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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
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report date:
1977

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Fed. Reg. 28 (119), 5582, 1963 (published by the FDA of the USA) and Draize and Kelley (Drug. Cosmet. Industr. 71 (1952) 36)
Deviations:
yes
Remarks:
: no reading after one hour
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Housing: individually
- Diet: they received no hay or other extraneous material that might enter the eyes
- The eyes of the animals were examined before testing and only those animals without observable eye defects are used

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
- Single treatment
- test substance was allowed to fall on the everted lower lid of one eye of each rabbit; the upper and lower eye lid were then carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material
- the untreated eye served as control
- the eyes were not washed following instillation and the animlas were released immediately
Observation period (in vivo):
24, 48 72 hours and 7 days after instillation of the test material
Number of animals or in vitro replicates:
six animals
Details on study design:
SCORING SYSTEM (FDA scoring scale):
- an animal is considered as giving a positive reaction if there is, at any of the readings:
* discernable opacity of the cornea (other than slight dulling of the normal lustre), 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
* obvious swelling in the conjunctivae (palpebral and bulbar, excluding the cornea and the iris) with partial eversion of the lids, or
* diffuse deep-crimson red with individual vessels not easily discernible
- the test is considered positive if 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 of the 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

TOOL USED TO ASSESS SCORE:
- oculat 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 fuorescein-impreganted papers
- after flushing the excess fluorescein solution, the eyes 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 considerd a severe eye irritant.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
< 1
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: only in animal #3 cornea score 1; all others were scored 0
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
< 1
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: only in animal #3 iris score 1; all others were scored 0
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: after 7 days animals # 4 and 6 were still scored 1 (scores after 24 h: > 1 and 1, respectively); all other animals were scored 0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: exception: animal #4, chemosis was fully reversible within 7 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
7 d
Score:
< 1
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
- The test material caused slight corneal damage, slight irititis and moderate redness and swelling of the conjunctivae in one rabbit and slight redness of the conjunctivae in the other five rabbits.
- During the seven-day observation period these eye lesions recovered incompletely so that at the seventh day reading slight redness of the conjunctivae was still observed in two out of six rabbits.
Other effects:
No other effects observed.

Any other information on results incl. tables

Table 2: Individual scores awarded to the ocular lesions elicited by Dicyandiamid

Rabbit No

cornea

iris

conjuntivae

redness

chemosis

After 24 hours

1

0

0

1

1

2

0

0

> 1

1

3

1

1

< 2

2

4

0

0

> 1

1

5

0

0

1

1

6

0

0

1

1

After 48 hours

1

0

0

1

0

2

0

0

1

1

3

0

0

1

1

4

0

0

1

1

5

0

0

1

0

6

0

0

 >1

1

After 72 hours

1

0

0

1

0

2

0

0

1

0

3

0

0

1

0

4

0

0

1

1

5

0

0

1

0

6

0

0

 >1

0

After 7 days

1

0

0

0

0

2

0

0

0

0

3

0

0

0

0

4

0

0

1

0

5

0

0

0

0

6

0

0

1

0

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this test and according to the FDA-standard the test material is not considered to be an eye irritant.
Executive summary:

In an acute eye irritation study according to FDA-standards, 0.1 ml of Dicyandiamid was instilled into the eyes of six albino rabbits (New Zealand White strain). Eyes were not washed afterwards. Animals then were observed after 24, 48, 72 hours and 7 days. Irritation was scored by the method of US EPA 560/6-82-001.

Under the experimental conditions employed, Dicyandiamid produced slight corneal damage, slight irititis and moderate redness and swelling of the conjunctivae in one rabbit and slight redness of the conjunctivae in the other five rabbits. During the seven-day observation period these eye lesions recovered incompletely so that at the seventh day reading slight redness of the conjunctivae was still observed in two out of six rabbits.

According to the FDA-standard the test material is not considered to be an eye irritant.