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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:
From Fab.15, 1988 to June 13,1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test substance was administered to 6 rabbits. Three rabbits received the substance on an eye and skin. The other 3 rabbits received the substance on an eye and their eyes were washed after the administration.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Japan Lab Animals Co., Ltd (Osaka, Japan)
- Age at study initiation: no data
- Weight at study initiation: 2.12 to 2.67 kg
- Housing: individually in an aluminium net cage with a suspension system
- Diet (e.g. ad libitum): ca. 100g/day solid rabbit food (CR-1, CLEA Japan, Inc, Osaka, Japan)
- Water (e.g. ad libitum): freely access to purified well water filtered
- Acclimation period: 21 to 35 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24+/-3°C
- Humidity (%): 60+/-15%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 g of the test substance on the conjunctival sac of the one side of lower eyelid.
The eyelids were held for 1 second after the administration to prevent the substance to overflow from the eye.
Duration of treatment / exposure:
For the "unwashed group" (2 males, 1 female), the eyes with administration were not washed and the other eyes were treated as control.
The "washed group" (1 male, 2 females) was separately treated with the same administration but the eyewash with 300 ml of slightly warm water for 1 minute 30 seconds after administration.
Observation period (in vivo):
Observations was conduted at 1, 24, 48, 72 hours after the administration for the washed group, and 96h, 1, 2, 3, 4, 5, 6 weeks for the unwashed group.
Number of animals or in vitro replicates:
"unwashed group" (2 males, 1 female),
"washed group" (1 male, 2 females)
Details on study design:
Local reactions were numerically recorded following the evaluation standards by Draize.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
(severity)
Basis:
mean
Remarks:
3 rabbits "unwashed"
Time point:
other: mean 24-48-72 hours
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 6 weeks
Remarks on result:
other: Individual scores : 2 - 2 - 2
Irritation parameter:
cornea opacity score
Remarks:
(area)
Basis:
mean
Remarks:
3 rabbits "unwashed"
Time point:
other: mean 24-48-72 hours
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 6 weeks
Remarks on result:
other: Individual scores : 4 - 4 - 4
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 rabbits "unwashed"
Time point:
other: mean 24-48-72 hours
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 4 weeks
Remarks on result:
other: Individual scores : 1 - 1 - 1
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
3 rabbits "unwashed"
Time point:
other: mean 24-48-72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 3 weeks
Remarks on result:
other: Individual scores : 2 - 2 - 2
Irritation parameter:
conjunctivae score
Remarks:
(chemosis)
Basis:
mean
Remarks:
3 rabbits "unwashed"
Time point:
other: mean 24-48-72 hours
Score:
1.89
Max. score:
4
Reversibility:
fully reversible within: 3 weeks
Remarks on result:
other: Individual scores between 1 and 3
Irritation parameter:
conjunctivae score
Remarks:
(discharge)
Basis:
mean
Remarks:
3 rabbits "unwashed"
Time point:
other: mean 24-48-72 hours
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 3 weeks
Remarks on result:
other: Individual scores between 1 and 2
Irritant / corrosive response data:
At 1 hour after the administration of the test substance, all 3 animals in unwashed group showed iris congestion (grade 1), conjunctival redness (grade 2), and conjunctival chemosis (grade 3), and 2 animals in the same group showed cornea opacity (severity: grade 1; area : grade 3 or 4).
At 24 hours after the administration, the conjunctival chemosis was wakened to grade 2 and 3, but the iris congestion and conjunctival redness remained at the same grade. At this point, all 3 animals showed cornea opacity (severity grade 2, area grade 4), and all 3 animals showed new occurrence of discharge at grade 1 or 2. These local reactions were still observed at 96 hour at the similar grades.
Cornea opacity at the grade 3 was observed 2 weeks after the administration. The local reactions at the conjunctivae and iris congestion disappeared by 3 and 4 weeks, respectively, after the administration, but cornea opacity remained aven 6 weeks after the administration. Starting at 1 week after the administration, neavascular in cornea were observed.

In the washed group, at 1 hour after the administration of the test substance, all 3 animals showed iris congestion (grade 1) and conjunctival redness (grade 1), and conjunctival chemosis (grade 1 or 2). At 24 hours after the administration, the only reactions such as conjunctival redness (grade 1) and conjunctival chemosis (grade 1) were shown in 2 animals. At 72 hours, no local reaction was observed in any rabbit.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
1,3-diphenylguanidine was considered to be extremely irritating to the eyes in rabbits.
Executive summary:

The test substance was administered to 6 rabbits. Three rabbits received the substance on an eye and skin. The other 3 rabbits received the substance on an eye and their eyes were washed after the administration.

In the eye irritation test, a dose of 0.1g of 1,3-diphenylguanidine (Soxinol-D) was administered to one eye of each rabbit. After the administration, strong cornea opacity, conjunctival chemosis, obvious iris congestion, conjunctival redness, a low level of eye discharge and neovascular in cornea were observed. The local reaction on the conjunctivae and the iris congestion disappeared in 3 weeks and 4 weeks, respectively, but local reactions in cornea were still recognized 6 weeks after the administration.

Based on these results, 1,3-diphenylguanidine was considered to be extremely irritating to the eyes in rabbits.

When the test was repeated with a group of 3 rabbits and eyes were washed 30 seconds after administration, obvious iris congestion, conjunctival chemosis, and a low level of conjunctival redness were observed after the administration. All of these local reactions disappeared within 72 hours after the administration, and therefore, there was a washing effect.