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BUTYLATED HYDROXYTOLUENE AND RELATED AGENTS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) are antioxidants commonly used as food preservatives.

Specific Substances

    A) BUTYLATED HYDROXYANISOLE
    1) BHA
    2) (1,1-dimethylethyl)-4-methoxyphenol
    3) tert-butyl-4-methoxyphenol
    4) butyl hydroxyanisole
    5) tert-butyl hydroxyanisole
    6) 2(3)-tert-butyl-4-hydroxyanisole
    7) 3(2)-tert-butyl-4-methoxyphenol
    8) CAS 25013-16-5
    BUTYLATED HYDROXYTOLUENE
    1) 2,6-BIS(1,1-DIMETHYLETHYL)-4-METHYLPHENOL
    2) 2,6-DI-TERC.BUTYL-P-KRESOL (CZECH)
    3) 2,6-DI-TERT-BUTYL-1-HYDROXY-4-METHYLBENZENE
    4) 2,6-DI-TERT-BUTYL-4-METHYLPHENOL
    5) 2,6-DI-TERT-BUTYL-P-CRESOL
    6) 2,6-DI-TERT-BUTYL-P-METHYLPHENOL
    7) 2,6-DI-TERT-BUTYLCRESOL
    8) 2,6-tert-Butyl-4-methylphenol
    9) 3,5-DI-TERT-BUTYL-4-HYDROXYTOLUENE
    10) 4-HYDROXY-3,5-DI-TERT-BUTYLTOLUENE
    11) 4-METHYL-2,6-DI-TERC. BUTYLFENOL (CZECH)
    12) 4-METHYL-2,6-DI-TERT-BUTYLPHENOL
    13) 4-METHYL-2,6-TERT BUTYLPHENOL
    14) ANTIOXIDANT 4K
    15) ANTIOXIDANT KB
    16) AO 4K
    17) Antrancine 8
    18) BHT
    19) BHT (FOOD GRADE)
    20) BUKS
    21) BUTYLATED HYDROXYTOLUENE
    22) BUTYLHYDROXYTOLUENE
    23) CAO 1
    24) CAO 3
    25) DALPAC
    26) DBPC
    27) DBPC (TECHNICAL GRADE)
    28) DEENAX
    29) DI-TERT-BUTYL-P-CRESOL
    30) DI-TERT-BUTYLCRESOL
    31) DIBUNOL
    32) DIBUTYLATED HYDROXYTOLUENE
    33) IMPRUVAL
    34) IMPRUVOL
    35) IONOL
    36) IONOL 1
    37) IONOLE
    38) Ionol CP
    39) METHYLDI-TERT-BUTYLPHENOL
    40) NCI-C03598
    41) NONOX TBC
    42) O,O'-DI-TERT-BUTYL-P-CRESOL
    43) PARABAR 441
    44) PARANOX 441
    45) PHENOL, 2,6-BIS(1,1-DIMETHYLETHYL)-4-METHYL-
    46) STAVOX
    47) SUSTANE BHT
    48) Sustane
    49) TENAMEN 3
    50) TENOX BHT
    51) TOPANOL
    52) TOPANOL O
    53) TOPANOL OC
    54) ANTIOXIDANT DBPC
    55) BDPC
    56) DBMP
    57) P 21

    1.2.1) MOLECULAR FORMULA
    1) C15-H24-O

Available Forms Sources

    A) FORMS
    1) BHT
    a) Capsules containing 250 mg are available in health food outlets.
    B) USES
    1) BHA
    a) BHA is an antioxidant commonly used as a food preservative. It also used in cosmetics, food coating materials, waxes, and vitamin A preparations (Verhagen et al, 1991). Food products regulated by the Food, Drug, and Cosmetic Act may contain BHA and BHT up to a total concentration of 0.02% of the food's total fat content. Food products regulated by the Meat Inspection Act and the Poultry Inspection Act may contain up to 0.01% of each individual antioxidant, up to a combined total of 0.02% based on the weight of the fat (Branen, 1975).
    2) BHT
    a) BHT is an antioxidant commonly used as a food preservative. Foods can contain concentrations of 0.02%, while cosmetics may contain 0.01 to 0.1% (Bardazzi et al, 1988).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) are antioxidants commonly used as food preservatives. BHT is less commonly sold as a nutritional supplement and is also used in the production of plastics, rubbers, and petroleum products. BHA is also used in cosmetics, food coating materials, waxes, and vitamin A preparations.
    B) TOXICOLOGY: Unknown.
    C) EPIDEMIOLOGY: These are very uncommon poisons with only a handful of cases reported in the literature. Large overdoses produce mild to moderate symptoms with no confirmed fatalities reported in the literature.
    D) WITH POISONING/EXPOSURE
    1) Similar toxicities of BHT and BHA are expected to occur due to similar chemical structures. All information about overdose is from a few case reports. Chewing gum containing BHT produced symptoms of a disseminated urticarial rash. BHT overdose ingestions have resulted in headaches, dizziness, syncope, drowsiness, ataxia, slurred speech, and hallucinations.
    0.2.20) REPRODUCTIVE
    A) Conflicting data appear regarding teratogenicity. BHT is excreted in the breast milk of rats.

