pentasodium 4-amino-3-[{4-[(2,4-disulfonatophenyl)diazenyl]-3-methylphenyl}diazenyl]-5-hydroxy-6-[(4-nitro-2-sulfonatophenyl)diazenyl]naphthalene-1,7-disulfonate

Endpoint summary

Description of key information

LD50 oral, rat: > 2000 mg/kg bw

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:

2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
Janvier Labs SAS, Le Genest St. Isle, 53941 Saint Berthevin Cedex, France
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation:
8 - 12 weeks
- Weight at study initiation:
204 - 246 g
- Fasting period before study:
overnight
- Housing:
groups of one to five rats
- Historical data:
available
- Diet (e.g. ad libitum):
ad libitum
- Water (e.g. ad libitum):
ad libitum
- Acclimation period:
at least 5 days prior to start of dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
22 +/- 2°C
- Humidity (%):
45-65%
- Air changes (per hr): at least 8 per hour
- Photoperiod (hrs dark / hrs light):
12/12

IN-LIFE DATES: From: 2020-07-20 To: 2020-08-12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: stability in vehicle given

CLASS METHOD (if applicable)
- In the absence of data regarding the toxicity of the test item 300 mg/kg was chosen as the initial starting dose, since a severe toxicity which may necessitate humane euthanasia was not expected at this dose level.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

1 female for the pre-test with 300 mg/kg bw and 2000 mg/kg bw each
4 females for the main study with 2000 mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and inspections for morbidity / mortality were performed at least three times within the first six hours after application (i.e., 30 minutes and 1 hour, 2 hours and 4 hours after dosing), thereafter at least once daily for 14 days. Body weights were recorded on Day 0 (prior to dosing), Day 7, and 14.
- Necropsy of survivors performed: yes

Statistics:

not needed

Preliminary study:

In the sighting test with one female and a single dose of 2000 mg/kg bw

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One female (animal number 2) had to be humanely euthanised on day 1 after application due to deterioration of clinical signs.

Clinical signs:

other: Clinical signs included secretion of Harderian glands, fur stained by the test item, staining around the mouth, blue to black staining of the skin, staining of the urine and faeces. The euthanized animal showed the following additional symptoms: hunched p

Gross pathology:

Three animals showed dark kidneys, possibly due to test item residuals in the parenchyma.
For animal number 2 discoulouring of the following organs to blue was noted: fur, skin, orifices, tongue, pharynx, eyes, mucosa, small and large intestine, peritoneum, kidneys, and caecum. The skin of the urinary bladder was discoloured as well but the content was clear.
Additionally, fluffed-up cheeks and a thickened right masseter muscle, a filled stomach and a moniliform content of the small intestine and black content of the caecum was observed.

Interpretation of results:

GHS criteria not met

Executive summary:

The registered substance was tested at a starting dose of 300 mg/kg bw and at 2000 mg/kg bw in the main study of an acute oral toxicity study in female Wistar rats following OECD TG 420. One animal of the main test treated with 2000 mg/kg body weight was euthanized on day 1 after application due to deterioration of clinical signs that were, if compared to the symptoms observed in the four other animals dosed with 2000 mg/kg b.w., unexpectedly severe. Therefore, it is possible that these individual symptoms were incidental. Clinical signs in the other 4 animals included secretion of Harderian glands, and staining by the couloured test item of fur, mouth, skin, urine and faeces. The acute median lethal oral dose (LD50) was demonstrated to be > 2000 mg/kg bw.

Endpoint conclusion

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and, in the absence of an in vivo study by the oral route, no systemic effects after dermal exposure are predicted on the basis of non-testing approaches (e.g. read across, QSAR studies)

Endpoint conclusion

Quality of whole database:

No acute dermal toxicity expected.

Justification for classification or non-classification

No classification for acute oral toxicity is warranted (LD50 oral, rat > 2000 mg/kg bw). Based on this result no acute dermal toxicity is expected.