Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 30 july 2003 to 28 oct 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study, OECD TG 423 compliant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
temperature and humidity were sometimes outside of the target. The dose 200 mg/kg in not the one recommended in the guideline (300 mg/kg).
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: on the day of treatment, the animals were approximately 6 weeks old,
- Weight at study initiation: on the day of treatment, the animals had a mean body weight ± standard deviation of 184 ± 9 g for the males and 171 ± 4 g for the females.
- Fasting period before study: The animals were fasted for an overnight period of approximately 18 hours before dosing, but had free access to water.
Food was given back approximately 4 hours after administration of the test item.
- Housing: The animals were housed in polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm). Each cage contained one to seven animals of the same sex during the acclimation period and three rats of the same sex and group during the treatment period.
- Identification: individually by earnotches.
- Diet (e.g. ad libitum): All the animals had free access to A04 C pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France)
- Water (e.g. ad libitum): Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From: 30 july 2003 To: 28 aug 2003

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
The test item was prepared in corn oil and was administered by oral route (gavage), under a volume of 10 mL/kg, to groups of fasted Sprague-Dawley rats.
Doses:
200 and 2000 mg/kg
No. of animals per sex per dose:
3 males at 200 mg/kg.
3 males and 3 females at 2000 mg/kg.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.
The animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, observation of the main organs.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
1/3 females was found dead on day 2, at 2000 mg/kg
Clinical signs:
At the 200 mg/kg dose-level, hypoactivity and piloerection were observed in all males on day 1; piloerection persisted in 1/3 animals on day 2. Recovery was complete for all animals on day 3.

At the 2000 mg/kg dose-level, hypoactivity or sedation, piloerection and dyspnea were recorded in all males on days 1 and 2; dyspnea persisted in all males on day 3.
In females, 1/3 animals was found dead on day 2; hypoactivity or sedation, piloerection and dyspnea were noted prior to death. In both surviving animals, hypoactivity or sedation, piloerection and dyspnea, together with ocular secretions on day 2, were observed on days 1 and 2, then hypoactivity and dyspnea, together with piloerection and ocular secretions in one of them, were recorded on day 3. Hypoactivity and dyspnea persisted in one of them on days 4 and 5.
Body weight:
The body weight gain of the animals given 200 mg/kg was not affected by treatment with the test item.
The body weight gain of the surviving animals given 2000 mg/kg was reduced during the first week of the study when compared to CIT historical control animals.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Not classified for acute oral toxicity according to EU GHS (CLP 1272/2008).
Executive summary:

In an acute oral toxicity study (CIT, 2003), groups of Sprague-Dawley rats (male/female) were given a single administration of Guetol by gavage, at doses of 200 and 2000 mg/kg in corn oil. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days following the single administration of the test item.

Mortality occured in 1/3 female given 2000 mg/kg on day 2.

Clinical signs observed were hypoactivity, sedation, piloerection and dyspnea. They were fully reversible within 6 days.

Body weight in animals given 2000 mg/kg bw were reduced during the first week of the study, compared to the historical controls.

Under these experimental conditions, the LD50 by oral route was determined to be higher than 2000 mg/kg bw.

Based on these results, Guetol is considered as not harmful by oral route, according EC classification criteria (CLP 1272/2008).