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Administrative data

basic toxicokinetics, other
Assessment based on data set
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
Assessment has been based on existing data set for the substance and through assessment of similar substances in this class.

Data source

Reference Type:
other company data
Report date:

Materials and methods

Objective of study:
Test guideline
no guideline followed
GLP compliance:

Test material

Constituent 1
Chemical structure
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:
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
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

Results and discussion

Main ADME resultsopen allclose all
CJ303 had a low skin absorption rate and may be absorbed by inhalation.
CJ303 can be distributed in various tissues and does not accumulate in a specific organ.
No direct evidence showed that how CJ303 is metabolized.
Most anionic precursors or their metabolites are excreted into the bile through the liver and excreted with feces, while the cationic part is mainly excreted through the urine.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Based on the physical form (solid), water solubility (soluble), log P (not conducive to transdermal absorption), and molecular weight (1298.11 g / mol), the transdermal absorption rate was judged to be low (10%).
As the substance is a soluble solid, the content of the particle size distribution <100 μm is 72.31%, and exposure through the inhalation route may occur. In case of inhalation exposure, based on the physical form (solid) and water solubility of the substance, the substance may be quickly absorbed through the alveoli and enter the systemic circulation.
Details on distribution in tissues:
Generally, substances with smaller molecular weight and better water solubility will be widely distributed in the body. CJ303 is relatively water-soluble and can be distributed in the body. Based on CJ303's water solubility, particle size, and Log Kow value, it is unlikely to accumulate in organs or tissues such as lung, bone, and fat.
Transfer into organs
Test no.:
Transfer type:
other: kidneys
distinct transfer
Except for anions, sodium and lithium ions are mainly metabolized by the urine from the kidneys.
Details on excretion:
To promote excretion, lipophilic parent compounds may be converted into polar metabolites and excreted. Based on molecular weight of CJ303 and its main metabolites are more than 300, it is speculated that most anions are excreted into the bile through the liver and excreted with feces, and cations (sodium, lithium ions) are mainly excreted through urine.

Metabolite characterisation studies

Metabolites identified:
Details on metabolites:
None found.

Any other information on results incl. tables

There is no direct evidence showed that how CJ303 is metabolized.

Applicant's summary and conclusion

According to the existing physical and chemical data and health toxicology research data, CJ303 metabolites can be absorbed into the living body through the respiratory tract, the percutaneous absorption rate is reduced, and oral absorption is difficult to occur. Substances can be distributed in the body without accumulating in certain organisms. There is no direct evidence showed that how the substance is metabolized. Through the prediction of metabolic pathways and products, and the phenomenon of blue feces observed in animal experiments, it is possible that most of the maternal anabolic livers are excreted into the bile and excreted in the feces. Some are excreted mainly through the urine.
Executive summary:

CJ303 is a dark blue powder with a purity of 94.06% at 20°C and 101.3kPa. It contains anions, sodium and lithium ions. The molecular weight of the anions is 1298.11g/mol. log Pow is less than -5.82, particle size distribution:> 500μm: 0.15%; 355 ~ 500μm: 0.29%; 250 ~ 355μm: 0.36%; 180 ~ 250μm: 4.20%; 150 ~ 180μm: 9.14%; 100 ~ 150μm: 13.56%; 53 ~ 100μm: 40.42%; <53μm: 31.89%; Hydrolysis test results show that the hydrolysis rates of CJ303 in buffer solutions at pH 4.0, 7.0, and 9.0 are -0.2%, 0.6%, and -1.1%, and the hydrolysis rates are less than 10% at 50°C. Based on the above characteristics, the substance is not easily absorbed after oral exposure. The in vivo data are as follows: in the acute oral toxicity test, at the 2000 mg / kg bw dose level, no animals died or were dying or other important clinical symptoms of toxicity, all test animals gained normal weight, and significant clinical symptoms were observed. It was the rats that excreted dark blue feces in both steps, and one rat showed green urine in the second step. Visual inspection showed that all animals had dark green stains on both kidneys and mesenteric lymph nodes, and no other lesions were found. LD50 of female rats was greater than 2000 mg/kg bw; in repeated exposure test for 28 days, no obvious signs of poisoning were observed in animals at doses of 1000 mg / kg bw / day and below, and animals did not die. Blue feces were observed from the first day of the mouse experiment to the end of the experiment. This phenomenon is related to the properties of the declared substance and is not a toxic side effect. No abnormality was found in food intake and body weight, no significant abnormality was found in gross anatomy, and NOAEL was greater than 1000 mg / kg bw / day. In teratogenicity trials, no death or treatment-related clinical toxicity was observed in each dose group. Feces of the most rats in each dose group were blue after being poisoned, and there were no adverse reactions. The weight, food intake, and reproductive capacity of pregnant rats in each dose group had no significant effects. There were no adverse effects on fetal weight and sex distribution in each dose group, no abnormality was observed, maternal toxicity NOAEL = 1000 mg / kg bw / day, and offspring developmental toxicity NOAEL = 1000 mg / kg bw / day. Physical and chemical data (particle size <100 μm: 72.31%) showed that the substance may be absorbed through the respiratory tract. In the acute inhalation toxicity test, the main test used a concentration of 1.11 mg / L. One female animal died on the first day after exposure, after that, all the animals showed slow breathing, 6 of them had noisy breathing, the activity of dead animals decreased before death, and the surviving animals returned to normal after the second day. The skin and lungs were discolored, and the stomach and trachea had blue liquid. The skin, lungs, lung-related lymph nodes, and kidneys of the surviving animals turned blue and discolored. These symptoms were mainly related to the color of the test substance. LC50> 1.11 mg / L. Physical and chemical data show that the skin absorption rate of the substance is low, and no systemic toxicity was found in the acute transdermal, skin irritation, and skin sensitization tests. Due to its greater water solubility, the substance can be distributed in the body. There is no direct evidence of how the substance is metabolized or excreted, but the anionic part may be excreted into the bile via the liver, excreted with feces, and the cationic part excreted mainly through urine.