Agency for Toxic Substances and Disease Registry

Biologic monitoring (i.e., biomonitoring) is used to assess human exposures to environmental and workplace chemicals. Urinary biomonitoring data typically are adjusted to a constant creatinine concentration to correct for variable dilutions among spot samples. Traditionally, this approach has been used in population groups without much diversity. The inclusion of multiple demographic groups in studies using biomonitoring for exposure assessment has increased the variability in the urinary creatinine levels in these study populations. Our objectives were to document the normal range of urinary creatinine concentrations among various demographic groups, evaluate the impact that variations in creatinine concentrations can have on classifying exposure status of individuals in epidemiologic studies, and recommend an approach using multiple regression to adjust for variations in creatinine in multivariate analyses. We performed a weighted multivariate analysis of urinary creatinine concentrations in 22,245 participants of the Third National Health and Nutrition Examination Survey (1988-1994) and established reference ranges (10th-90th percentiles) for each demographic and age category. Significant predictors of urinary creatinine concentration included age group, sex, race/ethnicity, body mass index, and fat-free mass. Time of day that urine samples were collected made a small but statistically significant difference in creatinine concentrations. For an individual, the creatinine-adjusted concentration of an analyte should be compared with a "reference" range derived from persons in a similar demographic group (e.g., children with children, adults with adults). For multiple regression analysis of population groups, we recommend that the analyte concentration (unadjusted for creatinine) should be included in the analysis with urinary creatinine added as a separate independent variable. This approach allows the urinary analyte concentration to be appropriately adjusted for urinary creatinine and the statistical significance of other variables in the model to be independent of effects of creatinine concentration.

This toxicological profile is prepared in accordance with guidelines developed by the Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised and republished as necessary. The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects information for these toxic substances described therein. Each peer-reviewed profile identifies and reviews the key literature that describes a substance's toxicologic properties. Other pertinent literature is also presented, but is described in less detail than the key studies. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. CAS# 7439-92-1

This public health statement tells you about cadmium and the effects of exposure to it.The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in the nation. These sites are then placed on the National Priorities List (NPL) and are targeted for long-term federal clean-up activities. Cadmium has been found in at least 1,014 of the 1,669 current or former NPL sites. Although the total number of NPL sites evaluated for this substance is not known, the possibility exists that the number of sites at which cadmium is found may increase in the future as more sites are evaluated. This information is important because these sites may be sources of exposure and exposure to this substance may be harmful.When a substance is released either from a large area, such as an industrial plant, or from a container, such as a drum or bottle, it enters the environment. Such a release does not always lead to exposure. You can be exposed to a substance only when you come in contact with it. You may be exposed by breathing, eating, or drinking the substance, or by skin contact.If you are exposed to cadmium or cadmium compounds, many factors will determine whether you will be harmed. These factors include the dose (how much), the duration (how long), and how you come in contact with it. You must also consider any other chemicals you are exposed to and your age, sex, diet, family traits, lifestyle, and state of health.

There is scientific consensus that the global climate is changing, with rising surface temperatures, melting ice and snow, rising sea levels, and increasing climate variability. These changes are expected to have substantial impacts on human health. There are known, effective public health responses for many of these impacts, but the scope, timeline, and complexity of climate change are unprecedented. We propose a public health approach to climate change, based on the essential public health services, that extends to both clinical and population health services and emphasizes the coordination of government agencies (federal, state, and local), academia, the private sector, and nongovernmental organizations.

OBJECTIVE: This study determined the prevalence of autism for a defined community, Brick Township, New Jersey, using current diagnostic and epidemiologic methods. METHODS: The target population was children who were 3 to 10 years of age in 1998, who were residents of Brick Township at any point during that year, and who had an autism spectrum disorder. Autism spectrum disorder was defined as autistic disorder, pervasive developmental disorder-not otherwise specified (PDD-NOS), and Asperger disorder. The study used 4 sources for active case finding: special education records, records from local clinicians providing diagnosis or treatment for developmental or behavioral disabilities, lists of children from community parent groups, and families who volunteered for participation in the study in response to media attention. The autism diagnosis was verified (or ruled out) for 71% of the children through clinical assessment. The assessment included medical and developmental history, physical and neurologic evaluation, assessment of intellectual and behavioral functioning, and administration of the Autism Diagnostic Observation Schedule-Generic. RESULTS: The prevalence of all autism spectrum disorders combined was 6.7 cases per 1000 children. The prevalence for children whose condition met full diagnostic criteria for autistic disorder was 4.0 cases per 1000 children, and the prevalence for PDD-NOS and Asperger disorder was 2.7 cases per 1000 children. Characteristics of children with autism in this study were similar to those in previous studies of autism. CONCLUSIONS: The prevalence of autism in Brick Township seems to be higher than that in other studies, particularly studies conducted in the United States, but within the range of a few recent studies in smaller populations that used more thorough case-finding methods.

