Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 75-65-0 Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • tert-Butyl alcohol
  • TERT-BUTANOL
  • 2-METHYL-2-PROPANOL
  • 2-METHYLPROPAN-2-OL
  • TBA
  • T-BUTANOL
  • TERTIARY BUTYL ALCOHOL
  • T-BUTYL HYDROXIDE
  • TRIMETHYL CARBINOL
  • TRIMETHYL METHANOL

Human Toxicity Excerpts

  • Symptomatology: 1. Central nervous system: headache, muscle weakness, giddiness, ataxia, confusion, delirium, coma. 2. Gastrointestinal: nausea, vomiting, diarrhea (odor of the alcohol in excreta). 3. Irritation of skin, eyes, throat from vapor or liquid. Cough and dyspnea. 4. Death from resp failure. 5. Disturbances of cardiac rhythm. 6. Occasional complications: a. Gastrointestinal hemorrhage b. Renal damage with glycosuria c. Liver damage d. Cardiac failure e. Pulmonary edema f. Methemoglobin formation reportedly from amyl alcohols. /Alcohols (higher)/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-14]**PEER REVIEWED**
  • TERTIARY ALCOHOLS ARE METABOLIZED SLOWLY AND INCOMPLETELY, SO THAT THEIR TOXIC EFFECTS ARE ESPECIALLY PERSISTENT. /ALCOHOLS, HIGHER/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-14]**PEER REVIEWED**
  • ... BUTYL ALCOHOLS HAVE PRODUCED FEW CASES OF POISONING IN INDUSTRY BECAUSE OF THEIR LOW VOLATILITY. /BUTYL ALCOHOLS/ [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 559]**PEER REVIEWED**
  • On the human skin, no reaction other than slight erythma and hyperemia followed the contact with ... /tert-butyl alcohol/. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 174]**PEER REVIEWED**
  • ETHANOL & CERTAIN SHORT CHAIN ARYL (BENZYL) & ALIPHATIC (PROPYL, BUTYL) ALCOHOLS PRODUCED UP TO 10 FOLD INCR IN CYCLIC AMP CONCN IN PURIFIED HUMAN PERIPHERAL BLOOD LYMPHOCYTES. ETHANOL CONCN AS LOW AS 80 MG/DL PRODUCED SIGNIFICANT ELEVATIONS IN LYMPHOCYTE CYCLIC AMP. [ATKINSON JP ET AL; J CLIN INVEST 60 (2): 284-94 (1977)]**PEER REVIEWED**
  • Application of 2-methylpropanol-2 to the skin of human volunteers resulted in only slight erythema & hyperemia. [Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. Second Edition. Volume 3 Alcohols and Esters. New York, NY: Elsevier, 1992., p. 72]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • LIKE THE OTHER BUTYL ALCOHOLS, TERTIARY BUTYL ALCOHOL IS A ... /CNS DEPRESSANT/, STRONGER IN ANIMALS THAN BUTANOL-1 OR ISOBUTYL ALCOHOL ... . [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 354]**PEER REVIEWED**
  • SYMPTOMS OF ... INTOXICATION FOLLOWING IP INJECTION IN RATS ARE VIRTUALLY IDENTICAL TO THAT OF ETHANOL, ALBEIT THAT 2-METHYLPROPANOL-2 WAS 1.5 TIMES MORE POTENT THAN ETHANOL. ... DEPRESSION OF THE CNS IN RATS WAS REPORTED AT 108 MG/KG. ... CHANGES IN ORGANISM: A SLIGHT FATTY INFILTRATION OF LIVER AND KIDNEYS WAS OBSERVED FOLLOWING DEEP NARCOSIS. AFTER IP ADMIN OF LETHAL DOSES OF 2-METHYLPROPANOL-2, POST-MORTEM EXAM OF THE LIVERS SHOWED AN ABNORMAL DARK COLORATION. [Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. Second Edition. Volume 3 Alcohols and Esters. New York, NY: Elsevier, 1992., p. 70]**PEER REVIEWED**
  • ORAL ADMIN OF TERT-BUTYL ALCOHOL IN RATS ELICITED A THREEFOLD INCR IN LIVER MICROSOMAL ENZYME ACTIVITY 24 HR LATER. [National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 697]**PEER REVIEWED**
