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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02-16 Apr 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 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

yes

Remarks:

occlusive dressing was used

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

Aug 1998

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Food and Argricultural Materials Inspection Centre (FAMIC), 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:

standard acute method

Limit test:

yes

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:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: 294-338 g (males); 206-215 g (females)
- Housing: individually in labeled Makrolon cages (MIII 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 GmbH, 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: 02 Apr 2014 To: 16 Apr 2014

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: 25 cm² for males and 18 cm² for females on the back
- % coverage: 10
- Type of wrap if used: The formulation was in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminum foil and elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing: Skin was cleaned of residual test substance using tap water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 10 mL/kg bw
- Concentration: 20%
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

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

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Slight scales or slight chromodacryorrhoea were observed on the treated skin-area on Day 3 for one male and one female animal, respectively.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

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