Substances Included Synonyms

Therapeutic Toxic Class

A)

1) Depending on the conditions, the vapors or fumes of nitric acid may actually be a mixture of nitric acid and various oxides of nitrogen; the composition may vary with temperature, humidity, and contact with other organic materials (Lewis, 1996).

Specific Substances

1) Acide nitrique
2) Acido nitrico
3) Aqua Fortis
4) Azotic acid
5) Azotowy kwas
6) Engraver's acid
7) Hydrogen nitrate
8) Kyselina dusicne
9) Nital
10) Nitric acid
11) Nitric acid (Over 40%)
12) Nitric acid (Red Fuming)
13) Nitric acid (White Fuming)
14) Nitrous fumes
15) Nitryl hydroxide
16) Red fuming nitric acid
17) Salpetersaure
18) Salpeterzuuroplossingen
19) Molecular formula: H-N-O3
20) CAS 7697-37-2
21) ACID NITRIQUE (FRENCH)
22) NITRIC ACID, FUMING
23) NITRIC ACID, OTHER THAN FUMING, WITH MORE THAN 40% ACID
24) NITRIC ACID, OTHER THAN FUMING, WITH NOT MORE THAN 40% ACID
25) NITRIC ACID, OTHER THAN RED FUMING
26) NITRIC ACID, OTHER THAN RED FUMING, WITH MORE THAN 70% NITRIC ACID
27) NITRIC ACID, OTHER THAN RED FUMING, WITH NOT MORE THAN 70% NITRIC ACID

1.2.1) MOLECULAR FORMULA
1) H-N-O3

Available Forms Sources

A)

1) Nitric acid is actually a solution of nitrogen dioxide (NO2) in water and is available commercially in several forms. It is often used in an aqueous solution (Pohanish, 2002).
2) ANHYDROUS nitric acid is prepared by distillation of concentrated nitric acid with concentrated sulfuric acid or by fractional crystallization of concentrated nitric acid (Budavari, 1996). It develops color from nitrogen oxide formation in light (Lewis, 2001; Budavari, 1996).
3) FUMING nitric acid is concentrated nitric acid containing an excess of dissolved nitrogen dioxide. It is prepared from concentrated nitric acid by passing nitrogen dioxide into it or by adding a small amount of a reducing agent such as formaldehyde. Fuming nitric acid is a yellow to brownish-red, clear, strongly fuming, very corrosive liquid (Budavari, 1996).
4) CONCENTRATED nitric acid is greater than 40% nitric acid in water (AAR, 1996). It is available commercially as the 68% and 56% solutions in water (Gosselin et al, 1984).

B)

1) Nitric acid releases oxides of nitrogen into the air upon exposure to light (Lewis, 1996); therefore exposure to nitric acid potentially involves exposure to oxides of nitrogen (Harbison, 1998; Lederer, 1985), especially nitrogen dioxide (Budavari, 1996).
2) Depending on the conditions, the vapors or fumes of nitric acid may actually be a mixture of nitric acid and various oxides of nitrogen. The composition may vary with temperature, humidity, and contact with other organic materials (Lewis, 1996).
3) Nitric acid is formed in photochemical smog from the reaction between nitric oxide and hydrocarbons (Heicklen, 1987). Individuals living in heavily polluted areas may receive chronic inhalation exposure to nitric acid.
4) Workers in the following professions may be exposed to nitrogen oxides or nitric acid: glassblowing, engraving and electroplating, underground blasting operations and other mining, farming (silage and fertilizers), welding, fire fighting, and industrial chemistry. Nitrogen oxides, found in the exhaust of engines that burn fossil fuels, are a component of the air pollution that contributes to acid rain. Currently, levels in polluted air are probably not high enough to contribute to respiratory disease (Ellenhorn, 1997).

C)

1) Nitric acid is used in the manufacture of ammonium nitrate for fertilizer and explosives, organic synthesis (drugs, dyes, explosives, cellulose nitrate, nitrate salts), metallurgy, photoengraving, etching steel, urethanes, rubber chemicals, reprocessing spent nuclear fuel, and for ore flotation (AAR, 1996; Lewis, 2001).
2) The production of nitric acid is the sixth largest chemical industry in the United States (Pohanish, 2002). Nitric acid is used in the production of fertilizers, manufacture of gunpowder and explosives, etching, bright-dipping (metal cleaning), electroplating, photoengraving, production of rocket fuel, manufacture of pesticides, dyestuffs, pharmaceuticals, cellulose nitrate, and manufacture of inorganic and organic nitrates (Pohanish, 2002; ITI, 1995; Budavari, 1996). Nitric acid has also been used as a cauterizing agent for warts in veterinary medicine (Budavari, 1996).
3) Nitric acid is formed in photochemical smog from the reaction between nitric oxide and hydrocarbons (Heicklen, 1987). Individuals living in heavily polluted areas may receive chronic inhalation exposure to nitric acid.

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) WITH POISONING/EXPOSURE

1) Nitric acid can be corrosive to the skin, eyes, nose, mucous membranes, respiratory and gastrointestinal tracts, or any tissue with which it comes in contact. Severe burns can occur with necrosis and scarring. Milder exposures can cause irritation of the eyes, skin, mucous membranes and respiratory and digestive tracts.

0.2.3)

A) WITH POISONING/EXPOSURE

1) Delayed dyspnea, circulatory collapse, and weak or rapid pulse can occur.

0.2.4)

A) WITH POISONING/EXPOSURE

1) Conjunctivitis, corneal ulcers and necrosis, corneal opacity, nasal irritation, throat burn or irritation, and necrosis and edema of the upper airway may occur. Dental discoloration or erosion may occur with chronic exposure.

0.2.5)

A) WITH POISONING/EXPOSURE

1) Shock, cardiac insufficiency, and ischemic lesions may be noted.

0.2.6)

A) WITH POISONING/EXPOSURE

1) Respiratory tract irritation, delayed effects, pulmonary function changes, chemical pneumonitis, pulmonary edema, and dyspnea may occur.

0.2.7)

A) WITH POISONING/EXPOSURE

1) Headache can occur.

0.2.8)

A) WITH POISONING/EXPOSURE

1) Gastritis, hemorrhagic gastritis, esophageal and gastric burns can occur.

