Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From December 12, 2007 to January 04, 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The batch tested is a commercial product

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
December 17, 2001
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 6 to 7 weeks old
- Weight at study initiation: 150 to 174 grams
- Fasting period before study: overnight prior to dosing (Day –1) up to 4 hours after
dosing
- Housing: Polycarbonate cages measuring 42.5x26.6x18 cm during study, with stainless steel mesh lid and floor.
- Diet (e.g. ad libitum): 4 RF 18 (Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI) Italy)) ad libitum
- Water (e.g. ad libitum): drinking water supplied to each cage via a water bottle ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 2°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): approximately 15 to 20 air changes per hour
- Photoperiod (hrs dark / hrs light): artificial (fluorescent tubes), daily light/dark cycle of
12/12 hours

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 0.5% acqueous solution of carboxymethylcellulose

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality and morbidity twice daily, clinical signs in the day of dosing (on dosing, approximately 0.5, 2 and 4 hours after dosing) and daily thereafter (14 days), body weight on allocation (Day-1), Days 1, 2, 8 and 15 or when found
dead.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred in the three female animals initially dosed at 2000 mg/kg.
Clinical signs:
Step 1
Piloerection was recorded in all animals on the day of dosing and on Day 2. Additionally, brown staining of the cage tray was recorded on Day 2. Recovery occurred by Day 3.
Step 2
The same clinical signs of step 1 were recorded: piloerection on the day of dosing and on Day 2 and brown staining on the cage tray on Day 2 only. Recovery occurred by Day 3.
Body weight:
At the end of the observation period, changes in body weight were within the expected range for this strain and age of animals.
Gross pathology:
No external or internal abnormalities were observed at necropsy examination performed at the end of the observation period in all the animals dosed at 2000 mg/kg (step 1 and 2).

Applicant's summary and conclusion

Interpretation of results:
other: CLP criteria not met
Conclusions:
LD50 > 2000 mg/kg bw
Executive summary:

Method

The acute toxicity of the test item was investigated following a single oral administration (10 ml/kg in 0.5% carboxymethylcellulose in water) to the Sprague Dawley rat (6 female animals/group) followed by a 14-day observation period, according to the OECD guideline 423.

Observations

A first sub-group of 3 female animals was initially dosed at 2000 mg/kg (step 1). No mortality occurred and a second sub-group of animals, similarly composed, was then dosed at the same dose level (step 2) bringing the group size up to 6 animals.

In both steps mortality did not occur and clinical signs were limited to piloerection (Day 1 and 2) and brown staining on the cage tray (Day 2). Recovery occurred by Day 3.

At the end of the observation period, changes in body weight were within the expected range for this strain and age of animals.

The animals were killed at the end of the observation period and all animals were subjected to necropsy examination.

No external or internal abnormalities were observed in all the animals dosed at 2000 mg/kg (step 1 and 2).

Conclusion

The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg body weight.