1,4-Diazabicyclo[2.2.2]octane-2-methanol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 Feb - 21 Mar 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

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:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Health Care Inspectorate, Ministry of Health, Welfare and Sport, Den Haag, The Netherlands

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

{1,4-diazabicyclo[2.2.2]octan-2-yl}methanol

EC Number:

692-731-2

Cas Number:

76950-43-1

Molecular formula:

C7H14N2O

IUPAC Name:

{1,4-diazabicyclo[2.2.2]octan-2-yl}methanol

Details on test material:

- Name of test material (as cited in study report): [trade name]
- Substance type: off-white powder with lumps
- Analytical purity: 90.7% (subsequent information by sponsor)
- Impurities (identity and concentrations): 1,5-diazabicyclo[3.2.2]nonane-3-ol 8.9% (subsequent information by sponsor)
- Expiration date of the lot/batch: 20 Dec 2014
- Storage condition of test material: at room temperature in the dark
- Other: pH: 11.0 at concentration of 10%

Test animals

Species:

rat

Strain:

other: Wistar strain Crl:WI (Han) (outbred, SPF-quality)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 8 - 9 weeks
- Weight at dosing: 144-187 g
- Fasting period before study: food was withdrawn overnight prior to dosing and until 3-4 hours after administration of the test substance
- Housing: group housing of 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm) containing sterilized sawdust as bedding material and paper as cage-enrichment
- Diet: pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiäten, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 18 Feb 2014 To: 21 March 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 3% and 20%
- Amount of vehicle: 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: according to Guideline

Doses:

step 1: 300 mg/kg bw
step 2 and 3: 2000 mg/kg bw

No. of animals per sex per dose:

3 females per step (in total 9 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability was checked twice daily. Clinical signs were observed at periodic intervals on the day of dosing (Day 1) and once daily thereafter until Day 15. Body weights were determined on Days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: According to OECD Guideline 423, Annex 2d, a cut-off value of 5000 mg/kg bw was derived based on a limit test with 2000 mg/kg bw, since no mortality occurred in any step.

Mortality:

No mortality occurred.

Clinical signs:

other: At 300 mg/kg bw hunched posture and piloerection were noted for all animals between Days 1 and 4. At 2000 mg/kg bw hunched posture and piloerection were noted in 3/6 animals on Day 1.

Gross pathology:

At 300 mg/kg bw macroscopic post mortem examination did not reveal any abnormalities.
At 2000 mg/kg bw abnormalities of the liver (several, beige, focus/foci) were found in two animals, at macroscopic examination. Macroscopic examination of the other animals did not reveal any abnormalities.

Applicant's summary and conclusion

Interpretation of results:

other:

Remarks:

CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

CLP: not classified
DSD: not classified