0.2.9)

A) WITH POISONING/EXPOSURE

1) Ischemic lesions may occur secondary to hypotension.

0.2.10)

A) WITH POISONING/EXPOSURE

1) Renal failure has occurred most likely secondary to prolonged hypotension.

0.2.11)

A) WITH POISONING/EXPOSURE

1) Metabolic acidosis may occur.

0.2.13)

A) WITH POISONING/EXPOSURE

1) Methemoglobinemia, hemolysis and leukocytosis may occur.

0.2.14)

A) WITH POISONING/EXPOSURE

1) Severe burns, ulceration, scarring, dermatitis, and yellow staining of the skin may be observed.

0.2.20)

A) Fetotoxicity, biochemical effects, and metabolic effects have been seen in exposed experimental animals. Induction of fetal methemoglobinemia is possible.
B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation.

0.2.22)

A) WITH POISONING/EXPOSURE

1) HAZARDOUS DECOMPOSITION PRODUCTS

a) Poisonous nitrogen oxides, hydrogen nitrate and acid fumes may be produced if heated to decomposition. Nitrogen peroxide may be generated in the presence of excessive heat or humidity (HSDB , 1998).

Laboratory Monitoring

A)

Treatment Overview

0.4.2)

A) Do not induce emesis.
B) Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation.
C) 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.
D) Observe patients with ingestion carefully for the possible development of esophageal or gastrointestinal tract irritation or burns. If signs or symptoms of esophageal irritation or burns are present, consider endoscopy to determine the extent of injury.
E) Steroid use is controversial. Surgical consultation should be obtained if GI tract necrosis or perforation are suspected.
F) METHEMOGLOBINEMIA: Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.
G) METHYLENE BLUE: INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules and 10 mg/1 mL (1% solution) vials. Additional doses may sometimes be required. Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection. NEONATES: DOSE: 0.3 to 1 mg/kg.
H) Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome.

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.

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.
B) Prolonged initial flushing and early ophthalmologic consultation are advisable.

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.

Range Of Toxicity

A)

Clinical Effects

Summary Of Exposure

A)

1) Nitric acid can be corrosive to the skin, eyes, nose, mucous membranes, respiratory and gastrointestinal tracts, or any tissue with which it comes in contact. Severe burns can occur with necrosis and scarring. Milder exposures can cause irritation of the eyes, skin, mucous membranes and respiratory and digestive tracts.

Vital Signs

3.3.1)

A) WITH POISONING/EXPOSURE

1) Delayed dyspnea, circulatory collapse, and weak or rapid pulse can occur.

3.3.2)

A) WITH POISONING/EXPOSURE

1) DELAYED DYSPNEA - Coughing, chest pain, and dyspnea may be delayed for 4 to 30 hours after acute overexposure (Hathaway et al, 1996).

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 respirations. Circulatory collapse is one of the most common immediate causes of death from overexposure (Gosselin et al, 1984; Finkel, 1983). Sudden circulatory collapse can occur from acute nitric acid poisoning (Finkel, 1983).

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 respirations. Circulatory collapse is one of the most common immediate causes of death from overexposure (Gosselin et al, 1984).

Heent

3.4.1)

A) WITH POISONING/EXPOSURE

1) Conjunctivitis, corneal ulcers and necrosis, corneal opacity, nasal irritation, throat burn or irritation, and necrosis and edema of the upper airway may occur. Dental discoloration or erosion may occur with chronic exposure.

3.4.2)

A) WITH POISONING/EXPOSURE

1) DENTAL DISCOLORATION/EROSION - Yellow discoloration or erosion of teeth can occur from prolonged or chronic exposure to nitric acid. Erosion is thought not to be as frequent as that from exposure to sulfuric or hydrochloric acids (ITI, 1995; Finkel, 1983).

3.4.3)

A) WITH POISONING/EXPOSURE

1) CONJUNCTIVITIS - Nitric acid vapor is a strong irritant at lower concentrations and can cause conjunctivitis (ITI, 1995) CHRIS, 1998) and even necrosis of the conjunctiva (Gosselin et al, 1984).
2) CORNEAL ULCERS/NECROSIS/PERFORATION - Liquid nitric acid can cause severe pain, corneal ulcers, or severe burns of the corneal epithelium if splashed in the eye (ITI, 1995) CHRIS, 1998). Reduced vision or blindness can occur from direct eye contact (Sittig, 1991). Perforation of the globe and loss of ocular contents may occur (Grant & Schuman, 1993).
3) CORNEAL OPACITY - Immediate corneal clouding can occur (Finkel, 1983).

a) With exposure to strong acids, the cornea may become vascularized and opaque or may soften with sloughing of the whole stroma (Grant & Schuman, 1993). Short of such drastic sequelae, permanent damage and visual impairment can occur from nitric acid eye splashes (Hathaway et al, 1996).

3.4.5)

A) WITH POISONING/EXPOSURE

1) IRRITATION - Nitric acid is a strong irritant of the mucous membranes and upper respiratory tract. Symptoms of acute exposure to the vapor or mist include dryness of the nose and irritation of mucous membranes (Hathaway et al, 1996).

3.4.6)

A) WITH POISONING/EXPOSURE

1) CORROSION/ULCERATION - Corrosion of mucous membranes of the mouth, throat, and esophagus can occur; necrotic areas become yellow (Gosselin et al, 1984).
2) BURNS - Ingestion of nitric acid produces effects which resemble those of the more frequently documented hydrochloric acid (Gosselin et al, 1984).
3) UPPER AIRWAY INJURY/EDEMA - Inhalation or ingestion can cause injury to the upper airways resulting in edema that can be life threatening (Gosselin et al, 1984).
4) IRRITATION - Acute exposure to nitric acid can cause coughing and dryness of the throat, which may be delayed for up to 30 hours (Hathaway et al, 1996).

Cardiovascular

3.5.1)

A) WITH POISONING/EXPOSURE

1) Shock, cardiac insufficiency, and ischemic lesions may be noted.

3.5.2)

A) SHOCK

1) WITH POISONING/EXPOSURE

a) Sudden circulatory collapse can occur with respiratory symptoms no more severe than in mild cases (Finkel, 1983).
b) CASE REPORT - Severe metabolic acidosis (pH 7.1) and abdominal perforation occurred in a 55-year-old woman who intentionally ingested an unknown amount of nitric acid. Despite treatment, the patient rapidly developed hypotension and circulatory collapse. She died within 10 hours of exposure (Shetty et al, 2008).

