which is especially important for reactive analytes. This work extends the capability of a previously demonstrated method for using Fourier transform infrared (FT-IR) absorption spectroscopy for quantitatively evaluating the composition of vapor streams containing hazardous materials at Acute Exposure Guideline Levels (AEGL) to include test conditions colder than laboratory ambient temperatures. The described method covers the use of primary reference spectra to establish analyte concentrations, the generation of secondary reference spectra suitable for measuring analyte concentrations under specified testing environments, and the use of additional reference spectra and spectral profile strategies to mitigate the uncertainties due to impurities and water condensation within the low-temperature (7 °C, -5 °C) test cell. Important benefits of this approach include verification of the test analyte concentration with characterized uncertainties by in situ measurements co-located with the detector under test, near-real-time feedback, and broad applicability to toxic industrial chemicals.

An approach for the development of emergency response levels for halogenated hydrocarbons

Emergency exposure guidance levels have been developed for many halogenated hydrocarbons. These can be employed in the event of accidental releases or terrorist actions. However, for a chemical release involving a substance without existing guidance levels, there is a need to be able to develop one rapidly. Two data sources are available, the Acute Exposure Guideline Levels (AEGL) and Emergency Response Guideline Levels (ERPG). The subset of halogenated hydrocarbons and related substances included in these data sources represent 30 chemicals and 41 risk assessments. The ratios for serious toxicity/annoyance level and for potential lethality/serious toxicity were calculated. On reviewing the results, the geometric means provided the best basis for extrapolation. When the geometric means of the ratios of ERPG-3/ERPG-2 and AEGL-3/AEGL-2 were calculated their combined mean was 4.40. The geometric standard deviation for the combined data set was 2.00 suggesting the data were homogeneous. Likewise, calculation of the geometric means for ERPG-2/1 and AEGL-2/1 the combined ratio was 3.93. The geometric standard deviation for the combined set was 1.46, again suggesting homogeneity of the data. The review described in this paper confirmed that the time default “n” values of 3 and 1 (ten Berge et al., 1986) are appropriate for extrapolation to shorter and longer exposure times, respectively.

Fourier Transform Infrared Absorption Spectroscopy for Quantitative Analysis of Gas Mixtures for Homeland Security Applications

Abstract Chemical detectors are crucial tools for first responders during emergency-response scenarios and for continuous monitoring of public spaces for general safety. For those who depend upon chemical detectors for safety and security, ensuring that detectors alarm at specified levels is critical. During detector performance evaluation, the accurate delivery of known concentrations of the chemical target to the detector is a key aspect of the test. Referee methods enable the analyte test concentration and associated uncertainties in the analyte test concentration to be validated by independent analysis, which is especially important for reactive analytes. This work demonstrates a method to use Fourier transform infrared (FT-IR) absorption spectroscopy for quantitatively evaluating the composition of vapor streams containing hazardous materials at acute exposure guideline levels (AEGL) under test conditions defined in recently published standard specifications for chemical vapor detectors. The described method covers the use of primary reference spectra to establish analyte concentrations, the generation of secondary reference spectra suitable for measuring analyte concentrations under specified testing environments, and the use of referee feedback to compensate for depletion of the test analyte. Important benefits of this approach included verification of the test analyte concentration with characterized uncertainties by in situ measurements co-located with the detector under test, near-real-time feedback, and broad applicability to toxic industrial chemicals.

Cargo-specific accidental release impact zones for hazardous materials: risk and consequence comparison for ammonia and hydrogen fluoride

Impacts of hazardous material releases during transport depend on the characteristics of the cargo, incident location and time, weather conditions (i.e., wind direction and speed), and land use. The objectives of this research were to characterize the dispersion characteristics of two hazardous materials (ammonia and hydrogen fluoride) in relation to meteorological parameters, land use, and cargo characteristics; and evaluate the health risks associated with the exposure after accidental releases. The magnitudes of the impact zones were compared in relation to atmospheric stability and exposure levels. Impact zones were estimated by areal locations of hazardous atmospheres software and imported to ArcGIS. For ammonia, the areas impacted by exposure levels over 1100 ppm Acute Exposure Guideline Level 3 (AEGL-3) were limited to less than 0.3 miles downwind from the incident location under unstable atmospheric conditions, which favor high vertical mixing and rapid dilution, and extended further downwind to distances between 0.5 and 0.7 miles under stable atmospheric conditions. For hydrogen fluoride, the AEGL-3 impact zone (exposure levels over 44 ppm) extended between 0.6 and 0.9 miles directly downwind from the incident location under unstable conditions, and reached approximately 2.0 miles directly downwind from the incident location under stable atmospheric conditions. The results were compared with the Emergency Response Guideline (ERG 2012) and showed agreement. The multilevel analysis of impacts after hazardous material releases during transport (i.e., type of material, geographical data, dispersion profile, meteorological information) can be used for implementing appropriate response and mitigation measures for accidental releases of hazardous cargo.

