Calcium neodecanoate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018-01-01 to 2018-01-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2017-10-09

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed on 2015-06-05

Test material

Test material information

Constituent 1

Reference substance name:

Calcium neodecanoate

EC Number:

248-375-1

EC Name:

Calcium neodecanoate

Cas Number:

27253-33-4

Molecular formula:

C20H38CaO4

IUPAC Name:

[(3,3,5,5-tetramethylhexanoyl)oxy]calcio 3,3,5,5-tetramethylhexanoate

Test material form:

solid: particulate/powder

Details on test material:

- State of aggregation: white powder

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature; in a tightly closed container

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 15 weeks old
- Weight at study initiation: 3.7 kg
- Housing: individually housed in ABS-plastic or Noryl rabbit cages, floor 4200 cm²
- Diet (ad libitum): autoclaved hay and to 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

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of the test item applied in the conjunctival sac of one eye. Untreated eye served as control.

Duration of treatment / exposure:

not applicable

Observation period (in vivo):

1, 24, 48 and 72 hours as well as 4 to 21 days after test item application

Duration of post- treatment incubation (in vitro):

not applicable

Number of animals or in vitro replicates:

1 male rabbit

Details on study design:

PREPARATION OF THE ANIMALS
Within 24 hours before the test and immediately prior to the application both eyes of the animal were examined.
Approx. 22 hours before the application the eyes were examined with the aid of a fluorescein solution (Fluoreszein SE Thilo®). The eyes were rinsed with physiological saline 0.9 % NaCl after the examination. The animal did not showed eye irritation, ocular defects, or pre-existing corneal injury.

INITIAL AND CONFIRMATORY TEST
The in vivo test was performed initially using one animal. The results of the initial test indicated that the test item is corrosive or severe irritant to the eye using the procedure described. Therefore, no additional animals were treated due to animal welfare reasons.

USE OF TOPICAL ANESTHETICS AND SYSTEMIC ANALGESICS
One hour before the application of the test item, 0.01 mg/kg of buprenorphine (Temgesic® 0.3 mg/mL) was administered subcutaneously in order to achieve a therapeutic level of systemic analgesia. Approx. 5 minutes prior to the application of the test item, 1-2 drops of an ocular anaesthetic (Proparakaine-POS® hydrochloride ophthalmic 0.5% solution) were administered in both the treated and the control eye of the animal.
To prevent pain and distress after the application of the test item the animal was treated with doses of buprenorphine and meloxicam (Metacam® 5 mg/mL) to provide a continued therapeutic level of systemic analgesia. Treatment with the analgesic medication was conducted from 11 hours post-application (day 0) upto 6 days post-application.

REMOVAL OF TEST SUBSTANCE
- Washing: treated eye was rinsed with physiological saline 0.9 % NaCl.
- Time after start of exposure: 1 hour after the application
The eyes were not rinsed to remove residues of the test item, foreign bodies or incrustation 24 hours after application.

SCORING SYSTEM: according to Draize scale

TOOL USED TO ASSESS SCORE: slit lamp biomicroscope / fluorescein
24 hours post-application and from then on daily until end of the observation period, the treated eye was examined with the aid of a fluorescein solution and a slit lamp biomicroscope. After the examination the eye was rinsed with physiological saline 0.9% NaCl.

OBSERVATIONS
- body weight: prior to the administration and at least at the end of the observation period
- clinical observations: nature, severity and duration were recorded

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not reversible

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 10 days

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

not reversible

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not reversible

Irritant / corrosive response data:

Animal # 1:
- conjunctival redness: the animal mainly shows slight to moderate conjunctival redness (grade 1 or 2) from 1 hour until day 21 post-application. The effect was not fully reversible within the observation period of 21 days after application of the test material.

- conjuctival chemosis: moderate conjunctival chemosis (grade 2) was detected 1 hour post-application until 48 hours post-application and slight conjunctival chemosis (grade 1) was observed from 72 hours until day 21 post-application, except for day 8 post-application (no chemosis; grade 0). The effect was not fully reversible within the observation period of 21 days after application of the test material.

- iris: slight iris lesions (grade 1) was observed from 24 hours post-application until day 9 post-application. The effect was fully reversible within day 10 after application of the test material.

- corneal opacitiy: slight corneal opacity (grade 1) was observed throughout the whole observation period of 21 days, except for 24 hours and 48 hours after application (moderate corneal opacitiy ; grade 2). The effect was not reversible within 21 days.

Local effects were observed. The observed local effects mainly comprise moderate to slight hypersecretion, vascularisation from dorsal rim to corneal lesion, and slight unevenness on corneal surface.
Upon fluorescein examinations starting 24 hours post-application, the treated eye of the animal showed corneal lesions (starting with approx. 80% of the area) which were not completely reversible within 21 days.

Other effects:

- clinical observations: neither mortality nor significant clinical signs of toxicity were observed.
- body weight: the body weight development was within the expected range.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The substance is serious eye damaging.
According to the EC Regulation No. 1272/2008 and subsequent adaptations, the substance is classified as a serious eye damaging (Category 1; H318).