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4
Chlorine

This chapter reviews the physical and chemical properties and toxicokinetic, toxicologic, and epidemiologic data on chlorine. The Subcommittee on Submarine Escape Action Levels used this information to assess the health risk to Navy personnel aboard a disabled submarine from exposure to chlorine gas and to evaluate the submarine escape action levels (SEALs) proposed to avert serious health effects and substantial degradation in crew performance from short-term exposure (up to 10 d). The subcommittee also identifies data gaps and recommends research relevant for determining the health risk attributable to exposure to chlorine.

BACKGROUND INFORMATION

Chlorine is an abundant, naturally occurring halogen gas that does not occur in nature in its elemental state (Table 4–1). However, chlorine combines readily with inorganic and organic substances, with the exception of rare gases other than xenon), and nitrogen (Budavari 1989). When formed, chlorine is a diatomic gas with a pungent, suffocating odor. Chlorine can be formed if seawater makes contact with submarine batteries, and it therefore poses a health (survival) risk in a disabled submarine. To protect the health of submarine personnel until they can be rescued submarine escape action levels (SEALs) are needed to avoid



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Review of Submarine Escape Action Levels for Selected Chemicals 4 Chlorine This chapter reviews the physical and chemical properties and toxicokinetic, toxicologic, and epidemiologic data on chlorine. The Subcommittee on Submarine Escape Action Levels used this information to assess the health risk to Navy personnel aboard a disabled submarine from exposure to chlorine gas and to evaluate the submarine escape action levels (SEALs) proposed to avert serious health effects and substantial degradation in crew performance from short-term exposure (up to 10 d). The subcommittee also identifies data gaps and recommends research relevant for determining the health risk attributable to exposure to chlorine. BACKGROUND INFORMATION Chlorine is an abundant, naturally occurring halogen gas that does not occur in nature in its elemental state (Table 4–1). However, chlorine combines readily with inorganic and organic substances, with the exception of rare gases other than xenon), and nitrogen (Budavari 1989). When formed, chlorine is a diatomic gas with a pungent, suffocating odor. Chlorine can be formed if seawater makes contact with submarine batteries, and it therefore poses a health (survival) risk in a disabled submarine. To protect the health of submarine personnel until they can be rescued submarine escape action levels (SEALs) are needed to avoid

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Review of Submarine Escape Action Levels for Selected Chemicals TABLE 4–1 Chemical and Physical Properties CAS number 7782–50–5 Molecular formula Cl2 Molecular weight 70.9 Color Greenish-yellow Odor Suffocating Odor threshold 0.2–0.4 ppm Boiling point –34.05°C Melting point –101.00°C Density (water=1) 1.5649 at boiling point Vapor density 1.4085 at 20°C Solubility Water, alkalies Conversion factors 25°C, 1 atm 1 ppm=2.9 mg/m3 1 mg/m3=0.34 ppm Abbreviations: CAS, Chemical Abstract Service. Source: Budavari (1989) adverse health effects or degradation in crew performance following short-term exposures to chlorine. This chapter presents the available toxicity information on chlorine and the subcommittee’s evaluation of the Navy’s proposed SEALs. Chlorine is used in the manufacture of many products, as a bleaching compound for residential and commercial use, and as a biocide for municipal water and waste treatment (i.e., purifying and disinfecting water, detinning and dezincing iron) (Budavari 1989). It also was used as chemical-warfare agent in World War I (Withers and Lees 1987). TOXICOKINETIC CONSIDERATIONS There are few toxicokinetic studies of chlorine inhalation, and there have been no toxicokinetic studies on dermal exposure to chlorine. Absorption Absorption of chlorine is primarily via the upper respiratory tract. Chlorine is moderately soluble and, thereby, considered a Category I gas (EPA 1994). Because of its reactivity at localized sites, chlorine is not readily absorbed systemi-

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Review of Submarine Escape Action Levels for Selected Chemicals cally. Dermal absorption is possible, but that constitutes a secondary and minor route of exposure. Chlorine reacts with moisture in tissue, resulting in a release of hydrochloric and hypochlorous acids (Budavari et al. 1996; Perry et al. 1994). Nodelman and Ultman (1999a, b) used a bolus inhalation method to study the absorption and distribution of inhaled chlorine during a single breath. Five male and five female volunteers were exposed to chlorine by nose and mouth separately at a concentration of 3 ppm (parts per million). Chlorine was predominantly absorbed in the upper respiratory system (nasal passages, mouth, pharynx), regardless of administration route, with less than 5% of the inspired chlorine found beyond the upper airway and none found in the respiratory air spaces. Distribution Inhaled chlorine is predominantly retained in the upper respiratory tract (Nodelman and Ultman 1999a, b), and is a known irritant. At low doses (≤2.5 ppm for up to 2 h), approximately 95% of chlorine is effectively scrubbed in the upper respiratory tract. At higher concentrations, it reaches the lungs and can exert toxic effects (EPA 1994). Metabolism and Disposition There are no studies on the metabolism of chlorine after inhalation or dermal exposure. Chlorine gas reacts at the localized site, resulting in little absorption into the systematic blood system (Eaton and Klaassen 1996). HUMAN TOXICITY DATA There have been many studies of the toxicity of chlorine in exposed human populations. The subject was of interest during World War I, when chlorine was used as a weapon and the lethality of exposure was widely documented. But lethal concentrations in accidental exposures often are not documented so experimental animal studies must be used. Chlorine is detectable at low, nonlethal concentrations. It is an irritant to eyes, nose, and throat at concentrations less than 0.5 ppm for 4 h. Data sources regarding the toxicity of chlorine include experimental studies with human volunteers and animals; accidentally exposed cohorts of workers, communities, or individuals; warfare studies; and epidemiologic occupational investigations. Each of these data sources is reviewed below and summarized in

