Hydrogen Chloride

National Research Council (US) Committee on Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

National Research Council (US) Committee on Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 3. Washington (DC): National Academies Press (US); 2009.

Cover of Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants

Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 3.

Show details

< Prev Next >

3Hydrogen Chloride

This chapter summarizes the relevant epidemiologic and toxicologic studies of hydrogen chloride. It presents selected chemical and physical properties, toxicokinetic and mechanistic data, and inhalation-exposure levels from the National Research Council and other agencies. The committee considered all that information in its evaluation of the U.S. Navy’s 1-h, 24-h, and 90-day exposure guidance levels for hydrogen chloride. The committee’s recommendations for hydrogen chloride exposure levels are provided at the end of this chapter with a discussion of the adequacy of the data for defining the levels and the research needed to fill the remaining data gaps.

PHYSICAL AND CHEMICAL PROPERTIES

Hydrogen chloride is a colorless, corrosive, nonflammable gas with a pungent odor (Budavari et al. 1989). Leonardos et al. (1969) determined the odor threshold of hydrogen chloride to be 10 ppm by using a standardized procedure, a trained odor panel, and high-purity hydrogen chloride; the odor was described by the panel as “pungent.” A wide range of odor thresholds (HSDB 2008) have since been reported. On the basis of a literature review, Amoore and Hautala (1983) reported the odor threshold as 0.77 ppm. The irritating concentration has been reported as 33 ppm (Ruth 1986).

Hydrogen chloride is highly soluble in water and forms hydrochloric acid. Because hydrogen chloride is so hygroscopic, airborne hydrogen chloride is typically an aerosol of hydrochloric acid. Selected physical and chemical properties are shown in Table 3-1.

TABLE 3-1

Physical and Chemical Properties of Hydrogen Chloride.

OCCURRENCE AND USE

Hydrogen chloride is found naturally in the environment, is produced by the digestive system of most mammals, is a byproduct of many industrial processes, and is used primarily to synthesize inorganic and organic chemicals, such as chlorine, ethylene dichloride, and methyl chloride (Hisham and Bommaraju 2005).

Hydrogen chloride has been measured in the submarine atmosphere. Data collected on three nuclear-powered attack submarines indicate a range of 1-3 ppb (Hagar 2008). Whether the reported concentrations are representative of the submarine fleet is not known; few details were provided about the conditions on the submarines when the samples were taken. The committee located no other exposure data for the submarine environment. Hydrogen chloride emissions in the submarine are thought to arise from decomposition of halogenated hydrocarbons and refrigerants (Hagar 2008).

SUMMARY OF TOXICITY

The toxicity of hydrogen chloride has been the subject of a number of reviews (NRC 1987; EPA 1995; Lam and Wong 2000; NRC 2002, 2004; ACGIH 2003). At high concentrations, hydrogen chloride is an irritant to the mucous membranes, eyes, and skin. Accidental exposure to gaseous products or mix tures containing high concentrations of hydrogen chloride can result in a spectrum of chronic effects, including recurrent acute respiratory illnesses and asthma. Prolonged hypoxemia is noted in case reports, but details of exposure duration are unknown. The maximum tolerable concentration in prolonged exposure of humans has been reported as 10 ppm, with a maximum tolerable concentration for a few hours of 10-50 ppm (Henderson and Hagard 1943). Respiratory tract effects in laboratory animals range from mild to moderate irritation at low concentrations (less than 100 ppm) to nasal lesions at moderate concentrations (100-500 ppm) and pulmonary damage at high concentrations (greater than 500 ppm). Death can result from severe pulmonary injury. Hydrogen chloride can cause functional and morphologic respiratory tract injuries, depending on exposure concentration and duration (Darmer et al. 1974; Hartzell et al. 1985; Burleigh-Flayer et al. 1985; Kaplan et al. 1988, 1993a, cited in NRC 2004; Stavert et al. 1991). Because of its high water solubility, most hydrogen chloride that is inhaled should be absorbed in the upper respiratory tract (Morris and Smith 1982), and this should result in low availability for systemic toxicity. However, hepatic, myocardial, and renal damage was observed in laboratory animals after repeated exposure at high concentrations (Machle et al. 1942). Those effects may be attributed to disturbances in acid-base metabolism or to reduction in blood oxygen concentrations resulting from pulmonary damage. Data on the genotoxicity, immunotoxicity, and male reproductive toxicity of hydrogen chloride exposure are either nonexistent or too sparse to support conclusions. Neither epidemiologic studies nor lifetime animal cancer bioassays have yielded evidence of an association between hydrogen chloride exposure and cancer (Bond et al. 1991; IARC 1992; Sellakumar et al. 1985).

Effects in Humans

Accidental Exposures

Accidental exposure can occur when hydrogen chloride is the sole agent or the dominant agent in a mixture, such as one produced by combustion of polyvinyl chloride. Published reports describe immediate skin, eye, and respiratory tract irritation, particularly in the nose, pharynx, larynx, and tracheobronchial tree. The reports described below do not include exposure concentrations, so they are of little use in setting exposure guidelines; they are provided as secondary, supportive evidence of the outcomes observed in quantitative animal exposure studies.

A 41-year-old nonsmoking nonatopic man with stable, mild asthma developed rapidly progressive bronchospasm and acute respiratory failure requiring mechanical ventilation after cleaning a pool for 1 h with a product that contained hydrochloric acid. Severe asthma requiring oral corticosteroids and repeated hospitalizations persisted a year after the accident (Boulet 1988). A 57-year-old man with a 12-pack-year cigarette-smoking history developed irritant-induced asthma after exposure to a hydrochloric acid and phosgene mixture (Tarlo and Broder 1989).

Finnegan and Hodson (1989) provided an overview of the 47 cases of hydrogen chloride fume inhalation in the registry of the poison center of Guy’s Hospital, London. Exposure sources, durations, and circumstances were not specified. The dominant initial symptoms were nausea and vomiting, with bronchospasm in those with a history of asthma and one report of laryngospasm. Symptoms typically resolved in a week. Rosenthal et al. (1978) reported persistent hypoxemia lasting for months in one of 11 workers exposed to a gaseous mixture of hydrogen chloride, phosphorus oxychloride, phosphorus pentachloride, oxalyl chloride, and oxalic acid. Evidence of alveolar injury in the workers included reduction in diffusion capacity (three workers) and a finding of lung rales on physical examination (two workers).

The following case is presented in detail because of the extensive clinical characterization of persistent hypoxemia, which indicated the ability of mixed hydrogen chloride vapor and mist to cause delayed-onset deep lung or parenchymal injury. The case also illustrates a propensity for recurrent acute respiratory illness after such an injury. A chemical factory released vapors that contained an unknown high concentration of hydrogen chloride, water, and trace amounts of phosphorous trichloride. The release resulted in a 15-min exposure of a 34-year-old woman who was working on her boat in an open marina 300 ft away. As reported by Finnegan and Hodson (1989), the strength of the mixture caused the paint on the boat to blister. The woman was hospitalized on the same day for symptoms of skin, eye, and respiratory tract irritation and for tachypnea, facial erythema, and hoarseness. She was discharged on the third day but readmitted with dyspnea while talking and with hypoxemia without hypercapnea, corrected with 24-28% oxygen. Further evaluation to identify the cause of the hypoxemia showed a normal anatomic shunt of 3.2%, a normal ventilation-perfusion scan (which excluded pulmonary thromboembolism), and normal total lung capacity but reduced residual volume. Exercise challenge during this interval showed marked desaturation (from 94% to 82%). The hypoxemia persisted for a month despite treatment with prednisone, salbutamol, and beclomethasone. Hypoxemia recurred during two later viral infections that required hospitalization.

