HYDROGEN CHLORIDE

Classification | Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

Specific Substances

1) Acide chlorhydrique
2) Acido chloridrico
3) Chlorohydric acid
4) Chlorowodor
5) Chlorwasserstoff
6) Hydrochloric acid, anhydrous
7) Hydrochloric acid
8) Hydrochloric acid gas
9) Hydrochloric acid, trimer
10) Hydrochloride
11) Hydrogen chloride
12) Hydrogen chloride, anhydrous
13) Hydrogen chloride dimer
14) Spirits of salt
15) NIOSH/RTECS MW 4025000
16) Molecular Formula: Cl-H
17) CAS 7647-01-0
18) CHLOORWATERSTOF (DUTCH)
19) CHLORWASSERSTOFF (GERMAN)
20) HYDROGEN CHLORIDE (GAS ONLY)
21) HYDROGEN CHLORIDE, REFRIGERATED LIQUID (CRYOGENIC LIQUID)

1.2.1) MOLECULAR FORMULA
1) HCl
2) Cl-H

Available Forms Sources

1) Hydrochloric acid is commercially available as a 31% or 35% w/w solution in water (Ashford, 1994).
2) Hydrochloric acid is available in the following grades (HSDB , 2001):

1) NF (National Formulary) Diluted (10%)
2) USP (United States Pharmacopoeia) (35-38%)
3) Technical (generally 18, 20, 22, 23 deg baume, which corresponds to approximately 23, 31, 35, 37% hydrogen chloride).

1) Hydrogen chloride is produced as a byproduct of dehydrochlorination reactions; during the reaction of hydrogen and chlorine; as a byproduct of sodium sulfate production when using the Hargraves process or Mannheim process; as a byproduct of the reaction between natural sodium chloride and sulfuric acid; as a byproduct of potassium sulfate production involving either salt formation or the Hargraves process; from waste gas production; and during the Meyer Process when sodium chloride reacts with sodium bisulfite (Ashford, 1994) Bingham et al, 2001; (HSDB , 2001).

1) Anhydrous hydrogen chloride is utilized in polymerization, isomerization, alkylation, hydrochlorination, and nitration organic reactions, as well as in the production of vinyl chloride from acetylene, alkyl chlorides from olefins, and arsenious chloride from arsenious oxide. It is also used in the production of pharmaceutical hydrochlorides and chlorine, rubber, as a gaseous flux for babbiting operations, and in the leather tanning, electroplating, and food processing industries (AAR, 2000; ACGIH, 1991; (Bingham et al, 2001; Budavari, 1996; Lewis, 1993).
2) Hydrogen chloride in aqueous solution (hydrochloric acid) is used in the neutralization of basic systems; as a pharmaceutical aid (acidifier; used in human and veterinary medicine); in oil and gas-well treatment; in removing scale from boilers and heat exchange equipment; in the production of chlorides; in tin and tantalum ore refining; as a laboratory reagent; as a catalyst and solvent in organic synthesis; in pickling and cleaning of metal products; in the hydrolyzing of starch and proteins; in the refining of sugar, oils, fats, and wax; and in the preparation of various food products. Additionally, it is sold to the public as 'muriatic acid' where it finds a variety of uses in the household and in construction (ACGIH, 1991; (Ashford, 1994; Budavari, 1996).

Overview

Life Support

Clinical Effects

0.2.1)

A) USES: Anhydrous hydrogen chloride is used in the production of pharmaceutical hydrochlorides and chlorine, rubber, as a gaseous flux for babbiting operations. It is also used in the leather tanning, electroplating, and food processing industries. Hydrogen chloride in aqueous solution (hydrochloric acid) has many commercial and industrial uses.
B) TOXICOLOGY: Acids cause coagulation necrosis. Hydrogen ions desiccate epithelial cells, causing edema, erythema, tissue sloughing and necrosis, with formation of ulcers and eschars.
C) EPIDEMIOLOGY: Exposure is rare. Hydrogen chloride is typically available for industrial purposes.
D) WITH POISONING/EXPOSURE

1) Hydrogen chloride exposure is unusual; limited data regarding specific human toxicity following hydrogen chloride exposure is available. The following effects could be expected to occur, based on exposure data of other acids.
2) MILD TO MODERATE ORAL TOXICITY: Patients with mild ingestions may only develop irritation or grade I (superficial hyperemia and edema) burns of the oropharynx, esophagus or stomach; acute or chronic complications are unlikely. Patients with moderate toxicity may develop grade II burns (superficial blisters, erosions and ulcerations) are at risk for subsequent stricture formation, particularly gastric outlet and esophageal. Some patients (particularly young children) may develop upper airway edema.
3) SEVERE ORAL TOXICITY: May develop deep burns and necrosis of the gastrointestinal mucosa. Complications often include perforation (esophageal, gastric, rarely duodenal), fistula formation (tracheoesophageal, aortoesophageal), and gastrointestinal bleeding. Upper airway edema is common and often life threatening. Hypotension, tachycardia, tachypnea and, rarely, fever may develop. Other rare complications include metabolic acidosis, hemolysis, renal failure, disseminated intravascular coagulation, elevated liver enzymes, and cardiovascular collapse. Stricture formation (primarily gastric outlet and esophageal, less often oral) is likely to develop long term. Esophageal carcinoma is another long term complication.

a) PREDICTIVE: The grade of mucosal injury at endoscopy is the strongest predictive factor for the occurrence of systemic and GI complications and mortality. Initial signs and symptoms may not reliably predict the extent of GI burns.

4) INHALATION EXPOSURE: Mild exposure may cause dyspnea, pleuritic chest pain, cough and bronchospasm. Severe inhalation may cause upper airway edema and burns, hypoxia, stridor, pneumonitis, tracheobronchitis, and rarely acute lung injury or persistent pulmonary function abnormalities. The current NIOSH IMMEDIATELY DANGEROUS TO LIFE OR HEALTH (IDLH) air concentration for hydrogen chloride is 50 ppm. No significant effects have been seen with chronic exposure to low levels of gaseous hydrogen chloride.
5) OCULAR EXPOSURE: Ocular exposure can produce severe conjunctival irritation and chemosis, corneal epithelial defects, limbal ischemia, permanent vision loss and in severe cases perforation.
6) DERMAL EXPOSURE: A minor exposure can cause irritation and partial thickness burns. More prolonged or a high concentration exposure can cause full thickness burns. Complications may include cellulitis, sepsis, contractures, osteomyelitis and systemic toxicity.

0.2.3)

A) Shock, rapid breathing and pulse, circulatory collapse and other changes to pulse, blood pressure, and respiration may occur.

0.2.4)

A) Dental discoloration or erosion, bleeding gums, corneal necrosis, conjunctivitis, eye and nasal irritation, nasal ulceration, nose bleeds, throat irritation and ulceration have been observed.

0.2.5)

A) Circulatory collapse and ischemic lesions may occur.

0.2.6)

A) Changes in breathing pattern, irritation, changes in pulmonary function, corrosion and edema of the respiratory tract, chronic bronchitis and noncardiogenic pulmonary edema have been observed.

0.2.8)

A) Gastritis, burns, gastric hemorrhage, dilation, edema, necrosis, and strictures may occur.

0.2.9)

A) Ischemia and hepatotoxicity may be observed.

0.2.10)

A) Nephritis and renal failure may occur.

0.2.11)

A) Hyperchloremic metabolic acidosis may occur.

