Community Exposure to Toluene Diisocyanate

In August 1996, residents of a Randolph County, North Carolina, community contacted the Agency for Toxic Substances and Disease Registry (ATSDR) because of health concerns from possible exposure to chemical emissions from a polyurethane manufacturing plant.

The facility produced polyurethane foam by reacting a resin with toluene diisocyanate (TDI) and water. Emissions from the foam-making process were directed to stacks, which vented them to ambient air. Emissions could also escape from air vents in the building. TDI exposure was of public health concern because TDI can cause respiratory irritation and asthma, which some residents had reported.

TDI is a very volatile liquid used in the production of polyurethane foams and as an ingredient in automobile paint. It is a severe irritant to mucous membranes of the eyes and respiratory tract. Exposure to TDI has sensitized some workers, resulting in asthmatic attacks after very low subsequent exposures to TDI. High-dose inhalation can lead to chest tightness; coughing; breathlessness; inflammation of the bronchi with sputum production and wheezing; hypersensitivity pneumonitis; and noncardiogenic pulmonary edema. Euphoria, ataxia, and mental aberrations can occur in addition to the respiratory symptoms.

In response to the community's concerns, ATSDR and the then State of North Carolina Department of Environment Health and Natural Resources (NCDEHNR)* conducted ambient air monitoring to characterize air contamination near the plant. Using a direct-monitoring instrument, ATSDR staff detected TDI in ambient air of a residential area near the facility. Concentrations of TDI in excess of 29 parts per billion (ppb) were detected at a monitoring station located about 100 feet outside the facility's fence line.

The presence of TDI was confirmed by an alternative method in which diisocyanates were captured on glycerol-impregnated filters, chemically derivatized, and analyzed using high performance liquid chromatography. ATSDR and NCDEHNR also detected methylene chloride and other volatile organic compounds in ambient air through air monitoring. These findings prompted ATSDR to issue a public health advisory on October 20, 1997 (1). ATSDR's public health advisory is a communication from the Administrator of ATSDR to the Administrator of the

US Environmental Protection Agency (EPA) that states ATSDR's concern that a public health threat exists of such importance and magnitude that immediate intervention should be taken by EPA. The health advisory is also provided to the appropriate EPA regional office and state health department.

In order to determine whether residents had been exposed to TDI emissions from the plant, ATSDR, in cooperation with the Randolph County Health Department (RCHD), initiated a biological exposure investigation. Residents who lived within a ¼-mile of the facility were invited to participate in the investigation. Because TDI reacts so quickly, exposure to TDI cannot be detected by testing for TDI itself; therefore, blood samples collected from 113 residents were tested for antibodies to TDI. The blood serum fractions were separated and analyzed by an enzyme-linked immunosorbent assay (ELISA) for Immunoglobulin G (IgG) and Immunoglobulin E (IgE) antibodies to TDI and the closely related chemicals hexamethylene diisocyanate (HDI) and diphenylmethane diisocyanate (MDI).

IgE and IgG are two of five classes of human immunoglobulins. IgG antibodies are involved in the immune system's response to foreign substances that it has encountered before (i.e., the secondary or recall response). IgE antibodies are involved in allergies. The presence of a TDI-specific antibody (IgG and IgE) indicates exposure to TDI but is not an indicator of TDI hypersensitivity. Individuals who have TDI antibodies do not always develop hypersensitivity, and people who are hypersensitive to TDI do not always have detectable TDI-specific antibodies.

Of the 113 participants tested, 10 (9%) had antibodies to 1 or more of the diisocyanates (2). Nine had IgG antibodies to TDI, and one had IgE antibodies to TDI. Four had antibodies that reacted with more than one diisocyanate.

Individuals with positive antibody tests were interviewed to identify possible sources of exposure to diisocyanates. One reported having occupational exposure to TDI or other diisocyanates. Two reported using polyurethane varnishes, a possible source of diisocyanates, in their homes. None of the other seven positive individuals reported exposure to known sources of diisocyanates. ATSDR concluded that the presence of TDI antibodies in these individuals could have resulted from exposure to TDI in residential ambient air near the facility.

Some residents who lived near the facility reported health effects that they attributed to emissions from the plant; therefore, individuals who tested positive for diisocyanate antibodies, as well as individuals who were experiencing symptoms of respiratory disease, were encouraged to seek further evaluation arranged by NCDEHNR at Duke University Medical Center.

Because of public health concerns about the plant, the State Health Director issued an "Order to Abate a Public Health Nuisance" on September 3, 1997. Polyurethane foam production at the plant has not resumed since the order was issued.

