diethylmethoxyborane

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:

other: GLP-guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

425-380-9

EC Name:

-

Cas Number:

7397-46-8

Molecular formula:

C5H13BO

IUPAC Name:

methyl diethylborinate

Details on test material:

- Name of test material (as cited in study report): DEMB
- Physical state: Water-white liquid
- Analytical purity: 99.4 %
- Lot/batch No.: 183
- Expiration date of the lot/batch: August 01, 1997
- Stability under test conditions: in the vehicle dry propylene glycol stable for 16-20 h
- Storage condition of test material: At room temperature in the dark
- Other: Density 0.76 g/ml

Test animals

Species:

rat

Strain:

other: Wistar strain Crl:(WI) BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: Approx. 6 or 8 weeks
- Weight at study initiation: males: 177 g; female: 138 g
- Fasting period before study: Food was withheld overnight prior to dosing until approximately 3-4 hours after administration of the test substance.
- Housing: 5 animals/cage (main study); single housing in the pilot study
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 50 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on their physical and chemical properties.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): Because DEMB is a highly flammable liquid in open air, all procedures were carried out in a glove-box under nitrogen. The test substance was expelled from the original container into a clean vial. Immediately after weighing, the formulation was prepared on volume/volume basis by adding the appropriate amount of the vehicle (The formulations for the pilot study were prepared in propylene glycol and were used within 10 minutes after preparation. For the main study formulation (prepared approx. 18 hours prior to use), the propylene glycol was dried by addition of silica-gel at least several hours before use) and subsequently mixing to homogeneity. Adjustments were made for the specific gravity of the test substance and the vehicle. For the different dose levels, the concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of ml/kg body weight. Homogeneity was accomplished to a visually acceptable level.

Doses:

Pilot study: 2000, 500, 50 mg/kg bw
Main study: 50 mg/kg bw

No. of animals per sex per dose:

Pilot study:
2000 mg/kg: 2 male/2 female
500 mg/kg: 1 male/1 female
50 mg/kg: 1 male/1 female

Main study:
50 mg/kg: 5 male/5 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: twice daily; weighing in the pilot study: day 1 and 8 and in the main study: day 1,2,3,4,8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organs, histopathology

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 50 - < 500 mg/kg bw

Based on:

test mat.

Mortality:

2000 mg/kg: The two males died and the two female were killed in extremis within 1 hour after dosing.
500 mg/kg: The male and female died within 24 hours after dosing.
50 mg/kg: No mortality occurred in the pilot and the main study

Clinical signs:

50 mg/kg bw: hunched posture and uncoordinated movements were noted in all animals an day 1.

Body weight:

The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.

Gross pathology:

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

Applicant's summary and conclusion

Executive summary:

According to Annex VI of EU Regulation (EC) N0. 1272/2008 (CLP) and Annex I of EU directive 67/548/EEC, DEMB is classified as harmful if swallowed Cat 4 and R22, respectively.