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Review of Submarine Escape Action Levels for Selected Chemicals the accompanying tables (Tables 4–2 to 4–5). The information in the tables reflects the spectrum of chlorine gas exposure signs and symptoms (ranging from localized irritation to pulmonary edema and death). Experimental Studies Studies of chlorine exposure in humans are detailed in Tables 4–2 and 4–3. Table 4–2 presents early attempts to determine thresholds for irritant effects, and it is restricted to studies that focused on the irritant effects of chloride. The quality of these early data is questionable because some studies did not provide enough information to support their conclusions (Fieldner et al. 1921, as cited in NIOSH 1976), some used a small number of test subjects (Matt 1889, as cited by NIOSH 1976), and some reported difficulties in maintaining constant concentrations of chlorine within the exposure chambers (Rupp and Henschler 1967, as cited in NIOSH 1976). Table 4–3 presents findings from more recent studies that quantified exposure. Overall, they indicate that chlorine can be detected at concentrations as low as 0.5 ppm (possibly even lower) for 4 h and that it causes slight irritation of the eyes, nose, and throat (Anglen 1981). At higher concentrations, irritant effects are more pronounced, and there are effects on pulmonary function at 1 ppm, which can increase with duration (Rotman et al. 1983). The effects appear to be transient, resolving after exposure ceased. Experimental data support the conclusion that chlorine has both lethal and nonlethal effects in humans. Death can occur at high doses, and various effects, such as choking, coughing, and reactive airway dysfunction are seen at intermediate concentrations. Lower, nonlethal doses are associated with symptoms such as localized irritation of the eyes, nose, and throat. There are no data available where people have been exposed to chlorine gas at concentrations of 1–5 ppm or greater for more than 8 h. Accidental Exposures Numerous studies have examined the effects of accidental exposure to chlorine, and reviews of those studies have been published as well (e.g., NIOSH 1976; NRC 1976; WHO 1982) and will not be repeated here. In most of those studies, exposure to chlorine was high albeit not quantified. Overall, the studies indicate that exposure to high concentrations of chlorine causes effects in the respiratory tract (e.g., pulmonary edema, pneumonia, and tracheobronchitis) that can result in death (Römcke and Evensen 1940, as cited in WHO 1982; Baader 1952, as cited in NIOSH 1976; Dixon and Drew 1968; Adelson and Kaufman 1971).

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Review of Submarine Escape Action Levels for Selected Chemicals TABLE 4–2 Threshold Data on Chlorine from Older Experimental Studies Using Human Subjects Odor Detection (ppm) Ocular Irritation (ppm) Nasal Irritation (ppm) Throat Irritation (ppm) Cough (ppm) Reference 1.3 1.3–2.5 3.5 2.5 3.5 Matt 1889 (as cited in NIOSH 1976) 3.5 — — 15.1 30.2 Fieldner et al. 1921 (as cited in NIOSH 1976) 3.3 — — 6.6 — Vedder and Sawyer 1924 (as cited in NRC 1976) 0.044 — 0.09 0.09 0.09 Beck 1959 (as cited in NIOSH 1976) 0.2 0.2 0.2 0.2 0.2 Beck 1959 (as cited in NIOSH 1976) 0.3 1 1 1 1 Takhiroy 1960a,b (as cited in NRC 1976) 0.28–0.45 — — — — Ryazanov 1962   0.45 0.06 0.058 0.5 Rupp and Henschler 1967 (as cited in NIOSH 1976) Withers and Lees (1985) used lethality data from animal and human studies in a probit analysis to estimate concentrations that would be lethal to 50% (LC50) or to 10% (LC10) of a human population. They estimated a 30-min LC50 of 250 ppm for a normal population, 100 ppm for a susceptible population, and 210 ppm for the average population (combining normal and susceptible groups). The estimated LC10 for each population was 125 ppm, 50 ppm, and 80 ppm, respectively. Immediate effects of exposure to chlorine include choking, coughing, dyspnea, nausea, vomiting, anxiety, loss of consciousness, and eye and nasal irritation (Abhyankar et al. 1989; Beach et al. 1969; Chasis et al. 1947; Moulick et

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Review of Submarine Escape Action Levels for Selected Chemicals al. 1992; Shroff et al. 1988). Subjects who survive exposure to high concentrations (>100 ppm) or who are exposed to lower concentrations (30–60 ppm) exhibit labored breathing, airway obstruction, pulmonary edema, impaired pulmonary function, tracheobronchitis, pneumonia, cyanosis, and cough (Chasis et al. 1947; Colardyn et al. 1976; Joyner and Durel 1962, as cited in WHO 1982; Kaufman and Burkons 1971; Kowitz et al. 1967; Ploysongsang et al. 1982). Some investigators have found that the effects can persist for months or years (Kaufman and Burkons 1971; Kowitz et al. 1967; Schwartz et al. 1990; Sessa et al. 1970, as cited in WHO 1982); others have found no significant permanent damage (Faure et al. 1970, as cited in WHO 1982; Jones et al. 1986; Weill et al. 1969). There also are case reports of reactive airways dysfunction syndrome (RADS) associated with chlorine exposure (Alberts and do Pico 1996; Donnelly and FitzGerald 1990; Schönhofer et al. 1996). RADS is persistent hyper-reactivity of the airways that occurs after a single exposure to a high concentration of an irritant gas (Brooks et al. 1985). All reported RADS cases have resulted from accidental exposures in which exposure concentrations can be presumed to have been high. Schwartz et al. (1990) followed 20 accidentally exposed individuals for 12 yr and reported an increasing prevalence of low residual volume over time and an increase in airway reactivity. These findings suggest that acute exposure has long-term pulmonary sequella and that the presence of air trapping indicates long-term injury. Unfortunately, the chlorine exposure was not quantified. Other effects that have been reported after accidental exposure to chlorine, include palpable and painful liver (Tatarelli 1946, as cited in WHO 1982); anxiety, phobias, or hysteria (Chasis et al. 1947; Segaloff 1961, as cited in WHO 1982); electrocardiographic abnormalities (Leube and Kreiter 1971, as cited in WHO 1982); leukocytosis and elevated glutamate-pyruvate-transaminase (Leube and Kreiter 1971, as cited in WHO 1982); and brain hemorrhages (Baader 1952, as cited in NIOSH 1976). Table 4–3 summarizes some studies for which there are quantitative data on accidental exposure. The data from accidental chlorine exposure support the conclusion that dose is related to type and severity of health effect, which can range from localized irritation of the eyes, nose, and throat; to life-threatening respiratory symptoms that include pulmonary edema and pneumonia; to death.

