Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 9
SUBMARINE EXPOSURE GUIDANCE LEVELS FOR SELECTED HYDROFLUOROCARBONS: HFC-236fa, HFC-23, and HFC-404a 1 Introduction IN ACCORDANCE WITH the Montreal Protocol on Substances That Deplete the Ozone Layer, efforts are under way to replace the chlorofluorocarbons (CFCs) used in refrigeration units. One class of chemicals replacing the CFCs is the hydrofluorocarbons (HFCs). These chemicals do not contain chlorine and do not contribute to the destruction of the stratospheric ozone layer. Their use as replacements for the CFCs in refrigeration units is expected to expand. The U.S. Navy proposes to use HFC-236fa and HFC-404a as refrigerants aboard its submarines; specifically, HFC-236fa is being considered for use in centrifugal chillers, and HFC-404a is being considered for use in ice-cream machines. Because of the closed environment of submarines, the Navy plans to set emergency exposure guidance levels (EEGLs) and continuous exposure guidance levels (CEGLs) to protect its personnel from potential adverse health effects, both short- and long-term, caused by inhalation of those chemicals as the result of accidental releases. The Navy proposes to set a 1-hr EEGL of 2,000 parts per million (ppm), a 24-hr EEGL of 1,000 ppm, and a 90-day CEGL of 100 ppm for HFC-236fa and HFC-404a. The Navy also proposes to apply those guidance levels to HFC-23, a combustion product of HFC-236fa. These levels are the same as those established for chlorofluorocarbons CFC-12 and CFC-114.
OCR for page 10
SUBMARINE EXPOSURE GUIDANCE LEVELS FOR SELECTED HYDROFLUOROCARBONS: HFC-236fa, HFC-23, and HFC-404a STATEMENT OF TASK The National Research Council (NRC) was asked to conduct an independent evaluation of the Navy's proposed exposure guidance levels for HFC-236fa, HFC-23, and HFC-404a. The NRC assigned this task to the Committee on Toxicology (COT), which convened the Subcommittee on Exposure Guidance Levels for Selected Hydrofluorocarbons, a multidisciplinary group of experts, to review (1) the Navy's toxicity assessments of the three HFCs, (2) other data relevant to establishing EEGLs and CEGLs for these substances, and (3) the scientific validity of the Navy's proposed EEGLs and CEGLs, based on the relevance of existing animal studies for evaluating the health risks to humans, the completeness of the data base, the target organs of toxicity, and the appropriateness of the methods used to derive the exposure guidance levels (e.g., correctly adjusting for exposure durations and the use of uncertainty factors). The subcommittee was asked to review the three HFCs only in the context of use aboard submarines—vessels with male personnel only. The subcommittee was also asked to identify any deficiencies in the data bases on each HFC and to make recommendations for future research. Although products other than HFC-23 are formed during combustion of HFC-236fa or HFC-404a, HFC-23 was the only combustion product the subcommittee was asked to consider. APPROACH TO THE STUDY The subcommittee conducted a critical analysis of the available toxicity data on each of the HFCs and used the data to calculate possible EEGLs and CEGLs according to the guidelines outlined in the NRC' s report Criteria and Methods of Preparing Emergency Exposure Guidance Level (EEGL), Short-Term Public Emergency Guidance Level (SPEGL), and Continuous Exposure Guidance Level (CEGL) Documents (NRC 1986). The subcommittee also reviewed the Navy's toxicity assessments of the HFCs and used information provided in a 1996 report of the NRC titled Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 (NRC 1996), which provides a toxicity assessment and establishes EEGLs and CEGLs for HFC-134a, a component of HFC-404a. EXPOSURE GUIDANCE LEVELS Criteria and methods used to determine EEGLs and CEGLs are detailed in
OCR for page 11
SUBMARINE EXPOSURE GUIDANCE LEVELS FOR SELECTED HYDROFLUOROCARBONS: HFC-236fa, HFC-23, and HFC-404a an NRC (1986) report, and a brief description is provided below. Additional guidance is provided in two other NRC reports (NRC 1992, 1993). Emergency Exposure Guidance Levels An EEGL is defined as a ceiling guidance level for single emergency exposures usually lasting from 1 to 24 hr—an occurrence expected to be infrequent in the lifetime of a person. “Emergency” connotes a rare and unexpected situation with potential for significant loss of life, property, or mission accomplishment if not controlled. An EEGL can also be set for much shorter periods, such as 1-min or 5-min exposures. An EEGL specifies and reflects the subcommittee's interpretation of available information in the context of an emergency. An EEGL is acceptable only in an emergency, when some risks or some discomfort must be endured to prevent greater risks (such as fire, explosion, or massive release). Even in an emergency, exposure should be limited to a defined short period. Exposure at the EEGL might produce temporary discomfort, such as eye or upper-respiratory-tract irritation, headache, or increased respiratory rate. The EEGL is intended to prevent irreversible harm. Even though some reduction in performance is permissible, it should not prevent proper responses to the emergency (such as shutting off a valve, closing a hatch, removing a source of heat or ignition, or using a fire extinguisher). For example, in normal work situations, a degree of upper-respiratory-tract irritation or eye irritation causing discomfort would not be considered acceptable; during an emergency, however, such irritation would be acceptable if it did not cause irreversible harm or seriously affect judgment or performance. The EEGL for a substance represents the subcommittee's judgment based on evaluation of experimental and epidemiological data, mechanisms of injury, and, when possible, operation conditions in which emergency exposure might occur, as well as consideration of DOD goals and objectives. The EEGL is generally calculated on the basis of acute toxicity end points. However, even brief exposure to some substances might have the potential to increase the risk of cancer or other delayed effects. If the substance under consideration is carcinogenic, a cancer risk assessment is performed with the aim of providing an estimate of the exposure that would not lead to an excess risk of cancer greater than 1 in 10,000 exposed persons. The acceptable risk selected for military exposures is based on considerations of policy and objectives of DOD.
