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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics, other
Remarks:
Statement on Toxicokinetics
Type of information:
other: Statement on Toxicokinetics
Adequacy of study:
supporting study
Study period:
2013
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Objective of study:
other: Assumption on toxicokinetic following the procedure indicated in the “Guidance on information requirements and chemical safety assessment chapter R.7c” of the ECHA guidance document (version 1.1, November 2012).
Principles of method if other than guideline:
Assumption on toxicokinetic following the procedure indicated in the ECHA guidance R.7c (version 1.1, November 2012).
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Absorption is anticipated to be negligible / very low by oral, dermal and inhalation routes based on the physic-chemical properties: high molecular weight (740.31 < MW < 1232.98), low log Pow (calculated <-0.2) and slow solubility in water in an OECD TG 105 study with the saturation equilibrium not reached at 34 days.

Low absorption is confirmed by a 14 day oral gavage pilot study specifically designed to investigate potential compound uptake, distribution and excretion based on the intensive blue color of the compound.
Details on distribution in tissues:
Based on the low log Pow (<-0.2, calculated) and the slow solubility in water it is not likely that C.I. Direct Blue 264 distributes into cells. This assumption is supported by the 14 day pilot toxicity study in which no adverse effects were observed at the limit dose 1000 mg/kg bw/day. As indicated above blue color was seen only in the intestinal tract No other organ was colored blue. Furthermore, photometry of urinary samples gave no evidence that the test substance was excreted with the urine.
Based on the photometric urine analysis and the necropsy findings in this 14 day pilot study specifically designed to investigate potential compound uptake, distribution and excretion, no systemic absorption was observed.
Details on excretion:
Based on the low absorption potential of C.I. Direct Blue 264 excretion is anticipated mainly, if not exclusively, via the feces. This is supported by the 14 day pilot toxicity study. The only finding at clinical examinations was changed feces color, which was observed for all treated animals and is assumed to be due to the color of the test substance. Photometry of urinary samples gave no evidence that the test substance was excreted via urine.

Metabolite characterisation studies

Details on metabolites:
In vitro genotoxicity data do not indicate any genotoxic metabolites. C.I. Direct Blue 264 is not genotoxic in absence or presence of S9 extracts [Ames test, in-vitro micronucleus test and gene mutation assay in mammalian cells (HPRT)].

Applicant's summary and conclusion

Executive summary:

Absorption of C.I. Direct Blue 264 is assumed to be low via oral, dermal and inhalation routs based on physicochemical properties. This assumption is confirmed by a 14 day oral gavage pilot study specifically designed to investigate potential compound uptake, distribution and excretion based on the intensive blue color of the compound.

In this study no adverse effects were observed at the limit dose 1000 mg/kg bw/day.

Compound related blue color was seen only in the intestinal tract. No other organ was colored blue. Furthermore, photometry of urinary samples gave no evidence that the test substance was excreted with the urine.

Based on the photometric urine analysis and the necropsy findings in this 14 day pilot study systemic absorption of C.I. Direct Blue 264 is unlikely.