Benzenemethanol, α-[(1S)-2-(dimethylamino)-1-methylethyl]-α-ethyl-3-methoxy-, (αR)-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

April 24th, 2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2004/73/EC

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Benzenemethanol, α-[(1S)-2-(dimethylamino)-1-methylethyl]-α-ethyl-3-methoxy-, (αR)-

Cas Number:

809282-20-0

Molecular formula:

C15H25NO2

IUPAC Name:

Benzenemethanol, α-[(1S)-2-(dimethylamino)-1-methylethyl]-α-ethyl-3-methoxy-, (αR)-

Test material form:

solid: crystalline

Details on test material:

white crystalline solid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

One female albino New Zealand rabbit was supplied by the Elevage de Gérome (Quartier Labaste – F40260 Linxe).
It was kept during a minimal 5-day acclimatisation period.
During the test, the animal weighed between 2.47 and 2.54 kg.

Each animal was kept in an individual box installed in a conventional air conditioned animal husbandry; the environmental conditions were:
- Temperature: between 20˚C and 23˚C
- Relative humidity: between 45% and 66%

Drinking water (tap-water from public distribution system) and foodstuff were supplied freely.
Microbiological and chemical analyses of the water were carried out every six months by the Institut Européen de l’Environnement de Bordeaux (I.E.E.B.).

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Treatment: 0.1 g of the test item was instilled into the conjunctival sac of one eye, the other eye remained untreated serving as control.
Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were not treated.

Observation period (in vivo):

5 days

Number of animals or in vitro replicates:

Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were not treated.

Details on study design:

Treatment: 0.1 g of the test item was instilled into the conjunctival sac of one eye, the other eye remained untreated serving as control.
Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were not treated.
Grading of reactions:
Ocular examinations were performed on both right and left eyes 1 hour, 24, 48 and 72 hours following treatment, according to the numerical evaluation.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 2

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 48 h

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

The ocular reactions observed during the study have been moderate to severe and not reversible during 5 days of the test:
- At the conjunctivae: a moderate redness, noted 1 hour after the test item instillation and still noted at the end of the observation (D5), associated with a slight chemosis, noted 1 hour after the test item installation and still noted at the end of the observation (D5);
- At the corneal level: a moderate opacity, registered 24 hours after the test item instillation, and still noted at the end of the observation (D5);
- At the iris level: a congestion was noted the 2nd day of the test;
It was noted an ulceration on the nictitating membrane from the 1st day of the test. This lesion persisted for 72 hours.
Taking into account the severity of the reactions, the test was stopped the 5th day of the test, in accordance with the principles of animal welfare.

Any other information on results incl. tables

Time after treatment	Conjunctivae Chemosis (A)	Conjunctivae Discharge (B)	Conjunctivae Redness (C)	Iris Lesion (D)	Cornea Opacity (E)	Cornea Opacity (F)
1 hour	1	1	2	0	1	3
24 hours	1	0	2	1	2	3
48 hours	1	0	2	0	2	3
72 hours	1	0	2	0	2	2
Day 4 (D4)	1	0	2	0	2	1
Total (24, 48 & 72 hours)	3		6	1	6
Mean  (24, 48 & 72 hours)	1.0		2.0	0.3	2.0

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The results obtained, under these experimental conditions, enable to conclude that the test item T2955 needs to be classified as causing serious eyes damage (eye damage cat. 1; H318 Causes serious eye damage).

Executive summary:

Summary:

The test item T2955 was instilled, into the eye of one New Zealand rabbit at the dose of 0.1 g. The experimental protocol was established on the basis of the official method as defined in the OECD guideline no 405 dated April 24^th, 2002 and the test method B.5 of the directive 2004/73/EC.

 

The ocular reactions observed during the study have been moderate to severe and not reversible during 5 days of the test:

-        At the conjunctivae: a moderate redness, noted 1 hour after the test item instillation and still noted at the end of the observation (D5), associated with a slight chemosis, noted 1 hour after the test item installation and still noted at the end of the observation (D5);

-        At the corneal level: a moderate opacity, registered 24 hours after the test item instillation, and still noted at the end of the observation (D5);

-        At the iris level: a congestion was noted the 2^ndday of the test;

It was noted an ulceration on the nictitating membrane from the 1^stday of the test. This lesion persisted for 72 hours.

Taking into account the severity of the reactions, the test was stopped the 5^thday of the test, in accordance with the principles of animal welfare.

 

The results obtained, under these experimental conditions, enable to conclude that the test item T2955 needs to be classified causing serious eyes damage (eye damage cat. 1; H318 Causes serious eye damage).