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Review of Submarine Escape Action Levels for Selected Chemicals TABLE 4–3 Human Toxicity Data, Exposure to Chlorine Sample (n) Route Concentration (ppm) Duration Effect Reference EXPERIMENTAL STUDIES: Volunteers 3 Whole body 0.21–0.52 NR Investigators examined chlorine’s effect on chronaxie, the minimum time need to excite a tissue with a current twice the rheobasic strength, and on reactions to visual stimulus. Prolonged optical chronaxie was found at 0.52 ppm, but not between 0.21 and 0.34 ppm. Optical chronaxie values returned to baseline levels within 2–2.5 min after exposure ceased. Increased sensitivity to light was found at 0.52 ppm, but not at 0.28 ppm. NIOSH (1976) noted that this study measured fine alterations in physiology and their importance to human health is poorly understood. Takhirov 1960b (as cited in NRC 1976) 8 Whole body 0.5, 1, 2, 4.0 2 h No complaints at 0.5 or 1 ppm. At 2 ppm, subjects reported slight irritation of the eyes, nose, throat. At 4 ppm, subjects reported objectionable odor, irritation of the nose and throat, desire to cough. No effects on lung function between 0.5 and 2 ppm. Only 2–3 subjects exposed at 4 ppm remained in the exposure chamber for 2 h, so lung function was not reported for that group. Joosting and Verberk 1974

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Review of Submarine Escape Action Levels for Selected Chemicals Sample (n) Route Concentration (ppm) Duration Effect Reference 31 Whole body 0.5, 1, 2.0 4 h At the two lower concentrations, subjects detected odor and reported throat irritation and an urge to cough. At 2 ppm, effects were reported to be more irritating. Anglen 1981 8 Whole body 0.5, 1.0 8 h (with 30-min or 1-h break for testing after 4 h) Pulmonary function tests were performed at 4 and 8 h. At 4 h, small but statistically significant changes were observed at 1 ppm, including changes in FEV1, PEFR, FEF50, and FEF25, TLC, Raw, and difference in nitrogen concentration. At 8 h, there were alterations in forced vital capacity, FEV1, PEFR, FEF50, FEF25, and Raw. Most of these values returned to normal the next day. Rotman et al. 1983 WARFARE EXPOSURE STUDIES: Soldiers 700 Whole body NR NR Review of medical records of soldiers gassed with chlorine. Acute effects included death, dyspnea, pulmonary edema, bronchitis, pneumonia, asthma. Long-term effects (4 yr after exposure) included “irritable heart” (condition not described). There appeared to be no correlation between acute pulmonary effects and health status 4 yr later. Meakins and Priestly 1919 838 (from 1,843 casualities) Whole body NR NR Review of medical records 8–10 yr after exposure. 4 deaths attributed to “later effect of chlorine gasing.” Subjects had bronchopneumonia, lobar pneumonia, purulent pleurisy, tubercular Gilchrist and Matz 1933

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Review of Submarine Escape Action Levels for Selected Chemicals   meningitis. Survivors exhibited pulmonary tuberculosis, bronchitis, pleurisy, neurocirculatory asethnia, tachycardia, dyspnea, nephritis, laryngitis, valvular heart disease, keratitis, conjunctivitis. Most subjects made complete recovery. 9 subjects had long-term effects, such as pulmonary tuberculosis, bronchitis, chronic adhesive pleurisy.   Whole body 10–1,000 NR Investigators concluded that chlorine is subjectively identified at 10 ppm, produces slight effects at 20 ppm, and causes death at 1,000 ppm within 5 min. “Asphyxiating phase” occurs up to 36 hr after exposure and includes irritation of the throat, coughing, dyspnea, aphonia, bardycardia, pulsus tardus, cyanosis, subnormal temperature. Death during this phase was attributed to pulmonary edema. “Post-asphyxiating phase” occurs when pulmonary edema subsides and bronchitis develops. Other effects include headache, nausea, vomiting, weakness, diarrhea. Gerchik 1939 ACCIDENTAL EXPOSURE STUDIES 85 Whole body 30–60 (Estimated) NR Acute effects included cough, dyspnea, expectoration, respiratory problems. Some of the more severe effects were death, pulmonary edema, bronchopneumonia. Effects were more severe in individuals undergoing physical exertion. Most reported chronic effect was dyspnea. Römcke and Evensen 1940 (as cited in WHO 1982); Hoveid 1956 (as cited in NRC 1976)

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Review of Submarine Escape Action Levels for Selected Chemicals Sample (n) Route Concentration (ppm) Duration Effect Reference 100 (65 casualties, with 15 hospitalized) Whole body 10–400 NR 1 death and 10 cases of pulmonary edema. Subjects exhibited dyspnea, coughing, vomiting, eye irritation, and burns of the face. Chest X-rays of hospitalized patients showed fine miliary mottling of the lungs. No evidence of pneumonitis, and findings disappeared 12 d after exposure. Joyner and Durel 1962   Hysteria after exposure reported, particularly among individuals with “slight tendencies toward neurosis.” 1 physician reported cases of congestive heart failure in elderly subjects; all responded to treatment. Segaloff 1961 (as cited in WHO 1982)   7-yr follow-up of the 12 most severely affected subjects indicated no permanent lung damage. Weill et al. 1969 88 (25 with prior exposure at lower doses) Whole body 66 ppm NR Immediate effects included dyspnea, coughing, irritation of the eyes and throat, headache, giddiness, chest pain, abdominal discomfort. Subjects also exhibited hilar congestion, bronchial vasculature markings, respiratory incapacitation, tracheobronchial congestion, chronic bronchitis, scattered hemorrhages, bronchial erosion. Bronchial smears taken from 28 subjects 5 d after exposure showed basal-cell and goblet-cell hyperplasia, acute inflammation, and chromatolysis Shroff et al. 1988

