Registration Dossier

Administrative data

Description of key information

The test substance was not classified as either a skin irritant or an eye irritant based on the results of in vivo studies.

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:
20 September 1983 to 26 September 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted to acceptable standards.
Qualifier:
according to
Guideline:
other: "Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965).
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Healthy New Zealand White rabbits were used. These were aged 12-14 weeks with average body weights of 2.19 kgs (male) and 2.15 kgs. (female) and were obtained from a commercial supplier (Hacking and Churchill) Six rabbits (3 and 3 )were acclimatized in the test area for one week prior to the start of the trial.

Husbandry
The rabbits were caged singly in an experimental room maintained at a temperature of 16°C (± 1°) and a relative humidity of 50 - 70%. Animals were exposed to artificial light for 10 hours daily from 08.00 - 18.00 hours. A commercial diet (Labsure, Christopher Hill Group)was fed ad lib. Filtered water acidified to approximately pH 3 was available at all times.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL test substance was applied
Duration of treatment / exposure:
24 hours
Observation period:
14 days or until any effects had resolved
Number of animals:
6
Details on study design:
Twenty four hours prior to the dermal application, the backs of the rabbits were shaved over an area consisting of at least 10% of the total body surface. Two test sites lateral to the mid line of the back were used on each rabbit. Immediately before the application of the test compound, the right hand site was abraded with the point of a sterile hypodermic needle. The abrasions were sufficiently deep to penetrate the stratum corneum, but not to damage the dermis. The left hand site remained intact.

0.5 ml of the compound as supplied was applied to each test site on a 2.5 cm square gauze pad. These were covered with aluminium foil secured with "Transpore" surgical tape. The test sites were then covered by a 6" wide "Coban"-self adhesive bandage in order to retain the testsubstance in close contact with the skin. After 24 hours the dressing was removed and the intact and abraded application sites were assessed for oedema and erythema. A further assessment was made at 72 hours and for any further period considered necessary up to 14 days.

The assessment of the macroscopic skin reaction was made according to the following grading system:

Primary Irritation Score

0: Non irritating
0.1- 0.5: Minimally irritating
0.6 - 1.5: Slightly irritating
1.6 - 3.0: Mildly irritating
3.1- 5.0: Moderately irritating
5.1 - 6.5: Severely irritating
6.6 - 8.0: Extremely irritating





Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean
Time point:
other: At 24 hours and at 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: Intact skin. No assessment done at 48 hours.
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean
Time point:
other: At 24 hours and at 72 hours
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin. No assessment done at 48 hours
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean
Time point:
other: At 24 hours and at 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: Intact skin. No assessment done at 48 hours.
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
mean
Time point:
other: At 24 hours and at 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin. No assessment done at 48 hours.
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
mean
Time point:
other: At 24 hours and at 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: Intact skin. No assessment done at 48 hours.
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
mean
Time point:
other: At 24 hours and at 72 hours
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin. No assessment done at 48 hours.
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean
Time point:
other: At 24 hours and at 72 hours
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin. No assessment done at 48 hours.
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean
Time point:
other: At 24 hours and at 72 hours
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: Intact skin. No assessment done at 48 hours.
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean
Time point:
other: At 24 hours and at 72 hours
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: Intact skin. No assessment done at 48 hours.
Irritation parameter:
edema score
Basis:
animal #4
Remarks:
mean
Time point:
other: At 24 hours and at 72 hours
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: Intact skin. No assessment done at 48 hours.
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
mean
Time point:
other: At 24 hours and at 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: Intact skin. No assessment done at 48 hours.
Irritation parameter:
edema score
Basis:
animal #6
Remarks:
mean
Time point:
other: At 24 hours and at 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin. No assessment done at 48 hours.
Irritant / corrosive response data:
24 hours
Slight/well defined erythema was seen:on 3/6 intact and 4/6 abraded sites. Very slight oedema was seen on 5/6 intact and 4/6 abraded sites. Slight oedema was seen on one abraded site.

