Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

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

Constituent 1
Chemical structure
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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
3 384 mg/kg bw
95% CL:
2 975 - 3 848
Sex:
female
Dose descriptor:
LD50
Effect level:
2 743 mg/kg bw
95% CL:
2 470 - 3 046
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 046 mg/kg bw
95% CL:
2 768 - 3 353
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:
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 of these signs were observed more frequently in the highest dose groups. Some rats which received 3296 and 4285 mg/kg bw also exhibited hypothermia and hypopnea. Most surviving rats appeared normal by Day 8.
Body weight:
No remarkable changes or differences were observed during the study period.
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).