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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From 22 October 2012 to 05 November 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across study hence maximum reliability rating of 2 assigned according to ECHA guidance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
Octadecanoic acid, 12-hydroxy-, reaction products with ethylenediamine
IUPAC Name:
Octadecanoic acid, 12-hydroxy-, reaction products with ethylenediamine
Constituent 2
Reference substance name:
100545-48-0
Cas Number:
100545-48-0
IUPAC Name:
100545-48-0
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material: Octadecanoic acid, 12-hydroxy-, reaction products with ethylenediamine

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Argenvilliers, France
- Age at study initiation: 2 to 4 months old on the day of treatment
- Mean body weight at study initiation: 2788 g (range: 2700 g to 2945 g)
- Fasting period before study: No
- Housing: The animals were individually housed in noryl cages
- Diet: 110 pelleted diet (free access)
- Water: Tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: At least 5 d before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3°C
- Humidity: 50 ± 20%
- Air changes: approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h.

IN-LIFE DATES: From 23 October 2012 to 05 November 2012.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: a quantity of 0.5 g/flank was used.


DOSE FORMULATION PREPARATION
- The test substance was used in its original form. The pH of the test substance was measured with pH paper in order to confirm that the pH value is > 2 and < 11.5.
- Dose formulations preparations were prepared by the testing laboratory extemporaneously on the day of each administration.
- The dose formulation preparations were stored at room temperature and delivered to the study room in paper bags.
Duration of treatment / exposure:
3 min, 1 h, 4 h
Observation period:
1, 24, 48 and 72 h after removal of the dressing; if relevant, daily until reversibility of reactions
Number of animals:
Three males
Details on study design:
RATIONALE FOR STUDY DESIGN
- The sequential study design was as follows:
The test substance was applied for 3 minutes on the skin of a single animal 1:
- as no full thickness destruction of skin tissue was observed in the first hour after removal of the pad, the test substance was applied on another treatment site for 1 h,
After the 1-h application on animal 1:
- as no full thickness destruction of skin tissue was observed in the first hour after removal of the pad, the test substance was applied on another treatment site for 4 h,
After the 4-h application on animal 1:
- as mean value from grading at 24, 48 and 72 h after patch removal was < 2.3 for erythema and for edema, the test substance was applied on the skin of two other animals for 4 h (in animal 2 and 3).
For each animal, the day of dose application was recorded as Day 1 of its observation period.


TEST SITE
- The test substance was placed on a gauze pad, moistened with drinking water treated by reverse osmosis, which was then applied to a skin area of approximately 6 cm2. A quantity of 0.5 g/flank was used. During each exposure time, a dry gauze pad was applied to the opposite flank, in order to check that no alteration of the skin is induced by the semi-occlusive dressing and restraining bandage. The untreated flank acted as control.
- The gauze pad was held in place by a non-irritating semi-occlusive dressing and a restraining bandage.


REMOVAL OF TEST SUBSTANCE
After required period of contact with the skin, the dressing was removed. After removal of the dressing, any residual test substance was wiped off by means of moistened cotton pad with drinking water treated by reverse osmosis.


CLINICAL EXAMINATIONS
- Morbidity and mortality: Each animal was checked for mortality or morbidity once a day during the treatment and observation periods.
- Clinical signs: Each animal was observed once a day, at approximately the same time, for the recording of clinical signs.
- Body weight: The body weight of each animal was recorded on the day of treatment and at the end of the evaluation of cutaneous reactions.
- Examination of cutaneous reactions: For each exposure period, cutaneous reactions were evaluated approximately 1, 24, 48 and 72 h after removal of the dressing.

SCORING SYSTEM:
Dermal irritation was graded in each animal according to the following scoring scale:
- Erythema and eschar formation:
0 no erythema
1 very slight erythema (barely perceptible)
2 well-defined erythema
3 moderate to severe erythema
4 severe erythema (beet redness) to slight eschar formation (injuries in depth).

- Edema formation:
0 no edema
1 very slight edema (barely perceptible)
2 slight edema (edges of area well-defined by definite raising)
3 moderate edema (raised approximately 1 millimeter)
4 severe edema (raised more than 1 millimeter and extending beyond area of exposure).

- Any other lesions were noted, if applicable.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48, 72 h (mean)
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: Day 7
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, 72 h (mean)
Score:
1
Max. score:
2
Reversibility:
fully reversible within: Day 3
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48, 72 h (mean)
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: Day 4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48, 72 h (mean)
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48, 72 h (mean)
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48, 72 h (mean)
Score:
0
Max. score:
0
Irritant / corrosive response data:
CUTANEOUS REACTIONS:
- After a 3-minute exposure in animal 1, no cutaneous reactions were observed.
- After a 1-h exposure, a well-defined erythema (grade 2) was noted in animal 1 from Day 1 to Day 3, followed by a very slight erythema (grade 1) on Days 4 and 5. In addition, a very slight edema (grade 1) was observed on day 1.
- After a 4-h exposure, a well-defined erythema (grade 2) was noted from Day 1 until Day 2 in 2/3 animals (i.e., in animal 2 and 3) and until Day 3 in 1/3 animals (i.e., in animal 1), followed by a very slight erythema (grade 1) up to Day 3 in animal 2, Day 4 in animal 3 or Day 7 in animal 1.
- Mean scores calculated for each animal over 24, 48 and 72 h were as follows:
- erythema: 1.7, 1.0, 1.3; showing no significant inflammation,
- edema: 0.0, 0.0; 0.0; showing no significant inflammation.
Other effects:
MORTALITY: No unscheduled deaths occurred during the study.
CLINICAL SIGNS: No clinical signs indicative of systemic toxicity were observed in any animals.
BODY WEIGHT: The body weight of the animals was unaffected by the test substance treatment.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the study conditions, the test substance was considered to be slightly irritating when applied topically to rabbits.
Executive summary:

An in vivo study in New Zealand White rabbits was run according to OECD Guideline 404 and EU Method B.4 in compliance with GLP.

Here, 0.5 g of the undiluted test substance (moistened with drinking water treated by reverses osmosis) was applied to a skin area of approximately 6 cm2under semi-occlusive conditions for 4 h. Each animal was observed once a day for mortality and clinical signs. The cutaneous reactions were evaluated approximately 1, 24, 48 and 72 h after removal of the dressing and then daily until the reversibility of cutaneous reactions. The mean values of the scores for erythema and edema were calculated for each animal. Body weight was recorded at the beginning and the end of the observation period. No unscheduled deaths occurred during the study and no clinical signs were noted in any animal. The body weight of the animals was unaffected by treatment. After a 4 h exposure, a well-defined erythema was noted from Day 1 until Day 2 in 2/3 animals or until Day 3 in 1/3 animals, followed by a very slight erythema up to Days 3, 4 or 7. Mean scores calculated for each animal over 24, 48 and 72 h were as follows:

-        Erythema: 1.7, 1.0, 1.3; showing no significant inflammation;

-        Edema: 0.0, 0.0; 0.0; showing no significant inflammation.

Under the study conditions, the test substance produced slight skin irritation in rabbits which was reversible within 7 d