A neighborhood exposure occurred when a container truck leaked 200 gal of hydrochloric acid while parked 150 ft from a mobile-home park; hydrogen chloride was later found in nearby ditches and a pond (Kilburn 1996). The acute illness among the investigating officer and residents included burning and tearing eyes, burning throat, headache, chest pain, shortness of breath, and influenza-like complaints. Follow-up assessment 20 months after the exposure compared findings between 45 adults and 24 children living in the zone of the cloud of fumes and 56 adults and 39 children living in a similar mobile-home court 1.4 miles from the site. The exposed group showed more respiratory symptoms, such as phlegm production and shortness of breath, than the reference group. After adjustment for sex, age, height, and cigarette-smoking, exposed adults showed lower mean forced vital capacity (FVC; 70% vs 79%) and lower forced expiratory volume at 1 s (FEV₁; 61% vs 72%). Self-reports of mood state showed greater tension, depression, anger, extreme fatigue, and confusion and lower vigor in the exposed group.

Dyer and Esch (1976) performed a clinical study of 170 firefighters who were exposed one to four times to polyvinyl chloride thermal degradation products. Acute symptoms included pain in the throat, neck, and anterior part of the chest; dyspnea; severe headache; dizziness; and irregular pulse. Electrocardiography showed that 20% had extrasystoles. Twelve firefighters required hospitalization and treatment with oxygen, bronchodilators, antihistamines, and decongestants. None had to retire because of permanent airway disorders.

Markowitz et al. (1989) conducted a retrospective cohort study of 80 fire-fighters exposed in 1985 to burning polyvinyl chloride; they used 15 unexposed firefighters as control subjects. Air analysis during a recreation of the polyvinyl chloride combustion showed the primary decomposition products to be hydrogen chloride (6,800 ppm), carbon monoxide (9,300 ppm), carbon dioxide (26,000 ppm), and methane (1,760 ppm). Smaller quantities of benzene (146 ppm) and other organic compounds, primarily acetylene (420 ppm), were detected. The concentrations of nitric oxide, nitrogen dioxide, methyl pyrrole, and an unidentified chlorinated agent were 3-6 ppm. Phosgene, vinyl chloride, dioctylphthalate, and polychlorinated biphenyls were not detected. One hour after the fire began, firefighters reported rashes and eye irritation. Five to 6 weeks after the incident, symptoms with a higher relative risk in exposed firefighters included eye irritation, skin irritation, rash or itching, sore throat, headache, restlessness, dizziness, blurred vision, stomach pain, tingling or numbness, dry mouth, chest pain, wheezing, coughing, shortness of breath, increased thirst, muscle or joint pain, tiredness, and daytime drowsiness.

Promisloff et al. (1990) reported the development of reactive-airways dysfunction syndrome (RADS) in three Philadelphia police officers after exposure to toxic fumes from a roadside truck accident. The accident resulted in a large chemical spill and fire on a major highway. Exposures were to sodium hydroxide and hydrochloric acid generated by hydrolysis of silicon tetrachloride and trichlorosilane. Exposure concentrations were not discussed. In summary, the officers developed persistent coughing and headache within hours of exposure and exertional dyspnea and wheezing later. Inhalation challenge showed airway hyperreactivity to methacholine; exercise challenge showed no oxyhemoglobin desaturation. Initial spirometry was normal, but an accelerated decline in function (decreases in FEV₁ and FEV₁/FVC%) occurred over the following year.

Experimental Studies

Human exposure studies performed in laboratories in the late 1800s and first half of the 1900s remain an important source of hydrogen chloride exposure-response information (Table 3-2). A limitation of the data is that the meth ods and results are reported in less detail than current practice dictates. Elkins (1959) recommended a maximum allowable concentration of 5 ppm on the basis of immediate symptoms of nose and throat irritation. Lower concentrations might have promoted tooth decay but were not considered to be harmful. All concentrations above 10 ppm were reported as highly irritating, although some workers adapted over time. Workplace exposure measurements included 16 ppm in waste carbonizing, 11 ppm in acid dipping, and 23 ppm in tanning processes.

TABLE 3-2

Hydrogen Chloride: Human Exposure Studies.

Henderson and Hagard (1943) reported that hydrogen chloride at 35 ppm caused irritation of the throat on short exposure, and 10 ppm was the maximum concentration tolerable for prolonged exposure. The maximum concentration tolerable for a few hours was 10-50 ppm, the maximum concentration tolerable for 1 h was 50-100 ppm, and concentrations of 1,000-2,000 ppm were reported as dangerous for even short exposure.

Heyroth (1963) cited an 1889 dissertation that reported that work is impossible when one inhales hydrogen chloride at 50-100 ppm, difficult but possible at 10-50 ppm, and undisturbed at 10 ppm.

Stevens et al. (1992) exposed 10 18- to 25-year-old asthmatics to low concentrations of hydrogen chloride (0.8 and 1.8 ppm) in a controlled human exposure study. The subjects were exposed three times: once to filtered air, once to hydrogen chloride at 0.8 ppm, and once to hydrogen chloride at 1.8 ppm. Exposures were separated by at least a week. The 45-min exposure was evenly divided into two periods of exercise separated by a period of rest. The exercise consisted of walking on a treadmill at 2 mph with an inclination of 10%. The subjects reported no increases in respiratory symptoms and had insignificant changes in pulmonary function between pre-exposure and postexposure measurements. There was a significant rise in oral ammonia concentrations—a finding that was counterintuitive in that the authors had expected a slight decrease because of neutralization caused by the inhaled acid gas. The authors concluded that people who had mild asthma had no adverse respiratory effects of exposure to hydrogen chloride at low concentrations.

Occupational and Epidemiologic Studies

Kremer et al. (1995) conducted a cross-sectional study to evaluate the relationship between occupational exposure to low concentrations of airway irritants and airway responsiveness to histamine, a marker of airway hyperreactivity. Of a cohort of 688 male workers, 119 were potentially exposed to acid mists containing sulfur dioxide and hydrogen chloride vapors and aerosols of sulfate and hydrogen chloride. Company policies prevented employment of workers who might be exposed to the acid mists if they had a suspected history of asthma-like symptoms during the 5-year period before the study. Time-weighted average (7-h, TWA) concentrations were determined by personal sampling and indicated maximum concentrations of 0.3 mg/m³ for sulfur dioxide vapor, of 2.1 mg/m³ for hydrogen chloride aerosol, and of 0.5 mg/m³ for sulfate aerosol. For some work operations, peak hydrogen chloride vapor exposures of up to 40 mg/m³ (27 ppm) occurred (averaging a few minutes). There was a trend toward a reduced prevalence of histamine reactivity in the acid-mist group; however, the mixed exposure and pre-employment selection bias limit the usefulness of this study in the present analysis.

