Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From January 11 to February 1, 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted in compliance with OECD Guideline No. 423 without deviation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
inspected on September 22, 1999 / signed on January 18, 2000
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Physical state: White solid (but some samples were received as liquid, due to stability in supercooled state)
- Storage condition of test material: At room temperature, protected from light and under nitrogen atmosphere


Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa Credo, 69210 L’Arbresle, France
- Age at study initiation: ca. 6 weeks
- Weight at study initiation (mean): Males - 175 ± 10 g; females - 142 ± 1 g
- Fasting period before study: 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 substance.
- Housing: The animals were housed in polycarbonate cages (48 cm x 27 cm x 20 cm). Each cage contained one to seven animals of the same sex during the acclimatization period and three rats of the same sex during the treatment period.
- Diet: A04 C pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France), ad libitum
- Water: Drinking water filtered by a FG Millipore membrane (0.22 micron), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 30-70%
- Air changes (per hr): Approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: January 11, 2000 To: February 1, 2000

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 and 200 mg/mL
- Amount of vehicle: 10 mL/kg bw.
- Lot/batch no.: 107H1649

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw; The volume administered to each animal was adjusted according to body weight determined on the day of treatment.

DOSAGE PREPARATION: On the day of treatment, the test substance was ground to a fine powder using a mortar and pestle, then was prepared at the chosen concentrations in the vehicle.
Doses:
200 mg/kg bw (males only) and 2000 mg/kg bw (males and females)
No. of animals per sex per dose:
3 males (200 mg/kg bw)
3 males and 3 females (2000 mg/kg bw)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations: Animals were observed frequently during the hours following administration of the test substance, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day until day 15.
- Frequency of weighing: Animals were weighed individually just before administration of the test substance on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: Yes; On day 15, all surviving animals were killed by carbon dioxide asphyxiation and a macroscopic examination was performed. The animal found dead during the study was subjected to a macroscopic examination as soon as possible.
Statistics:
None

Results and discussion

Preliminary study:
Not applicable
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: One male was found dead on day 2 at the dose level of 2000 mg/kg bw.
Mortality:
No deaths were observed in the three males given 200 mg/kg bw. One male was found dead on day 2 at the dose level of 2000 mg/kg bw.
Clinical signs:
- No clinical signs were observed in the three males given 200 mg/kg bw.
- At the 2000 mg/kg bw dose-level, hypoactivity or sedation and piloerection were noted in all animals on day 1; dyspnea was observed in a few animals and coma was recorded in two males. On day 2, one male was found dead; hypoactivity, dyspnea and piloerection persisted in the surviving males. No clinical signs were observed in any females. From day 4 until the end of the observation period, no clinical signs were noted in the surviving animals.
Body weight:
The body weight gain of the males given 200 mg/kg bw was lower than that of laboratory historical control animals between day 1 and day 8. The body weight gain of the surviving animals given 2000 mg/kg bw was not affected by treatment with the test substance.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities in the animal found dead during the study and in the surviving animals killed at the end of the study.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
not classified
Conclusions:
Oral LD50 Combined > 2000 mg/kg bw. Under the test conditions, the test material is not classified for acute oral toxicity according to the annex I of the Regulation EC No. 1272/2008 (CLP) and of the GHS.
Executive summary:

In an acute oral toxicity study performed according to OECD Guideline No. 423/EU Method B.1 tris and in compliance with GLP, test substance was administered by oral route (gavage) to Sprague-Dawley rats at doses of 200 mg/kg bw (3 males) or 2000 mg/kg bw (3 males + 3 females), under a volume of 10 mL/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

 

No clinical signs and no deaths were observed in the three males given 200 mg/kg bw. At the 2000 mg/kg bw dose-level, hypoactivity or sedation and piloerection were noted in all animals on day 1; dyspnea was observed in a few animals and coma was recorded in two males. On day 2, one male was found dead; hypoactivity, dyspnea and piloerection persisted in the surviving males. No clinical signs were observed in any females. From day 4 until the end of the observation period, no clinical signs were noted in the surviving animals. The body weight gain of the males given 200 mg/kg bw was lower than that of historical control animals between day 1 and day 8. The body weight gain of the surviving animals given 2000 mg/kg bw was not affected by treatment with the test substance. No apparent abnormalities were observed at necropsy in the animal found dead during the study and in the surviving animals killed at the end of the study.

                                        

Oral LD50 Combined > 2000 mg/kg bw.

 

Under the test conditions, the test material is not classified for acute oral toxicity according to the annex I of the Regulation EC No. 1272/2008 (CLP) and of the GHS.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.