Detection and Health Significance of Antibodies to Toluene Diisocyanate

Occupational exposure to toluene diisocyanates (TDI) and other diisocyanates can cause irritation of the eyes, upper and lower respiratory tract, and skin. In some workers, exposure to TDI results in sensitization (i.e., hyperresponsiveness to TDI at concentrations much below those affecting most persons). It has been estimated that 5% to 10% of workers exposed to diisocyanates develop occupational asthma (3). The exposure level of TDI that causes sensitization is not well characterized, but it can occur at levels below the Occupational Safety and Health Administration's short-term exposure level of 20 ppb (4).

It has been estimated that 10% to 30% of symptomatic workers develop IgE antibodies to diisocyanates (3). In one study of 1,780 workers exposed to diisocyanates in the workplace, IgE antibodies to diisocyanates were detected in 13.6% of symptomatic workers and 8.4% of all workers (5). Symptomatic workers were those who had experienced bronchial asthma, chronic bronchitis, rhinitis, or conjunctivitis. In a representative subgroup of this same population, IgG antibodies were somewhat more prevalent, being detected in 24% of symptomatic workers and 17% of asymptomatic workers.

Several of the participants in the ATSDR investigation in Randolph County had positive antibody reactions to more than one diisocyanate. This is not unexpected, since cross-reactivity of diisocyanate antibodies has been observed previously (5,6). In one study, about 60% of positive sera cross-reacted to varying degrees with one or more diisocyanates (5).

Occupational exposure to TDI and other diisocyanates can lead to asthma and hypersensitivity pneumonitis; however, the presence of TDI antibodies does not necessarily lead to clinical disease. Occupational studies have demonstrated that some workers have both antibodies to TDI and exposure to TDI, yet they remain asymptomatic. Conversely, occupational asthma occurs in some TDI workers in the absence of TDI antibodies. Therefore, the presence or absence of TDI antibodies is a poor predictor of clinical disease. In ATSDR's investigation, antibodies to diisocyanates were used as a biomarker of exposure. ATSDR is also considering the possibility of conducting further medical evaluation.

For more information, contact Theresa Kilgus, MPH, at ATSDR, 1600 Clifton Rd, NE, MS E32, Atlanta, GA 30333; telephone (404) 639-4143; fax (404) 639-0654; e-mail tak9@cdc.gov. The public health advisory is also available at / advisories/971020.html.

The National Institute for Occupational Safety and Health's Alert "Preventing Asthma and Death from Diisocyanate Exposure" is also available at http://www.cdc.gov/niosh/asthma.html.

1. Agency for Toxic Substances and Disease Registry. Public health advisory for Trinity American Corporation, Glenola Industrial Drive, Randolph County, North Carolina. Atlanta: US Department of Health and Human Services; 1997 Oct 20.
2. Agency for Toxic Substances and Disease Registry. Trinity American Corporation health consultation. Atlanta: US Department of Health and Human Services; 1998 Feb 13.
3. Bernstein JA. Overview of diisocyanate occupational asthma. Toxicol 1996;111:181-189.
4. American Conference of Governmental Industrial Hygienists. Documentation of the threshold limit values and biological exposure indices. 5th Edition; Cincinnati, OH: American Conference of Governmental Industrial Hygienists; 1986.
5. Bauer X, Marek W, Ammon J, et al. Respiratory and other hazards of isocyanates. Int Arch Occup Environ Health 1994;66:141-152.
6. Keskinen H, Tupasela O, Tikkainen U, Nordman H. Experiences of specific IgE in asthma due to diisocyanates. Clinical Allergy 1988;18:597-604.

* NCDEHNR has been reorganized since these activities into the North Carolina Department of Health and Human Services and the North Carolina Department of Environment and Natural Resources. (Back to text.)

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HHIN Responds to Questions on Radioactive Materials and Health

Janice Englehart, MPH, MSW; Laura Leonard, MPH; and Jean Woodward, BTh, of the Hanford Health Information Network and Georgia Moore, MS, ABJ, ATSDR

Health agencies and professionals often face the challenge of answering questions from the public about a subject on which scientists don't agree. This is especially true when the subject evokes fear, such as radiation exposure and health.

One program that has faced these challenges—the Hanford Health Information Network (HHIN)—could be a model for others. HHIN provides information on the known and potential health effects of exposure to radioactive substances released between 1944 and 1972 from the Hanford Nuclear Reservation in south central Washington state. HHIN is a collaborative effort of Washington, Oregon, and Idaho state health agencies and nine Indian nations.

