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BUTYRIC ACID

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Butyric acid is an industrial chemical used for chemical synthesis and as a food additive.

Specific Substances

    A) No Synonyms were found in group or single elements

Available Forms Sources

    A) USES
    1) MANUFACTURING: Used in the manufacture of artificial flavorings (esters), as a food additive, to decalcify hides, and in the production of varnishes.
    2) FOODS: Found in essential oils of various herbs and spices, and in butter (as the ester) in concentrations of 4 to 5% (Budavari, 1989).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Butyric acid is a mild to moderate irritant that causes easily reversible changes after termination of exposure.
    B) Systemic symptoms are unlikely, but if large amounts were ingested, nausea, vomiting, and CNS depression might occur. Inhalation of high concentrations may produce dyspnea and bronchial irritation.
    0.2.4) HEENT
    A) EYES - Liquid may burn skin and eyes. Vapor is irritating to eyes.
    B) NOSE - Vapor is irritating to nose.
    C) THROAT - Vapor is irritating to throat. If inhaled will cause coughing.
    0.2.5) CARDIOVASCULAR
    A) In animals, small doses produce little or no effect. Larger doses may depress blood pressure and impair cardiac function.
    0.2.6) RESPIRATORY
    A) May cause coughing or dyspnea if inhaled.
    0.2.7) NEUROLOGIC
    A) Animals given large intravenous doses develop CNS depression and convulsions.
    0.2.8) GASTROINTESTINAL
    A) Necrotic changes were seen in the gastrointestinal system when mice were fed 500 mg/kg.
    0.2.10) GENITOURINARY
    A) Necrotic changes were seen in the kidneys, bladder, and ureter when mice were given 500 mg/kg orally.
    0.2.13) HEMATOLOGIC
    A) Increases in lymphocytes and neutrophils were seen in experimental animals. Splenic changes were seen in mice fed 500mg/kg.
    0.2.14) DERMATOLOGIC
    A) A mild to moderate dermal irritant, causing erythema, burning, and epidermal scaling.
    0.2.16) ENDOCRINE
    A) In animals it has been shown to cause an increase in plasma insulin and a small rise in plasma pancreatic glucagon.
    0.2.20) REPRODUCTIVE
    A) In a frog embryo teratogenesis assay, microencephaly and defects in eye and gut formation were most commonly seen.

Laboratory Monitoring

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

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) 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.
    B) Because of potential GI tract irritation, do NOT induce emesis.
    C) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    D) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    0.4.3) INHALATION EXPOSURE
    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.
    0.4.4) EYE EXPOSURE
    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) DERMAL EXPOSURE
    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).

Range Of Toxicity

    A) No human data was found. In animals, atmospheric concentrations of 40 milligrams per liter produced lethargy and dyspnea within 90 minutes.

Clinical Effects

Summary Of Exposure

    A) Butyric acid is a mild to moderate irritant that causes easily reversible changes after termination of exposure.
    B) Systemic symptoms are unlikely, but if large amounts were ingested, nausea, vomiting, and CNS depression might occur. Inhalation of high concentrations may produce dyspnea and bronchial irritation.

Heent

    3.4.1) SUMMARY
    A) EYES - Liquid may burn skin and eyes. Vapor is irritating to eyes.
    B) NOSE - Vapor is irritating to nose.
    C) THROAT - Vapor is irritating to throat. If inhaled will cause coughing.
    3.4.3) EYES
    A) BURNS - Liquid will burn skin and eyes. Vapor is irritating to eyes (HSDB , 1994).
    B) ANIMAL STUDIES
    1) RABBITS - An unspecified volume of a 5% solution produced severe corneal damage (Smyth et al, 1954).
    2) RABBITS - In a standard open Draize test, 250 micrograms was applied to rabbit eyes, resulting in a severe reaction (RTECS , 1994).
    3) EWES - Continuous infusion of butyrate decreased ruminal epithelial cell proliferation and caused a thickening of the stratum corneum. Daily short-term infusions produced stimulation of ruminal epithelial cell proliferation.
    a) Histological examination revealed parakeratotic changes in the stratum corneum (Galfi, 1986).
    4) CHICKENS - Butyric acid was added to the normal diet of 5 day old chickens at 15 mM/L; the stimulating effect on keratinization was not restricted to ruminal epithelium, but also occurred in the crop (Galfi, 1985).
    3.4.5) NOSE
    A) Vapor is irritating to nose (HSDB , 1994).
    3.4.6) THROAT
    A) Vapor is irritating to throat. When inhaled may cause coughing (HSDB , 1994).

