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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994
Reference Type:
other: Amendment
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of the test substance used in the study report: Asta-C6-Acetal
- Physical state: liquid, achromatic
- Storage: refrigerator, exclusion of light

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae Gmbh, Biberach, FRG
- Age at study initiation: young adults
- Weight at study initiation: 150 - 300 g
- Fasting period before study: 16 hours
- Housing: single housing; stainless stell wire mesh cages, type DK-III (Becker & Co., Castrop-Rauzel, FRG); no bedding in the cages; sawdust in the waste trays
- Diet: ad libitum, Kliba-labordiaet 343, Klingentalmuehle AG Kaiseraugst, Switzerland
- Water: ad libitum, tap water
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes: fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Remarks:
DAB 10
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 4 and 40 g/100 mL
- Amount of vehicle: 5 mL/kg
- Justification for choice of vehicle: the test substance was insoluble in water

CLASS METHOD
- Rationale for the selection of the starting dose: based on the physical and chemical characteristics of the test substance and the composition, no pronounced acute oral toxicity was expected. Therefore a starting dose of 2000 mg/kg bw was chosen as a first step.
Doses:
200 and 2000 mg/kg
No. of animals per sex per dose:
Experiment 1 (2000 mg/kg): 3 females
Experiment 2 (200 mg/kg): 3 females
Experiment 3 (200 mg/kg): 3 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights were determined shortly before administration (day 0), weekly thereafter and at the end of the study (before fasting period). A check concerning general observations and mortality was made twice each working day and once on weekends and on public holidays.
- Necropsy of survivors performed: yes. Withdrawal of food at least 16 hours before killing with CO2; then necropsy with gross-pathological examination.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
- All animals exposed to 2000 mg/kg died, within 1 day after exposure.
- No mortality observed in animals exposed to 200 mg/kg.
Clinical signs:
- Female animals exposed to 2000 mg/kg: A poor general state, dyspnea, apathy, and paresis were observed in all animals, between time of exposure and 4 hours after exposure. Atonia and erythema were observed in all animals, between 1 and 4 hours after exposure. Lying in the lateral position was observed in 2 animals, between 1 and 4 hours after exposure. Lying in the abdominal position and twitching was observed in 1 animal, 1 hour after exposure. Staggering was observed in 1 animal, during exposure. Ataxia was observed in all animals, 3 hours after exposure. Salivation was observed in all animals, 1 hour after exposure. Exsiccosis was oberved in 2 animals, 4 hours after exposure. Piloerection was observed in 2 animals, between 3 to 4 hours after exposure.
- Female animals exposed to 200 mg/kg: No clinical signs were observed in all animals.
- Male animals exposed to 200 mg/kg: An impaired general state and dyspnea were observed in 2 animals, between 1 and 5 hours after exposure. Piloerection was observed in all animals, between 1 and 5 hours after exposure.
Body weight:
- Mean body weight female animals exposed to 2000 mg/kg: 189 g at study start
- Mean body weight female animals exposed to 200 mg/kg: 187 g at study start, 244 g after 13 days
- Mean body weight male animals exposed to 200 mg/kg: 199 g at study start, 297 g after 13 days
Gross pathology:
- Congestion agonal was observed in all female animals exposed to 2000 mg/kg
- No pathologic findings noted in all animals exposed to 200 mg/kg

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information
Conclusions:
Under the conditions of this study the oral LD50 in Wistar rats is between 200 and 2000 mg/kg bw.
Executive summary:

In GLP-compliant EU Method B1 guideline study modified according to the acute toxic class method , 3 female Wistar rats were exposed to 2000 mg/kg bw, and 3 male and 3 female Wistar rats were exposed via oral gavage to 200 mg/kg bw of the test substance dissolved in olive oil DAB. After an observation period of 14 days the surviving animals were necropsied. Several signs of toxicity were noted in the animals exposed to 2000 mg/kg bw, all of which died within 1 day. Gross pathology showed agonal congestion in these animals. No mortality was observed in animals exposed to 200 mg/kg bw. The LD50 was therefore determined to be between 200 and 2000 mg/kg bw.