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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
January, from 14th to 28th, 2009
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
The reliability of the source read-across study was established to be R1: guideline study
Justification for type of information:
Justification for read-across is detailed at section 13.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
December 17th, 2001
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy breeding, S. Pietro al Natisone (UD).
- Weight at study initiation: 192 - 202 g.
- Housing: transparent polycarbonate cages (425 x 266 x 180 mm); animals were housed 5 per cage.
- Fasting period before study: test animals were fasted overnight before the beginning of the test. 4 hours after exposure, regular pellet diet was provided.
- Diet: pellet diet from Harlan Italy.
- Water: purified water, ad libitum.
- Quarantine: 5 days.
- Health check: the animals were subjected to a veterinary examination to ensure their suitability for the study.

ENVIRONMENTAL CONDITIONS
- Illumination: fluorescent light lamp.
- Photoperiod: 12 hours light and 12 hours dark.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: weekly weight control. Mortality, main organic functions evaluation, skin evaluation, mucous evaluation mobility and sensitivity evaluation were conducted at 30 min, at 2 and 4 hours and after 1, 2, 5, 6, 7, 8, 9, 12, 13 and 14 days of exposure.
- Necropsy of survivors performed: at the end of the study period.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed
Clinical signs:
During the test, all animals showed piloerection 4 hours after the exposure, tucked up abdomen 24 hours after the exposure.Those symptoms disappeared in two animals after 7 days from the test start, in three animals after 8 days from the test start.
Body weight:
A weight increase was observed in all test animals.
Other findings:
Two animals showed a moderate mucous enteritis and one animal showed a slight mucous enteritis.

Any other information on results incl. tables

Weight increase

Female N. Weighed gain (g)
1 13
2 10
3 10
4 16
5 16

Body weight of treated animals, registered at the test start, after 7 and after 14 days of treatment.

Female N. Start (g) Mid period (g) End (g)
1 197 199 210
2 202 203 212
3 200 203 210
4 195 198 211
5 192 195 208
X 197.2 199.6 210.2
DS 3.96 3.44 1.48

X= average

SD= standard deviation

Applicant's summary and conclusion

Interpretation of results:
other: not classified, according to the CLP Regulation
Conclusions:
LD50 (rat female) > 2000 mg/kg bw
Executive summary:

Method

Acute oral toxicity study of the test item in Sprague Dawley rats was performed according to the OECD Guidelines No. 420 - Acute Oral Toxicity – fixed dose. In the present study, conducted as a ‘limit test’, single oral administration of the test item was made to a single group of five female Sprague Dawley rats at the dose of 2000 mg/kg bw, to assess its acute toxicity, through oral gavage.

After 4 hours from the administration, the normal pellet diet was provided. Following their treatment, the rats were observed for incidence of mortality and signs of toxicity for 14 days and then sacrificed and subjected to a necropsy examination. The rats were observed for: mortality, main organic functions evaluation, skin evaluation, mucous evaluation, mobility and sensitivity evaluation. The body weight was weekly recorded.

Observations

When tested at the dose of 2000 mg/kg bw, the test item did not induce any mortality in any of the treated rats. The body weight gained by treated rats was lower than species and strain standard during the first week of the study, and not found to be adversely affected during the second week. At gross necropsy, 2 animals showed a moderate mucous enteritis and 1 animal showed a slight enteritis. During the study, all animals showed piloerection 4 hours after treatment and tucked up abdomen after 24 hours from the administration. These symptoms disappeared in 2 animals after 7 days from the test start, and after 8 days in the other 3 tested animals.

Results

Based on these results, and according to the criteria for classification of chemicals OECD 420 the test article, is not classified under CLP regulation.