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

Endpoint summary

Description of key information

Acute toxicity: via oral route

No adverse effects at 2000 mg/kg

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:

Single dose

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

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

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

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Limited exposure evisaged.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-06-02

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Justification for type of information:

The structure of the read-across substance is the para form of the CJ301 without the meta form. However, this difference does not influence the toxicity of the CJ301. CJ301 contains Li/Na salt form and the read-across substances contains only Na salt. This will not lead to difference on the toxicity results.

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1981

GLP compliance:

yes

Limit test:

yes

Species:

rat

Strain:

other: Wistar KFM-Han. SPF

Type of coverage:

occlusive

Vehicle:

other: Dest. Wasser + 4 % CMC-Na-Salz

Duration of exposure:

24h

Doses:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Other findings:

Colouration of the skin surface.
In addition, the female rats exhibited erythema, scaling and a weight loss during the observation period. All of the above-mentioned symptoms disappeared at the end of the observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

No death was observed after the application. Therefore, the test substance is not classified for acute dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute toxicity: via oral route

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 5 or Unclassified, with harmonized LD50 cut-off value at 5,000 mg/kg or Unclassified.

Justification for selection of acute toxicity – dermal endpoint
The LD50 of the read-across substance was 2000 mg/kg/bw.