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Review of Submarine Escape Action Levels for Selected Chemicals   of columnar epithelial cells. 15 subjects exhibited columnar epithelial cell syncitia, nonpigmented alveolar macrophages, and proliferating fibroblasts and capillary fragments. Evidence of epithelial regeneration and repair by fibrosis 15–25 d after exposure.   14 Whole body 30 ppm NR 5 subjects had pre-existing COAD. Immediate effects in all subjects included lacrimation, sneezing, coughing, sputum, retrostenal burning, dyspnea, apprehension, vomiting. Among non-COAD subjects, all effects disappeared within 2 wk and pulmonary function was normal at 6 mo. Among COAD subjects, effects persisted and there was no improvement in pulmonary function at 6 mo. Abhyankar et al. 1989 82 Whole body 66 ppm (found 2 h after leak) <1 h All subjects exhibited dyspnea, cough, bronchospasm. Other effects included irritation of the eyes and throat, headache, abdominal pain, vomiting, giddiness. 5 subjects had cyanosis, X-rays showed cases of patchy infiltrates, hilar congestion. Pulmonary function was affected in most subjects; bronchoscopy revealed tracheobronchial mucosal irritation. Some subjects had hemorrhagic spots, erosions, ulcers. In a follow-up of 16 patients for 1 yr, 4 reported Moulick et al. 1992

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Review of Submarine Escape Action Levels for Selected Chemicals Mouse: 24–34 Whole body 9.3 6 h/d for 5 d Lesions found in anterior respiratory epithelium adjacent to the dorsal meatus and in respiratory epithelium, included exfoliation, inflammation erosion, ulceration, necrosis. Tracheal lesions and terminal bronchiolitis, with occlusion of the affected bronchioles by serocellular exudate. Recovery minimal to moderate after 72 h. LOAEL: 9.3 Buckley et al. 1984 Guinea pig: NR Whole body 1.7 5 h/d for 87 d Some animals pre-exposed to tubercle bacilli, others were not. Deaths occurred among pre-exposed animals. LOAEL: 1.7 Arloing et al. 1940 (as cited in WHO 1982) Dog: 4 Whole body 24–30 30 min Clinical signs included lacrimation, salivation, retching, vomiting. Variable effects on pulse, respiratory rate, increases in body temperature. LOAEL: 24 Barbour 1919 (as cited in NIOSH 1976) Dog: 3 Whole body 180–200 30 min Clinical signs included lacrimation, salivation, retching, vomiting, reduction in muscle activity, dyspnea. Slight decrease in body temperature. No evidence of bronchitis or pulmonary edema. LOAEL: 180 Barbour 1919 (as cited in NIOSH 1976) Dog: NR Whole body 800–900 30 min 85% mortality. Decreases in body temperature. Surviving animals unable to regulate body temperature when exposed to high or low external temperatures. NA Barbour 1919 (as cited in NIOSH 1976)

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Review of Submarine Escape Action Levels for Selected Chemicals Species: No. per Group Route Concentration (ppm) Duration Effect NOAEL, LOAEL (ppm) Reference Monkey: 4 Whole body 0.1, 0.5, 2.3 6 h/d, 5 d/wk for 1 yr At the highest concentration, the only significant clinical effect observed was ocular irritation. Histopathologic examinations revealed changes in nasal passages and trachea of a few animals, including focal epithelial hyperplasia with loss of cilia, decreased number of goblet cells. A few of the animals exposed to 0.5 pm had mild lesions in the nasal passages. NOAEL: 0.5 LOAEL: 2.3 Klonne et al. 1987 Abbreviations: LD50, median lethal dose; LOAEL, lowest observable adverse effect level; NOAEL, no observed adverse effect level; NR, not reported; ppm, parts per million; SPD, spontaneous pulmonary disease; SPF, specific pathogen-free.

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Review of Submarine Escape Action Levels for Selected Chemicals review of the toxicity of chlorine (NRC 1976) which reported that men can work uninterrupted when exposed at 1–2 ppm, and that severe irritation of the eyes, nose, and respiratory tract is observed after a few minutes of exposure to 5 ppm. ADDITIONAL RECOMMENDATIONS FROM THE NRC AND OTHER ORGANIZATIONS Table 4–6 presents exposure limits for chlorine recommended by other organizations. The 24-h emergency exposure guidance level (EEGL) is the most relevant guidance level to compare to the SEALs (NRC 1984). EEGLs were developed for healthy military personnel in emergency situations. An important difference between EEGLs and SEALs is that EEGLs allow mild, reversible health effects, whereas SEALs allow moderate, reversible health effects. That is, SEALs allow effects that are somewhat more intense or potent than those for EEGLs. Therefore, SEAL values are higher than the corresponding EEGL values. SUBCOMMITTEE ANALYSIS AND RECOMMENDATIONS Submarine Escape Action Level 1 On the basis of its review of human and experimental animal health-effects and related data, the subcommittee concludes that the Navy’s recommended SEAL 1 of 2 ppm for chlorine is too high. The subcommittee recommends a SEAL 1 of 1 ppm. The subcommittee recognizes that the dose-response curve for chlorine is steep and therefore, the margin of safety is narrow. The subcommittee’s conclusion is based on studies in which human volunteers exposed to chlorine at a concentration of 0.5–4 ppm for 2–8 h complained or irritation of the eyes, nose, and throat (Joosting and Verberk 1974; NRC 1976; Anglen 1981; Rotman et al. 1983). Volunteers exposed at a concentration of 1 ppm for 8 h had transient pulmonary function changes; however, volunteers exposed at a concentration of 0.5 ppm for 8 h had only trivial pulmonary function changes (Rotman et al. 1983). The SEAL 1 is further supported by a study in which monkeys exposed to chlorine at 2 ppm for 6 h/d, 5 d/wk for 1 yr exhibited no histopathologic lesions of the lower respiratory tract (Klonne et al. 1987). That study would indicate that the recommended SEAL 1 has some margin of safety even if the exposure to chlorine lasts for 10 d.

