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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:
05/04/1997 - 11/06/1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP, Guideline study: Nine rabbits instead of 3 (92/69/EEC B.5) were used, the eyes of 6 rabbits remaining unwashed (regulatory requirement in US) and the eyes of 3 animals washed 30 seconds after instillation of test article. Clinical signs and body weights (after treatment) not reported.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(1987)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Version / remarks:
(1982)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF 59 NohSan no. 4200 (1985)
Deviations:
no
GLP compliance:
yes

Test material

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

Test animals / tissue source

Species:
rabbit
Strain:
other: New Zealand White (Hra:(NZW)SPF)
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 14-18 weeks old
- Weight at study initiation: 2334 - 2694 g
- Sex: males and females

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 g
Duration of treatment / exposure:
- Exposure period: Washed group: 3 rabbits 30-second exposure; Unwashed group: 6 rabbits 96 h
- Post-exposure period: 14-days
Observation period (in vivo):
- The treated eyes of all animals were examined for ocular irritation reactions 1, 24, 48, 72 and 96 hours and 7 and 14 days after instillation.
Number of animals or in vitro replicates:
9 rabbits, 6 males and 3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: With water (both eyes of 3 rabbits for 1 minute)
- Time after start of exposure: 30 seconds

SCORING SYSTEM: Irritation reactions were graded and scored according to the Draize technique. Sodium fluorescein examinations were performed to assist the visualisation of possible corneal lesions

- pH: no data
- Statistics: no statistical analyses were employed

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Remarks:
according to the method of Kay & Calandra
Basis:
mean
Remarks:
total eye irritation score at each interval for all animals / no. animals in the group
Time point:
other: 1 hour
Score:
13
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: unwashed group
Irritation parameter:
overall irritation score
Remarks:
according to the method of Kay & Calandra (1962)
Basis:
mean
Remarks:
total eye irritation score at each interval for all animals / no. animals in the group
Time point:
other: 24 hours
Score:
14.8
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: unwashed group
Irritation parameter:
overall irritation score
Remarks:
according to the method of Kay & Calandra (1962)
Basis:
mean
Remarks:
total eye irritation score at each interval for all animals / no. animals in the group
Time point:
other: 48 hours
Score:
6.7
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: unwashed group
Irritation parameter:
overall irritation score
Remarks:
according to the method of Kay & Calandra (1962)
Basis:
mean
Remarks:
total eye irritation score at each interval for all animals / no. animals in the group
Time point:
other: 72 hours
Score:
3.2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: unwashed group
Irritation parameter:
overall irritation score
Remarks:
according to the method of Kay & Calandra (1962)
Basis:
mean
Remarks:
total eye irritation score at each interval for all animals / no. animals in the group
Time point:
other: 96 hours
Score:
1.8
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: unwashed group
Irritation parameter:
overall irritation score
Remarks:
according to the method of Kay & Calandra (1962)
Basis:
mean
Remarks:
total eye irritation score at each interval for all animals / no. animals in the group
Time point:
other: 7 days
Score:
2.2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: unwashed group
Irritation parameter:
overall irritation score
Remarks:
according to the method of Kay & Calandra (1962)
Basis:
mean
Remarks:
total eye irritation score at each interval for all animals / no. animals in the group
Time point:
other: 14 days
Score:
0
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: unwashed group
Irritation parameter:
overall irritation score
Remarks:
according to the method of Kay & Calandra (1962)
Basis:
mean
Remarks:
total eye irritation score at each interval for all animals / no. animals in the group
Time point:
other: 1 hour
Score:
12
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: washed group
Irritation parameter:
overall irritation score
Remarks:
according to the method of Kay & Calandra (1962)
Basis:
mean
Remarks:
total eye irritation score at each interval for all animals / no. animals in the group
Time point:
other: 24 hours
Score:
14.7
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: washed group
Irritation parameter:
overall irritation score
Remarks:
according to the method of Kay & Calandra (1962)
Basis:
mean
Remarks:
total eye irritation score at each interval for all animals / no. animals in the group
Time point:
other: 48 hours
Score:
8.3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: washed group
Irritation parameter:
overall irritation score
Remarks:
according to the method of Kay & Calandra (1962)
Basis:
mean
Remarks:
total eye irritation score at each interval for all animals / no. animals in the group
Time point:
other: 72 hours
Score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: washed group
Irritation parameter:
overall irritation score
Remarks:
according to the method of Kay & Calandra (1962)
Basis:
mean
Remarks:
total eye irritation score at each interval for all animals / no. animals in the group
Time point:
other: 96 hours
Score:
3.3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: washed group
Irritation parameter:
overall irritation score
Remarks:
according to the method of Kay & Calandra (1962)
Basis:
mean
Remarks:
total eye irritation score at each interval for all animals / no. animals in the group
Time point:
other: 7 days
Score:
1.3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: washed group
Irritation parameter:
overall irritation score
Remarks:
according to the method of Kay & Calandra (1962)
Basis:
mean
Remarks:
total eye irritation score at each interval for all animals / no. animals in the group
Time point:
other: 14 days
Score:
0
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: washed group
Irritant / corrosive response data:
The unwashed eyes of 4 of 6 animals showed slight (grade 1) corneal opacity with epithelial peeling, and iridial irritation in 2 of 6 animals within 24 hours of instillation of dinotefuran (Table 1 and Table 2). The reaction was accompanied by slight to moderate (grade 1 or 2) erythema, chemosis and clear or purulent discharge in all 6 animals. The eyes of 4 of the animals had returned to normal appearance within 96 hours of instillation and the remaining 2 animals had returned to normal 14 days after instillation. A positive reaction occurred in 3 of 3 animals in the washed group and was characterised by slight corneal opacity and slight to moderate erythema, chemosis and discharge. With the exception of one of 3 animals that showed slight erythema and chemosis on day 7, the washed eyes of all animals returned to normal appearance by 96 hours. The appearance of the eyes of the 3rd animal had returned to normal on day 14. The mean irritation scores for all ocular reactions according to Commission Directive 93/21/EEC (Annex VI) were greatest at 24 hours in both the washed and unwashed groups (Table 1). Thereafter, they progressively declined until day 14 at which time all animals in the washed and unwashed eye groups were free of all ocular irritation reactions. None of the individual animal or group mean irritation scores exceeded the EU criteria for classification as “irritating to eyes”.

