Registration Dossier

Diss Factsheets

Administrative data

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

Data source

Reference
Reference Type:
other: final report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline required

Test material

Constituent 1
Chemical structure
Reference substance name:
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-)
EC Number:
304-149-5
EC Name:
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-)
Cas Number:
94246-75-0
Molecular formula:
C23H11ClCuN7O11S3.3K
IUPAC Name:
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-)
impurity 1
Chemical structure
Reference substance name:
Potassium chloride
EC Number:
231-211-8
EC Name:
Potassium chloride
Cas Number:
7447-40-7
Molecular formula:
ClK
IUPAC Name:
potassium chloride
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study report): Reactive Blue 234 - Other name: Ostazin Blue H-5R- Lot/batch No.: 8002- Expiration date of the lot/batch: unlisted

Results and discussion

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.