  • IN RATS FED FOR 21 DAYS ON BALANCED LIQUID DIET CONTAINING EITHER ETHANOL (90 ML/L) OR T-BUTANOL (20 ML/L), SIGNS OF A WITHDRAWAL REACTION WERE FIRST OBSERVED 2-4 HR AFTER REMOVING ETHANOL FROM THE DIET. SIMILAR SIGNS OF WITHDRAWAL BUT MORE SEVERE AND DELAYED FOR 4-6 HR WERE OBSERVED IN ANIMALS AFTER REMOVING T-BUTANOL FROM DIET. AFTER REMOVING THE ALCOHOL, BLOOD ETHANOL LEVELS FELL BELOW THE LOWEST MEASURABLE CONCN (10 MG/100 ML) WITHIN 4 HR, WHEREAS T-BUTANOL WAS DETECTABLE FOR MORE THAN 8 HR. [WOOD J, LAVERTY R; PROC UNIV OTAGO MED SCH 54 (3): 86-7 (1976)]**PEER REVIEWED**
  • SIGNS OF INTOXICATION IN ANIMALS EXPOSED TO VAPORS OF TERT-BUTYL ALCOHOL ARE SIMILAR TO THOSE OF THE OTHER BUTYL ALCOHOLS, I.E. ATAXIA & NARCOSIS. IT HAS, HOWEVER, A STRONGER NARCOTIC ACTION UPON MICE THAN HAS NORMAL OR ISOBUTYL ALCOHOL. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 174]**PEER REVIEWED**
  • In the results for mutagenicity in L5178Y mouse lymphoma cells, t-butyl alcohol tested negative. /Dose not specified/ [NTP; Review of Current DHHS, DOE & EPA Research Related to Tox p.80 (1985) NTP-85-056]**PEER REVIEWED**
  • In the results for cytogenetic effects in Chinese hamster ovary cells, t-butyl alcohol tested negative for chromosome aberrations, and negative for sister chromatid exchanges. [NTP; Review of Current DHHS, DOE & EPA Research Related to Tox p.80 (1985) NTP-85-056]**PEER REVIEWED**
  • The effects of n-butyl and t-butyl alcohol on the respiration of electrically stimulated and unstimulated slices of rat brain cortical tissue were studied. n-Butyl alcohol, at a concn of 9 mM, and t-butyl alcohol, at a concn of 41 mM, reduced the respiration of stimulated tissue by about 11.5%, and depressed respiration of unstimulated tissue. It is concluded that the alcohols ... act primarily by interfering with mechanisms closely related to the excitation cycle in conducting membranes. [Lindbohm R, Wallgren H; Acta Pharmacol Toxicol 19 (1): 53-8 (1962)]**PEER REVIEWED**
  • In the rat, the order of incr lethality by single dose oral admin is ... ethyl, isopropyl (and sec-butyl), n-butyl, tert-butyl, isobutyl ... alcohols. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-12]**PEER REVIEWED**
  • The butyl alcohols are ... 2 to 5 times more toxic than ethanol when tested acutely in the rat. ... Toxic symptoms from butyl ... alcohol are usually more severe and more prolonged than those in ethanol intoxication. /Alcohols, higher/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-13]**PEER REVIEWED**
  • t-Butyl alcohol was evaluated for mutagenicity in the Salmonella/microsome preincubation assay using the standard protocol approved by the National Toxicology Program. t-Butyl alcohol was tested at doses of 0, 100, 333, 1000, 3333, and 10,000 ug/plate in four Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) in the presence and absence of Aroclor induced rat or hamster liver S9. t-Butyl alcohol was negative in these tests and the highest ineffective dose level tested in any Salmonella tester strain was 10,000 ug/plate. [Zeiger E et al; Environ Mutagen 9: 1-110 (1987)]**PEER REVIEWED**