0.2.13)

A) Coagulopathy has been reported following an acute ingestion of hydrochloric acid.

0.2.14)

A) Burns, ulceration, scarring, blanching, and irritation may occur.

0.2.20)

A) Fetotoxicity, developmental abnormalities, and possible resistance to hydrogen chloride by inhalation during pregnancy have been noted.
B) At the time of this review, no data were available on the possible effects of hydrogen chloride exposure during lactation.
C) No information about possible male reproductive effects was found in available references at the time of this review.

0.2.21)

A) There has been a lack of conclusive data regarding the carcinogenicity of this agent; however, carcinogenic effects may occur when this agent is in combination with other substances.

Laboratory Monitoring

Treatment Overview

0.4.2)

A) There is very little information available regarding the treatment of hydrogen chloride-induced injury; the following data is derived from experience with other acids.
B) MILD TO MODERATE ORAL TOXICITY

1) Within the first 12 hours of exposure, if burns are absent or grade I severity, patient may be discharged when able to tolerate liquids and soft foods by mouth. If mild grade II burns, admit for intravenous fluids, slowly advance diet as tolerated. Perform barium swallow or repeat endoscopy several weeks after ingestion (sooner if difficulty swallowing) to evaluate for stricture formation.

C) SEVERE ORAL TOXICITY

1) Resuscitate with 0.9% saline; blood products may be necessary. Early airway management in patients with upper airway edema or respiratory distress. Early (within 12 hours) gastrointestinal endoscopy to evaluate for burns. Early bronchoscopy in patients with respiratory distress or upper airway edema. Early surgical consultation for patients with severe grade II or grade III burns, large deliberate ingestions, or signs, symptoms or laboratory findings concerning for tissue necrosis or perforation.

D) DILUTION

1) Dilute with 4 to 8 ounces of water may be useful if it can be performed shortly after ingestion in patients who are able to swallow, with no vomiting or respiratory distress; then the patient should be NPO until assessed for the need for endoscopy. Neutralization, activated charcoal, and gastric lavage are all contraindicated.

E) AIRWAY MANAGEMENT

1) Aggressive airway management in patients with deliberate ingestions or any indication of upper airway injury. Severe edema may make intubation difficult; be prepared for surgical airway management (cricothyroidotomy) in patients with severe upper airway edema.

F) ENDOSCOPY

1) Should be performed as soon as possible (preferably within 12 hours, not more than 24 hours) in any patient with acid ingestion. The grade of mucosal injury at endoscopy is the strongest predictive factor for the occurrence of systemic and GI complications and mortality. The absence of visible oral burns does NOT reliably exclude the presence of esophageal burns.

G) BRONCHOSPASM

1) Treat with oxygen, inhaled beta agonists and consider systemic corticosteroids

H) CORTICOSTEROIDS

1) The use of corticosteroids to prevent stricture formation is controversial. Corticosteroids should not be used in patients with grade I or grade III injury, as there is no evidence that it is effective. Evidence for grade II burns is conflicting, and the risk of perforation and infection is increased with steroid use, so routine use is not recommended.

I) STRICTURE

1) A barium swallow or repeat endoscopy should be performed several weeks after ingestion in any patient with grade II or III burns or with difficulty swallowing to evaluate for stricture formation. Recurrent dilation may be required. Some authors advocate early stent placement in these patients to prevent stricture formation.

J) SURGICAL MANAGEMENT

1) Immediate surgical consultation should be obtained on any patient with grade III or severe grade II burns on endoscopy, significant abdominal pain, metabolic acidosis, hypotension, coagulopathy, or a history of large ingestion. Early laparotomy can identify tissue necrosis and impending or unrecognized perforation, early resection and repair in these patients is associated with improved outcome.

K) PATIENT DISPOSITION

1) OBSERVATION CRITERIA: Patients with an acid ingestion should be sent to a health care facility for evaluation. Patients with an endoscopic evaluation that demonstrates no burns or only minor grade I burns and who can tolerate oral intake can be discharged to home.
2) ADMISSION CRITERIA: Symptomatic patients, and those with endoscopically demonstrated grade II or higher burns should be admitted. Patients with respiratory distress, grade III burns, or extensive grade II burns, acidosis, hemodynamic instability, gastrointestinal bleeding, or large ingestions should be admitted to an intensive care setting.

L) PITFALLS

1) The absence of oral burns does NOT reliably exclude the possibility of significant esophageal burns.
2) Patients may have severe tissue necrosis and impending perforation requiring early surgical intervention without having severe hypotension, rigid abdomen, or radiographic evidence of intraperitoneal air.
3) Patients with any evidence of upper airway involvement require early airway management before airway edema progresses.
4) The extent of eye injury (degree of corneal opacification and perilimbal whitening) may not be apparent for 48 to 72 hours after the burn. All patients with acidic eye injury should be evaluated by an ophthalmologist.

M) DIFFERENTIAL DIAGNOSIS

1) Alkaline corrosive ingestion, gastrointestinal hemorrhage, or perforated viscus.

0.4.3)

A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
B) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
C) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
D) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
E) Respiratory tract irritation, if severe, can progress to pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
F) ISOPROTERENOL/AMINOPHYLLINE

1) In rabbits, treatment with isoproterenol and aminophylline significantly reduced the increased pulmonary artery pressure, vascular permeability, and fluid-flux associated with hydrochloric acid injury.

0.4.4)

A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.

0.4.5)

A) OVERVIEW

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
2) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
3) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
4) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.

Range Of Toxicity

Clinical Effects

Summary Of Exposure

Vital Signs

3.3.1)

A) Shock, rapid breathing and pulse, circulatory collapse and other changes to pulse, blood pressure, and respiration may occur.

3.3.2)

A) WITH POISONING/EXPOSURE

1) PATTERN - Changes in respiratory pattern may occur at 0.067 to 0.134 ppm (Finkel, 1983), a range much lower than the TLV.
2) EFFECTS IN ANIMALS - Rapid, shallow breathing was observed in rats and mice by the end of an inhalation exposure to hydrogen chloride gas or hydrochloric acid aerosol (Darmer et al, 1974).

3.3.4)

A) WITH POISONING/EXPOSURE

1) CIRCULATORY COLLAPSE - Exposure to strong mineral acids may produce circulatory collapse with clammy skin, weak and rapid pulse, and shallow respiration. Circulatory collapse is one of the most common immediate causes of death from overexposure (Gosselin et al, 1984).

3.3.5)

A) WITH POISONING/EXPOSURE

1) WEAK/RAPID PULSE - Exposure to strong mineral acids may produce circulatory collapse with clammy skin, weak and rapid pulse, and shallow respiration. Circulatory collapse is one of the most common immediate causes of death from overexposure (Gosselin et al, 1984).

Heent

3.4.1)

A) Dental discoloration or erosion, bleeding gums, corneal necrosis, conjunctivitis, eye and nasal irritation, nasal ulceration, nose bleeds, throat irritation and ulceration have been observed.

3.4.2)

A) WITH POISONING/EXPOSURE

1) DENTAL DISCOLORATION/EROSION - Discoloration of exposed incisors and erosion of dental enamel can occur from prolonged or chronic exposure to hydrogen chloride (Bingham et al, 2001; Finkel, 1983).
2) BLEEDING - Exposure to mists of heated metal pickling solutions may cause bleeding of the gums (Bingham et al, 2001).

