1,3-diphenylguanidine

Eye irritation

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

Test material information

Constituent 1

Reference substance name:

1,3-diphenylguanidine

EC Number:

203-002-1

EC Name:

1,3-diphenylguanidine

Cas Number:

102-06-7

Molecular formula:

C13H13N3

IUPAC Name:

1,3-diphenylguanidine

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

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

(severity)

Basis:

mean

Remarks:

3 rabbits "unwashed"

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 6 weeks

Remarks on result:

other: Individual scores : 2 - 2 - 2

Results 2

Irritation parameter:

cornea opacity score

Remarks:

(area)

Basis:

mean

Remarks:

3 rabbits "unwashed"

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 6 weeks

Remarks on result:

other: Individual scores : 4 - 4 - 4

Results 3

Irritation parameter:

iris score

Basis:

mean

Remarks:

3 rabbits "unwashed"

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 4 weeks

Remarks on result:

other: Individual scores : 1 - 1 - 1

Results 4

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

3 rabbits "unwashed"

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 3 weeks

Remarks on result:

other: Individual scores : 2 - 2 - 2

Results 5

Irritation parameter:

chemosis score

Remarks:

(chemosis)

Basis:

mean

Remarks:

3 rabbits "unwashed"

Time point:

24/48/72 h

Score:

1.89

Max. score:

4

Reversibility:

fully reversible within: 3 weeks

Remarks on result:

other: Individual scores between 1 and 3

Results 6

Irritation parameter:

conjunctivae score

Remarks:

(discharge)

Basis:

mean

Remarks:

3 rabbits "unwashed"

Time point:

24/48/72 h

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.