4-[(4-chloro-6-{[(3 or 4)-sulfophenyl]amino}-1,3,5-triazin-2-yl)amino]-2-{[1-ethyl-2-hydroxy-4-methyl-6-oxo-5-(sulfonatomethyl)-1,6-dihydropyridin-3-yl]diazenyl}benzenesulfonic acid, lithium sodium salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Single dose

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-[(4-chloro-6-{[(3 or 4)-sulfophenyl]amino}-1,3,5-triazin-2-yl)amino]-2-{[1-ethyl-2-hydroxy-4-methyl-6-oxo-5-(sulfonatomethyl)-1,6-dihydropyridin-3-yl]diazenyl}benzenesulfonic acid, lithium sodium salts

EC Number:

942-795-5

Molecular formula:

Not applicable; this UVCB substance contains: C24H20ClN8O11S3.xLi.yNa, (x + y) = 3; 0 < (x,y) < 3 with 748.9 < MW < 797.0 g/mol (UVCB substance), C24H21N8O12S3.xLi.yNa, (x + y) = 3; 0 < (x,y) < 3 with 730.4 < MW < 778.6 g/mol (UVCB substance), C18H15Cl2N7O8S2.xLi.yNa, (x + y) = 2; 0 < (x,y) < 2 with 606.2 < MW < 638.3 g/mol (UVCB substance), C21H17N8O9S3.xLi.yNa, (x + y) = 3; 0 < (x,y) < 3 with 642.4 < MW < 690.5 g/mol (UVCB substance), C30H25N9O14S4.xLi.yNa, (x + y) = 4; 0 < (x,y) < 4 with 891.5 < MW < 955.7 g/mol (UVCB substnace), and traces of NaCl and Na2SO4.

IUPAC Name:

4-[(4-chloro-6-{[(3 or 4)-sulfophenyl]amino}-1,3,5-triazin-2-yl)amino]-2-{[1-ethyl-2-hydroxy-4-methyl-6-oxo-5-(sulfonatomethyl)-1,6-dihydropyridin-3-yl]diazenyl}benzenesulfonic acid, lithium sodium salts

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: BioLASCO Taiwan Co., Ltd (Taipei, Taiwan)
- Age at study initiation: 8-10 week old
- Housing: one or two animals per cage
- Diet: ad libitum
- Water: ad libitum
- Temperature (°C): 20.2-22.1 °C
- Humidity (%): 41.0-68.4%
- Photoperiod (hrs dark / hrs light): 12-hrs dark / 12-hrs light cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Water for injection (WFI)

Doses:

Dose Step 1: 2000 mg/kg
Dose Step 2: 2000 mg/kg

No. of animals per sex per dose:

Dose Step 1: three
Dose Step 2: three

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Any other information on results incl. tables

Respectively, the mortalities andclinical observations in Dose Step 1 and 2 as below:

In Dose Step 1

No mortality occurred within the first three dayspost-dose. All dose animals tolerated the dose well and survived to termination on Day 15.Hair loss of the forelimb was noted for two out of three assigned study animal. One animal (ID No. 0002) exhibited red-stained hair at the nose on Day 13 and Day 14.

In Dose Step 2

All dose animals tolerated the dose well and survived to termination on Day 15.One animal (ID No. 0005) exhibited yellow stained hair at the head at 0.5 hours post dose on Day 1.One animal (ID No. 0004) excreted soft brown feces from 0.5 hour post dose through Day 3 and became normal thereafter. There were no records of animal observations on Day 12 and Day 13.

 

In Dose Step 1 and 2, body weights increased throughout the study period and gross examination at termination revealed no remarkable changes or lesions in all dose animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

or Unclassified

Conclusions:

According to OECD 423 test method a, the harmonized LD50 cut-off value of CJ301 was 5000 mg/kg. Therefore, CJ301 was Category 5 or Unclassified based on GHS criteria.

Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315001-GN which is based on the SOP for the OECD 423 and OECD 423 (OECD, 2002).A total of 6 female Sprague-Dawley rats were orally dosed with CJ301 in two dose steps of three animals each, at 2000 mg/kg b.w. for both Dose Step 1 and Dose Step 2. All animals in the two dose steps tolerated the test article well with increasing body weights and no mortality, moribundity, or gross findings reported. The only remarkable clinical signs observed were red stained hair at nose on one animal in Dose Step 1 and excretion of soft brown feces in one animal in Dose Step 2. Hair loss was observed at the forelimb of certain study animals in Dose Step 1, but they were not likely dose-related. In absence of mortality, moribund state, or other significant clinical signs of toxicity, these results place CJ301 in the GHS Category Unclassified, with harmonized LD50 cut-off value at 5,000 mg/kg or Unclassified.