3.4.3)

A) WITH POISONING/EXPOSURE

1) CORNEAL NECROSIS - Hydrogen chloride can cause corneal necrosis at high concentrations (ITI, 1985). Reduced vision or blindness can occur from eye contact (Sittig, 1985).

a) With strong acids in general, the cornea may become vascularized and opaque or may soften with sloughing of the whole stroma. Perforation of the globe and loss of ocular contents may occur (Grant & Schuman, 1993).

2) CONJUNCTIVITIS - Eye irritation can occur from exposure to lower concentrations (ITI, 1985).
3) EFFECTS IN ANIMALS - Hydrogen chloride was an irritant or corrosive to the eyes in studies in animals.

a) Hydrogen chloride (as hydrochloric acid) was a mild eye irritant in rabbits at a dose of 5 milligrams applied for 30 seconds in a rinsed Draize test (RTECS , 2001).
b) Hydrogen chloride gas or hydrochloric acid aerosol produced corneal erosion and clouding in rats and mice (Darmer et al, 1974).

3.4.5)

A) WITH POISONING/EXPOSURE

1) IRRITATION - Hydrogen chloride is a strong irritant of the mucous membranes and upper respiratory tract. Its strong irritant properties generally are adequate warning to prevent overexposure (Hathaway et al, 1996).
2) ULCERATION - Occasionally ulceration of the nose can occur (Hathaway et al, 1996).
3) BLEEDING - Exposure to mists of heated metal pickling solutions may cause nose bleeds (Bingham et al, 2001).

3.4.6)

A) WITH POISONING/EXPOSURE

1) IRRITATION - Acute exposure to hydrogen chloride can cause coughing, burning of the throat, and a choking sensation (Hathaway et al, 1996). Inhalation can cause laryngitis and bronchitis (Sittig, 1985).

a) Acute exposures over 5 ppm can be irritating to the throat; 35 ppm was irritating in a short exposure, and 50 to 100 ppm was barely tolerable for 1 hour (ACGIH, 1986).

2) ULCERATION - Occasionally ulceration and bleeding of the oral mucosa, throat, and larynx can occur (Hathaway et al, 1996).
3) NECROSIS - Esophageal necrosis can be fatal following oral exposure (Sittig, 1985).

Cardiovascular

3.5.1)

A) Circulatory collapse and ischemic lesions may occur.

3.5.2)

A) TACHYARRHYTHMIA

1) WITH POISONING/EXPOSURE

a) SUMMARY - Clammy skin, weak and rapid pulse, and shallow respiration may be seen with ingestion of liquid hydrogen chloride.

B) HYPOTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) Exposure to strong mineral acids may produce circulatory collapse with clammy skin, weak and rapid pulse, and shallow respiration. Circulatory collapse is one of the most common immediate causes of death from overexposure (Gosselin et al, 1984).

C) MYOCARDIAL ISCHEMIA

1) WITH POISONING/EXPOSURE

a) Ischemic lesions in the heart may occur after several hours of uncorrected circulatory collapse (Gosselin et al, 1984).

Respiratory

3.6.1)

A) Changes in breathing pattern, irritation, changes in pulmonary function, corrosion and edema of the respiratory tract, chronic bronchitis and noncardiogenic pulmonary edema have been observed.

3.6.2)

A) DISORDER OF RESPIRATORY SYSTEM

1) WITH POISONING/EXPOSURE

a) BREATHING PATTERN - Changes in respiratory pattern may occur at 0.067 to 0.134 ppm (Finkel, 1983), a range much lower than the TLV.
b) IRRITATION - Hydrogen chloride is a strong irritant of the upper respiratory tract in acute exposures. Immediate effects of acute exposure are cough, burning of the throat and a choking sensation (Hathaway et al, 1996).
c) Mild exposures may produce overt symptoms resembling acute viral upper respiratory infection but with absence of fever, myalgias and lymphocytosis (Proctor & Hughes, 1978).
d) PULMONARY FUNCTION - Changes in pulmonary function (FVC and FEV 1 second) can occur with high, acute or moderate chronic exposure (Proctor & Hughes, 1978).

1) Some accommodation with respect to pulmonary function may occur in chronic exposures (Proctor & Hughes, 1978).
2) At 2 weeks following exposure to hydrochloric acid, 13 of 16 workers with persistent respiratory symptoms had abnormalities on pulmonary function tests (Froneberg et al, 1982).

e) CORROSIVE - Inhalation of large amounts of hydrogen chloride can be corrosive to the respiratory tract, with structural damage and injury to the lungs (Proctor & Hughes, 1978) ACGIH, 1986; CHRIS, 1985).

B) ACUTE LUNG INJURY

1) WITH POISONING/EXPOSURE

a) Noncardiogenic pulmonary edema can occur in severe cases of acute exposure to hydrogen chloride (Hathaway et al, 1996).

C) PULMONARY HEMORRHAGE

1) WITH POISONING/EXPOSURE

a) A firefighter died after exposure to hydrogen chloride released by thermal degradation of polyvinyl chloride. Postmortem examination revealed severe pulmonary hemorrhage and edema due to chemical pneumonitis (Dryer & Esch, 1976).

D) BRONCHITIS

1) WITH POISONING/EXPOSURE

a) Chronic exposure may be associated with chronic bronchitis (ACGIH, 1986).

E) LARYNGISMUS

1) WITH POISONING/EXPOSURE

a) In severe overexposures, generally where escape is not possible, laryngeal spasm can occur (Hathaway et al, 1996).

F) EDEMA OF LARYNX

1) WITH POISONING/EXPOSURE

a) Inhalation can cause glottic edema (Sittig, 1985).

3.6.3)

A) ANIMAL STUDIES

1) RESPIRATORY DISORDER

a) Inhalation exposure in animals caused labored breathing, pulmonary edema, atelectasis, alveolar emphysema and death from acute pulmonary injury or secondary infection (Darmer et al, 1974; Machle et al, 1942). Ibuprofen prevented the development of pulmonary edema in exposed rats in one study (Shinozawa et al, 1986). Baboons showed no significant effects after exposure to 500, 5,000, or 10,000 ppm for 15 minutes (Kaplan et al, 1988).
b) EFFECTS IN ANIMALS - Hydrogen chloride gas had similar toxicity to hydrochloric acid aerosol in rats and mice, with the respiratory tract being the primary target from acute exposures (Darmer et al, 1974).

1) There was 100% mortality in rabbits and guinea pigs exposed to 6.5 mg/L for 30 minutes. Acute respiratory damage was the cause of immediate death, while secondary infections caused delayed deaths (Machle et al, 1942).
2) Respiratory damage included moderate to severe alveolar emphysema, atelectasis, edema of the lung, and occasional spotting of lung tissue in rats and mice exposed by inhalation. Epithelial tissue in tracheal passages was severely damaged. Survivors had labored "clicking" breathing and bloody discharges from nares indicative of purulent bronchitis (Darmer et al, 1974).
3) Rats were exposed to a synthetic smoke to which hydrogen chloride was added. Ibuprofen, administered shortly after exposure, prevented the development of pulmonary edema (Shinozawa et al, 1986).
4) Baboons were exposed to hydrogen chloride 500, 5,000, or 10,000 ppm for 15 minutes. The animals survived without any significant effects on pulmonary function during the 3 months after exposure (Kaplan et al, 1988).

