Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 Aug 2016 to 14 Sep 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17 December 2001
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
30 May 2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nousan No. 8147
Version / remarks:
2000
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
Specific details on test material used for the study:
- Name of test item: Orasol Red 363
- Test item No.: 16/0076-1
- Batch identification: 001-151902
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han) SPF
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: animals of comparable weight (± 20% of the mean weight of 181.3 g)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: Single housing; Makrolon cage, type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water: Tap water ad libitum
- Acclimation period: Acclimatization period of at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3
- Humidity (%): 30 – 70
- Air changes (per hr): Approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 p.m. – 6.00 a.m. / 6.00 a.m. – 6.00 p.m.)

There were no deviations from these ranges, which influenced the results of the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 g/100mL
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

DOSAGE PREPARATION (if unusual): The test item was prepared for each test group shortly before administration by stirring with a high speed homogenizer (Ultra-Turrax) and a magnetic stirrer.
The homogeneity of the test item preparation during administration was ensured by stirring with a magnetic stirrer.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: By request of the sponsor a starting dose of 2000 mg/kg bw was chosen in the first step with 3 female animals. Because no mortality occurred, 2000 mg/kg bw were administered to another group of 3 female animals in the second step.
Doses:
2000 mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes. Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations.
- Other examinations performed:
- clinical signs: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.
- mortality: A check for any dead or moribund animals was made at least once each workday.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
In all animals of the first test group red discolored defecation and red discolored urine were noted from hour 2 until hour 5.

In all animals of the second test group impaired general state and piloerection were noted from hour 3 until hour 5, while red discolored defecation and red discolored urine were seen in these animals from hour 4 until study day 2.
Body weight:
The body weights of the animals increased within the normal range throughout the study period with two exceptions in the first administration group. The body weights of these animals increased during the first observation week but stagnated during the second week. This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth.
Gross pathology:
There were no macroscopic pathological findings in all animals sacrificed at the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met