Possible carcinogenic effects of hydrogen chloride were evaluated with a nested case-control study of 308 lung-cancer cases and 616 comparison workers among a cohort of 19,608 chemical-manufacturing employees (Bond et al. 1991). Exposure reconstruction was performed by an industrial hygienist familiar with plant operations. The duration of hydrogen chloride exposure was calculated by summing the time spent on jobs with a TWA greater than zero. Cumulative exposure was derived by multiplying the time spent on each job by the midpoint of the TWA range for that job and summing across all jobs. Workers were then classified into four exposure groups: 0, 0.1-3.9, 4-12.4, and at least 12.5 ppm-years. There was no association between hydrogen chloride exposure and lung cancer whether analyzed by duration of exposure, cumulative exposure, highest average exposure, or latency.

Coggon et al. (1996) assessed the risk of cancer from inhalation of mineral-acid mists with a cohort study and a nested case-control study of 15 men with upper aerodigestive tumors in a 93% follow-up sample of 4,401 men employed since 1950 at two battery plants and two steel works in Britain. The 15 upper aerodigestive cancers included four of the lip, three of the larynx, two of the tongue, one of the nasal sinus, two of the gum or retromolar area, two of the pharynx or nasopharynx, and one of the tonsil. The odds ratio (OR) was doubled for cumulative acid exposure, measured according to whether a person had worked for over 5 years in jobs with exposures in excess of 1 mg/m³ (OR, 2.0; 95% confidence interval [CI], 0.4-10). There was no dose-response relationship for risk related to maximum exposure to acid mists. There was no information on smoking and alcohol consumption in the cohort, but the authors stated that lung cancer in men with definite exposure to acid mists was close to expectation (standardized mortality ratio, 0.98; 95% CI, 0.78-1.22).

Effects in Animals

Acute Toxicity

Acute exposures of laboratory animals to hydrogen chloride were summarized in reviews by NRC (1987, 2002, 2004), Lam and Wong (2000), and ACGIH (2003). A number of LC₅₀ values have been calculated for exposure times ranging from 5 to 60 min in rats and mice (Higgins et al. 1972, cited in NRC 2004; MacEwen and Vernot 1972, cited in NRC 1987; Darmer et al. 1974; Wohlslagel et al. 1976, cited in NRC 2004; Vernot et al. 1977; Anderson and Alarie 1980, cited in NRC 2004). Mice appear to be more sensitive than rats to the lethal effects of hydrogen chloride. For a 60-min exposure, the LC₅₀ values in mice were 1,108 ppm (Wohlslagel et al. 1976, cited in NRC 2004) and 1,322 ppm (MacEwan and Vernot 1972, cited in NRC 2004). NRC (2004) combined rat and mouse LC₅₀ data for exposures of 1-100 min and, on the basis of regression analysis, determined that n = 1 was appropriate for application of the relationship Cⁿ × t = k, where C = concentration, t = time, and k = constant, defined by ten Berge et al. (1986) for time-scaling.

Nonhuman primates, guinea pigs, rabbits, rats, and mice have been used in a number of nonlethal single-exposure investigations of hydrogen chloride. Baboons (n = 1, 2, or 3) were exposed to a range of hydrogen chloride concentrations for 5-15 min to assess respiratory effects and the potential of hydrogen chloride to impair escape behavior (Kaplan 1987; Kaplan et al. 1985, cited in NRC 1987, 2004; Kaplan et al. 1986, cited in NRC 2002; Kaplan et al. 1988). Concentrations of 16,570 and 17,290 ppm (5 min) caused severe dyspnea and resulted in delayed death due to pneumonia and pulmonary edema (Kaplan et al. 1985, cited in NRC 1987, 2004). At 500, 5,000, or 10,000 ppm (15 min), respiratory rate and minute volume were increased, arterial oxygen decreased (5,000 and 10,000 ppm), but lung function was normal when measured 3 days and 3 months after exposure (Kaplan et al. 1988). Irritant effects ranged from coughing and frothing at the mouth at lower concentrations (810-940 ppm) to profuse salivation, blinking, and head-shaking at higher concentrations (16,570-17,290 ppm), but there was no loss of escape capability at 11,400 or 17,290 ppm. No sign of irritation was observed in a baboon exposed to hydrogen chloride at 190 ppm for 5 min (Kaplan et al. 1985, cited in NRC 1987, 2004). It should be noted that individual baboons may have been used for more than one exposure (NRC 2004).

Four groups of investigators have studied the effects of acute (15-30 min) hydrogen chloride exposure in guinea pigs (Kaplan et al. 1993b, cited in NRC 2004; Malek and Alarie 1989; Burleigh-Flayer et al. 1985; Machle et al. 1942). Results were not always consistent among studies, perhaps because of the different study designs and end points monitored. Hydrogen chloride was shown to be a sensory and pulmonary irritant at exposure concentrations of 320-1,380 ppm (Burleigh-Flayer et al. 1985). Kaplan et al. (1993b, cited in NRC 2004) observed a decrease in respiratory rate at 520 or 3,940 ppm but little effect on blood gases and a decrease in arterial pH in animals exposed only at 3,940 ppm.

Malek and Alarie (1989) focused on time to incapacitation by using a chamber exercise-wheel apparatus. Guinea pigs exercised on the wheel for 10 min before the start of hydrogen chloride exposure. The authors observed gasping and death in guinea pigs exposed at 586 ppm. Hydrogen chloride concentrations of 140 and 162 ppm caused coughing, gasping, and incapacitation; time to incapacitation was 16.5 and 1.3 min, respectively. Guinea pigs exposed at 107 ppm showed only mild irritation (details were not provided) and were not incapacitated during the 30 min of exposure.

Machle et al. (1942) exposed groups of three guinea pigs and three rabbits to hydrogen chloride at various concentrations (about 34-14,000 ppm) and for various times (5 min to 6 h). Animals that survived 2 months or longer were killed. Detailed results were not provided, but no animals survived exposure to hydrogen chloride at 679 ppm for 6 h. At lower concentrations, mild inflammatory reactions with some peribronchial fibrosis and lymph node hyperplasia were observed in the guinea pigs. Lobular pneumonia and pulmonary abscesses were observed in rabbits exposed at lower concentrations. However, no pathologic changes (presumably in lungs, liver, kidneys, and heart) were observed in animals exposed at the lowest concentration studied (34 ppm 6 h/day, 5 days/week for 4 weeks).

