Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics, other
Remarks:
Expert Statement
Type of information:
other: Expert Statement
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Expert Statement, no study available

Data source

Reference
Reference Type:
other: Expert Statement
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Objective of study:
absorption
distribution
excretion
metabolism

Test material

Constituent 1
Reference substance name:
Carbonic acid disodium salt, reaction products with aniline, 4-nitrobenzenamine, p-phenylenediamine, sodium sulfide, sulfur and p-toluidine
EC Number:
290-904-3
EC Name:
Carbonic acid disodium salt, reaction products with aniline, 4-nitrobenzenamine, p-phenylenediamine, sodium sulfide, sulfur and p-toluidine
Cas Number:
90268-98-7
Molecular formula:
Molecular formula is not available
IUPAC Name:
Carbonic acid disodium salt, reaction products with aniline, 4-nitrobenzenamine, p-phenylenediamine, sodium sulfide, sulfur and p-toluidine
Test material form:
solid: particulate/powder
Details on test material:
Test item: Yellow 22
Appearance: ocher clay, solid
CAS No. 90268-98-7
EC No. 290-904-3
Storage: room temperature

Test animals

Details on test animals or test system and environmental conditions:
not applicable

Administration / exposure

Positive control reference chemical:
not applicable
Details on study design:
not applicable
Details on dosing and sampling:
not applicable
Statistics:
not applicable

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 2.81 mg/L does not favour absorption. Taken together, the physiochemical properties indicate that the substance is not bioavailable following the oral route. This assumption is confirmed by the results of acute and repeated dose oral toxicity studies (OECD 423, OECD 422 DRF and OECD 422 main study). No substance related effects or mortality were observed.
The volatility indicates whether a substance may be available for inhalation as a vapour. Volatility decreases with increased molecular weight. In particular due to the high molecular weight absorption of the test item 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, the 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 item has a water solubility of 2.81 mg/L, therefore not supporting dermal absorption.
Details on distribution in tissues:
In general, the smaller the molecule, the wider the distribution. Based on its molecular weight distribution (no fractions below 3460 Da) and the hydrophilicity (log Pow <-0.7) it is assumed, that if absorbed, the test substance is not widely distributed and that distribution is only within the aqueous compartment of the organism. Furthermore, an accumulation within adipose tissue can be excluded.
Details on excretion:
Leuco Sulfur Yellow 22 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, HPRT test and Chromosome Aberration test it can be assumed that the test substance is not enzymatically activated (toxified) during the metabolism as the metabolic activated test substance showed no higher toxicity compared to the test substance without metabolic activation. Furthermore, available data indicate that the test substance is not susceptible to hydrolysis. Therefore an unaltered passage of the parent substance through the stomach can be presumed.

Applicant's summary and conclusion

Conclusions:
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. The substance is excreted in faeces.
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, HPRT test and Chromosome Aberration test. Due to the size of the molecule and the poor water solubility excretion via feces is assumed.