This public health statement tells you about chromium and the effects of exposure to it.The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in the nation. These sites are then placed on the National Priorities List (NPL) and are targeted for long-term federal clean-up activities. Chromium has been found in at least 1,127 of the 1,699 current or former NPL sites. Although the total number of NPL sites evaluated for this substance is not known, the possibility exists that the number of sites at which chromium is found may increase in the future as more sites are evaluated. This information is important because these sites may be sources of exposure and exposure to this substance may be harmful.When a substance is released either from a large area, such as an industrial plant, or from a container, such as a drum or bottle, it enters the environment. Such a release does not always lead to exposure. You can be exposed to a substance only when you come in contact with it. You may be exposed by breathing, eating, or drinking the substance, or by skin contact.If you are exposed to chromium, many factors will determine whether you will be harmed. These factors include the dose (how much), the duration (how long), the form (chromium VI as opposed to chromium III), and how you come in contact with it. You must also consider any other chemicals you are exposed to and your age, sex, diet, family traits, lifestyle, and state of health.

BACKGROUND: Extreme heat events (EHEs) are increasing in frequency in large U.S. cities and are responsible for a greater annual number of climate-related fatalities, on average, than any other form of extreme weather. In addition, low-density, sprawling patterns of urban development have been associated with enhanced surface temperatures in urbanized areas. OBJECTIVES: In this study. we examined the association between urban form at the level of the metropolitan region and the frequency of EHEs over a five-decade period. METHODS: We employed a widely published sprawl index to measure the association between urban form in 2000 and the mean annual rate of change in EHEs between 1956 and 2005. RESULTS: We found that the rate of increase in the annual number of EHEs between 1956 and 2005 in the most sprawling metropolitan regions was more than double the rate of increase observed in the most compact metropolitan regions. CONCLUSIONS: The design and management of land use in metropolitan regions may offer an important tool for adapting to the heat-related health effects associated with ongoing climate change.

The workshop was designed to present what is known about the production of micronuclei, what protocols are now accepted or proposed internationally, what new results have been obtained, and what new methods and protocols are likely to be forthcoming. This report is designed to convey the flavour of the workshop and to provide the essence of the new information. After the workshop an effort was made to determine what single protocol would satisfy the requirements set for the micronucleus test by as many regulatory agencies as possible. The result, reported here, includes the requirements of six regulatory authorities in Canada, the European Economic Community, the Organization for Economic Co-operation and Development, Japan, and the United States.

BACKGROUND: Atrial fibrillation, the most common sustained disturbance of heart rhythm, is associated with a 5-fold increase in the incidence of ischemic stroke. METHODS AND RESULTS: The National Hospital Discharge Survey was used to estimate the annual number and prevalence of hospitalizations with atrial fibrillation among men and women 35 years of age or older. From 1985 through 1999, hospitalizations increased from 154 086 to 376 487 for a first-listed diagnosis and from 787 750 to 2 283 673 for any diagnosis. Prevalence was higher among successive age groups. Age-standardized prevalence was consistently higher among men than women. In 1999, essential hypertension, ischemic heart disease, congestive heart failure, and diabetes were prominent coexisting conditions. The number of male patients discharged home decreased from 77% to 63%, whereas the number of discharges to long-term care increased from 9% to 15%; the corresponding values for women were 72% to 56% and 15% to 23%. A slight increase in discharges to short-term care was indicated, whereas no trends were noted for in-hospital mortality. CONCLUSIONS: Hospitalizations for atrial fibrillation have increased dramatically (2- to 3-fold) in recent years. The public health burden of atrial fibrillation is enormous and expected to continue to increase over the next decades. Primary prevention of atrial fibrillation must be recognized and pursued as a complementary management strategy for reducing cardiovascular morbidity and mortality.

