7-[{4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-2-(carbamoylamino)phenyl}diazenyl]naphthalene-1,3,6-trisulfonic 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:

From December 21, 2015 to December 15, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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 type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

dilithium(1+) sodium 7-[(1E)-2-{4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-2-(carbamoylamino)phenyl}diazen-1-yl]naphthalene-1,3,6-trisulfonate

EC Number:

942-667-9

Molecular formula:

Not applicable; this UVCB substance contains: C20H13ClN9O10S3.xLi.yNa, (x + y) = 3; 0 < (x,y) < 3 with 691.8 < MW < 739.9 g/mol (UVCB substance), C20H14N9O11S3.xLi.yNa, (x + y) = 3; 0 < (x,y) < 3 with 673.4 < MW < 721.5 g/mol (UVCB substnace), and traces of NaCl.

IUPAC Name:

dilithium(1+) sodium 7-[(1E)-2-{4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-2-(carbamoylamino)phenyl}diazen-1-yl]naphthalene-1,3,6-trisulfonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: 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

Doses:

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

No. of animals per sex per dose:

Dose Step 1: three female
Dose Step 2: three female

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. Two animals (ID No. 0032 and 0033) were seen to have mild decreased activity in the first three days post dose. Two animals (ID No. 0031 and 0033) excreted orange colored urine and then no abnormal excretion was reported after Day 3. Hair loss of the forelimb was noted for one animal (ID No. 0031) on Day 6 and persistent to study completion.

In Dose Step 2

All dose animals tolerated the dose well and survived to termination on Day 15. Two animals (ID No. 0034 and 0036) excreted orange colored urine and then two animals (ID No. 0034 and 0035) excreted red colored feces. No abnormal excretion was reported after Day 3. Red stained hair over the ano-genital area was noted for one animal (ID No. 0034) on Day 1 through Day 3. 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:

Category 5 based on GHS criteria

Remarks:

or Unclassified

Conclusions:

According to OECD 423 test method a, the harmonized LD50 cut-off value of CJ312 was 5000 mg/kg. Therefore, CJ312 was Category 5 or Unclassified based on GHS criteria.

Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315006-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 CJ312 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 or moribundity reported. The only remarkable clinical signs observed were mild decrease in activity in the first three days post dose in Dose Step 1; and excretion of orange urine in both dose steps and red feces in Dose Step 2, both within the first three days post dose. Isolated instances of forelimb hair loss were also noted for one animal in Dose Step 1. In absence of mortality, moribund state, or other significant clinical and gross signs of toxicity, these results place CJ312 in the GHS Category 5 or Unclassified, with harmonized LD50 cut-off value at 5,000 mg/kg or Unclassified.