72 hours
Very slight oedema was seen on 3/6 intact and abraded sites.

6 days

All sites were normal.


The reactions were similar on intact and abraded sites. The primary irritation score was 1.1
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the results of an in vivo study in New Zealand White rabbits, the test substance was not classified as a skin irritant.
Executive summary:

According to the results of an in vivo study in New Zealand White rabbits, the test substance was not classified as a skin irritant.

The mean oedema score and the mean erythema score for each of the 6 rabbits at 24 hours and at 72 hours was less than or equal to 1. All effects were fully reversible within 6 days.

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:
20 September to 23 September 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted to acceptable standards.
Qualifier:
according to
Guideline:
other: Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965)
Deviations:
yes
Principles of method if other than guideline:
The test was carried out in accordance with the procedure set out in the "Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965), with slight modification.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Animals
Healthy New Zealand White rabbits were used. These were aged 12-14 weeks with average body weights of 2.19 kgs (2 females) and 2.15 kgs. (2 males) and were obtained from a commercial supplier (Hacking and Churchill). Six rabbits (3 males and 3 females) were acclimatized in the test area for one week prior to the start of the trial.

Husbandry
The rabbits were caged singly in an experimental room maintained at a temperature of l6°C (± 1°)and a relative humidity of 50 - 70%. Animals were exposed to artificial light for 10 hours daily from 08.00 - 18.00 hours. A commercial diet (Labsure, Christopher Hill. Group)was fed ad lib. Filtered water acidified to approximately pH3 was available at all times.
Vehicle:
unchanged (no vehicle)
Controls:
other:
Amount / concentration applied:
0.1 ml of the test compound were instilled into the conjunctival sac of the left eye.
Duration of treatment / exposure:
30 seconds
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
Six rabbits
Details on study design:
The eyes of the experimental animals were examined and found normal prior to the test. 0.1 ml of the test compound were instilled into the conjunctival sac of the left eye. The eyelids were then held closed for 1 second. The right eye served as a control. After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits with approximately 200 ml. of warm water.

The rabbits were examined 1, 24, 48 and 72 hours after application of the test compound and for any further period that was considered necessary. The ocular reactions were scored by the method described in "Appraisal of the Safety of Chemicals in Food Drugs and Cosmetics" page 51, published by the Association of Food and Drug Officials of the U.S.A. Fluorescein (Fluorets -Smith and Nephew Pharmaceuticals Limited)was used as an aid in assessing corneal damage.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: At 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
other: Not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: At 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: At 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
other: Not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
other: At 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
other: At 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
other: Not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
other: At 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
other: Not applicable
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
for all 6 animals
Time point:
other: At 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
for all 6 animals
Time point:
other: At 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
for all 6 animals
Time point:
other: At 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: Not applicable
Irritant / corrosive response data:
Conjunctiva

A very slight reaction was seen 2/3 washed and 3/3 unwashed eyes in 1 hour after compound application.

3/3 washed and 1/3 unwashed eyes were normal at 24 hours. The remaining 2/3 unwashed eyes were normal at 48 hours.

The reactions seen in unwashed eyes were similar to those in washed eyes.
Other effects:
None
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on these results, the substance is not classified as an eye irritant.
Executive summary:

Based on these results, the substance is not classified as an eye irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

According to the results of an in vivo study in New Zealand White rabbits, the test substance was not classified as a skin irritant.

According to the results of an in vivo study in New Zealand White rabbits, the test substance was not classified as an eye irritant.


Justification for selection of skin irritation / corrosion endpoint:
Only 1 study is available for the test substance.

Justification for selection of eye irritation endpoint:
Only 1 study is available for the test substance.

Justification for classification or non-classification

The above studies have all been ranked reliability 2 according to the Klimisch et al system. This ranking was deemed appropriate because the studies were conducted in compliance with acceptable guidelines. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008).