Registration Dossier

Administrative data

Description of key information

In a valid GLP OECD 423 study in female rats, a single dose of the registered substance at 2000mg/kg bw resulted in no mortality, therefore leading to a LD50 at the cut-off value of 5000mg/kg bw.

There were no signs of toxicity in any animal of step 1. However, all animals of step 2 showed slight signs of acute oral toxicity. The most relevant clinical finding in the animals of step 2 treated with the test item at a dose of 2000 mg/kg bw was piloerection between 120 min and 240 min post-application. No clinical signs were recorded in all animals of step 2 240 min after administration until end of study.

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 macroscopic findings were observed in any animal of any step.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
OECD 423, v. 2001
EC 440/2008 B.1, v. 2008
EPA OPPTS 870.1000, EPA 712-C-02-189/190, v. 2002
Deviations:
no
Principles of method if other than guideline:
Guideline method
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-10 weeks
- Weight at study initiation: Step 1: 155–162 g; Step 2: 159–177 g
- Fasting period before study: 16 to 19 hours (access to water was permitted)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: >=5 days

ENVIRONMENTAL CONDITIONS
- Full barrier in an air-conditioned room
- Temperature: 22 +/- 3 °C
- Relative humidity: 55 +/- 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 0426)
- 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)
- The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 02102171114)
- Certificates of food, water and bedding are filed for two years at BSL Munich and afterwards archived at Eurofins Munich
- Adequate acclimatisation period (at least five days) under laboratory conditions


IN-LIFE DATES: From: To: 17.1.2018-14.2.2018
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
None used

MAXIMUM DOSE VOLUME APPLIED:
2000mg/kg bw applied as such. Max. animal weight: 177 grams

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no toxicity expected based on structural analogue
Doses:
2000 mg/kg bw in step 1 and 2
No. of animals per sex per dose:
3 f
Control animals:
no
Details on study design:
Duration of observation period following administration: 14 days
Frequency of observations and weighing: All animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality. The animals were weighed on day 1 (prior to the administration) and on days 8 and 15. 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.
Necropsy of survivors performed: At the end of the observation period all animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally (CP-Pharma; lot no.: 17C202; expiry date: 28 February 2019) at a dosage of 250-400 mg/kg bw.
All animals were subjected to gross necropsy and examined macroscopically for gross pathological changes. In the absence of gross pathological changes no tissues were preserved for a possible histopathological evaluation.
Statistics:
N/A
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
See table.
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:
None

Step

Animal No. / Sex

Starting Dose (mg/kg bw)

Timepoint

Observations

1

1 / Female

2000

0 min – 15 d

nsf

2 / Female

0 min – 15 d

nsf

3 / Female

0 min – 15 d

nsf

2

4 / Female

0 – 120 min

nsf

120 – 180 min

Slight piloerection

180 – 240 min

Moderate piloerection

240 min – 15 d

nsf

5 / Female

0 – 120 min

nsf

120 – 180 min

Slight piloerection

180 – 240 min

Moderate piloerection

240 min – 15 d

nsf

6 / Female

0 – 120 min

nsf

120 – 180 min

Slight piloerection

180 – 240 min

Moderate piloerection

240 min – 15 d

nsf

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study, a single oral application of the test item Direct Yellow 147 to rats at a dose of 2000 mg/kg body weight was associated with slight signs of toxicity but no mortality.
The median lethal dose of Direct Yellow 147 after a single oral administration to female rats, observed over a period of 14 days is LD50 cut-off (rat): 5000 mg/kg bw
Executive summary:

Under the conditions of the present study, a single oral application of the test item Direct Yellow 147 to rats at a dose of 2000 mg/kg body weight was associated with slight signs of toxicity but no mortality.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
1

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The substance does not need to be classified for acute toxicity or STOT SE via the oral route of exposure. No systemic effects were observed in the in vivo skin sensitization study with the read-across substance. Therefore an acute toxicity study via the dermal route is not required.

Exposure via the inhalation route is unlikely to occur owing to the liquid form of the substance and low vapour pressure.

Justification for classification or non-classification

Classification for acute toxicity is not required under the CLP regulation.