Blue MGi 1037-Na (notification presscake)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2016-11-02 to 2016-12-12

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:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

473-160-6

EC Name:

-

Molecular formula:

Hill formula: C24 H15 Cu F2 N7 Na3 O9 S2

IUPAC Name:

dicopper(2+) hexasodium 2-[(E)-{[(Z)-(2-{3-[(2,6-difluoropyrimidin-4-yl)amino]-2-oxido-5-sulfonatophenyl}hydrazin-2-id-1-ylidene)(phenyl)methyl]imino}amino]-4-sulfonatobenzoate 2-[(E)-{[(Z)-(2-{3-[(4,6-difluoropyrimidin-2-yl)amino]-2-oxido-5-sulfonatophenyl}hydrazin-2-id-1-ylidene)(phenyl)methyl]imino}amino]-4-sulfonatobenzoate

Specific details on test material used for the study:

Purity: ca 88.0 %

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: TOXI COOP ZRT., 1103 Budapest, Hungary
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 192 - 194 g (first step), 203 - 206 g (second step)
- Fasting period before study: overnight (diet)
- Housing: Group caging (3 animals/cage)
- Diet: ssniff® SM R/M-Z+H complete diet ad libitum, ssniff Spezialdiäten GmbH, D-59494 Soest, Germany
- Water: tap water ad libitum
- Acclimation period: 6 days in first step and 7 days in second step

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: above 10 air exchanges/hour by central air-condition system
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: November 09, 2016 To: November 25, 2016

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Batch Number: 1608-5511

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: Formulations were prepared just before the administration and stirred continuously during the treatment. The correction factor of 1.14 was taken into consideration for the preparation of the test item formulation.

CLASS METHOD
- Rationale for the selection of the starting dose: Starting dose was selected on the basis of the available information about the test item. The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step and thus the test was finished as the stopping criteria of Annex 2d of OECD Guideline No. 423 were met.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: General state, external appearance, behavior and clinical symptoms after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h after the treatment and once each day (twice each day for mortality) for 14 days thereafter; body weights on day 0 (just before the treatment), on day 7 and on day 15
- Necropsy of survivors performed: Yes
- Other examinations performed: Macroscopic examination

Statistics:

Not applicable

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

No deaths occurred after administration of 2000 mg/kg bw.

Clinical signs:

other: In group 1 clinical signs of reaction comprised of blue coloured faeces (5 cases of 57 observations) and diarrhoea (3/57). Blue coloured faeces (score +3) was detected in all animals on the treatment day between 2 and 4 hours after the treatment. Diarrho

Gross pathology:

Severe hydrometra was found in two females of the group 1 and in one female of group 2. Hydrometra is physiological finding and connected to the cycle of the animal. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 in rats was determined to be > 2000 mg/kg bw.

Executive summary:

An acute toxic class method according to OECD TG 423 was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, therefore treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 (presented in Appendix VII) was first met. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out 15th day after the treatment.

No lethality was noted at single oral dose of 2000 mg/kg bw.

In the first step, disturbance of the autonomic functions (diarrhoea) was observed in one animal related with test item effect on the treatment day between 2 and 4 hours after the treatment. However, blue coloured faeces was detected in all animals on the treatment day between 2 and 4 hours after the treatment. This symptom was connected with the physical property of the test item.

In the second step, disturbance of the autonomic functions (diarrhoea) was observed in one animal related with test item effect on the treatment day between 3 and 4 hours after the treatment. However, blue coloured faeces was detected in all animals between the treatment day and Day 1. This symptom was connected with the physical property of the test item.

The body weight development was undisturbed in all animals.

All organs of the animals treated with 2000 mg/kg bw proved to be free of treatment related gross pathological changes.

The oral LD50 in rats was determined to be > 2000 mg/kg bw.