4-[(3-chlorophenyl)(1H-imidazol-1-yl)methyl]-1,2-benzenediamine dihydrochloride

Repeated dose toxicity: oral

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: OECD-guideline No. 407 (May 12, 1981. Adopted) EEC Directive 67/548/EEC

GLP compliance:

yes

Limit test:

yes

Test animals

Species:

rat

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

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 20 mg/kg bw/day
Male: 5 animals at 80 mg/kg bw/day
Male: 5 animals at 320 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 20 mg/kg bw/day
Female: 5 animals at 80 mg/kg bw/day
Female: 5 animals at 320 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:

Clinical observations:
T001625 did not lead to adverse effects on clinical
behaviour and physical appearance in Wistar rats when dosed
by oral gavage at 20 and 80 mg/kg body weight/day for 28
days. Salivation was noted at 320 mg/kg body weight/day.

Opthalmoscopic examination did not reveal any abnormalities.

There was no relevant adverse effect on body weight and body
weight gain.

Laboratory findings:
T001625 did not produce relevant adverse effects on
haematological parameters. A decrease in haematocrit in
males at 80 and 320 mg/kg body weight/day and a decrease in
haemoglobin and red blood cells in males at 80 mg/kg body
weight/day and in males and females at 320 mg/kg body
weight/day are considered drug-related.

There was no relevant adverse effect on biochemical
parameters in male and female rats dosed up to 320 mg/kg
body weight/day.

There was no relevant adverse effect on urinary parameters
when dosed by oral gavage at 20 and 80 mg/kg body weight/day
for 28 days. A decrease in creatinine at 320 mg/kg body
weight/day is considered drug-related.

Effects in organs:
There were no relevant adverse effects on organ weights of
male Wistar rats when dosed by oral gavage at 20 and 80
mg/kg body weight/day. An increase in absolute and relative
weight of the liver in females dosed at 320 mg/kg body
weight/day and of the adrenals in all T001625-dosed females
and males dosed at 320 mg/kg body weight/day is considered
drug- and dose-related.

There were no macroscopic changes, except for the presence
of swollen adrenals in one male at 320 mg/kg body weight/day
and in females dosed at 80 mg/kg body weight/day.

In males dosed at 320 mg/kg body weight/day drug-related
changes were adrenocortical hypertrophy and hepatocytic
swelling. Drug- and dose-related changes in female rats
were adrenocortical hypertrophy (all dose levels), ovarian
changes (80 and 320 mg/kg body weight/day), hepatocytic
swelling and vacuolation, and hyperplasia of the splenic red
pulp (320 mg/kg).

Effect levels

Dose descriptor:

NOAEL

Effect level:

80 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