(R)-quinuclidin-3-ol

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:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(R)-quinuclidin-3-ol

EC Number:

246-857-6

EC Name:

(R)-quinuclidin-3-ol

Cas Number:

25333-42-0

Molecular formula:

C7H13NO

IUPAC Name:

quinuclidin-3-ol

Test material form:

solid: crystalline

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Germany
- Age at study initiation: at least 6 weeks old
- Weight at study initiation: at least 1.0 kg
- Housing: Individually in labelled cages with perforated floors
- Diet (e.g. ad libitum): Standard Laboratory rabbit diet, approx. 100 g per day. Pressed hay provided twice per week
- Water (e.g. ad libitum): Free access to tap-water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12h dark/12h light

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.4mL

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

1

Details on study design:

TEST SITE
- Area of exposure: 150sq.cm
- Type of wrap if used: Metalline patch 2 x 3 cm. Patch mounted on micropore tape wrapped with Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) hours

SCORING SYSTEM:
- Method of calculation: using numerical scoring system in table 1 below

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Max. score:

4

Reversibility:

not reversible

Remarks on result:

not determinable

Remarks:

Not scored due to eschar formation

Results 6

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Max. score:

4

Remarks on result:

not determinable

Remarks:

Not scored due to eschar formation

Irritant / corrosive response data:

On 25% of the treated surface, black discolouration of the skin (a sign of necrosis) was present after 1 and 24 hours, resulting in eschar formation. A thick black scab was noted after 72 hours. Erythema score 4 was indcated for the aforementioned skin effects. Reactions seen in the remaining skin area (75%) resulted in erythema scores between well defined and moderate to severe erythema. Scoring of oedema was not possible after 48 and 72 hours due to eschar formation and/scab formation.

Other effects:

The animal was sacrified for humane reasons after 72 hours based on the severity of the skin effects, and no other animals treated.

No staining of the treated skin by the test substance was observed.

No symptoms of systemic toxicity were observed in the animal during the test period.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Remarks:

Not possible to sub-categorise based on data available

Conclusions:

This substance is corrosive to skin under the conditions of the test.