Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The test item was administered at a single dose by gavage using a feeding tube.
In order to get the test item in a solution or suspension, which is applicable to the animals, aqua ad injectionem (AlleMan Pharma, lot no. 605070, expiry date: 30/04/2017) was evaluated as vehicle and was considered to be adequate. This vehicle was chosen due to its non-toxic characteristics.
For all animals of the first step, 0,3 g of the test item was dissolved in the vehicle to gain a final volume of 10 mL and to achieve a dose of 300 mg/kg body weight at a dose volume of 10 mL/kg body weight.
For all animals of the second and third step, 0, 05 g of the test item was dissolved in the vehicle to gain a final volume of 10 mL and to achieve a dose of 50 mg/kg body weight at a dose volume of 10 mL/kg body weight.
Doses:
Animals were treated with test item at a dose of 50 mg/kg bw and at a dose of 300 mg/kg bw.
No. of animals per sex per dose:
3 Female Rats/ 300 mg/kg body weigh
6 Female Rats/ 50 mg/kg body weight
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: once daily until the end of the observation period.
- Frequency of weighing: on day 1 (prior to the administration) and on days 8 and 15.
- Necropsy performed: yes
- Other examinations performed: clinical signs, body weight, morbidity and mortality.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
200 mg/kg bw
Based on:
test mat.
Mortality:
All animals that were treated with test item at a dose of 50 mg/kg bw (step 2 and 3) survived until the end of the study showing signs of toxicity.
All animals treated with the test item at a dose of 300 mg/kg bw (step 1) died spontaneously within 60 minutes post dosing.
Clinical signs:
The most relevant clinical findings in the animals treated with the test item at a dose of 300 mg/kg bw were reduced spontaneous activity, slow movements, piloerection, ataxia, half eyelid-closure, prone position, cyanosis and abnormal breathing.
The most relevant clinical findings in the animals treated with the test item at a dose of 50 mg/kg bw were reduced spontaneous activity, hunched posture, piloerection, prone position, half eyelid-closure, ataxia, slow movements and sunken flanks. All animals recovered within up to 3 days post-dose.
Body weight:
Throughout the 14-day observation period, the weight gain of the surviving animals was within the normal range of variation for this strain.
Gross pathology:
Macroscopic findings of surviving animals: At necropsy, no macroscopic findings were observed in any animal of any step.
Macroscopic findings of animals not having survived until the end of the observation period: Necropsy revealed dark discoloured intestinal sections such as duodenum, jejunum, ileum and caecum.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Under the conditions of the present study, a single oral application of the test item Basic Yellow 1 to rats at a dose of 300 mg/kg body weight was associated with signs of toxicity and mortality.
Under the conditions of the present study, a single oral application of the test item Basic Yellow 1 to rats at a dose of 50 mg/kg body weight was associated with signs of toxicity but no mortality.
The median lethal dose of Basic Yellow 1 after a single oral administration to female rats, observed over a period of 14 days is:
LD50 cut-off (rat): 200 mg/ kg bw
Executive summary:

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 (step 1). The test item was suspended in aqua ad injectionem (sterile water) at a concentration of 30 mg/mL and administered at a dose volume of 10 mL/kg.

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 50 mg/kg body weight (step 2 and 3). The test item was suspended in aqua ad injectionem (sterile water) at a concentration of 5 mg/mL and administered at a dose volume of 10 mL/kg.

All animals used in the study after their entrance at BSL 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.

ll animals treated with the test item at a dose of 300 mg/kg bw (step 1) died spontaneously within 60 minutes post dosing.

The most relevant clinical findings in the animals treated with the test item at a dose of 300 mg/kg bw were reduced spontaneous activity, slow movements, piloerection, ataxia, half eyelid-closure, prone position, cyanosis and abnormal breathing.

All animals that were treated with test item at a dose of 50 mg/kg bw (step 2 and 3) survived until the end of the study showing signs of toxicity.

The most relevant clinical findings in the animals treated with the test item at a dose of 50 mg/kg bw were reduced spontaneous activity, hunched posture, piloerection, prone position, half eyelid-closure, ataxia, slow movements and sunken flanks. All animals recovered within up to 3 days post-dose.

Throughout the 14-day observation period, the weight gain of the surviving animals was within the normal range of variation for this strain.

Macroscopic findings of surviving animals:

At necropsy, no macroscopic findings were observed in any animal of any step.

Macroscopic findings of animals not having survived until the end of the observation period:

Necropsy revealed dark discoloured intestinal sections such as duodenum, jejunum, ileum and caecum.

Conclusion

Under the conditions of the present study, a single oral application of the test item Basic Yellow 1 to rats at a dose of 300 mg/kg body weight was associated with signs of toxicity and mortality.

Under the conditions of the present study, a single oral application of the test item Basic Yellow 1 to rats at a dose of 50 mg/kg body weight was associated with signs of toxicity but no mortality.

The median lethal dose of Basic Yellow 1 after a single oral administration to female rats, observed over a period of 14 days is:

LD50 cut-off (rat): 200 mg/ kg bw