4-tert-butyl-3-hydroxy-2,6-xylylacetonitrile

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No. 8147

GLP compliance:

yes (incl. QA statement)

Remarks:

BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany

Test material

Test material information

Constituent 1

Reference substance name:

4-tert-butyl-3-hydroxy-2,6-xylylacetonitrile

EC Number:

259-766-1

EC Name:

4-tert-butyl-3-hydroxy-2,6-xylylacetonitrile

Cas Number:

55699-10-0

Molecular formula:

C14H19NO

IUPAC Name:

2-(4-tert-butyl-3-hydroxy-2,6-dimethylphenyl)acetonitrile

Details on test material:

- Name of the test substance used in the study report: 4-tert-Butyl-3-hydroxy-2,6-xylylacetonitrile

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Centre Lago S.A., 01540 Vonnas, France
- Age at study initiation: 4 - 5 months
- Weight at study initiation: 3.32 - 3.75 kg
- Housing: single housing, stainless steel wire mesh cages with grating, floor area 3000 cm2; wooden gnawing blocks (Typ KNH E-041) as enrichment from Abedd Lab. and Vet. Service GmbH Vienna, Austria
- Diet: 130 g/day, Kliba-Labordiät (Kaninchen & Meerschweinchenhaltung "GLP"), Provimi Kliba SA, Kaiseraugst BASEL, Switzerland)
- Water: ad libitum, tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -24
- Humidity (%): 30 -70
- Air: fully air-conditioned
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

A single dose to the conjunctival sac of the right eyelid: 0.1 mL bulk volume (about 37 mg of the comminuted test substance)

Duration of treatment / exposure:

24 h

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: 3 to 6 mL of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe
- Time after start of exposure: 24 h

SCORING SYSTEM:
- Approx. 1, 24, 48 and 72 h after application and then in weekly intervals (maximally up to day 28).

TOOL USED TO ASSESS SCORE:
- Daylight tubes "Lumilux" (L58W/860 PLUS ECO 25x1, Osram, Germany)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24 - 72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24 - 72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24 - 72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

Moderate conjunctival redness was noted in all animals 1 hour after application and decreased to slight in all animals until 24 hours. Slight conjunctival redness persisted in one of the animals up to 48 hours. Slight conjunctival chemosis was observed in all animals 1 hour after application. Slight discharge was noted in two animals 1 hour after appliction. In addition, injected scleral vessels in a circumscribed area were noted in the animals during the observation period. The ocular reactions were reversible in all animals within 72 hours after application at latest.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information

Conclusions:

Under the conditions of the test the substance is considered to be not corrosive or irritating to the eye.

Executive summary:

In an OECD 405 guideline study performed in accordance with GLP, the potential of the test substance to cause damage to the conjunctiva, iris or cornea was assessed by a single ocular application of 0.1 mL bulk volume (about 37 mg) of the test substance to one eye of three White New Zealand rabbits. About 24 hours after application the eye was rinsed with tap water. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application. The average score (24 to 72 hours) for irritation was calculated to be 0 for corneal opacity, iris, chemosis, and 0.4 for conjunctival redness (in which three animals had a score of 0.7, 0.3 and 0.3 respectively). The findings were reversible within 72 hours after application. It was concluded that the test substance was not irritating to the eye.