Fatty acids, C9-13-neo-, copper salts

Skin irritation / corrosion

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2015-07-28

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2018-04-26

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, C9-13-neo-, copper salts

EC Number:

292-985-0

EC Name:

Fatty acids, C9-13-neo-, copper salts

Cas Number:

91031-79-7

IUPAC Name:

Fatty acids, C9-13-neo-, copper salts

Test material form:

other: highly viscous, sticky

Details on test material:

- State of aggregation: highly viscous, sticky, green

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

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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

Test system

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

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

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

Results 6

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.

Applicant's summary and conclusion

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).