Review of Submarine Escape Action Levels for Selected Chemicals (2002)

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

Hydrogen chloride is a colorless, nonflammable gas with a pungent, suffocating odor (ACGIH 1991). It is very hygroscopic and produces fumes in moist air. The chemical and physical properties of hydrogen chloride are summarized in Table 5–1.

Hydrogen chloride is an important industrial chemical. The anhydrous form is used in making alkyl chlorides and vinyl chloride from olefins and acetylene, respectively, and in hydrochlorination, alkylation, and polymerization reactions (Sax and Lewis 1987). The hydrated form of hydrogen chloride is hydrochloric acid, which also is used in idustrial processes.

Hydrogen chloride can be produced from thermodegradation of chlorinated polymers (e.g., polyvinyl chloride (PVC) and chlorinated acrylics) (Coleman and Thomas 1954). When chlorinated polymers are heated to 300–900°C in air, more than 99.9% of the chlorine atoms are released as hydrogen chloride; the remaining chlorine atoms are released as carbonyl chloride. No chlorine gas is formed. Hydrogen chloride has been detected in fires involving the combustion of chlorinated polymers, most commonly PVC (Dyer and Esch 1976; Gold et al. 1978; Jankovic et al. 1991). Of hydrogen chloride released from PVC in fires, more than 2% was adsorbed to soot particles, and only about 0.8% reached the alveoli (Stone et al. 1973 as cited in the NRC 2000).

Data on the absorption, distribution, metabolism, and excretion of hydrogen chloride are sparse. There are reports of severe nonlactic metabolic acidosis developing rapidly after ingestion of hydrochloric acid (suggesting systemic absorption from the gastrointestinal tract), but this effect has not been reported after dermal exposure to concentrated hydrochloric acid or after inhalation of hydrogen chloride vapor or aerosol. No studies were found on upper respiratory

tract absorption of hydrogen chloride; however, it is known that two other water-soluble gases, hydrogen fluoride and formaldehyde, are readily taken up by the upper respiratory tract (Morgan and Monticello 1990). Extrapolating results from studies of those gases to hydrogen chloride is difficult because both of them have significant systemic toxicity. Liver and kidney effects have been observed in experimental animals exposed by inhalation to hydrogen chloride, which suggests that the gas is absorbed from the respiratory tract (EPA 1994). However, the effects also could be attributed to disturbance of acid-base metabolism or to decreased blood oxygen concentrations attendant to pulmonary damage. Chloride ions derived from hydrogen chloride absorbed in the upper respiratory tract should be distributed throughout the body (NRC 2000). Hydrogen chloride is not metabolized.

Hydrogen chloride is a strong irritant that primarily affects the respiratory tract, resulting in coughing, pain, inflammation, edema, and desquamation (NRC 1987). Because it is soluble in water and reacts with the surface components of the upper respiratory tract, hydrogen chloride is usually retained there. At high concentrations, it is possible that the scrubbing capacity of the upper respiratory tract could be overwhelmed and penetration to the bronchioles and alveoli could occur. Other effects that can result from exposure to moderate or high concentrations include nasal lesions, pulmonary edema, retrosternal pain, and dyspnea (Ellenhorn 1997). Severe pulmonary injury can result in death. Because chloride ions are normal electrolytes in the body, prolonged exposures to low concentrations or brief exposures to high concentrations will not perturb the electrolyte homeostasis in the body enough to result in any systemic toxicity (NRC 2000). This section reviews the available human toxicity data on hydrogen chloride; some of which are summarized in Table 5–2. No epidemiology studies were found.

Stevens et al. (1992) exposed 5 men and 5 women (aged 18–25) to filtered air or to hydrogen chloride at 0.8 ppm (parts per million) or 1.8 ppm for 45 min.The 45-min exposure sessions consisted of a 15-min exercise period on a treadmill walking at 2 miles per hour at an elevation grade of 10%, followed by a 15-minute rest period and then by another 15-min exercise period. Subjects were asked to report any symptoms, such as upper respiratory effects (sore

throat, nasal discharge), lower respiratory effects (cough, chest pain or burning, dyspnea, wheezing), and other effects (fatigue, headache, dizziness, unusual taste or smell). Pulmonary function measurements were performed, including total respiratory resistance, thoracic gas volume at functional residual capacity, forced expiratory volume, forced vital capacity, and maximal flow at 50% and 75% of expired vital capacity. Nasal work of breathing and oral ammonia concentrations also were measured. No adverse treatment-related effects were observed.

