Cholesterol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

june 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study is performed according to OECD and EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF guidelines (2000); including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Cholesterol

EC Number:

200-353-2

EC Name:

Cholesterol

Cas Number:

57-88-5

Molecular formula:

C27H46O

IUPAC Name:

cholest-5-en-3-ol

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): cholesterol
- Substance type: powder
- Physical state: solid
- Stability under test conditions: stable
- Storage condition of test material: at room temperature in the dark

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, Kisslegg, Germany
- Age at study initiation: at least 6 weeks
- Weight at study initiation: 1733 to 2267 grams
- Housing: individually inlabeled cages with perforated floors (Ebeco, germany) and shelters (Ebeco, Germany)
- Diet: ad libitum pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad, Italy); Hay (Technilab-BMI BV, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, The Netherlands).
- Water: free access to tap water.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 11 June 2012 To: 22 June 2012

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied (volume or weight with unit): on average 21.6 mg (range 21.4-21.7 mg), a volume of approximately 0.1 mL

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

1, 24, 48 and 72 hours after instillation

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: according to guideline (scoring system presented in OECD 405

TOOL USED TO ASSESS SCORE: fluorescein (2% solution)

OTHER OBSERVATIONS: mortality/viability: twice daily; toxicity: at least once daily; body weight: before exposure and after the final observation.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

other: mean of 3 animals

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

other: mean of 3 animals

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

other: mean of 3 animals

Time point:

other: 24, 48 and 72 hours

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 4

Irritation parameter:

chemosis score

Basis:

other: mean of 3 animals

Time point:

other: 24, 48 and 72 hours

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Instillation of approximately 0.1 mL cholesterol (approximately 22 mg) into one eye of each of three rabbits resulted in irritation of the conjunctivae (redness, chemosis and discharge). Irridial irritation grade 1 was observed for one animal at 1 hour after instillation. The irritation was fully reversible within 24, 48 or 72 hours in the respective animals. No corneal opacity nor corneal epithelial damage has been observed.
Remnants of the substance were present in the eyes of all animals at approximately 1 hour after instilation.

Other effects:

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

Any other information on results incl. tables

Mean value eye irritation scores        (Mean 24, 48 and 72 hours )
			conjunctivae
Animal	corneal opacity	iris	redness	chemosis
1	0.0	0.0	0.0	0.0
2	0.0	0.0	0.3	0.0
3	0.0	0.0	0.7	0.3

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results with the eye irritation study, cholesterol is considered non-irritating to eyes. As a result, cholesterol does not have to be classified and has no obligatory labelling requirements for eye irritation acoording to GHS and EU Regulation 1272/2008.

Executive summary:

An eye irritation study with cholestrol was performed according to OECD and EC guidelines. Three rabbits received approximately 0.1 mL (approximately 22 mg) cholesterol in one eye. Irritation of the eye was scored after 1, 24, 48 and 72 hours after instillation of the substance in the eye.

Irritation of the conjunctivae (redness, chemosis and discharge) was observed. Iridial irritation grade 1 was observed for one animal at 1 hour after instillation. The irritation was fully reversible within 24, 48 or 72 hours in the respective animals. No corneal opacity nor corneal epithelial damage has been observed. Remnants of the substance were present in the eyes of all animals at approximately 1 hour after instilation. Based on these results, Cholesterol needs not to be classified and has no obligatory labelling requirements for eye irritation according to

-Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011),

-Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures