Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted according to EPA method and GLPs; no purity information was provided on the actual test material used in the study.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: Study used a Modified Draize test with a classification scheme proposed by Kay and Calandra (1962). Interpretation of Eye Irritation Tests. Journal of the Society of Cosmetic Chemists. 13(6), pp. 281-289.
Deviations:
not specified
Qualifier:
according to
Guideline:
other: Health Effects Tests Guidelines, US EPA 8/78
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): Arconol

Arconol is a mixture whose primary component is tertiary butyl alcohol. Information on Arconol provided by the manufacturer states the following Wt% specifications for the composition:
Tertiary butyl alcohol - 91% min (93.8% typical)
Acetone - 2.0% max
Water - 1.7% max
Other organics - 2.0% max
Butanes - balance

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
-Source: Langshaw Farms Inc., Augusta MI
-Animals: 4 males, 5 females
-Age: young adult
-Quarantine period: 20 days
-Weight at study initiation: 2224-2852 g
-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: 8 April 1981
-Date of study termination: 12 May 1981

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
Test material was applied in a single application to the right eye. No further treatment was performed on six rabbits. The eyes of three rabbits were flushed with water ~30 sec after instillation for about 1 minute.
Observation period (in vivo):
16 days for unwashed group; 34 days for washed group
Number of animals or in vitro replicates:
9 (6 unwashed eyes, 3 washed eyes)
Details on study design:
Removal of test substance:
-Washing (3/9 animals)
-Time after start of exposure: about 30 sec

Observation period: all animals were scored for irritation at 24, 48, 72 and 96 hr and 7, 10, 13 and 16 days. Observations for the washed group continued on days 19, 22, 25, 28, 31 and 34.

Scoring System: a modified Draize system was used for ocular irritation scores. The study also used a classification system proposed by Kay and Calandra (1962) which takes into account the extent and persistence of irritation and the overall consistency of the data. The Kay and Calandra system has not been compared with other classification systems.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 h
Score:
41
Max. score:
110
Reversibility:
fully reversible within: 16 days
Remarks on result:
other: In six unwashed eyes, irritation was observed in all animals at 96 h. Irritation had decreased from a maximum of 41.0/110 at 24 h to 32.7/110 at 96 h. All animals were normal by day 16.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 h
Score:
30.3
Max. score:
110
Reversibility:
not fully reversible within: 34 days
Remarks on result:
other: In three washed eyes, irritation was observed in all animals at 96 h. By day 7, one animal was normal and the total group average score had decreased from a maximum of 30.3 at 72 h to 12.0. All animals were judged normal on day 22.

Any other information on results incl. tables

Unwashed eyes:

The maximum average irritation score in unwashed eyes was 41.0/110 at 24 hours. Group average scores at 24-hr were: cornea 24.0/80; iris 5.0/10; conjunctiva 12.0/20.  All six animals exhibited corneal opacity ≥1 at the 24, 48 and 72-hour observation period. By day 7, one male and two females were normal. Total individual scores for the two other males were also 0/110 on day 7 but 5-10% of the treated area tested positive with fluorescein. On day 10, corneal effects were again observed in these same two males with scores of 25/80 and 5/80. In the remaining female, the total individual score was 2.5/110 on day 7, based on scores of 2.5, 0 and 0 for cornea, iris and conjunctiva, respectively. All unwashed eyes were normal by day 16. In all test animals, a positive response of corneal opacity ≥1 and conjunctival redness ≥2 calculated as the mean scores following grading at 24, 48, and 72 hours after instillation of the test material was observed.

  

Washed eyes:

The maximum average irritation score in washed eyes was 30.3/110 at 72 hours. Group average scores at 72-hr were: cornea 17.1/80; iris 4.2/10; conjunctiva 9.0/20. One male was normal by day 7. Although both females were judged normal on day 22, one animal again exhibited corneal effects on day 25 (total corneal score 6.3) and which continued to study termination on day 34 (total corneal score 2.5). The total corneal scores for this animal were lower at the four preceding observation periods (day 13 – 5.0, day 16 – 5.0, day 19 – 2.5, day 22 – 0) so the relevance of this effect is unknown.

Applicant's summary and conclusion

Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Arconol, a product containing predominantly tertiary butyl alcohol (91% minimum), caused moderate irritation when instilled into the eyes of New Zealand albino rabbits. In 6/6 unwashed eyes, there was complete reversibility of all effects by Day 16. In 3 eyes which were washed immediately following instillation of the test material, all scores for cornea, iris and conjunctiva were 0 on Day 22; however, 2/3 animals again exhibited corneal effects, described as vascularization, on Day 25 until study termination on Day 34. The scores for cornea and iris were less than 3 and 1.5, respectively, averaged over 24, 48 and 72 hours for both the washed and unwashed groups. There was insufficient information in the test report to explain the effects observed in washed eyes following a period of normalcy.

Based on the presence of corneal effects in one of six unwashed eyes at the 7 day but not at the 21 day observation period, tertiary butyl alcohol is classifiable for Eye Irritation according to GHS.
Executive summary:

In a primary eye irritation study, 0.1 mL of Arconol (a product containing predominantly tertiary butyl alcohol [91% minimum] and low levels of acetone, water, other organics, and butanes) was instilled into the eyes of young adult New Zealand Albino rabbits (4 males, 5 females).  Of these, 3 had their eyes washed after treatment and 6 were unwashed.  Animals were observed for 16 days (unwashed eyes) or 34 days (washed eyes).  Irritation was scored by the method of Draize. 

  

For all six animals in the unwashed group, a positive response of corneal opacity  ≥1 and conjunctival redness ≥2 calculated as the mean scores following grading at 24, 48 and 72 hours after instillation of the test material was observed.  All effects in unwashed eyes were fully reversible in 16 days. For all three animals in the washed group, a positive response of corneal opacity ≥1 was observed. All animals were normal on day 22.  Corneal effects were again observed in a single animal in the washed group on day 25 and these effects continued until study termination on day 34.  Since the score for corneal effects (6.3) on day 25 was higher than the scores on day 13 (5.0), day 16 (5.0), day 19 (2.5) and day 22 (0), no conclusion can be drawn about the significance of the effects observed in this single animal.  In this study, Arconol containing ≥91% tertiary butyl alcohol was an eye irritant.