Cham E. Dallas

A consensus-based educational framework and competency set for the discipline of disaster medicine and public health preparedness.

BACKGROUND Various organizations and universities have developed competencies for health professionals and other emergency responders. Little effort has been devoted to the integration of these competencies across health specialties and professions. The American Medical Association Center for Public Health Preparedness and Disaster Response convened an expert working group (EWG) to review extant competencies and achieve consensus on an educational framework and competency set from which educators could devise learning objectives and curricula tailored to fit the needs of all health professionals in a disaster. METHODS The EWG conducted a systematic review of peer-reviewed and non-peer reviewed published literature. In addition, after-action reports from Hurricane Katrina and relevant publications recommended by EWG members and other subject matter experts were reviewed for congruencies and gaps. Consensus was ensured through a 3-stage Delphi process. RESULTS The EWG process developed a new educational framework for disaster medicine and public health preparedness based on consensus identification of 7 core learning domains, 19 core competencies, and 73 specific competencies targeted at 3 broad health personnel categories. CONCLUSIONS The competencies can be applied to a wide range of health professionals who are expected to perform at different levels (informed worker/student, practitioner, leader) according to experience, professional role, level of education, or job function. Although these competencies strongly reflect lessons learned following the health system response to Hurricane Katrina, it must be understood that preparedness is a process, and that these competencies must be reviewed continually and refined over time.

Vulnerability of populations and the urban health care systems to nuclear weapon attack--examples from four American cities.

BackgroundThe threat posed by the use of weapons of mass destruction (WMD) within the United States has grown significantly in recent years, focusing attention on the medical and public health disaster capabilities of the nation in a large scale crisis. While the hundreds of thousands or millions of casualties resulting from a nuclear weapon would, in and of itself, overwhelm our current medical response capabilities, the response dilemma is further exacerbated in that these resources themselves would be significantly at risk. There are many limitations on the resources needed for mass casualty management, such as access to sufficient hospital beds including specialized beds for burn victims, respiration and supportive therapy, pharmaceutical intervention, and mass decontamination.ResultsThe effects of 20 kiloton and 550 kiloton nuclear detonations on high priority target cities are presented for New York City, Chicago, Washington D.C. and Atlanta. Thermal, blast and radiation effects are described, and affected populations are calculated using 2000 block level census data. Weapons of 100 Kts and up are primarily incendiary or radiation weapons, able to cause burns and start fires at distances greater than they can significantly damage buildings, and to poison populations through radiation injuries well downwind in the case of surface detonations. With weapons below 100 Kts, blast effects tend to be stronger than primary thermal effects from surface bursts. From the point of view of medical casualty treatment and administrative response, there is an ominous pattern where these fatalities and casualties geographically fall in relation to the location of hospital and administrative facilities. It is demonstrated that a staggering number of the main hospitals, trauma centers, and other medical assets are likely to be in the fatality plume, rendering them essentially inoperable in a crisis.ConclusionAmong the consequences of this outcome would be the probable loss of command-and-control, mass casualties that will have to be treated in an unorganized response by hospitals on the periphery, as well as other expected chaotic outcomes from inadequate administration in a crisis. Vigorous, creative, and accelerated training and coordination among the federal agencies tasked for WMD response, military resources, academic institutions, and local responders will be critical for large-scale WMD events involving mass casualties.

Physiological pharmacokinetic modeling of inhaled trichloroethylene in rats

The pharmacokinetics of trichloroethylene (TCE) was characterized during and following inhalation exposures of male Sprague-Dawley rats. The blood and exhaled breath TCE time-course data were used to formulate and assess the accuracy of predictions of a physiologically based pharmacokinetic (PB-PK) model for TCE inhalation. Fifty or 500 ppm of TCE was inhaled by unanesthetized rats of 325-375 g for 2 hr through a miniaturized one-way breathing valve. Repetitive samples of the inhaled and exhaled breath streams, as well as arterial blood, were collected concurrently during and for 3 hr following the exposures and analyzed for TCE by headspace gas chromatography. Respiratory rates and volumes were continuously monitored and used in conjunction with the pharmacokinetic data to delineate uptake and elimination profiles. Levels of TCE in the exhaled breath attained near steady-state soon after the beginning of exposures, and were then directly proportional to the inhaled concentration. Exhaled breath levels of TCE in rats were similar in magnitude to values previously published for TCE inhalation exposures of humans. Levels of TCE in the blood of the 50 ppm-exposed animals also rapidly approached near steady-state, but blood levels in the 500 ppm-exposed animals rose progressively, reaching concentrations 25- to 30-fold higher than in the 50 ppm group during the second hour of exposure. The 10-fold increase in inhaled concentration resulted in an 8.7-fold increase in cumulative uptake, or total absorbed dose. These findings of nonlinearity indicate that metabolic saturation ensued during the 500 ppm exposure. The PB-PK model was characterized as blood flow-limited with TCE eliminated unchanged in the exhaled breath and by saturable liver metabolism. The uptake and elimination profiles were accurately simulated by the PB-PK model for both the 50 and 500 ppm TCE exposure levels. Such a model may be quite useful in risk assessments in predicting internal (i.e., systemically absorbed) doses of TCE and other volatile organics under a variety of exposure scenarios.

