9-(2-carboxyphenyl)-3,6-bis(diethylamino)xanthylium bis[3-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]-4-hydroxy-N-3-(isopropoxypropyl)benzenesulphonamidato(2-)]cobaltate(1-)

Endpoint summary

Description of key information

The acute oral LD50 was determined to be > 2000 mg/kg body weight.

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:

15 Aug 2016 to 14 Sep 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

17 December 2001

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

30 May 2008

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No. 8147

Version / remarks:

2000

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

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

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han) SPF

Sex:

female

Details on test animals or test system 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- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.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.

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.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: 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

Gross pathology:

There were no macroscopic pathological findings in all animals sacrificed at the end of the observation period.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

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

An acute oral toxicity study (Bioassay, 2017) was conducted according to the OECD-Guideline 423. A dose of 2000 mg/kg of the test item was administered by gavage to two test groups of three fasted Wistar rats each (6 females). No mortality occurred. No clinical signs were observed. 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. There were no macroscopic pathological findings at the end of the observation period.

Justification for classification or non-classification

Based on the available information classification for acute oral toxicity is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.