Calcium bis(2-ethylhexanoate)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-01-07 to 2013-01-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 2002-04-24

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2012-11-30

Test material

Test material information

Constituent 1

Reference substance name:

Calcium bis(2-ethylhexanoate)

EC Number:

205-249-0

EC Name:

Calcium bis(2-ethylhexanoate)

Cas Number:

136-51-6

Molecular formula:

C8H16O2.1/2Ca

IUPAC Name:

calcium bis(2-ethylhexanoate)

Test material form:

other: solidified liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS - New Zealand White (Hsdlf:NZW) strain rabbit
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: 2.28 kg
- Housing: the animal was housed in a suspended cage.
- Diet (ad libitum): 2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK)
- Water (ad libitum): mains drinking water
- Acclimation period: at least five days

The animal was provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 17 to 23°C
- Relative humidity: 30 to 70%
- Air exchange: at least fifteen changes per 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): A volume of 0.1 mL of the test item, which was found to weigh approximately 84 mg was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes.
The test item was ground before use.

Duration of treatment / exposure:

not applicable

Observation period (in vivo):

approximately 1 hour and 24, 48 and 72 hours as well as on Days 7, 14 and 21 following treatment

Number of animals or in vitro replicates:

1 male rabbit

Details on study design:

Immediately before the start of the test, both eyes of the provisionally selected test rabbit were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. An animal free of ocular damage was used.

INITIAL AND CONFIRMATORY TEST
Initially, a single rabbit was treated. Immediately after administration of the test item, an assessment of the initial pain reaction was made according to the six point scale (please refer to table 2 in the field "Any other information on materials and methods incl. tables" below).
After consideration of the ocular responses produced in this animal, no additional animals were treated.

SCORING SYSTEM: according to the Draize scale
Any other ocular effects were also noted.
Any clinical signs of toxicity, if present, were also recorded.
The animal’s body weight was recorded on Day 0 (the day of dosing) and at the end of the observation period.

TOOL USED TO ASSESS SCORE: examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

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

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Initial pain reaction: slight initial pain was observed.

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: 14 days

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: Severe to minimal discharge was observed 1 hour to 7 days of observation.

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: 7 d observation: area of hemorrhage, approx. 3 mm x 4 mm, inside lower eyelid. Scab, approx. 3 mm x 3 mm, on outer lower eyelid. Alopecia around the treated eye; 14 d observation: small area of hemorrhage on the nictitating membrane.

Irritant / corrosive response data:

Diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation were noted in the treated eye one hour after treatment and at the 24, 48, 72-Hour and 7-Day observations. Minimal conjunctival irritation was noted in the treated eye at the 14 and 21-Day observations.
An area of hemorrhage, approximately 3 mm x 4 mm in size, inside the lower eyelid of the treated eye and a scab, approximately 3 mm x 3 mm in size, on the outer lower eyelid of the treated eye were noted at the 7-Day observation. Alopecia around the treated eye was also noted at the 7-Day observation. A small area of hemorrhage on the nictitating membrane was noted in the treated eye at the 14-Day observation.
The persistence of reactions in the treated eye at the 21-Day observation was considered to be indicative of irreversible ocular damage.
Severe to minimal discharge was observed 1 hour to 7 days of observation.

Other effects:

The animal showed expected gain in body weight during the study.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material is severely irritating to the eyes.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the substance is classified as Category 1.