After citizens demanded information about Hanford's past radioactive releases, Congress authorized funds for the three state health agencies to develop a program, which became HHIN. Comments from a broad representation of interested citizens and groups led to HHIN's guiding principles: respect the dignity of individuals and their right to make personal decisions with the most complete information available and provide information from a wide variety of sources and points of view.

Since 1993, HHIN has answered questions from citizens and health care providers through its toll-free lines, publications, and community outreach. HHIN's publications and newsletter are also available on the Internet at http://www.doh.wa.gov/hanford/. Topics include how radioactivity may affect the body; cancer; and potential health effects from iodine-131, plutonium, strontium, and other radionuclides (Table 1 describes some of these effects). HHIN also offers a self-study curriculum for health care providers.

HHIN has six service/information centers across the three states, a Tribal Service Program, and a national outreach effort. HHIN health educators speak before citizen groups and health care providers, and have fostered networking groups where people share their concerns.

HHIN also initiated the Hanford Health Information Archives—a voluntary collection of personal records and health information from people exposed to Hanford's releases. The collection is housed at the Foley Center Library at Gonzaga University in Spokane, Washington, and is open to the public. Part of the collection is also available on the Internet at http://www.hhia.org.

An impact evaluation showed that HHIN has made a difference in audience members' awareness and knowledge. Those who had more than one contact with HHIN or who had direct contact (by phone or in person) reported the greatest impact. Behavioral changes included an increase in self-monitoring of health.

Nearly 45,000 people have asked to receive updates through HHIN's newsletter. In 1997 there were 10,000 visits to the HHIN web site.

The need for information will increase. The results of a federally funded thyroid study will be released in late 1998, and the Agency for Toxic Substances and Disease Registry's Hanford Medical Monitoring Program for thyroid disease screening of residents will begin. Because HHIN's federal funding ends in September 1998, the three states are requesting a 3-year reauthorization.

For more information, contact the HHIN Resource Center, 506 Second Ave, Suite 2400, Seattle, WA 98104; telephone (800) 959-7660; Internet http://www.doh.wa.gov/hanford/.

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Table 1: Radioactive Substances and Health

Substances are radioactive because their atomic structures are unstable or as a result of nuclear reactions. Radioactive substances can give off or emit different types of energy or radiation. These include alpha particles, beta particles, and gamma rays, which are produced in the atom's nucleus. Some radioactive substances emit one or more types of radiation. The effects of high-level exposures can include burns, acute radiation sickness, and death. High-level exposures usually occur in occupational or medical settings or during accidents or war. The long-term health risks include cancer, birth defects, infertility, and genetic abnormalities. Because each type of radiation has different physical properties, the risks and potential effects on health of each are different. Some forms of radiation can penetrate the skin; others affect the body only if inhaled, ingested, absorbed through the skin, or enter through a wound. The effect of radioactive substances once inside the body depends on a number of factors, including how fast the substances decay (their half-lives), the energy level of the decay, and how long they stay and where they are located in the body.

Alpha particles are positively charged and made up of two protons and two neutrons. They lose their energy quickly and do not penetrate the surface of the skin. They can enter the body through a cut in the skin, ingestion, or inhalation. They can cause intense ionizations when they interact with matter and result in significant local damage if taken into the body. Uranium-238 and plutonium-239 are examples of alpha sources.

Beta particles are positively or negatively charged electrons produced inside the nucleus. They can easily penetrate human tissue before losing all of their energy. Like alpha particles, they cause damage to the body, but do not have as much energy or potential to damage the body as alpha particles. Iodine-131, phosphorus-32, strontium-90, and tritium are examples of beta particle sources. The effects of beta particle sources on the body depend on whether or not they are stored in tissue or excreted.

Gamma rays are photons or electromagnetic waves spontaneously given off by certain radioactive substances. Gamma rays are not charged and pass through the human body at the speed of light. As gamma rays pass through the body, they interact with and may damage cells. Uranium-238, iodine-131, and cesium-137 are examples of gamma ray sources.

Some Radioactive Substances in the Environment

Cesium-137 is the most common of cesium's radioactive isotopes to be encountered. It is produced during fissioning of either uranium or plutonium fuels and is found in the environment as a result of worldwide fallout associated with atmospheric weapons tests. It is also used in industry as a sealed gamma ray source for measuring the thickness of materials and in medicine as a sealed source for therapy and as a tracer substance. Because its chemical forms can be water soluble, cesium-137 can be distributed almost uniformly in body fluids and is rapidly eliminated by the kidneys. The biologic half-life of cesium-137 ranges from 68 to 165 days. Exposure to cesium-137 can increase the risk of cancers such as leukemia.

