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

Endpoint summary

Description of key information

In the in vivo skin irritation test with rabbits (OECD 404) no cutaneous reactions (erythema and oedema) were observed whatever the examination time (1, 24, 48, and 72 hours). No classification for skin irritation is indicated.

In the in vivo eye irritation test with rabbits (OECD 405) severe eye damage was observed in the first rabbit, leading to stop the test on day 5 in accordance with the principles of animal welfare. No test was performed anymore with the other 2 rabbits.

These test results indicate classification: Eye Damage, cat. 1; H318.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin 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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

April 24th, 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

2004/73/EC

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Remarks:

albino

Details on test animals or test system and environmental conditions:

Three female albino New Zealand rabbits were supplied by the Elevage de Gérome (Quartier Labaste – F40260 Linxe).
They were kept during a minimal 5-day acclimatisation period.
During the test, the animals weighed between 2.34 and 2.70 kg.

Housing:
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 24˚C
- Relative humidity: between 45% and 67%

Food and drink:
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.).

Type of coverage:

occlusive

Preparation of test site:

clipped

Remarks:

Approximately 24 hours before treatment, the left and right flank were clipped with an electric clipper, from the scapular to lumbar region.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Treatment:
The test item was applied, as supplied, at a dose of 0.5 g, on an undamaged skin of one flank of each animal. The patch was secured in position with a strip of surgical adhesive tape. After the removal of the patch, the treated area was rinsed with distilled water.
On the opposite flank, an untreated area was served as the control.

Duration of treatment / exposure:

The skin reactions were appreciated after 1, 24, 48 and 72 hours after removal of the test item.

Observation period:

The skin reactions were appreciated after 1, 24, 48 and 72 hours after removal of the test item.

Number of animals:

3

Details on study design:

The test item was applied, as supplied, at a dose of 0.5 g, on an undamaged skin of one flank of each animal. The patch was secured in position with a strip of surgical adhesive tape. After the removal of the patch, the treated area was rinsed with distilled water.
On the opposite flank, an untreated area was served as the control.

Initially, one animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.

Macroscopic examination and evaluation of the skin irritation:
The skin reactions were appreciated after 1, 24, 48 and 72 hours after removal of the test item.
This examination consists in assessing the irritant reactions in the treated zone, compared to a control area.
The following sales are used:
Erythema and Eschar formation, scale 0 (no erythema) to 4 (severe erythema – beef redness – with eschars formation preventing grading of erythema)
Oedema, scale 0 (no oedema) to 4 (severe oedema – raised more than 1 mm, and extending beyond area of exposure).

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No cutaneous reactions (erythema and oedema) were observed whatever the examination time (1, 24, 48, and 72 hours).

Interpretation of results:

GHS criteria not met

Conclusions:

Not irritating to skin.

Executive summary:

Summary:

The test item T2955 was applied, as supplied, at the dose of 0.5 g, under semi-occlusive dressing during 4 hours on an undamaged skin area of three rabbits. The experimental protocol was established from the OECD guideline no 404, dated April 24^th, 2002 and the test method B.4 of the directive no 2004/73/EC.

 

No cutaneous reactions (erythema and oedema) were observed whatever the examination time (1, 24, 48, and 72 hours).

 

The results obtained, under these experimental conditions, enable to conclude that the test item T2955 need not to be classified, according to the criteria for classification, packaging and labelling of dangerous substances and preparations in compliance with the EEC directives 67/548, 2001/59 and 99/45. No symbol and risk phrase are required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

April 24th, 2002

Deviations:

no

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)

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.).

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.

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

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

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

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.

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

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).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)