CJ309

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:

Reaction products of 2,7-Naphthalenedisulfonic acid, 4-amino-6-[2-[5-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-2-sulfophenyl]diazenyl]-3-[2-(2,5-disulfophenyl)diazenyl]-5-hydroxy-, pentasodium salt and lithium chloride

Molecular formula:

Not applicable; this UVCB substance contains: C25H14ClN10O16S5.xLi.yNa, (x + y) = 5; 0 < (x,y) < 5 with 940.9 < MW < 1021.1 g/mol (UVCB substance), and traces of NaCl.

IUPAC Name:

Reaction products of 2,7-Naphthalenedisulfonic acid, 4-amino-6-[2-[5-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-2-sulfophenyl]diazenyl]-3-[2-(2,5-disulfophenyl)diazenyl]-5-hydroxy-, pentasodium salt and lithium chloride

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 (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 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.

Clinical signs:

other:

Any other information on results incl. tables

Respectively, the mortalities and clinical 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. For the first three days post dose, pilo-erection was noted for one animal (ID No. 0026) and mild decreased activity was noted for one animal (ID No. 0025). Abnormally colored mucus membrane (blue) was also noted for all three study animals on Day 1 through Day 8 and the signs for two animals (ID No. 0026 and 0027) persisted to Day 12. All study animals were seen to excrete blue colored feces for the first three days post dose. For two animals (ID No. 0025 and 0027), the blue colored feces had watery consistency with the first two to three days post dose. Two study animals (ID No. 0026 and 0027) were seen to excrete blue colored urine and the signs then persisted through the first three days. For all animals,blue stained hair over the ano-genital area, forepaws, hindpaws, and/or muzzle was noted in the first two or three days post dose. Butfor one animals(ID No. 0025), blue stained hair over the ano-genital area was noted from Day 1 through Day 12.

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 blue colored feces for the first three days post dose and then one animal (ID No. 0030) persisted to seven days post dose. For two animals (ID No. 0028 and 0029), the blue colored feces had watery consistency with the first two to three days post dose.One animal (ID No. 0028) was also seen to have red stained hair at the nose in the first two days post dose and excretion of soft brown feces half an hour post dose. All study animals were seen to excrete blue colored urine. The signs for two animals (ID No. 0028 and 0029) and one animals (ID No. 0030) persisted through the first three days and seven days,respectively. For all animals,blue stained hair over the ano-genital area, forepaws, hindpaws, and/or muzzle was noted in the first two or three days post dose. 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 diffuse, dark brown discoloration in both kidneys of all study 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 CJ309 was 5000 mg/kg. Therefore, CJ309 was Category 5 or Unclassified based on GHS criteria.

Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315005-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 CJ309 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 excretion of blue urine and feces within the first three to seven days post dose. Transient pilo-erection, decreased activity, and abnormally colored mucus membrane (blue) was also observed for some animals in either dose step. On the other hand, gross examination revealed dark brown discoloration of the kidneys of all study animals in both dose steps, suggestive of possible test article effect on the kidney at 2000 mg/kg b.w. or higher. In absence of mortality, moribund state, or other significant clinical and gross signs of toxicity, these results place CJ309 in the GHS Category 5 or Unclassified, with harmonized LD50 cut-off value at 5,000 mg/kg or Unclassified.