3-oxo-4-azaandrost-5-ene-17β-carboxylic acid

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: Directive 84/449/EEC, Annex V, Method B7 and OECD Guideline No. 407

GLP compliance:

yes

Limit test:

no

Test animals

Species:

other: Rat, Sprague Dawley CD

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

other: 1% aqueous methylcellulose

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 10 mg/kg bw/day
Male: 5 animals at 150 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 10 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:

Clinical observations:
Clinical Signs:

There were no mortalities or clinical signs of reaction
following treatment with the test substance.



Bodyweights:

There were no statistically significant differences between
bodyweight gains of the rats treated with the test substance
and those of controls.


Food Consumption:

Slightly higher food consumption was recorded for male and
female rats receiving the test substance. However, these
increases were slight and not dose dependent.


Water consumption:

Virtual assessment of water consumption during weeks 1, 3
and 4 indicated an increase in water consumption in the high
and intermediate dose groups for male rats and at all
dosage levels for the female rats, confirmed by daily
weighing in week 2.


Water consumption for the low dose group revealed a slight
numerical increase in water consumption for the females only
.

Laboratory findings:
Haematology:

A significant decrease in the number of lymphocytes was seen
in male rats in the high and intermediate dose groups
(P<0.01) in comparison with controls. This was reflected in
a significantly lower total white blood cell count for males
at these dosage levels (P<0.5). A lower haemoglobin
concentration was calculated for female rats in the high and
intermediate dose groups (P<0.05 and P<0.01 respectively)
compared with controls, accompanied by a slightly lower
packed cell volume (P<0.05). Changes were minor in nature
and values were within the expected range for rats of this
age and sex. The differences seen were not considered
attributable to treatment.


Intergroup variation in the remaining parameters measured
revealed no significant differences from controls.


Biochemistry:

Significantly lower sodium ion levels were recorded for
female rats in the high and intermediate dose groups

(P<0.05) in comparison with controls. Male rats in the high
dose groups showed an increase in cholesterol levels

(P<0.05). However, these changes were minor in nature and
within the expected range for rats of this age and strain.
These differences were neither statistically significant nor
dosage dependent. Intergroup variation among remaining
parameters revealed no other significant differencres from
controls.

Effects in organs:
Organ weights:

For female rats in all dose groups unadjusted brain weights
were significantly increased (P<0.05) in comparison with
controls. However, differences were not dosage-dependent and
analysis of adjusted values did not show statistical
significance. Also, all values in the high dose group were
within normal range. These difference were considered not to
be treatment related.


There were no significant differences in organ weights
between control and treated animals. In both sexes there was
a tendency for lower adrenal weights in comparison with
controls in particular in the high dose group.
Differences, however, were not significant and the majority
of individual values fell within the expected range.


Macroscopic pathology:

The macroscopic examination performed at termination
revealed no changes attributable to treatment.


Microscopic pathology:

No treatment-related changes were observed. All
histopathological findings were considered to be of no
toxicological importance.

Effect levels

Dose descriptor:

NOAEL

Effect level:

1 000 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