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a progressive and fatal neuromuscular disease; the majority of ALS patients die within 2-5 years of receiving a diagnosis (1). Familial ALS, a hereditary form of the disease, accounts for 5%-10% of cases, whereas the remaining cases have no clearly defined etiology (1). ALS affects persons of all races and ethnicities; however, whites, males, non-Hispanics, persons aged ≥60 years, and those with a family history of ALS are more likely to develop the disease (2). No cure for ALS has yet been identified, and the lack of proven and effective therapeutic interventions is an ongoing challenge. Treatments currently available, Edaravone and Riluzole, do not cure ALS, but slow disease progression in certain patients (3,4). This report presents National ALS Registry findings regarding ALS prevalence in the United States for the period January 1-December 31, 2015. In 2015, the estimated prevalence of ALS cases was 5.2 per 100,000 population with a total of 16,583 cases identified. Overall, these findings are similar to the 2014 ALS prevalence and case count (5.0 per 100,000; 15,927 cases) (2). Prevalence rates by patient characteristics (most common in whites, males, and persons aged ≥60 years) and U.S. Census regions are consistent with ALS demographics and have not changed from 2014 to 2015 calendar years. The algorithm used to identify cases from national administrative databases was updated from the International Classification of Diseases, Ninth Revision (ICD-9) to the ICD-10 codes for claims starting on October 1, 2015, with no apparent effect on case ascertainment. Data collected by the National ALS Registry are being used to better describe the epidemiology of ALS in the United States and to facilitate research on the genetics, potential biomarkers, environmental pollutants, and etiology for ALS.

This public health statement tells you about manganese and the effects of exposure to it.The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in the nation. These sites are then placed on the National Priorities List (NPL) and are targeted for long-term federal clean-up activities. Manganese has been found in at least 869 of the 1,699 current or former NPL sites. Although the total number of NPL sites evaluated for this substance is not known, the possibility exists that the number of sites at which manganese is found may increase in the future as more sites are evaluated. This information is important because these sites may be sources of exposure and exposure to this substance may harm you.When a substance is released either from a large area, such as an industrial plant, or from a container, such as a drum or bottle, it enters the environment. Such a release does not always lead to exposure. You can be exposed to a substance only when you come in contact with it. You may be exposed by breathing, eating, or drinking the substance, or by skin contact.If you are exposed to manganese, many factors will determine whether you will be harmed. These factors include the dose (how much), the duration (how long), and how you come in contact with it. You must also consider any other chemicals you are exposed to and your age, sex, diet, family traits, lifestyle, and state of health.

OBJECTIVE: A recent HIV outbreak in a rural network of persons who inject drugs (PWID) underscored the intersection of the expanding epidemics of opioid abuse, unsterile injection drug use (IDU), and associated increases in hepatitis C virus (HCV) infections. We sought to identify US communities potentially vulnerable to rapid spread of HIV, if introduced, and new or continuing high rates of HCV infections among PWID. DESIGN: We conducted a multistep analysis to identify indicator variables highly associated with IDU. We then used these indicator values to calculate vulnerability scores for each county to identify which were most vulnerable. METHODS: We used confirmed cases of acute HCV infection reported to the National Notifiable Disease Surveillance System, 2012-2013, as a proxy outcome for IDU, and 15 county-level indicators available nationally in Poisson regression models to identify indicators associated with higher county acute HCV infection rates. Using these indicators, we calculated composite index scores to rank each county's vulnerability. RESULTS: A parsimonious set of 6 indicators were associated with acute HCV infection rates (proxy for IDU): drug-overdose deaths, prescription opioid sales, per capita income, white, non-Hispanic race/ethnicity, unemployment, and buprenorphine prescribing potential by waiver. Based on these indicators, we identified 220 counties in 26 states within the 95th percentile of most vulnerable. CONCLUSIONS: Our analysis highlights US counties potentially vulnerable to HIV and HCV infections among PWID in the context of the national opioid epidemic. State and local health departments will need to further explore vulnerability and target interventions to prevent transmission.

