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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24-hour application followed by 14-day observation period
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study; conducted to be in compliance with EPA/TSCA Health Effects Testing Guidelines, 40 CFR Part 798.1100 (EPA OTS 798.1100). Some deviations; noted in "Overall Remarks" section.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
: Minor deviations from the guideline occurred. There was no information provided on test material purity or actual temperature and humidity in the testing area. These deviations were not sufficient to impact the validity of the study.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): tert-butyl acetate
- Appearance: clear, colorless liquid
- Received at testing laboratory: 7/14/97
- Source of test material: Arco Chemical Company (now LyondellBasell Industries)
- Specific gravity of test material: 0.85
- Storage condition of test material: room temperature and humidity
- Purity of test material: not reported; test material used as received

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS:
-Source: Ace Animals, Boyertown, PA (received on 7/8 and 7/15/97)
-Animals: 5/sex
-Age: young adults (born weeks of 4/20 through 5/18/97)
-Quarantine period: at least one week
-Weight at Study Initiation: males were 2.1 - 2.4 kg and females were 2.0 - 2.1 kg (weight variation did not exceed +/- 20% of the mean weight)
-Housing: 1/cage in suspended wire cages
-Bedding: placed beneath the cages and changed at least 3x/week
-Diet: Purina® Rabbit Chow® Diet # 5321 provided daily
-Water: ad libitum
-Identification method: uniquely numbered metal ear tag
-Method of Animal Distribution: randomly assigned

ENVIRONMENTAL CONDITIONS:
-Room temperature: controlled; values not specified
-Humidity: not reported
-Light: 12 hour light/dark cycle

IN-LIFE DATES:
-Date of start of experiment: 7/23/97
-Date of experiment termination: 8/6/97

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
On the day prior to application of the test material, the dorsal area of the trunk of each animal was clipped free of hair. The prepared site was approximately 10% of the body surface and remained intact. A single dose of the test material, administered as received, was applied to the prepared site at a dose level of 2000 mg/kg bw. The dose was based on the sample weight as calculated from the specific gravity. The test material was applied under a four-layered surgical gauze patch (10 x 15 cm). The torso was wrapped with plastic and secured with non-irritating tape. After a period of 24 hours, the wrappings were removed.
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: animals were checked twice daily
-Body weights: recorded pre-test, weekly, and at death or termination of survivors
-Observation of clinical signs: 1, 2, and 4 hours post-dose, and once daily for 14 days
-Evaluation of dermal irritation: the test sites were scored for dermal irritation at 24 hours post-dose and on days 7 and 14 using the numerical Draize scoring code (range of 0 = normal to 4 = severe for erythema/eschar and edema). The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction.
-Necropsy performed: yes on all animals
-Gross pathology exam: all animals; abnormal tissues were preserved in 10% buffered formalin for possible future microscopic examination.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
All animals survived the 2000 mg/kg bw dermal application.
Clinical signs:
Dermal reactions were absent at all observation periods. Instances of diarrhea were noted in 3/10 rabbits during the first week of the study. There were no other abnormal clinical signs evident during the study.
Body weight:
Body weight changes were normal for all rabbits.
Gross pathology:
Necropsy findings were normal for 9/10 rabbits. Kidney abnormalities (pitted - moderate) were noted in one female rabbit.

Any other information on results incl. tables

Based upon the data obtained, the Minimum Lethal Dose (MLD) for tertiary butyl acetate 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:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
In an acute dermal toxicity test, no deaths were reported when a limit dose of 2000 mg/kg bw of undiluted tertiary butyl acetate was applied to the clipped skin of male and female New Zealand rabbits for twenty-four hours under occlusive wrap. No signs of irritation were reported and animals gained weight normally. Other than diarrhea observed during the first week in 3 of 10 animals and moderate pitted kidneys observed at necropsy in one female rabbit, no other abnormalities were noted. Diarrhea is a common finding in rabbits and the gross abnormalities observed in the single female rabbit are insufficient to classify tertiary butyl acetate as a systemic toxicant following a single dermal application.

Tertiary butyl acetate 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 according to Directive 67/548/EEC, the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. Based on an absence of significant systemic signs, tertiary butyl acetate is also not classified under Directive 67/548/EEC, the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 for Specific Target Organ Toxicity – Single Exposure for the dermal route of exposure.
Executive summary:

Under the conditions of this study, the dermal LD50 of tertiary butyl acetate in male and female New Zealand White rabbits was > 2000 mg/kg bw. No mortality was observed in the study and all animals gained weight normally over the observation period. No signs of irritation, necrosis, ulceration or evidence of tissue destruction were reported. Other than diarrhea during the first week for 3 of 10 rabbits, no other abnormal signs were noted at this dose level. Necropsy of animals revealed pitted kidneys (moderate) for one female. No other gross abnormalities were noted. Based on the results of this study, tertiary butyl acetate is not acutely toxic to rabbits via the dermal route and therefore is expected to present a low toxicity hazard upon skin contact under conditions of normal use.