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Review of Submarine Escape Action Levels for Selected Chemicals TABLE 4–6 Exposure Recommendations from Other Organizations Organization Type of Exposure Recommendation Exposure Limit, ppm Reference ACGIH TLV-TWA (8 h/d during 40-h workweek) 0.5 ACGIH 1999   TLV-STEL (15 min) 1   AIHA ERPG-1 1 AIHA 2001   ERPG-2 3     ERPG-3 20   DFG MAK (8 h/d during 40-h workweek) Peak Limit (5 min maximum duration, 8 times per shift) 0.5 1 DFG 1997 NAC Proposed 8-h AEGL-1 0.5 Federal Register   Proposed 8-h AEGL-2 0.71 October 30, 1997.   Proposed 8-h AEGL-3 7.1 62(210):58839–58851. NIOSH REL-TWA (10 h/d during 40-hr workweek) 0.5 NIOSH 2001   IDLH 10   NRCa EEGL (1 h) 3 NRC 1984   EEGL (24 h) 0.5     CEGL (90 d) 0.1   OSHA PEL-TWA (ceiling value) 1 OSHA 1999b aGuidelines were established for use by the military. bOccupational Safety and Health Standards. Code of Federal Regulations. Part 1910. 1000 Air Contaminants. Abbreviations: ACGIH, American Conference of Governmental Industrial Hygienists; AEGL, acute exposure guideline level; AIHA, American Industrial Hygiene Association; CEGL, continuous exposure guidance level; DFG, Deutsche Forschungsgemeinschaft; EEGL, emergency exposure guidance level; ERPG, emergency response planning guidelines; IDLH, immediately dangerous to life and health; MAK, maximum concentration values in the workplace; NAC, National Advisory Committee; NRC, National Research Council; OSHA, Occupational Safety and Health Administration; PEL, permissible exposure limit; REL, recommended exposure limit; STEL, short-term exposure limit; TLV, Threshold Limit Value; TWA, time-weighted average.

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Review of Submarine Escape Action Levels for Selected Chemicals Submarine Escape Action Level 2 On the basis of its review of human and experimental animal health-effects and related data, the subcommittee concludes that the Navy’s proposed SEAL 2 of 5 ppm for chlorine is too high. The subcommittee recommends a SEAL 2 of 2.5 ppm for chlorine. That recommendation is supported by a study in which 3 human volunteers exposed to chlorine at a concentration of 4 ppm for 2 h were able to tolerate the exposure and volunteers exposed at a concentration of 2 ppm for 2 h did not have significant changes in lung function (Joosting and Verberk 1974). The subcommittee’s recommended SEAL 2 is also supported by the study by Klonne et al. (1987), which is described above. The subcommittee concludes that most crew members should be able to tolerate the irritant effects of chlorine exposure at concentrations below 2.5 ppm for 24 h. DATA GAPS AND RESEARCH NEEDS Additional studies on the toxicity of chlorine in experimental animals are needed to better define the health effects of exposure at concentrations of 0.5–4 ppm, 24 h/d for up to 10 d. These studies should include evaluation of short-term effects, on pulmonary function and on long-term effects such as inflammation of the respiratory tract and pulmonary fibrosis. Studies are also needed on the interactive effects of chlorine with other gases found in disabled submarines. Additional studies on chlorine toxicity in animals and, possibly, on human volunteers are needed to better define the health effects of chlorine gas exposure at 0.5–5 ppm, 24 h/d up to 7–10 d. Long-term exposure data for humans and animals is needed to approximate a disabled submarine situation. These studies should include evaluation of short-term effects on pulmonary function and long term effects such as pulmonary fibrosis. As is the case for all irritant toxic gases reviewed in this report. REFERENCES Abhyankar, A., N.Bhambure, N.N.Kamath, S.P.Pajankar, S.T.Nabar, A.Shrenivas, A.C.Shah, and S.N.Deshmukh. 1989. Six month follow-up of fourteen victims with short-term exposure to chlorine gas. J. Soc. Occup. Med. 39(4):131–132. ACGIH (American Conference of Governmental Industrial Hygienists). 1999. TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents. Biological Exposure Indices. Cincinnati, OH: ACGIH. Adelson, L., and J.Kaufman. 1971. Fatal chlorine poisoning: Report of two cases with clinicopathologic correlation. Am. J. Clin. Pathol. 56(4):430–442.

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Review of Submarine Escape Action Levels for Selected Chemicals AIHA (American Industrial Hygiene Association). 2001. The AIHA 2001 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook Fairfax, VA: American Industrial Hygiene Association. Alberts, W.M., and G.A.do Pico. 1996. Reactive airways dysfunction syndrome. Chest 109(6):1618–1626. Anglen, D.M. 1981. Sensory Response on Human Subjects to Chlorine in Air. PhD. Dissertation. University of Michigan. Arloing, F., E.Berthet, and J.Viallier. 1940. Action of chronic intoxication by low concentration chlorine fumes on experimental guinea pigs. [in French]. Presse Med. 48:361. Baader, E.W. 1952. Chlorine anhydride poisoning (the Walsum disaster). [in Spanish]. Med. Deporte Trab.17:5252, 5254, 5256, 5258–5259. Barbour, H.G. 1919. The effects of chlorine upon the body temperature. J. Pharmacol. Exp. Ther. 14:65–73. Barrow, C.S., and R.G.Smith. 1975. Chlorine induced pulmonary function changes in rabbits. Am. Ind. Hyg. Assoc. J. 36:398–403. Barrow, C.S., and W.H.Steinhagen. 1982. Sensory irritation tolerance development to chlorine in F-344 rats following repeated inhalation. Toxicol. Appl. Pharmacol. 65(3):383–389. Barrow, C.S., Y.Alarie, J.C.Warrick, and M.F.Stock 1977. Comparison of the sensory irritation response in mice to chlorine and hydrogen chlorine. Arch. Environ. Health 32(2):68–76. Barrow, C.S., R.J.Kociba, L.W.Rampy, D.G.Keyes, and R.R.Albee. 1979. An inhalation toxicity study of chlorine in Fischer-344 rats following 30 days exposure. Toxicol. Appl. Pharmacol. 49(1):77–88. Beach, F.X., E.S.Jones, and G.D.Scarrow. 1969. Respiratory effects of chlorine gas. Br. J. Ind. Med. 26(3):231–236. Beck, H. 1959. Pp. 1–7, 16–19, 21–31, 44–54 in Experimental Determination of the Olfactory Thresholds of Some Important Irritant Gases (Chlorine, Sulphur Dioxide, Ozone, Nitrous Gases) and Symptoms Induced in Humans by Low Concentrations, [in German]. Ph. D. Thesis. Universität Würzburg. Bell, D.P., and P.C.Elmes. 1965. The effects of chlorine gas on the lungs of rats without spontaneous pulmonary disease. J. Pathol. Bacteriol. 89:307–317. Bitron, M.D., and E.F.Aharonson. 1978. Delayed mortality of mice following inhalation of acute doses of CH2O, SO2, Cl2, and Br2. Am. Ind. Hyg. Assoc. J. 39(2):129– 138. Brooks, S.M., M.A.Weiss, and I.L.Bernstein. 1985. Reactive airways dysfunction syndrome. Case reports of persistent airways hyperreactivity following high-level irritant exposures. J. Occup. Med. 27(7):473–476. Buckley, L.A., X.Z.Jiang, R.A.James, K.T.Morgan, and C.S.Barrow. 1984. Respiratory tract lesions induced by sensory irritants at the RD50 concentration. Toxicol. Appl. Pharmacol. 74(3):417–429. Budavari, S., ed. 1989. Pp. 323–324 in The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 11th Ed. Rahway, NJ: Merck. Budavari, S., M.J.O’Neil, A.Smith, P.E.Heckelman, and J.F.Kinneary. 1996. The

