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Skin irritation / corrosion

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skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
4 hour exposure followed by 72 hour observation period
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to EPA OTS 798.4470 guideline for a dermal irritation study.
Reason / purpose for cross-reference:
reference to other study

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
according to guideline
EPA OTS 798.4470 (Acute Dermal Irritation)
not specified
GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
tert-butyl acetate
EC Number:
EC Name:
tert-butyl acetate
Cas Number:
Molecular formula:
tert-butyl acetate
Constituent 2
Reference substance name:
tertiary butyl acetate
tertiary butyl acetate
Details on test material:
-Name of test material (as cited in study report): tert-butyl acetate
-Appearance: clear, colorless liquid
-Date received: 7/14/97
-Source: Arco Chemical Company (now LyondellBasell Industries)
-Storage Conditions: room temperature and humidity
-Purity: not reported; used as received

Test animals

New Zealand White
Details on test animals or test system and environmental conditions:
-Source: Ace Animals, Boyertown, PA (received on 7/15/97)
-Animals: 3/sex
-Age: young adults (born weeks of 4/27 through 5/18/97)
-Quarantine period: at least one week
-Weight at Study Initiation: 2.0 - 2.2 kg
-Housing: 1/cage in suspended wire-mesh cages
-Bedding: placed beneath the cages and changed at least 3x/week
-Diet: Purina® Rabbit Chow® Diet # 5321
-Water: freely available at all times
-Identification method: uniquely numbered metal ear tag
-Method of Animal Distribution: no data

-Room temperature: controlled
-Light: 12 hour light/dark cycle

-Date of study initiation: 7/22/97
-Date of study termination: 7/25/97

Test system

Type of coverage:
Preparation of test site:
other: The day prior to administration of the test material, the dorsal area of the trunk of each rabbit was clipped free of hair. The prepared site was approximately 10 x 15 cm and remained intact.
unchanged (no vehicle)
other: Naive areas of skin surrounding the application sites served as a control.
Amount / concentration applied:
0.5 mL/rabbit
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
6 (3 males and 3 females)
Details on study design:
-Test material administration:
For each rabbit, the test material (0.5 mL) was placed under a 2.5 x 2.5 cm, 4 ply surgical gauze patch secured with non-irritating tape and wrapped in plastic in a semi-occlusive manner. The plastic was then completely covered with non-irritating tape.

-Test material exposure:
The test material was kept in contact with the skin for a period of 4 hours, at which time the wrappings were removed and residual test material was removed by gentle washing with distilled water.

Test sites were scored for dermal irritation at 30 - 60 minutes after removal of wrappings, and at 24, 48, and 72 hours following patch removal. The skin was evaluated for ulceration, necrosis, or any tissue destruction and erythema and edema were scored according to the numerical Draize technique. The general health of the rabbits was monitored at each observation time.

-Body weights:
Recorded pretest

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Time point:
other: 24 hours
Max. score:
fully reversible within: 48 hours
Remarks on result:
other: The mean erythema score was based on the mean of all irritation scores for erythema recorded at the 24 hour observation interval. At the 24-hour examinations, signs of irritation were limited to erythema (grade 1) for 4/6 rabbits.
Irritation parameter:
erythema score
Time point:
other: 48 and 72 hours
Max. score:
other: not applicable
Remarks on result:
other: The mean erythema score was based on the mean of all irritation scores for erythema recorded at the 48- or 72-hour observation intervals. No signs of erythema were evident at the 48- or 72-hour examinations.
Irritation parameter:
edema score
Time point:
other: 24, 48, and 72 hours
Max. score:
other: No signs of edema were noted.
Remarks on result:
other: The mean edema score was based on the mean of all irritation scores for edema recorded at the 24, 48, or 72 hour observation intervals. Edema was absent at all observation intervals.
Irritant / corrosive response data:
There was no edema noted in any of the animals during the observation period. Very slight erythema was noted for 5/6 rabbits at 1 hour and for 4 of 6 rabbits at 24 hours. Response scores for erythema ranged from 0 to 1. All animals were normal by the 48-hour observation period.
Other effects:
There were no abnormal systemic signs noted during the observation period.

Any other information on results incl. tables

All rabbits (6/6) were graded as "0" for edema at the 1-, 24 -, 48 -, and 72-hour examinations. Four of six rabbits (4/6) showed minimal erythema (score of 1) at the 24-hour observation period while 2/6 rabbits were normal. All rabbits were graded as "0" for erythema at the 48- and 72-hour examinations.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Migrated information Criteria used for interpretation of results: OECD GHS
Tertiary butyl acetate is not classified as a primary skin irritant. Absent to minimal erythema and no edema were observed when the test material was applied to intact skin under semi-occlusive contact for 4 hours. All effects were fully reversible by the 48-hour observation.

Based on a total absence of edema, a mean erythema score of 0.66 at 24 hours, and full reversibility of erythema by 48 hours following application of test material to intact skin for 4 hours, tertiary butyl acetate is not classifiable for Skin Irritation/Corrosion according to 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. In accordance with EU Directive 67/548/EEC, tertiary butyl acetate must carry the R66 risk phrase “Repeated exposure may cause skin dryness or cracking”. Annex VII to CLP Regulation (EC) No. 1272/2008 contains translation tables to translate risk phrases assigned under Directive 67/548/EEC into supplementary labeling requirements under CLP. The corresponding label statement under CLP Regulation (EC) No. 1272/2008 is EUH066 “Repeated exposure may cause skin dryness or cracking.”
Executive summary:

In a primary dermal irritation study, young adult New Zealand white rabbits (3 males, 3 females) were exposed to 0.5 mL of tertiary butyl acetate applied for 4 hours under semi-occlusive contact to intact skin. Animals were then observed for 72 hours. Irritation was scored by the method of Draize. No edema was noted. The test material caused minimal erythema at 1 and 24 hours in some rabbits but no signs of erythema were present at the 48- or 72-hour observation periods. Tertiary butyl acetate is not considered a dermal irritant under conditions of this study.