Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2016-2017
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:
adopted 17 December 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
30 May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
EPA 712-C-02-190, December 2002
Deviations:
no
Qualifier:
according to
Guideline:
other: Directive 2010/63/EU and the national legislation defined in the animal protection law concerning the protection of animals used for experimental and other scientific procedures
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Appearance: solid yellow powder

Test animals

Species:
rat
Strain:
other: WISTAR Crl: WI(Han)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females, nulliparous and non-pregnant: yes
- Age at study initiation: 8 – 12 weeks old
- Weight at day of administration:
step 1: 154 – 165 g
step 2: 151 – 163 g
step 3: 165 – 170 g
- Fasting period before study: Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.
- Housing: in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet: ad libitum, free access to Altromin 1324 maintenance diet for rats and mice
- Water: ad libitum, free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: Adequate acclimatisation period (at least five days) under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity:55 ± 10%
- Air changes: 10 x /hour
- Photoperiod: Artificial light, sequence being 12 hours light, 12 hours dark

IN-LIFE DATES:
From:
Acclimatisation Period:
Step 1, animals no. 1 - 3: 05 to 09 January 2017
Step 2, animals no. 4 - 6: 05 to 11 January 2017
Step 3, animals no. 7 - 9: 05 to 16January 2017

To: 31 January 2017

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: aqua ad injectionem
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
Step 1: The test item was suspended with the vehicle aqua ad injectionem (sterile water) at a concentration of 0.03 g/mL and administered at a dose volume of 10 mL/kg.
Step 2 and 3: The test item was suspended with the vehicle aqua ad injectionem (sterile water) at a concentration of 0.2 g/mL and administered at a dose volume of 10 mL/kg.
- Justification for choice of vehicle: This vehicle was chosen due to its non-toxic characteristics.
- Lot/batch no.: AlleManPharma lot no. 605070, expiry date: 04/2019

MAXIMUM DOSE VOLUME APPLIED: The test item was administered at a dose volume of 10 mL/kg body weight.

DOSAGE PREPARATION : Test item preparation was done just before application.

CLASS METHOD
- Rationale for the selection of the starting dose: According to OECD Guideline 423 the starting dose was selected to be 300 mg/kg body weight because of no toxicological information about the test item. No compound-related mortality was recorded for any animal of step 1 or 2. Based on these results and according to the acute toxic class method regime further testing with 2000 mg/kg bw was required.
Doses:
Step 1: 300 mg/kg bw
Step 2: 2000 mg/kg bw
Step 3 : 2000 mg/kg bw
No. of animals per sex per dose:
3 per step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
- Necropsy of survivors performed: yes

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:
The test item showed no mortality after a single dose administration at 300 mg/kg and 2000 mg/kg bw.
Clinical signs:
The test item showed no acute oral toxicity characteristics after a single dose administration at 300 mg/kg and 2000 mg/kg bw.
Body weight:
None of the animals showed weight loss during the observation period.
Gross pathology:
No specific gross pathological changes were recorded for any animal.
Other findings:
- Histopathology: In the absence of gross pathological changes no tissues were preserved for a possible histopathological evaluation.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose (LD50) of Mordant Red 11 after a single oral administration to female rats, observed over a period of 14 days is > 2000 mg/ kg bw. According to Annex I of Regulation (EC) 1272/2008 the test item has no obligatory labelling requirement for toxicity and is not classified.
Executive summary:

The acute oral toxicity of the test item to rats was assessed according to OECD 423 guideline and under GLP without significant deviations to the guideline.

One group of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 300 mg/kg body weight. Two groups each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. In all groups, the test item was suspended with the vehicle aqua ad injectionem (sterile water) at a concentration of 0.03 g/mL and 0.2 g/mL, respectively, and administered at a dose volume of 10 mL/kg.

All animals used in the study after their entrance at the test facility were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study without showing any test-item related signs of toxicity. Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain. At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.

On the basis of the test results and in conformity with the criteria given in Annex I of Regulation (EC) 1272/2008 the substance should not be classified.