BARIUM: RATIONALE FOR A NEW ORAL REFERENCE DOSE

The U.S. Environmental Protection Agency (EPA) has an established oral reference dose (RfD) value for Ba of 0.07 mg Ba/kg/d based on a 1984 investigation that reported hypertension. In this study, the toxicological data for Ba has been reevaluated and a revised oral RfD is proposed. The toxicokinetic, acute, and chronic toxicity, carcinogenicity, and reproductive animal studies as well as epidemiological and occupational health human studies for Ba exposure were reviewed for applicability to an oral RfD. The available human studies have some utility but suffer from either a small population size, a short exposure regimen, or difficulties in identifying definitive Ba exposure in the study population. As a result, the available long-term animal studies were found to be more appropriate for the RfD derivation. A dose-response assessment of no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) values determined that kidney effects are the most sensitive endpoint for adverse health effects related to chronic soluble Ba ingestion in mammals. The most complete animal studies were conducted by the National Toxicology Program (NTP, 1994) and the lowest species NOAELs were 75 mg Ba/kg/d in male mice and 60 mg Ba/kg/d for male rats. The male rats were identified to be the most sensitive population tested and their NOAEL value was selected for extrapolation to an oral RfD. Application of overall uncertainty factors to the lowest NOAEL value from a chronic animal study of either 90 (based on an approach proposed by Dourson, 1994) or the generally accepted 100 results in an oral RfD of 0.66 mg Ba/kg/d or 0.6 mg Ba/kg/d, respectively. It is proposed to use the more conservative value of 0.6 mg Ba/kg/d. This reassessment results in nearly an order of magnitude increase in the U.S. EPA oral RfD for Ba.The U.S. Environmental Protection Agency (EPA) has an established oral reference dose (RfD) value for Ba of 0.07 mg Ba/kg/d based on a 1984 investigation that reported hypertension. In this study, the toxicological data for Ba has been reevaluated and a revised oral RfD is proposed. The toxicokinetic, acute, and chronic toxicity, carcinogenicity, and reproductive animal studies as well as epidemiological and occupational health human studies for Ba exposure were reviewed for applicability to an oral RfD. The available human studies have some utility but suffer from either a small population size, a short exposure regimen, or difficulties in identifying definitive Ba exposure in the study population. As a result, the available long-term animal studies were found to be more appropriate for the RfD derivation. A dose-response assessment of no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) values determined that kidney effects are the most sensitive endpoint for adverse health effects related to chronic soluble Ba ingestion in mammals. The most complete animal studies were conducted by the National Toxicology Program (NTP, 1994) and the lowest species NOAELs were 75 mg Ba/kg/d in male mice and 60 mg Ba/kg/d or male rats. The male rats were identified to be the most sensitive population tested and their NOAEL value was selected for extrapolation to an oral RfD. Application of overall uncertainty factors to the lowest NOAEL value from a chronic animal study of either 90 (based on an approach proposed by Dourson, 1994) or the generally accepted 100 results in an oral RfD of 0.66 mg Ba/kg/d or 0.6 mg Ba/kg/d, respectively. It is proposed to use the more conservative value of 0.6 mg Ba/kg/d. This reassessment results in nearly an order of magnitude increase in the U.S. EPA oral RfD for Ba.

Flow cytometric DNA analysis of ducks accumulating 137Cs on a reactor reservoir.

The objective of this study was to detect red blood cell (rbc) DNA abnormalities in male, game-farm mallard ducks as they ranged freely and accumulated 137Cs (radiocesium) from an abandoned nuclear reactor cooling reservoir. Prior to release, the ducks were tamed to enable recapture at will. Flow cytometric measurements conducted at intervals during the first year of exposure yielded cell cycle percentages of DNA (G0/G1, S, G2 + M phases) of rbc, as well as coefficients of variation (CV) in the G0/G1 phase. DNA histograms of exposed ducks were compared with two sets of controls which were maintained 30 and 150 miles from the study site. 137Cs live wholebody burdens were also measured in these animals in a parallel kinetics study, and an approximate steady-state equilibrium was attained after about 8 months. DNA histograms from 2 of the 14 contaminated ducks revealed DNA aneuploid-like patterns after 9 months exposure. These two ducks were removed from the experiment at this time, and when sampled again 1 month later, one continued to exhibit DNA aneuploidy. None of the control DNA histograms demonstrated DNA aneuploid-like patterns. There were no significant differences in cell cycle percentages at any time point between control and exposed animals. A significant increase in CV was observed at 9 months exposure, but after removal of the two ducks with DNA aneuploidy, no significant difference was detected in the group monitored after 12 months exposure. An increased variation in the DNA and DNA aneuploidy could, therefore, be detected in duck rbc using flow cytometric analysis, with the onset of these effects being related to the attainment of maximal levels of 137Cs body burdens in the exposed animals.