OBJECTIVE: Although trisomy 13 and trisomy 18 are generally considered to be lethal, long-term survival of patients has been reported. We sought to evaluate mortality in people with trisomy 13 or 18 using 2 population-based strategies. METHODS: In the first analysis, infants who had trisomy 13 or 18 and were born during 1968-1999 were identified using the Metropolitan Atlanta Congenital Defects Program, a population-based birth defects surveillance system. Dates of death were documented using hospital records, Georgia vital records, and the National Death Index. In the second analysis, we used the Multiple-Cause Mortality Files compiled from US death certificates from 1979 through 1997. Using these 2 analyses, we examined median survival time or median age at death, survival beyond 1 year of age, and factors associated with longer survival. RESULTS: Using Metropolitan Atlanta Congenital Defects Program, we identified 70 liveborn infants with trisomy 13 and 114 liveborn infants with trisomy 18. Median survival time was 7 days (95% confidence interval [CI]: 3-15) for people with trisomy 13 and 14.5 days (95% CI: 8-28) for people with trisomy 18. For each condition, 91% of infants died within the first year. Neither race nor gender affected survival for trisomy 13, but for trisomy 18, girls and infants of races other than white seemed to survive longer. The presence of a heart defect did not seem to affect survival for either condition. Using MCMF, we identified 5515 people with trisomy 13 and 8750 people with trisomy 18 listed on their death certificates. Median ages at death for people with trisomy 13 and trisomy 18 both were 10 days; 5.6% of people with trisomy 13 and 5.6% of people with trisomy 18 died at age 1 year or greater. Race and gender seemed to affect survival in both conditions, with girls and blacks showing higher median ages at death. CONCLUSIONS: Although survival is greatly affected by trisomy 13 and trisomy 18, 5% to 10% of people with these conditions survive beyond the first year of life. These population-based data are useful to clinicians who care for patients with these trisomies or counsel families with infants or fetuses who have a diagnosis of trisomy 13 or 18.

The effects of public drinking water contamination on birth outcomes were evaluated in an area of northern New Jersey. After excluding plural births and chromosomal defects, 80,938 live births and 594 fetal deaths that occurred during the period 1985-1988 were studied. Information on birth outcome status and maternal risk factors was obtained from vital records and the New Jersey Birth Defects Registry. Monthly exposures during pregnancy were estimated for all births using tap water sample data. Odds ratios of > or = 1.50 were found for the following: total trihalomethanes with small for gestational age, central nervous system defects, oral cleft defects, and major cardiac defects; carbon tetrachloride with term low birth weight, small for gestational age, very low birth weight, total surveillance birth defects, central nervous system defects, neural tube defects, and oral cleft defects; trichloroethylene with central nervous system defects, neural tube defects, and oral cleft defects; tetrachloroethylene with oral cleft defects; total dichloroethylenes with central nervous system defects and oral cleft defects; benzene with neural tube defects and major cardiac defects; and 1,2-dichloroethane with major cardiac defects. Total trihalomethane levels > 100 ppb reduced birth weight among term births by 70.4 g. By itself, this study cannot resolve whether the drinking water contaminants caused the adverse birth outcomes; therefore, these findings should be followed up utilizing available drinking water contamination databases.

CONTEXT: The World Trade Center Health Registry provides a unique opportunity to examine long-term health effects of a large-scale disaster. OBJECTIVE: To examine risk factors for new asthma diagnoses and event-related posttraumatic stress (PTS) symptoms among exposed adults 5 to 6 years following exposure to the September 11, 2001, World Trade Center (WTC) terrorist attack. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal cohort study with wave 1 (W1) enrollment of 71,437 adults in 2003-2004, including rescue/recovery worker, lower Manhattan resident, lower Manhattan office worker, and passersby eligibility groups; 46,322 adults (68%) completed the wave 2 (W2) survey in 2006-2007. MAIN OUTCOME MEASURES: Self-reported diagnosed asthma following September 11; event-related current PTS symptoms indicative of probable posttraumatic stress disorder (PTSD), assessed using the PTSD Checklist (cutoff score > or = 44). RESULTS: Of W2 participants with no stated asthma history, 10.2% (95% confidence interval [CI], 9.9%-10.5%) reported new asthma diagnoses postevent. Intense dust cloud exposure on September 11 was a major contributor to new asthma diagnoses for all eligibility groups: for example, 19.1% vs 9.6% in those without exposure among rescue/recovery workers (adjusted odds ratio, 1.5 [95% CI, 1.4-1.7]). Asthma risk was highest among rescue/recovery workers on the WTC pile on September 11 (20.5% [95% CI, 19.0%-22.0%]). Persistent risks included working longer at the WTC site, not evacuating homes, and experiencing a heavy layer of dust in home or office. Of participants with no PTSD history, 23.8% (95% CI, 23.4%-24.2%) reported PTS symptoms at either W1 (14.3%) or W2 (19.1%). Nearly 10% (9.6% [95% CI, 9.3%-9.8%]) had PTS symptoms at both surveys, 4.7% (95% CI, 4.5%-4.9%) had PTS symptoms at W1 only, and 9.5% (95% CI, 9.3%-9.8%) had PTS symptoms at W2 only. At W2, passersby had the highest rate of PTS symptoms (23.2% [95% CI, 21.4%-25.0%]). Event-related loss of spouse or job was associated with PTS symptoms at W2. CONCLUSION: Acute and prolonged exposures were both associated with a large burden of asthma and PTS symptoms 5 to 6 years after the September 11 WTC attack.

