Registration Dossier

Administrative data

Description of key information

Skin corrosion/irritation: not irritating (OECD 404; GLP)

Eye irritation: no information available, since testing was technically not feasible

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:
2018-07-16 to 2018-09-01
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:
2015-07-28
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
signed 2018-04-26
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature in a sealed container
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: approx 54, 55 and 59 weeks old
- Weight at study initiation: 3.9 – 4.7 kg
- Housing: individually housed in ABS-plastic or Noryl rabbit cages, floor 4200 cm2
- Diet (ad libitum): autoclaved hay and Altromin 2123 maintenance diet for rabbits, rich in crude fibre
- Water (ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3 °C
- Relative humidity: 55 ± 10 %
- Air changes: at least 10 x / hour
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test item
In order to ensure good skin contact, it was moistened with aqua ad injectionem.
Duration of treatment / exposure:
animal #1: 3 minutes, 1 hour and 4 hours
animal #2: 4 hours
animal #3: 4 hours
Observation period:
animal #1: 13 days
animal #2: 14 days
animal #3: 11 days
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
- Area of exposure/Type of wrap if used: approx. 24 hours before the test, the fur was removed from the dorsal area of the trunk by using an electric clipper. The test item was applied to a small area (approx. 6 cm²) of skin on one side of the dorsal area and covered with a gauze patch, which was held in place with a non-irritating tape. The untreated other side served as control. The test item was applied to the patch first, moistened with the smallest amount of aqua ad injectionem and then applied to the skin. The patch was fixed with a semi-occlusive dressing. The limits of the application site were marked with an ink marker.

INITIAL AND CONFIRMATORY TESTING
As there was no information about the skin irritation/ corrosion potential of the test item, a single animal test was employed. Up to three test patches were applied sequentially to the animal. The first patch was removed after three minutes. As no clear signs of serious skin reaction were observed, a second patch was applied at a different site and removed after one hour. As the observations at this stage indicate that exposure could humanely be allowed to extend to four hours, a third patch was applied and removed after four hours, and the response was graded. No corrosive effect was observed after the last patch had been removed, so the animal was further observed.

The results of the initial test did not indicate the test item to be corrosive or a severe irritant to the skin using the procedure described. In order to confirm the response, two additional animals were treated in the same manner.

REMOVAL OF TEST SUBSTANCE
At the end of the exposure period, sterile water was used to remove residual test item from the application site in animal no. 1. Due to better solubility, cottonseed oil, animals was subsequently used to remove residual test material for animal no.1 and immediately after patch removal for animal no. 2 and animal no. 3 and daily repeated until no residues were observed. The solvent was used without altering the existing response or the integrity of the epidermis.

OBSERVATION TIME POINTS
- animal #1: immediatley and 1 hour, 48, 72 and 96 hours after patch removal
- animal #2: 1 hour, 24, 48 and 72 hours after patch removal
- animal #3: 1 hour, 24, 48 and 72 hours after patch removal

SCORING SYSTEM
according to the Draize scale

FURTHER OBSERVATIONS
- body weights: prior to the administration and at the end of the observation period
- local effects such as hyperplasia, scaling, discolouration, fissures and scabs
- systemic effects
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 72, 96 and 120 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 13 days
Remarks on result:
other: Due to delayed symptom onset, the mean score is calculated from the values 72, 96 and 120 hours after patch removal
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 72, 96 and 120 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Due to delayed symptom onset, the mean score is calculated from the values 72, 96 and 120 hours after patch removal
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #2
Time point:
other: 72, 96 and 120 h
Score:
1.67
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Due to delayed symptom onset, the mean score is calculated from the values 72, 96 and 120 hours after patch removal
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
ANIMAL #1:
After patch removal during and immediately after sequential application (3 min, 1 hour, 4 hours) determination of skin irritation was not possible in animal no. 1 due to green discolouration of the application sites. However, no signs of serious skin reaction were observed. 72 hours after test item administration of 4 hours a delayed onset of symptoms was observed in this animal starting with a moderate erythema (score 2) and slight oedema (score 1). Erythema score decreased on day 6 and remained slight for another week (score 1). Oedema disappeared on day 7. From day 10 to day 12 scaling was noted on the application site. By 13 days after exposure all signs of irritation had disappeared. The mean erythema score of animal no. 1, following grading at 72, 96 and 120 hours after installation of the test material, was calculated to be 2.00. The mean oedema score of animal no. 1, following grading at 72, 96 and 120 hours after exposure, was calculated to be 1.00.

ANIMAL #2:
In animal no. 2 no effects were observed at 1 and 24 hours after patch removal. At 48 hours a slight erythema was noted which was more pronounced during the following 4 days (erythema grade 2), decreased to erythema grade 1 on study day 7 but persisted until study end. Slight oedema was observed at one time point (6 days post-application). Eschar was noted 5 days after exposure, followed by crust on the following 2 days and scaling from 7 to 12 days after patch removal. The mean erythema score of animal no. 2, following grading at 48, 72 and 96 hours after installation of the test material, was calculated to be 1.67.

ANIMAL #3:
Animal no. 3 showed erythema grade 1 at 24 and 48 hours after patch removal. Erythema was increased to grade 2 at 72 hours, 4 and 5 days after patch removal, and was fully reversed by day 6. Scaling was noted from day 5 to day 10 after exposure. The mean erythema score of animal no. 3, following grading at 24, 48 and 72 hours post-application, was calculated to be 1.33.
Other effects:
- Neither mortalities nor significant clinical signs of toxicity but local adverse effects were observed.
- There were no significant body weight changes during the observation period, the body weight development was within the expected range.
- Residual test item at the application site was noted during sequential application in animal no. 1 and up to 11 days after patch removal (4-hours exposure) in all animals.
Interpretation of results:
other: not irritating to the skin
Conclusions:
According to Regulation (EC) No 1272/2008 and subsequent adaptations, the test item is not irritating to skin and does not require classification and labelling.
According to UN GHS, the test item causes mild skin irritation and requires classification and labelling (Category 3).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin corrosion/irritation:

The OECD 439 (GLP) test method was was not applicable, due to the physical form of the substance (highly viscous and sticky).

The OECD 435 test method was not applicable, since the receptor fluid was not activated by the test substance. Thus, an in vivo skin irritation study (OECD 404; GLP) was conducted. In this study, the substance displayed no irritating properties to the skin.

Eye irritation:

The OECD 437 (GLP) test method was was not applicable, due to the physical form of the substance (highly viscous and sticky).

Thus, an in vivo follow-up test (OECD 405; GLP) was foreseen, but were not performed, since pre-tests indicated that testing is technically not feasible.

Justification for classification or non-classification

Skin irritation:

Fatty acids, C9 -13 -neo-, copper salts does not possess a skin irritating potential based on an in vivo OECD 404 test and does not require classification according to Regulation (EC) No 1272/2008 and its subsequent adaptations

Eye irritation:

No hazard conclusion can be made with regard to local effects to the eyes, since the substance cannot be applied in in vitro or in vivo eye irritation test systems due to the physical form.

Fatty acids, C9 -13 -neo-, copper salt is not classified for eye irritating effects because of lacking data.