The uptake and elimination of 1,1,1-trichloroethane during and following inhalation exposures in rats☆☆☆

The pharmacokinetics of 1,1,1-trichloroethane (TRI) was studied in male Sprague-Dawley rats in order to characterize and quantify TRI uptake and elimination oby direct measurements of the inhaled and exhaled compound. Fifty or 500 ppm TRI was inhaled for 2 hr through a one-way breathing valve by unanesthetized rats of 325-375 g. Repetitive samples of the separate inhaled and exhaled breath streams, as well as arterial blood, were collected concurrently both during and following TRI inhalation and analyzed for TRI by gas chromatography. Respiratory rates and volumes were continuously monitored during and following exposure and were used in conjunction with the pharmacokinetic data to characterize profiles of uptake and elimination. TRI was very rapidly absorbed from the lung, in that substantial levels were present in arterial blood at the first sampling time (i.e., 2 min). Blood and exhaled breath concentrations of TRI increased rapidly after the initiation of exposure, approaching but not reaching steady state during the 2-hr exposures. The blood and exhaled breath concentrations were directly proportional to the exposure concentration during the exposures. Percentage uptake of TRI decreased 30-35% during the first hour of inhalation, diminishing to approximately 45-50% by the end of the exposure. Total cumulative uptake in the 50 and 500 ppm groups over the 2-hr inhalation exposures was determined to be 6 and 48 mg/kg body wt, respectively. By the end of the exposure period, 2.1 and 20.8 mg, respectively, of inhaled TRI was eliminated from rats inhaling 50 and 500 ppm TRI. A physiological pharmacokinetic model for TRI inhalation was utilized to predict blood and exhaled breath concentrations for comparison with observed experimental values. Overall, values predicted by the physiological pharmacokinetic model for TRI levels in the blood and exhaled breath were in close agreement with measured values both during and following TRI inhalation.

Oral Toxicity of 1,2-Dichloropropane: Acute, Short-Term, and Long-Term Studies in Rats

The objective of this investigation was to characterize the acute and short- and long-term toxic potency of orally administered 1,2-dichloropropane (DCP). In the acute and short-term studies, male rats of 250-300 g were gavaged with 0, 100, 250, 500, or 1000 mg DCP/kg in corn oil once daily for up to 10 consecutive days. Although ingestion of DCP caused body weight loss and CNS depression, few other toxic effects were manifest 24 hr after a single dose of the chemical. Morphological changes were limited to liver centrilobular cells in 500 and 1000 mg/kg rats. Similarly, elevated activity of some serum enzymes occurred only at these two highest dose levels. Hepatic nonprotein sulfhydryl (NPS) levels were decreased and renal NPS levels increased at 24 hr. In the short-term study resistance developed to DCP hepatotoxicity over the 10 consecutive days of exposure, as reflected by progressively lower serum enzyme levels and by decreases in the severity and incidence of toxic hepatitis and periportal vacuolization. Nucleolar enlargement in hepatocytes, however, was observed at all dosage levels at 5 and 10 days. There were a number of manifestations of hemolytic anemia, including erythrophagocytosis in the liver, splenic hemosiderosis and hyperplasia of erythropoietic elements of the red pulp, renal tubular cell hemosiderosis, and hyperbilirubinemia. Urinalyses and histopathology revealed no evidence of nephrotoxicity. In the long-term study, male rats initially weighing 180-200 g were gavaged five times weekly for up to 13 weeks with 0, 100, 250, 500, or 750 mg DCP/kg. As over one-half the 750 mg/kg group died within 10 days, the survivors were sacrificed. Histopathological changes in the 750 mg/kg animals included mild hepatitis and splenic hemosiderosis, as well as adrenal medullary vacuolization and cortical lipidosis, testicular degeneration and a reduction in sperm, and increased number of degenerate spermatogonia in the epididymis in some members of the group. Similar testicular and epididymal degenerative change also were observed in some 500 mg/kg animals after 13 weeks of dosing. There was a progressive increase in the number of deaths in the 500 mg/kg group, such that more than 50% were dead by 13 weeks. No deaths occurred in the 100 or 250 mg/kg groups. The DCP dosage regimen also produced a dose-dependent decrease in body weight gain. DCP exhibited very limited hepatotoxic potential and no apparent nephrotoxic potential in the long-term study. Slight elevations in serum ornithine-carbamyltransferase activity, periportal vacuolization, and active fibroplasia in the liver were seen in the 500 mg/kg animals.