Any other information on results incl. tables

Table 1: Group mean irritation scores according to Commission Directive 93/21/EEC (Annex VI)

Observation

Mean irritation scores in the:

 

Unwashed group at:

Washed group at:

 

1hr

24hr

48hr

72hr

96hr

1hr

24hr

48hr

72hr

96hr

Corneal opacity

0.2

0.7

0.2

0.2

0.2

0.0

1.0

0.0

0.0

0.0

Iris lesion

0.2

0.3

0.2

0.0

0.0

0.0

0.0

0.0

0.0

0.0

Erythema

2.0

2.0

1.3

0.8

0.3

2.0

2.0

1.7

1.3

1.0

Edema

2.0

1.5

1.2

0.3

0.2

2.3

1.7

1.3

0.7

0.7

Table 2: Individual irritation scores

Observation

Time

Individual scores

 

 

unwashed group

washed group

 

 

1

2

3

4

5

6

7

8

9

Cornea

1hr

0 / 0

0 / 0

1 / 1

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

(severity/area)

24hr

0 / 0

0 / 0

1a/ 1

1a/ 1

1a/ 1

1a/ 2

1a/ 1

1a/ 1

1a/ 2

(A / B)

48hr

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

1a/ 1

0 / 0

0 / 0

1a/ 1

 

72hr

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

1a/ 1

0 / 0

0 / 0

0 / 0

 

96hr

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

1 / 1

0 / 0

0 / 0

0 / 0

 

7days

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

1 / 1

0 / 0

0 / 0

0 / 0

 

14days

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

Iris

1hr

0

0

1b

0

0

0

0

0

0

(C)

24hr

0

0

1b

0

0

1b

0

0

0

 

48hr

0

0

0

0

0

1b

0

0

0

 

72hr

0

0

0

0

0

0

0

0

0

 

96hr

0

0

0

0

0

0

0

0

0

 

7days

0

0

0

0

0

0

0

0

0

 

14days

0

0

0

0

0

0

0

0

0

Redness

1hr

2c

2c

2c

2c

2c

2c

2c

2c

2c

(D)

24hr

2c

2c

2c

2c

2c

2c

2c

2c

2c

 

48hr

1

1

1

1

2c

2c

2

1

2c

 

72hr

0

1

0

1

1

2

1

1

2c

 

96hr

0

0

0

1

0

1

1

0

2

 

7days

0

0

0

1

0

2

0

0

1

 

14days

0

0

0

0

0

0

0

0

0

Chemosis

1hr

2

2

2

2

2

2

2

2

3

(E)

24hr

1

2

1

1

1

3

2

1

2

 

48hr

1

1

1

1

1

2

1

1

2

 

72hr

0

0

0

0

1

1

0

0

2

 

96hr

0

0

0

0

0

1

0

0

2

 

7days

0

0

0

0

0

1

0

0

1

 

14days

0

0

0

0

0

0

0

0

0

Discharge

1hr

1d

1d

2d

2e

2e

2d

0

0

1e

(F)

24hr

0

1d

1d

1d

1d

2d

0

0

0

 

48hr

0

0

0

0

0

0

0

0

0

 

72hr

0

0

0

0

0

0

0

0

0

 

96hr

0

0

0

0

0

0

0

0

0

 

7days

0

0

0

0

0

0

0

0

0

 

14days

0

0

0

0

0

0

0

0

0

acorneal epithelial peeling;

binjected;

cblanching;

dclear discharge;

epurulent discharge

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Dinotefuran is slightly irritating to the eyes of the rabbit but does not require classification in the EU under the provisions of Commission Directive 93/21/EEC, Annex VI (1993), and no risk phrase is required in respect of ocular irritation. Dinotefuran is slightly irritating to both irrigated and unirrigated rabbit eyes, based on the classification system of Kay & Calandra (1962) (category IV according to EPA classification criteria and not classified according to GHS criteria).