B) MYOCARDIAL ISCHEMIA

1) WITH POISONING/EXPOSURE

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

C) HEART FAILURE

1) WITH POISONING/EXPOSURE

a) CASE REPORT - A worker exposed to nitric acid fumes developed increasing cardiac and respiratory insufficiency and died on day 21 of illness (Fraenkel, 1902).

Respiratory

3.6.1)

A) WITH POISONING/EXPOSURE

1) Respiratory tract irritation, delayed effects, pulmonary function changes, chemical pneumonitis, pulmonary edema, and dyspnea may occur.

3.6.2)

A) DISORDER OF RESPIRATORY SYSTEM

1) WITH POISONING/EXPOSURE

a) Nitric acid is a strong irritant of the upper respiratory tract in acute exposures; the irritation is expected to be similar to that of other strong acids (ACGIH, 1998).
b) DELAYED EFFECTS - Coughing, dryness of the throat and nose, chest pain, and dyspnea can be delayed for 4 to 30 hours after acute overexposure (Hathaway et al, 1996). Severity of symptoms may be no different between mild cases and those who will later show sudden circulatory collapse (Finkel, 1983). (Refer also to PULMONARY EDEMA)

1) CASE REPORT - A case has been reported of a man who died 19 days after an accident with nitric acid. The authors warn against mistakenly diagnosing miliary tuberculosis and against drawing the conclusion from prolonged survival time and absence of subjective symptoms that inhalation of nitrous fumes has been without ill effects (Schmid, 1974).

B) LARYNGISMUS

1) WITH POISONING/EXPOSURE

a) In severe overexposures, when escape is not possible, laryngeal spasm or edema can occur (Gosselin et al, 1984; Hathaway et al, 1996). Laryngeal edema is one of the frequent causes of death from overexposure to nitric acid (Gosselin et al, 1984).

C) EDEMA OF LARYNX

1) WITH POISONING/EXPOSURE

a) Inhalation or ingestion can cause glottic edema (Sittig, 1991). Glottic edema is one of the most frequent causes of death from overexposure to nitric acid (Gosselin et al, 1984).

D) ACUTE LUNG INJURY

1) WITH POISONING/EXPOSURE

a) Pulmonary edema, which is usually delayed and can be fatal, can occur in severe cases of acute exposure to fumes or mist of nitric acid. NO2 causes increased capillary permeability in the lungs. The resultant pulmonary edema has included accumulations of toxic neutrophils and altered immunoglobulin concentrations (Hajela et al, 1990).
b) DELAYED ONSET - Three men died of rapidly progressive pulmonary edema of delayed onset after inhalation of fumes from an accidental nitric acid explosion (Hajela et al, 1990).

E) PNEUMONIA

1) WITH POISONING/EXPOSURE

a) Inhalation or aspiration of nitric acid can cause chemical pneumonitis (ACGIH, 1998; (Gosselin et al, 1984).

F) LACK OF EFFECT

1) WITH POISONING/EXPOSURE

a) CONDITION NOT AGGRAVATED - ASTHMA - Cough and exacerbation of asthma symptoms were positively associated with hydrogen ion concentration and sulfates, but not associated with nitric acid, nitrates or sulfur dioxide, based on environmental measurements, daily survey of asthmatics, and modeling. Nitric acid and nitrates were not directly measured (Ostro et al, 1991).

3.6.3)

A) ANIMAL STUDIES

1) BRONCHIECTASIS

a) RODENTS

1) Hamsters or rats instilled intratracheally with nitric acid exhibited functional, structural, and biochemical pulmonary changes.

a) Functional airway changes included acute bronchitis, acute bronchiolitis, obliterative bronchiolitis, bronchiolectasia, and bronchiectasis up to 60 days after a single intratracheal instillation of 0.5% nitric acid (Coalson & Collins, 1985).

2) Structural changes included decreased lung volumes, decreased internal surface areas, and increased total weight (Coalson & Collins, 1985).
3) Biochemical changes included increases in collagen and elastin, both fibrotic responses (Coalson & Collins, 1985).
4) Rats given 1% nitric acid intratracheally showed evidence of bronchiolitis, alveolitis, and increased pulmonary absorption of drugs 1 to 4 days after treatment, results which suggested increased porosity and alteration of integrity of lipoid regions of the membrane (Gardiner & Schanker, 1976).
5) Nitric acid mist at 63 mg/m(3) had no apparent effect on rats in a single exposure (ACGIH, 1998).

b) DOGS

1) AIRWAY OBSTRUCTION AND PULMONARY RESISTANCE - Seven dogs exposed to nebulized 1% nitric acid for four weeks experienced small airway obstruction, increased pulmonary resistance, and delayed hyperresponsiveness to histamine (Fujita et al, 1988).
2) ALTERED PULMONARY FUNCTION - Peters and Hyatt (1986) report canine exposure (1% nitric acid on alternate days for 4 weeks) resulted in decreased total lung capacity, vital capacity, and dynamic compliance; and increased pulmonary resistance and ratio of functional residual capacity to total lung capacity.

a) Histologically, there was widespread chronic airway inflammation, slight peribronchiolar fibrosis, slight epithelial changes, and an increase in smooth muscle (Peters & Hyatt, 1986).

Neurologic

3.7.1)

A) WITH POISONING/EXPOSURE

1) Headache can occur.

3.7.2)

A) HEADACHE

1) WITH POISONING/EXPOSURE

a) Acute inhalational overexposure can produce headache and a sensation of fullness in the head (Finkel, 1983).

B) FATIGUE

1) WITH POISONING/EXPOSURE

a) If exposure to nitric acid occurs under conditions favoring formation of nitric oxide and methemoglobinemia, symptoms of headache, vertigo, loss of coordination and mental facilities, and weakness can occur.

Gastrointestinal

3.8.1)

A) WITH POISONING/EXPOSURE

1) Gastritis, hemorrhagic gastritis, esophageal and gastric burns can occur.

