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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 April 2008 to 18 December 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to testing guideline; adequate coherence between data, comments and conclusions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

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
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): CAE
- Substance type: UVCB
- Physical state: orange to brown liquid
- Purity test date: 23/01/2008
- Lot/batch No.: 1456
- Expiration date of the lot/batch: 18/12/2008
- Stability under test conditions: no information
- Storage condition of test material: at room temperature and away from light

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier (53940 Le Genest-Saint-Isle, France)
- Age at study initiation: about 8 weeks
- Weight at study initiation: 210 ± 6 g
- Fasting period before study: yes
- Housing: polycarbonate cages with stainless steel lid
- Diet (e.g. ad libitum): SSNIFF R/M-H pelleted maintenance diet, ad lib
- Water (e.g. ad libitum): filtered tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/-2°C
- Humidity (%): 50% +/-20%
- Air changes (per hr): 12 cycles per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 09 April 2008 To: 07 May 2008

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 to 200 g/L
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: forms a solution
- Lot/batch no. (if required): not applicable
- Purity: not indicated

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: as no information on the toxic potential of the test item was available, for animal welfare reasons, the starting dose-level of 300 mg/kg was chosen
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
3 F
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations made regularly the day of treatment and then at least once a day; weight recorded on the day before administration, on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
Not applicable

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality was observed
Clinical signs:
300 mg/kg: none.

2000 mg/kg: Hypoactivity (all the animals) and piloerection (3/6 animals) were noted within 6 hours of treatment.
Body weight:
300 mg/kg: When compared to CIT historical control animals, a slightly lower body weight gain was noted in 1/3 females between day 8 and day 15, without affecting the mean body weight gain at the end of the study. The body weight gain of the other animals was not affected by treatment with the test item.

2000 mg/kg: When compared to CIT historical control animals, a slightly lower body weight gain was noted in 1/6 females between day 1 and day 8 (returning to normal thereafter). The body weight gain of the other animals was not affected by treatment with the test item.
Gross pathology:
At necropsy, no apparent abnormalities were observed in any animal
Other findings:
None

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions of this study, the oral LD50 of the test item CAE was higher than 2000 mg/kg in rats.

According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations), concerning the potential toxicity by oral route, the test item should not be classified.
Executive summary:

The test item CAE was prepared in corn oil and was administered by oral route (gavage), under a volume of 10 mL/kg, to groups of three fasted female Sprague-Dawley rats.

The study design was as follows: 

Dose-level

(mg/kg)

Volume

(mL/kg)

Female

300

10

3

2000

10

3

2000

10

3

 

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.

All animals were subjected to necropsy.

The interpretation of results was based on the classification critera laid down in Council Directive 67/548/EEC (and subsequent adaptations).

Dose-level of 300 mg/kg (three animals)

No deaths and no clinical signs were observed.

When compared to CIT historical control animals, a slightly lower body weight gain was noted in 1/3 females between day 8 and day 15, without affecting the mean body weight gain at the end of the study. The body weight gain of the other animals was not affected by treatment with the test item.

 

Dose-level of 2000 mg/kg (three females then confirmation on three other females)

No deaths occurred.

Hypoactivity (all the animals) and piloerection (3/6 animals) were noted within 6 hours of treatment.

When compared to CIT historical control animals, a slightly lower body weight gain was noted in 1/6 females between day 1 and day 8 (returning to normal thereafter). The body weight gain of the other animals was not affected by treatment with the test item.

 

At necropsy, no apparent abnormalities were observed in any animal.