Gastrointestinal

3.8.1)

A) Gastritis, burns, gastric hemorrhage, dilation, edema, necrosis, and strictures may occur.

3.8.2)

A) GASTRITIS

1) WITH POISONING/EXPOSURE

a) Gastritis, burns, gastric hemorrhage, dilation, edema, necrosis, and strictures are seen with ingestion of liquid hydrogen chloride.
b) There have been many cases of gastritis in Russian workers exposed to hydrogen chloride (as hydrochloric acid) (ACGIH, 1986).

B) BURN

1) WITH POISONING/EXPOSURE

a) Hydrochloric acid can cause severe burns of the stomach with pain, nausea and vomiting (Hathaway et al, 1996).

1) Ingestion may result in corrosion of mucous membranes, esophagus, stomach, and duodenum (Munoz et al, 2001; HSDB , 2001). Esophageal and duodenal necrosis can be fatal following oral exposure (Munoz et al, 2001; Sittig, 1985).

C) GASTROINTESTINAL HEMORRHAGE

1) WITH POISONING/EXPOSURE

a) Vomiting of fresh blood has occasionally been seen in patients who have ingested strong acid (Gosselin et al, 1984).

D) CAUSTIC ESOPHAGEAL INJURY

1) WITH POISONING/EXPOSURE

a) Esophageal dilation and atony have been reported following ingestion of muriatic acid (Muhletaler et al, 1980).

E) ESOPHAGITIS

1) WITH POISONING/EXPOSURE

a) Mucosal and submucosal edema of the esophagus has been seen on esophagograms following ingestion of muriatic acid (Muhletaler et al, 1980).

F) STRICTURE OF ESOPHAGUS

1) WITH POISONING/EXPOSURE

a) DELAYED EFFECTS - Strictures may follow from several weeks to several years later in patients who survive an acute episode of ingesting strong acid (Muhletaler et al, 1980; Gosselin et al, 1984).

Hepatic

3.9.1)

A) Ischemia and hepatotoxicity may be observed.

3.9.2)

A) LIVER DAMAGE

1) WITH POISONING/EXPOSURE

a) Ischemic lesions may occur in the liver after several hours of uncorrected circulatory collapse (Gosselin et al, 1984).
b) Exposed guinea pigs developed hepatic injury.

3.9.3)

A) ANIMAL STUDIES

1) HEPATOCELLULAR DAMAGE

a) Guinea pigs exposed to 0.05 to 20.5 mg/L hydrogen chloride for 5 minutes to 120 hours appeared to be more sensitive than rabbits and an adult female monkey. Gross pathological changes in the liver, including widespread parenchymal edema, congestion, necrosis and hemorrhage, were seen in 45 of 57 guinea pigs that died (Machle et al, 1942).

2) HEPATOCELLULAR DAMAGE

Genitourinary

3.10.1)

A) Nephritis and renal failure may occur.

3.10.2)

A) NEPHRITIS

1) WITH POISONING/EXPOSURE

a) Ingestion of hydrogen chloride may cause nephritis (HSDB , 1992).

B) RENAL FAILURE SYNDROME

1) WITH POISONING/EXPOSURE

a) Kidney failure and decreased urine output can occur after several hours of uncorrected circulatory collapse (Gosselin et al, 1984).

Acid-Base

3.11.1)

A) Hyperchloremic metabolic acidosis may occur.

3.11.2)

A) ACIDOSIS

1) WITH POISONING/EXPOSURE

a) Hyperchloremic metabolic acidosis developed in a patient following accidental chlorine gas exposure. It was postulated that the mechanism for production of the acidosis was the absorption of hydrochloric acid following the reaction of chlorine gas with tissue water (Szerlip & Singer, 1984).
b) Metabolic acidosis occurred in all patients (n=21) who presented with gastrointestinal necrosis following ingestion of high concentration (24% to 32%) hydrochloric acid (Munoz et al, 2001). The pH of each patient, upon presentation, was between 6.9 and 7.2.

Hematologic

3.13.1)

A) Coagulopathy has been reported following an acute ingestion of hydrochloric acid.

3.13.2)

A) BLOOD COAGULATION PATHWAY FINDING

1) WITH POISONING/EXPOSURE

a) Coagulopathy occurred in several patients following ingestion of high concentration (24% to 32%) hydrochloric acid (Munoz et al, 2001).

3.13.3)

A) ANIMAL STUDIES

1) ANEMIA HYPOCHROMIC

a) Six-hour daily exposures to hydrogen chloride at 100 ppm, repeated for 50 days, resulted in a slightly diminished hemoglobin content in rabbits, guinea pigs, and pigeons (HSDB , 2001).

Dermatologic

3.14.1)

A) Burns, ulceration, scarring, blanching, and irritation may occur.

3.14.2)

A) CHEMICAL BURN

1) WITH POISONING/EXPOSURE

a) Hydrogen chloride is corrosive to the skin, producing severe burns, ulceration, and scarring (Sittig, 1985). Subcutaneous tissues may be affected, becoming blanched and bloodless (Sax, 1984).

B) SKIN IRRITATION

1) WITH POISONING/EXPOSURE

a) Hydrogen chloride in lower concentrations is a primary irritant of the skin (RTECS , 1988).

C) DERMATITIS

1) WITH POISONING/EXPOSURE

a) Repeated exposure to low concentrations can produce dermatitis (Sittig, 1985; Hathaway et al, 1996).

Reproductive

3.20.1)

3.20.2)

A) FETOTOXICITY

1) ANIMAL STUDIES

a) Hydrogen chloride inhaled at 450 milligrams/cubic meter/1 hour given 1 day prior to mating was fetotoxic and produced functional insufficiency in lungs and kidneys in the offspring of female rats (RTECS , 1988). Similar results were found when hydrogen chloride was given to rats during pregnancy (Pavlova, 1976).

3.20.3)

A) TOLERANCE INCREASED

1) ANIMAL STUDIES

a) Pregnant rats were more resistant to hydrogen chloride by inhalation than nonpregnant ones (Saniotskiy, 1976).

3.20.4)

A) LACK OF INFORMATION

1) At the time of this review, no data were available on the possible effects of hydrogen chloride exposure during lactation.

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS7647-01-0 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) IARC Classification

a) Listed as: Hydrochloric acid
b) Carcinogen Rating: 3

1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.

3.21.2)

A) There has been a lack of conclusive data regarding the carcinogenicity of this agent; however, carcinogenic effects may occur when this agent is in combination with other substances.

3.21.3)

A) CARCINOGENICITY RISK

1) In one occupational study, exposure to hydrogen chloride at airborne concentrations up to 3000 mcg/m(3) for several years did not increase the risk for death from lung cancer (Bond et al, 1991). No increased overall mortality, overall cancer, or cancer of the larynx or lung were seen in a cohort of 2678 men employed at battery and steel works since 1950 who were exposed to mineral acid mists, but those exposed to hydrochloric and sulfuric acids at airborne levels exceeding 1 mg/m(3) for at least 5 years had a moderate increase in cancer of the upper aerodigestive tract (Coggon et al, 1996).
2) Hydrogen chloride can react with FORMALDEHYDE to form bis(choromethyl) ether (BCME), a known human carcinogen (Frankel, 1974; Tou & Kallow, 1974; Kallow & Solomon, 1973; IARC, 1974).

