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Administrative data

repeated dose toxicity: oral
other: acute oral toxicity
Type of information:
experimental study
Adequacy of study:
other information
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant study. Adequate for assessment.

Data source

Reference Type:
study report

Materials and methods

Test guideline
according to guideline
other: OECD 423
GLP compliance:
Limit test:

Test material

Constituent 1
Reference substance name:
Test material form:
solid: crystalline
Details on test material:
Appearance: white crystals.

Test animals

Details on test animals or test system and environmental conditions:
Females are to be nulliparous and non-gravid.
Age: 8-12 weeks at the time of administration.
Number: 3 animals per step.

Administration / exposure

Route of administration:
oral: gavage
Details on oral exposure:
Sterile water was chosen on the basis of the physical-chemical characteristics of the test substance as vehicle.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
The substance was administered to animals deprived of food since the previous day. It was administered to the animals as a single dose, by gavage, using a cannula of appropriate size.
Doses / concentrations
Doses / Concentrations:
The dose volume was 10 mL/kg.
no data
No. of animals per sex per dose:
a group of three females was treated with the starting dose of 2000 mg/kg, followed by an additional group of three females at the same dose level to confirm the results obtained during the first step.


Observations and examinations performed and frequency:
Animals w ere examined clinically twice on the day of treatment (between 30 and 90 minutes after administration an d then again between 3 and 4 hours post-dose). Thereafter they was examined clinically at least once a day for 4 days.
Sacrifice and pathology:
Full clinical examination: on D1 between 30 and 90 minutes after administration and on D7 the animals were submitted to a full clinical examination outside the housing cage, including functional and neurobehavioural tests. As no clinical changes were recorded on D7, the full clinical examination was not repeated al the termination of each step ofthe study (D14).
Other examinations:
All animals surviving to the end of the 14-day monitoring period was euthanised on D15 by subtotal exsanguination, after sodium pentobarbital anaesthesia by the intraperitoneal route. All animals were subjected to gross necropsy and their organs (liver, spleen, kidneys, stomach, intestines, gonads/reproductive tract, lungs and heart) were examined macroscopically. All organs showing macroscopic signs of pathology was fixed in an appropriate fixative for possible histopathological examination.
Remaining tissues were disposed of after the dispatch of the final report.
All data were recorded as and when obtained using forms identified by the study number. Data were presented tabulated by dose level and time, nature, severity and duration of effects. Results of the body weight were given as means ± SEM (Standard Errar of the Mean).

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
During the full clinical examination on D7, reduced or increased spontaneous locomotor activity or vocalisation w ere noted in two animals of the first step.
no mortality observed
Description (incidence):
During the full clinical examination on D7, reduced or increased spontaneous locomotor activity or vocalisation w ere noted in two animals of the first step.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Mean weight gain in treated animals was normal when compared with strain data.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified

Effect levels

Dose descriptor:
dose level:
Effect level:
> 2 000 other: mg/kg bw
Based on:
not specified

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Under the experimental conditions adopted, oral administration of the test sabstance at a dose of 2000 mg/kg caused no mortality and did not reqnire enthanasia during 14-day periods, in the female Sprague-Dawley Rat.

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