Case studies of hydrogen sulphide occupational exposure incidents in the UK

The UK Health and Safety Executive has investigated several incidents of workplace accidents involving hydrogen sulphide exposure in recent years. Biological monitoring has been used in some incidents to determine the cause of unconsciousness resulting from these incidents and as a supporting evidence in regulatory enforcement. This paper reports on three case incidents and discusses the use of biological monitoring in such cases. Biological monitoring has a role in identifying hydrogen sulphide exposure in incidents, whether these are occupational or in the wider environment. Sample type, time of collection and sample storage are important factors in the applicability of this technique. For non-fatal incidents, multiple urine samples are recommended at two or more time points between the incident and 15h post-exposure. For routine occupational monitoring, post-shift samples should be adequate. Due to endogenous levels of urinary thiosulphate, it is likely that exposures in excess of 12ppm for 30min (or 360ppm/min equivalent) would be detectable using biological monitoring. This is within the Acute Exposure Guideline Level 2 (the level of the chemical in air at or above which there may be irreversible or other serious long-lasting effects or impaired ability to escape) for hydrogen sulphide.

Investigations of chemical warfare agents and toxic industrial compounds with proton‐transfer‐reaction mass spectrometry for a real‐time threat monitoring scenario

Security and protection against terrorist attacks are major issues in modern society. One especially challenging task is the monitoring and protection of air conditioning and heating systems of buildings against terrorist attacks with toxic chemicals. As existing technologies have low selectivity, long response times or insufficient sensitivity, there is a need for a novel approach such as we present here. We have analyzed various chemical warfare agents (CWAs) and/or toxic industrial compounds (TICs) and related compounds, namely phosgene, diphosgene, chloroacetone, chloroacetophenone, diisopropylaminoethanol, and triethyl phosphate, utilizing a high-resolution proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOFMS) instrument with the objective of finding key product ions and their intensities, which will allow a low-resolution quadrupole mass spectrometry based PTR-MS system to be used with high confidence in the assignment of threat agents in the atmosphere. We obtained high accuracy PTR-TOFMS mass spectra of the six compounds under study at two different values for the reduced electric field in the drift tube (E/N). From these data we have compiled a table containing product ions, and isotopic and E/N ratios for highly selective threat compound detection with a compact and cost-effective quadrupole-based PTR-MS instrument. Furthermore, using chloroacetophenone (tear gas), we demonstrated that this instrument's response is highly linear in the concentration range of typical Acute Exposure Guideline Levels (AEGLs). On the basis of the presented results it is possible to develop a compact and cost-effective PTR-QMS instrument that monitors air supply systems and triggers an alarm as soon as the presence of a threat agent is detected. We hope that this real-time surveillance device will help to seriously improve safety and security in environments vulnerable to terrorist attacks with toxic chemicals.

How are asthmatics included in the derivation of guideline values for emergency planning and response?

Guideline values for emergency planning and response are aimed to protect the general public, including asthmatics and other susceptible groups, during sudden airborne releases of chemicals. A precondition of asthma may increase the individual susceptibility to acute exposures. This paper studies to what extent experimental data on asthmatics are included in the rationale and derivation of guideline values. An analysis of the Technical Support Documents (TSDs) of the Acute Exposure Guideline Levels (AEGLs) shows that only 23 of the 176 TSDs include references to experimental studies on asthmatics, 30 include a statement on asthmatics but no reference to experimental data, and 123 lack any explicit statement on asthmatics. The TSDs were further compared with the support documents of nine other programs for acute or occupational short-term values. All programs were incomplete with respect to experimental data on asthmatics. Omission of asthmatics may interfere with trustful and efficient health protective actions. We suggest that the availability of data on asthmatics should be carefully examined in the development of guideline values, and that the lack of such data should be explicitly noted. In the latter case, available data for other irritants may be used to justify an appropriate assessment factor.

