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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
04 Sep 2007 - 19 Sep 2007 (experimental)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Study summary in tabular form available, scientifically acceptable

Data source

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

Materials and methods

Principles of method if other than guideline:
Range-finding study for OECD 422 study.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3-Methylbutan-1-ol (abbreviation IAA)
- Analytical purity: 99.8 %
- Lot/batch No.: 82934

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Crj:CD(SD)
- Age at study initiation: 7 weeks

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1% CMC-Na solution (containing 1% Tween 80)
Duration of treatment / exposure:
14 days
Frequency of treatment:
once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 15, 60, 250, and 1000 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
3
Control animals:
yes, concurrent vehicle
Positive control:
no

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

FOOD CONSUMPTION: Yes

WATER CONSUMPTION: Yes

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes

CLINICAL CHEMISTRY: Yes

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: No

Results and discussion

Results of examinations

Details on results:
CLINICAL SIGNS AND MORTALITY
- 1000 mg/kg bw: Death was confirmed in 1 female animal each on day 6 and day 9 of administration. On the day before, these two animals had shown no abnormalities. The deaths were thought to be due to test substance administration, but necropsy revealed no abnormalities.
At the highest dose of 1000 mg/kg bw slight sedation in behavior was observed in both sexes after administration, but returned to normal in approx. 30 min. Since this finding was observed only in the high-dose group, it was judged to be test substance related.

BODY WEIGHT AND WEIGHT GAIN
The deceased and the surviving animals in all dose groups showed a normal body weight gain. No abnormalities as compared to the control group were observed.

HAEMATOLOGY
At 250 mg/kg bw a slight increase in polymorphonuclear cell count (1/3, male) was observed.
At 60 mg/kg bw a slight increase in polymorphonuclear cell count (1/3, female) was observed.
These changes are thought to be of no toxicological significance since they were slight changes without dose-response relationship and incidental changes in one animal.

CLINICAL CHEMISTRY
At 250 mg/kg bw a slight increase in LDH (1/3, female) and in triglyceride (mean, males) was observed.
At 60 mg/kg bw a slight increase in GPT (1/3, male), in LDH (each in 1/3, male/female), in triglyceride (each in 1/3, male/female) and a slight decrease in total cholesterol (1/3, female) was observed.
At 15 mg/kg bw a slight decrease in LDH (mean, female) was observed.
These changes are thought to be of no toxicological significance since they were slight changes without dose-response relationship.

ORGAN WEIGHTS
- Absolute organ weights:
At 1000 mg/kg bw a slight increase in thymus weight (1/3, male) was observed.
At 250 mg/kg bw a slight increase in liver weight (1/3, male), a slight decrease in adrenal weight (1/3, male), a slight decrease in thymus weight (1/3, female), and a slight decrease in testis weight (1/3, male) were observed.
At 15 mg/kg bw a slight decrease in thymus weight (1/3, female) was observed.
These changes are thought to be of no toxicological significance since they were slight changes without dose-response relationship and incidental changes in one animal.
- Relative organ weights:
At 15 mg/kg bw a slight decrease in the relative weight of the thymus (1/3, female) was observed.
This change is thought to be of no toxicological significance since it was a slight change without dose-response relationship and an incidental change in one animal.

GROSS PATHOLOGY
In the animals sacrificed at the end of the study, no abnormalities were observed.
In the deceased animals, the following findings were described:
- no hemorrhage in the abdominal cavity (intestines, liver, stomach)
- retention of gas in the stomach or intestinal tracts
- dark red changes in the lung and thymus, and dark red coloration of the liver.
These changes were observed as post-mortem changes.

Effect levels

Dose descriptor:
NOAEL
Effect level:
250 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: sedation and mortality at the highest dose tested

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion