Registration Dossier

Administrative data

Description of key information

Skin irritation / corrosion

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 17 July 1992) and Method B4 of Commission Directive 93/21/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

The test material, BMS 214702-01, produced a primary irritation index of 0.0 to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations.

Eye irritation / corrosion

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 test material produced a maximum total score of 37.0 but was considered to cause irriversible damage to the rabbit eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 2 December 1998 and 5 December 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 17 July 1992
Deviations:
yes
Remarks:
On one occasion the temperature was below the limit specified in the protocol (17 C). This deviation was considered not to affect the purpose or integrity of the study
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
Commission Directive 92/69/EEC
Deviations:
yes
Remarks:
On one occasion the temperature was below the limit specified in the protocol (17 C). This deviation was considered not to affect the purpose or integrity of the study
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Animals were supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK. At the start of the study the animals weighed 2.74 to 3.24 kg and were twelve to sixteen weeks old. After a minimum acclimatisation period of five days each 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 animals were individually housed in suspended metal cages. 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 16 to 20 C and relative humidity of 43 to 54%. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Remarks:
Material was used as supplied
Controls:
no
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 h
Observation period:
72 hours
Number of animals:
3
Details on study design:
On the day before the test each rabbit was clipped free of fur from the dorsal flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.

On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5g of test material, moistened with 0.5 ml of distilled water, was introduced under a 2.5cm x 2.5cm cotton gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5cm x 4.0cm). To prevent the animals from interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.

Four hours after application the corset and patches were removed from each animal and any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.

Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the scale 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.31.
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No dermal reactions were noted during the study.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material, BMS 214702-01, produced a primary irritation index of 0.0 to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations. No symbol and risk phrase are required.
Executive summary:

Methods

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 17 July 1992) and Method B4 of Commission Directive 93/21/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 4 -hour, semi-occluded application of the test material to the intact skin of three rabbits produced no dermal reactions

Conclusions

The test material, BMS 214702-01, produced a primary irritation index of 0.0 to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations. No symbol and risk phrase are required.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
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.
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
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
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

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

The test material, BMS 214702-01, produced a maximum total score of 37.0 and was considered to cause irreversible damage to the rabbit eye, 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). Therefore classified as H318: Causes serious eye damage.