Registration Dossier

Administrative data

Endpoint:
eye irritation, other
Remarks:
In vivo test available by Letter of access. Since the criteria for classification as serious damage to eyes are met in vitro test does not need to be conducted on the basis of the already available data as stated by Column 2 of REACH Annex VII sect. 3.2.
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: powder or cake
Details on test material:
- Name of test material (as cited in study report): 2,4,6-Trimethyl phenol (TMP, Mesitol)
- Batch #: (Grade 8093)
- Description: White crystalline powder or cake
- Physical state: Solid
- Stability: Stability under normal storage and use conditions
- Storage: Room temperature (in hood preferably)
- Color: White

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, MA
- Age at study initiation: at least 10 weeks old (adult)
- Weight at study initiation: 2.16 – 2.45 kg
- Housing: Individual housing (Suspended stainless-steel cages); Bedding: Hardwood chips, (non-contact), Prochip, Harlan Teklad, Madison, WI
- Diet: TEK 8630 Rabbit Diet, Harlan Teklad, Madison, WI, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: minimum 5 days, under the same conditions as for the actual test

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12-Hour light/dark cycle, full spectrum fluorescent lights

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animal
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
4 days
Number of animals or in vitro replicates:
3: 1 male and 2 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: Eyes were rinsed with USP water for injection
- Time after start of exposure: 24 hours

SCORING SYSTEM:
- Eyes were examined at 1, 24, 48, and 72 hours after treatment for corneal opacity, iritis, conjunctival redness and chemosis. After recording the observations at 24 hours, the eyes of all rabbits were examined with the aid of fluorescein to further characterize corneal opacity
- Eye corrosion is defined as irreversible ocular damage. The ocular irritation scores shall be evaluated in conjunction with the nature and reversibility of the scores observed

TOOL USED TO ASSESS SCORE: hand-slit lamp andd fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24 - 72 hours
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 4 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24 - 72 hours
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24 - 72 hours
Score:
1.67
Max. score:
4
Reversibility:
not fully reversible within: 4 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24 - 72 hours
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 4 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24 - 72 hours
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24 - 72 hours
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24 - 72 hours
Score:
1.67
Max. score:
3
Reversibility:
not fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24 - 72 hours
Score:
1.67
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24 - 72 hours
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 4 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24 - 72 hours
Score:
3.67
Max. score:
4
Reversibility:
not fully reversible within: 4 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24 - 72 hours
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24 - 72 hours
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 4 days
Irritant / corrosive response data:
- Corneal opacity was observed in all treated eyes by the 24-hour observation point. The corneal opacity did not resolve by the end of the study.
- Moderate iris response was observed in all treated eyes by the 24-hour observation point. The iris response persisted for the duration of the study.
- Conjunctival redness was observed in all animals by the 1-hour observation point. The redness progressed and persisted for the duration of the study.
- Slight chemosis observed in all treated eyes by the 1-hour observation point progressed to moderate or severe chemosis by the end of the study.
- Fluorescein staining w as observed in one animal by the 24-hour observation point. Fluorescein staining did not return to normal by the end of th e study. No fluorescein staining w as observed in the other animals.
- Corrosion: Pannus development was observed in 1 animal on day 3 and 2 animals on day 4.
Other effects:
- Body weight: All of the animals exhibited an increase in body weight during the course of the study.
- Clinical observations: No overt signs of toxicity were evident during the course of the study in any of the animals.

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the substance is considered to be corrosive to the eyes.
Executive summary:

2,4,6-Trimethyl Phenol (TMP, Mesitol) was evaluated for its potential to cause an irritating and/or corrosive effect on the eye in a GLP-compliant OECD 405 guideline study. Three New Zealand White rabbits received a single ocular application of 0.1 g in the conjunctival sac of the left eye. The test substance was washed out after 24 hours. Pannus development was observed in three out of three treated eyes by Day 4 of the study. Pannus development is deemed irreversible damage to the ocular tissue and as a result, the test was terminated. In addition, corneal opacity and effects on the iris were observed in all treated eyes by the 24-hour observation point and persisted for the duration of the study. Conjunctival redness was observed in all animals by the 1 -hour observation point, progressed, and persisted for the duration of the study. Slight chemosis was observed in all treated eyes by the 1-hour observation point progressed to moderate or severe chemosis by the end of the study. In conclusion, the substance is considered to be corrosive to the eyes.