Characterizing concentrations of diethylene glycol and suspected metabolites in human serum, urine, and cerebrospinal fluid samples from the Panama DEG mass poisoning.

CONTEXT: Diethylene glycol (DEG) mass poisoning is a persistent public health problem. Unfortunately, there are no human biological data on DEG and its suspected metabolites in poisoning. If present and associated with poisoning, the evidence for use of traditional therapies such as fomepizole and/or hemodialysis would be much stronger. OBJECTIVE: To characterize DEG and its metabolites in stored serum, urine, and cerebrospinal fluid (CSF) specimens obtained from human DEG poisoning victims enrolled in a 2006 case-control study. METHODS: In the 2006 study, biological samples from persons enrolled in a case-control study (42 cases with new-onset, unexplained AKI and 140 age-, sex-, and admission date-matched controls without AKI) were collected and shipped to the Centers for Disease Control and Prevention (CDC) in Atlanta for various analyses and were then frozen in storage. For this study, when sufficient volume of the original specimen remained, the following analytes were quantitatively measured in serum, urine, and CSF: DEG, 2-hydroxyethoxyacetic acid (HEAA), diglycolic acid, ethylene glycol, glycolic acid, and oxalic acid. Analytes were measured using low resolution GC/MS, descriptive statistics calculated and case results compared with controls when appropriate. Specimens were de-identified so previously collected demographic, exposure, and health data were not available. The Wilcoxon Rank Sum test (with exact p-values) and bivariable exact logistic regression were used in SAS v9.2 for data analysis. RESULTS: The following samples were analyzed: serum, 20 case, and 20 controls; urine, 11 case and 22 controls; and CSF, 11 samples from 10 cases and no controls. Diglycolic acid was detected in all case serum samples (median, 40.7 mcg/mL; range, 22.6-75.2) and no controls, and in all case urine samples (median, 28.7 mcg/mL; range, 14-118.4) and only five (23%) controls (median, < Lower Limit of Quantitation (LLQ); range, < LLQ-43.3 mcg/mL). Significant differences and associations were identified between case status and the following: 1) serum oxalic acid and serum HEAA (both OR = 14.6; 95% C I = 2.8-100.9); 2) serum diglycolic acid and urine diglycolic acid (both OR > 999; exact p < 0.0001); and 3) urinary glycolic acid (OR = 0.057; 95% C I = 0.001-0.55). Two CSF sample results were excluded and two from the same case were averaged, yielding eight samples from eight cases. Diglycolic acid was detected in seven (88%) of case CSF samples (median, 2.03 mcg/mL; range, < LLQ, 7.47). DISCUSSION: Significantly elevated HEAA (serum) and diglycolic acid (serum and urine) concentrations were identified among cases, which is consistent with animal data. Low urinary glycolic acid concentrations in cases may have been due to concurrent AKI. Although serum glycolic concentrations among cases may have initially increased, further metabolism to oxalic acid may have occurred thereby explaining the similar glycolic acid concentrations in cases and controls. The increased serum oxalic acid concentration results in cases versus controls are consistent with this hypothesis. CONCLUSION: Diglycolic acid is associated with human DEG poisoning and may be a biomarker for poisoning. These findings add to animal data suggesting a possible role for traditional antidotal therapies. The detection of HEAA and diglycolic acid in the CSF of cases suggests a possible association with signs and symptoms of DEG-associated neurotoxicity. Further work characterizing the pathophysiology of DEG-associated neurotoxicity and the role of traditional toxic alcohol therapies such as fomepizole and hemodialysis is needed.

Formaldehyde levels in FEMA-supplied travel trailers, park models, and mobile homes in Louisiana and Mississippi.

In 2006, area physicians reported increases in upper respiratory symptoms in patients living in U.S. Federal Emergency Management Agency (FEMA)-supplied trailers following Hurricanes Katrina and Rita. One potential etiology to explain their symptoms included formaldehyde; however, formaldehyde levels in these occupied trailers were unknown. The objectives of our study were to identify formaldehyde levels in occupied trailers and to determine factors or characteristics of occupied trailers that could affect formaldehyde levels. A disproportionate random sample of 519 FEMA-supplied trailers was identified in Louisiana and Mississippi in November 2007. We collected and tested an air sample from each trailer for formaldehyde levels and administered a survey. Formaldehyde levels among all trailers in this study ranged from 3 parts per billion (ppb) to 590 ppb, with a geometric mean (GM) of 77 ppb [95% confidence interval (CI): 70-85; range: 3-590 ppb]. There were statistically significant differences in formaldehyde levels between trailer types (P < 0.01). The GM formaldehyde level was 81 ppb (95% CI: 72-92) among travel trailers (N = 360), 57 ppb (95% CI: 49-65) among mobile homes (N = 57), and 44 ppb (95% CI: 38-53) among park models (N = 44). Among travel trailers, formaldehyde levels varied significantly by brand. While formaldehyde levels varied by trailer type, all types tested had some levels ≥ 100 ppb.