Three male police officers (aged 36–45) were exposed to unknown concentrations of sodium hydroxide, silicon tetrachloride, and hydrogen chloride from a roadside chemical spill (Promisloff et al. 1990). The officers developed reactive airways dysfunction syndrome (RADS), a type of bronchospastic airway disease that occurs after a single exposure to high concentrations of an irritating vapor, fume, or smoke. Subsequently episodes of bronchospasmcan be triggered by inhalation exposure to any irritant substance. A 41-yr old male (nonsmoker) with a history of asthma developed RADS after cleaning a pool with a solution containing hydrogen chloride (concentration not reported) (Boulet 1988).

No reports were found that described accidental dermal exposure to hydrogen chloride in humans. Even after dermal exposure to concentrated hydrochloric acid resulting in significant burns, there have been no reported cases suggesting systemic absorption or systemic toxicity.

Stokinger (1981) reported that repeated occupational exposure to hydrogen chloride mist at a high but not quantified concentration resulted in bleeding of the gums and nose and ulceration of the mucous membranes. Dental erosion (but not an increase in dental caries) was reported in 555 workers exposed to acids in battery, pickling, plating, and galvanizing operations (Ten Bruggen Cate 1968). These workers were exposed to various mineral acids, including hydrogen chloride.

Numerous experimental animal studies have examined the toxicity of hydrogen chloride. They are summarized below; the experimental details are presented in Table 5–3.

Several laboratories examined lethality as a result of inhalation exposure to hydrogen chloride. Rat LC₅₀ (the concentration that causes death in 50% of test animals) ranges from 31,000 to 41,000 ppm for a 5-min exposure (Darmer et al. 1974; Higgins et al. 1972). Rat LC₅₀ values for a 30-min exposure are 4,700 ppm for hydrogen chloride vapor and 5,600 ppm for aerosol (Darmer et al. 1974). The LC₅₀ for a 60-min exposure is 3,124 ppm (Wohlslagel et al. 1976). Guinea pigs exposed at 586 ppm for 3 min died (Malek and Alarie 1989), but no deaths were reported in guinea pigs exposed at 162 ppm for 30 min (Malek and Alarie 1989). Two of eight guinea pigs exposed at 1,040 or 1,380 ppm for 30 min died, but no deaths were reported in guinea pigs exposed at 320 or 680 ppm for 30 min (Burleigh-Flayer et al. 1985).

Nonlethal toxicity studies demonstrate that hydrogen chloride is a sensory and respiratory irritant. At relatively low concentrations and short exposure times, hydrogen chloride can cause changes to the upper respiratory tract. Rats exposed at 200–1,500 ppm for 30 min showed a decrease in respiratory rate and minute volume, and nasal pathology (Hartzell et al. 1985; Stavert et al. 1991). Respiratory tract irritation was observed in rats exposed at 1,800–4,500 ppm for 60 min (Wohlslagel et al. 1976) and at 11,800–57,000 for 5 minutes (Kaplan et al. 1986; Darmer et al. 1974).

Mice showed extreme respiratory irritation when exposed at 410–5400 ppm for 60 min, 560–2,500 ppm for 30 min, or 3,200–30,000 ppm for 5 min (Darmer et al. 1974; Doub 1933; Wohlslagel et al. 1976). Guinea pigs exposed at 107 ppm for 30 min showed only mild sensory irritation, but guinea pigs exposed at 140– 1,040 ppm for 30 min showed more severe sensory irritation or incapacitation (Burleigh-Flayer et al. 1985; Malek and Alarie 1989). Exposure at 190 ppm for 5 min did not cause adverse effects in a baboon, but exposure at 500 or 5,000 ppm for 30 min caused increased respiratory rate and minute volume (Kaplan et al. 1988). Baboons exposed at 16,600–17,300 ppm for 5 min showed pulmonary edema, pneumonia, and bacterial infections; the animals died weeks after the exposure (Kaplan et al. 1988).

Although some reports state that vapor is more toxic at a given concentration than is aerosol because of the lack of desiccating activity with aerosols, hydrogen chloride is so water reactive that the emergency exposure guidance level documentation (NRC 1987) states that published reports are assumed to deal with hydrogen chloride aerosol unless specifically stated otherwise. Because of the predicted cold and humid atmosphere in a disabled submarine, exposures would likely be to aerosol rather than vapor. In rats and mice, there was no significant difference in toxicity between vapor and aerosol exposure at various concentrations.

