Halon Replacements - American Chemical Society

Chapter 10

Toxicological Properties of Halon Substitutes 1

Downloaded by STANFORD UNIV GREEN LIBR on October 6, 2012 | http://pubs.acs.org Publication Date: May 5, 1997 | doi: 10.1021/bk-1995-0611.ch010

Stephanie R. Skaggs , Ted A. Moore, and Robert E. Tapscott Center for Global Environmental Technologies, New Mexico Engineering Research Institute, University of New Mexico, Albuquerque, NM 87131

Halon fire extinguishing agents are used throughout the world to protect valuable electronics, oil and gas production operations, military systems, as well as a number of other critical facilities. Unfortunately, halons deplete stratospheric ozone, causing destruction at 3 to 16 times the rate of CFC-11 (a common refrigerant). As a consequence, the production of halons was prohibited on December 31, 1993 by an international treaty, the Montreal Protocol. This ban on halon production resulted in a search for replacement chemicals for firefighting and explosion protection applications. Replacements must satisfy the following three criteria in order to be successful candidates: effectiveness, cleanliness, and environmental acceptability (low ozone depletion and global warming potentials). It is also necessary that a replacement agent be as non-toxic as possible relative to possible exposures and generate minimal toxic and corrosive decomposition products during the suppression event. Herein, the toxicological aspects of halon replacements are discussed. The specific toxic endpoints of concern for halocarbon candidates, as well as the kinds of toxicity testing required for halon replacements, will be addressed. The paper will also provide a summary of the toxicological properties for the most promising near term halon replacements. Associated decomposition product formation will be briefly discussed. Toxicity Considerations Considerations of the short- and long-term health hazards of exposure are of key importance when deciding which compounds hold potential for use in explosion and fire protection. Human and animal research indicates several principal adverse health effects caused by halocarbons. They can stimulate or suppress the central nervous system (CNS) to produce symptoms ranging from lethargy and unconsciousness to convulsions and tremors (7). Halocarbons can cause cardiac arrhythmias and can 1

Current address: HTL/KIN-TECH Division, Pacific Scientific, 3916 Juan Tabo, Northeast, Albuquerque, NM 87111 0097-6156/95/0611-0099$12.00/0 © 1995 American Chemical Society In Halon Replacements; Miziolek, A., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1997.


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sensitize the heart to epinephrine (adrenaline) (2). Inhalation of halocarbons can pro duce bronchioconstriction, reduce pulmonary compliance, depress respiratory volume, reduce mean arterial blood pressure, and produce tachycardia (rapid heartbeat) (3). These agents can cause organ damage by degradation products of metabolism (4). Halocarbons can cause reproductive and developmental abnormalities such as infertility, fewer uterine implants, and teratogenic anomalies (5). They can also produce cancerous or mutagenic effects (6). CNS effects, cardiac sensitization, and pulmonary disorders appear to be reversible upon termination of exposure to these chemicals. Organ toxicity, reproductive effects, cancer and mutagenicity, on the other hand, are latent effects, and sequelae (delayed effects) are usual. The immediate effects of halocarbon exposure on the nervous system, cardiovascular system, and respiratory system appear to be caused by the compound itself. However, it is thought that the latent effects that take place in specific organs, such as the liver, kidneys, and reproductive organs, are possibly caused by the degradative products formed when the halocarbons enter into metabolic processes. Both the immediate effects and the latent damage must be considered when evaluating potential candidates for firefighting. Regulatory Considerations Title V I of the 1990 Clean Air Act Amendments implements the restrictions imposed by the Montreal Protocol for the United States. Title VI, Section 612 requires that the US Environmental Protection Agency (EPA) enact regulations making it unlawful to replace any CFC or halon with any replacement that "may present adverse effects to human health or the environment, where the Administrator has identified an alternative to such replacement that — (a) reduces the overall risk to human health and the environment; and (b) is currently or potentially available." Section 612 requires the E P A to publish lists of both prohibited and acceptable substitutes. Risk assessments are performed under the Significant New Alternatives Policy (SNAP) program to determine the acceptability of substitutes. This indicates that toxicological considerations are a major concern when developing halon replacement agents. Cardiac sensitization occurs at a lower concentration than the concentrations necessary to elicit toxic responses such as anesthesia or lethality. Therefore, regulatory and standard setting authorities have used cardiac sensitization thresholds as the criteria for determining acceptability for use in areas where human occupancy may occur. In addition, the phenomenon of cardiac sensitization is particularly important in firefighting because under the stress of the fire event, higher levels of epinephrine are secreted by the body which increases the possibility of sensitization.

