Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Conducted under OECD and EU methods, and under GLP conditions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Substance type: off white powder
- Physical state: solid
- Storage condition of test material: room temperatire until 14 October 2013 and then approximately 4° C in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: supplied by Harlan Laboratories UK Ltd.
- Age at study initiation: 12-20 weeks old
- Weight at study initiation: 2.29 to 3.06kg
- Housing: Suspended cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23° C
- Humidity (%): 30-70%
- Air changes (per hr): 15 changes per hour
- Photoperiod: 12 hrs dark /12 hrs light

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): At each test site 0.5g of test item, moistened with 0.5ml of distilled water


Duration of treatment / exposure:
First rabbit was treated with test material on 3 sites on its back and covered with patches. Duration was 3 minutes, 1 hour and 4 hours after application for the 3 test sites.
Second and third Rabbits were treated with test material in one site on their backs , covered with patches and was left there in contact with the skin for 4 hour period.
Observation period:
Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary
irritation
Number of animals:
3 rabbits
Details on study design:
TEST SITE
- Area of exposure: Back of rabbit
- Type of wrap if used: Cotton gauze patch and rabbit was wrapped in an elasticated corset for duration of exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any residual test item was removed by gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: First Rabbit test substance was removed from 3 different sites after 3 minutes, 1 hour and 4 hours respectively.
Second and Third Rabbit, test substance (1site) was removed after a 4 hour exposure period.

SCORING SYSTEM:

Erythema and Eschar Formation 0
No erythema 1
Very slight erythema (barely perceptible) Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to eschar formation preventing grading of erythema 4

Edema Formation
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-defined by definite raising) 2
Moderate edema (raised approximately 1 millimeter) 3
Severe edema (raised more than 1 millimeter and extending beyond the area of exposure) 4

The scores for erythema and edema at the 24 and 72-Hour readings were totaled for the three test rabbits and this total was divided by 6 to give the primary irritation index of the test item. The test item was classified according to the following scheme devised by Draize, J.H. (1959):

Primary Irritation Index Classification of Irritancy

0 Non-irritant
> 0 to 2 Mild irritant
> 2 to 5 Moderate irritant
> 5 to 8 Severe irritant






Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 72 hoours
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 72 hours
Score:
ca. 0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
other: A value of 4 was noted in report but only due to a technician error obervation not performed at 24 hr and exact numerical value impossible to report. Left at zero to be consistent with other animals.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 72 hours
Score:
ca. 0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
other: A value of 4 was noted in report but only due to a technician error obervation not performed at 24 hr.and exact numerical value impossible to report. Left at zero to be consistent with other animals.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritant / corrosive response data:
SKIN REACTIONS

3-Minute Exposure Period:
The individual scores for erythema/eschar and edema are given in Table 1 (attached below) . No evidence of skin irritation was noted during the
study.

1-Hour Exposure Period:
The individual scores for erythema/eschar and edema are given in Table 1 (attached below). No evidence of skin irritation was noted during the
study.

4-Hour Exposure Period:
The individual scores for erythema/eschar and edema are given in Table 2 (attached below). No evidence of skin irritation was noted during the
study.

Body Weight:
Individual body weights and body weight change are given in Table 3 (attached below) . All animals showed expected gain in body weight during the study.
Other effects:
For animal #2: A value of 4 was noted in report but only due to a technician error obervation not performed and exact numerical value impossible to report. Reprt here as zero to be consistent with other animals.

Any other information on results incl. tables

Results attached below as follows:

Table 1 Individual Skin Reactions Following 3 -Minute and 1 Hour Exposures

Table 2 Individual Skin Reachtions Following 4 -Hour Exposure

Table 2 : Individual Body Weights and Body Weight Change

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test site, the test substance, produced a primary irritation index of 0.0 - 1.3* and was classified as non-irritant to mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

* A value of 1.3 was noted in report but only due to a technician error obervation not performed on animal #2 at 24 hrs and exact numerical value impossible to report. In results section reported as zero to be consistent with other animals.

Therefore, Boronic Acid would not be classified as an irritant according to GHS or EC CLP 1272/2008.