Laboratory Monitoring

    A) Fluid and electrolyte status should be monitored, with particular attention to serum potassium levels.
    B) Monitor prothrombin time or international normalized ratio (INR) in symptomatic patients.
    C) A neurologic exam may be indicated in symptomatic patients.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) There is very little data regarding BHT and BHA toxicity; treatment is symptomatic and supportive. Correct fluid and electrolyte abnormalities in symptomatic patients.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Significant toxicity following overdose is rare.
    C) DECONTAMINATION
    1) PREHOSPITAL and /or HOSPITAL: Gastrointestinal decontamination is NOT indicated. DERMAL EXPOSURE: Ideally, decontaminate with another lipophilic agent such as polyethylene glycol; however, water, saline, and soap can be used. EYE EXPOSURE: Rinse with copious amounts of normal saline.
    D) AIRWAY MANAGEMENT
    1) Airway support is unlikely to be necessary; compromise has not been reported following overdose ingestion and is not anticipated.
    E) ANTIDOTE
    1) None.
    F) ENHANCED ELIMINATION
    1) Symptoms are self-limiting; there have been no reports of patients requiring enhanced elimination. It is unknown if hemodialysis, hemoperfusion and plasmapheresis would be useful following an oral exposure.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: Asymptomatic patients can be managed at home. Any patient with an altered mental status, weakness, or syncope should be evaluated at a healthcare facility.
    2) OBSERVATION CRITERIA: Patients with an altered mental status, weakness, or syncope should be evaluated at a healthcare facility and observed for 6 hours, or until signs and symptoms resolve.
    3) ADMISSION CRITERIA: Patients with persistent hypokalemia, ataxia, or other severe symptoms should be admitted to a medical floor. Patients with persistent hypokalemia and weakness should be monitored with telemetry.
    4) CONSULT CRITERIA: Consult a poison center or a medical toxicologist if a patient develops respiratory failure, hemodynamic instability, or any other symptoms not expected with this exposure.
    H) PITFALLS
    1) Common errors for managing these patients include failing to screen electrolytes, failing to look for other exposures, and not identifying other similar presenting medical conditions.
    I) DIFFERENTIAL DIAGNOSIS
    1) Altered mental status may also be produced by a wide range of toxic exposures (eg, alcohols, anticonvulsant, antidepressant, antipsychotic, hallucinogen, sedative-hypnotic, opioid, withdrawal) and non-toxicologic causes (eg, CNS or systemic infection, hypercarbia, hypoglycemia, hypoxemia, intracranial bleeding, trauma). Hypokalemia can be produced by other toxic exposures (eg, catecholamines, chloroquine, diuretics, hydrocarbons, insulin).
    0.4.4) EYE EXPOSURE
    A) Rinse with copious amounts of normal saline.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Ideally, decontaminate with another lipophilic agent such as polyethylene glycol; however, water, saline, and soap can be used. The urticarial rash is usually self-limiting and does not require specific treatment, although antihistamines can be used.

Range Of Toxicity

    A) TOXICITY: Case reports show that symptoms can develop anywhere from 4 to 80 grams in an adult. A toxic dose has not been reported in children. BHA: Ingestion of 0.5 mg/kg for 10 days appeared to be well-tolerated in healthy volunteers.

Clinical Effects

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) VASCULITIS
    1) BHT/CASE REPORT: A disseminated urticarial eruption of the legs, forearms, abdomen, and back occurred in a 30-year-old woman following a recent dietary change of regularly chewing gum containing chlorophylla (E140), menthol, and BHT. Within 1 week following cessation of chewing the gum, the eruption resolved; however, the eruption recurred following oral rechallenge with BHT (Moneret-Vautrin et al, 1986).
    B) CONTACT DERMATITIS
    1) Allergic contact dermatitis has been reported following use of foods, cosmetics, and pharmaceuticals containing BHT (Dissanayake & Powell, 1989; Bardazzi et al, 1988) and BHA (Fisher, 1986; Tosti et al, 1987).

