[No public or meaningful name is available]

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

Principles of method if other than guideline:

European Community (EC) Council Directive 96/54/EC, Annex
IV.D, replacing EC Directive 67/548/EEC, Part B : Methods
for the Determination of Toxicity and other Health Effects;
B.7: "Repeated Dose (28 days) Toxicity (oral)". Official
Journal of the European Communities No. L248, September
1996.


Organisation for Economic Co-operation and Development
(OECD), OECD Guidelines for Testing of Chemicals, Section 4,
Health Effects, No. 407: "Repeated Dose 28-day Oral
Toxicity Study in Rodents", Paris Cedex, 27 July 1995.


United States Environmental Protection Agency (EPA). Health
Effects Test Guidelines, OPPTS 870.3050, Repeated dose 28-
day oral toxicity study in rodents. Office of Prevention,
Pesticides and Toxic Substances (7101), EPA 712-C-00-366,
July 2000.

GLP compliance:

yes

Limit test:

no

Test animals

Species:

other: Rat: Wistar Crl:(WI) BR

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

other: Polyethylene glycol 400

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 50 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 50 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:
There were no clinical signs of toxicity noted during the
observation period. Treated animals showed increased
salivation immediately after dosing.



Hearing ability, pupillary reflex, static righting reflex
and grip strength were normal in all animals. The variation
in motor activity did not indicate a relation with
treatment.


Body weights and body weight gain of treated animals
remained in the same range as controls over the study
period.


No toxicologically significant changes in food intake before
or after correction for body weight were noted over the
treatment period.

Laboratory findings:
A slight effect was seen on haematological parameters in
females receiving 1000 mg/kg/day manifest as significant
reductions in haemoglobin and haematocrit. A decrease in
MCHC was seen in males at this dose level.

Effects in organs:
The following (statistically significant) changes in organ
weights were noted:

- Increased absolute and relative liver weights in males and
females at 1000 mg/kg/day. Absolute liver weight was
increased with approximately 50% compared to control liver
weights; and increased relative weights of liver in females
at 50 mg/kg/day.


- Increased absolute and relative kidney weights in males
and females at 1000 mg/kg/day (absolute kidney weights not
statistically significant for males). Absolute kidney weight
was increased with approximately 13 and 28% for males and
females respectively, compared to control kidney weights.


- The statistically significant higher relative liver
weights of females at 50 mg/kg/day occurred in the absence
of a more pronounced change at the next higher dose level.
Also, the mean (relative) liver weight remained within the
range considered normal for rats of this age and strain. No
toxicological significance was therefore ascribed to this
change.


The following were - related microscopic findings were
observed:

- Adrenal zona fasciculata hypertrophy ( in 2/4 females
at 50 mg/kg/day (minimal degree), 2/5 females at 150
mg/kg/day (minimal degree) and 4/5 females at 1000 mg/kg/day
(minimal to mild degree);

- Hepatic hypertrophy in 3/5 males at 1000 mg/kg/day
(minimal degree); and

thyroid epithelium hypertrophy (minimal degree) in 3/5 males
at 50 mg/kg/day, 2/4 males at 150 mg/kg/day and 2/5 males
at 1000 mg/kg/day.

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:

< 50 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