2-methylpropan-2-ol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Single dose, 14-day post exposure observation period

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to generally accepted guidelines for acute oral study

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-methylpropan-2-ol

EC Number:

200-889-7

EC Name:

2-methylpropan-2-ol

Cas Number:

75-65-0

Molecular formula:

C4H10O

IUPAC Name:

2-methylpropan-2-ol

Constituent 2

Reference substance name:

tertiary butyl alcohol

IUPAC Name:

tertiary butyl alcohol

Details on test material:

-Identity (according to report): t-butyl alcohol
-Purity: 99.9% per sponsor

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
-Source: Charles River Laboratories Inc., Portage Michigan
-Animals: 20 males, 20 females
-Age: young adult
-Quarantine period: 12 to 18 days
-Weight at study initiation: 200-291 grams
-Housing: individual hanging wire-mesh cages
-Diet: Purina® Certified Rodent Chow® #5002
-Identification method: ear tag
-Method of Animal Distribution: computer-generated table of random numbers

ENVIRONMENTAL CONDITIONS: no information

IN-LIFE DATES:
-Date of study initiation: 13 May 1981
-Date of study termination: 27 May 1981

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Each dose of undiluted material was warmed to 30 °C before administration by gastric intubation. Each animal received a single dose.

Doses:

1950 mg/kg bw (2.6 mL/kg bw); 2535 mg/kg bw (3.4 mL/kg bw); 3296 mg/kg bw (4.4 mL/kg bw); 4285 mg/kg bw (5.7 mL/kg bw)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

-Duration of observation period following administration: 14 days
-Mortality/morbidity evaluation: 0-4 hr, then daily
-Body weights: no information on frequency of examination
-Observation of clinical signs: daily
-Necropsy of survivors performed: yes
-Gross pathology exam: all animals

Statistics:

The following references were cited for estimation of the LD50 (95% Confidence Limits):

Weil C.S., 1952. Tables for Convenient Calculation of Median Effective Dose and Instruction in Their Use, Biometrics, 8:249-263.

Thompson, WR and Weil, CS, 1952. On the Construction Tables for Moving Average Interpolation, Biometrics, 8:51/54.

Eby, R, 1957. Statistical Tables for Dose Evaluation, Report No. 5711, Miles-Ames Research Laboratory, Elkhart, Indiana.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

3 384 mg/kg bw

95% CL:

2 975 - 3 848

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

2 743 mg/kg bw

95% CL:

2 470 - 3 046

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 046 mg/kg bw

95% CL:

2 768 - 3 353

Effect levels 4

Sex:

male/female

Dose descriptor:

other: LOAEL

Effect level:

1 950 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Clinical signs observed at the LOAEL included piloerection, ataxia, decreased limb tone and low carriage. Surviving rats normal by Day 5 at this dose level. No deaths in male or female rats seen at this dose level.

Mortality:

No deaths occurred in either sex in the 1950 mg/kg bw dose group. One female died on Day 5 in the 2535 mg/kg bw dose group. Two males died on Day 1 and all females were dead by Day 3 in the 3296 mg/kg bw group. All animals died by Day 3 in the 4285 mg/kg bw group.

Clinical signs:

other: Piloerection, ataxia, decreased limb tone and low carriage were observed in all dose groups. Major clinical signs in the 2535, 3296 and 4285 mg/kg bw dose groups were prostration, impaired righting reflex, bradypnea, hypoactivity and lacrimation. Most o

Gross pathology:

No compound-related macroscopic lesions were observed in the low-dose group. Test-material related hemorrhage and congestion in various visceral organs were observed in a few animals during postmortem examination of animals dying on study or sacrificed at the termination of the study. This effect on blood vessel integrity was found generally among males and females in the two highest dose groups.

Applicant's summary and conclusion

Interpretation of results:

other: Classified as Category V according to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) but there is no Category 5 in CLP regulation (EC) No. 1272/2008; classified as Category 3 for Specific Target Organ Toxicity.

Remarks:

Criteria used for interpretation of results: OECD GHS

Conclusions:

In an acute oral toxicity test, the oral LD50 was 3384 mg/kg bw in male rats, 2743 mg/kg bw in female rats, and 3046 mg/kg bw for both sexes combined when administered a single dose of tertiary butyl alcohol. Clinical signs indicating reversible effects on the central nervous system included piloerection, ataxia, decreased limb tone, low carriage, prostration, impaired righting reflex, bradypnea, hypoactivity and lacrimation. Signs were generally dose dependent and occurred more frequently in the higher dose groups.

Based on LD50 values of >2000 but <5000 mg/mg bw for male and female rats, tertiary butyl alcohol would be classified as Category V for acute lethality by the oral route under UN GHS; however, there is no Category V in CLP regulation No. 1272/2008. Therefore, tertiary butyl alcohol is not classified for acute lethality according to EU CLP GHS in this study. Based on clinical signs indicating reversible effects on the central nervous system, tertiary butyl alcohol is classified as Category 3 for classification and labeling under GHS for Specific Target Organ Toxicity – Single Exposure.

Executive summary:

Under the conditions of this study, the oral LD50 of tertiary butyl alcohol is 3384 mg/kg bw in male rats, 2743 mg/kg bw in female rats, and 3046 mg/kg bw combined.  Exposure to large oral doses of tertiary butyl alcohol may cause transient, reversible CNS effects.  Similar LD50 values and clinical signs were observed in studies conducted by Schaffarzick and Brown (1952) and Munch (1972).