Several scientists reported acute hydrogen chloride exposure studies in rats that resulted in nonlethal effects. Exposures to hydrogen chloride at 11,800 ppm and higher for 5 min produced extreme irritation of the mucous membranes, eyes, and respiratory tract (Darmer et al. 1974; Kaplan et al. 1986, cited in NRC 2002). Rats did not lose their ability to escape via a signal-avoidance task unless the exposure concentration of hydrogen chloride were high enough to induce death (87,600 ppm) (Kaplan 1987, cited in ACGIH 2003; Kaplan et al. 1988, cited in ACGIH 2003). Irritation of the eyes, mucous membranes, and respiratory tract and erythema occurred when animals were exposed at 1,800-4,500 ppm for 1 h, and 20% or higher mortality occurred when rats were exposed at 2,600 ppm or higher for 1 h (Wohlslagel et al. 1976, cited in NRC 2002). Concentration-related decreases in respiratory rate and minute volume were observed after 30-min exposures at 200 ppm and higher (Hartzell et al. 1985). The RD₅₀ (the concentration that produces a 50% decrease in respiratory frequency) was determined to be 560 ppm. Stavert et al. (1991) showed dramatic differences in response to hydrogen chloride exposure between nose-breathing rats and mouth-breathing rats. The mouth-breathing rats were fitted with a mouthpiece attached to an endotracheal tube. At 1,300 ppm for 30 min, 46% of the mouth-breathing rats and 6% of the nose-breathing rats died. Survivors were killed 24 h after exposure, and their nasal cavities, tracheas, and lungs were examined microscopically. Epithelial-cell necrosis and severe inflammation were observed in the tracheas of mouth-breathing rats, but the findings were limited to the nasal cavities of nose-breathing rats. Similarly, lung weights were increased in the mouth-breathing rats compared with control animals, but not in the nose-breathing rats. In summary, functional respiratory effects were observed in rats after 30-min exposure to hydrogen chloride at 200 ppm or higher, and lethality was observed in mouth-breathing rats exposed at 1,300 ppm for the same duration.

Mice appear to be more sensitive to acute hydrogen chloride exposures than rats (Higgins et al. 1972, cited in NRC 2004). In general, mice die at hydrogen chloride concentrations that are about one-third of the concentrations that kill rats. Studies in mice by Doub (1933, cited in NRC 2002), Darmer et al. (1974), Wohlslagel et al. (1976, cited in NRC 2002, 2004), Lucia et al. (1977), Barrow et al. (1977, 1979), and Kaplan et al. (1993b) yielded the following observations:

5-min exposures. Hydrogen chloride produced severe irritation of the mucous membranes and eyes and some irritation of exposed skin at concentrations of 3,200 ppm or higher.
10-min exposures. Hydrogen chloride is a sensory irritant with an RD₅₀ of 309 ppm. A decrease in respiratory rate was observed above 40 ppm, and small superficial ulcerations were observed in respiratory epithelium of the nasal cavity near its junction with squamous epithelium at a concentration as low as 17 ppm. As the concentration of hydrogen chloride increased, the mucosal ulcerations increased in severity and extent, gradually extending up the sides and septum of the nasal cavity.
15-min exposures. Hydrogen chloride produced a decrease in respiratory rate at 475 ppm or higher followed by 50% or greater mortality after exposure. The time between exposure and death was inversely related to exposure concentration. No abnormal histopathologic findings were observed in the respiratory tract (nares to lungs) of the 475-ppm exposure group, but causes of death were not stated.
30-min exposures. Hydrogen chloride produced severe irritation of the mucous membranes and some irritation of exposed skin at concentrations of 410 ppm or higher.
60-min exposures. Hydrogen chloride produced irritation of the mucous membranes and eyes, respiratory distress, corneal opacity, and erythema at concentrations of 560 ppm or higher. Twenty percent mortality was observed at 560 ppm.

In summary, minimal microscopic lesions were observed in the nasal cavities of mice exposed to hydrogen chloride at 17 ppm for 10 min, but this information was not consistent with results of other studies, which showed no lesions at 475 ppm for 15 min. However, mortality was observed in mice exposed to hydrogen chloride at 475 ppm for 15 min or at 560 ppm for 1 h. A slight decrease in respiratory rate occurs at 40 ppm, and the RD₅₀ was 309 ppm.

Repeated Exposures and Subchronic Toxicity

A few inhalation studies of hydrogen chloride that used more than a single exposure have been performed in laboratory animals. Buckley et al. (1984) investigated the induction of respiratory tract lesions in mice after exposure to chemical sensory irritants. Histopathologic lesions were observed in the nasal cavity after exposure to hydrogen chloride at 310 ppm 6 h/day for 3 days. Lesions included exfoliation, erosion, ulceration, and necrosis of the nasal respiratory epithelium. However, nasal cavity lesions were minimal in the olfactory epithelium, and no effects were observed in the lungs of mice exposed to hydrogen chloride. In a 4-week study by Machle et al. (1942), no histopathologic lesions (presumably in the lungs, liver, kidneys, and heart) were observed in three rabbits, three guinea pigs or one monkey exposed to hydrogen chloride at 34 ppm 6 h/day, 5 days/week. However, several months elapsed after exposure before all animals were killed and examined for histologic effects.

A 90-day inhalation toxicity study was conducted by Toxigenics (1984). Both sexes of F344 and Sprague-Dawley rats (31 males and 21 females per strain per group) and B6C3F1 mice (31 males and 21 females per group) were subjected to whole-body exposure to hydrogen chloride at 0, 10, 20, or 50 ppm 6 h/day, 5 days/week for 13 weeks. An interim necropsy of 15 males and 10 females per group took place the day after the fourth exposure. End points included clinical observations, body weight, hematologic findings, serum chemistry, urinalysis findings, and histopathologic lesions of selected tissues. All 50-ppm exposure groups had a reduction in body-weight gain, which was observed after as few as four exposures. Minimal to mild rhinitis was observed in rats in all groups exposed to hydrogen chloride. The degree of rhinitis was concentration- and duration-dependent and was confined to the anterior portion of the nasal cavity. There were no changes in hematologic, serum chemistry, or urinalysis measures or histopathologic findings beyond the nasal cavity in the exposed rats compared with control rats.

In mice, body-weight gain was decreased in the 50-ppm exposure group. Histopathologic lesions (minimal to mild intracytoplasmic “eosinophilic globules”) were observed in the epithelial cells lining the nasal turbinates of mice in all groups exposed to hydrogen chloride. Effects were more prevalent in females than in males, and eosinophilic globules were not observed in male mice in the 20-ppm and 10-ppm groups. Mice in the 50-ppm group also had minimal lesions of the lips (ulcerative cheilitis). There were no changes in hematologic, serum chemistry, or urinalysis measures or histopathologic findings beyond the nasal cavity and perioral areas in exposed mice compared with control mice.

The results of the 90-day study indicate that 10 ppm is a lowest observed-adverse-effect level (LOAEL) in light of the minimal rhinitis and minimal eosinophilic globules in nasal turbinates observed in rats and mice, respectively.

