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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:
October 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Remarks:
BR strain (VAF plus)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent
- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: mean females:102 g and males 104 g
- Fasting period before study: overnight before dosing
- Housing: groups of up to 5, by sex, in grid-bottomed cages suspended over cardboard lined excreta trays
- Diet: pelleted diet (SQC Rat and Mouse Maintenance Diet No. 1 Expanded, produced by Special Diets Services, Witham, Essex), ad libitum
- Water: drinking water, ad libitum
- Acclimation period: at least 5 days before dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23
- Humidity (%): 44 - 65
- Air changes: air conditioned
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: according to OECD guideline 420, not further specified

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg

DOSAGE PREPARATION:
The test article was formulated in corn oil at a concentration of 200mg/mL to achieve a dose level of 2000 mg/kg bodyweight using an individual dose volume of 10mL/kg. All formulations were freshly prepared on the day of dosing.
Rationale for the selection of the starting dose: Results of a range finding study with 500 and 2000 mg/kg bw.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were examined shortly after dosing and approximately 30 minutes, one, 2 and 4 hours after dosing for signs of toxicity or changes in appearance or behaviour. Animals were examined daily thereafter for a further 14 days. On the day of dosing all animals were weighed in order to calculate the individual dose volume to be administered. Animals were weighed again on days 2, 3, 4, 8 and 15.
- Necropsy of survivors performed: yes at the end of the 15 day observation period. The carcasses were subject to a gross necropsy, which included the opening of the thoracic and visceral cavities, opening and examination of the stomach and representative sections of the gastro-intestinal tract and examination of the major organs.

Results and discussion

Preliminary study:
1st female dosed with 500mg/kg bw: Piloerection and hunched posture noted 4 hours after dosing; animal appeared healthy thereafter and survived treatment. 2nd female dosed with 2000mg/kg bw: No apparent effect; animal survived treatment.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
There were no clinical signs of toxicity throughout the observation period.
Body weight:
There was no adverse effect on bodyweight gain in animals of either sex.
Gross pathology:
There were no abnormalities detected at necropsy.

Applicant's summary and conclusion

Interpretation of results:
other: not classified
Remarks:
based on CLP criteria
Conclusions:
Under the conditions of the test, the oral LD50 was > 2000 mg/kg bw. Based on this result, the substance does not need to be classified for acute toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).
Executive summary:

An acute oral fixed dose study was performed according to OECD TG 420 and in compliance with GLP. 10 Crl: CD (SD) rats (5 male/5 female) were exposed to a single dose of 2000 mg/kg bw test substance by oral gavage. Animals were observed for 14 -days after dosing for clinical signs and body weight gain. After 14 days gross necropsy was performed. No clinical signs of toxicity throughout the observation period were observed and there was no adverse effect on bodyweight gain in animals of either sex. No abnormalities were detected at necropsy. Under the conditions of the test, the LD50 was determined to be > 2000 mg/kg bw. Based on this result, the substance does not need to be classified for acute toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).