To date, health effects of exposure to the September 11, 2001 disaster in New York City have been studied in specific groups, but no studies have estimated its impact across the different exposed populations. This report provides an overview of the World Trade Center Health Registry (WTCHR) enrollees, their exposures, and their respiratory and mental health outcomes 2-3 years post-9/11. Results are extrapolated to the estimated universe of people eligible to enroll in the WTCHR to determine magnitude of impact. Building occupants, persons on the street or in transit in lower Manhattan on 9/11, local residents, rescue and recovery workers/volunteers, and area school children and staff were interviewed and enrolled in the WTCHR between September 2003 and November 2004. A total of 71,437 people enrolled in the WTCHR, for 17.4% coverage of the estimated eligible exposed population (nearly 410,000); 30% were recruited from lists, and 70% were self-identified. Many reported being in the dust cloud from the collapsing WTC Towers (51%), witnessing traumatic events (70%), or sustaining an injury (13%). After 9/11, 67% of adult enrollees reported new or worsening respiratory symptoms, 3% reported newly diagnosed asthma, 16% screened positive for probable posttraumatic stress disorder (PTSD), and 8% for serious psychological distress (SPD). Newly diagnosed asthma was most common among rescue and recovery workers who worked on the debris pile (4.1%). PTSD was higher among those who reported Hispanic ethnicity (30%), household income < $25,000 (31%), or being injured (35%). Using previously published estimates of the total number of exposed people per WTCHR eligibility criteria, we estimate between 3,800 and 12,600 adults experienced newly diagnosed asthma and 34,600-70,200 adults experienced PTSD following the attacks, suggesting extensive adverse health impacts beyond the immediate deaths and injuries from the acute event.

Concern for exposures to drinking water contaminants and their effects on adverse birth outcomes has prompted several studies evaluating chlorination disinfection by-products and chlorinated solvents. Some of these contaminants are found to be teratogenic in animal studies. This review evaluates 14 studies on chlorination disinfection by-products such as trihalomethanes (THMs) and five studies on chlorinated solvents such as trichloroethylene (TCE). The adverse birth outcomes discussed in this review include small for gestational age (SGA), low birth weight, preterm birth, birth defects, spontaneous abortions, and fetal deaths. Because of heterogeneities across the studies in the characterization of birth outcomes, the assessment and categorization of exposures, and the levels and mixtures of contaminants, a qualitative review was conducted. Generally, the chief bias in these studies was exposure misclassification that most likely underestimated the risk, as well as distorted exposure-response relationships. The general lack of confounding bias by risk factors resulted from these factors not being associated with drinking water exposures. The studies of THMs and adverse birth outcomes provide moderate evidence for associations with SGA, neural tube defects (NTDs), and spontaneous abortions. Because fewer studies have been conducted for the chlorinated solvents than for THMs, the evidence for associations is less clear. Nevertheless, the findings of excess NTDs, oral clefts, cardiac defects, and choanal atresia in studies that evaluated TCE-contaminated drinking water deserve follow-up.

Complex environmental health problems--like air and water pollution, hazardous waste sites, and lead poisoning--are in reality a constellation of linked problems embedded in the fabric of the communities in which they occur. These kinds of complex problems have been characterized by some as "wicked problems" wherein stakeholders may have conflicting interpretations of the problem and the science behind it, as well as different values, goals, and life experiences. Accordingly, policy makers, public health professionals, and other stakeholders who grapple with these problems cannot expect to effectively resolve them by relying solely on expert-driven approaches to problem solving. Rather, they need to acknowledge that wicked environmental health problems are most likely to yield to (1) the application of effective community health promotion skills, (2) a sustained commitment to sound toxicological and epidemiological science, (3) the application of systems thinking, and (4) transparent communication among all stakeholders.

