Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Reference substance 001
EC Number:
920-427-4
Details on test material:
- Name of test material (as cited in study report): Zorgol 48
- Substance type: UVCB substance
- Physical state: orange liquid
- Analytical purity: not applicable
- Lot/batch No.: 20100223161335
- Code number: PH-10/0131
- Expiration date of the lot/batch: 2011-02-09
- Stability under test conditions: no data
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevange JANVIER (53940 Le Genest St. Isle, France)
- Age at study initiation: 8 weeks
- Weight at study initiation: 172 - 204 g
- Fasting period before study: yes
- Housing: in groups of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid containing sawdust bedding
- Diet (e.g. ad libitum): M20-SDS, ad libitum
- Water (e.g. ad libitum): tap water from public distribution system, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25°C
- Humidity (%): 30 - 70%
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12 /12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no vehicle

MAXIMUM DOSE VOLUME APPLIED: 2.23 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no data
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Six female Sprague Dawley rats
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation 0.5, 1, 3, and 4 hours after administration, daily thereafter; weighing at day 0C before administrationof test substance then at day 2, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: highest dose tested
Mortality:
No mortality was observed during the study.
Clinical signs:
Observations at first day of the test: decrease in spontaneous activity (3/6 and muscle tone (2/6), piloerrection (3/6), staggering gait (3/6).
After 24 h all animals recovered normal behaviour.
Body weight:
No effects regarding body weight evolution were observed during the study.
Gross pathology:
No treatment related effects were observed by macroscopical examination of the animals at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of the test item Zorgol 48 is higher than 2000 mg/kg body weight by oral route in the rat.
In accordance with the OECD guideline n°423, the LD50 cut-off of the test item may be considered higher than 5000 mg/kg body weight by oral route in the rat.
Executive summary:

An acute oral toxicity study was performed using the acute toxic class method according to OECD test guideline 423. Groups of three fasted female Sprague-Dawley rats for each of step 1 and step 2 were given a single oral dose of the test item Zorgol 48 as such by gavage at a dose of 2000 mg/kg bw. Test animals were observed for 14 days.

 

No mortality was noticed following administration of this dose at step 1 and 2. Clinical findings were only noted at the first day (decrease in spontaneous activity and muscle tone - 3 and 2 of 6 animals respectively, piloerrection - 3 of 6 animals, staggering gait - 3 of 6 animals). After 24 hours all animals recovered normal behaviour. Development of body weight was found to be normal. Necropsy did not reveal any findings.

 

The oral LD50 of Zorgol 48 is higher than 2000 mg/kg bw in the rat (Colas/Laus, 2010).

In accordance with OECD TG 423, the LD50 cut-off of Zorgol 48 may be considered higher than 5000 mg/kg bw. Zorgol 48 is of low acute oral toxicity.

 

This oral toxicity study is acceptable and satisfies the guideline requirement for an oral toxicity test (OECD423) in rats.