Registration Dossier

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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes (incl. certificate)
Remarks:
Experimental Toxicology and Ecology, BASF Aktiengesellschaft, 67056 Ludwigshafen/Rhein, Germany
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Borane-tetrahydrofuran complex in tetrahydrofuran 1M
- Physical state: Liquid
- Analytical purity: The test substance was characterized analytically.
- Lot/batch No.: 101202346 resp. 101202350
- Storage condition of test material: Refrigerator, exclusion of air (covered with N2 )
- Homogeneity: The test substance was homogeneous by visual inspection

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd Laboratory Animal Services, Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: approx. 8-12 weeks)
- Weight at study initiation: 176-189
- Fasting period before study: At least 16 hours before administration (water available ad libitum)
- Housing: Single housing in stainless steel wire mesh cages, type DK-III (Becker & Co., Castrop-Rauxel, FRG)
- Diet: Kliba-Labordiät (Maus / Ratte Haltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12h/12h (6.00 a.m.-6.00 p.m./6.00 p.m.-6.00 a.m)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
- Time of day of administration: In the morning
- Amounts administered: 300 mg/kg: 0.34 mL/kg, 500 mg/kg: 0.57 mL/kg, 2000 mg/kg: 2.27 mL/kg,

CLASS METHOD
- Rationale for the selection of the starting dose: Based on the physical and chemical characteristics of the test substance and its composition a starting dose of 300 mg/kg body weight has been chosen in the first step with 3 female animals. Because all animals survived, 2,000 mg/kg body weight were administered to 3 female animals in a second step. As all animals died at the second step, 500 mg/kg body weight were administered to 3 female animals in a third step. Because no animals died at the third step, 500 mg/kg body weight have been tested in a fourth step with another group of 3 female animals. Because all animals survived the fourth step the study was terminated.
Doses:
300, 500, 2000 mg/kg
No. of animals per sex per dose:
3 animals at 2000 and 300 mg/kg, 6 animals at 500 mg/kg.
Control animals:
no
Details on study design:
- Duration of observation period following administration: At least 14 days
- Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and at the end of the study . Additionally, at day of death in animals that died or were sacrificed moribund starting with study day 1.
- Signs and symptoms: Several times on the day of administration, at least once each workday for the individual animals
- Mortality: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Pathology: Necropsy with gross-pathology examination on the last day of the observation period after killing by CO2-inhalation. Necropsy of all animals that died before as early as possible after death.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 500 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals of the 2,000 mg/kg administration group were found dead on study days 1 and 2. No mortality occurred in the 500 and 300 mg/kg administration groups.
Clinical signs:
Clinical observation in the 2,000 mg/kg administration group revealed poor general state, dyspnoea, abdominal and lateral position, piloerection, salivation and lacrimation and were observed from hour 0 until including study day 1 after administration.

Clinical observation in the 500 mg/kg administration groups revealed impaired general state, dyspnoea and piloerection and were observed from hour 1 until including hour 4 after administration (5 females) resp ..from hour 0 until including study day 6 after administration (1 female) .

No clinical observations were observed during clinical examination in the 300 mg/kg
administration group .

Body weight:
The mean body weights of the administration groups increased throughout the study period.
Gross pathology:
The following macroscopic pathologic findings were observed in the animals that died (2,000 mg/kg (3 females)): red discoloration of the glandular stomach (2 females), few brown erosions/ulcers in the glandular stomach, diameter up to 20 mm (1 female) and discoloration of contents of the small intestine (3 females). No macroscopic pathologic abnormalities were noted in the animals examined at termination of the study (500 mg/kg: 6 females; 300 mg/kg: 3 females).

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information