Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24-hr application followed by 14-day observation period
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to generally accepted guidelines for acute dermal study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
, see principles of test method.
Qualifier:
equivalent or similar to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
, see principles of test method.
Principles of method if other than guideline:
Test parameters were similar to those outlined in EPA OPPTS 870.1200 and EU Method B.3. However, there was no information provided on environmental conditions in the test area, test material was applied to abraded skin only, and there was no information provided on method of test material application, i.e. occluded vs. non-occluded.
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
-Identity (according to report): t-butyl alcohol
-Purity: 99.9% per sponsor

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS:
-Source: Kuiper's Rabbit Ranch, Gary, Indiana
-Animals: 5/sex
-Age: young adult
-Quarantine period: 16 days
-Weight at study initiation: 2409-3400 grams
-Housing: individual hanging wire-mesh cages
-Diet: Purina® Certified Rabbit Chow® #5322
-Identification method: ear tag
-Method of Animal Distribution: computer-generated table of pseudo-random numbers

ENVIRONMENTAL CONDITIONS: no information

IN-LIFE DATES:
-Date of study initiation: 24 April 1981
-Date of study termination: 8 May 1981

Administration / exposure

Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
A single dose was administered undiluted as received to each of ten animals. Application was to abraded skin for 24 hours.
Duration of exposure:
24 hours
Doses:
1 dose at 2000 mg/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: daily
-Body weights: evaluated; no information on frequency of examination during the study period
-Observation of clinical signs: daily
-Evaluation of Dermal Irritation: both treated and untreated skin of each rabbit was evaluated and scored (range of 0-none to 3-marked) for erythema, edema, atonia, desquamation, coriaceousness, fissuring, eschar and exfoliation.
-Necropsy performed: yes on all animals
-Gross pathology exam: all animals
-Histopathology: treated and untreated skin was examined in each animal

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Effects observed included ataxia, prostration, ocular discharge and moderate skin irritation.
Mortality:
None of the rabbits died during the study period.
Clinical signs:
The major effects observed during the study period were ataxia in all animals and injected iris (both eyes) in 5 males and 4 females. One male rabbit also exhibited prostration. All of the rabbits appeared normal by Day 1 with the exception of one female which exhibited purulent ocular discharge on Days 6-14. Based on the latency period and the relative lack of irritation at earlier observation periods or in other animals, it is unlikely that this effect was related to test material administration.
Body weight:
No remarkable changes or differences were observed in the body weights during the study period.
Gross pathology:
There were no compound-related macroscopic changes observed during post mortem examination of animals sacrificed at the termination of the study.
Other findings:
Microscopically, dermal inflammatory cell infiltrate occurred in both treated and untreated skin of rabbits. However, in general, the severity and extent of these changes were comparatively less in the untreated skins. Trace or mild acanthosis and hyperkeratosis were seen in the treated skin of five rabbits (one male and four females), but not in any of the untreated skins examined. Mild dermal fibroplasia was observed in the treated skin of four rabbits (one male and three females), but was absent in any of the untreated skin examined.

All of the rabbits exhibited the following signs of dermal irritation: erythema, edema and desquamation ranging from very slight (score 0.5) to moderate (score 2.0-2.5), and fissuring ranging from very slight (score 0.5) to slight (score 1.0-1.5). Coriaceousness and atonia ranging from very slight (score 0.5) to slight (score 1.0-1.5) were observed in some animals.

Any other information on results incl. tables

Based upon the data obtained, the Minimum Lethal Dose (MLD) for tertiary butyl alcohol -99.9% was found to be greater than 2000 mg/kg bw when administered once dermally to albino rabbits for 24 hours.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified for Acute Toxicity; classified as Category 3 for Specific Target Organ Toxicity – Single Exposure
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
In an acute dermal toxicity test, no deaths were reported when a limit dose of 2000 mg/kg bw of undiluted tertiary butyl alcohol was applied to the abraded skin of male and female New Zealand rabbits for twenty-four hours. The only effects related to test substance administration were reversible central nervous system effects in all animals and injected iris in all males and four of five females.

Tertiary butyl alcohol was not acutely toxic by the dermal route in rabbits at a dose of 2000 mg/kg bw and is not classified for acute lethality by the dermal route under GHS. 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 dermal LD50 of tertiary butyl alcohol in male and female New Zealand White rabbits was > 2000 mg/kg bw.  Exposure to large dermal doses of tertiary butyl alcohol may cause transient, reversible CNS effects.  Twenty-four hour contact with abraded skin also caused slight to moderate site of contact dermal irritation in all animals.