3.21.4)

A) NEOPLASM

1) ANIMAL STUDIES

a) bis-(CHLOROMETHYL) ETHER FORMATION - Hydrogen chloride can react with FORMALDEHYDE to form bis(chloromethyl)ether (BCME), a human carcinogen (Frankel et al, 1982; (Tou & Kallow, 1974; Kallow & Solomon, 1973; IARC, 1974). Hydrogen chloride mixed with formaldehyde under conditions where BCME would be formed produced nasal tumors in rats (Albert, 1982).
b) In a study in rats, the incidence of nasal cancer was increased in all animals who received formaldehyde vapors regardless of concurrent exposure to hydrogen chloride. It was concluded that hydrogen chloride did not significantly influence the nasal carcinogenicity of formaldehyde (Sellakumar et al, 1985).

B) CHROMOSOME DISORDER

1) Hydrogen chloride has been shown to be genotoxic in bacteria, in Drosophila melanogaster, and in grasshoppers (RTECS , 2001).
2) Hydrogen chloride induced sex chromosome loss and nondisjunction in Drosophila melanogaster when given by inhalation at 100 parts per million for 24 hours (RTECS , 2001). It also had the same effects when given orally at 100 parts per million (RTECS , 2001).

C) LACK OF EFFECT

1) ANIMAL STUDIES

a) Hydrogen chloride given by inhalation at 10 parts per million for 6 hours per day during the lifetime of rats was not carcinogenic (Albert, 1982).

Genotoxicity

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Obtain a complete blood count and electrolytes in all patients with significant burns after acid ingestion.
B) In patients with signs and symptoms suggesting severe burns, perforation, or bleeding (or adults with deliberate, high volume or high concentration ingestions), obtain renal function tests, liver enzymes, serial CBC, INR, PT, PTT, fibrinogen, fibrin degradation products, type and crossmatch for blood, and monitor urine output and urinalysis. Serum lactate and base deficit may also be useful in these patients.
C) Monitor pulse oximetry or arterial blood gases in patients with signs and symptoms suggestive of upper airway edema or burns.
D) Obtain an upright chest x-ray in patients with signs and symptoms suggesting severe burns, perforation, or bleeding (or adults with deliberate, high volume or high concentration ingestions) to evaluate for pneumomediastinum or free air under the diaphragm. The absence of these findings does NOT rule out the possibility of necrosis or perforation of the esophagus or stomach. Obtain a chest radiograph in patients with pulmonary signs or symptoms.
E) Several weeks after ingestion, barium contrast radiographs of the upper GI tract are useful in patients who sustained grade 2 or 3 burns, to evaluate for strictures.
F) Because of its reactivity, acrylyl chloride would not be expected to exist in the free form in biological fluids.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Obtain a complete blood count and electrolytes in all patients with significant burns after acid ingestion. In patients with signs and symptoms suggesting severe burns, perforation, or bleeding (or adults with deliberate, high volume or high concentration ingestions), obtain renal function tests and liver enzymes.

B) COAGULATION STUDIES

1) In patients with signs and symptoms suggesting severe burns, perforation, or bleeding (or adults with deliberate, high volume or high concentration ingestions), obtain INR, PT, PTT, fibrinogen, fibrin degradation products, and type and crossmatch for blood.

4.1.3)

A) OTHER

1) Monitor urine output and urinalysis in patients will significant gastrointestinal burns, perforation, or bleeding.

4.1.4)

A) OTHER

1) MONITORING

a) Monitor pulse oximetry or arterial blood gases in patients with signs and symptoms suggestive of upper airway burns.
b) Preplacement and periodic physical examination are indicated for workers with potential hydrogen chloride exposure with emphasis on the respiratory tract, skin, eyes and teeth; FVC and FEV (1 second) pulmonary function tests are recommended (Proctor & Hughes, 1978; Sittig, 1985).

Radiographic Studies

1) Esophagrams in the acute and subacute phase demonstrate edema, hemorrhage, ulcerations, atony, and dilation. Strictures of the esophagus may be present in the chronic phase. These radiographic findings are not different from those found in alkaline corrosive esophagitis (Muhletaler et al, 1980).
2) Krypton esophageal transit studies and manometric measurements correlated better with residual clinical symptoms and functional outcomes than did morphological findings of stenosis late (3 months to 7 years) after caustic ingestions (Cadranel et al, 1990).

1) Periodic chest roentgenogram is indicated with chronic exposure or for monitoring recovery from acute overexposure (Proctor & Hughes, 1978).

1) Abdominal CT scans were performed on 5 patients who ingested glacial acetic acid. Diffuse edematous thickening of the walls of the esophagus and stomach were found in all patients. Wedge-shaped low density areas in the liver were found in 3 patients; clinically these 3 developed hepatic failure, hemolysis, metabolic acidosis and coagulopathy, and 2 of these patients died. The authors postulated that wedge-shaped low densities in the liver after acid ingestion may represent areas of hepatic necrosis secondary to toxin absorption into the portal circulation (Kim et al, 2007).

Methods

1) Hydrogen chloride can be collected by passing contaminated air through water or alkaline solution and subsequent determination of hydrogen chloride or chloride ion. However, many analytical methods suffer from possible interferences.

a) The sample can be titrated with AgNO3 with chromate indicator, or formation of AgCl from AgNO3 can be determined photometrically by light transmission. Hydrogen chloride and chlorides can react with thiocyanate in the presence of excess ferric ions in a colorimetric reaction (Clayton & Clayton, 1982).

2) A chloride ion electrode can measure concentrations as low as 0.35 ppm (Clayton & Clayton, 1982).

Treatment

Life Support

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Symptomatic patients, and those with endoscopically demonstrated grade II or higher burns should be admitted. Patients with respiratory distress, grade III burns, or extensive grade II burns, acidosis, hemodynamic instability, gastrointestinal bleeding, or large ingestions should be admitted to an intensive care setting.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Patients with an acid ingestion should be sent to a health care facility for evaluation. Patients with an endoscopic evaluation that demonstrates no burns or only minor Grade I burns and who can tolerate oral intake can be discharged to home.

Monitoring

Oral Exposure

6.5.1)

A) SUMMARY

1) Esophageal or gastrointestinal tract burns may occur after ingestion. The role of gastric decontamination is unclear.

B) ACTIVATED CHARCOAL

1) Activated charcoal is NOT effective in adsorbing acids and could obscure findings on esophagoscopy.

6.5.2)

A) SUMMARY

1) Esophageal or gastrointestinal tract burns may occur after ingestion. The role of gastric decontamination is unclear.

B) ACTIVATED CHARCOAL

1) Activated charcoal should NOT be used. It may cause vomiting which can worsen caustic gastrointestinal injury, and may obscure endoscopy findings.

6.5.3)

A) CONTRAINDICATED TREATMENT

1) Do not induce vomiting or give bicarbonate to neutralize. Addition of buffer to strong acid causes an exothermic reaction and an immediate rise in solution temperature (Maull et al, 1985a; Penner, 1980).
2) A report concerning emergency surgical resection of the alimentary tract following caustic ingestions has indicated that 5 out of 6 patients sustained injuries beyond the pylorus as a result of gastric lavage (Wu & Lai, 1993).

B) DILUTION

1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).

C) INSERTION OF NASOGASTRIC TUBE

1) It has been suggested that following a large ingestion of strong acids, a nasogastric tube should be passed and suction performed in an attempt to remove as much acid as possible prior to cold water dilution which may result in an exothermic reaction and worsen the burn (Penner, 1980).
2) Many authorities oppose this procedure fearing esophageal or gastric perforation. A soft nasogastric or orogastric tube should only be passed within 90 minutes following the large ingestion of a strong acid.