Musculoskeletal

    3.15.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) MUSCLE WEAKNESS
    a) Muscle weakness was reported following chronic administration to animals and was attributed to potassium depletion (Deichmann et al, 1955).

Reproductive

    3.20.1) SUMMARY
    A) Conflicting data appear regarding teratogenicity. BHT is excreted in the breast milk of rats.
    3.20.2) TERATOGENICITY
    A) MENINGOMYELOCELE
    1) CASE REPORT - Conflicting data appear regarding teratogenicity. BHT has been documented in cord blood of an infant born with a lumbrosacral meningomyocele (Dowty et al, 1976).
    B) MENTAL STATUS CHANGES
    1) MICE - Behavioral abnormalities have been noted in offspring of pregnant mice who were fed BHT (Malkinson, 1983).
    C) LACK OF EFFECT
    1) MONKEYS - Studies in rhesus monkeys demonstrated no adverse fetal effects (Allen, 1976).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) RATS - BHT is excreted in the breast milk of rats. Hyperactive behavior was noted in nursing offspring of rats treated with BHT (Meyer & Hansen, 1980).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS128-37-0 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) IARC Classification
    a) Listed as: Butylated hydroxytoluene (BHT)
    b) Carcinogen Rating: 3
    1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    B) IARC Carcinogenicity Ratings for CAS2503-16-5 (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) HUMAN STUDIES
    A) CARCINOMA
    1) BHT does not appear to be carcinogenic by itself. When combined with other mutagens, BHT augments the tumor-promoting effects of some carcinogens (ie, radiation, urethane) but protects against the effects of others (benzo-a-pyrene, aminoanthracene, homidium, proflavine) (Malkinson, 1983).
    2) Dietary levels of 2% BHA induced squamous cell tumors of the forestomach in rodents. Similar epithelial tissue is found in the esophagus, pharynx, larynx, oral cavity, and anorectal junction in humans. BHA had no effect on esophageal tissue in the rodents, presumably due to rapid transit time, limiting the extent of exposure. It is felt that BHA does not pose a human risk of esophageal cancer at food additive levels (Grice, 1988).

Summary Of Exposure

    A) USES: Butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) are antioxidants commonly used as food preservatives. BHT is less commonly sold as a nutritional supplement and is also used in the production of plastics, rubbers, and petroleum products. BHA is also used in cosmetics, food coating materials, waxes, and vitamin A preparations.
    B) TOXICOLOGY: Unknown.
    C) EPIDEMIOLOGY: These are very uncommon poisons with only a handful of cases reported in the literature. Large overdoses produce mild to moderate symptoms with no confirmed fatalities reported in the literature.
    D) WITH POISONING/EXPOSURE
    1) Similar toxicities of BHT and BHA are expected to occur due to similar chemical structures. All information about overdose is from a few case reports. Chewing gum containing BHT produced symptoms of a disseminated urticarial rash. BHT overdose ingestions have resulted in headaches, dizziness, syncope, drowsiness, ataxia, slurred speech, and hallucinations.

Heent

    3.4.3) EYES
    A) IRRITATION: Dust may be an eye irritant.
    3.4.5) NOSE
    A) IRRITATION: Dust may be a nose and throat irritant.

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) BRONCHOSPASM
    1) BHT-sensitive patients who were challenged with 125 to 250 mg of BHT orally developed exacerbation of asthma and vasomotor rhinitis (Fisherman & Cohen, 1973).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RESPIRATORY DISORDER
    a) MICE: Administration of BHT to certain strains of mice in doses of 250 mg/kg or greater, produces damage to type I pneumocytes in the lung. This effect is enhanced in the presence of BHA (Thompson & Trush, 1988). A reactive metabolite of BHT, BHT-quinone methide, is responsible for toxicity (Yamamoto et al, 1988). Lung damage does not appear to occur in other animal species (Witschi et al, 1989).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) WITH POISONING/EXPOSURE
    a) BHT: Weakness, followed by dizziness and a brief loss of consciousness has been reported (Shlian & Goldstone, 1986).
    B) DROWSY
    1) BHA/CASE SERIES: Drowsiness was reported in 4 of 7 subjects given 300 to 450 mg of BHA orally (Cloninger & Novey, 1974).
    C) DISTURBANCE IN SPEECH
    1) WITH POISONING/EXPOSURE
    a) BHT/CASE REPORT: Dizziness, ataxia, and slurred speech were described following ingestion of 80 grams in a 24-year-old woman (Grogan, 1986).
    D) HALLUCINATIONS
    1) WITH POISONING/EXPOSURE
    a) BHT/CASE REPORT: Visual and auditory hallucinations were described for several hours after ingestion of 80 grams in a 24-year-old woman (Grogan, 1986).
    E) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) BHT/CASE REPORT: Severe frontal headache began within several hours of ingestion of 80 grams (Grogan, 1986).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) WITH POISONING/EXPOSURE
    a) BHT/CASE REPORT: Ingestion of 4 grams BHT by a 22-year-old caused epigastric pain and vomiting (Shlian & Goldstone, 1986).