Chronic Toxicity

The study conducted by Sellakumar et al. (1985) provides the only inhalation toxicity data on exposures to hydrogen chloride lasting more than 90 days (data reported at an interim stage in Albert et al. 1982). A single group of 100 male Sprague-Dawley rats was exposed to hydrogen chloride at 10 ppm 6 h/day, 5 days/week for 128 weeks (lifetime). The group exposed only to hydrogen chloride was part of a larger study that involved exposure of four additional groups of rats to air only (control group), to formaldehyde at 15 ppm, to a mixture of hydrogen chloride at 10 ppm and formaldehyde at 15 ppm, and to vapors of hydrogen chloride at 10 ppm and formaldehyde at 15 ppm that were not mixed but were introduced simultaneously and separately into the exposure chamber. End points included daily clinical observations, body weights, gross necropsy findings, and histopathologic findings of the nasal cavity, trachea, lar ynx, lung, kidneys, testes, and other organs in which gross lesions were observed. Only results for the respiratory tract were presented in detail. The incidences of epithelial or squamous-cell hyperplasia (in 62 of 99 animals) and squamous-cell metaplasia (in nine of 99 animals) in the nasal cavity of rats exposed only to hydrogen chloride were greater than incidences observed in air-only control animals (51 of 99 and five of 99, respectively). Incidences of tracheal hyperplasia (in 26 of 99) and laryngeal hyperplasia (in 22 of 99) were increased in the rats exposed only to hydrogen chloride compared with air-only control rats (six of 99 and two of 99, respectively). For developing an inhalation reference concentration for hydrogen chloride, the U.S. Environmental Protection Agency considered a concentration of 10 ppm in this study as a LOAEL (EPA 1995).

Reproductive Toxicity in Males

No data on male reproductive toxicity of hydrogen chloride were found in the literature. Results of repeated inhalation exposure studies in rats and mice (Toxigenics 1984) did not reveal histopathologic effects in male reproductive organs.

Immunotoxicity

No data on immunotoxicity of hydrogen chloride were found in the literature.

Genotoxicity

Genotoxicity studies of hydrogen chloride are sparse. There are no in vivo genotoxicity inhalation studies of hydrogen chloride, such as a mouse micronucleus assay. Results of an adenovirus SA7 transformation assay of Syrian hamster embryo cells with hydrochloric acid concentrations of 31-500 μg/mL were negative (Casto and Hatch 1978, cited in Heidelberger et al. 1983). However, at a concentration of 25 μg/well, hydrochloric acid was positive in an Escherichia coli DNA-repair assay (McCarroll et al. 1981); and at a concentration of 100 ppm for 24 h, chromosomal nondisjunction was induced in Drosophila melanogaster (RTECS 2008).

Carcinogenicity

Sellakumar et al. (1985) performed a lifetime study of exposure of male Sprague-Dawley rats to hydrogen chloride. A summary of the experimental de sign and results is provided in the section “Chronic Toxicity.” The authors counted tumors observed in the respiratory tract and total number of tumors in organs outside the respiratory tract. There was no evidence of excess tumor formation in animals exposed only to hydrogen chloride compared with the control group. The combination of hydrogen chloride and formaldehyde did not affect the incidence of nasal cavity carcinogenesis compared with the incidence of nasal tumors observed in the formaldehyde-only exposure group. The conclusion was that hydrogen chloride did not promote the carcinogenicity of formaldehyde.

TOXICOKINETIC AND MECHANISTIC CONSIDERATIONS

Toxicokinetic studies of hydrogen chloride were not found in the literature. The high water solubility of hydrogen chloride indicates rapid adsorption of hydrogen chloride on mucous membranes after inhalation. Morris and Smith (1982) predicted that more than 99% of inhaled hydrogen fluoride would be absorbed by the upper respiratory tract in rats. Because hydrogen chloride, like hydrogen fluoride, has high water solubility and reactivity, it should also be highly absorbed in the upper respiratory tract of rats. Inhalation studies of hydrogen chloride in laboratory animals have shown tissue injury in the most anterior regions of the nasal cavity with much less or even negligible injury in the posterior areas of the nasal cavity or downstream in the trachea and lungs (Buckley et al. 1984; Stavert et al. 1991). The high water solubility and rapid dissolution of hydrogen chloride partly explain the low systemic toxicity observed after hydrogen chloride exposure (Machle et al. 1942; Toxicogenics 1984; Sellakumar et al. 1985). However, high concentrations of hydrogen chloride (for example, greater than 500 ppm) appear to saturate the absorption or buffering capacities of the nasal mucosa, and pulmonary damage—such as congestion, mild hemorrhage, and multifocal acute alveolitis—is observed more frequently (Burleigh-Flayer et al. 1985; Kaplan et al. 1993b). Tracheal injury was also observed in mouth-breathing rats exposed to hydrogen chloride at 1,300 ppm for 30 min, but no lower respiratory effects were observed in nose-breathing rats under the same exposure conditions (Stavert et al. 1991). Thus, humans may be more susceptible to lung effects when breathing through their mouths than when breathing through their noses under identical exposure conditions.

Once absorbed into the mucous layers and membranes, hydrogen chloride is not metabolized but dissociates into hydrogen ions and chloride ions (pK, -7 in aqueous medium). The hydrogen ions react with water to produce hydronium ions, which, as proton donors, react readily with organic molecules. That reaction is presumably responsible for cellular injury and, if severe enough, cell death. Fluid accumulates at the site of injury and explains why pulmonary edema and such other factors as vascular changes and interference in gaseous transfer (of oxygen in particular) are associated with the cause of animal death (Machle et al. 1942; Darmer et al. 1974). The chloride ions derived from dissociation of hydrogen chloride are likely to be distributed throughout the body because they are normal electrolytes. In general, it is presumed that chloride ions generated from hydrogen chloride inhalation—even brief exposures at high concentrations—are not sufficient to perturb the body’s electrolyte balance.

INHALATION EXPOSURE LEVELS FROM THE NATIONAL RESEARCH COUNCIL AND OTHER ORGANIZATIONS

A number of organizations have established or proposed acceptable exposure limits or guidelines for inhaled hydrogen chloride. Selected values are summarized in Table 3-3.

TABLE 3-3

Selected Inhalation Exposure Levels for Hydrogen Chloride from the National Research Council and Other Agencies.

COMMITTEE RECOMMENDATIONS

The committee’s recommendations for EEGL and CEGL values for hydrogen chloride are summarized in Table 3-4. The current U.S. Navy values are provided for comparison.

TABLE 3-4

Emergency and Continuous Exposure Guidance Levels for Hydrogen Chloride.

1-Hour EEGL

Biologic end points that were considered the most relevant for derivation of the 1-h EEGL were mild irritation of the eyes and mucosal surfaces and alterations in respiratory frequency at hydrogen chloride concentrations that produced reversible effects. Alteration in respiratory rate is a sensitive indicator of sensory and pulmonary irritation (ASTM International 2004). Chemicals that decrease respiratory frequency by 20-50% are considered moderate irritants (ASTM International 2004). An approximate 10% decrease in respiratory rate was observed in mice exposed to hydrogen chloride at 40 ppm for 10 min (Barrow et al. 1977). The RD₅₀ values in mice and rats were 309 ppm (Barrow et al. 1977) and 560 ppm (Hartzell et al. 1985), respectively. Fifteen-minute exposures of baboons at 500 ppm (Kaplan et al. 1988) and 30-min exposures of rats at 200 ppm (Hartzell et al. 1985), of sedentary guinea pigs at 320 ppm (Burleigh-Flayer et al. 1985), and of exercising guinea pigs at 107 ppm (Malek and Alarie 1989) produced alterations in respiratory rate or mild irritation, which returned to normal after exposure. However, exercising guinea pigs exposed at 140 ppm or higher exhibited respiratory distress and incapacitation (Malek and Alarie 1989). The small superficial ulcerations in nasal respiratory epithelium of mice that Lucia et al. (1977) found after a 10-min exposure at 17 ppm were considered reversible lesions of insufficient concern for setting a 1-h EEGL.

