(R)-quinuclidin-3-ol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

22 March 1996

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

Official Journal No. L248, 30.9.96

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

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:

rat

Strain:

Sprague-Dawley

Remarks:

Hsd:Sprague-Dawley(CD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon
- Females (if applicable) nulliparous and non-pregnant: Not specified
- Age at study initiation: 5 - 7 weeks
- Weight at study initiation: 93 - 120g
- Fasting period before study: overnight and then 4 hours after dosing
- Housing: metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 40-70%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12h dark / 12h light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

CLASS METHOD
- Rationale for the selection of the starting dose: starting dose when no information is available to suggest testing at a lower dose.

Doses:

200 and 2000 mg/kg

No. of animals per sex per dose:

200 mg/kg - 3 males, 3 females
2000 mg/kg - 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals checked twice per day; weighed on Day 1 (prior to dosing), Day 8 and Day 15, or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination of cranial, thoracic and abdominal cavities, macroscopic appearance of all examined organs recorded

Statistics:

None.

Results and discussion

Preliminary study:

3 females rates dosed at 2000 mg/kg. 2 died within 4 hours of dosing and other sacrificed after 5 hours due to the severity of the clinical signs.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50 cut-off

Effect level:

> 200 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2000 mg/kg: 2 deaths, 1 sacrifice
200 mg/kg: no mortality

Clinical signs:

other: 2000 mg/kg: prior to death - piloerection, hunched posture, underactivity and abnormal gait in all animals 200 mg/kg: no clinical signs observed

Gross pathology:

2000 mg/kg: congestion of the brain in one animal and the liver of a second animal. A small heart was recorded for one female. Congestion and fluid content were noted in the stomach and along the alimentary tract of all three animals
200 mg/kg: no abnormalities were revealed in macroscopic examination

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Equivalent to Xn, R22 classifiaction under Directive 67/548EEC

Conclusions:

The LD50 value of the test substance was determined to be <2000 mg/kg but >200 mg/kg in this study.