Radioactive iodines (especially iodine-131, -132, and -129) are important fission products from nuclear weapons tests and nuclear reactors. They are volatile substances and once released into the atmosphere can return to earth via precipitation, contaminating land, vegetation, and ultimately the food and water supply. Iodine-131 has a half-life of 8.05 days and emits several medium-energy beta particles and mostly low-energy gamma rays. Exposure to radioactive iodine usually results from inhalation; however, ingestion of contaminated milk has been the primary route of exposure following fallout events. An increased frequency of thyroid nodules and cancers have been reported in persons exposed to radioactive iodine from nuclear fallout. The risk of thyroid cancer appears to be life-long and dependent on age at time of exposure (e.g., infants and young children are at highest risk) and dose of 1-131 received.

Plutonium is an artificially produced element used as a fuel in nuclear power reactors and in nuclear weapons. It emits two high-energy alpha particles and has a radiation half-life of 24,390 years. Inhalation is the most common route of entry into the body; workers may also be exposed through puncture wounds. Inhaled plutonium can destroy small local masses of lung tissue and may result in lung cancer. Some of the inhaled plutonium can reach thoracic lymph nodes and the blood and be distributed elsewhere in the body. Exposure to plutonium may increase the risk of bone, liver, or lung cancer; leukemia; or chromosome aberrations.

Radon results from the radioactive decay of radium, a common element in rock and soil derived from the decay of uranium. As a gas, it can build up in buildings and is a source of alpha radiation. The alpha radiation may contribute to changes in cells in the respiratory tract that result in lung cancer.

Strontium-90 emits a relatively high-energy beta particle, giving rise to yttrium-90, which then emits a beta particle of even higher energy. It is used in medicine and industry. Once in the body, it becomes deposited in bone where the high-energy beta particles irradiate both the bone and adjacent bone marrow. Exposure to strontium may increase the risk of leukemia, bone cancer, or a weakened immune system.

Naturally occurring uranium consists of uranium-238 (99.27%), uranium-235 (0.72%), and uranium-234 (0.0054%). Uranium-235 is extracted or concentrated from natural uranium for use in nuclear weapons or nuclear power reactors. The uranium remaining after uranium-235 has been removed is referred to as depleted uranium; however, this uranium continues to be a radiation as well as a chemical hazard. Radioactive uranium is responsible for significant alpha radioactivity contamination in the environment. The amount of natural uranium that is absorbed by the body depends on the uranium's physical state, chemical form, and the route of exposure. Most uranium that is retained in the body is stored in bone and kidneys. Exposure to uranium may increase the risk of kidney disease, non-malignant respiratory disease, or lung cancer.

Main Source: ATSDR. Case studies in environmental medicine: ionizing radiation. Atlanta: US Department of Health and Human Services; 1993.

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Hazardous Materials Emergency Response Training Pays Off in Rural Community

Cynthia Lewis-Younger, MD, MPH, Rocky Mountain Center for Occupational and Environmental Health and and Sandra Marsh, MS, Utah Area Health Education Center

About 16% of hazardous substances releases, other than petroleum products, are associated with transportation accidents. Though at risk, many rural communities are not prepared to handle such incidents. To address this problem in Utah, the University of Utah piloted a hazardous materials awareness training program for responders and medical personnel in Juab County.

Juab County is largely rural and much of the traffic consists of hazardous materials transport. At risk in the event of an accident, most of the county's inhabitants live adjacent to transportation routes, including residents of Nephi (population 3,500) and Mona (population 600).

Eight months after the training, participants had to put their skills to use responding to a transportation accident involving hazardous substances. The incident provided an opportunity not only to evaluate the training program but to help identify problems associated with responding to hazardous waste accidents in a rural community. This information can be used to assist other rural communities in improving their ability to prevent injury from exposure to hazardous materials released in transportation accidents.

The University of Utah's Utah Area Health Education Center (UAHEC) formed a team to develop and conduct the training program as a pilot for similar training to be offered throughout Utah. The team consisted of personnel from UAHEC; the Rocky Mountain Center for Occupational and Environmental Health (RMCOEH); the University of Utah Health Sciences Center's Division of Emergency Medicine; the Utah Department of Public Safety's Division of Comprehensive Emergency Management; and residents of Juab County with emergency response responsibilities.

On April 30 and May 1, 1996, the team presented the program to 45 Juab County physicians, nurses, emergency medical technicians, public safety and fire department personnel, and first responders at the Nephi hospital.

