2-ethylhexanoic acid, manganese salt

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-12-03 to 2013-01-03

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:

2-ethylhexanoic acid, manganese salt

EC Number:

240-085-3

EC Name:

2-ethylhexanoic acid, manganese salt

Cas Number:

15956-58-8

Molecular formula:

C8H16O2.xMn

IUPAC Name:

2-ethylhexanoic acid, manganese salt

Test material form:

other: solid lump

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: 2.29 or 2.72 kg
- Housing: the animals were individually 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 93 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.

Duration of treatment / exposure:

not applicable

Observation period (in vivo):

Approximately 1 hour and 24, 48 and 72 hours as well as Days 7 and 14 following treatment

Number of animals or in vitro replicates:

2 male rabbits

Details on study design:

Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were 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 the first treated animal, a second animal was 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.
Individual body weights were 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: practically no initial pain was observed. Area of cornea involved: one quarter (or less) but not zero (observed from 24 hours to day 7); Slight opacity was observed on day 7 of observation.

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: 7 days

Remarks on result:

other: Slight inflammation of iris was observed at the 1 hour observation. Slight to severe discharge was observed from 1 hour of observation to day 7 of observation.

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Moderate conjunctivae redness was observed at the 1 hour and 7 day observation.

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Moderate chemosis was observed at the 1 hour and 7 day observation.

Results 5

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Initial pain reaction: slight initial pain was observed. Area of cornea involved: one quarter (or less) but not zero (observed from 24 hours to 72 hours).

Results 6

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Slight inflammation of iris was observed at the 1 hour and 7 day observation. Slight to moderate discharge was observed from 1 hour of observation to day 7 of observation.

Results 7

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Moderate conjunctivae redness was observed at the 1 hour and slight conjunctivae redness was observed on day 7 of observation.

Results 8

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Moderate chemosis was observed at the 1 hour and slight chemosis was observed on day 7 of observation.

Irritant / corrosive response data:

Scattered or diffuse corneal opacity was noted in both treated eyes at the 24, 48 and 72-Hour observations and in one treated eye at the 7-Day observation.
Iridial inflammation was noted in both treated eyes one hour after treatment, at the 24, 48 and 72-Hour observations and in one treated eye at the 7-Day observation.
Moderate conjunctival irritation was noted in both treated eyes one and 24 hours after treatment. Severe conjunctival irritation was noted in one treated eye at the 48 and 72-Hour observations. Moderate conjunctival irritation was noted in the other treated eye at the 48-Hour observation with minimal conjunctival irritation at the 72-Hour observation. Moderate conjunctival irritation was noted in one treated eye and minimal conjunctival irritation was noted in the other treated eye at the 7-Day observation.
Both treated eyes appeared normal at the 14-Day observation.

Other effects:

- Body weight: both animals showed expected gain in bodyweight during the study.

Applicant's summary and conclusion

Interpretation of results:

Category II

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

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