Acute inhalation study of allyl alcohol for derivation of acute exposure guideline levels

An acute, whole-body inhalation study for allyl alcohol in Sprague-Dawley rats was designed to support derivation of AEGL values, with emphasis on establishing NOAELs for irreversible effects of different exposure concentrations and durations. Groups of 10 rats were exposed for 1 hour (0, 50, 200, or 400 ppm), 4 hours (0, 20, 50, or 100 ppm), or 8 hours (0, 10, 20, or 50 ppm). Clinical evaluations were performed during exposure and in an open field within 22–71 minutes after termination of exposure. Clinical pathology, gross necropsy, and histopathology (nasal tissues, larynx, trachea, lungs/bronchi, liver, and kidneys) were evaluated 14 days after exposure. Mortality was limited to 1 male exposed for 8 hours to 50 ppm. Clinical findings of gasping, rales, increased respiration noted at higher exposure levels were rapidly reversed. No treatment-related findings were observed in the liver and kidneys, or in the lungs of surviving animals. Histopathology in the nasal cavity was noted at all exposure levels following 1, 4, or 8 hours of exposure. Mild nasal inflammation was found at the lowest exposure levels (50-ppm/1-hour, 20-ppm/4-hour, and 10-ppm/8-hour). These effects were considered reversible and were not associated with related clinical signs. Severe, irreversible nasal olfactory epithelial lesions were present in 50 ppm/8-hour males. The NOELs for irreversible effects were 400-ppm/1-hour, 100-ppm/4-hour, and 20-ppm/8-hour. The incidence of severe findings was positively dependent on both concentration and the exposure duration. In contrast, the incidence of mild reversible findings did not appear to be dependent on duration.

Assessing the impact of the duration and intensity of inhalation exposure on the magnitude of the variability of internal dose metrics in children and adults

The objective of this study was to assess the impact of the exposure duration and intensity on the human kinetic adjustment factor (HKAF). A physiologically based pharmacokinetic model was used to compute target dose metrics (i.e. maximum blood concentration (Cmax) and amount metabolized/L liver/24 h (Amet)) in adults, neonates (0–30 days), toddlers (1–3 years), and pregnant women following inhalation exposure to benzene, styrene, 1,1,1-trichloroethane and 1,4-dioxane. Exposure scenarios simulated involved various concentrations based on the chemical’s reference concentration (low) and six of U.S. EPA’s Acute Exposure Guideline Levels (AEGLs) (high), for durations of 10 min, 60 min, 8 h, and 24 h, as well as at steady-state. Distributions for body weight (BW), height (H), and hepatic CYP2E1 content were obtained from the literature or from P3M software, whereas blood flows and tissue volumes were calculated from BW and H. The HKAF was computed based on distributions of dose metrics obtained by Monte Carlo simulations [95th percentile in each subpopulation/median in adults]. At low levels of exposure, ranges of Cmax-based HKAF were 1–6.8 depending on the chemical, with 1,4-dioxane exhibiting the greatest values. At high levels of exposure, this range was 1.1–5.2, with styrene exhibiting the greatest value. Neonates were always the most sensitive subpopulation based on Cmax, and pregnant women were most sensitive based on Amet in the majority of the cases (1.3–2.1). These results have shown that the chemical-specific HKAF varies as a function of exposure duration and intensity of inhalation exposures, and sometimes exceeds the default value used in risk assessments.

Emergency responder health: what have we learned from past disasters?

As the Deepwater Horizon disaster unfolds in the Gulf of Mexico, public health practitioners are having a sinking deja vu feeling. Once again, environmental disaster has struck, and tens of thousands of emergency responders—some professionals, but many more volunteers—have swung into action, potentially risking their health as they work to clean up the worst oil spill in U.S. history. Veterans of similar disasters are wondering if historical lessons learned can help keep the damage to a bare minimum. But a paucity of hard data on emergency responder health makes it difficult even to ask the right questions. “Emergency responders have not been adequately studied,” says Gina Solomon, codirector of the occupational and environmental medicine residency and fellowship program at the University of California, San Francisco, and a senior scientist with the Natural Resources Defense Council. “They tend to be ignored.” Professional emergency responders such as firefighters may not put much emphasis on health effects studies. “They are going to do what they need to do regardless of their own safety,” says Don Donahue, executive director of the Center for Health Policy & Preparedness at the Potomac Institute for Policy Studies, who has firefighters in his extended family. “They have to be a little crazy by definition.” That heroic approach is manna for the people they save, but firefighters may pay a price with disorders such as cancer. Studies of cancers in firefighters have had mixed results, but there is evidence linking this occupation with brain, thyroid, esophageal, bladder, testicular, prostate, and cervical cancers, as well as melanoma and Hodgkin disease (Bates1 and Ma et al.2 are two such studies). Health risks tend to be even greater for the many nonprofessional emergency responders who rush to the scene of crises such as oil spills, terrorist attacks, hurricanes, train derailments, and chemical releases. Those workers often don’t have the training and advanced equipment that protect professional emergency responders to some degree. These and many other factors make it a daunting challenge to protect the health of emergency responders during disasters.

