2-ethylhexanoic acid, iron salt

Endpoint summary

Description of key information

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

Eye irritation:

In vitro testing of the most representative test material of 2 -ethylhexanoate, iron salt was technically not feasible due to its physical form being sticky. Thus, a second test material with a lower iron content, still within the boundary composition, was used for testing. A BCOP test according to OECD 437 resulted in an IVIS score >3 and < 55, no prediction can be made (GLP). Thus, a follow-up study, namely the EpiOcular test method (OECD 492; GLP) was conducted. However, with the OECD 492 study a prediction of the ocular irritation potential of could not be made.

Thus, an in vivo follow-up study (OECD 405; GLP) was initiated to evaluate whether the substance has irritative/corrosive properties to the eyes. The study was not yet completed.

However, preliminary data (1h/24 h/48h/72h) from the initial test (animal 1) do not indicate corrosive or irritative effects.

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:

2018-08-14 to 2018-08-27

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: in a closed container, do not expose to air - keep on cool place

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 57 and 53 weeks old
- Weight at study initiation: 3.8 – 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)

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

Observation period:

animal #1: 72 hours
animal #2: 6 days

Number of animals:

2 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 the test item was expected to produce severe irritancy/corrosion, 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 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, one additional animals were treated in the same manner.

REMOVAL OF TEST SUBSTANCE
As the test item showed a water-repellent effect, an appropriate solvent, cottonseed oil was used for rinsing the application site 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: immediatley and 1 hour, 48, 72 and 96 hours after patch removal
- animal #2: 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:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

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:

fully reversible within: 6 days

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

ANIMAL #1:
After patch removal during sequential application (3 min, 1 hour) no signs of irritation were noted in animal no. 1. Erythema grade 1 was first observed 24 hours after 4-hour exposure. The effect was reversible within 72 hours after application of the test material. The mean erythema score of animal no. 1, following grading at 24, 48 and 72 hours after installation of the test material, was calculated to be 0.67.

ANIMAL #2:
Animal no. 2 showed erythema grade 1 from 1 hour until 5 days after patch removal. The effect disappeared within 6 days after application. The mean erythema score of animal no. 2, 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.
- A slight discolouration at the application site due to residual test item was noted at every time of observation in both 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 irritation/corrosion:

In vitro testing of the most representative test material of 2 -ethylhexanoate, iron salt was technically not feasible due to its physical form being sticky. Thus, a second test material with a lower iron content, still within the boundary composition, was used for in vitro testing. The test item turned out to be either corrosive or irritating to the skin(OECD 439; GLP). Since the RhE test methods covered by OECD TG 439 cannot resolve between UN GHS Categories 1 or 2, a follow-up study was conducted according to OECD 435 (GLP). However, the OECD 435 test method was not applicable, since the receptor fluid was not activated by the test substance. Consequently, an in vivo study (OECD 404, GLP) was conducted with the most representative test material.

Eye irritation:

In vitro testing of the most representative test material of 2 -ethylhexanoate, iron salt was technically not feasible due to its physical form being sticky. Thus, a second test material with a lower iron content, still within the boundary composition, was used for testing. A BCOP test according to OECD 437 resulted in an IVIS score >3 and < 55, no prediction can be made (GLP). Thus, a follow-up study, namely the EpiOcular test method (OECD 492; GLP) was conducted. However, with the OECD 492 study a prediction of the ocular irritation potential of could not be made.

Thus, an in vivo follow-up study (OECD 405; GLP) was initiatedto evaluate whether the substance has irritative/corrosive properties to the eyes. The study was not yet completed.

However, preliminary data (1h/24 h/48h/72h) from the initial test (animal 1) do not indicate corrosive or irritative effects.

Justification for classification or non-classification

Skin irritation:

The substance does not possess a skin irritation potential based on an in vivo OECD 404 test and does not require classification as skin irritant 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 in vitro test systems cannot be used for classification and the in vivo test is ongoing.

2 -ethylhexanoate, iron salt is not classified for eye irritating effects because of lacking data.