Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline used

Data source

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

Materials and methods

Test guideline
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
Details on test material:
Mitsuboshi Chemical Co., Ltd.: purity >99%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ORGANISMS
age: 5 weeks
weight at initiation: 168-183 g for males, 138-162 g for females
pellet food and water: free take

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Sesame oil
Details on oral exposure:
Application volume: 5ml/kg bw
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
28 days exposure, 14 days recovery period
Frequency of treatment:
once a day
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 100, 300 and 1000 mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
6
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: 14 days for 0 mg/kg and 1000 mg/kg group

Examinations

Observations and examinations performed and frequency:
clinical signs and mortality: every day
body weight: twice a week, total 9 times during the 28 days, and additional 4 times during the 14 days recovery period
food consumption: once a week (24hr consumption)
water consumption: not checked
Hematology: checked
Clinical Chemistry: checked
Organ weights: checked

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOEL
Effect level:
300 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: Reversible and slight effects in hematology, clinical chemistry and gross necropsy
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: No adverse effects observed

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

PRELIMINARY EXAMINATION
4 Males and 4 females were used for the 14 days Preliminary
Examination.
Any toxicological effects in the clinical signs, body
weight, food consumption, urinary findings, hematological
findings, blood chemical findings and weight of organs was
not observed in the animals of any groups up to 2000
mg/kg/day.
At necropsy enlargement of cecum was observed in all animals

at 2000 mg/kg/day group.
HISTOLOGICAL AND STATISTICAL RESULTS
general: No change in mortality and behavior were observed
in any groups.
body weight and food consumption: No toxic effect was
observed in any groups.
urinary findings: Increase of specific gravity and decrease
of pH were observed in 1000mg/kg males. However no related
change was observed in other findings.
hematological findings: Slight decrease of white blood cell
count (due lymphopenia) were observed in 1000mg/kg males. No
pathological change was observed in the lymphatic tissues,
such as marrowcyte, thymus, lymphknote and spleen.
blood chemical finding: Slight increase of GPT in females,
slight decrease of total cholesterol in males and slight
decrease of glucose in females were observed in 1000mg/kg
group. However, including liver, no pathological change was
observed in any of related organs. According to the author,
the change is within normal range, based on their other
study data.
necropsy finding: Slight enlargement of cecum was observed
in one male and one female in 1000mg/kg group. However no
diarrhea and no growth abnormalities were observed.
weight of organs: Decrease of thymus weight in 100mg/kg and
increase of spleen weight in all dose levels in female were
observed. However those changes were no relation with dose
levels.
remark: All of above changes returned to normal during 14
days recovery period.

Applicant's summary and conclusion

Conclusions:
Toxicological effects were decrease of white blood cell count, total cholesterol and urine pH and enlargement of
cecum in male at 1000 mg/kg/day; increase of GPT, decrease of glucose and enlargement of cecum in female at 1000 mg/kg/day.
NOEL for Repeat Dose Toxicity to rats is 300mg/kg/day in both sexes.