3-Piperidinamine, N,4-dimethyl-1-(phenylmethyl)-, hydrochloride (1:2), (3R,4R)-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 27 Jan to 05 Feb 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study run to a method comparable with current guidelines and to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(3R,4R)-1-benzyl-N,4-dimethylpiperidin-3-amine dihydrochloride

EC Number:

700-696-2

Cas Number:

1062580-52-2

Molecular formula:

C14H22N2.2HCl

IUPAC Name:

(3R,4R)-1-benzyl-N,4-dimethylpiperidin-3-amine dihydrochloride

Details on test material:

Batch No.: SKN045-008
Purity: Not specified

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK.
- Age at study initiation: 12 to 20 weeks old
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: Individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to mains food.
- Water (e.g. ad libitum): Free access to mains drinking water.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23℃
- Humidity (%): 30 to 70%
- Air changes (per hr): At least 15 changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.

IN-LIFE DATES: From: 27 Jan 2009 To: 05 Feb 2009

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (approx. 51 mg)
- Concentration (if solution):

Duration of treatment / exposure:

One second

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 males

Details on study design:

Initially, a single rabbit was treated. A volume of 0.1 mL of the test material, which was found to weigh approx. 51 mg was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test material, an assessment of the initial pain reaction was made according to the six point scale.
After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation.
Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
Individual bodyweights were recorded on Day 0 ( the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0

Max. score:

0

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0

Max. score:

0

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: Mean of 24, 48 and 72 hours

Score:

ca. 0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: Mean of 24, 48 and 72 hours

Score:

ca. 0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

No corneal or iridial effects were noted during the study.
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-hour observation.
All treated eyes appeared normal at the 48-hour observation.

Any other information on results incl. tables

All animals showed expected gain in bodyweight during the study.

Individual eye irritation scores

Rabbit	Time after treatment	Cornea	Iris	Conjunctivae
				Redness	Chemosis	Discharge
68200	1 hour 24 hours 48 hours 72 hours	0 0 0 0	0 0 0 0	2 1 0 0	2 1 0 0	2 1 0 0
68215	1 hour 24 hours 48 hours 72 hours	0 0 0 0	0 0 0 0	2 1 0 0	2 1 0 0	2 1 0 0
68216	1 hour 24 hours 48 hours 72 hours	0 0 0 0	0 0 0 0	2 1 0 0	2 1 0 0	2 1 0 0

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance was slightly irritating to rabbit eye.