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Description of key information

Key value for chemical safety assessment

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There are no experimental toxicokinetic data available for the substance and this statement is based on the available physico-chemical and toxicological data. This comprises inter alia studies on skin irritation/corrosion, eye irritation, skin sensitization, in vitro mutagenicity and acute and repeated dose oral toxicity. The assumption on toxicokinetics follows the procedure indicated in the “Guidance on information requirements and chemical safety assessment chapter R.7c” of the ECHA guidance document (version 3.0, June 2017).

Available physico-chemical information taken into account:

Physical appearance: Bayscript Blaukomonente TEA-Salz is a brown-violet, crystalline solid at 20°C and 1013 hPa.

Boiling point: A decomposition of the substance is observable at around 140°C. Therefore it was not feasible to determine a boiling point.

Particle size distribution: No data available

Molecular weight range: 871 - 1031 g/mol (UVCB)

Water solubility: Highly soluble. The substance is marketed as aqueous solution, therefore, it can be concluded that the substance has high water solubility.

Log Pow: The partition coefficient was estimated from QSAR calculations for the three main components and determined to be in the range of 1.82 - 3.72.

Vapor pressure: Anticipated to be low and estimated by QSAR for the three main components to be 0 Pa at 25 °C.

Estimation of oral absorption: Oral absorption can be assumed, based on the physico-chemical properties (soluble in water, log Pow for the three main components in the range favourable for absorption). A Combined Repeated Dose Toxicity and Reproductive/Developmental Toxicity Screening Study with the substance according to OECD guideline 422 resulted in several findings which were related to the colour of the test substance. The whole body and several organs of animals treated with 1000 mg/kg bw appeared discoloured. Coloured kidneys were observed starting at 100 mg/kg bw indicating the UVCB substance is already absorbed at this dose. This is further evidenced by purple/blue stained urine noticed after acute oral dosing of 300 mg/kg bw and higher.

Overall: oral absorption is assumed based on physicochemical properties and toxicological studies with oral exposure.

Estimation of dermal absorption: Dermal absorption is likely based on log Pow for the three main components in the range of 1.82 - 3.72 and on the good water solubility. On the other hand the relatively high molecular weight does not favour dermal uptake.

Other parameters relevant for dermal absorption: The substance is not irritating to the skin, thus it does not affect the skin barrier. Dermal uptake could not be demonstrated in a skin sensitization study (based on read across), since the substance showed no sensitising potential.

Estimation of absorption via inhalation: Vapor pressure is anticipated to be low and estimated by QSAR for the three main components to be negligible at 25 °C; no information on particle size distribution is available. No acute inhalation toxicity study is available to estimate potential absorption.

Overall: absorption by inhalation of aerosol or dust might be assumed but vapor pressure is low.

Overall estimation of absorption: Some absorption is anticipated by oral, dermal and inhalation route.

Estimation of distribution: Based on the log Pow (1.82 - 3.72) and the high water solubility it is likely that the substance will distribute into the body after being systemically available. This assumption is supported by the Combined Repeated Dose Toxicity and Reproductive/Developmental Toxicity Screening Study in which the whole body and several organs of animals treated with 1000 mg/kg bw/day appeared discoloured. Coloured kidneys were observed starting at 100 mg/kg bw indicating the UVCB substance is distributed into kidneys at this dose.

Estimation of accumulation: In general highly water soluble particles have a low potential to accumulate in tissue.

Estimation of metabolism: In vitro genotoxicity data do not indicate the generation of DNA-reactive metabolites due to hepatic biotransformation, since the substance revealed negative results in the available in vitro genotoxicity tests (Ames test, HPRT, MNT in vitro), conducted in the absence and in the presence of a metabolising system.

Estimation of excretion: Purple/blue stained urine and blue/purple/black stained feces were noted after a single dose of 300 and 2000 mg active ingredient/ kg bw (OECD TG 420), demonstrating that excretion via urine is possible. Furthermore, the kidney as the primary target organ (based on OECD TG 422) suggest a renal excretion pathway.