Hydrogen 9-amino-7-phenyl-5-(phenylamino)-4,10-disulphonatobenzo[a]phenazinium, disodium salt

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

Expert statement

Type of information:

other: Expert statement

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Evaluation of all available information with rgard to toxicokinetic properties.

Qualifier:

no guideline required

Principles of method if other than guideline:

Evaluation of all available information with regard to toxicokinetic properties of the test item

GLP compliance:

no

Details on absorption:

Based on the subacute (28-day) oral toxicity study absorption of toxicologically significant amounts of Acid Violet 50 via the gastrointestinal tract is not assumed since no obvious discoloration of inner organs was observed throughout the body. Discolorations were seen exclusively in the intestinal content.
Systemic availability seems to be negligible after dermal exposure since no systemic signs of intoxication were seen after occlusive administration of 2000 mg Acid Violet 50 per kg body weight in rats in the acute dermal toxicity study. Indications of a significant dermal absorptive potential were also not revealed by testing for primary irritation in rabbits. The notion of very limited dermal absorption is also corroborated by the molecular structure containing two sulfonic acid anions.

Details on distribution in tissues:

Based on the results of the subacute oral toxicity study discolorations were observed in the digestive tract only. Thus, it can be concluded, that Acid Violet 50 is not absorbed through the gastrointestinal tract and not systemically available within the organism in toxicologically relevant amounts. Histopathological findings indicate no deposition of the dye in any tissues.
There were no signs of bioaccumulation of the test material after dosing in the subacute toxicity study. This view is supported by the physical-chemical properties and the molecular structure.

Details on excretion:

Taking into account the physico-chemical properties and the molecular structure of the dye it is assumed that the main route of excretion will be the faeces.
Most of the dose, if not all, is expected to just pass through the digestive tract without being absorbed. This notion is confirmed by the exclusive discoloration of faeces observed in the subacute study.

Metabolites identified:

no

Details on metabolites:

Acid Violet 50 proved to be inactive in the Ames-test with and without exogenous metabolic activation. It was not genotoxic in the HPRT and chromosomal aberration assay in vitro. This indicates that Acid Violet 50 is not metabolically active. Metabolites, if any are formed, are not more toxic than the parent compound.
No effects were seen in the subacute study except for a discoloration of intestinal content. No functional or structural impairments were detected. Therefore, Acid Violet 50 is considered to just pass through the intestinal tract without significant metabolism.

Conclusions:

Based on all available data, Acid Violet 50 does not exhibit conspicuous toxicokinetic behaviour in the sense of accumulative and/or delayed effects with regard to the individual parameters absorption, distribution, metabolism and excretion.
The results from studies with dermal exposure do not indicate that Acid Violet 50 has a definite dermal absorptive potential. Acid Violet 50 is not absorbed from the gastrointestinal tract in significant amounts.
Indications of an intense metabolism or a bio-accumulative potential do not exist as no acute nor delayed toxicity occurred. Additionally no increase in severity of systemic effects was observed in the subacute oral toxicity study, which also points to no bio-accumulation potential as well as to excretion of Acid Violet 50 and/or metabolites.

Executive summary:

Based on the available data on Acid Violet 50 relevant information exists to make a qualitative evaluation of the toxicokinetic profile of this compound. This is in line with animal welfare considerations because additional animal tests are avoided by such an evaluation.

 

The results of basic toxicity testing give no reason to anticipate unusual characteristics with regard to the toxicokinetics of Acid Violet 50. The data indicate that there is no relevant dermal absorption. Acid Violet 50 is not absorbed from the gastro-intestinal tract or through skin in toxicologically significant amounts. Indications of a bio-accumulative potential as well as a metabolism towards genotoxic sub-structures do not exist. Excretion of systemically available Acid Violet 50 and/or potential metabolites via the kidney can be assumed.

Description of key information

There are no indications that the test item is significantly absorped from the digestive tract or through skin. Consequently, neither distribution, metabolism nor excretion are expected.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential