Reaction products of cuprate(4-), [C-(aminosulfonyl)-C-[[[2-[[4-chloro-6-[(2,5-disulfophenyl)amino]-1,3,5-triazin-2-yl]amino]ethyl]amino]sulfonyl]-29H,31H-phthalocyanine-C,C-disulfonato(6-)-N29,N30,N31,N32]-, tetrasodium and lithium chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From November 22, 2016 to June 06, 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

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 cuprate(4-), [C-(aminosulfonyl)-C-[[[2-[[4-chloro-6-[(2,5-disulfophenyl)amino]-1,3,5-triazin-2-yl]amino]ethyl]amino]sulfonyl]-29H,31H-phthalocyanine-C,C-disulfonato(6-)-N29,N30,N31,N32]-, tetrasodium and lithium chloride

EC Number:

942-810-5

Molecular formula:

C43H24ClCuN15O16S6.xLi.yNa, (x + y) = 4; 0 < (x,y) < 4 with 1341.9 < MW < 1374 g/mol (UVCB substance), and traces of NaCl and NaSO4

IUPAC Name:

Reaction products of cuprate(4-), [C-(aminosulfonyl)-C-[[[2-[[4-chloro-6-[(2,5-disulfophenyl)amino]-1,3,5-triazin-2-yl]amino]ethyl]amino]sulfonyl]-29H,31H-phthalocyanine-C,C-disulfonato(6-)-N29,N30,N31,N32]-, tetrasodium 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: 9-10 week old
- Housing: one or two animals per cage
- Diet: ad libitum
- Water: ad libitum
- Temperature (°C): 11.4-25.7 °C
- Humidity (%): 30.7-94.4%
- 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:

2000 mg/kg b.w.

No. of animals per sex per dose:

For Dose Step 1: three females
For Dose Step 2: three females

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

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.Excretion of feces with deep blue coloration was noted as early as 4 hours post dose and the feces with deep blue discoloration also appeared unformed on Day 1 for one animal (ID No. 0007). Other observations include the deep blue-stained hair in the ano-genital area of one animal on Day 1 (ID No. 0007) was noted. Green or deep blue-stained skin over feet or tail was noted for all of the study animal.

In Dose Step 2

All dose animals tolerated the dose well and survived to termination on Day 15. Excretion of feces with deep blue coloration was noted as early as 4 hours post dose for two out of three animals (ID Nos. 0010 and 0012). The feces with deep blue discoloration also appeared unformed on Day 1 for ID No. 0010. Reports of feces with deep blue discoloration persisted through Day 7 for animals. The excretion of urine of unusual color (green) was also reported for one animal (ID No. 0012) on Day 1 through Day 5. Green or deep blue-stained skin over feet or tail was noted for all of the study animal.

 

In Dose Step 1 and 2, body weights increased throughout the study period. Gross examination at termination revealeddark green discoloration in both kidneys and mesenteric lymph node of all animals in Dose Step 1 and diffuse, dark green discoloration in both kidneys and mesenteric lymph node of all animals in Dose Step 2. No other remarkable changes or lesions were noted in the remaining study animals in either Dose Step 1 or Dose Step 2.

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 CJ303 was 5000 mg/kg. Therefore, CJ303 was Category 5 or Unclassified based on GHS criteria.

Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65316016-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 CJ303 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 remarkable clinical signs observed were excretion of deep blue feces in both dose steps and green urine for one animal in Does Step 2. Isolated instances of hair stain in ano-genital area or stained skin over feet or tail were also noted for one animal in Dose Step 1 or in both dose steps. Gross examination revealed dark green discoloration of the kidneys and mesenteric lymph node of all animals, which while resulting in no discernable clinical changes might require follow-up in longer-term toxicology studies with histopathology examination. In absence of mortality, moribund state, or other significant clinical and gross signs of toxicity, these results place CJ303 in the GHS Category 5 or Unclassified, with harmonized LD50 cut-off value at 5,000 mg/kg or Unclassified.