To derive a 1-h EEGL, the extensive data sets of respiratory-rate alterations and RD₅₀ determinations in laboratory animals exposed to hydrogen chloride were used as predictive measures of hydrogen chloride irritancy in humans. Alarie (1981) has used the mouse RD₅₀ value to derive 8-h Threshold Limit Values (TLVs) of dozens of chemical irritants empirically. Schaper (1993) developed an extensive database on 295 airborne materials with RD₅₀ values and demonstrated a high correlation of TLVs with 0.03 times the RD₅₀ (there were TLVs for 89 chemicals). For hydrogen chloride, the proposed TLV would be 9.3 ppm (0.03 times 309 ppm). Because the TLV is defined as a level of exposure that a typical worker can experience without an unreasonable risk of disease or injury, the committee recommends 9 ppm as the 1-h EEGL. Experimental studies in humans support that recommendation. Elkins (1959) concluded that exposures to hydrogen chloride at 5 ppm or higher were immediately irritating and exposures at over 10 ppm highly irritating, although some workers developed some tolerance. Henderson and Hagard (1943) reported that 50-100 ppm for 1 h was the maximum tolerable concentration and that 10 ppm for prolonged exposure was the maximum tolerable concentration.

24-Hour EEGL

There is no firm database for establishing a 24-h EEGL. To derive the 24-h EEGL, the committee considered two approaches: one based on sensory irritation and the other on histopathology of the nasal cavity. The first approach uses the empirically derived 8-h TLV of 9.3 ppm—a value that is considered to be preventive of sensory irritation in humans (described above)—and applies an uncertainty factor of 3 to account for extrapolation of 8-h responses to continuous 24-h exposures (9.3/3 = about 3 ppm). It is unclear whether the concentration-time relationship defined by ten Berge et al. (1986) applies for sensory irritation from hydrogen chloride, but in this case, the use of an uncertainty factor of 3 gives the same result as applying that relationship (9 ppm for 8 h = 3 ppm for 24 h), assuming n = 1. The second approach uses the LOAEL from the 90-day inhalation toxicity study in rats and mice (Toxigenics 1984) and applies an uncertainty factor of 3 to account for interspecies differences (10/3 = about 3 ppm). Additional uncertainty factors for extrapolating a LOAEL to no-observed-adverse-effect level (NOAEL) or a 6-h exposure to a 24-h exposure were not applied because the lesions observed in the 90-day study (minimal to mild rhinitis in rats and minimal to mild intracytoplasmic eosinophilic globules in nasal epithelium in mice) were considered tolerable and reversible for a single 24-h exposure. Thus, the same value was derived with the two approaches, and 3 ppm is recommended as a 24-h EEGL.

90-Day CEGL

Biologic end points that were considered the most relevant for derivation of the 90-day CEGL were histopathologic changes in tissues of the respiratory tract after repeated hydrogen chloride exposure. Two long-term inhalation toxicity studies, a 90-day study in rats and mice (Toxigenics 1984) and a lifetime (128-week) study in rats (Sellakumar et al. 1985), concluded that minimal to mild alterations in the upper respiratory tract (nasal cavity) and middle respiratory tract (larynx to trachea) resulted from exposure to hydrogen chloride at 10 ppm. The lesions (such as rhinitis and tracheal hyperplasia) were considered neither tumorigenic nor life-threatening. With 10 ppm as a minimal-effect LOAEL, a 90-day CEGL of 1 ppm was derived as follows. An uncertainty factor of 3 was applied to obtain a NOAEL from the LOAEL. The lesions observed at 10 ppm were due to superficial irritation and were minimal in severity, so an uncertainty factor of 3 was used rather than the standard default of 10. An additional uncertainty factor of 3 was applied for interspecies extrapolation. The lesions observed in the 90-day study were consistent between species and strains of laboratory animals, so the default factor of 10 for interspecies extrapolation was reduced. As discussed in Chapter 1, the use of two uncertainty factors of 3 is rounded to 10, so the resulting 90-day CEGL value is 1 ppm (10/10). An additional adjustment for extrapolating from intermittent exposure (6 h/day 5 days/week) to continuous exposure (24 h/day 7 days/week) was not applied because the rhinitis observed in the 90-day study did not increase in severity given the findings in the 128-day study. Both studies appear to have performed thorough histopathologic evaluations of the animals’ respiratory tract, so the duration of exposure to hydrogen chloride at low concentrations does not appear to be a critical factor in producing effects. Support that the committee’s CEGL value is protective is the epidemiologic study by Kremer et al. (1995), in which workers exposed to hydrogen chloride aerosols at 2.1 mg/m³, sulfur dioxide vapor at 0.3 mg/m³, and sulfate aerosols at 0.5 mg/m³ for several years, including peak exposure to hydrogen chloride vapor at up to 40 mg/m³ (27 ppm) for some work operations, did not show airway hyperreactivity.

DATA ADEQUACY AND RESEARCH NEEDS

Information in the scientific literature suggests that concentration, not exposure duration, is responsible for irritant effects of chemical irritants. Well-designed inhalation toxicity studies are needed to demonstrate that that observation applies to hydrogen chloride. Little is known about the acid-base buffering capacity of mucous membranes and tissues of the respiratory tract. Because hydrogen chloride dissociates rapidly to hydronium ions on contact with tissue surfaces, studies designed to quantitate the acid-buffering capacity of mucosal surfaces and tissues of the nasal cavity may be of value for studying dosimetry and threshold effects of hydrogen chloride.

