(2S,3S)-2-benzhydryl-N-[(5-tert-butyl-2-methoxy-phenyl)methyl]quinuclidin-3-amine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

(2S,3S)-2-benzhydryl-N-[(5-tert-butyl-2-methoxy-phenyl)methyl]quinuclidin-3-amine

EC Number:

831-973-7

Cas Number:

147116-67-4

Molecular formula:

C32H40N2O

IUPAC Name:

(2S,3S)-2-benzhydryl-N-[(5-tert-butyl-2-methoxy-phenyl)methyl]quinuclidin-3-amine

Test material form:

solid: granular

Remarks:

Granular white powder

Details on test material:

Granular white powder

Specific details on test material used for the study:

Sponsor's identification ". CJ-11.972
Description . white solid
Batch number 52855-16-4
Date received 11 April 2001
Storage conditions room temperature in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Three New Zealand White rabbits were supplied by David Percival Ltd. Moston. Sandbach.
Cheshire, UK. At the start of the study the animals weighed 2.65 to 2.94 kg and were twelve to
sixteen weeks old. After an acclimatisation period of at least five days each animal was given a
number unique within the study which was written with a black indelible marker-pen on the inner
surface of the ear and on the cage label.
The animals were individually housed in suspended metal cages. Free access to mains drinking
water and food (STANRAB SOC Rabbit Diet, Special Diets Services Ltd, Witham. Essex. UK)
was allowed throughout the study. The diet and drinking water were considered not to contain any
contaminant of a level that might have affected the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23 C and 30 to 70%
respectively. Any occasional deviations from these targets were considered not to have affected
the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per
hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00
to l 8:00) and twelve hours darkness.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

On the day of the test a suitable test site was selected on the hack of each rabbit. A quantity of
0,5 g of the test material was introduced onto a 2.5 cm x 2,5 cm cotton gauze patch, moistened
with 0,5 ml of distilled water and then placed in position on the shorn skin.

Duration of treatment / exposure:

Four hours

Observation period:

Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the
test sites were examined for evidence of primary irritation

Number of animals:

Three

Details on study design:

Measurement of pil
The pH of a 10% w/w aqueous preparation of the test material was determined prior to
commencement of the study and found to be 7.7.

On the day of the test a suitable test site was selected on the hack of each rabbit. A quantity of
0,5 g of the test material was introduced onto a 2.5 cm x 2,5 cm cotton gauze patch, moistened
with 0,5 ml of distilled water and then placed in position on the shorn skin. The patch was
secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with
the patches. the trunk of each rabbit was wrapped in an elasticated corset and the animals were
returned to their cages for the duration of the exposure period.

Four hours after application the corset and patches were removed from each animal and any
residual test material removed by gentle swabbing with cotton wool soaked in distilled water.
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the
test sites were examined for evidence of primary irritation and scored according to the scale set out in the guideline.

The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the three test
rabbits (12 values) and this total was divided by six to give the primary irritation index of the test
material. The test material was classified according to the following scheme devised by
Draize J 1-I (1959) "Dermal Toxicity" In: Appraisal of the Safety of Chemicals in Foods. Drugs
and Cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, p.47:

Primary Irritation Index Classification of Irritancy
0 Non-irritant
>0 to 2 Mild irritant
>2 to 5 Moderate irritan(
>5 to 8 Severe irritant
If irreversible alteration of the dermal tissue is noted in any rabbit. as judged by the Study
Director.. which include ulceration and clear necrosis or signs of scar tissue, the test material is
classified as corrosive to rabbit skin. Classification according to Draize may. therefore. not be
applicable,

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

no indication of irritation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test material produced a primary irritation index of 0.0 and was classified as
NON-IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive
effects were noted.
The test material did not meet the criteria for classification as irritant or corrosive according, to the
DJ labelling regulations Commission Directive 93/21/EEC.