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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
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The test material, E 2932.01 (TMPD), a white powder, was received on August 1, 1986 and was stored at ambient temperature.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Nine (9) New Sealand White strain rabbits in the weight range 2.4 to 3.5 kg, prior to treatment on day 1 and approximately 11 to 15 weeks of age were obtained from Froxfield Rabbits, Petersfield, Hampshire, England. The rabbits selected for the study were all acclimated to the laboratory environment.

Each animal was identified by a numbered aluminum tag placed through the edge of one ear. This number was unique within the HRC Industrial toxicology Department throughtout the duration of the study. The rabbits were individually housed in metal cages with performated floors in Building R 14, Room 2. They had free access to tap water and SDS Standard Rabbit Diet.

Animal room temperature was maintained at approximately 19 degrees C and relative humidity at 30-70%. Air exchanges was maintained at approximately 19 air changes per hour and lighting was controlled to give 12 hours of artificial light in each 24-hour period.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
4.5mg of test material was applied to each treated eye
Duration of treatment / exposure:
one single administration
Observation period (in vivo):
21 days post-exposure
Number of animals or in vitro replicates:
nine (9)
Details on study design:
Rabbits were allocated to two treatment groups. For group 1, a total of six rabbits were used, wherein E 2932.01 (4.5mg) was applied directly to the corneal surface of one eye of each animal, and the eyelids were immediately released. The test material was allowed to remain for the duration of the study. The contralateral eye remained untreated and served as a control.

For group 2, a total of three rabbits were used, wherein 4.5mg of E 2932.01 was applied directly to to corneal surface of one eye of each animal. Approximately 4 seconds after instillation of the test material the treated eyes were rinsed using 20 mL of lukewarm tap water.

OBSERVATIONS AND SCORING

Examination of the eyes were made 1, 2, 3, 4, and 7 days after instillation. Observation of the eyes was aided by the use of a handheld torch.

Grading and scoring of the ocular lesions were performed based on a Numerical scoring system as described by Draize (1959).

MAXIMUM AVERAGE SCORE

The total score for the eye (P&G score) is the sum of all the scores obtained for the cornea, iris and conjunctivae. The maximum average score (MAS) was calculated by averaging the highest total P&G score on any one day.

MEDIAN RECOVERY TIME

The median number of days for the eyes to clear was calculated by placing the animals in sequential order with regard to persistence of the response to treatment. Teh average number opf days of the eyes of the third and fourth animal in the series to become normal was then calculated to the nearest 0.1 day.

CLASSIFICATION

The test substance is considered to be non-irritant when no corneal damage, on iridial inflammation or conjuctival grades in excess of 1 are observed at the 24 hour reading.

A slight irritant is characterized by any of the following changes at the 24 hour or subsequent readings, which clear by day 7:

opacity of cornea (other than a slight dulling)
iridial inflammation
conjunctival grades 2 and above
conjunctival grades of 1 persisting beyond 24 hours

A moderate irritant is characterized by changes/lesions in the ocular tissues persisting beyond 7 days but clearing by day 21.

A severe irritant is a test substance that produces reactions persisting beyond ay 21 or that produces a necrotic lesion.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Remarks:
group 1
Basis:
mean
Time point:
other: 24 hour
Score:
7
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Remarks:
group 1
Basis:
mean
Time point:
other: 48 hour
Score:
5
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Remarks:
group 1
Basis:
mean
Time point:
other: 72 hour
Score:
3
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Remarks:
group 1
Basis:
mean
Time point:
other: 4 days
Score:
1
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Remarks:
group 1
Basis:
mean
Time point:
other: 7 days
Score:
0
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Remarks:
group 2
Basis:
mean
Time point:
other: 24 hour
Score:
2
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48 hour
Score:
0
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
other: Average score calculated
Remarks:
average score calculated
Time point:
7 d
Score:
7
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
7 d
Score:
7
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
7 d
Score:
7
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
other:
Time point:
7 d
Score:
7
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
7 d
Score:
2
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
rinse after 4 sec
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
7 d
Score:
2
Max. score:
110
Reversibility:
not fully reversible within: mild conjuction was seen
Remarks:
mild conjuction was seen
Remarks on result:
probability of weak irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
7 d
Score:
2
Max. score:
110
Reversibility:
fully reversible
Remarks:
rinse after 4 sec
Remarks on result:
no indication of irritation
Remarks:
rinse after 4 sec
Irritation parameter:
chemosis score
Basis:
mean
Time point:
7 d
Score:
2
Max. score:
110
Reversibility:
fully reversible
Remarks:
rinse after 4 sec
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Group 1 (no rinse)

Corneal opacity developed in one animal. Transient iritis was seen in one animal. A diffuse crimson red colorization was seen in two animals ans was accompanied in one by considerable swelling with partial eversion of the eyelids. Mild conjuctival reactions were observed in two animals. Two animals did not show any observable response to treatment throughout the observation period. The MAS and median recovery time were calculated to be 7 and 2.5 days, respectively.

Group 2 (rinsed)

No corneal damage or iridial inflammation was seen in ay of the animals. Transient mild conjuctival reactions were observed in two animals. One animal did not show any observable response to treatment throughout the observation period. The MAS was calculated to be 2.

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
E 2932.01 (TMPD) is considered to be a slight irritant
Executive summary:

The test material (TMPD) was instilled in one eye of 9 rabbits; in 6 rabbits (group 1), the test material was not disturbed following treatment, while in 3 rabbits (group 2), the treated eye was rinsed with tap water approximately 4 seconds after instillation. For rabbits in Group 1, Corneal opacity developed in one animal. Transient iritis was seen in one animal. A diffuse crimson red colorization was seen in two animals ans was accompanied in one by considerable swelling with partial eversion of the eyelids. Mild conjuctival reactions were observed in two animals. Two animals did not show any observable response to treatment throughout the observation period. The maximum average score (MAS) and median recovery time were calculated to be 7 and 2.5 days, respectively. For rabbits in Group 2, no corneal damage or iridial inflammation was seen in ay of the animals. Transient mild conjuctival reactions were observed in two animals. One animal did not show any observable response to treatment throughout the observation period. The MAS was calculated to be 2. For both groups, the highest MAS was observed at 24 hours after treatment, and all findings were fully reversible during the observation period. From these data, TMPD is considered to be a slight irritant.