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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 19 - June 02, 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to OECD and in accordance with GLP. The study material is well characterized.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
and 21 CFR 28
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
424-660-8
EC Name:
-
Cas Number:
224631-15-6
Molecular formula:
Hill formula: C18H26N4O5S CAS formula: C18H26N4O5S
IUPAC Name:
(S)-2,5-dioxopyrrolidin-1-yl 2-(3-((2-isopropylthiazol-4-yl)methyl)-3-methylureido)-3-methylbutanoate

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles Rivers, Portagge, Michigan
- Age at study initiation: 6 weeks
- Weight at study initiation: 100 to 120g on arrival, 6 days prior to treatment
- Fasting period before study: overnight.
- Housing: individually in hanging stainless steel cage
- Diet: Certified Rodent Chow ad libitum
- Water: tap water ad libitum
- Acclimation period: 6 days before

ENVIRONMENTAL CONDITIONS
- Temperature: 70 - 72°F
- Humidity : Ambient
- Photoperiod :12hrs light/12rhs dark

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
corn oil
Details on oral exposure:
Dose concentration: 2000 mg/kg
Dose Volume: 20 ml/kg
Doses:
Single dose: 2g/kgBW at a dose level of 20ml/kgBW
No. of animals per sex per dose:
5 females/males per dose
Control animals:
no
Details on study design:
All animals were observed frequently on day of dosing and daily thereafter for at least 13 days after treatment for a total of 14 days. Day of treatment = day 0.
Daily observations included signs of toxicity in addition to lethality.
Animals weighed on a weekly basis.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was 0 (zero) mortality
Clinical signs:
Decreased activity and diarrhoea observed in male and female rats following treatment.
Dyspnea was observed in male rats.
All signs observed were confined to the day of treatment.
None of the rats died in the study.
Body weight:
No apparent treatment related changes effects on body weights were observed.
Gross pathology:
No gross morphological changes were observed in rats that were euthanzsed and necropsied at the end of the 2 week observation period.

Applicant's summary and conclusion

Conclusions:
LD50 was greater than the limit dose of 2000mg/kgBW