3.8.2)

A) GASTRIC ULCER

1) WITH POISONING/EXPOSURE

a) Ingestion of nitric acid can cause esophageal corrosion or stricture, necrosis and perforation of the stomach, especially at the pylorus, and occasionally injury to the small bowel (Gosselin et al, 1984).
b) CASE REPORT - One case of extensive injury to the jejunum after ingestion of 1 to 2 ounces of nitric acid has been reported (Adams & Skucas, 1980).
c) Pyloric stenosis often follows from several weeks (Boikan & Singer, 1930) to several years later (Gray & Holmes, 1948) in patients who survive an acute episode of ingesting strong acid (Gosselin et al, 1984).

B) ULCER OF ESOPHAGUS

1) WITH POISONING/EXPOSURE

a) Esophageal necrosis can be fatal from oral exposure (Sittig, 1991) but is probably less common than with ingestion of strongly alkaline materials (Gosselin et al, 1984).

C) GASTROINTESTINAL PERFORATION

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Severe metabolic acidosis and evidence of abdominal perforation occurred in a 55-year-old woman who intentionally ingested an unknown amount of nitric acid. The patient's condition rapidly progressed to circulatory collapse. Postmortem findings showed dark brown to black (charring) discoloration of the mucosal surface of the stomach, along with a single perforation (5 x 3 cm) in the pyloric region. The external surface of the stomach and large intestine also showed dark black to brownish discoloration (Shetty et al, 2008).

D) GASTRITIS

1) WITH POISONING/EXPOSURE

a) Ingestion of nitric and other strong acids can cause epigastric pain, nausea, and vomiting of mucoid and "coffee ground" material (Gosselin et al, 1984).
b) Vomiting of fresh blood has occurred in patients who have ingested strong acid (Gosselin et al, 1984).

Hepatic

3.9.1)

A) WITH POISONING/EXPOSURE

1) Ischemic lesions may occur secondary to hypotension.

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).

Genitourinary

3.10.1)

A) WITH POISONING/EXPOSURE

1) Renal failure has occurred most likely secondary to prolonged hypotension.

3.10.2)

A) 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) WITH POISONING/EXPOSURE

1) Metabolic acidosis may occur.

3.11.2)

A) METABOLIC ACIDOSIS

1) WITH POISONING/EXPOSURE

a) GENERAL: Because it is a strong acid, exposure to nitric acid may produce metabolic acidosis.
b) Severe metabolic acidosis (pH 7.1; serum base deficit -20.7) occurred in a 55-year-old woman who intentionally ingested an unknown amount of nitric acid. Her condition rapidly deteriorated with evidence of abdominal perforation and circulatory collapse. She died within 10 hours of exposure (Shetty et al, 2008).

Hematologic

3.13.1)

A) WITH POISONING/EXPOSURE

1) Methemoglobinemia, hemolysis and leukocytosis may occur.

3.13.2)

A) METHEMOGLOBINEMIA

1) WITH POISONING/EXPOSURE

a) If nitric acid has been in contact with organic materials or in other conditions likely to release nitric oxide, methemoglobin may be formed as a result of exposure to nitric oxide and or nitric dioxide (Proctor et al, 1989). Hypoxia with cyanosis, headache, dizziness, vomiting, weakness, loss of coordination and mental facilities, drowsiness, and death from respiratory arrest can occur.
b) Symptoms of methemoglobinemia occur at levels of methemoglobin greater than 15 percent, and levels of 80 percent may be fatal.

1) Methemoglobinemia can often have an insidious onset even in potentially fatal cases. Prompt medical attention is necessary to prevent progression of the symptoms to an irreversible state (see TREATMENT).

B) HEMOLYSIS

1) WITH POISONING/EXPOSURE

a) Destruction of erythrocytes may occur from exposure to oxides of nitrogen (Finkel, 1983), possibly a secondary effect of methemoglobinemia.

C) LEUKOCYTOSIS

1) WITH POISONING/EXPOSURE

a) Leukocytosis is common from exposure to strong mineral acids (Gosselin et al, 1984).

Dermatologic

3.14.1)

A) WITH POISONING/EXPOSURE

1) Severe burns, ulceration, scarring, dermatitis, and yellow staining of the skin may be observed.

3.14.2)

A) SKIN NECROSIS

1) WITH POISONING/EXPOSURE

a) Nitric acid is corrosive to the skin, producing severe burns, ulceration, and scarring (Sittig, 1991).

B) DERMATITIS

1) WITH POISONING/EXPOSURE

a) Exposure to dilute concentrations may produce dermatitis. The epithelium usually becomes hardened without being destroyed (Hathaway et al, 1996).

C) DISCOLORATION OF SKIN

1) WITH POISONING/EXPOSURE

a) Nitric acid can stain the skin and mucosal surface a yellow or yellowish-brown color, due to the xanthoproteic reaction from denatured colored proteins (Finkel, 1983; Hathaway et al, 1996; Shetty et al, 2008).

1) There was postmortem evidence of yellowish discoloration ("xanthoproteic reaction") of the oral mucosa and the esophagus in a 55-year-old woman who intentionally ingested an unknown amount of nitric acid (Shetty et al, 2008).

Reproductive

3.20.1)

A) Fetotoxicity, biochemical effects, and metabolic effects have been seen in exposed experimental animals. Induction of fetal methemoglobinemia is possible.
B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation.

3.20.2)

A) ANIMAL STUDIES

1) SKELETAL MALFORMATION

a) Nitric acid was fetotoxic and had biochemical or metabolic effects in neonates when given at relatively high oral doses to pregnant rats (RTECS, 2002).

2) LACK OF EFFECT

a) In one study rats, mice, and guinea pigs were chronically exposed to nitric acid at an airborne concentration of 4 ppm with no apparent ill effects (Gray et al, 1954).

3.20.3)

A) HUMANS

1) METHEMOGLOBINEMIA

a) If exposure to nitric acid is under conditions favoring formation of nitric oxide, then there is some risk of methemoglobin formation in the mother and fetus. The fetus is believed to be more susceptible to methemoglobinemia than the mother because fetal hemoglobin is more easily oxidized to methemoglobin than the adult form and the need for oxygen is greater in the fetus than in the mother (Mansouri, 1985).