Hepatic

    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATIC NECROSIS
    a) MICE: Administration of BHT 500 mg/kg orally to glutathione-depleted mice resulted in extensive centrilobular necrosis by 24 hours. Administration of 1800 mg of BHT in the absence of a glutathione-depletor did not result in any liver histopathology (Mizutani et al, 1987).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) COAG./BLEEDING TESTS ABNORMAL
    1) BHT: Bleeding time was prolonged in 7 BHT-sensitive patients challenged orally with 125 to 250 mg of BHT (Fisherman & Cohen, 1973).
    B) METHEMOGLOBINEMIA
    1) CASE SERIES: An outbreak of methemoglobinemia in a pediatric ward (ages 6 to 15 weeks) was associated with the addition of an antioxidant mixture containing BHT, BHA, and propyl gallate to the infant formula (Nitzan et al, 1979).
    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) PROTHROMBIN DECREASED
    a) Hypoprothrombinemia resulting in fatal hemorrhage has been seen in some laboratory animals. The minimum amount to produce hypoprothrombinemia was 0.017% for one week, the equivalent of 14.7 mg/kg/day in humans (Takahashi & Hiraga, 1978). These abnormalities were corrected by administration of vitamin K.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Fluid and electrolyte status should be monitored, with particular attention to serum potassium levels.
    B) Monitor prothrombin time or international normalized ratio (INR) in symptomatic patients.
    C) A neurologic exam may be indicated in symptomatic patients.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Fluid and electrolyte status should be monitored in significant acute or chronic ingestions, with particular attention to serum potassium levels.
    B) COAGULATION STUDIES
    1) Monitor prothrombin time or international normalized ratio (INR) in symptomatic patients.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) A neurologic exam may be indicated in symptomatic patients.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with persistent hypokalemia, ataxia, or other severe symptoms should be admitted to a medical floor. Patients with persistent hypokalemia and weakness should be monitored with telemetry.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Asymptomatic patients can be managed at home. Any patient with an altered mental status, weakness, or syncope should be evaluated at a healthcare facility.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or a medical toxicologist if a patient develops respiratory failure, hemodynamic instability, or any other symptoms not expected with this exposure.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with an altered mental status, weakness, or syncope should be evaluated at a healthcare facility and observed for 6 hours, or until signs and symptoms resolve.

Monitoring

    A) Fluid and electrolyte status should be monitored, with particular attention to serum potassium levels.
    B) Monitor prothrombin time or international normalized ratio (INR) in symptomatic patients.
    C) A neurologic exam may be indicated in symptomatic patients.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) PREHOSPITAL: Gastrointestinal decontamination is NOT indicated. Dermal exposures should be irrigated with water to remove the exposure.
    6.5.2) PREVENTION OF ABSORPTION
    A) Gastrointestinal decontamination is not indicated.
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) There is very little data regarding BHT and BHA toxicity; treatment is symptomatic and supportive. Correct fluid and electrolyte abnormalities in symptomatic patients.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treatment is symptomatic and supportive. Significant toxicity following overdose is rare.
    B) MONITORING OF PATIENT
    1) Fluid and electrolyte status should be monitored, with particular attention to serum potassium levels.
    2) Monitor prothrombin time or international normalized ratio (INR) in symptomatic patients.
    3) A neurologic exam may be indicated in symptomatic patients.

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).
    6.9.2) TREATMENT
    A) SUPPORT
    1) The urticarial rash is usually self-limiting and does not require specific treatment, although antihistamines can be used.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) SUMMARY
    1) Symptoms are self-limiting; there have been no reports of patients requiring enhanced elimination. It is unknown if hemodialysis, hemoperfusion and plasmapheresis would be useful following an oral exposure.

