2-[{6-[(4-amino-6-chloro-1,3,5-triazin-2-yl)(methyl)amino]-1-hydroxy-3-sulfonaphthalen-2-yl}diazenyl]naphthalene-1,5-disulfonic 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 01, 2016. Singler dose

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:

2-[{6-[(4-amino-6-chloro-1,3,5-triazin-2-yl)(methyl)amino]-1-hydroxy-3-sulfonaphthalen-2-yl}diazenyl]naphthalene-1,5-disulfonic acid, lithium sodium salts

EC Number:

942-710-1

Molecular formula:

Not applicable; this UVCB substance contains: C24H15ClN7O10S3.xLi.yNa, (x + y) = 3; 0 < (x,y) < 3 with 713.8 < MW < 762.0 g/mol (UVCB substance), C24H16N7O11S3.xLi.yNa, (x + y) = 3; 0 < (x,y) < 3 with 695.4 < MW < 743.5 g/mol (UVCB substnace), C21H14N3O10S3.xLi.yNa, (x + y) = 3; 0 < (x,y) < 3 with 585.3 < MW < 633.5 g/mol (UVCB substnace), and traces of NaCl.

IUPAC Name:

2-[{6-[(4-amino-6-chloro-1,3,5-triazin-2-yl)(methyl)amino]-1-hydroxy-3-sulfonaphthalen-2-yl}diazenyl]naphthalene-1,5-disulfonic 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 females
Dose Step 2: Three females

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 days post-dose. All dose animals tolerated the dose well and survived to termination on Day 15. All study animals were seen to excrete orange colored urine on the first five days. Hair loss of the forelimb was noted for one assigned study animal (ID No. 0009) on Day 6 and persistent throughout the remainder of the study period.

 In Dose Step 2

All dose animals tolerated the dose well and survived to termination on Day 15. All study animals were seen to excrete orange colored urine on the first three days. Two animals (ID No. 0010 and 0012) were seen to excrete red colored feces and the signs then persisted through the first seven days post dose. One animal (ID No. 0011)exhibited orange stained hair over the dorsalneck area on Day 1 and Day 2. 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

Conclusions:

According to OECD 423 test method a, the harmonized LD50 cut-off value of CJ302 was 5000 mg/kg. Therefore, CJ302 was Category 5 or Unclassified based on GHS criteria.

Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315002-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 CJ302 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 excretion of orange colored urine in both Dose Step and red feces in Dose Step 2. Hair loss was observed at the forelimb of one 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 CJ302 in the GHS Category 5 or Unclassified, with harmonized LD50 cut-off value at 5,000 mg/kg or Unclassified.