Registration Dossier

Administrative data

repeated dose toxicity: oral
Adequacy of study:
other information

Data source

Reference Type:
other: Body responsible for the test

Materials and methods

Test guideline
according to
other: 96/54/EG, B.7; OECD 407 (1995)
GLP compliance:
Limit test:

Test animals

other: rat, Wistar Rj:WI (IOPS Han.)

Administration / exposure

Route of administration:
oral: unspecified
other: diet
Details on oral exposure:
Method of administration:
oral via diet
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 7.9 mg/kg bw/day
Male: 5 animals at 38 mg/kg bw/day
Male: 5 animals at 194 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 8.5 mg/kg bw/day
Female: 5 animals at 44 mg/kg bw/day
Female: 5 animals at 208 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 treatment-related clinical signs in any dose
group throughout the study period. At 2500 ppm mean body
weight was reduced in females by 6 to 7 % between days 15
and 29, when compared to controls. Between days 8 and 15,
there was a mean body weight gain of +1.7 g/day (statisti-
cally significant) in females, compared with a gain of

+3.4 g/day in the corresponding controls. Thereafter, mean
body weight gain was comparable to controls in females.
Overall between days 1 and 29, the cumulated body weight
gain was reduced by 25 % in females (not statistically
significant) when compared to the corresponding control
values. Mean food consumption in females was decreased by
between 8 % and 15 % at each measured interval from day 11
onwards, the effects being statistically significant between
days 11 to 15 and days 22 to 25.

No treatment-related changes were observed during the
neurotoxicity assessment including exploratory locomotor
activity, open field observations, sensory reactivity, and
forelimb and hindlimb grip strength.

Laboratory findings:
Haematology revealed slightly lower mean red blood cell
count (-7 %, not statistically significant), haemoglobin
concentration (-8 %, statistically significant) and
hematocrit (-8 %, statistically significant) in females at
2500 ppm.

Clinical biochemistry revealed statistically significant
lower mean total bilirubin concentration of -50 % in females
at 2500 ppm.

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

Effects in organs:
In females receiving 2500 ppm a lower mean terminal body
weight (-6 %, not statistically significant) was observed at
the end of treatment. The mean absolute and relative liver
weights were slightly higher (18 to 25 %) in females at

2500 ppm when compared to controls. However, there was no
corresponding histopathologic change in the livers of these

Effect levels

Dose descriptor:
Effect level:
> 208 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

Classified as: Not classified