1) While some small degree of methemoglobinemia can be tolerated by the fetus, the upper limits of a safe fetal level are not known (Mansouri, 1985).
2) Possible effects of methemoglobinemia on the fetus include neurological defects or developmental delays and stillbirths.
3) Effects of methemoglobinemia would be expected to be more severe during the last trimester of pregnancy because the fetal demand for oxygen is greatest at that time.

2) ABORTION

a) Women working in the photolithographic and diffusion areas in a semiconductor manufacturing plant were found to be at increased risk for spontaneous abortions (Pastides et al, 1988). Such clean-room workers are exposed to sulfuric and nitric acids, but are also exposed to solvents and other chemicals used in photoetching of silicon microchips. Solvents are known to produce similar effects and are more likely responsible for the observed effects.

B) ANIMAL STUDIES

1) Nitric acid was fetotoxic when given at relatively high oral doses to pregnant rats; rats, mice, and guinea pigs chronically exposed to nitric acid at 4 ppm had no apparent ill effects (BJ Dabney , 1992).

3.20.4)

A) LACK OF INFORMATION

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

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS7697-37-2 (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) Not Listed

3.21.3)

A) CARCINOMA

1) At the time of this review, no data were found which labeled nitric acid as a known human carcinogen in the absence of other exposures (ACGIH, 1998; (US DHHS, 1994; HSDB , 1998; IRIS , 1998; RTECS , 1998; IARC, 1987; IARC, 1992).
2) Exposure to nitric acid in combination with other inorganic acids occurs in many industries. Occupational exposure to strong inorganic-acid mists containing sulfuric acid has been ranked in IARC Group 1: carcinogenic to humans (IARC, 1992).
3) CASE REPORTS - Increased incidence of some types of cancer were reported among production or maintenance workers at a nitric acid plant. However, due to concomitant exposure to asbestos and other chemicals, and lack of nitric acid exposure quantification, the interpretation of the data is limited (IARC, 1992).
4) CASE REPORTS - Other studies reviewed by the IARC (1992) have reported an increased risk of multiple myeloma or laryngeal, lung, or kidney cancer in workers exposed to "acids" (by self-report) or inorganic acid solutions which may have included sulfuric acid (most common), hydrochloric acid and nitric acid.
5) Nitrates can generally be reduced to nitrites in the body, which in turn can react with amines to form mutagenic and possibly carcinogenic N-nitrosamines (Fishbein, 1975).

3.21.4)

A) LACK OF INFORMATION

1) Studies in experimental animals were not available to the IARC (1992). At the time of this review, no data were found concerning carcinogenic effects of nitric acid exposure alone in experimental animals (ACGIH, 1998; (US DHHS, 1994; HSDB , 1998; IRIS , 1998; RTECS , 1998; IARC, 1987).

Genotoxicity

A)

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count and liver and kidney function tests is suggested for patients with significant exposure.

B) HEMATOLOGIC

1) If cyanosis is present, monitor methemoglobin levels.

4.1.3)

A) URINALYSIS

1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring urinalysis is suggested for patients with significant exposure.

4.1.4)

A) OTHER

1) MONITORING

a) Preplacement and periodic physical examination are indicated, with emphasis on the respiratory tract, skin, eyes, and teeth, FVC and FEV (1 sec) pulmonary function tests (Hathaway et al, 1996; Sittig, 1991), and examination of teeth for dental erosion (Sittig, 1991).
b) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.

2) PULMONARY FUNCTION TESTS

a) If respiratory tract irritation is present, it may be useful to monitor pulmonary function tests.

Radiographic Studies

A)

1) Periodic chest roentgenogram is indicated with chronic exposure or for monitoring recovery from acute overexposure (Hathaway et al, 1996).
2) If respiratory tract irritation is present, monitor chest x-ray.
3) A chest x-ray is recommended as part of the annual physical examination of workers exposed to nitric acid (Pohanish, 2002).

Methods

A)

1) Nitric acid can be analyzed from ambient air by collecting a sample on an impinger containing water, followed by analysis using ion-specific electrode (A-10) (Sittig, 1991).

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.

6.3.3)

6.3.3.1) ADMISSION CRITERIA/INHALATION

A) All persons with potential acute exposure to nitrogen oxides should be observed in-hospital for 6 hours (Haddad et al, 1998).

Monitoring

A)

Oral Exposure

6.5.2)

A) EMESIS/NOT RECOMMENDED

1) Do not induce emesis.

B) NASOGASTRIC TUBE

1) INDICATIONS: Consider insertion of a small, flexible nasogastric tube to aspirate gastric contents after large, recent ingestion of caustics. The risk of worsening mucosal injury (including perforation) must be weighed against the potential benefit.
2) PRECAUTIONS:

a) SEIZURE CONTROL: Is mandatory prior to gastric emptying.
b) AIRWAY PROTECTION: Alert patients - place in Trendelenburg and left lateral decubitus position, with suction available. Obtunded or unconscious patients - cuffed endotracheal intubation. COMPLICATIONS:

1) Complications of gastric aspiration may include: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach (Vale, 1997). Combative patients may be at greater risk for complications.

C) ACTIVATED CHARCOAL

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

6.5.3)

A) SUPPORT

1) There is little information specific to the treatment of nitric acid ingestion. Most of the following information is derived from experience with ingestion of other caustic materials.

B) IRRIGATION

1) The mouth should be irrigated with copious amounts of water.
2) 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).
3) Diluting acids with water has been shown not to be effective in altering the pH. Diluting 50 mL of 9.5 percent hydrochloric acid with 800 milliliters of water resulted in a pH change of from 0.99 to 1.73 (Maull et al, 1985).

C) BURN

1) SUMMARY: 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.

D) 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.

E) 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, 1989; 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).

F) DIETARY FINDING

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

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

H) 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, 1984).
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, 1993). 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.

I) 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.

J) METHEMOGLOBINEMIA

1) If cyanosis is present or there is a possibility that nitric acid exposure may have caused methemoglobinemia, monitor methemoglobin levels.
2) SUMMARY

a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.

3) METHYLENE BLUE

a) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
b) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
c) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
d) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).

4) TOLUIDINE BLUE OR TOLONIUM CHLORIDE (GERMANY)

a) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.

