Tetrasodium 8-[[4-[(4-amino-3-sulphonatophenyl)azo]-6-sulphonatonaphthyl]azo]-5-[[6-(benzoylamino)-1-hydroxy-3-sulphonato-2-naphthyl]azo]naphthalene-2-sulphonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

other: Assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information.

Adequacy of study:

key study

Study period:

June 2017 – August 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

Test material information

Constituent 1

Reference substance name:

Tetrasodium 8-[[4-[(4-amino-3-sulphonatophenyl)azo]-6-sulphonatonaphthyl]azo]-5-[[6-(benzoylamino)-1-hydroxy-3-sulphonato-2-naphthyl]azo]naphthalene-2-sulphonate

EC Number:

274-427-8

EC Name:

Tetrasodium 8-[[4-[(4-amino-3-sulphonatophenyl)azo]-6-sulphonatonaphthyl]azo]-5-[[6-(benzoylamino)-1-hydroxy-3-sulphonato-2-naphthyl]azo]naphthalene-2-sulphonate

Cas Number:

70210-31-0

Molecular formula:

C43H30N8O14S4.4Na

IUPAC Name:

tetrasodium 8-[[4-[(4-amino-3-sulphonatophenyl)azo]-6-sulphonatonaphthyl]azo]-5-[[6-(benzoylamino)-1-hydroxy-3-sulphonato-2-naphthyl]azo]naphthalene-2-sulphonate

impurity 1

Reference substance name:

unknown impurities

IUPAC Name:

unknown impurities

Test material form:

solid: particulate/powder

Details on test material:

Batch No.: 7031/2007Stability/Expiration: Feb 2018Storage: The test substance should be stored in dry room in dark in supplied container at the room temperature.

Results and discussion

Any other information on results incl. tables

Toxicokinetics evaluation

Acute studies

The test substance, Direct Blue 85, was applied to laboratory animals (rat, mice, rabbit) 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, sporadic information about clinical signs of intoxication were noted (results provided by Sponsor). Method of testing is not known, but really high dose levels were tested and LD50 was established as 9.607 (9.024 – 10.23) g/kg.

After single dermal administration of the test substance to rats, no clinical signs of intoxication were observed (results provided by Sponsor). The 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. According to result of acute eye irritation/corrosion test (experimental result) the test substance is non-irritant for the rabbit eyes.

The substance provides 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

Results from the experimental Combined Repeated Dose Toxicity study with the Reproduction/Developmental Toxicity Screening Test showed, that the test substance did not cause any mortality of animals. The test substance did not interfere with normal growth of treated parental animals. Haematological examination of males was without changes and females showed sporadic findings only. Biochemical examination of treated males and females revealed minimal changes. During biometry of organs, significant changes related to administration of the test substance were not detected.

Microscopical evaluation showed that the test substance orally administered at the dose level of 1000 mg/kg/day did not cause any histopathological changes in any examined organs. Effect of the test substance treatment was not observed during histopathological examination.

All stated changes was considered as biologically insignificant. The NOAEL (No Observed Adverse Effect Level) for REPEATED DOSE TOXICITY was established as 1000 mg/kg body weight/day. 

 

Reproduction and development

The number of females achieving pregnancy, sperm parameters and microscopical structure of reproductive organs in both parental males and females seemed to be not affected by the test substance administration. Evaluation of prenatal development of pups did not show any adverse effect of the test substance treatment.

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

Conclusions:

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). The test substance 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 test substance is not a sensitizer.The repeated oral administration of the test substance did not evoke the toxic answer of organism and no signs of systemic toxicity were observed. Test substance did not influence reproduction parameters of males and females. Development of pups was not influenced by the test substance administration. 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.