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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
repeated dose toxicity: oral
Adequacy of study:
other information

Data source

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

Materials and methods

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

Test animals

Species:
other: rat, Wistar Hsd Cpb:WU

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: 2 % Cremophor EL in Wasser. "ENGLISH" 2 % Cremophor EL in water.
Details on oral exposure:
Method of administration:
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 0 mg/kg bw/day
Male: 5 animals at 40 mg/kg bw/day
Male: 5 animals at 200 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 40 mg/kg bw/day
Female: 5 animals at 200 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
There were no treatment-related deaths or other differences
from control for other parameters measured, including
clinical appearance, body weight, food and water consumption
that were considered to be related to treatment.

No test substance-related effects were detected during
functional observational battery including functional
observations and grip strength measurements; and motor
activity measurements.

Laboratory findings:
Haematology revealed statistically significant decreased
MCHC values and shortened thromboplastin time (HQick) for
the 1000 mg/kg bw/d females.

Clinical biochemistry revealed slightly increased
cholesterol concentrations in both sexes at 200 and

1000 mg/kg bw/d (statistically significant in females).
Concentrations of urea and protein were statistically
significantly increased in males and females at

1000 mg/kg bw/d.

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

Effects in organs:
At 200 and 1000 mg/kg bw/d males and females showed
statistically significantly increases in absolute and
relative liver weights. The deviations of the relative liver
weights from controls were + 14 % and + 37 % in males and

+ 20 % and + 57 % in females.

At necropsy distinct lobulation and enlargement of the
livers were seen in males at 200 mg/kg bw/d and in both
sexes at 1000 mg/kg bw/d.

Microscopy revealed test substance-related findings in the
liver, thyroid gland and kidney. In the liver hepatocellular
hypertrophy and cytoplasmic change was observed in both
males and females receiving 200 and 1000 mg/kg bw/d. In the
thyroid gland, an increased incidence of follicular cell
hypertrophy was seen in males at 200 and 1000 mg/kg bw/d and
in females at 1000 mg/kg bw/d. In males an increased
severity of hyaline droplet accumulation was noted in the
proximal tubules of the kidneys at 200 and 1000 mg/kg bw/d.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
40 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
NOEL
Effect level:
40 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:
Classified as: Not classified