REFERENCES

ACGIH (American Conference of Governmental Industrial Hygienists). 2003. Threshold Limit Values (TLVs) for Chemical Substances and Physical Agents and Biological Exposure Indices (BEIs) for 2003. American Conference of Governmental Hygienists, Cincinnati, OH.
Alarie, Y. 1981. Dose-response analysis in animal studies: Prediction of human responses. Environ. Health Perspect. 42:9-13. [PMC free article: PMC1568799] [PubMed: 7333265]
Albert, R.E., A.R. Sellakumar, S. Laskin, M. Kuschner, N. Nelson, and C.A. Snyder. 1982. Gaseous formaldehyde and hydrogen chloride induction of nasal cancer in the rat. J. Natl. Cancer Inst. 68(4):597-603. [PubMed: 6951075]
Amoore, J.E., and E. Hautala. 1983. Odor as an aid to chemical safety: Odor thresholds compared with Threshold Limit Values and volatilities for 214 industrial chemicals in air and water dilution. J. Appl. Toxicol. 3(6):272-290. [PubMed: 6376602]
Anderson, R.C., and Y. Alarie. 1980. Acute lethal effects of polyvinylchloride thermal decomposition products in normal and cannulated mice. P. A3 [Abstract 9] in Abstract of Papers Society of Toxicology Nineteenth Annual Meeting, March 9-11, 1980, Washington, DC.
ASTM (American Society for Testing and Materials) International. 2004. Standard Test Method for Estimating Sensory Irritancy of Airborne Chemicals. ASTM E981-04. West Conshohocken, PA: ASTM International. 11pp.
Barrow, C.S., Y. Alarie, M. Warrick, and M.F. Stock. 1977. Comparison of the sensory irritation response in mice to chlorine and hydrogen chloride. Arch. Environ. Health 32(2):68-76. [PubMed: 849012]
Barrow, C.S., H. Lucia, and Y.C. Alarie. 1979. A comparison of the acute inhalation toxicity of hydrogen chloride versus the thermal decomposition products of polyvinyl chloride. J. Combust. Toxicol. 6:3-12.
Bond, G.G., G.H. Flores, B.A. Stafford, and G.W. Olsen. 1991. Lung cancer and hydrogen chloride exposure: Results from a nested case-control study of chemical workers. J. Occup. Med. 33(9):958-961. [PubMed: 1744744]
Boulet, L.P. 1988. Increases in airway responsiveness following acute exposure to respiratory irritants: Reactive airway dysfunction syndrome or occupational asthma? Chest 94(3):476-481. [PubMed: 2842114]
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. [PubMed: 6740688]
Budavari, S., M.J. O’Neil, A. Smith, and P.E. Heckelman, editor. , eds. 1989. Hydrogen chloride. P. 759 in The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 11th Ed. Rahway, NJ: Merck.
Burleigh-Flayer, H., K.L. Wong, and Y. Alarie. 1985. Evaluation of the pulmonary effects of HCl using CO₂ challenges in guinea pigs. Fundam. Appl. Toxicol. 5(5):978-985. [PubMed: 3934024]
Casto, B.C., and G.G. Hatch. 1978. Pp. 62-75 in Transformation Hamster Embryo Cells. Progress Report NIH-NCI-N01-CP-45615. U.S. Department of Health, Education and Welfare, National Institutes of Health, National Cancer Institute, Bethesda, MD.
Coggon, D., B. Pannett, and G. Wield. 1996. Upper aerodigestive cancer in battery manufacturers and steel workers exposed to mineral acid mists. Occup. Environ. Med. 53(7):445-449. [PMC free article: PMC1128511] [PubMed: 8704867]
Darmer, K.I., E.R. Kinkead, and L.C. DiPasquale. 1974. Acute toxicity in rats and mice exposed to hydrogen chloride gas and aerosols. Am. Ind. Hyg. Assoc. J. 35(10):623-631. [PubMed: 4419129]
Doub, H.P. 1933. Pulmonary changes from inhalation of noxious gases. Radiology 21:105-113.
Dyer, R.F., and V.H. Esch. 1976. Polyvinyl chloride toxicity in fires. Hydrogen chloride toxicity in fire fighters. JAMA 235(4):393-397. [PubMed: 946083]
Elkins, H.B. 1959. Hydrogen chloride. Pp. 79-80 in The Chemistry of Industrial Toxicology, 2nd Ed. New York, NY: John Wiley & Sons.
EPA (U.S. Environmental Protection Agency). 1995. Hydrogen Chloride (CASRN 7647-01-0). Integrated Risk Information System, U.S. Environmental Protection Agency [online]. Available: http://www.epa.gov/iris/subst/0396.htm [accessed March 5, 2009].
Finnegan, M.J., and M.E. Hodson. 1989. Prolonged hypoxaemia following inhalation of hydrogen chloride vapour. Thorax 44(3):238-239. [PMC free article: PMC461766] [PubMed: 2705159]
Hagar, R. 2008. Submarine Atmosphere Control and Monitoring Brief for the COT Committee. Presentation at the First Meeting on Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants, June 17, 2008, Washington, DC.
Hartzell, G.E., H.W. Stacy, W.G. Switzer, D.N. Priest, and S.C. Packham. 1985. Modeling of toxicological effects of fire gases: IV. Intoxication of rats by carbon monoxide in the presence of an irritant. J. Fire Sci. 3(4):263-279.
Heidelberger, C., A.E. Freeman, R.J. Pienta, A. Sivak, J.S. Bertram, B.C. Casto, V.C. Dunkel, M.W. Francis, T. Kakunaga, J.B. Little, and L.M. Schechtman. 1983. Cell transformation by chemical agents – a review and analysis of the literature. Mutation Research 114:283-385. [PubMed: 6339891]
Henderson, Y., and H.W. Hagard. 1943. Hydrochloric acid (Hydrogen chloride). Pp. 126-127 in Noxious Gases and Principles of Respiration Influencing Their Action, 2nd Rev. Ed. New York: Reinhold Publishing Corp.
Heyroth, F.F. 1963. Halogens. Pp. 831-857 in Industrial Hygiene and Toxicology, 2nd Rev. Ed., Vol. II. Toxicology, D.W. Fassett, editor; , and D.D. Irish, editor. , eds. New York: Interscience.
Higgins, E.A., V. Fiorca, A.A. Thomas, and H.V. Davis. 1972. Acute toxicity of brief exposures to HF, HCl, NO₂ and HCN with and without CO. Fire Technol. 8(2):120-130.
Hisham, M.W.M., T.V. Bommaraju. 2005. Hydrogen chloride. Pp. 808-837 in KirkOthmer Encyclopedia of Chemical Technology, Vol. 13, J.I. Kroschwitz, editor; , and A. Seidel, editor. , eds. Hoboken, NJ: Wiley-Interscience.
HSDB (Hazardous Substances Data Bank). 2008. Hydrogen Chloride (CASNR. 7647-01-0). TOXNET, Specialized Information Services, U.S. National Library of Medicine, Bethesda, MD [online]. Available: http://toxnet.nlm.nih.gov/ [accessed March 3, 2009].
IARC (International Agency for Research on Cancer). 1992. Hydrochloric acid. Pp. 189-211 in Occupational Exposures to Mists and Vapours from Strong Inorganic Acids; and Other Industrial Chemicals. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Vol. 54. Lyon, France: IARC.
Jacobs, M.B. 1967. Common poisonous compounds of the halogens. Pp. 635-641 in The Analytical Toxicology of Industrial Inorganic Poisons. New York: Interscience Publishers.
Kaplan, H.L. 1987. Effects of irritant gases on the avoidance/escape performance and respiratory response of the baboon. Toxicology 47(1-2):165-179. [PubMed: 3686529]
