Reaction mass of 5,5'-{(phenylmethanediyl)bis[benzene-4,1-diyl-diazene-2,1-diyl]}bis{1-[3-(dimethylamino)propyl]-4-methyl-6-oxo-3-(pyridinium-1-yl)-1,6-dihydropyridin-2-olate} hydrochloride and 5,5’-[3,4’-(phenylmethanediyl)diphenylene]bis(diazene-2,1-diyl)bis{1-[3-(dimethylamino)propyl]-4-methyl-6-oxo-3-(pyridinium-1-yl)-1,6-dihydropyridin-2-olate} hydrochloride

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: expert statement

Adequacy of study:

key study

Study period:

2011-01-17 to 2012-05-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study. Expert statement based on all study results available for target compound (substance registred) and source (analogue) chemical.

Data source

Reference

Reference Type:

other: expert statement

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

no guideline required

Deviations:

not applicable

Principles of method if other than guideline:

The Toxicokinetic Assessment is meant to fulfil the requirement as defined in the REGULATION (EC) No 1907/2006 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 18 December 2006 requests in Annex VIII, point 8.8.1:
"Assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information."

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Analogue substance

IUPAC Name:

Analogue substance

Radiolabelling:

no

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: no bioaccumulation based on expert statement evaluating the available data
Based on the available data there is no indication for a critical bioaccumulation potential of the registered substance.

Executive summary:

Data on the toxicokinetics of the registration substance are not available. However, toxicity data indicate that this compound and/or metabolites are absorbed from the gastro-intestinal tract following oral administration. Direct evidence in the form of plasma data is not available. Dermal absorption of the registration substance is expected to be low. This view of limited penetration is supported by the molecular weight (> 500) and a log Pow of about -1.4 at 23 °C, which is in line with appendix R.7.12-4 of the REACH endpoint guidance R.7. as well as by data from a dermal toxicity study which revealed no specific acute systemic toxicity at the limit doses of 2000 mg/kg body weight in rats. Due to the very low vapour pressure of the registration substance, inhalation is not a major exposure route of concern.

The systemic effects stated above indicate that the substance is distributed throughout the body after oral absorption. Due to the high water solubility and the low partition coefficient accumulation in fatty tissues is very unlikely.

As the compound features already high water solubility it is questionable whether it is extensively metabolised. The finding that urine and faeces were coloured yellow in the repeated dose study with the analogue substance support the conclusion that large amounts of the substance registered are not metabolised and excreted via urine and feces. Possible metabolic reactions are cleavage of the azo-group by azo-reductase, epoxidation of arenes, demethylation of tertiary amino groups and formation of quinone-type chemicals. A recently performed Ames test for azo-dyes with the substance registered (according to Prival modification, i.e. with Hamster S9) demonstrated a negative result. Therefore, there is no evidence for a reductive reconstruction of the azo-dye by bacteria. Phase-II-metabolism might include acetylation of amine groups, sulfatation or UDPglucuronidation of hydroxy/phenol-moieties. Metabolites generally would have high water solubility and thereby good characteristics for excretion.

As the substance registered is highly water soluble urinary excretion is most likely. Based on the available data there is no indication for a critical bioaccumulation potential of the substance registered.