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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation, other
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17.05.1995 - 19.05.1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
evaluation of eye response refering to Draize's method: 1959
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
419-240-6
EC Name:
-
Cas Number:
171054-89-0
Molecular formula:
Hill formula: C28H37NO7 CAS formula: (C11H12O3)2.C6H13NO
IUPAC Name:
bis(4-(4-methylphenyl)-4-oxobutanoic acid); 4-ethylmorpholine
Test material form:
solid: crystalline
Details on test material:
Substance quality: >97%
Batch No.: E- 007K107SLL

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
One New Zealand White rabbit supplied by David Percival Ltd., Moston, Sandbach, Cheshire, UK, was used. At the start of the study the animal weighed 3.08 kg and was approximately twelve to six weeks old. After a minimum acclimatisation period of five days the animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animal was housed in a suspended metal cage. Free access to mains drinking water and food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd., Witham, Essex, UK) was allowed throughout the study.
The animal room was maintained at a temperature of 17 to 20 °C and relative humidity of 49 to 58%. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours continous light and 12 hours darkness.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
about 1 s
Observation period (in vivo):
1 h, 24 h, 48 h
Number of animals or in vitro replicates:
1 animal
Details on study design:
Immediately before the start of the test, both eyes of the provisionally selected test rabbit was examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope.
A volume of 0.1 mL of the test material, which was found to weigh approximately 17 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. 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. The left eye remained and was used for control purposes. Immediately after administration of the test material, an assassment of the initial pain reaction was made.
Assessment of ocular damage/irritation was made approximately 1, 24 and 48 hours following treatment, according to the numerical evaluation given in Appendix I, (from Draize J.H. (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Acedemy of Sciences, Washington D.C. p.48 to 49).
Any other ocular effects were also noted. 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:
iris score
Basis:
animal #1
Time point:
other: 1 h
Score:
5
Max. score:
10
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24 h
Score:
5
Max. score:
10
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
iris score
Basis:
animal #1
Time point:
48 h
Score:
5
Max. score:
10
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 1 h
Score:
40
Max. score:
80
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24 h
Score:
40
Max. score:
80
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
48 h
Score:
40
Max. score:
80
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 1 h
Score:
2
Max. score:
6
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
6
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
48 h
Score:
2
Max. score:
6
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 1 h
Score:
2
Max. score:
8
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
8
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
48 h
Score:
2
Max. score:
8
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
other: discharge score
Basis:
animal #1
Time point:
other: 1 h
Score:
3
Max. score:
6
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
other: discharge score
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
6
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
other: discharge score
Basis:
animal #1
Time point:
48 h
Score:
3
Max. score:
6
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #1
Time point:
other: 1 h
Score:
59
Max. score:
110
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #1
Time point:
24 h
Score:
57
Max. score:
110
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #1
Time point:
48 h
Score:
59
Max. score:
110
Reversibility:
other: On humane grounds the study was determined prematurely after the 48 hour observation time due to the severity of the eye irritation.
Irritant / corrosive response data:
Areas of translucent corneal opacity were noted in the treated eye one hour after treatment and at the 24 and 48-hour observations. Sloughing of the cornea was noted in the treated eye one hour after treatment.
Other effects:
Sloughing of the cornea and lower conjunctival membrane together with pale green discolouration of the nictitating membrane was observed.

Iridial inflammation was noted in the treated eye one hour after treatment and at the 24 and 48-hour observations.
Moderate conjunctival irritation was noted in the treated eye one hour after treatment and at the 24 and 48-hour observations.
Pale green discolouration of the nicitating membrane was noted in the treated eye one hour after treatment. Sloughing of the lower conjunctival membrane was noted in the treated eye at the 48-hour observation.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test material produced a maximum score of 59.0 and was classified as 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.
The test material was also considered to be irritant according to EU labelling regulations. It is reasonable to assume that the symbol "Xi", the indication of danger "irritant" and the highest risk phrase R41 "RIKS OF SERIOUS DAMAGE TO EYES" are therefore required.
Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 February 1987) and Method B5 of Comission Directive 92/69/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 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

A single application of the test material to the non-irrigated eye of one rabbit produced areas of translucent corneal opacity, iridial inflammation and moderate conjunctival irritation. Other ocular effects noted were sloughing of the cornea and lower conjunctival membrane and pale green discolouration of the nicitating membrane. The animal was killed for humane reasons immediately after the 48-hour observation in accordance with current UK Home Office guidelines. No further animals were treated.