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: Well-conducted study done according to guideline in force at the time. Documentation is sufficient but not extensive, also as was practice when the study was done. Study was performed prior to GLP regulations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Remarks:
Study was performed prior to GLP regulations

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: clear, colourless liquid
Details on test material:
None

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
None

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml of test material as supplied
Duration of treatment / exposure:
Eyelids were held shut for at least one second
Observation period (in vivo):
Seven days
Number of animals or in vitro replicates:
One
Details on study design:
In general the techniques of tests as published by the FDA of the United States (Fed. Reg 28 (119), 5582, 1963) and Draize and Kelley (Drug Cosmet. Industr. 71 (1952) 36) are followed.

Six New Zealand White albino rabbits are used for each test substance. The animals are caged individually and receive no hay or other extraneous material that might enter the eyes. The eyes of the animals are examined before testing and only those animals without observable eye defects are used. One tenth of a milliliter of the test substance, or in case of solids or semi-solids, 100 milligrams of the test substance, is allowed to fall on the everted lower lid of one eye of each rabbit; the upper and lower eye lid are then carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material. The other eye, remaining untreated, serves as a control. The eyes are not washed following instillation and the animals are released immediately. The eyes are examined at 24, 48, 72 hour and 7 days after instillation of the test material.

An animal is considered as giving a positive reaction if there is, at any of the readings, discernable opacity of the cornea (other than a slight dulling of the normal luster), or ulceration of the cornea, or inflammation of the iris (other than a slight deepening of the folds (rugae) or a slight circumcorneal injection), or if such substances produce in the conjunctivae (palpebral and bulbar, excluding the cornea and iris) an obvious swelling with partial eversion of the lids, or a diffuse deep-crimson red with individual vessels not easily discernable. The FDA-scoring scale is used. The test is considered positive is four or more of the animals in the test group of six rabbits exhibit a positive reaction. If one animal exhibits a positive reaction, the test is regarded as negative. If two or three animals exhibit a positive reaction, the test is repeated, using a different group of six animals. The second test is considered as positive if three or more of the animals exhibit a positive reaction. If only one or two animals in the second test exhibit a positive reaction, the test is again repeated with a different group of six animals. Should a third test be needed, the substance will be regarded as an irritant if two or more animals exhibit a positive response.

Ocular reactions are read using a binocular magnifying glass. The diagnosis of corneal damage is confirmed, if necessary, by staining the eyes of the animals with fluorescein-impregnated papers. After flushing the excess fluorescein solution, the eye are examined in a dark room under ultraviolet illumination. A substance which has elicited corneal and/or iris lesions which have not cleared by the seventh day reading, is considered a severe eye irritant.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24 hours
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 48 hours
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Time point:
other: 72 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
7 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 7 days
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24 hours
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 48 hours
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 72 hours
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 7 days
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24 hours
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 48 hours
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 72 hours
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 7 days
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24 hours
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 48 hours
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 72 hours
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 7 days
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
Because of the severity of the ocular lesions caused by TMPH, this substance was examined in only one rabbit instead of six. The ocular effects were as follows: moderate to severe corneal opacity, slight iritis, moderate redness of the conjunctivae and swelling with lids about half closed. No recovery was observed during seven days after treatment.
Other effects:
None reported

Any other information on results incl. tables

See table above.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information
Conclusions:
The present eye irritation test showed TMPH to be a very severe eye irritant.
Executive summary:

TMPH was examined for its primary skin and eye irritating properties.  Because of the severity of the ocular lesions caused by TMPH, this substance was examined in only one rabbit instead of six. The ocular effects were as follows: moderate to severe corneal opacity, slight iritis, moderate redness of the conjunctivae and swelling with lids about half closed. No recovery was observed during seven days after treatment. TMPH, tested in one eye, appeared to be a very severe eye irritant.