Cardiovascular

    3.5.1) SUMMARY
    A) In animals, small doses produce little or no effect. Larger doses may depress blood pressure and impair cardiac function.
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Small doses produce little effect (Clayton & Clayton, 1982).
    b) Large doses depress blood pressure and impair cardiac function. This may be due to formation of the ketone bodies beta-hydroxybutyrate and acetoacetate (von Oettingen, 1960).

Respiratory

    3.6.1) SUMMARY
    A) May cause coughing or dyspnea if inhaled.
    3.6.2) CLINICAL EFFECTS
    A) TOXIC INHALATION INJURY
    1) May cause coughing and dyspnea if inhaled (CHRIS , 1994).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) RABBITS - Exposure to 40 milligrams per liter in the air for 90 minutes produced dyspnea, bronchial and capillary dilation, and emphysema (Danishevskii & Monastyrskaya, 1960).

Neurologic

    3.7.1) SUMMARY
    A) Animals given large intravenous doses develop CNS depression and convulsions.
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) RABBITS - 1.6 grams per kilogram of the sodium salt IV produced CNS depression (von Oettingen, 1960).
    b) Atmospheric concentrations of 40 milligrams per liter for 90 minutes produced lethargy (Danishevskii & Monastyrskaya, 1960).
    c) DOG - 860 milligrams per kilogram of the sodium salt IV produced CNS depression (von Oettingen, 1960).
    2) SEIZURES
    a) MOUSE - 800 milligrams/kilogram given intravenously produced convulsions and altered the seizure threshold (RTECS , 1994).

Gastrointestinal

    3.8.1) SUMMARY
    A) Necrotic changes were seen in the gastrointestinal system when mice were fed 500 mg/kg.
    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) MOUSE - Necrotic changes were seen in the gastrointestinal system when mice were fed 500 milligrams/kilogram (Toksikologiya Novykh Promyshlennykh Khimicheskikh Veshchestv, 1962).

Genitourinary

    3.10.1) SUMMARY
    A) Necrotic changes were seen in the kidneys, bladder, and ureter when mice were given 500 mg/kg orally.
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) MOUSE - Necrotic changes were seen in the kidneys, bladder, and ureter when mice were given 500 milligrams/kilogram orally (Toksikologiya Novykh Promyshlennykh Khimicheskikh Veshchestv, 1962).

Hematologic

    3.13.1) SUMMARY
    A) Increases in lymphocytes and neutrophils were seen in experimental animals. Splenic changes were seen in mice fed 500mg/kg.
    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) INHALATION EXPOSURE - Mice, rats, and rabbits exposed to air concentrations of 0.1 to 0.2 milligrams per liter of butyric acid developed massive increases in the number of circulating lymphocytes and neutrophils (Stasenkova & Kochetkova, 1962).
    2) SPLEEN DISORDER
    a) MOUSE - Changes were seen in the spleens of mice fed 500 milligrams/kilogram (Toksikologiya Novykh Promyshlennykh Khimicheskikh Veshchestv, 1962).

Dermatologic

    3.14.1) SUMMARY
    A) A mild to moderate dermal irritant, causing erythema, burning, and epidermal scaling.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) Butyric acid is a mild dermal irritant (Budavari, 1989). CHRIS (1994) calls it a moderate irritant, stating that second degree burns may occur after a few minutes of contact.
    2) EXPERIMENTAL APPLICATION when applied to intact skin for 52 minutes, erythema was just noticeable, and there was only a moderate burning sensation followed by epidermal scaling over the next 24 hours (Oettel, 1936).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) RABBITS - In the closed rabbit skin patch irritation test, 10 mg of butyric acid produced a severe reaction in 24 hours; in the open test, 500 mg elicited only a moderate response (Clayton & Clayton, 1982).