OCR for page 12
SUBMARINE EXPOSURE GUIDANCE LEVELS FOR SELECTED HYDROFLUOROCARBONS: HFC-236fa, HFC-23, and HFC-404a In estimating the EEGL for a substance that has multiple biological effects, all end points—including respiratory, neurological, reproductive (in both sexes), developmental, carcinogenic, and other organ-related effects—are evaluated, and the most important is selected. If confidence in the available data is low or if important data are missing, appropriate uncertainty factors are used and the rationale for their selection is stated. Generally, EEGLs have been developed for exposure to single substances, although emergency exposures often involve complex mixtures of substances and thus have a potential for toxic synergism. In the absence of other information, guidance levels for complex mixtures can be developed from EEGLs by assuming as a first approximation that the toxic effects are simply additive—thus implying a proportional reduction in EEGLs for each of the constituents of a mixture. Continuous Exposure Guidance Levels The CEGL is a ceiling guidance level set to prevent adverse health effects, either immediate or delayed, of prolonged exposures and to prevent degradation in crew performance that might endanger the objectives of a particular mission as a consequence of continuous exposure for up to 90 days. In contrast with EEGLs, CEGLs are intended to provide guidance for exposures under what is expected to be normal operating conditions in a submarine for periods of up to 90 days. Some conditions, such as slight headache, which might be acceptable for short periods under emergency conditions would not be permissible for long-term exposures. Because long-term exposures are repeated or continuous, detoxification and excretion are of special importance as they relate to the potential of the chemical to accumulate in the body. Special Considerations One important consideration that is commonly used in establishing exposure guidance levels for the general public is variability among humans in sensitivity to the effects of chemicals. A default uncertainty factor of 10 is typically used to protect susceptible individuals. However, the subcommittee believes that using an uncertainty factor to account for intraspecies variability is not necessary because the submariner population is all male, young (18-30 years of age), and healthier than the general population, having passed rigorous physical and psychological examinations.
OCR for page 13
SUBMARINE EXPOSURE GUIDANCE LEVELS FOR SELECTED HYDROFLUOROCARBONS: HFC-236fa, HFC-23, and HFC-404a Another consideration in the derivation of the EEGLs and CEGLs is the inhalation toxicokinetics of the HFCs. In general, the uptake of an inhaled HFC is a function of the rate of respiration (pulmonary ventilation), solubility of the HFC in the blood (blood:gas partition coefficient), pulmonary blood flow (cardiac output), and partial pressure of HFC in the blood. Because of the marked difference in pulmonary ventilation between rodents and humans, rodents will reach a constant HFC arterial pressure much more rapidly than will humans. These differences could be important for short-term exposures, but would likely be of less importance for long-term exposures where both humans and rodents would ultimately reach steady-state arterial concentrations of the gases. STRUCTURE OF THE REPORT The results of the subcommittee's evaluation of HFC-236fa, HFC-23, and HFC-404a are presented in Chapter 2, Chapter 3, and Chapter 4, respectively. For each agent, the subcommittee evaluates inhalation data on the toxicokinetics; acute, subchronic, and chronic toxicity; reproductive effects; developmental effects; genotoxicity; and carcinogenic effects. In addition, special consideration is given to data on cardiac sensitization because inhalation of HFCs and similar compounds are known to make the mammalian heart abnormally sensitive to epinephrine, resulting in cardiac arrhythmia and possibly death. REFERENCES NRC (National Research Council). 1986. Criteria and Methods of Preparing Emergency Exposure Guidance Level (EEGL), Short-Term Public Emergency Guidance Level (SPEGL), and Continuous Exposure Guidance Level (CEGL) Documents. Washington D.C: National Academy Press. NRC (National Research Council). 1992. Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants. Washington D.C: National Academy Press. NRC (National Research Council). 1993. Guidelines for Developing Community Emergency Exposure Levels for Hazardous Substances. Washington D.C: National Academy Press. NRC (National Research Council). 1996. Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 . Washington D.C: National Academy Press.
Representative terms from entire chapter: