Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Betweem 10 December 1998 amd 31 December 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Nature of substance: Applied as supplied

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 3.04 kg and was twelve to sixteen weeks old. After an acclimatisation period of at least 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 a 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, Witham, Essex, UK) was allowed throughout the study.

The animal room was maintained at a temperature of 17 to 22 C and relative humidity of 43 to 65%. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours light and twelve hours darkness.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
47 mg (volume of 0.1 ml)
Duration of treatment / exposure:
Directly after application 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
Observation period (in vivo):
Assessment of ocular damage / irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48-49.

Additional observations were made on Days 7, 14 and 21 to assess the reversibility of the ocular effects.
Duration of post- treatment incubation (in vitro):
Not relevant
Number of animals or in vitro replicates:
1

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
24/48/72 h
Score:
1
Max. score:
1
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
24/48/72 h
Score:
2
Max. score:
2
Remarks on result:
other: Max. duration: 14 h; Max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
24/48/72 h
Score:
2
Max. score:
2
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
24/48/72 h
Score:
1.3
Max. score:
1.3
Irritation parameter:
conjunctivae score
Remarks:
(discharge)
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
24/48/72 h
Score:
3
Max. score:
3
Irritant / corrosive response data:
A single application of the test material to the non-irrigated eye of one rabbit produced translucent corneal opacity, iridial inflammation and moderate conjunctival irritaion. Other ocular effects noted were vascularisation of the cornea, a pale appearance of the nictitating membrane, petechial haemorrhage of the nictitating membrane and ectropion. The persistence of vascularisation at the 21-day observation was considered to be an irreversible effect.

Reversibility of any observed effect: Changes not fully reversible within 21 days

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Translation from Directive 67/548/EEC to CLP
Conclusions:
The test material, BMS 214702-01, produced a maximum total score of 37.0 and was considered to be corrosive to the rabbit eye due to irreversible effects, according to a modified version of the Kay and Calandra System (Kay J H and Calandra J C, J. Soc. Cosmet. Chem., 1962, 13, 281-289)

The test material produced positive criteria in the treated rabbit according to EU labelling regulations and was considered to be irritant to the rabbit eye. It is reasonable to assume the symbol "Xi" and highest risk phrase R41 "Risk of serious damage to eyes" are therefore required.
Executive summary:

Methods

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 Commission 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.

Results

A single application of the test material to the non-irrigated eye of one rabbit produced translucent corneal opacity, iridial inflammation and moderate conjunctival irritation. Other ocular effects noted were vascularisation of the cornea, a pale appearance of the nictitating membrane, petechial haemorrhage of the nicitating membrane and ectroption. The persistence of vascularisation at the 21-day observation was considered to be an irreversible effect.

Conclusions

The test material produced a maximum total score of 37.0 but was considered to be corrosive to the rabbit eye due to irreversible effects.

The test material was also considered to be irritant according to EU labelling regulations. It is reasonable to assume that the symbol "Xi" and highest risk phrase R41 "Risk of serioud damage to eyes" are therefore required