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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
72-hour observation period
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to EPA OTS 798.4500 guideline for an eye irritation study.

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 798.4500 (Acute Eye Irritation)
Deviations:
not specified
GLP compliance:
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
-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 / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
-Source: Ace Animals, Boyertown, PA (received on 7/15/97)
-Animals: 6 males
-Age: young adults (born weeks of 4/27 through 5/18/97)
-Quarantine period: at least one week
-Weight at Study Initiation: 2.2 - 2.4 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; provided daily
-Water: provided ad libitum
-Identification method: uniquely numbered metal ear tag
-Method of Animal Distribution: no data

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

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

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The remaining untreated eye of each rabbit served as a control.
Amount / concentration applied:
0.1 mL for one eye of each rabbit
Duration of treatment / exposure:
single dose
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6 males
Details on study design:
-Test material administration: For each rabbit, the test material (0.1 mL) was placed by syringe into the conjunctival sac of one eye of each rabbit. After instillation, the lids were held together briefly to insure adequate distribution of the test material.

-Observations: Using a hand held auxiliary source of illumination, the treated eye of each rabbit was examined for irritation of the cornea, iris, and conjunctiva at 1, 24, 48, and 72 hours post dose. Ocular reactions were scored according to the scale of weighted scores for grading severity of ocular lesions (Draize, 1944). The eyes of all rabbits were examined with sodium fluorescein at 24 hours. The general health of the rabbits was monitored at each observation time.

-Body weights: Recorded pretest

Reference:
Draize et al., 1944. J. Pharm. Exp. Ther. 82:377-389

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-hour
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Corneal opacity (rated 2 on a scale of 0 to 4) was observed in 1/6 animals at 24 hours. All signs resolved by 48 hours.
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-hour
Score:
0.17
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Iris effects (rated 1 on a scale of 0 to 2) were observed in 1/6 animals at 24 hours. All signs resolved by 48 hours.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24-hour
Score:
1.5
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Conjunctival redness (rated 1 or 2 on a scale of 0 to 3) was observed in 6/6 animals at 24 hours. All signs resolved by 72 hours.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48-hour
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Conjunctival redness (rated 1 on a scale of 0 to 3) was observed in 6/6 animals at 48 hours. All signs resolved by 72 hours.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-hour
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Chemosis (rated 2 on a scale of 0 to 4) was observed in 1/6 animals at 24 hours. All signs resolved by 48 hours.
Irritation parameter:
other: Discharge
Basis:
mean
Time point:
other: 24-hour
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Discharge (rated 2 on a scale of 0 to 3) was observed in 1/6 animals at 24 hours. All signs resolved by 48 hours.
Irritant / corrosive response data:
By the 72-hour examination period, all eyes appeared clinically normal. Corneal opacity (Grade 2) was limited to 1/6 eyes at the 24-hour observation period. No other signs of opacity were noted throughout the study. Irritation of the iris (Grade 1) was observed for 3/6 eyes at the 1-hour examination and for 1/6 eyes at the 24-hour examination. No other signs of iris irritation were seen during the study. Redness (Grade 2) and chemosis (Grade 2) along with a discharge (Grade 2) were noted for all eyes at the 1-hour examination. Redness (Grade 1 or 2) persisted to the 24- or 48-hour examination; chemosis (Grade 2) and discharge (Grade 2) were noted at 24 hours for a single eye. No further signs of chemosis or discharges were noted after the 24-hour examination. Fluorescein staining was noted only for the single eye with corneal opacity. No signs of necrosis, ulceration or evidence of tissue destruction were noted at any time during the study.
Other effects:
There were no abnormal systemic signs noted during the observation period.

Any other information on results incl. tables

The highest primary irritation score for any individual rabbit (out of a possible maximum score of 110), calculated using the weighted Draize scale, was 17/110 at the 1-hour examination, 12/110 at the 24-hour examination, and 2/110 at the 48-hour examination. The mean primary irritation score for the 6 rabbits using the weighted Draize scale was 14.5 at 1 hour, 6.8 at 24 hours, and 2 at 48 hours. Based on the individual and mean data, tertiary butyl acetate is considered practically non-irritating to the rabbit eye.

 

Classification of irritation ratings correspond to the following definitions derived from data obtained from test methods described in 16 CFR 1500.42:

-Practically non-irritating: Average Draize score 0.00 - 15.0

-Slightly irritating: Average Draize score 15.1 - 25.0

-Moderately irritating: Average Draize score 25.1 - 50.0

-Severely irritating: Average Draize score 50.1 - 110.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: 16 CFR 1500.42
Conclusions:
Tertiary butyl acetate was, at most, slightly irritating when instilled into the eyes of New Zealand albino rabbits. Using the Draize scale of weighted scores, the highest average score (14.5 out of a possible score of 110) was observed at the 1-hr observation period. In 6/6 unwashed eyes, there was complete reversibility of all effects by the 72-hour observation period. In addition, no abnormal systemic signs of toxicity were observed.

Corneal opacity (Grade 2), observed in 1/6 animals at the 24-hour observation only, was completely reversible by the 48-hour observation. Fluorescein staining was noted in this one eye at 24 hours. Iritis (Grade 1) was observed in 3/6 animals at the 1-hour examination and in 1/6 animals at 24 hours. No signs of iris irritation were observed at subsequent examinations. Erythema (Grade 2), chemosis (Grade 2) and a discharge (Grade 2) were observed in all eyes one hour after test substance administration. Discharge (Grade 2) and chemosis (Grade 2) were seen in a single eye at 24 hours. No further signs of chemosis or discharges were noted after the 24-hour examination. Erythema (Grade 1 or 2) persisted to the 24- or 48-hour observation. All eyes were clinically normal at 72 hours. Although tertiary butyl acetate caused moderate initial irritation, the reported Draize scores, number of affected animals for each category, and duration of responses were insufficient to classify tertiary butyl acetate for eye irritation 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.
Executive summary:

In a primary eye irritation study, young adult New Zealand white rabbits (6 males) were exposed to 0.1 mL of tertiary butyl acetate in one eye. Animals were then observed for 72 hours. Ocular reactions were scored according to the scale of weighted scores for grading severity of ocular lesions (Draize, 1944). The eyes of all rabbits were examined with sodium fluorescein at 24 hours. The maximum total score (MTS) was calculated to determine severity of irritation. The test material caused minimal eye irritation which was completely reversible by 72 hours. Tertiary butyl acetate was not an eye irritant in animals under conditions of this study.