D) BURN

1) Burns of the oropharynx, esophagus, stomach, and duodenum may occur. Complications such as stricture, perforation, gastrointestinal bleeding and gastric outlet obstruction are related to the depth of burn. Early (within 24 hours) endoscopy should be performed to assess the severity of injury and guide future management.

E) ENDOSCOPIC PROCEDURE

1) SUMMARY: Obtain consultation concerning endoscopy as soon as possible and perform endoscopy within the first 24 hours when indicated.
2) INDICATIONS: Most studies associating the presence or absence of gastrointestinal burns with signs and symptoms after caustic ingestion have involved primarily alkaline ingestions. Because acid ingestion may cause severe gastric injury with fewer associated initial signs and symptoms, endoscopic evaluation is recommended in any patient with a definite history of ingestion of a strong acid, even if asymptomatic.
3) RISKS: Numerous large case series attest to the relative safety and utility of early endoscopy in the management of caustic ingestion.

a) REFERENCES: Gaudreault et al, 1983; Symbas et al, 1983; Crain et al, 1984; (Schild, 1985; Moazam et al, 1987; Sugawa & Lucas, 1989; Previtera et al, 1990; Zargar et al, 1991; Vergauwen et al, 1991; Gorman et al, 1992; Nuutinen et al, 1994)

4) The risk of perforation during endoscopy is minimized by (Zargar et al, 1991):

a) Advancing across the cricopharynx under direct vision
b) Gently advancing with minimal air insufflation
c) Never retroverting or retroflexing the endoscope
d) Using a pediatric flexible endoscope
e) Using extreme caution in advancing beyond burn lesion areas
f) Most authors recommend endoscopy within the first 24 hours of injury, not advancing the endoscope beyond areas of severe esophageal burns, and avoiding endoscopy during the subacute phase of healing when tissue slough increases the risk of perforation (5 to 15 days after ingestion) (Zargar et al, 1991).

5) GRADING

a) Several scales for grading caustic injury exist. The likelihood of complications such as strictures, obstruction, bleeding and perforation is related to the severity of the initial burn (Zargar et al, 1991):
b) Grade 0 - Normal examination
c) Grade 1 - Edema and hyperemia of the mucosa; strictures unlikely.
d) Grade 2A - Friability, hemorrhages, erosions, blisters, whitish membranes, exudates and superficial ulcerations; strictures unlikely.
e) Grade 2B - Grade 2A plus deep discreet or circumferential ulceration; strictures may develop.
f) Grade 3A - Multiple ulcerations and small scattered areas of necrosis; strictures are common, complications such as perforation, fistula formation, or gastrointestinal bleeding may occur.
g) Grade 3B - Extensive necrosis through visceral wall; strictures are common, complications such as perforation, fistula formation, or gastrointestinal bleeding are more likely than with 3A.

6) FOLLOW UP - If burns are found, follow 10 to 20 days later with barium swallow or esophagram.

F) ULTRASONOGRAPHY

1) A small study suggests that esophageal ultrasonography may be useful in predicting the likelihood of strictures after corrosive ingestion (Kamijo et al, 2004).

a) Miniprobe ultrasonography was performed endosopically at the site of the most severe lesion in 11 patients with corrosive esophageal injury. Grading was as follows: grade 0 distinct muscular layers without thickening (5 patients); grade I distinct muscular layers with thickening (4 patients): grade II obscured muscular layers with indistinct margins 1 patient); and grade III muscular layers that could not be differentiated (1 patient). Lesions were also classified as to whether the area of worst damage involved part of the circumference (type a) or the entire circumference (type b).
b) Strictures did not develop in patients with grade 0 or 1 lesions. A transient stricture developed in the patient with a grade IIa lesion. A stricture that required repeated dilatation developed in the patient with a grade IIIb lesion.

G) CORTICOSTEROID

1) CORROSIVE INGESTION/SUMMARY: The use of corticosteroids for the treatment of caustic ingestion is controversial. Most animal studies have involved alkali-induced injury (Haller & Bachman, 1964; Saedi et al, 1973). Most human studies have been retrospective and generally involve more alkali than acid-induced injury and small numbers of patients with documented second or third degree mucosal injury.
2) FIRST DEGREE BURNS: These burns generally heal well and rarely result in stricture formation (Zargar et al, 1989a; Howell et al, 1992). Corticosteroids are generally not beneficial in these patients (Howell et al, 1992).
3) SECOND DEGREE BURNS: Some authors recommend corticosteroid treatment to prevent stricture formation in patients with a second degree, deep-partial thickness burn (Howell et al, 1992). However, no well controlled human study has documented efficacy. Corticosteroids are generally not beneficial in patients with a second degree, superficial-partial thickness burn (Caravati, 2004; Howell et al, 1992).
4) THIRD DEGREE BURNS: Some authors have recommended steroids in this group as well (Howell et al, 1992). A high percentage of patients with third degree burns go on to develop strictures with or without corticosteroid therapy and the risk of infection and perforation may be increased by corticosteroid use. Most authors feel that the risk outweighs any potential benefit and routine use is not recommended (Boukthir et al, 2004; Oakes et al, 1982; Pelclova & Navratil, 2005).
5) CONTRAINDICATIONS: Include active gastrointestinal bleeding and evidence of gastric or esophageal perforation. Corticosteroids are thought to be ineffective if initiated more than 48 hours after a burn (Howell, 1987).
6) DOSE: Administer daily oral doses of 0.1 milligram/kilogram of dexamethasone or 1 to 2 milligrams/kilogram of prednisone. Continue therapy for a total of 3 weeks and then taper (Haller et al, 1971; Marshall, 1979). An alternative regimen in children is intravenous prednisolone 2 milligrams/kilogram/day followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks then tapered (Anderson et al, 1990).
7) ANTIBIOTICS: Animal studies suggest that the addition of antibiotics can prevent the infectious complications associated with corticosteroid use in the setting of caustic burns. Antibiotics are recommended if corticosteroids are used or if perforation or infection is suspected. Agents that cover anaerobes and oral flora such as penicillin, ampicillin, or clindamycin are appropriate (Rosenberg et al, 1953).
8) STUDIES

a) ANIMAL

1) Some animal studies have suggested that corticosteroid therapy may reduce the incidence of stricture formation after severe alkaline corrosive injury (Haller & Bachman, 1964; Saedi et al, 1973a).
2) Animals treated with steroids and antibiotics appear to do better than animals treated with steroids alone (Haller & Bachman, 1964).
3) Other studies have shown no evidence of reduced stricture formation in steroid treated animals (Reyes et al, 1974). An increased rate of esophageal perforation related to steroid treatment has been found in animal studies (Knox et al, 1967).

b) HUMAN

1) Most human studies have been retrospective and/or uncontrolled and generally involve small numbers of patients with documented second or third degree mucosal injury. No study has proven a reduced incidence of stricture formation from steroid use in human caustic ingestions (Haller et al, 1971; Hawkins et al, 1980; Yarington & Heatly, 1963; Adam & Brick, 1982).
2) META ANALYSIS

a) Howell et al (1992), analyzed reports concerning 361 patients with corrosive esophageal injury published in the English language literature since 1956 (10 retrospective and 3 prospective studies). No patients with first degree burns developed strictures. Of 228 patients with second or third degree burns treated with corticosteroids and antibiotics, 54 (24%) developed strictures. Of 25 patients with similar burn severity treated without steroids or antibiotics, 13 (52%) developed strictures (Howell et al, 1992).
b) Another meta-analysis of 10 studies found that in patients with second degree esophageal burns from caustics, the overall rate of stricture formation was 14.8% in patients who received corticosteroids compared with 36% in patients who did not receive corticosteroids (LoVecchio et al, 1996).
c) Another study combined results of 10 papers evaluating therapy for corrosive esophageal injury in humans published between January 1991 and June 2004. There were a total of 572 patients, all patients received corticosteroids in 6 studies, in 2 studies no patients received steroids, and in 2 studies, treatment with and without corticosteroids was compared. Of 109 patients with grade 2 esophageal burns who were treated with corticosteroids, 15 (13.8%) developed strictures, compared with 2 of 32 (6.3%) patients with second degree burns who did not receive steroids (Pelclova & Navratil, 2005).