  • Changes in the cytochrome p450 enzyme systems were investigated in the liver, kidney, and lung of rats exposed to butanol and its isomers at 2000 ppm for 3 days and at 500 ppm for 5 days. A pronounced increase in the microsomal p450 was observed in the kidney, with sec-butanol and tert-butanol causing 47% and 36% increases, respectively. The lung and liver microsomal p450 was unaltered. The induction of p450 was greater at lower concentration. A longer duration of exposure is required for the enzyme induction in the kidney, whereas the concentration is an important factor for its induction in the liver. [Aarstad K et al; Arch Toxicol Suppl 8: 418-21 (1985)]**PEER REVIEWED**
  • Male Wistar rats were randomly assigned to either an ethanol or t-butyl alcohol (2-methylpropan-2-ol) group (n= 10). Each rat in the ethanol group received ip injections of 0, 1.5, and 3.0 g/kg ethanol which were separated by intervals of 4 days. The t-butyl alcohol group received 0, 0.3, or 0.6 g/kg ip injections of t-butyl alcohol at 4 day intervals. Rectal temperature and blood glucose were measured immediately before and 1, 2, and 3 hr after injections. Both alcohols produced hyperglycemic and hypothermic effects whose magnitude and time course are nearly identical. Both effects were dose dependent and time dependent. Evaluation of the association between the peak thermic and glycemic responses gave a peak value from the high dose at 3 hr after injection. For t-butyl alcohol the correlation was -0.879 (n= 12). [Atrens DM et al; Alcohol 6 (3): 183-7 (1989)]**PEER REVIEWED**
  • A CORRELATION BETWEEN HYPNOTIC POTENCY OF ALIPHATIC ALCOHOL & ABILITIES TO DISRUPT STRUCTURE OF NEURONAL MEMBRANE IN VITRO WAS ESTABLISHED. SIGNIFICANT REDN IN ORDER PARAMETER WERE OBSERVED @ NERVE BLOCKING CONCN. THE FOLLOWING ALCOHOLS WERE INVESTIGATED: ETHANOL, PROPANOL, 2-PROPANOL, BUTANOL, 2-BUTANOL, 2-METHYL-1-PROPANOL, 2-METHYL-2-PROPANOL. DISORDERING POTENCY OF EACH ALCOHOL WAS CLOSELY RELATED TO ITS MEMBRANE SOLUBILITY, BASED ON OIL/WATER PARTITION COEFFICIENT. [LYON RC ET AL; J PHARMACOL EXP THER 218 (3): 669-75 (1981)]**PEER REVIEWED**
  • ... Male & female F344/N rats & B6C3F1 mice were given t-butyl alcohol (>99% pure) in drinking water for ... 2 yr. ... 2 YEAR STUDY IN RATS: Groups of 60 F344/N rats were given 0, 1.25, 2.5, or 5 mg/ml t-butyl alcohol (males) or 0, 2.5, 5, or 10 mg/ml t-butyl alcohol (females) in drinking water for 2 yr. These correspond to average daily doses of approx 90, 200, or 420 mg t-butyl alcohol/kg bw for males & approx 180, 330, or 650 mg t-butyl alcohol/kg bw for females. ... 2 YR STUDY IN MICE: Groups of 60 male & 60 female B6C3F1 mice were given 0, 5, 10, or 20 mg/ml t-butyl alcohol in drinking water for 2 yr. Exposure levels of 5, 10, or 20 mg/mL delivered average daily doses of approx 540, 1,040, or 2,070 mg t-butyl alcohol/kg bw to males & approx 510, 1,020, or 2,110 mg/kg to females. CONCLUSIONS: Under the conditions of these 2 yr drinking water studies, there was some evidence of carcinogenic activity of t-butyl alcohol in male F344/N rats based on incr incidences of renal tubule adenoma or carcinoma (combined). There was no evidence of carcinogenic activity in female F344/N rats receiving 2.5, 5 or 10 mg/ml t-butyl alcohol. There was equivocal evidence of carcinogenic activity of t-butyl aicohol in male B6C3F1 mice based on the marginally incr incidences of follicular cell adenoma or carcinoma (combined) of the thyroid gland. There was some evidence of carcinogenic activity of t-butyl alcohol in female B6C3F1 mice based on incr incidences of follicular cell adenoma of the thyroid gland. [Toxicology & Carcinogenesis Studies of t-Butyl Alcohol in F344/N Rats and B6C3F1 Mice (Drinking water Studies). Technical Report Series No. 436 (1995) NTIS Publication No. PB96-162748 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709]**PEER REVIEWED**