Emergency planning and the Control of Major Accident Hazards (COMAH/Seveso II) Directive: An approach to determine the public safety zone for toxic cloud releases

The EU Control of Major Accidents Hazards Directive (Seveso II) requires an external emergency plan for each top tier site. This paper sets out a method to build the protection of public health into emergency planning for Seveso sites in the EU. The method involves the review of Seveso site details prescribed under the directive. The site safety report sets out the potential accident scenarios. The safety report's worst-case scenario, and chemical involved, is used as the basis for the external emergency plan. A decision was needed on the appropriate threshold value to use as the level of concern to protect public health. The definitions of the regulatory standards (air quality standards and occupational standards) in use were studied, how they are derived and for what purpose. The 10 min acute exposure guideline level (AEGL) for a chemical is recommended as the threshold value to inform decisions taken to protect public health from toxic cloud releases. The area delimited by AEGL 1 defines the population who may be concerned about being exposed. They need information based on comprehensive risk assessment. The area delimited by AEGL 2 defines the population for long-term surveillance when indicated and may include first responders. The area delimited by AEGL 3 defines the population who may present acutely to the medical services. It ensures that the emergency responders site themselves safely. A standard methodology facilitates discussions with plant operators and concerned public. Examples show how the methodology can be adapted to suit explosive risk and response to fire.

Impact of spatiotemporal fluctuations in airborne chemical concentration on toxic hazard assessment

Models widely used to assess atmospheric chemical-dispersion hazards for emergency response rely on acute exposure guideline level (AEGL) or similar concentration guidelines to map geographic areas potentially affected by corresponding levels of toxic severity. By ignoring substantial, random variability in concentration over time and space, such standard methods routinely underestimate the size of potentially affected areas. Underestimation due to temporal fluctuation – applicable to chemicals like hydrogen cyanide (HCN) for which peak concentrations best predict acute toxicity – becomes magnified by spatial fluctuation, defined as heterogeneity in average concentration at each location relative to standard-method predictions. The combined impact of spatiotemporal fluctuation on size of assessed threat areas was studied using a statistical-simulation assessment method calibrated to Joint Urban 2003 Oklahoma City field-tracer data. For a hypothetical 60-min urban release scenario involving HCN gas, the stochastic method predicted that lethal/severe effects could occur in an area 18 or 25 times larger than was predicted by standard methods targeted to a 60-min AEGL, assuming wind speeds ≥2.0 or ≤1.5 m/s, respectively. The underestimation doubled when the standard method was targeted to a 10-min AEGL. Further research and field data are needed for improved stochastic methods to assess spatiotemporal fluctuation effects.

Incorporation of Acute Dynamic Ventilation Changes into a Standardized Physiologically Based Pharmacokinetic Model

A seven-compartment physiologically based pharmacokinetic (PBPK) model incorporating a dynamic ventilation response has been developed to predict normalized internal dose from inhalation exposure to a large range of volatile gases. The model uses a common set of physiologic parameters, including standardized ventilation rates and cardiac outputs for rat and human. This standardized model is validated against experimentally measured blood and tissue concentrations for 21 gases. For each of these gases, body-mass-normalized critical internal dose (blood concentration) is established, as calculated using exposure concentration and time duration specified by the lowest observed adverse effect level (LOAEL) or the acute exposure guideline level (AEGL). The dynamic ventilation changes are obtained by combining the standardized PBPK model with the Toxic Gas Assessment Software 2.0 (TGAS-2), a validated acute ventilation response model. The combined TGAS-2P model provides a coupled, transient ventilation and pharmacokinetic response that predicts body mass normalized internal dose that is correlated with deleterious outcomes. The importance of ventilation in pharmacokinetics is illustrated in a simulation of the introduction of Halon 1301 into an environment of fire gases.

Development and Application of Acute Exposure Guideline Levels (AEGLs) for Chemical Warfare Nerve and Sulfur Mustard Agents

Acute exposure guideline levels (AEGLs) have been developed for the chemical warfare agents GB, GA, GD, GF, VX, and sulfur mustard. These AEGLs were approved by the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances after Federal Register publication and comment, and judged as scientifically valid by the National Research Council Committee on Toxicology Subcommittee on AEGLs. AEGLs represent general public exposure limits for durations ranging from 10 min to 8 h, and for three levels of severity (AEGL-1, AEGL-2, AEGL-3). Mild effects are possible at concentrations greater than AEGL-1, while life-threatening effects are expected at concentrations greater than AEGL-3. AEGLs can be applied to various civilian and national defense purposes, including evacuation and shelter-in-place protocols, reentry levels, protective clothing specifications, and analytical monitoring requirements. This report documents development and derivation of AEGL values for six key chemical warfare agents, and makes recommendations for their application to various potential exposure scenarios. This submission was sponsored by a contractor of the U.S. government under contract DE-AC05-00OR22725. Accordingly, the U.S. government retains a nonexclusive, royalty-free license to publish or reproduce these documents, or to allow others to do so, for U.S. government purposes. These documents may be freely distributed and used for noncommercial, scientific and educational purposes.