5) Hyperbaric oxygen therapy may be used to maintain tissue oxygenation in cases of severe methemoglobinemia not responsive to methylene blue, while preparing for emergency exchange transfusion (Hall et al, 1986).

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) ISOPROTERENOL

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 (Mizus et al, 1985).

B) BRONCHOSPASM

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

C) 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.

D) 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).

E) CORTICOSTEROID

1) Administration of steroids may have a place in the treatment of chronic sequelae from inhalation exposure to nitric acid vapors (Kizer, 1984).

F) OBSERVATION REGIMES

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

G) AIRWAY MANAGEMENT

1) If severe upper airway edema is present, obstruction of the airway could occur.
2) Ensure airway patency and adequacy of oxygenation and ventilation.
3) Endotracheal intubation on creation of a surgical airway could be required in severe cases.

H) 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) INJURY OF GLOBE OF EYE

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

a) ASSESSMENT CAUSTIC EYE BURNS: It may take 48 to 72 hours after the burn to assess correctly the degree of ocular damage (Brodovsky et al, 2000).
b) The 1965 Roper-Hall classification uses the size of the corneal epithelial defect, the degree of corneal opacification and extent of limbal ischemia to evaluate the extent of the chemical ocular injury (Brodovsky et al, 2000; Singh et al, 2013):

1) GRADE 1 (prognosis good): Corneal epithelial damage; no limbal ischemia.
2) GRADE 2 (prognosis good): Cornea hazy; iris details visible, ischemia less than one-third of limbus.
3) GRADE 3 (prognosis guarded): Total loss of corneal epithelium; stromal haze obscures iris details; ischemia of one-third to one-half of limbus.
4) GRADE 4 (prognosis poor): Cornea opaque; iris and pupil obscured, ischemia affects more than one-half of limbus.

c) A newer classification (Dua) is based on clock hour limbal involvement as well as a percentage of bulbar conjunctival involvement (Singh et al, 2013):

1) GRADE 1 (prognosis very good): 0 clock hour of limbal involvement and 0% conjunctival involvement.
2) GRADE 2 (prognosis good): Less than 3 clock hour of limbal involvement and less than 30% conjunctival involvement.
3) GRADE 3 (prognosis good): Greater than 3 and up to 6 clock hour of limbal involvement and greater than 30% to 50% conjunctival involvement.
4) GRADE 4 (prognosis good to guarded): Greater than 6 and up to 9 clock hour of limbal involvement and greater than 50% to 75% conjunctival involvement.
5) GRADE 5 (prognosis guarded to poor): Greater than 9 and less than 12 clock hour of limbal involvement and greater than 75% and less than 100% conjunctival involvement.
6) GRADE 6 (very poor): Total limbus (12 clock hour) involved and 100% conjunctival involvement.

3) MEDICAL FACILITY IRRIGATION

a) Begin irrigation immediately with copious amounts of water or sterile 0.9% saline, which ever is more rapidly available. Lactated Ringer's solution may also be effective. Once irrigation has begun, instill a drop of local anesthetic (eg, 0.5% proparacaine) for comfort; switching from water to slightly warmed sterile saline may also improve patient comfort (Singh et al, 2013; Spector & Fernandez, 2008; Ernst et al, 1998; Grant & Schuman, 1993a). In one study, isotonic saline, lactated Ringer's solution, normal saline with bicarbonate, and balanced saline plus (BSS Plus) were compared and no difference in normalization of pH were found; however, BSS Plus was better tolerated and more comfortable (Fish & Davidson, 2010).

1) Continue irrigation for at least an hour or until the superior and inferior cul-de-sacs have returned to neutrality (check pH every 30 minutes), pH of 7.0 to 8.0, and remain so for 30 minutes after irrigation is discontinued (Spector & Fernandez, 2008; Brodovsky et al, 2000a). After severe alkaline burns, the pH of the conjunctival sac may only return to a pH of 8 or 8.5 even after extensive irrigation (Grant & Schuman, 1993a). Irrigating volumes up to 20 L or more have been used to neutralize the pH (Singh et al, 2013; Fish & Davidson, 2010). Immediate and prolonged irrigation is associated with improved visual acuity, shorter hospital stay and fewer surgical interventions (Kuckelkorn et al, 1995; Saari et al, 1984).
2) Search the conjunctival sac for solid particles and remove them while continuing irrigation (Grant & Schuman, 1993a).
3) For significant alkaline or concentrated acid burns with evidence of eye injury irrigation should be continued for at least 2 to 3 hours, potentially as long as 24 to 48 hours if pH not normalized, in an attempt to normalize the pH of the anterior chamber (Smilkstein & Fraunfelder, 2002). Emergent ophthalmologic consultation is needed in these cases (Spector & Fernandez, 2008).

4) MINOR INJURY

a) SUMMARY

1) If ocular damage is minor, artificial tears/lubricants, topical cycloplegics, and antibiotics may be all that are needed.

b) ARTIFICIAL TEARS

1) To promote re-epithelization, preservative-free artificial tears/lubricants (eg, hyaluronic acid hourly) may be used (Fish & Davidson, 2010; Tuft & Shortt, 2009).

c) TOPICAL CYCLOPLEGIC

1) Use to guard against development of posterior synechiae and ciliary spasm (Brodovsky et al, 2000b; Grant & Schuman, 1993a). Cyclopentolate 0.5% or 1% eye drops may be administered 4 times daily to control pain (Tuft & Shortt, 2009; Spector & Fernandez, 2008).

d) TOPICAL ANTIBIOTICS

1) An antibiotic ophthalmic ointment or drops should be used for as long as epithelial defects persist (Brodovsky et al, 2000b; Grant & Schuman, 1993a). Topical erythromycin or tetracycline ointment may be used (Spector & Fernandez, 2008).

e) PAIN CONTROL

1) If pain control is required, oral or parenteral NSAIDs or narcotics are preferred to topical ocular anesthetics, which may cause local corneal epithelial damage if used repeatedly (Spector & Fernandez, 2008; Grant & Schuman, 1993a). However, topical 0.5% proparacaine has been recommended (Spector & Fernandez, 2008).