Rats and mice exposed by inhalation at 10–50 ppm for 6 h/d, 5 d/wk for 90 d exhibited no significant histopathology, although the rats exposed at 50 ppm did show mild rhinitis (Toxigenics 1983). Mice exposed at 310 ppm for 6 h/d for 5 d showed necrosis, exfoliation, erosion, and ulceration of the respiratory epithelium in the nose (Buckley et al. 1984). No effects were observed in guinea pigs exposed at 34 ppm for 6 h/d, 5 d/wk for 4 wk (Machle et al. 1942). Respiratory effects were observed in guinea pigs exposed at 67 ppm for 6 h/d for 5 d and at 100 ppm for 6 h/d for 50 d (Machle et al. 1942; Ronzani 1909, as cited in NRC 2000).

The Navy proposes to set a SEAL 1 of 2.5 ppm and a SEAL 2 of 25 ppm for exposure to hydrogen chloride. Those values appear to be based on the Short-Term Public Limits and the Public Emergency Limits (NRC 1987).

Recommended exposure guidance levels for hydrogen chloride from other organizations are summarized in Table 5–4. The 24-h emergency exposure guidance level (EEGL) is the most relevant guidance level to compare to the SEALs (NRC 1987). EEGLs were developed for healthy military personnel for 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, the SEALs are higher than the corresponding EEGLs.

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 1 of 2.5 ppm for hydrogen chloride is too conservative. The subcommittee

recommends a SEAL 1 of 20 ppm. No relevant human data are available on hydrogen chloride for deriving SEALs. The subcommittee’s recommended SEAL 1 is based on a study in which the RD₅₀ (50% decrease in respiratory rate) for hydrogen chloride was found to be 309 ppm in mice (Kane et al. 1979). Applying an uncertainty factor of 10 to account for interspecies differences, the SEAL 1 would be 31 ppm. Because of the paucity of human and animal data and the longer duration of exposure (up to 10 d), the subcommittee recommends a SEAL 1 of 20 ppm. At low concentrations (such as 20 ppm), the toxicity of hydrogen chloride depends on concentration, rather than dose (i.e., Haber’s Rule is not applicable) (NRC 1987). The subcommittee concludes that healthy submariners should be able to tolerate irritative effects associated with exposures to less than 20 ppm for up to 10 d. The subcommittee’s recommended SEAL 1 of 20 ppm is also supported by studies in which rats, mice, and guinea pigs were exposed to hydrogen chloride at 10–50 ppm for 6 h/d, 5 d/wk, for 90 d (rats and mice) or 28 d (guinea pigs) and no significant irritation or systemic effects were observed (Toxigenics 1983; Machle et al. 1942).

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 25 ppm for hydrogen chloride is too conservative. The subcommittee recommends a SEAL 2 of 35 ppm. The subcommittee’s recommendation is based on a study in which a baboon exposed at a concentration of 190 ppm hydrogen chloride for 5 min showed no signs of irritation and baboons exposed at a concentration of 500 ppm for 30 min had only minor, transient respiratory effects (Kaplan et al. 1988). The recommended SEAL 2 is further supported by a study in which guinea pigs exposed to hydrogen chloride at a concentration of 107 ppm for 30 min showed only mild sensory irritation and no incapacitation (Malek and Alarie 1989). Since the toxicity of hydrogen chloride depends on concentration, rather than dose, and Haber’s rule is not applicable to hydrogen chloride (NRC 1987), the subcommittee concludes that exposure of healthy submariners at 35 ppm for 24 h would produce moderate irritative effects that would be tolerable and would not produce irreversible health effects.

The subcommittee recommends that the Navy consider conducting the following studies:

• Healthy volunteers—people with no asthma or other respiratory sensitivities—be studied to determine the actual NOAEL and LOAEL for hydrogen chloride;

• The absorption (if any) of hydrogen chloride vapor and aerosol through intact human skin in vitro should be studied;

• Additional information on the interaction of hydrogen chloride and the other irritant gases should be obtained;

• Finally, the potential effects of hyperbaric atmospheres under the conditions found in a disabled submarine should be studied as they obtain in the case of hydrogen chloride exposures.

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