Hexanoic acid, 2-ethyl-, zinc salt, basic

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996-11-25 to 1996-12-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987-02-24

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Hexanoic acid, 2-ethyl-, zinc salt, basic

EC Number:

286-272-3

EC Name:

Hexanoic acid, 2-ethyl-, zinc salt, basic

Cas Number:

85203-81-2

Molecular formula:

C16H30O4Zn

IUPAC Name:

zinc(2+) bis(2-ethylhexanoate)

Test material form:

liquid: viscous

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Broekman Institue, Someren, The Netherlands
- Age at study initiation: approx. 7 weeks
- Weight at study initiation: 1289 - 1599 g
- Housing: individually in cages with perforated floors (Scanbur Denmark) and equipped with an automatic drinking system (ITL, Bergen, The Netherlands).
- Diet: standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands); approx. 100 g/day and hay (BMI, Helmond, The Netherlands) was provided once a week
- Water (ad libitum): tap-water diluted with decalcified water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21°C
- Relative humidity: 50%
- Air changes: approx. 15 air changes/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 mL of the test substance was instilled in the conjunctival sac of one eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.

Duration of treatment / exposure:

not applicable

Observation period (in vivo):

approximately 1, 24, 48 and 72 hours and 7, 14 and 21 days after instillation of the test substance (Exception: eyes of one animal were also examined daily from 21 days up to 29 days after instillation)

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the eyes, which were free from any abnormality.

SCORING SYSTEM: according to the Draize scale

TOOL USED TO ASSESS SCORE:
Immediately after the 24 hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. When considered necessary, this procedure was repeated to assess recovery.

In case standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp.
In cases of equivocal results when comparing the treated and untreated eyes, the illustrated guide from Consumer Product Safety Commission, Washington, D.C. 20207 was used for additional control purposes.

OBSERVATIONS:
- Mortality/viability: twice daily
- Toxicity: at least once daily
- Body weight: day of treatment (prior to instillation).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: 24 h: no opacity; epithelial damage max. 25% of cornea; white covered eyelids / 48 h: white covered eyelids/ 72 h: epithelial damage max. 25% of cornea; reduced elasticity of eyelids / 7d: epithelial damage 10% of cornea; pannus; neovascularisation

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: 24 h: redness of nictitating membrane / 48 h & 72 h: redness of eyelids & sclera / 7 d: redness of sclera

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: 24, 48 & 72 h: chemosis of eyelids / 48 & 72 h: chemosis of nictitating membrane / 48 h, 72 h & 7 d: chemosis of sclera

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 24 h: white covered eyelids

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: 24 h, 48 h, 72 h & 7d: redness of eyelids / 24 & 48 h: redness of nictitating membrane & sclera

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: 24 h: chemosis of eyelids; 48 h: chemosis of nictitating membrane and sclera

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: 24 h: no opacity; epithelial damage max. 25% of cornea; white covered eyelids / 48 h: white covered eyelids / 72 h: epithelial damage max. 25% of cornea / 7 d: epithelial damage max. 25% of cornea; eye lids stuck together & released by soaking with water

Results 10

Remarks on result:

other: 14 d: epithelial damage 10% of cornea; pannus, neovascularisation

Results 11

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: 7 d grade 1 was observed, fully reversible on 14 d

Results 12

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 21 days

Remarks on result:

other: 24 h, 48 h & 7 d: redness of eyelids / 48 h , 72 h, 7 d & 14 d: redness of sclera

Results 13

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: 24 h, 48 h & 72 h: chemosis of eyelids, nictitating membrane and sclera

Irritant / corrosive response data:

Two animals showed corneal injury consisting of opacity (maximum grade 1-2) and epithelial damage (maximum 25% of the corneal area). As a result of the corneal injury pannus, neovascularisation of the cornea, was apparent 7 days after instillation in one animal and 14 days after instillation in the second animal. The corneal injury had resolved within 14 days in the first animal and within 21 days in the second animal. No cornel injury was observed in the third animal. Iridic irritation grade 1 was observed in one animal after 1 hour, in the second animal after 1 and 24 hours and in the third animal after 1 hour and 7 days. The irritation of the conjunctivae consisted of redness, chemosis and discharge and had completely resolved within 14 days in two animals and within 21 days in the third animal.
A white covering was observed on the eyelids of all animals 24 and/or 48 hours after instillation. Reduced elasticity of the eyelids was noted in one animal 72 hours after instillation. The eyelids of another animal were struck together, 7 days after instillation and were released by soaking with abundant water.
Unexpectedly, one animal, which was free of any ocular irritation after 14 days, showed signs of ocular irritation between 21 and 29 days after instillation. The irritation consisted of corneal injury (opacity, epithelial damage and pannus), iridic irritation and conjunctival irritation. Minimal discharge persisted after 29 days (termination of the study). This irritation, which showed a relative slow recovery, was considered not to be related to the test substance treatment but to have been caused by accident. The latter results were excluded from interpretation.
There was no evidence of ocular corrosion.
No staining of peri-ocular tissue by the test substance was observed.

Other effects:

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material is irritating to the eye.
According to 67/548/EC and subsequent regulations, the test substance is classified as an eye irritant.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test substance is classified as Category 2.