5) SEVERE INJURY

a) SUMMARY

1) If the damage is minor, the above may be all that is needed. For grade 3 or 4 injuries, one or more of the following may be used, only with ophthalmologic consultation: acetazolamide, topical timolol, topical steroids, citrate, ascorbate, EDTA, cysteine, NAC, penicillamine, tetracycline, or soft contact lenses.

b) ARTIFICIAL TEARS

1) To promote re-epithelization, preservative-free artificial tears/lubricants (eg, hyaluronic acid hourly) may be used (Fish & Davidson, 2010; Tuft & Shortt, 2009).

c) PAIN CONTROL

1) If pain control is required, oral or parenteral NSAIDs or narcotics are preferred to topical ocular anesthetics, which may cause local corneal epithelial damage if used repeatedly (Spector & Fernandez, 2008; Grant & Schuman, 1993a). However, topical 0.5% proparacaine has been recommended (Spector & Fernandez, 2008).

d) CARBONIC ANHYDRASE INHIBITOR

1) Acetazolamide (250 mg orally 4 times daily) may be given to control increased intraocular pressure (Singh et al, 2013; Tuft & Shortt, 2009; Spector & Fernandez, 2008).

e) TOPICAL STEROIDS

1) DOSE: Dexamethasone 0.1% ointment 4 times daily to reduce inflammation. If persistent epithelial defect is present, discontinue dexamethasone by day 14 to reduce the risk of stromal melt (Tuft & Shortt, 2009). Other sources suggest that corticosteroids should be stopped if the epithelium has not covered surface defects by 5 to 7 days (Grant & Schuman, 1993b).
2) Topical prednisolone 0.5% has also been used. A further increase in corneoscleral melt may occur if topical steroids are used alone. In one study, topical prednisolone 0.5% was used in combination with topical ascorbate 10%; no increase in corneoscleral melt was observed when topical steroids were used until re-epithelization (Singh et al, 2013; Fish & Davidson, 2010).
3) In one retrospective study, fluorometholone 1% drops were administered every 2 hours initially, then decreased to four times daily when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete (Brodovsky et al, 2000a).

a) STUDY: The combination of intensive topical corticosteroids, topical citrate and ascorbate, and oral citrate and ascorbate was associated with improved best corrected visual acuity and a trend towards more rapid corneal reepithelialization in Grade 3 alkali burns in one retrospective study (Brodovsky et al, 2000a).

f) ASCORBATE

1) Oral or topical ascorbate may be used to promote epithelial healing and reduce the risk of stromal necrosis (Fish & Davidson, 2010).
2) DOSE: Ascorbate 10% 4 times daily topically or 1 g orally (2 g/day) (Singh et al, 2013; Tuft & Shortt, 2009).
3) Ascorbate is needed for the formation of collagen and the concentration of ascorbate in the anterior chamber is decreased when the ciliary body is damaged by alkali burns (Tuft & Shortt, 2009; Grant & Schuman, 1993b). In one retrospective study, ascorbate drops (10%) were administered every 2 hours, then decreased to 4 times a day when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete. These patients also received 500 mg of oral ascorbate 4 times daily, until discharge from the hospital (Brodovsky et al, 2000a).

a) STUDY: The combination of intensive topical corticosteroids, topical citrate and ascorbate, and oral citrate and ascorbate was associated with improved best corrected visual acuity and a trend towards more rapid corneal reepithelialization in Grade 3 alkali burns in one retrospective study (Brodovsky et al, 2000a).

g) CITRATE

1) Topical citrate may be used to promote epithelial healing and reduce the risk of stromal necrosis (Fish & Davidson, 2010).
2) DOSE: Potassium citrate 10% 4 times daily topically (Tuft & Shortt, 2009).
3) Citrate chelates calcium, and thereby interferes with the harmful effects of neutrophil accumulation, such as release of proteolytic enzymes and superoxide free radicals, phagocytosis and ulceration (Grant & Schuman, 1993b). In one retrospective study, 10% citrate drops were administered every 2 hours, then decreased to 4 times a day when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete. These patients also received a urinary alkalinizer containing 720 mg of citric acid anhydrous and 630 mg of sodium citrate anhydrous 3 times daily, until discharge from the hospital (Brodovsky et al, 2000a).

a) STUDY: The combination of intensive topical corticosteroids, topical citrate and ascorbate, and oral citrate and ascorbate was associated with improved best corrected visual acuity and a trend towards more rapid corneal reepithelialization in Grade 3 alkali burns in one retrospective study (Brodovsky et al, 2000a).

h) COLLAGENASE INHIBITORS

1) Inhibitors of collagenase can inhibit collagenolytic activity, prevent stromal ulceration, and promote wound healing. Several effective agents, such as cysteine, n-acetylcysteine, sodium ethylenediamine tetra acetic acid (EDTA), calcium EDTA, penicillamine, and citrate, have been recommended (Singh et al, 2013; Tuft & Shortt, 2009; Perry et al, 1993; Seedor et al, 1987).
2) TETRACYCLINE: Has been found to have an anticollagenolytic effect. Systemic tetracycline 50 mg/kg/day reduced the incidence of alkali-induced corneal ulcerations in rabbits (Seedor et al, 1987).
3) DOXYCYCLINE: Decreased epithelial defects and collagenase activity in a rabbit model of alkali burns to the eye (Perry et al, 1993). DOSE: 100 mg twice daily (Tuft & Shortt, 2009).

i) ANTIBIOTICS

1) An antibiotic ophthalmic ointment or drops should be used for as long as epithelial defects persist (Brodovsky et al, 2000b; Grant & Schuman, 1993a). Topical erythromycin or tetracycline ointment may be used (Spector & Fernandez, 2008). In patients with severe burns, a topical fluoroquinolone antibiotic drop 4 times daily may also be used (Tuft & Shortt, 2009). A topical fourth generation fluoroquinolone has been recommended as an antimicrobial prophylaxis in patients with large epithelial defect (Fish & Davidson, 2010).

j) TOPICAL CYCLOPLEGIC

1) Cyclopentolate 0.5% or 1% eye drops may be administered 4 times daily to control pain (Tuft & Shortt, 2009; Spector & Fernandez, 2008).

k) SOFT CONTACT LENSES

1) A bandage contact lens (eg, silicone hydrogel) may make the patient more comfortable and protect the surface (Fish & Davidson, 2010; Tuft & Shortt, 2009). Hydrophilic high oxygen permeability lenses are preferred (Singh et al, 2013). Soft lenses with intermediate water content and inherent rigidity may facilitate reepithelialization. The use of 0.5 normal sodium chloride drops hourly and artificial tears or lubricant eyedrops instilled 4 times a day may help maintain adequate hydration and lens mobility.

