Ethyl 2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment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

2002

Report date:

2002

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 Nosan No. 8147

GLP compliance:

yes (incl. QA statement)

Remarks:

BASF Aktiengesellschaft, Experimental Toxicology and Ecology, 67056 Ludwigshafen/Rhein, Germany

Test material

Test material information

Constituent 1

Reference substance name:

25533-17-6

IUPAC Name:

25533-17-6

Details on test material:

- Name of test material (as cited in study report): Trans-Tilidin-HCL-Hemidhydrat
- Physical state: solid white powder
- Storage: room temperature, exclusion of light and oxygen (storage under N2)

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: 3 - 4 months
- Weight at study initiation: 2.82 - 2.98 kg
- Housing: single housing, stainless steel wire mesh cages with grating; floor area: 3000 cm2
- Diet: 130 g/animal per day, Kliba-Labordiät (Provimi Kliba SA, Kaiseraugst, 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 rooms
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

Application volume: 0.1 mL bulk volume (about 49 mg of the comminuted test substance)

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

28 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: the test substance was washed out with tap water
- Time after start of exposure: 24 hours

READINGS: 1, 24, 48 and 72 h after application, and then in weekly intervals until end of observation period.

SCORING SYSTEM: For evaluation, the calculation of the mean values of corneal opacity, iris, conjunctival redness and chemosis for readings 24, 48 and 72 hours were quoted. Additionally, the reversibility of the observed findings was taken into account. The evaluation is based on the criteria of Annex VI of the Commission Directive 67/548/EEC that were in place on the date of report signature.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24 - 72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: #2 and #3

Time point:

other: 24 - 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24 - 72 h

Score:

0

Max. score:

2

Results 4

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24 - 72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24 - 72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal: #1 and #3

Time point:

other: 24 - 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24 - 72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 8

Irritation parameter:

chemosis score

Basis:

animal: #1 and #3

Time point:

other: 24 - 72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 9

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24 - 72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

- Severe conjunctival redness (grade 3), marked conjunctival chemosis (grade 3) and severe discharge (grade 3) were observed in all animals 1 hour after application. Severe conjunctival redness persisted in 1 animal up to 72 hours and decreased to slight (grade 1) 7 days after application, whereas in the two other animals conjunctival redness decreased to moderate (grade 2) at the 24-hour reading and was noted up to 72 hours after application.
- Marked conjunctival chemosis decreased in 1 animal to moderate (grade 2) 48 hours after application and was still present just at the 72-hour reading. Moderate conjunctival chemosis, noted in the other two animals 24 hours after application, decreased to slight (grade 1) after 48 hours and persisted up to 72 hours after application.
- At the 24-hour reading severe discharge was still exhibited by two animals and moderate discharge (grade 2) by one animal. Discharge decreased in all animals to slight (grade 1) 48 hours after application and was still noted in two animals 72 hours after application.
- Slight corneal opacity (grade 1) was observed in two animals at the 24-hour reading and persisted up to 72 hours after application.
- Moderate iritis (grade 1), seen in two animals 24 hours after application persisted up to 48 hours and increased in one animal to severe iritis (grade 2) 72 hours after
application.
- Moreover the animals exhibited injected scleral vessels in a circumscribed area as well as circular, small retraction in the eyelid, suppuration, contracted pupil, discharge of blood and white discolored parts of the nictitating membrane during the course of the study.
- The ocular reactions were reversible in two animals within 7 days and in one animal within 14 days.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information

Conclusions:

Under the conditions of the test, the substance is considered to be irritating to the eye.

Executive summary:

The potential to cause damage to the conjunctiva, iris of cornea was assessed, in a GLP complaint OECD 405 guideline study in 3 white Vienna rabbits subjected to a single ocular application of 0.1 mL (approx. 49 mg) of the test substance on day 0. About 24 hours after application the eye was rinsed with tap water. Slight to severe conjunctival redness, slight to marked conjunctival chemosis and slight to severe discharge were observed during the course of the study. In addition moderate or severe iritis and slight corneal opacity was noted within the first week of the observation period. Moreover the animals exhibited injected scleral vessels in a circumscribed area as well as circular, small retraction in the eyelid, suppuration, contracted pupil, discharge of blood and white discolored parts of the nictitating membrane during the study period. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 1.0 and 1.0 for corneal opacity, 0.0, 1.3 and 0.7 for iris lesions, 2.0, 3.0 and 2.0 for redness of the conjunctiva and 1.3, 2.3 and 1.3 for chemosis, for animals 1, 2, and 3 respectively. Findings were reversible within 14 days after application. It was concluded that the substance was irritating to the eye.