Registration Dossier

Administrative data

basic toxicokinetics, other
Type of information:
other: Expert Statement
Adequacy of study:
key study
Rationale for reliability incl. deficiencies:
other: Expert Statement, no study available

Data source

Reference Type:
other: Expert Statement
Report Date:

Materials and methods

Objective of study:
Test guideline
no guideline followed
GLP compliance:

Test material

Test material form:
Details on test material:
Test item: Leuco Sulfur Blue 13
Appearance: Bluish black, solid
CAS No: 12262-26-9

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Bioavailability via oral route is strongly linked to physico-chemical properties of the substance. Generally, oral absorption is favoured for molecular weights below 500 g/mol. Furthermore, a high water solubility of more than 100 mg/L enables the substance to readily dissolve in the gastrointestinal fluids, allowing direct uptake into the systemic circulation through aqueous pores or via carriage of the molecules across membranes with the bulk passage of water. The test item is an UVCB substance and does not have a defined molecular structure but consists of large molecules well above 500 g/mol. The water solubility of 0.95 mg/L does not favour absorption. Taken together, the physiochemical properties indicate that the test substance is not bioavailable following the oral route. This assumption is supported by the result of the acute toxicity study (OECD 423). No substance related effects and no coloraton of internal organs were observed.
The volatility indicates whether a substance may be available for inhalation as a vapour. Highly volatile substances are those with a boiling point below 50 °C and low volatile substances those with a boiling point above 150 °C. Furthermore, volatility decreases with increased molecular weight. The boiling point of the test substance was determined to be > 300 °C and >=90% of the test substance have a molecular weight exceeding 100000 g/mol. Based on this data a low vapour pressure is expected and absorption of Leuco Sulfur Blue 9 via inhalation route is not expected to occur.
Dermal uptake is favoured for substances with a molecular weight < 100 g/mol. The molecular weight of the substances is thus too large. In addition, substances must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Absorption is anticipated to be low to moderate if water solubility is between 1 and 100 mg/L. The test substance has a water solubility of 0.95 mg/L, therefore not supporting dermal absorption.
Details on distribution in tissues:
In general, the smaller the molecule, the wider the distribution. Due to the high molecular weight of the substance no wide distribution and limited to the aqueous compartment is expected if the subsance became systemically available. Due to the negative log Pow a bioaccumulation potential can be excluded.
Details on excretion:
The substance is most likely excreted via faeces due to its high molecular weight and its poor water solubility.

Metabolite characterisation studies

Details on metabolites:
The test substance is not expected to be bioavailable following oral, inhalative or dermal exposure. In case minor amounts become systemically bioavailable, a prediction of the metabolism is not possible as the test item is a UVCB substance with unknown structure. Based on the results of the Ames test and the HPRT and Chromosome Aberration test with the read acorss substance (Blue Sema, CAS No 1040873 -93 -5) it can be assumed that the test substance is not enzymatically activated (toxified) during the metabolism as the test substance showed no higher toxicity in the tests with metabolic activation system in comparison to the tests without metabolic activation.

Applicant's summary and conclusion

Due to the high molecular weight and low water solubility of the test substance no absorption is expected by the oral, inhalative or dermal route.
Executive summary:

Based on physicochemical characteristics (very high molecular weight, low water solubility) no absorption by the oral, inhalative or dermal route as well as no distribution of the test substance is expected. This assumption is further supported by the results of the acute oral toxicity study, revealing no substance related effects. In case minor amounts become systemically bioavailable, enzymatic activation (toxification) yielding in cytotoxic metabolites is not expected to occur as metabolic activation did not increase the toxicity of the test substance in an Ames test. Due to the size of the molecule and the poor water solubility excretion via feces is assumed.