In Halon Replacements; Miziolek, A., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1997.

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Toxicity Tests


Toxicity testing is the most time-consuming and expensive effort in the early development of a halon replacement. Estimates indicate that the cost range for the battery of toxicity tests required to satisfy regulatory and liability issues is $2-5 million per chemical (7). A number of toxicity tests have been suggested for halon replacement agents to facilitate a risk assessment decision. Below is the list of minimum likely toxicity tests required by the US E P A for fire extinguishing agents under the SNAP program: (8) • • • • • •

Range finder of acute toxicity (such as a limit test or LC50 test) Cardiac sensitization test Developmental toxicity test 4- or 13-week subchronic test Genetic toxicity screening test (such as the Ames test) Degradation byproduct test (not combustion toxicology)

Most of the tests listed above determine the toxicity due to short exposures. However, other longer exposure tests would likely be required to satisfy occupational concerns imposed during manufacture of the chemical and maintenance and service of the extinguisher systems. In determining the acceptability of a replacement for a particular application, a risk assessment is performed where the toxic concentrations of the chemical are compared to the likely exposure concentrations for specific scenarios of use. For applications where human exposure is possible, a replacement agent should not be toxic at exposure concentrations. Therefore, another "test" that might be required, as determined on a case-by-case basis, is one to determine the exposure concentration during the specific use of the replacement agent. Acute Toxicity Testing. Acute toxicity tests are usually concerned with the lethality manifested due to exposure within a relatively short time interval, usually on the order of minutes to days. Acute toxicity is often the result of a single exposure. Other manifestations besides lethality can include indications of anesthesia and eye or skin irritation. Sometimes pathological or histological examinations are performed on the test species to give indications of cause of death and tissues affected by the test chemical. Cardiac Sensitization Testing. Cardiac sensitization potential is usually tested in dogs outfitted with electrocardiographic (ECG) measurement devices (9). The dogs are trained to accept venipuncture, E C G monitoring, and a mask over their snouts for chemical exposure. The usual test sequence, and the protocol recommended by the SNAP program, involves administering epinephrine to animals to determine the individual dog's response to pharmacological doses of the drug, then exposing them to the test chemical by inhalation, and finally administering a second dose of


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epinephrine ("challenge dose") while the test chemical is being inhaled. Adverse effects are monitored on the E C G tracings. Adverse effects are considered as the appearance of 5 or more multifocal ectopic ventricular beats, fibrillation, or death. A standardized protocol is not universally accepted so variations on this method may be used, thus making comparison of studies difficult. The lowest observed adverse effect level (LOAEL) is the lowest concentration at which an adverse toxicological effect is observed. The no observed adverse effect level (NOAEL) is the highest concentration at which no adverse toxicological effects have been observed. Since heart arrhythmia is the first acute adverse physiological effect observed after exposure to most halocarbons, cardiac sensitization has been chosen as the adverse effect on which N O A E L and L O A E L values are based for halogenated halon replacements. Despite the acceptance of cardiotoxic threshold values in making regulatory decisions and settings standards, the N O A E L and L O A E L values determined in dogs are considered conservative for humans even in high-stress situations {10). The conservative nature of these values is contributed to several factors: (a) no certainty exists that dogs are a good model for humans for cardiac sensitization, (b) very high doses of epinephrine are used in the test method (epinephrine doses in the test animals are 10 times higher than the highest levels secreted in humans), (c) some dogs, and presumably some humans, are more susceptible to sensitization than others, and (d) two to four times more chemical is required to cause cardiac sensitization in the absence of exogenous epinephrine, even in artificially created situations of stress or fright in animals. Nevertheless, regulatory and standard-setting authorities are using results of cardiac sensitization tests to determine the acceptability of halon replacements for use in normally occupied total flood applications. If the cardiac sensitization value (LOAEL for US E P A or N O A E L for NFPA) is below the fire suppression or inertion design concentration, then the candidate is not acceptable for use in normally occupied total flood applications. Development Toxicity Testing. During the developmental toxicity test, pregnant animals (usually rats or rabbits) are subjected to the chemical in order to determine what effect the chemical has upon the developing fetus. Dams are exposed during the period of fetal organogenesis, and litters are evaluated for a number of endpoints, including number of viable offspring, types and incidence of skeletal and visceral malformations or variations, and body weight (77). Maternal toxicity endpoints, such as organ weights and clinical histopathology, are also assessed. Subchronic Toxicity Testing. Subchronic tests measure toxicity caused by repeated dosing over an extended time, but not such a long time period that it constitutes a significant portion of the expected lifespan of the test species. These tests provide information on essentially all types of chronic toxicity. Subchronic tests are frequently used to determine the No Observed Effect Level (NOEL), a value that is used in risk assessment calculations for occupational exposure. Although the 90-day


