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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:
07/02/1991-09/02/1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 405)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
referenced as Method B5 in Commission Directive 84/449/EEC
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston Sanbach, Cheshire, UK
- Age at study initiation: twelve to sixteen weeks old
- Weight at study initiation: 2.90 kg
- Housing: individually housed in a suspended metal cage
- Diet (e.g. ad libitum): ad libitum (Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bristol)
- Water (e.g. ad libitum): ad libitum (drinking water)
- Acclimation period: minimum acclimatisation period of five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): animal room maintained at 17-20°C
- Humidity (%): relative humidity of 52-57%
- Air changes (per hr): approximately 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the left eye remained untreated and was used for control purposes
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 ml of the test material, which was found to weigh approximately 98 mg (as measured by gently compacting the required volume into and adapted syringe)

Duration of treatment / exposure:
one second: The upper and lower eyelids were held together for about one second immediately after application, to prevent loss of the test material, and then released.
Observation period (in vivo):
1 hour, 24 and 48 hours following treatment
Number of animals or in vitro replicates:
one
Details on study design:
SCORING SYSTEM: Assessment of ocular damage/irritation was made according to the numerical evaluation from Draize J. H. 1959, Association of Food and Drug Officials of the united States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics".


TOOL USED TO ASSESS SCORE: examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
E: degree of opacity
Basis:
animal #1
Time point:
other: 1, 24, 48 hours
Score:
1 - 2
Max. score:
4
Reversibility:
not specified
Remarks:
animal killed after 48h
Irritation parameter:
cornea opacity score
Remarks:
F: area of opacity
Basis:
animal #1
Time point:
other: 1, 24, 48 hours
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks:
animal killed after 48h
Irritation parameter:
cornea opacity score
Remarks:
(E x F) x 5
Basis:
animal #1
Time point:
other: 1, 24, 48 hours
Score:
0 - 40
Max. score:
80
Irritation parameter:
iris score
Remarks:
D
Basis:
animal #1
Time point:
other: 1, 24, 48 hours
Score:
1
Max. score:
2
Reversibility:
not specified
Remarks:
animal killed after 48h
Irritation parameter:
iris score
Remarks:
D x 5
Basis:
animal #1
Time point:
other: 1, 24, 48 hours
Score:
5
Max. score:
10
Irritation parameter:
conjunctivae score
Remarks:
A: redness
Basis:
animal #1
Time point:
other: 1, 24, 48 hours
Score:
2 - 3
Max. score:
3
Reversibility:
not specified
Remarks:
animal killed after 48h
Remarks on result:
other: white areas over nictitating membrane. Sloughing of conjunctival membrane
Irritation parameter:
conjunctivae score
Remarks:
B: chemosis
Basis:
animal #1
Time point:
other: 1, 24, 48 hours
Score:
2
Max. score:
4
Reversibility:
not specified
Remarks:
animal killed after 48h
Irritation parameter:
conjunctivae score
Remarks:
C: discharge
Basis:
animal #1
Time point:
other: 1, 24, 48 hours
Score:
2
Max. score:
3
Reversibility:
not specified
Remarks:
animal killed after 48h
Irritation parameter:
conjunctivae score
Remarks:
(A + B + C) x 2
Basis:
animal #1
Time point:
other: 1, 24, 48 hours
Score:
12 - 14
Max. score:
20
Irritation parameter:
overall irritation score
Remarks:
Total score
Basis:
animal #1
Time point:
other: 1, 24, 48 hours
Score:
17 - 59
Max. score:
110
Irritant / corrosive response data:
A dulling of the normal luster of the corneal surface was noted in the treated eye one hour after treatment. Areas of diffuse corneal opacity were noted at the 24-hour observation with areas of grade 4 corneal opacity at the 48-hour observation.
Iridial inflammation was noted in the treated eye at the one, 24 and 48-hour observations.
Moderate conjunctival irritation was noted in the treated eye one hour after treatment and at 24 and 48-hour observations. White areas over the nictitating membrane were also noted at the 24 and 48-hour observations. Sloughing of the conjunctival membrane was noted in the treated eye at the 48-hour observation.
Due to severe ocular reactions the animal was killed for humane reasons immediately after the 48-hour observation in accordance with Home Office guidelines. No further animals were treated.

Any other information on results incl. tables

Individual scores and total scores for ocular irritation

Rabbit number and sex                IPR3                                             85 Male

(bodyweight Kg)                                                                                 (2.90)

Time after treatment

1 hour

24 hours

48 hours

CORNEA

E = degree of opacity

d

1

2

F = area of opacity

4

4

4

Score (E x F) x 5

0

20

40

IRIS

D

1

1

1

Score (D x 5)

5

5

5

CONJUNCTIVAE

A = redness

2

2 W

3 SlW

B = chemosis

2

2

2

2 = discharge

2

2

2

Score (A + B + C) x 2

12

12

14

Total score

17

37

59

IPR = initial pain reaction

Sl = sloughing of conjunctival membrane

d = dulling of the normal lustre of the corneal surface

W = white areas over nictitating membrane

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
The test material, DTBP, produced a maximum total score of 59 and was considered to be at least a severe irritant (class 6 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and calandra classification system (based on one rabbit only).
The test material produced positive criteria in the treated rabbit according to the EEC labelling regulations and was considered to be irritant to the rabbit eye.
Executive summary:

A study was performed to assess the irritancy potential of the test material, DTBP, to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion" referenced as Method B5 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 83/467/EEC).

A single application of the test material to the non-irrigated eye of one rabbit produced areas of grade 4 corneal opacity, iridial inflammation and moderate conjunctival irritation. Other adverse effects noted were a dulling of the normal lustre of the corneal surface, white areas over nictitating membrane and sloughing of the consjunctival membrane.

The test material, DTBP, produced a maximum total score of 59 and was considered to be at least a severe irritant (class 6 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and calandra classification system (based on one rabbit only).

The test material produced positive criteria in the treated rabbit according to the EEC labelling regulations and was considered to be irritant to the rabbit eye.