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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10.9. - 25.9.2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: performed according to OECD/EC test guidelines and GLP compliant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
tert-butyl N-[(1S,3S,4S)-4-hydroxy-4-[4-methoxy-3-(3-methoxypropoxy)phenyl]-1-[(2S,4S)-5-oxo-4-(propan-2-yl)oxolan-2-yl]-3-(propan-2-yl)butyl]carbamate
EC Number:
700-317-0
Cas Number:
934841-33-5
Molecular formula:
C30H49NO8
IUPAC Name:
tert-butyl N-[(1S,3S,4S)-4-hydroxy-4-[4-methoxy-3-(3-methoxypropoxy)phenyl]-1-[(2S,4S)-5-oxo-4-(propan-2-yl)oxolan-2-yl]-3-(propan-2-yl)butyl]carbamate
Details on test material:
Test substance name: SPPIOO C6
Mol. weight:551.73
CAS No.: not available
Batch No.:HH-853.35Kr
Purity: 99.2 % (A) - HPLC (Sum of isomers 1 and 2)
Significant impurities:sum of all impurities by HPLC: ........ 0.8 % (A)
Solvent content:
Isopropyl acetate: (CAS No. 108-21-4) ....... 1.9 % (w/w)
Methylcyclohexane: (CAS No. 108-87-2) ... 5.8 % (w/w)
Stability/Expiration: DEC-2007

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
laboratory albino rat (it is the preferred rodent species according to the guideline)
Wistar, monitored quality. Source: breeding farm BioTest S.LO., Komirovice, 281 25, CZ, RCH CZ 21760152
6 females, 8 - 10 weeks at the time application, acclimatisation 6 days,
animal room with monitoring conditions - 3 animals of one sex in one plastic breeding cage Velaz T4
ST 1 BERGMAN - standard pelleted diet ad libitum, (producer: Mill Kocanda, Jesenice u Prahy)
drinking tap water ad libitum (quality corresponding to Regulation No. 252/2004 Czech ColI. of Law)
room temperature 22 ± 3°C, permanently monitored, relative humidity 30 - 70 %, permanently monitored
light: 12-hour light/12 hour dark
sterilized shavings of soft wood, according to the internal rule, at the start of the study the weight
variation of animals was minimal and did not exceed ± 20 % of the mean weight for each sex
colour marks 1 - 3 on tail of animals, each cage was marked with the number of study, sex and dose of the test substance
certificate of good health condition - from breeding farm; no signs of diseases were observed at clinical check-in, during the
acclimatisation period and before the start of study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
Immediately before application the test substance was weighed, mixed in vehicle (olive
oil) and resulting suspension was administered to the stomach by tube. The single volume of
administered suspension was Iml/lOO g of animal body weight.

About twenty hours before oral administration the animals were not fed, water was given
ad libitum. Immediately before application the animals were weighed and distributed to
groups with 3 animals.
The feed was given to animals 3 hours after application of the test substance.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 (two groups of 3 females) at 2000 mg/kg
Control animals:
no
Details on study design:
Body weight: before application, the 8th day and before euthanasia of animals
Mortality: daily
Clinical examination: daily
Pathological examination: 15th day

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
The test substance administered at the dose of 2000 rug/kg caused no death of animals.
Clinical signs:
Clinical signs of intoxication were observed in all six animals (anaemic mucous membrane,
piloerection, decreased response to stimuli).
Body weight:
Weight increments were adequate to species, sex and age of animals in experiment.
Gross pathology:
Macroscopic changes (spleen - granular surface)
were diagnosed during pathological examination in one animal.
Other findings:
no

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance toxicity was evaluated on the basis of mortality, clinical signs of intoxication, body weight increments during the observation period and necropsy findings at the end of study. The test substance administered at the dose of 2000 mg/kg caused no death of animals.
Clinical signs of intoxication were observed: anaemic mucous membrane, piloerection, soft decreased response to stimuli - 3 hours after application in all six animals, 24 hours after application - without pathologic changes in all six animals. Macroscopic changes (spleengranular surface) were diagnosed during pathological examination in one animal (five animals without pathologic changes). According to the study results the value of LDso of the test substance SPPI00 C6 (in female rats) is higher than 2000 mg/kg of body weight.