Emerging areas of research reported during the CDC National Conference on Pfiesteria: from biology to public health.

Since its identification in 1996, the marine dinoflagellate Pfiesteria piscicida Steidinger & Burkholder has been the focus of intense scientific inquiry in disciplines ranging from estuarine ecology to epidemiology and from molecular biology to public health. Despite these research efforts, the extent of human exposure and the degree of human illness directly associated with Pfiesteria is still in the process of being defined. Unfortunately, during this same time Pfiesteria has also stimulated media coverage that in some instances jumped ahead of the science to conclude that Pfiesteria presents a widespread threat to human health. Political and economic forces also came into play when the tourism and seafood industries were adversely impacted by rumors of toxin-laden water in estuaries along the east coast of the United States. Amid this climate of evolving science and public concern, Pfiesteria has emerged as a highly controversial public health issue. In October 2000 Centers for Disease Control and Prevention sponsored the National Conference on Pfiesteria: From Biology to Public Health to bring together Pfiesteria researchers from many disparate disciplines. The goal of this meeting was to describe the state of the science and identify directions for future research. In preparation for the conference an expert peer-review panel was commissioned to review the existing literature and identify research gaps; the summary of their review is published in this monograph. During the meeting primary Pfiesteria researchers presented previously unpublished results. The majority of those presentations are included as peer-reviewed articles in this monograph. The discussion portion of the conference focused upon researcher-identified research gaps. This article details the discussion segments of the conference and makes reference to the presentations as it describes emerging areas of Pfiesteria research.

The potential impacts of climate variability and change on temperature-related morbidity and mortality in the United States.

Heat and heat waves are projected to increase in severity and frequency with increasing global mean temperatures. Studies in urban areas show an association between increases in mortality and increases in heat, measured by maximum or minimum temperature, heat index, and sometimes, other weather conditions. Health effects associated with exposure to extreme and prolonged heat appear to be related to environmental temperatures above those to which the population is accustomed. Models of weather-mortality relationships indicate that populations in northeastern and midwestern U.S. cities are likely to experience the greatest number of illnesses and deaths in response to changes in summer temperature. Physiologic and behavioral adaptations may reduce morbidity and mortality. Within heat-sensitive regions, urban populations are the most vulnerable to adverse heat-related health outcomes. The elderly, young children, the poor, and people who are bedridden or are on certain medications are at particular risk. Heat-related illnesses and deaths are largely preventable through behavioral adaptations, including the use of air conditioning and increased fluid intake. Overall death rates are higher in winter than in summer, and it is possible that milder winters could reduce deaths in winter months. However, the relationship between winter weather and mortality is difficult to interpret. Other adaptation measures include heat emergency plans, warning systems, and illness management plans. Research is needed to identify critical weather parameters, the associations between heat and nonfatal illnesses, the evaluation of implemented heat response plans, and the effectiveness of urban design in reducing heat retention.

The potential health impacts of climate variability and change for the United States: executive summary of the report of the health sector of the U.S. National Assessment.

We examined the potential impacts of climate variability and change on human health as part of a congressionally mandated study of climate change in the United States. Our author team, comprising experts from academia, government, and the private sector, was selected by the federal interagency U.S. Global Change Research Program, and this report stems from our first 18 months of work. For this assessment we used a set of assumptions and/or projections of future climates developed for all participants in the National Assessment of the Potential Consequences of Climate Variability and Change. We identified five categories of health outcomes that are most likely to be affected by climate change because they are associated with weather and/or climate variables: temperature-related morbidity and mortality; health effects of extreme weather events (storms, tornadoes, hurricanes, and precipitation extremes); air-pollution-related health effects; water- and foodborne diseases; and vector- and rodent-borne diseases. We concluded that the levels of uncertainty preclude any definitive statement on the direction of potential future change for each of these health outcomes, although we developed some hypotheses. Although we mainly addressed adverse health outcomes, we identified some positive health outcomes, notably reduced cold-weather mortality, which has not been extensively examined. We found that at present most of the U.S. population is protected against adverse health outcomes associated with weather and/or climate, although certain demographic and geographic populations are at increased risk. We concluded that vigilance in the maintenance and improvement of public health systems and their responsiveness to changing climate conditions and to identified vulnerable subpopulations should help to protect the U.S. population from any adverse health outcomes of projected climate change.

Excess hospital admissions during the July 1995 heat wave in Chicago.

