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Toxicological information

Acute Toxicity: oral

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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: guideline study with GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

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 (Acute Toxicity (Oral))
GLP compliance:
yes
Remarks:
BASF AG, Department of Toxicology
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Methylionone
- batch number: 09049610046
- physical state/appearance: liquid, yellowish clear
- storage conditions: refrigerator, exclusion of oxygen (store under nitrogen)
- analysis of test substance: the test substance has been characterized by analysis; the stability of the test substance over the study period has been proven by reanalysis; the test substance was monogeneous by visual inspection
- analysis of test substance preparations: the stability of the test substance in olive oil DAB 10 for a time period of 4 hours was confirmed by analysis
- conduct of analytics: central analytical department of BASF AG

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
- age: young adult
- weights at start of study: 150-300 g (+/- 20% of mean weight)
- identification: individual identification using cage cards and group identification by tail marking
- housing: single housing in fully air-conditioned rooms, central air conditioning guaranteed a range of 20-24°C 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: 12:12
- type of cage: stainless steel wire mesh cages, type DK-III
- bedding: no bedding in the cages, sawdust in the waste trays
- drinking water: tap water ad libitum per day
- diet: Kliba-Labordiät 343, Klingentalmühle AG, Kaiseraugst, Switzerland, ad libitum
- analysis of drinking water: the drinking water is regularly assayed for chemical contaminants by municipal authorities of Frankenthal and the technical services of BASF AG 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
- acclimatization period: acclimatization for at least 1 week
- fasting period: the animals were given no feed at least 16 hours before administration, but water was available ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: olive oil DAB 10
Details on oral exposure:
- reason for the vehicle: test substance could not be homogeneously distributed in aqua bidest
- form of administration: solution
- amounts administered: dose: 2000 mg/kg; concentration: 40 g/100 ml; administration volume: 5 ml/kg
- time of day of administration: in the morning
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- observation period: 17 days for males / 14 days for females
- body weight determination: individual body weights shortly before application (day 0), weekly thereafter and at the end of the study (before fasting period)
- signs and symptoms: recording of signs and symptoms several times on the day of administration and at least once each workday for the indiviual animals
- mortality: a check for any dead or moribund animals 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 hours before killing with CO2; then necropsy with grosspathology examination; necropsy of all animals that died before end of study as early as possible

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50 cut-off
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: no deaths observed
Mortality:
no mortality up to day 14 (females) and day 17 (males)
Clinical signs:
see table
Body weight:
see table
Gross pathology:
necropsy findings of sacrificed animals: organs without particular findings (3 males, 3 females)
Other findings:
clinical symptoms reversible

Any other information on results incl. tables

animal symptoms:

 

males

females

 

 cageside observations

 number of animals

  cageside observations

  number of animals

 impaired general state

 H1 - H4

 3

 H0 - H2

 2

 poor general state    

 H0 - D2

 3

dyspnoea

 H1 - H4

 3

 H0 - D2

 3

apathy    

 H0 - D2

 3

staggering

 H1 - H4

 3

 H0 - D2

 3

twitching    

 H4

 1

 saltatory spasm

 H1 - H3

 1

 
 spastic gait    

 D1 - D2

 1

 piloerection    

 H0 - D2

 3

 smeared fur    

 D2

 1

 exophthalmos    

 H0 - H1

 3

 S5    

 D2

 1

H: hour

D: day

S5: red smeared fur in the anogenital area

body weights:

   

day

 

 

 0

 7

 13

  male        

 1

175 

244 

273 

 2

175 

230 

263 

 3

175 

230 

281 

 mean

175 

235 

272 

  female        

 1

170 

202 

210 

 2

171 

194 

215 

 3

172

203 

215 

 mean

171

200 

213

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The oral acute toxicity of methylionone was tested in a study under GLP performed according to OECD Guideline 423 (BASF, 1999). Three male and three female Wistar rats were once administered by gavage with 2000 mg/kg bw in 5 ml/kg bw olive oil DAB 10. The following observation time was 17 days for males and 14 days for females. Although signs of toxicity were noted during the first days after application, the animals appeared normal after five days. Since no mortality was observed, the LD50 cut-off value was determined to be 5000 mg/kg bw.