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Review of Submarine Escape Action Levels for Selected Chemicals Merck Index, 12th Ed. Rahway, NJ: Merck. Capodaglio, E., G.Pezzagno, G.C.Bobbio, and F.Cazzoli. 1969. Respiratory function test in workers employed in electrolytic production of chlorine and sodium. [in Italian]. Med. Lav. 60(3):192–201. Chang, J.C., and C.S.Barrow. 1984. Sensory irritation tolerance and cross-tolerance in F-344 rats exposed to chlorine or formaldehyde gas. Toxicol. Appl. Pharmacol. 76(2):319–327. Chasis, H., J.A.Zapp, J.H.Bannon, J.L.Whittenberger, J.Helm, J.J.Doheny, and C.M. MacLeod. 1947. Chlorine accident in Brooklyn. Occup. Med. 4:152–176. Chester, E.H., D.G.Gillespie, and F.D.Krause. 1969. The prevalence of chronic obstructive pulmonary disease in chlorine gas workers. Am. Rev. Resp. Dis. 99(3):365–373. Colardyn, F., M.Van Der Straeten, J.Tasson, and J.Van Egmond. 1976. Acute chlorine gas intoxication. Acta Clin. Belg. 31(2):70–77. Das, R., and P.D.Blanc. 1993. Chlorine gas exposure and the lung: A review. Toxicol. Ind. Health. 9(3):439–455. Demnati, R., R.Fraser, G.Plaa, and J.L.Malo. 1995. Histopathological effects of acute exposure to chlorine gas on Sprague-Dawley rat lungs. J. Environ. Pathol. Toxicol. Oncol. 14(1):15–19. Demnati, R., R.Fraser, H.Ghezzo, J.G.Martin, G.Plaa, and J.L.Malo. 1998. Time-course of functional and pathological changes after a single high acute inhalation of chlorine in rats. Eur. Respir. J. 11(4):922–928. DFG (Deutsche Forschungsgemeinschaft). 1997. List of MAK and BAT Values 1997. Maximum Concentrations and Biological Tolerance Values at the Workplace, First Ed. Report No. 33. Weinheim: Wiley-VCH. Dixon, W.M., and D.Drew. 1968. Fatal chlorine poisoning. J. Occup. Med. 10(5):249– 251. Donnelly, S.C., and M.X.FitzGerald. 1990. Reactive airways dysfunction syndrome (RADS) due to chlorine gas exposure. Ir. J. Med. Sci. 159:275–277. Eaton, D.L., and C.D.Klaassen. 1996. Principles of toxicology. Pp. 13–33 in Casarett and Doull’s Toxicology: The Basic Science of Poisons, 5th Ed. New York McGraw Hill. Elmes, P.C., and D.Bell. 1963. The effects of chlorine gas on the lungs of rats with spontaneous pulmonary disease. J. Pathol. Bacteriol. 86:317–326. EPA (U.S. Environmental Protection Agency). 1994. Chlorine. Integrated Risk Information system. [Online]. Available: http://www.epa.gov/ngispgm3/iris/subst/0405.htm (Last updated: May 5, 1998). Evans, E.E. 1940. An X-ray study of the effects of industrial gases upon the human lung. Radiology 34(April):411–424. Faure, J., M.Sibille, H.Faure, C.Stephan, M.Yacoub, and J.Motin. 1970. Acute chlorine and phosgene poisoning (clinical and experimental study). [in French]. Poumon Coeur 26(8):913–929. Ferris, B.G., W.A.Burgess, and J.Worchester. 1967. Prevalence of chronic respiratory disease in a pulp mill and a paper mill in the United States. Br. J. Ind. Med. 24(1):26– 37.