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(13-week) subchronic toxicity test is not specific for carcinogenicity or mutagenicity endpoints, it is a definitive study that may give indications of the carcinogenic potential of highly potent mutagens and carcinogens. Genetic Toxicity Testing. Chemical carcinogenesis is usually the result of long-term exposure to a chemical that may occur generally during industrial processing and handling. To determine the potential carcinogenicity of an agent, genotoxicity (mutagenicity) screening tests are often performed. Positive mutagenicity results alert toxicologists to the possibility of carcinogenesis and indicate the need for subchronic exposure testing to develop industrial exposure standards. Examples of genotoxicity tests are the Ames test in bacteria, mouse lymphoma test, mouse micronucleus test, unscheduled D N A synthesis test in mammalian liver cells, sex-linked recessive mutation test in fruit flies, and sister chromatid exchange test in Chinese hamster ovary cells. Commercial Replacements for Total Flooding and Streaming A number of halon replacement candidates have been announced by industry for commercialization. In most cases, the toxicity testing is being completed by support from the manufacturers. These manufacturers not only must determine the toxicity of the chemicals to gain regulatory approval but also to satisfy product liability. As a result, the manufacturers often support additional toxicity testing in order to address this concern. Tables I and II present summaries of the toxicological information on commercially available Halon 1301 and 1211 replacements, respectively. Developmental and subchronic results have not been determined for many of the agents yet. Table I provides manufacturer recommended design concentrations to allow comparisons with cardiac sensitization N O A E L and L O A E L values. Those agents with cardiac sensitization values above the design concentrations are suitable for use in occupied areas. Because design concentrations are not typically thought of for streaming agents, exposure of personnel is difficult to determine and highly scenario-dependent. The E P A uses models and air monitoring data to determine i f exposure levels will exceed the cardiac sensitization L O A E L during discharge of portable extinguishers. During breathing zone personnel monitoring studies of halon replacement agents, firefighters were exposed to less than 0.1% agent concentration in simulated aircraft hangar exposures during discharge of 20- or 150-LB fire extinguishers in T-dock aircraft hangers (72) and in open pit, outdoor fire scenarios fought with 20- or 150L B fire extinguishers (73). Another study showed firefighter breathing zone concentrations less than 0.1% in real fire, simulated flightline scenarios with 150-LB extinguishers using either Halon 1211, HCFC-123, or FC-5-1-14 (14). Accordingly, in outdoor and T-hangar streaming scenarios similar to those indicated above, it is anticipated that firefighter exposure would not exceed concentrations greater than 0.1%. For streaming agents, this type of exposure information is compared to the cardiac sensitization values to determine the suitability of use in areas where human exposure might occur.


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Table I. Toxicological Summary of Halon 1301 Replacements

Candidate Agent"


h

Halon 1301 HBFC-22B1 HFC-23 HFC-125 HFC-227ea HFC-236fa HCFC-124 HCFC Blend A HCFC-123 HCFC-22 HCFC-124 FC-218 FC-3-1-10 CF I 3

Subchronic Acute Developmental Toxicity Toxicity Cardiac (lS-wk), (LCj or Sensitization, Toxicity, NOAEL, vol IVo ALC), NOAEL* vol% vol% vol% N* V

Halon Replacements - American Chemical Society

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