Naphthenic acids, nickel salts

Endpoint summary

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:

2018-07-23 to 2018-08-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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

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 or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: approx 42, 43 and 45 weeks old
- Weight at study initiation: 3.3 – 3.8 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: 72 hours
animal #2: 6 days
animal #3: 14 days

Number of animals:

3 male rabbits

Details on study design:

TEST SITE
- Area of exposure/Type of wrap if used: approx. 23 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 is 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, the residual test item was removed with sterile water from animal no. 1. As residues were still observed at the test site and due to better solubility, cottonseed oil was used for rinsing the application site of animal no.1 and for rinsing immediately after patch removal for animals no. 2 and 3. The solvent was chosen in order not to alter the existing response or the integrity of the epidermis. In animal no. 1, rinsing with cottonseed oil was repeated daily until 48 hours post-application as test item residues were still observed at the application site.

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:

24/48/72 h

Score:

0

Max. score:

4

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:

other: 48, 72 and 96 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

other: Due to delayed symptom onset, the mean score is calculated from the values 48, 72 and 96 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:

1.67

Max. score:

4

Reversibility:

not fully reversible within: 14 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) no signs of irritation were noted in animal no. 1. It did not show any signs of irritation until the end of the observation period at 72 hours after patch removal.

ANIMAL #2:
Animal no. 2 showed a delayed onset: no effects were observed at 1 and 24 hours after patch removal. At 48 hours erythema grade 1 was noted which was more pronounced during the following 2 days (erythema grade 2), decreased again to grade 1 and was completely reversed by 6 days after exposure. 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 hours after patch removal. Erythema was increased to grade 2 from 48 hours to 5 days after patch removal, and was decreased again on day 6 to score 1. This grade of irritation was not reversible but persisted until study termination 14 days after exposure. The mean erythema score of animal no. 3, following grading at 24, 48 and 72 hours post-application, was calculated to be 1.00.

Other effects:

- Neither mortalities nor significant clinical signs of toxicity 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 72 hours after patch removal in all animals.

Interpretation of results:

GHS criteria not met

Conclusions:

According to Regulation (EC) No 1272/2008 and subsequent adaptations, the test item is not irritating to the skin and does not require classification and labelling.

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:

Naphthenic acid, nickel 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.

Naphthenic acid, nickel salts is not classified for eye irritating effects because of lacking data.