Benzyl-N-(2-(2-methoxy-phenoxy)-ethyl)amine hydrochloride

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Benzyl-N-(2-(2-methoxy-phenoxy)-ethyl)amine hydrochloride

EC Number:

428-290-8

EC Name:

Benzyl-N-(2-(2-methoxy-phenoxy)-ethyl)amine hydrochloride

Cas Number:

120606-08-8

Molecular formula:

C16H20ClNO2

IUPAC Name:

benzyl[2-(2-methoxyphenoxy)ethyl]amine hydrochloride

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): Carvedilol 6/a intermediate (BEG HCl = Benzylaminoethoxy-guaiacol hydrochloride)
- Physical state: white, or almost white crystalline powder
- Lot/batch No.: S-3082/1
- Expiration date of the lot/batch: 02.2002
- Storage condition of test material: dry, cool place

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Breeder: Ferenc Sándor, address: Vörös Hadsereg street 131, Kartal, H-2173, Hungary
- Age at study initiation: adult (male)
- Weight at study initiation: 3416 g
at study termination: 3620 g
- Housing: individually in metal cages
- Diet (e.g. ad libitum): ad libitum, PURISTAR standard diet for rabbits (produced by AGRIBRANDS Europe)
- Water (e.g. ad libitum): tap water (for human consumption) from automatic self-supplying watering system
- Acclimation period: 22 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): 12-12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the contralateral eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of test item Carvedilol 6/a intermediate in pure state in a single dose

Duration of treatment / exposure:

The eyes of the test animals were not washed out after the application of the test item.

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

1

Details on study design:

REMOVAL OF TEST SUBSTANCE
The eyes of the test animals were not washed out after the application of the test item.

SCORING SYSTEM:
Draize (1959)

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

21 d

Score:

>= 98 - <= 110

Max. score:

110

Reversibility:

not reversible

Irritant / corrosive response data:

One hour after the treatment, the vessels were diffuse, beefy red. Swelling with lids more than half closed occured. Yellowish white, purulent discharge with moistening of the lids and hairs on consideralbe area around the eye was found. The cornea was opaque, involving greater than three quarters up to the whole area. Iris was not discernible through the opacity. The animal did not react to light.

24 hours after the treatment, redness, corneal and iris alterations could not be scored because the leids were glued together. Chemosis and discharge excretion have not changed comparing to the previous day.

48 and 72 hours after the treatment, the irritation symptoms have not changed comparing to the previous day.

1 week after the treatment, redness, corneal and iris alterations could not be scored because the lids were glued together. Swelling with lids about half closed and yellowish white, purulent discharge whit moistening of the lids and hairs on considerable area around the eye occured.

2 weeks after the treatment, the vessels were diffuse, beefy red. Swelling with lids about half closed occurred. Yellowish white, purulent discharge with moistening of the lids and hairs on considerable are around the eye was found. Hairless area around the eye also was found. The cornea was opaque, involving greater than three quarters up to the whole area. Vessel development was observed on the surface of the cornea. Iris was not discernible through the opacity.

3 week after the treatment, the irritation symptoms have not changed comparing to the previous week.

Applicant's summary and conclusion

Interpretation of results:

highly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item applied to the rabbit's eye mucosa proved to be highly irritant according to the observed irritation symptoms. The observed symptoms can be evaluated as irreversible alterations.