INTRODUCTION: This study describes medical conditions treated in all 47 non-VA hospitals in Cook County, IL during the 1995 heat wave. We characterize the underlying diseases of the susceptible population, with the goal of tailoring prevention efforts. METHODS: Primary and secondary discharge diagnoses made during the heat wave and comparison periods were obtained from computerized inpatient hospital discharge data to determine reasons for hospitalization, and comorbid conditions, respectively. RESULTS: During the week of the heat wave, there were 1072 (11%) more hospital admissions than average for comparison weeks and 838 (35%) more than expected among patients aged 65 years and older. The majority of this excess (59%) were treatments for dehydration, heat stroke, and heat exhaustion; with the exception of acute renal failure no other primary discharge diagnoses were significantly elevated. In contrast, analysis of comorbid conditions revealed 23% (p = 0.019) excess admissions of underlying cardiovascular diseases, 30% (p = 0.033) of diabetes, 52% (p = 0.011) of renal diseases, and 20% (p = 0.027) of nervous system disorders. Patient admissions for emphysema (p = 0.007) and epilepsy (p = 0.009) were also significantly elevated during the heat wave week. CONCLUSIONS: The majority of excess hospital admissions were due to dehydration, heat stroke, and heat exhaustion, among people with underlying medical conditions. Short-term public health interventions to reduce heat-related morbidity should be directed toward these individuals to assure access to air conditioning and adequate fluid intake. Long-term prevention efforts should aim to improve the general health condition of people at risk through, among other things, regular physician-approved exercise.

Volatile organic compound testing of a population living near a hazardous waste site.

Accurate measures of individual exposure are critical in reducing misclassification and establishing scientifically valid associations between health outcomes and exposures to environmental contaminants. As part of a community health study, the Agency for Toxic Substances and Disease Registry conducted exposure testing for volatile organic compounds (VOCs) in the blood of people residing near an industrial complex. The purposes of the study were to assess recent exposures to VOCs in this community and to assess the utility of conducting blood VOC testing on populations near hazardous waste sites. One hundred blood specimens from the target area and 106 blood specimens from the control area were collected for analysis. The blood VOC levels in the target-area participants were compared to those in the control area and to a national reference population. Of the 31 separate VOCs for which testing was done, only acetone was statistically significantly (p < 0.05) higher in target-area participants (1,636 parts per billion [ppb]) than in control-area participants (1,353 ppb). 1,1,1-Trichloroethane was found at higher geometric mean levels in the control group (0.169 ppb) than in the target group (0.115 ppb) (p = 0.01). Median blood levels of 2-butanone and 1,4-dichlorobenzene were slightly higher in both target- and control-area groups than in the national reference population, but neither area was statistically significantly higher than the national reference population for any contaminant measured. Overall, there appeared to be no association between residing in the target area and elevated blood VOC levels. Based on the results of this study, blood VOC testing should be limited to populations living near sites where environmental testing has shown recent, elevated VOC exposure, or where unusual circumstances of illness may be attributed to VOC exposure.

Removing the smoking confounder from blood volatile organic compounds measurements.

Because smoking is a major contributor to the internal dose levels of many volatile organic compounds (VOCs), it is difficult to assess other VOC exposures among smokers. Purge and trap/gas chromatography/isotope-dilution mass spectrometry was used to determine the internal dose of VOCs of smokers and nonsmokers. Median whole blood concentrations of benzene, styrene, and toluene were shown to be approximately two times higher among smokers than among nonsmokers. In addition, smoking elevated the blood levels of ethylbenzene, m-/p-xylene, and o-xylene when the log-transformed data were compared. Smoking also led to greatly increased levels of 2,5-dimethylfuran. These results indicate that blood levels of many VOCs are highly correlated with blood levels of 2,5-dimethylfuran and that this effect is primarily a result of smoking. The smoking confounder to blood levels of VOCs can be removed by including the concentration of blood 2,5-dimethylfuran concentration when evaluating results from a health and exposure evaluation. Determining the blood 2,5-dimethylfuran concentration appears to be an effective means of correcting the confounding influence of smoking and supplies a way of determining lower-level exposures that previously could not have been distinguished from the effects of smoking.

Case-control study of bladder cancer and water disinfection methods in Colorado.

A population-based case-control study of bladder cancer and drinking water disinfection methods was conducted during 1990-1991 in Colorado. Surface water in Colorado has historically been disinfected with chlorine (chlorination) or with a combination of chlorine and ammonia (chloramination). A total of 327 histologically verified bladder cancer cases were frequency matched by age and sex to 261 other-cancer controls. Subjects were interviewed by telephone about residential and water source histories. This information was linked to data from water utility and Colorado Department of Health records to create a drinking water exposure profile. After adjustment for cigarette smoking, tap water and coffee consumption, and medical history factors by logistic regression, years of exposure to chlorinated surface water were significantly associated with risk for bladder cancer (p = 0.0007). The odds ratio for bladder cancer increased for longer durations of exposure to a level of 1.8 (95% confidence interval 1.1-2.9) for more than 30 years of exposure to chlorinated surface water compared with no exposure. The increased bladder cancer risk was similar for males and females and for nonsmokers and smokers. Levels of total trihalomethanes, nitrates, and residual chlorine were not associated with bladder cancer risk after controlling for years of exposure to chlorinated water.