Team members gave lectures about hazardous materials and participants watched the video "Community Challenge: Hazardous Materials Response and the Emergency Medical System," which is produced by the Agency for Toxic Substances and Disease Registry (ATSDR). They received ATSDR's publications Managing Hazardous Materials Incidents, Volume I (Emergency Medical Services) and III (Medical Management Guidelines for Acute Chemical Exposures) and practiced decontamination procedures.

Participants rated the course as very beneficial. UAHEC was planning to conduct a reevaluation of the course after a year to measure long-term retention of information; however, 8 months after the pilot, a unique opportunity to evaluate its impact occurred.

About 10 AM on December 10, 1996, a tractor-trailer on I-15 rolled over near Mona. It came to rest on its side and within the hour began to burn. Because the truck was on its side, it was difficult to identify its markings. A local responder had to circle around the vehicle, avoiding the smoke, to get close enough to the rear of the truck to identify a Department of Transportation (DOT) placard "skull and crossbones 6," which indicates a poisonous material.

More specific information about the cargo was not immediately available. The driver didn't know what the cargo was and had left the shipping papers in the cab, which were deemed too dangerous to retrieve. Responders called the transportation company; however, the company had no mechanism for responding to emergencies. The company contact was finally able to determine that the cargo was sodium azide, a powerfully explosive compound that is highly reactive with water.

Firefighters couldn't extinguish the burning truck, it began to rain, and winds were carrying smoke toward homes and an elementary school. Some of the potential byproducts of burning sodium azide are also toxic, especially hydrazoic acid. Because Mona residents were being threatened by toxic fumes from a fire that couldn't be extinguished, officials decided to evacuate the community. The interstate was closed and over the next 2 days, the truck was allowed to burn itself out.

The only documented exposure to the smoke was one person who drove through it. Difficulties encountered by the community because of the accident and evacuation included problems created by panic and confusion (e.g., problems related to parents trying to find children at the elementary school and people forgetting critical medications) and members of the media trying to get stories.

Responding to the opportunity to evaluate the previous training program, UAHEC sent out a survey to responders within days of the accident. The survey was followed up in January with a debriefing session, which about 15 responders attended.

Training program participants found the lectures and ATSDR videotape and references useful in clarifying their roles in responding to the incident. Training in how to access information was also helpful to medical personnel, including helping them answer community members' questions. They generally believed that the awareness training had been helpful and were interested in more training. Overall, local responders believed that they were able to handle the incident well.

Several problems were identified through the incident. Responders didn't know who to call or how to access information about the chemical's behavior in the environment or potential health effects. They didn't remember contact numbers provided with reference materials and didn't have the references with them. Communication was difficult due to incompatible communication systems and overloading of local telephone lines.

Several lessons learned from this experience include the following:

• Rural communities need to develop and practice a coordinated disaster plan and the general public needs to be made aware of the plan as well.
• Special attention should be paid to reuniting children with parents and assisting elderly and disabled individuals.
• During an evacuation, provisions need to be made to obtain or have individuals bring critically needed medications.
• Because first responders and other emergency personnel in these communities are often part-time volunteers and not in uniform when they respond, some mechanism to identify first responders in these communities is needed.
• Communication and identification mechanisms need to be worked out prior to incidents.
• Training programs should incorporate more information about practical issues, including dealing with communication problems, panic, and identifying responders.
• Training program planners should recognize that information used infrequently will usually not be remembered in a crisis. Memory aids for critical contact numbers should be provided to as many individuals as possible. For example, following the debriefing, UAHEC provided community members with wallet-sized laminated cards with appropriate contact numbers.
• Problems with initial identification of cargo need to be solved. The responders believe that the DOT placard system is not helpful to those who do not routinely use it and labeling of vehicles needs to be sufficiently large to be seen from a safe distance.
• Transporters need to ensure that information can be obtained quickly by emergency responders and drivers should be adequately informed about their loads.

For more information, contact Cynthia Lewis-Younger, MD, MPH, University of Utah, RMCOEH, 75 S 2000 East, Salt Lake City, Utah 84112; telephone (801) 581-3841; fax (801) 585-3759; e-mail cyounger@dfpm.utah.edu.

To obtain copies of the ATSDR video or publications, contact the ATSDR Information Center at 1600 Clifton Rd, NE, MS E57, Atlanta, GA 30333; telephone (800) 447-1544; fax (404) 639-6359; e-mail atsdric@cdc.gov.

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This page last updated on October 28, 2003
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