Tripotassium [5-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-hydroxy-3-[(2-hydroxy-4-sulpho-1-naphthyl)azo]naphthalene-2,7-disulphonato(5-)]cuprate(3-)

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 2017 – April 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Objective of study:

toxicokinetics

Qualifier:

no guideline required

Toxicokinetics evaluation

Acute studies

The test substance, Reactive Blue 234, was applied to laboratory animals (rat, rabbit, guinea pig) during studies with different way of entry into organism (e.g. stomach, skin and eye).

After single oral administration of the test substance to rats, clinical signs of intoxication as regurgitation and diarrhoea were observed (results provided by Sponsor). Method of testing is not known, but really high dose levels were tested and LD50 was established as 7.459 (6.777-8.208) g/kg. The test substance after single oral administration of high dose level invoked the toxic answer of organism: death of animals occurred. The test substance penetrated into organism after single oral application – the systemic toxicity was observed.

After single dermal administration of the test substance to rats, no clinical signs of intoxication were observed (results provided by Sponsor). Method of testing is not known, but LD50 was established higher than 5 g/kg. No systemic toxicity was observed, so the substance probably did not enter the organism through the skin. According this result can be predicted that the test substance is non-toxic after single dermal application.

The test substance was tested for the evaluation of the potential ocular corrosivity or severe irritancy as measured by its ability to induce opacity and increased permeability in an isolated bovine cornea (BCOP Test). The classification according to UN GHS criteria for eye irritation or serious eye damage was: no prediction can be made (experimental result). The result from search provided by Sponsor demonstrate that the test substance is non-irritant for the rabbit eyes.

After single application on skin of rabbit (results provided by Sponsor), no skin irritation on intact skin was recorded.

The substance elicited negative sensitising response after topical application to the mouse ear in LLNA (experimental result). The animals exposed to the test substance at all concentrations showed no pathological and no other negative clinical symptoms of intoxication throughout the experiment.

 

Repeated toxicity study

Results from the experimental Combined Repeated Dose Toxicity study with the Reproduction/Developmental Toxicity Screening Test showed, that the test substance has different influence on male and female rats. The NOAEL (No Observed Adverse Effect Level) for REPEATED DOSE TOXICITY in MALES was established as lower than 250 mg/kg body weight/day. This judgement is based predominantly on significant changes in serum electrolytes concentrations - decreased value of chloride ions concentrations (dose-dependently and statistically significantly) and natrium ions (statistically significantly) and increased absolute (dose-dependently) and relative weight (statistically significantly) of kidneys in males were recorded. The target organ seems to be kidneys.

The NOAEL (No Observed Adverse Effect Level) for REPEATED DOSE TOXICITY in FEMALES was established as 1000 mg/kg body weight/day. No biologically or statistically significant changes were observed.

 

Examination of microscopic structure of reproductive organs, pituitary gland and thyroid gland did not revealed significant toxicological changes. Histopathological changes in ovaria, uterus and vagina related with reproduction cycle in females or previous pregnancy. Examination of sperm in males was without significant changes. Number of females showing evidence of copulation and number of females achieving pregnancy was not seriously affected. The NOAEL (No Observed Adverse Effect Level) for REPRODUCTION and DEVELOPMENT was established as 1000 mg/kg body weight/day.

Executive summary:

According to current valid guidance the test substance with the result of LD50 in acute oral test higher than 2000 mg/kg is considered as non-toxic (after single oral application).

Reactive Blue 234 did not penetrate into the organism through the skin after single application.

The test compound is considered to be non-irritating to the eye of rabbit.

The target organ of systemic toxicity after repeated oral administration in organism of males seems to be kidneys.

Results recorded during the reproduction part of study with repeated oral administration showed that the test substance did not penetrate into the testes and through the placental barrier.

No data about metabolism, distribution and excretion of the test substance were found.

Description of key information

Dermal absorption

The uptake of sulphonium salts can be slowed as a result of binding to skin components.

The substance is not a skin irritant or corrosive or a skin sensitizer.

Log P value <–1 suggests that a substance is not likely to be sufficiently lipophilic to cross the stratum corneum, therefore dermal absorption is likely to be low. The molecule with Mw > 500 may be too large for dermal uptake.

The Kow < -2.0 and Mw is 873.86 so it means for CSA only 10% absorption by dermal route.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100