  • Physical dependence following admin of 2-methylpropanol-2 was described for mice, rats & guinea pigs. About 5-6 hr after removal of 2-methylpropanol-2, a delayed withdrawal syndrome occurred with muscular rigidity, stiff curled tails, tremor, irritability & forelimb convulsions. A few rats even died because of audiogenic convulsions. The symptoms of withdrawal observed with 2-methylpropanol-2 & ethanol were similar in nature. However, the potency of 2-methylpropanol-2 to produce physical dependence is about 5 times > that of ethanol. [Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. Second Edition. Volume 3 Alcohols and Esters. New York, NY: Elsevier, 1992., p. 70]**PEER REVIEWED**
  • In the rat brain cortex slices, 2-methylpropanol-2 decr the response to electrical stimulation & reduced sodium influx, while the potassium efflux was hardly affected. [Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. Second Edition. Volume 3 Alcohols and Esters. New York, NY: Elsevier, 1992., p. 71]**PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Rats oral 3.5 g/kg bw [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 174]**PEER REVIEWED**
  • LD50 Rabbit oral 3.6 g/kg bw [Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. Second Edition. Volume 3 Alcohols and Esters. New York, NY: Elsevier, 1992., p. 69]**PEER REVIEWED**
  • LD50 Mouse ip 0.9 g/kg bw [Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. Second Edition. Volume 3 Alcohols and Esters. New York, NY: Elsevier, 1992., p. 69]**PEER REVIEWED**
  • LD50 Mouse iv 1.5 g/kg bw [Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. Second Edition. Volume 3 Alcohols and Esters. New York, NY: Elsevier, 1992., p. 69]**PEER REVIEWED**
  • LD50 Mouse subcutanous 3.9 g/kg bw [Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. Second Edition. Volume 3 Alcohols and Esters. New York, NY: Elsevier, 1992., p. 69]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • TERTIARY ALCOHOL ... AT LEAST IN PART ... ARE EXCRETED IN URINE AS GLUCURONIDES. /ALCOHOLS, HIGHER/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-14]**PEER REVIEWED**
  • ... AFTER ADMIN TERT-BUTYL ALCOHOL ORALLY TO RATS @ 2 G/KG ... THERE WAS RAPID ABSORPTION INTO BLOOD; 0.98% WAS EXCRETED IN URINE. AFTER IP ADMIN IN RATS @ 0.84 G/KG, EXPONENTIAL ELIMINATION FROM BLOOD OCCURRED, BUT MORE SLOWLY THAN THAT OF OTHER ALIPHATIC ALC; BLOOD HALF-LIFE WAS 13 HR. [National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 697]**PEER REVIEWED**
  • Low molecular weight alcohols are absorbed through the skin. /Low molecular weight alcohols/ [Baier RE ed; Am Chem Soc Adv in Chemistry Series 145: 41-123 (1975)]**PEER REVIEWED**
  • Based on the relatively low octanol/water partition coefficient and the fact that 2-methylpropanol-2 does not bioaccumulate, distribution ... over total body water is expected. 2-Methylpropanol-2 has been detected in mother's milk. [Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. Second Edition. Volume 3 Alcohols and Esters. New York, NY: Elsevier, 1992., p. 67]**PEER REVIEWED**

