Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 Dec 1994 - 29 Jun 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: done under GLP and OECD method

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Labs, MI
- Age at study initiation: ~6wks
- Weight at study initiation: (100 - 130g upon arrival)
- Housing: Hanging stainless steel, ventilated wire-bottomed cages
- Diet: Certified Rodent Chow ad libitum
- Water: free assess to tap water
- Acclimation period: 1 day followed by 5 - 6 days pre-treatment period.

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 71±6
- Humidity (%): Ambient
- Photoperiod (hrs dark / hrs light):12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Method of administration:
Gavage
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Dosing formulation assays performed on day 0 and day 21. Formulations were homogeneous and contained 101 - 109% of intended concentrations.
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: 1/day for 28 days.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 mg/kg
Basis:
other: gavage
Remarks:
Doses / Concentrations:
15mg/kg
Basis:
other:
Remarks:
Doses / Concentrations:
150mg/kg
Basis:
other: gavage
Remarks:
Doses / Concentrations:
500mg/kg
Basis:
other: gavage
No. of animals per sex per dose:
Male: 10 animals at 0 mg/kg bw/day
Male: 5 animals at 15 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Male: 10 animals at 500 mg/kg bw/day

Female:10 animals at 0 mg/kg bw/day
Female: 5 animals at 15 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 10 animals at 500 mg/kg bw/day
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: based on acute oral toxicity testing results
- Rationale for animal assignment: random

5 additional rats/sex/group were added to control and treatment groups to evaluate 2 week recovery

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule:twice daily on treatment days

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: prior to exposure and then twice a day

BODY WEIGHT: Yes
- Time schedule for examinations: prior to treatment and then twice weekly

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
Zero mortality
Mortality:
no mortality observed
Description (incidence):
Zero mortality
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
MORTALITY: Zero

Effect levels

Dose descriptor:
NOEL
Effect level:
> 500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no mortality and no observed effects

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
No significant toxicity was observed over the range of doses tested. NOEL is > 500 mg/kg/BW.