Endocrine

    3.16.1) SUMMARY
    A) In animals it has been shown to cause an increase in plasma insulin and a small rise in plasma pancreatic glucagon.
    3.16.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) LAMBS - The role of autonomic innervation in the control of pancreatic endocrine responses to IV infusions of butyrate was investigated in conscious 4 to 6 month old weaned lambs (Bloom & Edwards, 1985).
    1) IV butyrate produced a small rise in mean arterial plasma pancreatic glucagon concentration which was unlikely to have had any physiological effect and produced no consistent or statistically significant changes in mean plasma pancreatic polypeptide concentration in any of the groups studied.
    2) In contrast, butyrate produced an abrupt and substantial rise in mean plasma insulin concentration which rose to a peak incremental value of about 300 pica mol/L in normal control.

Reproductive

    3.20.1) SUMMARY
    A) In a frog embryo teratogenesis assay, microencephaly and defects in eye and gut formation were most commonly seen.
    3.20.2) TERATOGENICITY
    A) CONGENITAL ANOMALY
    1) Human data were not found.
    2) ANIMAL STUDIES
    a) FROGS - Dawson (1991) found, using a frog embryo teratogenesis assay, that 50% of the offspring were malformed at 400 mg per liter. Microencephaly and defects in eye and gut formation were most commonly seen.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS107-92-6 (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

Genotoxicity

    A) May induce a marked reduction in the growth rate, colony forming efficiency in soft agar, de novo synthesis of DNA, as well as inducing morphological changes.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    B) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring urinalysis is suggested for patients with significant exposure.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    4.1.3) URINE
    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.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

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

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Dilution may be helpful since butyric acid is a mild irritant. Emesis would NOT be necessary; if large amounts were ingested, CNS depression might occur.
    B) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    C) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) There is no specific antidote; observe for extensive vomiting, electrolyte loss, or CNS depression.
    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).

Inhalation Exposure

    6.7.1) DECONTAMINATION
    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) TREATMENT
    A) SUPPORT
    1) No specific treatment is indicated. Use symptomatic measures for specific symptoms.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    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).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) 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).

Range Of Toxicity

Summary

    A) No human data was found. In animals, atmospheric concentrations of 40 milligrams per liter produced lethargy and dyspnea within 90 minutes.

Minimum Lethal Exposure

    A) ANIMAL DATA
    1) Lethal concentrations via inhalation could not be reached in tests with mice, rats, and rabbits (Stasenkova & Kochetkova, 1962; Smyth et al, 1951).

Maximum Tolerated Exposure

    A) ANIMAL DATA
    1) RABBITS - Atmospheric concentrations of 40 milligrams per liter produced lethargy and dyspnea within 90 minutes (Danishevskii & Monastyrskaya, 1960).

Workplace Standards

    A) ACGIH TLV Values for CAS107-92-6 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS107-92-6 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS107-92-6 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    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
    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 CAS107-92-6 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAPERITONEAL)MOUSE:
    1) 3180 mg/kg (RTECS, 1994)
    B) LD50- (SUBCUTANEOUS)MOUSE:
    1) 3180 mg/kg (RTECS, 1994)
    C) LD50- (ORAL)RAT:
    1) 8.79 g/kg (Budavari, 1989)
    2) 2 g/kg (Izmerov et al, 1982)

Pharmacology Toxicology

Toxicologic Mechanism

    A) Local irritant (Clayton & Clayton, 1982)

Physicochemical

Physical Characteristics

    A) This compound exists as an oily, colorless liquid with an odor like rancid butter (CHRIS , 1994; HSDB , 1994).

Molecular Weight

    A) 88.10 (HSDB , 1994)

Other

    A) ODOR THRESHOLD
    1) 0.001 ppm (CHRIS , 1994)

References

General Bibliography

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