Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From September 29 to October 11, 2016
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Reliability of the source study is 1

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method

Test material

Constituent 1
Reference substance name:
Acid Brown 161:1 - Similar Substance 02
IUPAC Name:
Acid Brown 161:1 - Similar Substance 02
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Species: laboratory albino rat (it is the preferred rodent species according to the guideline)
- Supplier: SPF breeding, VELAZ s.r.o.
- Age: 8 weeks at the time application
- Acclimatisation: 12 days
- Housing: animal room with monitoring conditions – 3 animals of one sex in one plastic breeding cage
- Diet: pelleted standard diet for experimental animals ad libitum
- Water: drinking tap water ad libitum (quality corresponding to Regulation No. 252/2004 Czech Coll. of Law)

ENVIRONMENTAL CONDITIONS
- Temperature: room temperature 22 ± 3 °C, permanently monitored
- Relative humidity: 30 – 70 %, permanently monitored
- Photoperiod: 12-hour light/12 hour dark
- Bedding: shavings of soft wood

- Randomisation: according to internal SOP No.42
- Identification of animals: colour marks 1 - 3 on tail of animals, each cage was marked with the number of study, sex and dose of the test substance
- Health condition: certificate of good health condition – from breeding farm; no signs of diseases were observed at clinical check-in, during the acclimatisation period and before the start of study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Lot/batch no.: 1605100264

MAXIMUM DOSE VOLUME APPLIED:
1 mL/100 g of animal body weight
Doses:
2000 mg/kg of body weight
No. of animals per sex per dose:
Animal per sex per dose: 3
Total number of animals: 6
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Body weight: before application, 8th day and before euthanasia of animals
- Mortality: dailyClinical examination: daily
- Pathological examination: 15th day
- Necropsy of survivors performed: yes
- Other examinations performed: after application the animals were observed individually:
* the first day: twice (30 minutes and 3 hours after application)
* the second day: twice (in the morning and in the afternoon) and daily thereafter for 14 days.
Observations included changes in skin and fur, eyes, visible mucous membranes, behaviour of animals, somatomotor activity, reactions to stimuli, and presence of lacrimation, salivation and discharge from nostrils, function of respiratory, digestive and urogenital system. The results of the observations were recorded on special data sheets. All test animals survived to the end of study were sacrificed on the 15th day and gross necropsy was carried out. Nutritious status, body surface, body foramina, thoracic, abdominal and cranial cavity were evaluated. All gross macroscopic changes of organs and tissues were recorded on special data sheets.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality observed
Clinical signs:
Changes of colour of faeces associated with the colour of the test substance were observed first and second day during the clinical observation after the application. Soft faeces were observed on the day of the application. No other clinical signs of intoxication were observed after dosing 2000 mg/kg/body weight
Body weight:
Weight increments were adequate to species, sex and age of animals in experiment. No reduction of body weight was observed
Gross pathology:
No pathologic macroscopic changes were diagnosed during pathological examination

Any other information on results incl. tables

Preparation of experimental animals

About twenty hours before oral administration the animals were not fed, drinking water was given ad libitum. Immediately before application the animals were weighed and distributed to groups with 3 animals. The feed was given to animals 3 hours after application of the test substance.

Course of study

The dose level of 2000 mg/kg was used as the starting dose, because no toxicity of the test substance was estimated on the basis of information about testing of similar substances. Because this dose caused no death of females, the same dose of 2000 mg/kg level was sequentially applied for confirmation (application with time distance 24 hours) to group of 3 females. No death of animals was observed in this group of 3 females.

Testing schedule (according to OECD Test Guideline No. 423: Acute Oral Toxicity – Acute Toxic Class Method, Adopted 17th December 2001)

START: 2000 mg/kg – 3 females (Step No. 1) – no deaths ►2000 mg/kg – 3 females (Step No. 2): no deaths ► END of study

Body weight recording

Animals were weighed before application, at the 8th day of study and at the 15th day, before euthanasia of animals. Average body weight in a group was calculated from individual body weights. Body weight increments were calculated from body weight at the start of the study, the first week and at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified according to the CLP Regulation
Conclusions:
LD50 > 2000 mg/kg bw
Executive summary:

Method

The test was performed according EU Method B.1 tris: Acute Oral Toxicity - Acute Toxic Class Method. 

The test substance was administered in a single dose as a suspension in vehicle (water), given orally via gavage to female Wistar rats. The volume of administered suspension was 1 ml/100 g body weight of animals. 

The dose level of 2000 mg/kg bw was used as the starting dose, because no toxicity of the test substance was estimated on the basis of the information about testing of similar substances.

The dosing was performed sequentially in two groups of three females: group No. 1 - using the starting dose of 2000 mg/kg of body weight. No death of females caused this dose, dose of 2000 mg/kg of body weight was sequentially applied for confirmation to group No. 2.

 

Observation

The test substance administered at the dose of 2000 mg/kg bw caused no death of animals. Only changes of colour of faeces associated with the colour of the test substance were observed first and second day during the clinical observation after the application. Soft faeces were observed only on the day of the application. No other clinical signs of intoxication were detected during the whole study in all sixanimals administered by the dose 2000 mg/kg/body weight. No pathologic macroscopic changes were diagnosed during pathological examination.

 

Conclusion

LD50 > 2000 mg/kg bw