(1R)-2-{[2-(4-aminophenyl)ethyl]amino}-1-phenylethanol 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)

Rationale for reliability incl. deficiencies:

other: Study conducted to OECD guidelines and GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF, 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(1R)-2-{[2-(4-aminophenyl)ethyl]amino}-1-phenylethanol hydrochloride

EC Number:

700-425-8

Cas Number:

521284-22-0

Molecular formula:

C16H21ClN2O

IUPAC Name:

(1R)-2-{[2-(4-aminophenyl)ethyl]amino}-1-phenylethanol hydrochloride

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: Between 12 and 24 weeks old
- Weight at study initiation: At least 1.5 kg
- Housing: Individually housed in labelled cages with performated floors and shelters.
- Diet (e.g. ad libitum): Pelleted diet for rabbits at approximately 100g per day. Hay and wooden sticks were also available.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: At least 5 days before the start of treatment, under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 25°C
- Humidity (%): 40 to 70%
- Air changes (per hr): At least 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour light, 12 hour dark cycle

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Instillation on average of 82.9 mg (range 82.3 to 83.2 mg) of the test substance (a volume of approximately 0.1 mL).

Duration of treatment / exposure:

No test substance was observed on the eye at the first one hour observation check. This indicates it would have been removed by physiological mechanisms. Remnants of the test substance were noticed on the outside of the eyelid in one animal on Day 1.

If the test substance wasn't removed from the eye by physiological mechanisms at the first observation period of approximately 1 hour, the eye was rinsed with saline or distilled water.

Observation period (in vivo):

14 day observation period in surviving animals.

Number of animals or in vitro replicates:

3 (Study conducted in a stepwise manner and was started by treatment of a single rabbit (sentinel)). The two remaining animals were treated in a similar manner up to 3 weeks later, after considering the degree of eye irritation observed in the first animal.

Details on study design:

Eye irritation was assessed using the standard approach in the OECD 405 guidelines, which looks at corneal irritation (including the area of the cornea involved), Iris irritation, conjunctival irritation, chemosis, and evidence of discharge.

Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp.

Green staining after fluorescein treatment was used to determine the % of total corneal area effects.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of animals 1 and 2.

Time point:

other: 24, 48 and 72 hours

Score:

0.3

Max. score:

0.3

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

of animals 1 and 2

Time point:

other: 24, 48 and 72 hours

Score:

0.15

Max. score:

0.3

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

of animals 1 and 2

Time point:

other: 24, 48 and 72 hours

Score:

2.15

Max. score:

2.3

Reversibility:

fully reversible within: 14 days

Results 4

Irritation parameter:

conjunctivae score

Remarks:

chemosis

Basis:

mean

Remarks:

of animals 1 and 2.

Time point:

other: 24, 48 and 72 hours

Score:

1.65

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

Two animals showed similar eye irritation effects in the cornea, iris and conjunctivae approximately 1 hour after instillation.
Cornea: The corneal injury consisted of opacity and epithelial damage and resolved within 7 days.
Iris: Iridial irritation was observed and resolved within 24 hours in one of the animals, and within 48 hours in the other.
Conjunctivae: The irritation of the conjunctivae consisted of redness, chemosis, and discharge and completely resolved within 14 days in both animals.

There was no evidence of ocular corrosion.

Other effects:

One animal was found undergoing severe spasms followed by a comatose appearance approximately 45 minutes after instillation of the test substance. After this, the animal was sacrificed for humane reasons. Post mortem examination showed eye effects similar to the surviving rabbits.

As this effect was not seen in the two remaining rabbits (which both showed similar eye irritation effects and full reversibility) and that the sacrificed animal had mostly slightly lesser eye irritation findings, this effect is not considered to be evidence of systemic toxicity and was most likely a stress response of a potentially (prior to treatment) compromised animal.

Any other information on results incl. tables

Mean value eye irritations scores:

Animal	Mean 24, 48 and 72 hours
	Corneal Opacity	Iris	Conjunctivae
			Redness	Chemosis
1	0.3	0.3	2.0	1.3
2	0.3	0.0	2.3	2.0
3	-	-	-	-

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance showed eye irritation effects in two animals which were fully reversible by Day 14 of the observation period. One animal that was sacrificed for humane reasons had effects not attributed directly to treatment and systemic toxicity of the test substance.