Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

According to Annex VIII (section 8.8) and ECHA guidance document on information requirements and chemical safety assessment - chapter R.7c (ECHA, 2017), assessment of the toxicokinetic behaviour of a substance can be derived from the relevant available information including physicochemical and toxicological properties.

The substance is a blue viscous liquid which has a low water solubility (< 100mg/L at 20°C), its log Pow was estimated to be – 0.1. The vapour pressure of the substance was considered to be largely lower than 10-3 Pa at 20 °C. No melting point was observed down to -100°C.

Acute oral and dermal toxicity studies were performed on the substance. Effects were recorded during the acute oral toxicity study leading to an LD 50 cut-off value of 500 mg/Kg bw. No systemic signs related to the dermal administration of the test item were observed.

Corrosion and irritation studies carried out with the substance gave positive results with a resulting classification as Skin irritant cat. 2 and Eye irritant cat. 2. LLNA test came back positive leading to a classification as Skin sensitizer cat. 1B.

No mutagenicity was observed in an Ames test. In the L5178Y mouse lymphoma assay using the TK gene, a clear genotoxic activity of solutions of test item was observed in the presence of metabolic activation. Results of the in vitro chromosomal aberrations test on human lymphocytes also indicated a clear clastogenic activity of solutions of test item with metabolic activation and after a 20-hour long-term treatment without metabolic activation. Follow-up in-vivo study was conducted: in an in vivo mammalian erythrocytes micronucleus test performed in rat bone marrow combined to the in vivo mammalian alkaline Comet assay on liver, glandular stomach, duodenum and gonadal cells, the substance induced no genotoxic activity.

An OECD 422 study was conducted on the substance with rats: subchronic exposure to the substance did not cause any toxic effects in rats up to the highest dose tested, ie. 300 mg/Kg bw.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Absorption

Oral

Generally, the smaller the molecule the more easily it may be taken up. Molecular weights below 500 are favourable for absorption whereas molecular weights above 1000 do not favour absorption. Molecular weight of the substance is > 125 000 g/mol. Therefore, the absorption via oral route is not likely based on molecular weight.

However, there were toxic effects observed in an acute oral toxicity study with rats leading to an LD 50 cut-off value of 500 mg/Kg bw, showing that absorption via oral route occurs.

The substance is also a molybdenum-based substance. Based on numerous publications, Molybdenum absorption through the gastrointestinal occurs rapidly and almost completely (approx. 90% when given in water to fasted individuals), with little variation in absorption despite large variations in dose.

Dermal

Molecular weight of the substance is > 125 000 g/mol. Molecular weight less than 100 favours dermal uptake whereas above 500 the molecule may be too large. Therefore, a dermal absorption of the substance is unlikely having regards to the molecular weight only.

However, in-vitro skin irritation/corrosion studies showed that the substance is irritant for the skin and the eyes. As a consequence, an enhanced penetration of the substance due to damage to the skin surface is not excluded.

Skin sensitization study carried out also on the target substance came back positive, confirming that some dermal update occurs although it may only be a small fraction of the applied dose.

Inhalation

Absorption via inhalation route is not anticipated taking into account the vapour pressure of the substance and the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Distribution and Accumulation

In general, the smaller the molecule, the wider the distribution. The substance being a large macromolecule, the distribution in the tissues is not expected to be wide.

It is also unlikely that the molecule will diffuse through aqueous channels and pores due to its low water solubility (< 100 mg/L).

Metabolism

Evidence for differences in toxic potencies due to metabolic changes can be derived for instance from in vitro genotoxicity tests conducted with or without metabolic activation.

No effects with the substance were observed in a bacterial reverse mutation assay, indicating no reactivity of the substance or its metabolites under the test conditions.

In the L5178Y mouse lymphoma assay using the TK gene, a clear genotoxic activity of solutions of test item was observed in the presence of metabolic activation. Results of the in vitro chromosomal aberrations test on human lymphocytes also indicated a clear clastogenic activity of solutions of test item with metabolic activation and after a 20-hour long-term treatment without metabolic activation.

The substance however induced no genotoxic activity under the experimental conditions of an in-vivo micronucleus test combined with a Comet assay.

Excretion

Properties of the substance (molecular weight, water solubility) are not favourable for urinary excretion. Biliary excretion is more likely based on molecular weight.

Reference

Guidance on Information Requirements and Chemical Safety Assessment - Chapter R.7c - Endpoint specific guidance - version 3.0 from June 2017 (ECHA).