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)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: 96/54/EG, B.7; OECD 407 (1995)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
other: rat, HanBrl:Wist (SPF)

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: PEG 300
Details on oral exposure:
Method of administration:
oral by gavage
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Male: 5 animals at 50 mg/kg bw/day Male: 5 animals at 150 mg/kg bw/day Male: 10 animals at 450 mg/kg bw/day Male: 10 animals at 0 mg/kg bw/day Female: 5 animals at 50 mg/kg bw/day Female: 5 animals at 150 mg/kg bw/day Female: 10 animals at 450 mg/kg bw/day Female: 10 animals at 0 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
No mortality occurred during the study period.

There were no relevant test substance-related effects in
clinical appearance, body weight, food and water
consumption.

There were no relevant test substance-related effects during
functional observational battery, no changes in fore-limb
and hind-limb grip strength, and no differences in the mean
locomotor activity, respectively.

Laboratory findings:
No relevant test substance-related differences in hematology
parameters were noted.

Clinical biochemistry revealed statistically significant
increases of cholesterol and phospholipid levels in males
and females at 450 mg/kg bw/d. These findings disappeared at
the end of recovery period. Elevated phospholipid levels
were also noted in females given 50 and 150 mg/kg bw/d.
Triglycerides concentration was statistically significant
increased in females at 450 mg/kg bw/d, which was not
reversible after recovery period. The creatinine levels were
significantly decreased in males at 150 mg/kg bw/d and in
animals of both sexes at 450 mg/kg bw/d. Significantly
increased calcium levels were determined in males and
females given 450 mg/kg bw/d and additionally in females
given 150 mg/kg bw/d, respectively. The chloride levels were
significantly decreased in females at 450 mg/kg bw/d. The
protein levels were significantly increased in females at
150 and 450 mg/kg bw/d, whereas albumin levels and the

A/G ratios were significantly increased in females from all
treatment groups.

No test substance-related differences in urinalysis
parameters were noted when compared with the control values.

Effects in organs:
Test substance-related differences in organ weights were
observed in the liver of males and females. At

450 mg/kg bw/d females showed significantly increases in
both absolute and relative liver weight when compared with
controls.

Significantly increases in relative liver weights were noted
in males at 450 mg/kg bw/d and in females at 150 mg/kg bw/d.
Significantly elevated mean absolute and relative liver
weights were still present in females given 450 mg/kg bw/d
after recovery period of two weeks.

There were no gross lesion that could be attributed to
treatment with the test substance.

Microscopy of the liver revealed minimal to slight
centrilobular hepatocellular hypertrophy in animals of both
sexes at 150 and 450 mg/kg bw/d. This finding recovered
completely after treatment-free period. There was no further
sign for liver damage.

Effect levels

Dose descriptor:
NOAEL
Effect level:
450 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

Executive summary:

The NOAEL of the substance was considered to be 450 mg/kg bw/d.