Schedule-Controlled Operant Behavior of Rats During 1,1,1-Trichloroethane Inhalation: Relationship to Blood and Brain Solvent Concentrations1

The central nervous system is the principal target of 1,1,1-trichloroethane (TRI), and several studies of this volatile solvent have demonstrated effects on learned animal behaviors. There have been few attempts, however, to quantitatively relate such effects to blood or target organ (brain) solvent concentrations. Therefore, Sprague-Dawley rats trained to lever-press for evaporated milk on a variable interval 30-s reinforcement schedule were placed in an operant test cage and exposed to clean air for 20 min, followed by a single concentration of TRI vapor (500-5000 ppm) for 100 min. Additional rats were exposed to equivalent TRI concentrations for 10, 20, 40, 60, 80, or 100 min to determine blood and brain concentration vs. time profiles. Inhalation of 1000 ppm slightly increased operant response rates, whereas 2000, 3500, and 5000 ppm decreased operant response rates in a concentration- and time-dependent manner. Accumulation of TRI in blood and brain was rapid and concentration dependent, with the brain concentration roughly twice that of blood. Plots of blood and brain TRI concentrations against operant performance showed responding in excess of control rates at low concentrations, and decreasing response rates as concentrations increased. Linear regression analyses indicated that blood and brain concentrations, as well as measures of time integrals of internal dose, were strongly correlated with operant performance. Neurobehavioral toxicity in laboratory animals, as measured by changes in operant performance, can therefore be quantitatively related to internal measures of TRI exposure to enhance its predictive value for human risk assessment.

SCHEDULE-CONTROLLED OPERANT BEHAVIOR OF RATS FOLLOWING ORAL ADMINISTRATION OF PERCHLOROETHYLENE: TIME COURSE AND RELATIONSHIP TO BLOOD AND BRAIN SOLVENT LEVELS

Previous studies have indicated that human exposure to perchloroethylene (PCE) produces subtle behavioral changes and other neurological effects at concentration at or below the current occupational exposure limit. Since comparable effects in animals may be reflected by changes in schedule-controlled operant behavior, the ability of orally administered PCE to alter fixed-ratio (FR) responding for a food reward was investigated in male Sprague-Dawley rats. Furthermore, since behavioral effects of solvents are likely to be more closely related to blood or target tissue (i.e, brain) concentrations than administered dose, the relationship between the pharmacokinetic distribution of PCE and its effects on operant responding was also evaluated. Rats trained to lever-press for evaporated milk on an FR-40 reinforcement schedule were gavaged with 160 or 480 mg/kg PCE and immediately placed in an operant test cage for 90 min. Separate animals gavaged with equivalent doses of PCE were used to determine profiles of blood and brain concentrations versus time. Perchloroethylene produced changes in responding that varied not only with dose but also among animals receiving the same dose. Changes in the response rates of rats receiving 160 mg/kg PCE were either not readily apparent, restricted to the first 5 min of the operant session, or attributable to gavage stress and the dosing vehicle. However, 480 mg/kg produced either an immediate suppression of responding for 15-30 min before a rapid recovery to control rates or a complete elimination of lever-pressing for the majority of the operant session. Although the two doses of PCE produced markedly different effects on operant behavior during the first 30 min of exposure, differences in brain concentrations of PCE were minimal. Furthermore, the majority of animals receiving 480 mg/kg PCE fully recovered from response suppression while blood and brain levels of the solvent continued to rise. Thus, relationships between blood and brain PCE levels and performance impairment were not discernible over the monitored time course. Since the rapid onset of response suppression suggests that the precipitating event occurs within the first few minutes of exposure, it is possible that altered responding is related to the rate of increase in blood or brain concentrations rather than the absolute solvent concentrations themselves. The relationship between the pharmacokinetic distribution of solvents and their effects on the central nervous system is obviously complex and may involve acute neuronal adaptation as well as the dynamics of solvent distribution among the various body compartments.

Analyses of volatile C2 haloethanes and haloethenes in tissues: sample preparation and extraction

A tissue extraction procedure was developed which minimized loss of readily volatilizable compounds for subsequent quantification by headspace gas chromatography, and evaluated for perchloroethylene (PER), 1,1,1-trichloroethane, 1,1,2,2-tetrachloroethane, and 1,1,2-trichloroethylene. Of the procedures evaluated, joint isooctane and saline tissue homogenization had the most efficient recovery, ranging from 73 to 104% for the four halocarbons from seven different rat tissues. PER concentrations were also determined in tissues of rats following in vivo halocarbon administration. Recovery did not appear to be tissue-dependent, but did vary somewhat with test chemical, with the least volatile, most lipophilic compounds exhibiting the highest recovery.