1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No guideline study, no GLP. Results documented with limitations but acceptable for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1974

Report date:

1974

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: FDA, Vol. 37, No. 38, 1972

Deviations:

not specified

GLP compliance:

no

Remarks:

not required at time of testing

Test material

Test material information

Constituent 1

Reference substance name:

Octopirox

IUPAC Name:

Octopirox

Constituent 2

Reference substance name:

Piroctone olamine

IUPAC Name:

Piroctone olamine

Constituent 3

Reference substance name:

1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

EC Number:

272-574-2

EC Name:

1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

Cas Number:

68890-66-4

Molecular formula:

C14H23NO2.C2H7NO

IUPAC Name:

1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

Constituent 4

Reference substance name:

1-Hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2-pyridone, 2-aminoethanol salt

IUPAC Name:

1-Hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2-pyridone, 2-aminoethanol salt

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no details given

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 mg
- Concentration (if solution): undiluted product

no vehicle was used. Substance was applied as it is.

Duration of treatment / exposure:

group 1: 5min.
group 2: 24 h

Observation period (in vivo):

1, 24, 48, 72 h
7, 14, 21 d

Number of animals or in vitro replicates:

group 1: 5
group 2: 3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, 2min with 300 ml water
- Time after start of exposure:
group 1: 5 min post applicationem (5 animals)
group 2: 24 hrs post applicationem (3 animals)

SCORING SYSTEM:
cornea: 0 - 4
iris: 0 - 2
conjunctiva: a) redness 0 - 3; b) swelling 0 - 4

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein
- 0.1 mL of a 0.01 % fluorescein solution was used to detect damages to the cornea via a UV-lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

all animals

Time point:

other: 24h, 48h, 72h, 7d, 14d

Score:

> 1 - <= 3

Max. score:

3

Reversibility:

not reversible

Results 2

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

all animals

Time point:

other: 24h, 48h, 72h, 7d, 14d

Score:

> 1 - <= 4

Max. score:

4

Reversibility:

not reversible

Results 3

Irritation parameter:

iris score

Basis:

mean

Remarks:

all animals

Time point:

other: 24h, 48h, 72h, 7d, 14d

Score:

> 1 - <= 2

Max. score:

2

Reversibility:

not reversible

Results 4

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

all animals

Time point:

other: 24h, 48h, 72h, 7d, 14d

Score:

> 1 - <= 4

Max. score:

4

Reversibility:

not reversible

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The product caused severe eye-damage of the treated animals. According to the FDA-standards the product (not diluted) is to be considered as highly irritating.

Executive summary:

Primary eye irritation / corrosion of Octopirox was investigated in rabbits according to FDA guidelines. 50 mg of the undiluted test material was applied into the left eye of 8 rabbits, The right eye left untreated in all cases and served as a control. After 5 minutes exposure time the treated eye of 5 animals was rinsed for 2 minutes with warm tap water (group 1). In the remaining 3 animals the treated eyes were rinsed after 24 hours exposure time (group 2). Assessments were carried out 1, 24, 48 and 72 hours after rinsing of the eyes as well as 7 and 14 days. After application of the test substance the animals of group 1 exhibited definitely injected blood vessels of the conjunctiva as well as swellings with lids about half closed. The cornea showed easily translucent areas with details of the iris slightly obscured. In group 2 the conjunctiva of the animals had a diffuse beefy red clour as well as swellings with lids about half closed and the cornea showed nacreous areas of opacity with details of the iris not visible. Based on the severity of the effects observed they were judged to be irreverible.