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Metabolism/Metabolites

  • 2-METHYLPROPANOL-2, LIKE OTHER TERTIARY ALCOHOLS, IS MORE BIOLOGICALLY STABLE THAN SECONDARY BUTYL ALCOHOLS, THEREFORE LESS READILY METABOLIZED. IT UNDERGOES A RELATIVELY HIGH DEGREE OF CONJUGATION (24%) ... . [Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. Second Edition. Volume 3 Alcohols and Esters. New York, NY: Elsevier, 1992., p. 67]**PEER REVIEWED**
  • TERT-BUTANOL IS THE MOSTLY HIGHLY CONJUGATED OF THE BUTANOLS & RABBITS EXCRETE SOME 24% OF DOSE IN URINE AS THE GLUCURONIDE. [Parke, D. V. The Biochemistry of Foreign Compounds. Oxford: Pergamon Press, 1968., p. 214]**PEER REVIEWED**
  • EVIDENCE IS PRESENTED THAT T-BUTANOL SERVES AS SUBSTRATE FOR RAT LIVER MICROSOMES & THAT IT IS OXIDATIVELY DEMETHYLATED TO YIELD FORMALDEHYDE. [COHEN G, COHEN C; BIOCHEM & BIOPHYS RESEARCH COMM 97 (2): 730 (1980)]**PEER REVIEWED**
  • t-Butyl alcohol is not a substrate for alcohol dehydrogenase or for the peroxidative activity of catalase, therefore, it is used frequently as an example of a non-metabolizable alcohol. tert-Butyl alcohol is a scavenger of the hydroxyl radical and can be oxidized to formaldehyde and acetone from four different systems; (a) iron catalyzed oxidation of ascorbic acid (b) hydrogen peroxide and iron (c) coupled oxidation of xanthine oxidase, an enzymatic bound system (d) NADPH-dependent microsomal electron transfer, a membrane bound system. Because of its special biochemical properties, t-butyl alcohol may be a valuable probe for the detection of hydroxyl radicals in intact cells and in vivo. [Cederbaum AI et al; Biochem Pharmacol 32 (1983)]**PEER REVIEWED**
  • In vitro reactions with liver microsomes of mice produced tert-butanol from isobutane. [Tsukamoto S et al; J Toxicol Sci 10 (4): 323-32 (1985)]**PEER REVIEWED**
  • Male Wistar rats exposed to 50, 100, or 300 ppm methyl tertiary-butyl ether vapor ... showed ... blood concns of tert-butanol which were dose dependent indicating metabolic breakdown of the ether in vivo. [Salvolainen H et al; Arch Toxicol 57 (4): 285-8 (1985)]**PEER REVIEWED**
  • METABOLISM OF ETHANOL, PROPANOL, ISOPROPANOL, BUTANOL, ISOBUTANOL, SEC-BUTANOL, & TERT-BUTANOL WAS STUDIED AFTER ORAL ADMIN IN RABBITS. BLOOD PH WAS ON THE ACID SIDE WITH PROPANOL, BUTANOL, & ISOBUTANOL, AND ON THE ALKALINE SIDE WITH ISOPROPANOL & SEC-BUTANOL, BUT NO CHANGE WAS OBSERVED WITH ETHANOL & TERT-BUTANOL. BUTANOL & ISOBUTANOL HAD THE LOWEST RATE OF URINARY EXCRETION. ACETALDEHYDE AND ACETIC ACID WERE DETECTED AS THE URINARY METABOLITES OF ETHANOL AND PROPANOL, WHEREAS ISOBUTYRALDEHYDE & ISOVALERIC ACID WERE THE METABOLITES OF ISOBUTANOL. [SAITO M; NICHIDAI IGAKU ZASSHI 34 (8-9): 569-85 (1975)]**PEER REVIEWED**
  • The hydroxylation of isobutane led to the production of both t-butyl alcohol and isobutyl alcohol by resting cell suspensions of methane grown Methylosinus trichorsporium, at an optimum pH of 6-7, and an optimum temperature of 40 deg C. [Hou CT et al; Dev Microbiol 23: 477-82 (1982)]**PEER REVIEWED**

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TSCA Test Submissions

  • None found

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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Web page last updated on May 14, 2008