OCR for page 97
Review of Submarine Escape Action Levels for Selected Chemicals Ferris, B.G., S.Puleo, and H.Y.Chen. 1979. Mortality and morbidity in a pulp and paper mill in the United States: A ten-year follow-up. Br. J. Ind. Med. 36(2):127–134. Fieldner, A.C., S.R.Katz, and S.P.Kinney. 1921. Pp. 3–61 in Gas Masks for Gases Met in Fighting Fires. Tech. Paper 248. Washington, DC: U.S. Department of the Interior, Bureau of Mines. Gagnaire, F., S.Azim, P.Bonnet, G.Hecht, and M.Hery. 1994. Comparison of the sensory irritation response in mice to chlorine and nitrogen trichloride. J. Appl. Toxicol. 14(6):405–409. Geiling, E.M.K., and F.C.McLean. 1941. Progress Report on Toxicity of Chlorine Gas for Mice to Nov. 6, 1941. Office of Scientific Research and Development Report 286. U.S. National Defense Research Committee. 21 pp. Gerchik, M. 1939. Medical experience of Americans with chemical poison gas during the World War. Protar. 5(11):173–179. Gilchrist, H.L., and P.B.Matz. 1933. 1. Chlorine, 2. Mustard. Pp. 1–41 in The Residual Effects of Warfare Gases. Washington, DC: U.S. Government Printing Office. Gunnarsson, M., S.M.Walther, T.Seidal, G.D.Bloom, and S.Lennquist. 1998. Exposure to chlorine gas: Effects on pulmonary function and morphology in anesthetized and mechanically ventilated pigs. J. App. Toxicol. 18(4):249–255. Hoveid, P. 1956. The chlorine gas accident in Mjöndalen (Norway), January 26, 1940: An after investigation. [in Norwegian]. Nord. Hyg. Tid. 37:59–66. Jiang, X.Z., L.A.Buckley, and K.T.Morgan. 1983. Pathology of toxic responses to the RD50 concentration of chlorine gas in the nasal passages of rats and mice. Toxicol. Appl. Pharmacol. 71(2):225–236. Jones, R.N., J.M.Hughes, H.Glindmeyer, and H.Weill. 1986. Lung function after acute chlorine exposure. Am. Rev. Respir. Dis. 134(6):1190–1195. Joosting, P., and M.Verberk. 1974. Emergency population exposure: A methodological approach. Pp. 2,005–2,029 in Recent Advances in the Assessment of Health Effects of Environmental Pollution, International Symposium Proceedings, Vol. 4. Commission of the European Communities, World Health Organization, U.S. Environmental Protection Agency. NTIS PB261 480. Joyner, RE., and E.G.Durel. 1962. Accidental liquid chlorine spill in a rural community. J. Occup. Med. 4:152–154. Kaufman, J., and D.Burkons. 1971. Clinical, roentgenologic and physiologic effects of acute chlorine exposure. Arch. Environ. Health 23(1):29–34. Klonne, D.R., C.E.Ulrich, M.G.Riley, T.E.Hamm, Jr., K.T.Morgan, and C.S.Barrow. 1987. One-year inhalation toxicity study of chlorine in rhesus monkeys (Macaca mulatta). Fundam. Appl. Toxicol. 9(3):557–572. Kowitz, T.A., R.C.Reba, R.T.Parker, and W.S.Spicer. 1967. Effects of chlorine gas upon respiratory function. Arch. Environ. Health 14(4):545–558. Leube, G., and H.Kreiter. 1971. Acute chlorine poisoning. Case reports of 90 patients with acute poisoning, [in German]. Med. Klin. 66(10):354–357. Matt, L. 1889. Experimental Contributions to the Theory of the Effects of Poisonous Gases on Human Beings, [in German]. Inaugural dissertation. Julius-Maximilliams-Universität, Würzburg. Meakins, J.C., and J.G.Priestly. 1919. The after-effects of chlorine gas poisoning. Can. Med. J. 9:968–974.

OCR for page 97
Review of Submarine Escape Action Levels for Selected Chemicals Moulick, N.D., S.Banavali, A.D.Abhyankar, S.Borkar, J.Aiyengar, N.M.Kapadia, and R.C.Khokhani. 1992. Acute accidental exposure to chlorine fumes: A study of 82 cases. Indian J. Chest Dis. Allied Sci. 34(2):85–89. NIOSH (National Institute for Occupational Safety and Health). 1976. Criteria for a Recommended Standard Occupational Exposure to Chlorine. HEW Pub. No. (NIOSH) 76–170. U.S. Department of Health, Education, and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safety and Health, Washington, DC. NIOSH (National Institute for Occupational Safety and Health). 2000. Appendix A NIOSH Pocket Guide to Chemical Hazards. NIOSH Potential Occupational Carcinogens. [Online]. Available: http://www.cdc.gov/niosh/npg/nengapdx.htm. [April 30, 2001]. Nodelman, V., and J.S.Ultman. 1999a. Longitudinal distribution of chlorine absorption in human airways: Comparison of nasal and oral quiet breathing. J. Appl. Physiol. 86(6):1984–1993. Nodelman, V., and J.S.Ultman. 1999b. Longitudinal distribution of chlorine absorption in human airways: A comparison to ozone absorption. J. Appl. Physiol. 87(6):2073– 2080. NRC (National Research Council). 1976. Medical and Biological Effects of Environmental Pollutants Chlorine and Hydrogen Chlorine. Washington, DC: National Academy of Sciences. NRC (National Research Council). 1984. Emergency and Continuous Exposure Limits for Selected Airborne Contaminants, Vol. 2. Washington, DC: National Academy Press. Patil, L.R.S., R.G.Smith, A.J.Vorwald, and T.F.Mooney. 1970. The health of diaphragm cell workers exposed to chlorine. Am. Ind. Hyg. Assoc. J. 31(6):678–686. Perry, W.G., F.A.Smith, and M.B.Kent. 1994. The Halogens. Pp. 4482–4505 in Patty’s Industrial Hygiene and Toxicology, Vol. II, Part F. G.F.Clayton, and F.E.Clayton, eds. New York: John Wiley & Sons. Ploysongsang, Y., B.C.Beach, and R.E.DiLisio. 1982. Pulmonary function changes after acute inhalation of chlorine gas. South Med. J. 75(1):23–26. Römcke, O., and O.K.Evensen. 1940. The chlorine poisoning in Mjöndalen. [in Norwegian]. Nord. Med. 7:1224–1226. Rotman, H.H., M.J.Fliegelman, T.Moore, R.G.Smith, D.M.Anglen, C.J.Kowalski, and J.G.Weg. 1983. Effects of low concentrations of chlorine on pulmonary function in humans. J. Appl. Physiol. 54(4):1120–1124. Rupp, H., and D.Henschler. 1967. Effects of low chlorine and bromine concentrations on man. [in German]. Int. Arch. Arbeitsmed. 23(1):79–90. Ryazanov, V.A. 1962. Sensory physiology as basis for air quality standards. Arch. Environ. Health 5:480–491. Schlagbauer, M., and D.Henschler. 1967. Toxicity of chlorine and bromine in single and repeated inhalations. [in German]. Int. Arch. Arbeitsmed. 23(1):91–98. Schönhofer, B., T.Voshaar, and D.Köhler. 1996. Long-term lung sequelae following accidental chlorine gas exposure. Respiration 63(3):155–159. Schwartz, D.A., D.D.Smith, and S.Lakshminarayan. 1990. The pulmonary sequelae associated with accidental inhalation of chlorine gas. Chest 97(4):820–825.

