Disodium 6-hydroxy-5-[[4-[[4-(phenylamino)-3-sulphonatophenyl]azo]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:

December 2016 – January 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

Specific details on test material used for the study:

228-412-8disodium 6-hydroxy-5-[[4-[[4-(phenylamino)-3-sulphonatophenyl]azo]naphthyl]azo]naphthalene-2-sulphonate(Acid Black 26)

Results and discussion

Any other information on results incl. tables

Toxicokinetics evaluation

Acute studies

The test substance, Acid Black 26, 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 female rats, no clinical signs of intoxication were observed. Only coloured faeces were recorded within two days of observation period. The value of LD50 was established higher than 2000 mg/kg.

The result from internet search even reported the value higher than 5000 mg/kg.

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. The classification according to UN GHS criteria for eye irritation or serious eye damage was: no prediction can be made. The result from in vivo study reported that examination of eye after single application of substance to the conjunctival sac of rabbit eye demonstrate that the test substance is considered to be non-irritating for the rabbit eyes.

After single application on skin of rabbit, no skin irritation was recorded.

The substance elicited negative sensitising response in guinea pig maximisation test. The animals exposed to the test substance showed no erythema and oedema, 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 negative effect on animals. The value of NOAEL (No Observed Adverse Effect Level) for REPEATED DOSE TOXICITY was established as 500 mg/kg body weight/day both for MALES and FEMALES. Histopathological examination showed higher intensity of chronic progressive nephropathy in kidneys in both sexes. The influence of the test substance on kidneys could not be excluded because the intensity of chronic progressive nephropathy in kidneys was irreversibly increased with dose level. In satellite females the value of creatinine found during the biochemical examination was changed. This value of creatinine in satellite females were out in historical control limit and can be related with histopathological findings of kidneys.

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:

The test substance after single oral administration of high dose level did not invoke the toxic answer of organism. The systemic toxicity after oral administration was not observed.

No clinical signs of systemic intoxication were detected. After single application on skin of rabbit, no skin irritation was recorded. The results of sensitisation study - negative sensitising response, support conclusion that Acid Black 26 did not penetrate into the organism through the skin after single application.

Examination of eye after single application of substance to the conjunctival sac demonstrated, that the test substance was non-irritating to the eye of rabbit.

After repeated oral administration, the test substance caused systemic intoxication. The only one target organ of systemic toxicity in organism were kidneys.

Histopathological examination showed higher intensity of chronic progressive nephropathy in kidneys in both sexes. The influence of the test substance on kidneys could not be excluded because the intensity of chronic progressive nephropathy in kidneys was irreversibly increased with dose level. Changes related with the metabolism of the test substance were observed during the biochemical examination - in satellite females the value of creatinine found during the biochemical examination was changed. This value of creatinine in satellite females were out in historical control limit and can be related with histopathological findings of kidneys.

Examination of microscopic structure of reproductive organs, pituitary gland and thyroid gland did not revealed significant toxicological changes. 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. Mean number of pups per litter and sex ration were not affected by the test substance treatment. No differences in postnatal developmental were observed in pups at the treated groups.

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.