Importance: Risk of opioid use disorder, overdose, and death from prescription opioids increases as dosage, duration, and use of extended-release and long-acting formulations increase. States are well suited to respond to the opioid crisis through legislation, regulations, enforcement, surveillance, and other interventions. Objective: To estimate temporal trends and geographic variations in 6 key opioid prescribing measures in 50 US states and the District of Columbia. Design, Setting, and Participants: Population-based cross-sectional analysis of opioid prescriptions filled nationwide at US retail pharmacies between January 1, 2006, and December 31, 2017. Data were obtained from the IQVIA Xponent database. All US residents who had an opioid prescription filled at a US retail pharmacy were included. Main Outcomes and Measures: Primary outcomes were annual amount of opioids prescribed in morphine milligram equivalents (MME) per person; mean duration per prescription in days; and 4 separate prescribing rates-for prescriptions 3 or fewer days, those 30 days or longer, those with a high daily dosage (≥90 MME), and those with extended-release and long-acting formulations. Results: Between 2006 and 2017, an estimated 233.7 million opioid prescriptions were filled in retail pharmacies in the United States each year. For all states combined, 4 measures decreased: (1) mean (SD) amount of opioids prescribed (mean [SD] decrease, 12.8% [12.6%]) from 628.4 (178.0) to 543.4 (158.6) MME per person, a statistically significant decrease in 23 states; (2) high daily dosage (mean [SD] decrease, 53.1% [13.6%]) from 12.3 (3.4) to 5.6 (1.7) per 100 persons, a statistically significant decrease in 49 states; (3) short-term (≤3 days) duration (mean [SD] decrease, 43.1% [9.4%]) from 18.0 (5.4) to 10.0 (2.5) per 100 persons, a statistically significant decrease in 48 states; and (4) extended-release and long-acting formulations (mean [SD] decrease, 14.7% [13.7%]) from 7.2 (1.9) to 6.0 (1.7) per 100 persons, a statistically significant decrease in 27 states. Two measures increased, each associated with the duration of prescription dispensed: (1) mean (SD) prescription duration (mean [SD] increase, 37.6% [6.9%]) from 13.0 (1.2) to 17.9 (1.4) days, a statistically significant increase in every state; and (2) prescriptions for a term of 30 days or longer (mean [SD] increase, 37.7% [28.9%]) from 18.3 (7.7) to 24.9 (10.7) per 100 persons, a statistically significant increase in 39 states. Two- to 3-fold geographic differences were observed across states, measured by comparing the ratio of each state's 90th to 10th percentile for each measure. Conclusions and Relevance: In this study, across 12 years, the mean duration and prescribing rate for long-term prescriptions of opioids increased, whereas the amount of opioids prescribed per person and prescribing rate for high-dosage prescriptions, short-term prescriptions, and extended-release and long-acting formulations decreased. Some decreases were significant, but results were still high. Two- to 3-fold state variation in 5 measures occurred in most states. This information may help when state-specific intervention programs are being designed.

On September 6, 2019, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr). As of August 27, 2019, 215 possible cases of severe pulmonary disease associated with the use of electronic cigarette (e-cigarette) products (e.g., devices, liquids, refill pods, and cartridges) had been reported to CDC by 25 state health departments. E-cigarettes are devices that produce an aerosol by heating a liquid containing various chemicals, including nicotine, flavorings, and other additives (e.g., propellants, solvents, and oils). Users inhale the aerosol, including any additives, into their lungs. Aerosols produced by e-cigarettes can contain harmful or potentially harmful substances, including heavy metals such as lead, volatile organic compounds, ultrafine particles, cancer-causing chemicals, or other agents such as chemicals used for cleaning the device (1). E-cigarettes also can be used to deliver tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, or other drugs; for example, "dabbing" involves superheating substances that contain high concentrations of THC and other plant compounds (e.g., cannabidiol) with the intent of inhaling the aerosol. E-cigarette users could potentially add other substances to the devices. This report summarizes available information and provides interim case definitions and guidance for reporting possible cases of severe pulmonary disease. The guidance in this report reflects data available as of September 6, 2019; guidance will be updated as additional information becomes available.