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:
2018-07-30 to 2018-09-04
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
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:
animal #1: approximately 50 weeks old
animal #2: approximately 51 weeks old
animal #3: approximately 14-15 weeks old
- Weight at study initiation: 2.7 – 4.0 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)
Amount / concentration applied:
TEST MATERIAL
500 mg of the test item was first applied to a gauze patch, which was then carefully applied to the skin with good contact and uniform distribution of the test item on the skin. In order to ensure good contact with the skin, it was moistened with the smallest amount of aqua ad injectionem.
The vehicle was chosen due to its non-irritating characteristics.
Duration of treatment / exposure:
initial animal #1: 3 minutes, 1 hour and 4 hours
confirmatory animals #2 and #3: 4 hours
Observation period:
animal #1: 6 days
animal #2: 14 days
animal #3: 7 days
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
500 mg of the moistened test item was applied at a single dose to a small area (approximately 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 untreated other side served as control. The limits of the application site were marked with an ink marker. Access by the animal to the patch and ingestion or inhalation of the test chemical were prevented.

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. No serious skin reaction was observed, so a second patch was applied at a different site and removed after one hour. The observations at this stage indicated that exposure can humanely be allowed to extend to four hours, so a third patch was applied and removed after four hours, and the response was graded. No corrosive effect was observed after the last patch was removed, so the animal was further observed.
The results of the initial test indicated that the test item is not corrosive 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 animal #1. Thereafter, as the test item showed a water-repellent effect, an appropriate solvent, cottonseed oil was used for rinsing the application site in animal #1. For animal #2 and #3 solely cottonseed oil was used to remove test item residues immediately after patch removal. The solvent was chosen in order not to alter the existing response or the integrity of the epidermis.

OBSERVATION TIME POINTS
- animal #1: immediately and 1 hour, 24, 48,72 and 96 hours after patch removal
- animal #2 and #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:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
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:
2
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) signs of irritation were noted in animal #1 (erythema grade 1 immediately after the 1-hour and the 4-hour exposure periods). 1 hour later no signs of irritation were observed. Slight irritation was noted from 24 hours until 5 days after exposure and was fully reversible within 6 days after patch removal. The mean erythema score of animal #1, following grading at 24, 48 and 72 hours post-application, was calculated to be 1.00.

ANIMAL #2:
Animal #2 started showing erythema grade 1 at 24 hours after patch removal. This slight sign of irritation persisted until study end, 14 days after application. The mean erythema score of animal #2, following grading at 24, 48 and 72 hours after installation of the test material, was calculated to be 1.00.

ANIMAL #3:
Animal #3 showed erythema grade 1 at 1 hour after patch removal. Irritation score increased to erythema grade 2 24 hours after exposure and decreased again to grade 1 2 days later. By 7 days after application signs of irritation were fully reversible. The mean erythema score of animal #3, following grading at 24, 48 and 72 hours after installation of the test material, was calculated to be 2.00.
Other effects:
- No adverse changes apart from irritant/corrosive response data were observed at the skin sites. However,
- Test item residues were detected at the application sites in all animals almost throughout the whole observation period.
- Neither mortalities nor significant clinical signs of toxicity were observed.
- The body weight development was within the expected range.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item is not irritating to the skin.
According to Regulation (EC) No 1272/2008 and subsequent adaptations, the substance does not require classification as skin irritant.
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, tall-oil, manganese 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 drawn 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, tall-oil, manganese salts is not classified for eye irritating effects because of lacking data.