Kaplan, H.L., A.F. Grand, W.G. Switzer, D.S. Mitchell, W.R. Rogers, and G.E. Hartzell. 1985. Effects of combustion gases on escape performance of the baboon and the rat. J. Fire Sci. 3(4):228-244.
Kaplan, H.L., A.F. Grand, W.G. Switzer, D.S. Mitchell, W.R. Rogers, and G.E. Hartzell. 1986. Effects of combustion gases on escape performance of the baboon and the rat. Danger Properties of Industrial Materials Report (July/August):2-12.
Kaplan, H.L., A. Anzueto, W.G. Switzer, and R.K. Hinderer. 1988. Effects of hydrogen chloride on respiratory response and pulmonary function of the baboon. J. Toxicol. Environ. Health 23(4):473-493. [PubMed: 3129573]
Kaplan, H.L., W.G. Switzer, R.K. Hinderer, and A. Anzueto. 1993. a. A study on the acute and long-term effects of hydrogen chloride on respiratory response and pulmonary function and morphology in the baboon. J. Fire Sci. 11(6):459-484.
Kaplan, H.L., W.G. Switzer, R.K. Hinderer, and A. Anzueto. 1993. b. Studies of the effects of hydrogen chloride and polyvinyl chloride (PVE) smoke in rodents. J. Fire Sci. 11(6):512-552.
Kilburn, K.H. 1996. Effects of a hydrochloric acid spill on neurobehavioral and pulmonary function. J. Occup. Environ. Med. 38(10):1018-1025. [PubMed: 8899578]
Kremer, A.M., T.M. Pal, J.P. Schouten, and B. Rijcken. 1995. Airway hyperresponsiveness in workers exposed to low levels of irritants. Eur. Respir. J. 8(1):53-61. [PubMed: 7744194]
Lam, C.W., and K.L. Wong. 2000. Hydrogen chloride. Pp. 60-88 in Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Vol. 4. Washington, DC: National Academy Press.
Leonardos, G., D. Kendall, and N. Barnard. 1969. Odor threshold determinations of 53 odorant chemicals. J. Air Pollut. Control Assoc. 19(2):91-95.
Lucia, H.L., C.S. Barrow, M.F. Stock, and Y. Alarie. 1977. A semi-quantitative method for assessing anatomic damage sustained by the upper respiratory tract of the laboratory mouse, Mus musculis. J. Combust. Toxicol. 4:472-486.
MacEwen, J.D., and E.H. Vernot. 1972. Comparison of the acute toxicity response in rats and mice resulting from exposure to HCl gas and HCl aerosol. Pp. 59-62 in Toxic Hazards Research Unit Annual Technical Report: 1972. AMRL-TR-72-62. U.S. Aerospace Medical Research Laboratory, Wright-Patterson Air Force Base, OH.
Machle, W., K.V. Kitzmiller, E.W. Scott, and J.F. Treon. 1942. The effect of the inhalation of hydrogen chloride. J. Ind. Hyg. Toxicol. 24(8):222-225.
Malek, D.E., and Y. Alarie. 1989. Ergometer within a whole-body plethysmograph to evaluate performance of guinea pigs under toxic atmospheres. Toxicol. Appl. Pharmacol. 101(2):340-355. [PubMed: 2815087]
Markowitz, J.S., E.M. Gutterman, S. Schwartz, B. Link, and S.M. Gorman. 1989. Acute health effects among firefighters exposed to polyvinyl chloride (PVC) fire. Am. J. Epidemiol. 129(5):1023-1031. [PubMed: 2705423]
McCarroll, N.E., C.E. Piper, and B.H. Keech. 1981. An E coli microsusspension assay for the detection of DNA damage induced by direct-acting agents and promutagens. Environ. Mutagen. 3(4):429-444. [PubMed: 7021147]
Morris, J.B., and F.A. Smith. 1982. Regional deposition and absorption of inhaled hydrogen fluoride in the rat. Toxicol. Appl. Pharmacol. 62(1):81-89. [PubMed: 7064158]
NIOSH (National Institute for Occupational Safety and Health). 2005. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH). No. 2005-149. National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Cincinnati, OH [online]. Available: http://www.cdc.gov/niosh/npg/ [accessed Jan. 27, 2009].
NRC (National Research Council). 1987. Hydrogen chloride. Pp. 17-30 in Emergency and Continuous Exposure Guidance Levels for Selected Airborne Contaminants, Vol. 7. Ammonia, Hydrogen Chloride, Lithium Bromide, and Toluene. Washington, DC: National Academy Press.
NRC (National Research Council). 2002. Hydrogen chloride. Pp. 132-152 in Review of Submarine Escape Action Levels for Selected Chemicals. Washington, DC: National Academy Press.
NRC (National Research Council). 2004. Hydrogen chloride. Pp. 77-122 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 4. Washington, DC: The National Academies Press.
Promisloff, R.A., A. Phan, G.S. Lenchner, and A.V. Cichelli. 1990. Reactive airway dysfunction syndrome in three police officers following a roadside chemical spill. Chest 98(4):928-929. [PubMed: 2209150]
Rosenthal, T., G.L. Baum, U. Frand, and M. Molho. 1978. Poisoning caused by inhalation of hydrogen chloride, phosphorus oxychloride, phosphorus pentachloride, oxalyl chloride and oxalic acid. Chest 73(5):623-626. [PubMed: 648215]
RTECS (Registry of Toxic Effects of Chemical Substances). 2008. Hydrochloric Acid. RTECS No. MW4025000. CAS No. 7647-01-0. Registry of Toxic Effects of Chemical Substances, National Institute for Occupational Safety and Health [online]. Available: http://www.cdc.gov/niosh/rtecs/mw3d6aa8.html [accessed March 5, 2009].
Ruth, J.H. 1986. Odor thresholds and irritation levels of several chemical substances: A review. Am. Ind. Hyg. Assoc. J. 47(3):A142-A151. [PubMed: 3706135]
Schaper, M. 1993. Development of a database for sensory irritants and its use in establishing occupational exposure limits. Am. Ind. Hyg. Assoc. J. 54(9):488-544. [PubMed: 8379496]
Sellakumar, A.R., C.A. Snyder, J.J. Solomon, and R.E. Albert. 1985. Carcinogenicity of formaldehyde and hydrogen chloride in rats. Toxicol. Appl. Pharmacol. 81(3 Pt. 1):401-406. [PubMed: 4082190]
Stavert, D.M., D.C. Archuleta, M.J. Behr, and B.E. Lehnert. 1991. Relative acute toxicities of hydrogen fluoride, hydrogen chloride, and hydrogen bromide in nose- and pseudo-mouth-breathing rats. Fundam. Appl. Toxicol. 16(4):636-655. [PubMed: 1653158]
Stevens, B., J.Q. Koenig, V. Rebolledo, Q.S. Hanley, and D.S. Covert. 1992. Respiratory effects from the inhalation of hydrogen chloride in young adult asthmatics. JOM 34(9):923-929. [PubMed: 1447599]
Tarlo, S.M., and I. Broder. 1989. Irritant-induced occupational asthma. Chest 96(2):297-300. [PubMed: 2666043]
ten Berge, W.F., A. Zwart, and L.M. Appleman. 1986. Concentration-time mortality response relationship of irritant and systemically acting vapours and gases. J. Hazard. Mater. 13(3):301-309.
Toxigenics, Inc. 1984. 90-Day Inhalation Toxicity Study of Hydrogen Chloride Gas in B6C3F1 Mice, Sprague-Dawley Rats, and Fischer-344 Rats, Revised. Toxigenics Study 420-1087. Decauter, IL: Toxigenics, Inc. 68 pp.
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. [PubMed: 595018]
Wohlslagel, J., L.C. DiPasquale, and E.H. Vernot. 1976. Toxicity of solid rocket motor exhaust: Effects of HCl, HF, and alumina on rodents. J. Combust. Toxicol. 3:61-70.

Bookshelf ID: NBK219917

Contents