Registration Dossier

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: Acceptable, well documented study report which meets scientific principles. Study was conducted prior to GLP and OECD guideline implementation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: FDA Federal Register 38, No. 187 (1973)
Deviations:
not specified
Qualifier:
according to
Guideline:
other: company guideline similar to OECD 405
Deviations:
not applicable
Principles of method if other than guideline:
Mucosal tolerance was assessed after single application of 100 mg of the undiluted test substance into the conjunctival sac of the left eye of six rabbits. The right eye remained untreated as a control. The experiment was conducted according to FDA directives (Fed. Reg Vol. 38, No. 187, 1973). Evaluation was conducted 1, 7, 24, 48, 72h, and 7, 14, and 21 d after treatment by using a magnifying glass. 24h after treatment eyes were washed with physiol. saline. To assess the 48 and subsequent time points a drop of a 0.01% sodium fluorescein solution was instilled into the eyes.
GLP compliance:
no
Remarks:
prior to GLP implementation

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Chloranil

Test animals / tissue source

Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
Albino-Himalayan rabbits (SPF bred). Animals were housed individually. Commercially available rabbit maintenance diet and tapwater were fed ad libitum.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the right eye remained untreatewd and served as control
Amount / concentration applied:
Single dose of 100 mg undiluted test substance per animal administered to the conjunctival sac of one eye.
Duration of treatment / exposure:
24 h, thereafter the eyes were rinsed with physiol. saline.
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
6 animals treated with undiluted test substance
Details on study design:
Mucosal tolerance was assessed after single application of 100 mg of the undiluted test substance into the conjunctival sac of the left eye of six rabbits. The right eye remained untreated as a control. The experiment was conducted according to FDA directives (Fed. Reg Vol. 38, No. 187, 1973). Evaluation was conducted 1, 7, 24, 48, 72h, and 7, 14, and 21 d after treatment by using a magnifying glass. 24h after treatment eyes were washed with physiol. saline. To assess the 48 and subsequent time points a drop of a 0.01% sodium fluorescein solution was instilled into the eyes.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
other: animal # 16, 58, 67, 69 each
Time point:
other: mean of 24, 48, 72h
Score:
0
Reversibility:
other: no signs of irritation at any time
Irritation parameter:
cornea opacity score
Basis:
other: animal # 13
Time point:
other: mean of 24, 48, 72h
Score:
2
Reversibility:
fully reversible within: 7d
Irritation parameter:
cornea opacity score
Basis:
other: animal # 23
Time point:
other: mean of 24, 48, 72h
Score:
1.7
Reversibility:
not fully reversible within: 21 d
Irritation parameter:
iris score
Basis:
other: animal # 13, 16, 23, 58, 67, 69 each
Time point:
other: mean of 24, 48, 72h
Score:
0
Reversibility:
other: no signs of irritation at any time
Irritation parameter:
conjunctivae score
Basis:
other: animal # 69
Time point:
other: mean of 24, 48, 72h
Score:
1
Reversibility:
not fully reversible within: 21 d
Irritation parameter:
conjunctivae score
Basis:
other: animal # 16, 67 each
Time point:
other: mean of 24, 48, 72h
Score:
1.7
Reversibility:
fully reversible within: 72h in one animal and not fully reversible within 21 d in the other animal
Irritation parameter:
conjunctivae score
Basis:
other: animal # 13, 23, 58 each
Time point:
other: mean of 24, 48, 72h
Score:
2
Reversibility:
fully reversible within: 14 d in two animals and not fully reversible within 21 d in one animal
Irritation parameter:
chemosis score
Basis:
other: animal # 58
Time point:
other: mean of 24, 48, 72h
Score:
0.7
Reversibility:
fully reversible within: 14 d
Irritation parameter:
chemosis score
Basis:
other: animal # 16
Time point:
other: mean of 24, 48, 72h
Score:
1
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
other: animal # 67, 69 each
Time point:
other: mean of 24, 48, 72h
Score:
1.3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
other: animal # 23
Time point:
other: mean of 24, 48, 72h
Score:
1.7
Reversibility:
not fully reversible within: 21 d

Applicant's summary and conclusion

Interpretation of results:
other: Risk of serious damage to eyes.
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
Responses were obvious for cornea, conjunctivae redness, and conjunctivae chemosis, but mean scores calculated were below threshold values. However some effects were not fully reversible in three rabbits within the observation period of 21d. Based on these findings the test substance carries the risk to cause serious damage to eyes.
Executive summary:
Chloranil was tested for eye irritating properties according to a company guideline similar to OECD 405 and according to a FDA guideline (Fed. Reg. Vol 38, No. 187, 1973). Following this protocol 100 mg of the undiluted test substance were placed into the conjunctival sac of the left eye of 6 rabbits each. The right eye served as untreated control. 1, 7, 24, 48, 72h, and 7, 14, and 21 d after treatment eyes were examined. 24 h after treatment eyes were rinsed with physiol. saline. Mean scores (mean of 24, 48, and 72 h) were calculated for cornea, iris, conjunctivae redness, and conjunctivae chemosis for each rabbit. Responses were obvious for cornea, conjunctivae redness, and conjunctivae chemosis, but mean scores calculated were below threshold values. However some effects were not fully reversible in three rabbits within the observation period of 21d. Based on these findings the test substance carries the risk to cause serious damage to eyes.