Registration Dossier

Diss Factsheets

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:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
454-210-6
EC Name:
-
Cas Number:
13106-24-6
Molecular formula:
C13 H30 N . C H3 O4 S
IUPAC Name:
tributyl(methyl)azanium methyl sulfate
Details on test material:
Substance number: 97/272; batch number: 601
Degree of purity/content: 101 g/ 100 g (H-NMR)
Date of manufacturing: June 1997
Physical state/appearance: Solid (congealed melt), white
Storage conditions: Room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Strain: Wistar (chbb: thom (SPF))
Origin: Dr. K. Thomae GmbH, Biberach, FRG
Age of the animals: Young adult animals.
Animal weights at start of the study: Animals of comparable weight; (150g -300g) (+/- 20% of the mean weight).
Acclimatization period: Acclimatization for at least 1 week.
Room temperature relative humidity: The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 20 - 24 degrees centigrade for temperature and of 30 - 70 % for relative humidity. There were no deviations from these ranges, which influenced the results of the study.
Day/night rhythm: 12 h/12 h (6.00 a.m. - 6.00 p.m./ 6.00 p.m. - 6.00 a.m.)
Type of cage: Stainless steel wire mesh cages, type DK-III (Becker & Co., Castrop-Rauxel, FRG)
No. of animals per cage: Single housing.
Animal identification: Individual identification using cage cards and group identification by tail marking.
Bedding: No bedding in the cages; sawdust in the waste trays.
Drinking water: Tap water ad libitum per day.
Diet: Kliba-Labordiaet, Klingentalmuehle AG, Kaiseraugst, Switzerland, ad libitum.
Analysis of drinking water: The drinking water is regularly assayed for chemical contaminants by the municipal authorities of Frankenthal and the technical services of BASF Aktiengesellschaft as well as for the presence of germs by a contract laboratory.
Analysis of feed: The feed used in the study was assayed for chemical and microbiological contaminants.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Fasting period: The animals were given no feed at least 16 hours before administration, but water was available ad libitum.
Reason for the vehicle: Aqueous formulation corresponds to the physiological medium.
Concentration: 20000 mg/ml
Administration volume: 10 ml/kg bw
Doses:
Dose: 2000 mg/kg bw
No. of animals per sex per dose:
3
Details on study design:
Time of day of administration: In the morning
Observation period: 14 days
Body weight determination: Individual body weights shortly before application (day 0), weekly thereafter and at the end of the study.
Signs and symptoms: Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals; these records are maintained with the raw data.
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 at the last day of the observation period. Withdrawal of food at least 16 houre before killing with CO2; then necropsy with grosspathology examination. Necropsy of all animals that died before as early as possible.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Male: 0/3
Female: 1/3 (after 2 h; lt can not be excluded that the death was induced by gavage error.)
Clinical signs:
other: Signs of toxicity noted in 1 female animal of the 2000 mg/kg dose group (after 2 h) comprised poor general state, dyspnoea, abdominal position, atonia and diarrhea. In the other animals (2000 mg/kg; 3 males, 2 females) no signs of toxicity were seen.
Gross pathology:
Animal that died (no. 382):
Lung: Discolouration, diffuse, in all lobes, dark red, moderate
Caecum: Dilatation, moderate, contents liquid
Animals that were sacrificed (3 males, 2 females): organs without particular findings.

Any other information on results incl. tables

Table 1: Bodyweights (g) of 3 male and female animals at day 0, 7, and 13 after application.

 Male day 0   day 7  day 13
 cage 375  196  278  341
 cage 376  200  272  323
 cage 377  196  261  307
 Female      
 cage 381  186  221  235
 cage 382  185    
 cage 383  185  217 226 

Applicant's summary and conclusion