Abstracts

Case Reports

    A) ADULT
    1) BHT: Ingestion of 4 grams of BHT by a 22-year-old woman resulted in epigastric cramps, weakness, vomiting, within several hours followed by dizziness, confusion and brief loss of consciousness due to dehydration within 48 hours (Shlian & Goldstone, 1986).
    2) BHT: Ingestion of 80 grams of BHT by a 24-year-old woman resulted in dizziness and euphoria within 30 to 60 minutes, followed by frontal headache and hallucinations within several hours. Ataxia, dysarthria, and slow mentation were seen on examination. No electrolyte abnormalities were found (Grogan, 1986).

Range Of Toxicity

Summary

    A) TOXICITY: Case reports show that symptoms can develop anywhere from 4 to 80 grams in an adult. A toxic dose has not been reported in children. BHA: Ingestion of 0.5 mg/kg for 10 days appeared to be well-tolerated in healthy volunteers.

Therapeutic Dose

    7.2.1) ADULT
    A) SUMMARY
    1) Based on unknown criteria, the FDA has recommended a safe level of ingestion of BHT in foods at amounts not to exceed 0.5 milligrams per kilogram per day or 0.02 parts per million (Malkinson, 1983).
    7.2.2) PEDIATRIC
    A) SUMMARY
    1) The estimated daily intake of BHT is 2 to 9 milligrams per kilogram in children under 2, and 0.5 to 1.5 milligrams per kilogram in older children (FASEB, 1973).

Maximum Tolerated Exposure

    A) SPECIFIC SUBSTANCE
    1) BHT
    a) 4 grams produced gastritis in an adult (Shlian & Goldstone, 1986).
    b) 80 grams produced hallucinations, dysarthria and ataxia in an adult with no neurologic sequelae (Grogan, 1986).
    c) No evidence of human toxicity was reported following chronic ingestion of up to 6 grams daily for 30 days (Anon, 1978).
    2) BHA
    a) Ingestion of 0.5 milligram/kilogram BHA for 10 days produced no adverse effects in healthy volunteers (Verhagen & Kleinjans, 1989).

Workplace Standards

    A) ACGIH TLV Values for CAS128-37-0 (American Conference of Governmental Industrial Hygienists, 2010):
    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) Butylated hydroxytoluene (BHT)
    a) TLV:
    1) TLV-TWA: 2 mg/m(3)
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: IFV
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    b) IFV: Inhalable fraction and vapor.
    c) TLV Basis - Critical Effect(s): URT irr
    d) Molecular Weight: 220.34
    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) Under Study
    1) Butylated hydroxytoluene (BHT)
    a) TLV:
    1) TLV-TWA:
    2) TLV-STEL:
    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):
    d) Molecular Weight:
    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) ACGIH TLV Values for CAS2503-16-5 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    C) NIOSH REL and IDLH Values for CAS128-37-0 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: 2,6-Di-tert-butyl-p-cresol
    2) REL:
    a) TWA: 10 mg/m(3)
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH: Not Listed

    D) NIOSH REL and IDLH Values for CAS2503-16-5 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    E) Carcinogenicity Ratings for CAS128-37-0 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Butylated hydroxytoluene (BHT)
    a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    2) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Butylated hydroxytoluene (BHT)
    3) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    4) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 3 ; Listed as: Butylated hydroxytoluene (BHT)
    a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    5) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: 2,6-Di-tert-butyl-p-cresol
    6) MAK (DFG, 2002): Not Listed
    7) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    F) Carcinogenicity Ratings for CAS2503-16-5 :
    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

    G) OSHA PEL Values for CAS128-37-0 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

    H) OSHA PEL Values for CAS2503-16-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAPERITONEAL)MOUSE:
    1) 138 mg/kg (Lewis, 1996)
    B) LD50- (ORAL)MOUSE:
    1) 650 mg/kg (Lewis, 1996)
    C) LD50- (ORAL)RAT:
    1) 1700-1900 mg/kg (Deichmann et al, 1955)
    2) 890 mg/kg (Lewis, 1996)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) BHT is being promoted in daily doses of 250 to 2000 mg up to 6 grams/day for the prevention of genital herpes infections and certain types of cancer. There is no clinical evidence of efficacy for any of these conditions (Llaurado, 1983).

Toxicologic Mechanism

    A) It is theorized that BHT-quinone methide, an active metabolite of BHT, is responsible for disturbing the vitamin K redox cycle in BHT-induced hemorrhage (Takahashi, 1988) 1991).

Physicochemical

Physical Characteristics

    A) BHT: white crystalline solid, with a faint phenolic odor
    B) BHA: white or slightly yellow waxy solid with a faint phenolic odor

Molecular Weight

    A) BHT: 220.4
    B) BHA: 180.25

References

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