Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 June 2016 - 14 July 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Batch No.: UGe-RS Kilo 1
Color: Yellow
Odor: Not specific
Storage conditions: room temperature
Solubility and stability: Very good solubility in water, stable in solution at least 2 days
Expiring date: 12.12.2018
Correction factor: 1.07
Specific details on test material used for the study:
Batch No.: UGe-RS Kilo 1
Form: Powder
Color: Yellow
Odor: Not specific
Purity: 93.3 %
Storage conditions: room temperature
Solubility and stability: Very good solubility in water, stable in solution at least 2 days
Expiring date: 12.12.2018
Correction factor: 1.07

Test animals

Species:
rat
Strain:
Wistar
Remarks:
HSDHAN
Sex:
female
Details on test animals and environmental conditions:
3 animals/group
Sex: Female, nulliparous and non pregnant animals
Age of animals: Young adult rat, 10 weeks old in first, second and third step
Body weight range
at starting (first step): 160 - 164 g
Body weight range
at starting (second step): 161 - 164 g
Acclimatization time: 20 days in first step and 21 days in second step
Animal health: Only healthy animals were used for the study. Health status was certified by the study director.
Room: 13/1
Housing: Group caging (3 animals/cage)
Cage type: Type II polypropylene/polycarbonate.
Bedding: Laboratory bedding.
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 - 70 %
Ventilation: above 10 air exchanges/hour by central air-condition system.
The temperature and relative humidity were recorded daily during the study.

Animals received ssniff® SM R/M-Z+H complete diet for rats and mice produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany and tap water from municipal supply, as for human consumption from bottle ad libitum.

The diet and drinking water are periodically analysed and are considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. Copies of the relevant Certificates of Analysis are maintained in Toxi-Coop Zrt.’s archive.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Aqua purificata Ph.Hg. VIII., Batch number:1602-5519, Date of expiration: 19.08.2016, Produced by: Parma Produkt Kft.
Details on oral exposure:
Starting dose was selected on the basis of the available information about the test item.
The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 was met.

Doses:
2000 mg/kg
No. of animals per sex per dose:
3 femals/dose/step
Control animals:
no
Details on study design:
A single oral administration - followed by a fourteen-day observation period - was performed by gavage. The day before treatment the animals were fasted. The food but not water was withheld overnight. Animals were weighed before the application and the food was given back 3 hours after the treatment.
Duration of experimental period: 20 days in first step and 21 days in second step of acclimatization, treatment’s day, 14 days post-treatment observation period, necropsy on Day 15.
Animals were observed individually after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h after the treatment and twice each day for 14 days thereafter.

Individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

The body weights were recorded on day 0 (just before the treatment), on day 7 and on day 15 with a precision of 1 g.

At the end of the observation period all survivor rats were sacrificed under isofluran anaesthesia. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed, and any abnormality was recorded with details of its location, colour, shape and size.


Statistics:
The method used is not intended to allow statistical evaluation and the calculation of a precise LD50 value.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred at 2000 mg/kg bw single oral dose of Yellow LF 6911. All female rats in step 1 and step 2 survived until the end of the 14-day observation period.
Clinical signs:
In group 1 treated with 2000 mg/kg bw dose no treatment related symptoms were observed throughout the 14-day post-treatment period.
In group 2 treated with 2000 mg/kg bw dose no treatment related symptoms were observed throughout the 14-day post-treatment period.
Body weight:
The mean body weight of animals treated with 2000 mg/kg bw dose corresponded to their species and age throughout the study.
Gross pathology:
All animals treated with 2000 mg/kg bw dose survived until the scheduled necropsy on Day 15.
Moderate hydrometra was found in two animals (No.: 2149, 2151) of group 1 and severe hydrometra was detected in animal No.: 2162 of group 2. Hydrometra is physiological finding and connected to the cycle of the animal. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals treated with 2000 mg/kg bw dose.

Any other information on results incl. tables

Dose
(mg/kg bw)

Mortality
(dead/treated)

LD50
(mg/kg bw)

GHS
category

2000

0/6

between 5000 and 2000

5

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
LD50 value is above 2000 mg/kg bw. The test item was ranked into Category 5 of Globally Harmonized Classification System (GHS) described in the OECD Guideline No. 423
Executive summary:

No death occurred after the single 2000 mg/kg bw oral dose of Yellow LF 6911. There were no toxic clinical signs and any related to the effect of the test item found in body weights and body weight gains during the study. Autopsy revealed no treatment related pathological changes. LD50 value is above 2000 mg/kg bw. The test item was ranked into Category 5 of Globally Harmonized Classification System (GHS) described in the OECD Guideline No. 423