OCR for page 97
Review of Submarine Escape Action Levels for Selected Chemicals Segaloff, L. 1961. Task Sirocco. Community Reactin to an Accidental Chlorine Exposure. Project Summit. Contract No. DA-18–064-Cml-2757. Philadelphia, PA: The Institute for Cooperative Research, University of Pennsylvania. Sessa, T., L.Pecora, G.Vecchione, and R.Mole. 1970. The cardiorespiratory function in bronchopneumopathies caused by irritant gases. [in French]. Poumon Coeur 26(9):1097–1107. Shroff, C.P., M.V.Khade, and M.Srinivasan. 1988. Respiratory cytopathology in chlorine gas toxicity: A study in 28 subjects. Diagn. Cytopathol. 4(1):28–32. Silver, S.D., and F.P.McGrath. 1942. Chlorine: Median Lethal Concentration for Mice. Tech. Rep. 351. Edgewood Arsenal, MD: War Dept., Chemical Warfare Service. 14 pp. May 9. Silver, S.D., F.P.McGrath, and R.L.Ferguson. 1942. Chlorine: Median Lethal Concentration for Mice. Tech. Rep. 373. Edgewood Arsenal, MD: War Dept., Chemical Warfare Service. 11 pp. July 17. Skljanskaja, R.M., K.M.Klaus, and L.M.Ssidorowa. 1935. On the effect of chlorine on the female organism. [in German]. Arch. Hyg. Bakteriol. 114:103–114. Stokinger, H.E. 1981. The halogens and the nonmetals boron and silicon. Pp. 2,937– 3,043 in Patty’s Industrial Hygiene and Toxicology, 3rd Rev. Ed., Vol. 2B. Toxicology, G.D.Clayton and F.E.Clayton, eds. New York: John Wiley & Sons. Takhirov, M.T. 1960a. Basic principles for the determination of allowable chlorine concentration in the atmosphere of inhabited localities. Pp. 31–49 in Limits of Allowable Concentrations of Atmospheric Pollutants, Book 4, V.A.Ryazanov, ed. Translated by B.S.Levine. Washington, DC: U.S. Public Health Service, January 1961. (Available from the National Technical Information Service, Springfield, VA, as publication no. TT-60–21475). Takhirov, M.T. 1960b. Determination of limits of allowable concenraiton of chlorine in atmospheric air. Pp. 119–125 in U.S.S.R. Literature on Air Pollution and Related Occupational Diseases. A Survey, Vol. 3, B.S.Levine, ed. Washington, DC: U.S. Public Health Service. May 1960. (Available from the National Technical Information Service, Springfield, VA, as publication no. TT-60–21475). Tatarelli, G. 1946. Cumulative chlorine poisoning on board a submarine. Ann. Naval. Colonial Med. 51(3):337–348. (Translated from Italian by Leo Kanner Associates for Information Services Division, U.S. Environmental Protection Agency, Redwood City, CA. March 1973). Tawast, M., K.Linkama, and M.Siurala. 1956. Blood counts of industrial workers exposed to vaporized mercury and chlorine. Ann. Med. Int. Fenniae 45:59–61. Underhill, F.P. 1920. The Lethal War Gases, Physiology and Experimental Treatment. New Haven: Yale University Press. Vedder, E.B., and H.P.Sawyer. 1924. Chlorine as a therapeutic agent in certain respiratory diseases. JAMA 82:764–766. Vernot, E.H., J.D.MacEwen, C.C.Haun, and E.R.Kinkead. 1977. Acute toxicity and skin corrosion data for some organic and inorganic compounds and aqueous solutions. Toxicol. Appl. Pharmacol. 42(2):417–423. Weedon, F.R., A.Hartzell, and C.Setterstrom. 1940. Toxicity of ammonia, chlorine, hydrogen cyanide, hydrogen sulphide and sulphur dioxide gases. V. Animals. Contrib. Boyce Thompson Inst. 11:365–385.

OCR for page 97
Review of Submarine Escape Action Levels for Selected Chemicals Weill, H., R.George, M.Schwarz, and M.Ziskind. 1969. Late evaluation of pulmonary function after actue exposure to chlorine gas. Am. Rev. Respir. Dis. 99(3):374–379. WHO (World Health Organization). 1982. Chlorine and Hydrogen Chlorine, Environmental Health Criteria 21. IPCS International Programme on Chemical Safety. Geneva: World Health Organization. Winternitz, M.C., R.A.Lambert, L.Jackson, and G.H.Smith. 1920. The Pathology of Chlorine Poisoning. New Haven: Yale University School of Medicine. Withers, R.M.J., and F.P.Lees. 1985. The assessment of major hazards: The lethal toxicity of chlorine. Part 1. Review of information on toxicity. J. Hazard. Mater. 12:231–282. Withers, R.M.J., and F.P.Lees. 1987. The assessment of major hazards: The lethal toxicity of chlorine. J. Hazard. Mater. 15:301–342. Wolf, D.C., K.T.Morgan, E.A.Gross, C.Barrow, O.R.Moss, R.A.James, and J.A. Popp. 1995. Two-year inhalation exposure of female and male B6C3F1 mice and F344 rats to chlorine gas induces lesions confined to the nose. Fundam. Appl. Toxicol. 24:111–131. Zwart, A., and R.A.Woutersen. 1988. Acute inhalation toxicity of chlorine in rats and mice: Time-concentration-mortality relationships and effects on respiration. J. Hazard. Mater. 19:195–208.