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Administrative data

Description of key information

Acute oral toxicity:
- oral: LD50 cut-off >5000 mg/kg bw (rat, OECD 423), LD50 >5000 (rat)
- dermal: LD50 >5000 mg/kg bw (rat)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
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
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
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
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

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

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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Standard method but limited documentation
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
rabbits tested, 5000 mg/kg bw, observation period 14d
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Vehicle:
not specified
Duration of exposure:
not specified
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
8
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Other examinations performed: clinical signs, mortality
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
0/8 at 5000 mg/kg bw
Interpretation of results:
GHS criteria not met
Conclusions:
In this acute dermal toxicity test conducted in 8 rabbits, the LD50 was found to be above the highest tested dose of 5000mg/kg.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw

Additional information

Oral

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 LD 50 cut-off value was determined to be 5000 mg/kg bw.

In another study, ten rats (5 males, 5 females) were administered 5000 mg/kg bw orally (Givaudan, 1978). No deaths were observed within 14 days, thus the LD50 was determined to be >5000 mg/kg bw/day. The dose for the LD50 study had previously been determined in a range-finder test, in which 4 male and 4 female rats were adminstered 0.5, 1, 2, or 5 g/kg bw, no deaths were observed within 14 days (Givaudan, 1978).

In a third study, ten rats were administered orally with 5000 mg/kg bw (Moreno, 1973). As no mortality occurred within the 14 day post dosing observation time, the LD50 values was found to be >5000 mg/kg bw. Although no further data were given, this study was evaluated reliable as it is cited by the FFHPVC Terpene Consortium and the original data are from highly experienced and respected toxicologists.

In an acute oral range-finding toxicity test, individually housed mice aged 4-5 weeks were fasted for 4 hours and then orally intubated with 2, 5, or 10  ml/kg bw of undiluted test substance (2, 6 and 2 mice, respectively) (Quest, 1980). The mice were observed up to 7 days following treatment and dying mice were necropsied. All mice surviving to the end of the observation period were weighed, killed and examined post mortem. Due to observed mortality in the 5 and 10 ml/kg bw groups (1/6 and 2/2 respectively), the LD50 was calculated to be >5 and < 10 ml/kg bw and the methylionone was given a toxicity rating according to Hodge and Sterner’s classification.

Dermal

For evaluating the acute dermal toxicity, a concentration of 5000 mg/kg bw was tested in eight rabbits (Moreno, 1973). Since no mortality was observed during the 14 day observation period, the LD50 was determined as >5000 mg/kg bw. Although the report was short, this study was evaluated reliable as it is cited by the FFHPVC Terpene Consortium and the original data are from highly experienced and respected toxicologists.

Justification for classification or non-classification

Due to the results from different studies including one performed according to OECD Guideline 423, no classification is required.