Registration Dossier

Administrative data

Description of key information

Skin Irritation, rabbit: not irritating, OECD 404 (Mastrocco et al., 1986)
Eye Irritation, rabbit: not irritating, OECD 405 (Mastrocco et al., 1986)
Respiratory irritation: no data

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:
14 January 1986 to 17 January 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
3 male and 3 female rabbits
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
0.5g of the test material.
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
Test material (0.5g) was applied to the shaved skin of 3 male and 3 female rabbits, moistened with water and covered by a gauze pad, which was held in place by a tape for 4 hours. Collars prevented the rabbits from ingesting the test article. After the exposure period the test article was removed with a moist paper towel. One hours after removal of the gauze pad and 24, 48 and 72 hours after the application of the test article the skin reaction was scored according to the Draize scheme
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: Not applicable - no reactions observed
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: Not applicable - no reactions observed.
Irritant / corrosive response data:
No signs of dermal irritation were noted at any observation time.
Other effects:
None.

No signs of dermal irritation were noted at the 1, 24, 48 or 72 hour time points.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No signs of dermal irritation were noted at the 1, 24, 48 or 72 hour time points and it was concluded that benoxacor was not irritant to the skin of rabbits.
Executive summary:

A single topical application of 0.5g of benoxacor to the shaved skin of six NZW rabbits under an occluded dressing resulted in no signs of dermal irritation at any of the assessment time points. It was concluded that benoxacor was not irritating to the skin of rabbits.

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:
18 February 1986 to 4 March 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
4 male and 5 female rabbits
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
9
Details on study design:
CGA154281 (100 mg) was instilled into the conjunctiva! sac of the right eye of 4 male and 5 female rabbits. The eye lids were gently held together for about one second to prevent the loss of material. The left eyes served as a control. The eyes of one male and two female rabbits were rinsed after 30 seconds with tap water for about 60 seconds. The eyes of the remaining rabbits were rinsed with water 24 hours after instillation. Elizabethan collars prevented the rabbits from removing the test article.
One, 24, 48 and 72 hours as well as 7 and 14 days after instillation of the test article the eyes were scored according to the Draize scheme. Additionally ophthal-mological examinations were made pre dose and after 1, 7, and 14 days.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: not examined at 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.17
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: not examined at 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24,48,72 hr
Score:
1.61
Max. score:
3
Reversibility:
fully reversible within: 28 days
Remarks on result:
other: still present in 2 of 6 rabbits at 14 days, not examined 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24,48,72 hr
Score:
0.94
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: not examined at 7 days
Irritant / corrosive response data:
When the eyes were rinsed after 30 seconds, only minor signs of ocular irritation, i.e. conjunctival redness up to score 2 and conjunctival chemosis up to score 1 were observed. No signs of irritation were recorded at the 48 hour investigation.
The eyes rinsed after 24 hours displayed slight cornea (score 1) and iris lesions (score 1). Moderate conjunctival redness (up to score 3) and chemosis (up to score 2) were recorded. Beside slight conjunctival redness (score 1) in one male and one female rabbit, no signs of ocular irritation were recorded at 14 days. Both affected rabbits were free of any findings by 28 days.
Additionally, ocular discharge (score 1) was observed in all rabbits 1 and 24 hours after instillation of the test material. Discharge was also noted in one female after 72 and 168 hours, however, this was not considered test-article related, since discharge was also detected in the untreated eye. This female was killed due to poor physical condition on test day 7.


Mean Draize scores of ocular irritation

Cornea

Iris

Conjunctival
 redness

Chemosis

Time

rinsed

not rinsed

rinsed

not rinsed

rinsed

not rinsed

rinsed

not rinsed

1 h

0

0.33

0

0.17

1.33

2.00

0.67

1.00

24 h

0

0.17

0

0.33

1.00

2.00

0

1.33

48 h

0

0.33

0

0.17

0

1.67

0

1.00

72 h

0

0.17

0

0

0

1.17

0

0.50

14 days

0

0

0

0

0

0.33

0

0

28 days

0

0

0

0

0

0

0

0

Mean

24, 48, 72 h

0.22

0.17

1.61

0.94

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Although there were signs of irritation in the rabbit eye 24, 48 and 72 hours after instillation of benoxacor, these were fully reversible and were not of sufficient severity to warrant classification.
Executive summary:

A single dose of 100 mg was instilled into the conjunctival sac of the right eye of nine rabbits. The left eye remained untreated as a contralateral control.

Eyes of three of the treated animals were rinsed with tap water 30 seconds after instillation. Eyes of the remaining 6 rabbits were rinsed 24 hours after test substance instillation. Reactions were assessed using the standard Draize methods for ocular iirritation.

Data obtained when eyes were rinsed after 30 seconds are not relevant to the the assessment of benoxacor. When the eyes were rinsed after 24 hours, the mean scores for the 24-72 hour post-instilllation period form the basis for assessment of the need to classifiy the test material as an ocular irritant. In this study none of the mean scores and no two individual scores exceeded the threshold values for classification.

While benoxacor did induce some signs of ocular irritation the severity and duration of the reactions were insufficient to necessitate classification.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Guideline- and GLP-compliant studies on skin and eye irritation are available for benoxacor. Benoxacor has been tested in rabbits (Mastrocco et al., 1986). There was no evidence of skin irritation or corrosion in rabbits.

Data on benoxacor indicate that instillation of liquid test substance into the rabbit eye induced some evidence of irritation. Signs of eye irritation were fully reversible and were not of a severity that warrants classification and labelling (Mastrocco et al., 1986).

There is no information concerning respiratory irritation of benoxacor and no information on skin or eye irritation of benoxacor in humans.


Justification for selection of skin irritation / corrosion endpoint:
One reliable, GLP- and guideline-conform study available.

Justification for selection of eye irritation endpoint:
One reliable, GLP- and guideline-conform study available.

Justification for classification or non-classification

The available data on skin corrosion/irritation are considered reliable and adequate for the classification and labelling. The data on benoxacor indicate that the test material produces no evidence of skin irritation or corrosion. Based on the result, the substance does not meet the criteria for classification under the Directive 2001/59/EC, Annex VI, 3.2.6.1 as well as the criteria in the Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.2.2, as amended by Regulation (EC) No. 286/2011.

The available data on eye irritation are considered reliable and suitable for classification and labelling. Although there is some evidence of eye irritation, this is fully reversible and the severity is not sufficient to warrant classification. Based on the results, the substance does not meet the criteria for classification under the Directive 2001/59/EC, Annex VI, 3.2.6.2 as well as the criteria in the Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.3.2, as amended by Regulation (EC) No. 286/2011.