Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16/06/2011- 26/07/2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
other: EU Commission regulation N. 440/2008, L142, Annex part B, 30 May 2008
Qualifier:
according to
Guideline:
other: EPA OPPTS 870.1000 "Acute Toxicity testing background", EPA 712-C-02-189, december 2002
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to Art.9.2, No.7 of the German Act on Animal Welfare (10) the animals were bred for experimental purposes.

- Source: Charles River 97633 Sulzfeld Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-10 weeks old
- Weight at study initiation: Step 1 / animal 1-3: 167-169 g; Step 2 / animals 4-6: 170-183 g; Step 3/ animals 7-9: 152-168 g
- Housing: Full barrier in an air-conditioned room
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum): free access
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 10 x/hour
- Photoperiod (hrs dark / hrs light): artificial light 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
cotton seed oil
Doses:
1. group - Dosage of 2000 mg/kg bw. The test item was suspended in the vehicle cottonseed oil at a conc. of 0.2 g/ml and administered at a dose V of 10 mL/kg.
2. and 3. group - were treated with the test item by oral gavage administration at a dosage of 300 mg/kg bw. The test item was suspended in the vehicle cottonseed oil at a conc. of 0.03 g/ml and administered at a dose V of 10 mL/kg.
No. of animals per sex per dose:
3 per step
Control animals:
yes
Details on study design:
All animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
step 1 - all animals had to be sacrificed for ethical reasons 20.5 hours after dosing.
step 2 and 3 - all animals survived until the end of the study.
Clinical signs:
step 1 - The most relevant clinical findings in these animals were reduced spontaneous activity, prone position, ataxia, wasp waist, pilocrection, salivation, moving and eating the bedding, recumbency, lethargy, abnormal pinna reflex, half and complete eyelid-closure, dehydration, bw loss, hypothermia, dark orange coloured urine and diarrhoea.
step 2 and 3 - no signs of toxicity
Body weight:
step 1 - body weight loss
Gross pathology:
No specific gross pathological changes were recorded for any animal

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of the present study, a single oral application of the test item (ELV)DIARIL CHETONE to rats at a dose of 2000 mg/kg bw was associated with signs of toxicity and mortality.
Under the conditions of the present study, a single oral application of the test item (ELV)DIARIL CHETONE to rats at a dose of 300 mg/kg bw was associated with no signs of toxicity and mortality.
The median lethal dose of (ELV) DIARIL CHETONE after a single oral administration to female rats, observed over a period of 14 days is: LD50 cut-off: 500 mg/kg bw.

In conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC (7) the test item (ELV)DIARIL CHETONE has obligatory labelling requirement for toxicity.
According to Annex I of Regulation (EC) 1272/2008 (8) the test item (ELV)DIARIL CHETONE has obligatory labelling requirement for toxicity and is classified into Category 4.
According to OECD-GHS (9) the test item (ELV)DIARIL CHETONE has obligatory labelling requirement for toxicity and is classified into Category 4.