ALZON

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: Commission Directive 92/69/EEC, B7

GLP compliance:

yes

Limit test:

no

Test animals

Species:

other: rat, Sprague-Dawley

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

other: Arachis oil BP

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 1.5 mg/kg bw/day
Male: 5 animals at 15 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 1.5 mg/kg bw/day
Female: 5 animals at 15 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:

Clinical observations:
Mortality Data:

There were no treatment-related deaths during the study.


One male treated with 15 mg/kg/day was found dead at the
start of Day 2.


Clinical Observations:

Blue staining was apparent on the cage tray-liners of 150
mg/kg/day animals from Day 3 onwards and incidents of
increased salivation were detected either pre-dosing or up
to two minutes after dosing from Day 17 onwards.


No such observations were detected at other dose levels.


Bodyweight:

Males treated with 150 mg/kg/day showed a slight reduction
in bodyweight gain throughout the study period compared with
that of controls.


Females from this dose group and animals of either sex
treated with 15 or 1.5 mg/kg/day showed no adverse effect on
bodyweight development.


Food Consumption:

A slight reduction in food consumption was detected for
males treated with 150 mg/kg/day from Week 2 onwards.


No such effect was detected for 150 mg/kg/day females or
animals of either sex treated with 15 or 1.5 mg/kg/day.


Water Consumption:

No intergroup differences were detected.


Functional observations:

A statistically significant reduction in forelimb grip
strength was detected for females treated with 150 and 1.5
mg/kg/day compared with that of controls.

Laboratory findings:
Haematology:

A statistically significant increase in clotting
[prothrombin] time was detected for 150 and 15 mg/kg/day
females when compared with controls. The dose response,
however, was unconvincing and therefore the effect was not
considered to be a toxic one.


Blood Chemistry:

Animals of either sex treated with 150 mg/kg/day showed a
statistically significant increase in plasma bilirubin
compared with that of controls. There was also a
statistically significant decrease in aspartate amino
transferase in males treated with 150 mg/kg/day. The effect
was not seen in female animals.

Effects in organs:
Necropsy:

No treatment-related macroscopic abnormalities were
detected.


The decedent from the 1.5 mg/kg/day dose group showed
reddened lungs and a dark liver.


Organ Weights:

There was no organ weight changes that could be considered
to be a toxic effect. However, a slight but statistically
significant reduction in ovary weight, relative to body
weight, was detected for females treated with 15 mg/kg/day.


Histopathology:

No treatment-related microscopic changes were observed.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

150 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

2

Dose descriptor:

NOEL

Effect level:

1.5 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