Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed
Year:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
Deviations:
not specified
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Nature of substance: ESACURE 1001

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: aqueous solution of 0.5% methocel
Duration of treatment / exposure:
28 days
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
100 mg/kg bw/day (nominal)
Dose / conc.:
400 mg/kg bw/day (nominal)
Dose / conc.:
800 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 100 mg/kg bw/day
Male: 5 animals at 400 mg/kg bw/day
Male: 5 animals at 800 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 100 mg/kg bw/day
Female: 5 animals at 400 mg/kg bw/day
Female: 5 animals at 800 mg/kg bw/day

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
No toxicologically significant clinical signs were seen during the study and at the post-dose observations performed daily.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No statistically significant differences were observed in body weight or food consumption between control and treated groups throughout the study.
Haematological findings:
no effects observed
Description (incidence and severity):
No changes of toxicological significance were detected in haematological and coagulation parameters.
Urinalysis findings:
effects observed, non-treatment-related
Description (incidence and severity):
Urea levels were increased in both sexes from the low, mid and high dose groups when compared with controls. Although these changes achieved statistical significance at all dose-levels tested, they were considered without any toxicological significance because urea levels detected in all individual animals were within the expected range of historical data (mean, standard deviation: 41.1 mg/ml, 10.3 for males and 47.4 mg/ml, 10.3 for females). No toxicological significance was attributed to all other statistically significant changes observed as they were not corralted with the dose-level and were not consistent between sexes
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
Terminal body weight, absolute and relative organ weights were unaffected by treatment and no macroscopic change was seen in the sacrificed animals that could considered to be treatment-related
Neuropathological findings:
no effects observed
Description (incidence and severity):
Neurotoxicity tests and measurements performed at the end of treatment did not show changes attribuitable to treatment

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
800 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day
Dose descriptor:
NOEL
Effect level:
800 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Not classified