6) SURGICAL THERAPY

a) SURGICAL THERAPY CAUSTIC EYE INJURY

1) Early insertion of methylmethacrylate ring or suturing saran wrap over palpebral and cul-de-sac conjunctiva may prevent fibrinosis adhesions and reduce fibrotic contracture of conjunctiva, but the advantage of such treatments is not clear.
2) Limbal stem cell transplantation has been used successfully in both the acute stage of injury and the chronically scarred healing phase in patients with persistent epithelial defects after chemical burns (Azuara-Blanco et al, 1999; Morgan & Murray, 1996; Ronk et al, 1994).
3) In some patients, amniotic membrane transplantation (AMT) has been successful in improving corneal healing and visual acuity in patients with persistent epithelial defects after chemical burns. It can restore the conjunctival surface and decrease limbal stromal inflammation (Fish & Davidson, 2010; Sridhar et al, 2000; Su & Lin, 2000; Meller et al, 2000; Azuara-Blanco et al, 1999).
4) Control glaucoma. Remove any cataracts formed (Fish & Davidson, 2010; Tuft & Shortt, 2009).
5) In patients with severe injury, tenonplasty can be performed to promote epithelialization and prevent melting (Tuft & Shortt, 2009).
6) A keratoprosthesis placement has also been indicated in severe cases (Fish & Davidson, 2010). Penetrating keratoplasty is usually delayed as long as possible as results appear to be better with a greater lag time between injury and keratoplasty (Grant & Schuman, 1993a).

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

Enhanced Elimination

A)

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

B)

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

Abstracts

Case Reports

A)

1) One case of extensive injury to the jejunum after ingesting 1 to 2 ounces of nitric acid has been reported (Adams & Skucas, 1980).

Range Of Toxicity

Summary

A)

Minimum Lethal Exposure

A)

1) The lowest published lethal dose for humans is 110 mg/kg (RTECS, 2002).

Maximum Tolerated Exposure

A)

1) Finkel (1983) related nitrogen dioxide exposure level to effects -

NO2 CONCENTRATION		EFFECTS
ppm	mg/m(3)
25	47	Bronchitis, Bronchopneumonia; recovery
50	94	Bronchiolitis, focal pneumonitis; recovery
150	282	Bronchiolitis, fibrosa obliterans; fatal
300	564	Bronchopneumonia; fatal
500	940	Acute pulmonary edema; fatal

2) 100 ppm (inhalation) is considered to be immediately dangerous to life or health (EPA, 1985).
3) Membrane irritation occurs with exposure to 13 ppm. Exposure to 50 to 150 ppm will cause bronchitis or pneumonia (Haddad et al, 1998).
4) The TLV level of 2 ppm (TWA) was set to be intermediate between those for hydrochloric acid and sulfuric acid. It is believed to be sufficiently low to prevent irritation and corrosion, but not necessarily potentiation of the effects of nitrogen dioxide (ACGIH, 1998).
5) Induced bronchospasm in asthmatics has been potentiated by the inhalation of as little as 0.3 ppm nitrogen dioxide (Haddad et al, 1998).

B)

1) Nitric acid mist at 63 mg/m(3) had no apparent effect on rats in a single exposure (ACGIH, 1998).
2) Rats, mice, and guinea pigs tolerated 4 ppm of nitric acid in a chronic study with no apparent ill effects (Gray et al, 1954).

Workplace Standards

A)

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) Nitric acid

a) TLV:

1) TLV-TWA: 2 ppm
2) TLV-STEL: 4 ppm
3) TLV-Ceiling:

b) Notations and Endnotes:

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

c) TLV Basis - Critical Effect(s): URT and eye irr; dental erosion
d) Molecular Weight: 63.02

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 CAS7697-37-2 (National Institute for Occupational Safety and Health, 2007):

1) Listed as: Nitric acid
2) REL:

a) TWA: 2 ppm (5 mg/m(3))
b) STEL: 4 ppm (10 mg/m(3))
c) Ceiling:
d) Carcinogen Listing: (Not Listed) Not Listed
e) Skin Designation: Not Listed
f) Note(s):

3) IDLH:

a) IDLH: 25 ppm
b) Note(s): Not Listed

C) Carcinogenicity Ratings for CAS7697-37-2 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Nitric acid
2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
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): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Nitric acid
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 CAS7697-37-2 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Listed as: Nitric acid
2) Table Z-1 for Nitric acid:

a) 8-hour TWA:

1) ppm: 2

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

2) mg/m3: 5

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:
4) Skin Designation: No
5) Notation(s): Not Listed

Toxicity Information

7.7.1)

A) References: (RTECS, 2002; Lewis, 2000

Pharmacology Toxicology

Toxicologic Mechanism

A)

B)

C)

1) Chronic exposures to dangerous concentrations of the acid vapor are not frequent because of its properties as an irritant. When heated to decomposition, it emits highly toxic fumes of hydrogen nitrate and oxides of nitrogen (Lewis, 2000). However, lung damage in the absence of acute episodes has occurred from chronic exposure to nitrogen oxides and by inference could occur with nitric acid (Harbison, 1998).
2) Nitrogen oxides, when inhaled, react with water to form nitric acid in the lungs. The acid causes extensive localized damage which results in chemical pneumonitis or pulmonary edema (Haddad et al, 1998).

Physicochemical

Physical Characteristics

A)

1) The color is due to release of oxides of nitrogen (Budavari, 1996).

B)

Ph

A)

B)

Molecular Weight

A)

Other

A)

1) Currently not available (CHRIS , 2002)

Animal Toxicology

References

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NITRIC ACID

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Acid-Base

Hematologic

Dermatologic

Reproductive

Carcinogenicity

Genotoxicity

Monitoring Parameters Levels

Radiographic Studies

Methods

Life Support

Patient Disposition

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Enhanced Elimination

Case Reports

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Workplace Standards

Toxicity Information

Toxicologic Mechanism

Physical Characteristics

Ph

Molecular Weight

Other

General Bibliography