3) Smaller studies have questioned the value of steroids (Ferguson et al, 1989; Anderson et al, 1990), thus they should be used with caution.
4) Ferguson et al (1989) retrospectively compared 10 patients who did not receive antibiotics or steroids with 31 patients who received both antibiotics and steroids in a study of caustic ingestion and found no difference in the incidence of esophageal stricture between the two groups (Ferguson et al, 1989).
5) A randomized, controlled, prospective clinical trial involving 60 children with lye or acid induced esophageal injury did not find an effect of corticosteroids on the incidence of stricture formation (Anderson et al, 1990).

a) These 60 children were among 131 patients who were managed and followed-up for ingestion of caustic material from 1971 through 1988; 88% of them were between 1 and 3 years old (Anderson et al, 1990).
b) All patients underwent rigid esophagoscopy after being randomized to receive either no steroids or a course consisting initially of intravenous prednisolone (2 milligrams/kilogram per day) followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks prior to tapering and discontinuation (Anderson et al, 1990).
c) Six (19%), 15 (48%), and 10 (32%) of those in the treatment group had first, second and third degree esophageal burns, respectively. In contrast, 13 (45%), 5 (17%), and 11 (38%) of the control group had the same levels of injury (Anderson et al, 1990).
d) Ten (32%) of those receiving steroids and 11 (38%) of the control group developed strictures. Four (13%) of those receiving steroids and 7 (24%) of the control group required esophageal replacement. All but 1 of the 21 children who developed strictures had severe circumferential burns on initial esophagoscopy (Anderson et al, 1990).
e) Because of the small numbers of patients in this study, it lacked the power to reliably detect meaningful differences in outcome between the treatment groups (Anderson et al, 1990).

6) ADVERSE EFFECTS

a) The use of corticosteroids in the treatment of caustic ingestion in humans has been associated with gastric perforation (Cleveland et al, 1963) and fatal pulmonary embolism (Aceto et al, 1970).

H) HYPOTENSIVE EPISODE

1) SUMMARY

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

2) DOPAMINE

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

3) NOREPINEPHRINE

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

4) If hypotension is secondary to gastrointestinal bleeding, blood or blood products replacement therapy is the treatment of choice.

I) SURGICAL PROCEDURE

1) In severe cases of gastrointestinal necrosis or perforation, emergent surgical consultation should be obtained. The need for gastric resection or laparotomy in the stable patient is controversial (Chodak & Passaro, 1978; Dilawari et al, 1984a).
2) LAPAROTOMY/LAPAROSCOPY - Early laparotomy or laparoscopy should be considered in patients with endoscopic evidence of severe esophageal or gastric burns after acid ingestion to evaluate for the presence of transmural gastric or esophageal necrosis (Estrera et al, 1986; Meredith et al, 1988; Wu & Lai, 1993a). Emergent laparotomy should be strongly considered in any patient with hypotension, altered mental status, or acidemia (Hovarth et al, 1991).

a) STUDY - In a retrospective study of patients with extensive transmural gastroesophageal necrosis after caustic ingestion, all 4 patients treated in the conventional manner (endoscopy, steroids, antibiotics, and repeated evaluation for the occurrence of esophagogastric necrosis and perforation) died, while all 3 patients treated with early laparotomy and immediate esophagogastric resection survived (Estrera et al, 1986).
b) Wu & Lai (1993) reported the results of emergency surgical resection of the alimentary tract in 28 patients who had extensive corrosive injuries due to the ingestion of acids or other caustics. Operative mortality was most frequently associated with sepsis. Non-fatal bleeding, infections, biliary or bronchial fistulas were other noted complications. Morbidity and mortality were related to the severity of the damage and the extent of surgery required.

1) Immediate postoperative management included antibiotics, extensive respiratory care, tracheobronchial toilet, maintenance of fluid, electrolyte and acid-base balance, and jejunostomy feeding or total parenteral nutrition.

J) DIETARY FINDING

1) Depends on degree of damage as assessed by early endoscopy (Dilawari et al, 1984).

1) mild (grade I): may have oral feedings first day
2) moderate (grade II): may have liquids after 48 to 72 hours
3) severe (grade III): jejunostomy tube feedings after 48 to 72 hours

2) Observe for symptoms of gastric outlet obstruction, at which time parenteral fluids and/or hyperalimentation should be considered. Classically, this occurs at 3 weeks after ingestions.

K) FOLLOW-UP VISIT

1) Obtain a follow-up esophagram and upper GI series to evaluate presence or absence of secondary scarring and/or stricture formation about 2 to 4 weeks following ingestion.
2) A 3-year-old child developed esophageal stricture 2 years after the acid ingestion in a prospective study of 41 patients. This child had a normal barium study at one year after ingestion (Zargar et al, 1989).

L) OBSTRUCTION

1) Observe patients for symptoms of acute pyloric obstruction (pyloric spasm). If these develop, parenteral fluid administration and/or hyperalimentation may be required. This complication classically occurs about 3 weeks after ingestion.

Inhalation Exposure

6.7.1)

A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

6.7.2)

A) MEDICAL ASSESSMENT

1) Every person exposed to potentially dangerous levels of hydrogen chloride needs: thorough medical exam, including skin, eyes, and respiratory system; chest roentgenogram; and FVC and FEV (1 second).

B) BRONCHOSPASM

1) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.

C) ISOPROTERENOL

D) IRRITATION SYMPTOM

1) Respiratory tract irritation, if severe, can progress to noncardiogenic pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
2) There are no controlled studies indicating that early administration of corticosteroids can prevent the development of noncardiogenic pulmonary edema in patients with inhalation exposure to respiratory irritant substances, and long-term use may cause adverse effects (Boysen & Modell, 1989).

a) However, based on anecdotal experience, some clinicians do recommend early administration of corticosteroids (such as methylprednisolone 1 gram intravenously as a single dose) in an attempt to prevent the later development of pulmonary edema.

1) Anecdotal experience with dimethyl sulfate inhalation showed possible benefit of methylprednisolone in the TREATMENT of noncardiogenic pulmonary edema (Ip et al, 1989).

3) Anecdotal experience also indicated that systemic corticosteroids may have possible efficacy in the TREATMENT of drug-induced noncardiogenic pulmonary edema (Zitnik & Cooper, 1990; Stentoft, 1990; Chudnofsky & Otten, 1989) or noncardiogenic pulmonary edema developing after cardiopulmonary bypass (Maggart & Stewart, 1987).
4) It is not clear from the published literature that administration of systemic corticosteroids early following inhalation exposure to respiratory irritant substances can PREVENT the development of noncardiogenic pulmonary edema. The decision to administer or withhold corticosteroids in this setting must currently be made on clinical grounds.

E) ACUTE LUNG INJURY

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

F) HYPOTENSIVE EPISODE

1) SUMMARY

2) DOPAMINE

3) NOREPINEPHRINE

G) OBSERVATION REGIMES

1) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.

H) EXPERIMENTAL THERAPY

1) INTRATRACHEAL SURFACTANT - A study, conducted with rats, showed that surfactant, given intratracheally 1 minute and 10 minutes following aspiration of hydrochloric acid, prevented deterioration of gas exchange within the lungs. Groups of rats that were either given ventilation alone, received only saline intratracheally, or were given surfactant intratracheally 60 minutes and 90 minutes after hydrochloric acid aspiration, developed significant deterioration in gas exchange (Eijking et al, 1993). The surfactant given within 10 minutes of hydrochloric acid aspiration prevented respiratory failure, but did not prevent accumulation of plasma-derived proteins into the alveolar space, which may progressively lead to inhibition of the surfactant.

I) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

6.8.1)

A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

6.8.2)

A) CONSULTATION

1) Because of the potential for severe eye injury, prolonged initial flushing and early ophthalmologic consultation are advisable.

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

6.9.1)

A) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

6.9.2)

A) BURN

1) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.

B) HYPOTENSIVE EPISODE

1) SUMMARY

2) DOPAMINE

3) NOREPINEPHRINE

C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

1) If renal failure develops, hemodialysis may be required.

1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Abstracts

Case Reports

1) One report describes a healthy woman who developed hypoxemia and chronic, reversible pulmonary airflow obstruction after a single 15 minute exposure to hydrogen chloride gas. The woman first became dyspneic 3 days after the episode and has since been treated with inhaled corticosteroids (Finnegan & Hodson, 1989).

Range Of Toxicity

Summary

Minimum Lethal Exposure

1) Concentrations of 1300 to 2000 ppm are fatal to humans within a few minutes (Harbison, 1998; CGA, 1999). Minimum lethal exposures in humans ranged from 3000 ppm for 5 minutes to 1300 ppm for 30 and 81 minutes.

Maximum Tolerated Exposure

1) The maximum tolerated human exposure to this agent has not been delineated.

1) Workers found exposure to between 50 and 100 ppm hydrogen chloride for one hour as barely tolerable. Short exposures to 35 ppm caused throat irritation, and 10 ppm was the maximum concentration allowable for prolonged exposures. Any level above 5 ppm may be fairly characterized as disagreeable (ACGIH, 1991; (Bingham et al, 2001; Hathaway et al, 1996).
2) The OSHA PEL (permissible exposure limit) for hydrogen chloride is 5 ppm or 7 mg/m(3) (HSDB, 2006).
3) According to the World Health Organization, 45 mg/m(3) (30 ppm) is the upper limit of safety for man. However, if this exposure were continued daily at periods longer than one month, even this value may be unsafe (HSDB , 2001).
4) CARCINOGENICITY RATINGS:

a) The International Agency for Research of Cancer classifies hydrochloric acid as a Group 3 carcinogen (not classifiable as to its carcinogenicity to humans). Evidence of carcinogenicity was inadequate in both humans and experimental animals (IARC, 2001).

Workplace Standards

1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.

a) Adopted Value

1) Hydrogen chloride

a) TLV:

1) TLV-TWA:
2) TLV-STEL:
3) TLV-Ceiling: 2 ppm

b) Notations and Endnotes:

1) Carcinogenicity Category: A4
2) Codes: Not Listed
3) Definitions:

a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.

c) TLV Basis - Critical Effect(s): URT irr
d) Molecular Weight: 36.47

1) For gases and vapors, to convert the TLV from ppm to mg/m(3):

a) [(TLV in ppm)(gram molecular weight of substance)]/24.45

2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:

a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance

e) Additional information:

B) NIOSH REL and IDLH Values for CAS7647-01-0 (National Institute for Occupational Safety and Health, 2007):

1) Listed as: Hydrogen chloride
2) REL:

a) TWA:
b) STEL:
c) Ceiling: 5 ppm (7 mg/m(3))
d) Carcinogen Listing: (Not Listed) Not Listed
e) Skin Designation: Not Listed
f) Note(s):

3) IDLH:

a) IDLH: 50 ppm
b) Note(s): Not Listed

C) Carcinogenicity Ratings for CAS7647-01-0 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Hydrogen chloride

a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.

2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Hydrogen chloride
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 3 ; Listed as: Hydrochloric acid

a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.

4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Hydrogen chloride
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D) OSHA PEL Values for CAS7647-01-0 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Listed as: Hydrogen chloride
2) Table Z-1 for Hydrogen chloride:

a) 8-hour TWA:

1) ppm: 5

a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.

2) mg/m3: 7

a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.

3) Ceiling Value: (C) - An employee's exposure to this substance shall at no time exceed the exposure limit given.
4) Skin Designation: No
5) Notation(s): Not Listed

Toxicity Information

7.7.1)

A) References: Hathaway et al, 1996 Lewis, 2000 OHM/TADS, 2001 RTECS, 2001

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 40142 mcg/kg
b) 1449 mg/kg (Lewis, 2000)

2) TCLo- (INHALATION)RAT:

a) 1D pre, 450 mg/m(3) for 1H -- fetotoxicity; homeostasis (Lewis, 2000)
b) 685 mcg/m(3) for 24H/84D - continuous -- muscle contraction/spasticity; urine compositional changes; true chloinesterase

B) References: Hathaway et al, 1996 Lewis, 2000 OHM/TADS, 2001 RTECS, 2001
C) References: Hathaway et al, 1996 Lewis, 2000 OHM/TADS, 2001 RTECS, 2001
D) References: Hathaway et al, 1996 Lewis, 2000 OHM/TADS, 2001 RTECS, 2001
E) References: Hathaway et al, 1996 Lewis, 2000 OHM/TADS, 2001 RTECS, 2001

Pharmacology Toxicology

Toxicologic Mechanism

Physicochemical

Physical Characteristics

1) This compound is often utilized in aqueous solutions. Reagent grade solutions contain close to 38.0% hydrogen chloride (Budavari, 1996; NIOSH , 2001).

Ph

1) 1.0N is 0.10
2) 0.1N is 1.10
3) 0.01N is 2.02
4) 0.001N is 3.02
5) 0.0001N is 4.01

Molecular Weight

Animal Toxicology

Clinical Effects

11.1.12)

A) Exposures of 6 hours daily at 100 ppm repeated for 50 days caused only slight unrest and irritation of the eyes and nose of rabbits and guinea pigs; exposures of 2 to 6 hours at 1000 milligrams per cubic meter caused some deaths from laryngeal spasm, laryngeal edema, or rapidly developing pulmonary edema (HSDB , 2001).
B) The gas also causes necrosis of the tracheal and bronchial epithelium, atelectasis, emphysema, and damage to the pulmonary blood vessels (HSDB , 2001).

References

General Bibliography

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HYDROGEN CHLORIDE

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General Bibliography