Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Alchisor CAL 145 comprises alkenes C13-14 hydroformylation products with read-across from the chemically-similar Alchisor CAL 123 as defined in the `Read-Across Justification Document'. Where toxicological data exist for Alchisor CAL 123, these are representative of the Alchisor CAL 145 substance.

In Vitro

In Vitro Bacterial Reverse Mutation Assay: Alkenes, C11 -12 hydroformylation products, distn. residues was tested for mutagenic activity in Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA100 and in Escherichia coli WP2uvrA according to OECD guideline 471and the European Commission Annex V Test Method B13 and B14.

Two independent tests were conducted in triplicate in the absence and presence of a metabolic activator (S9 mix). The first test was conducted by the direct plate incorporation method, while the second test was conducted by the pre-incubation method. The test item was dosed at concentrations ranging from 17 to 5000 µg/plate in both assays. No evidence of mutagenic activity was obtained with any strain in either test.

It was concluded that Alkenes, C11 -12, hydroformylation products, distn. residues was not mutagenic in strains of Salmonella typhimurium and Escherichia coli when tested in acetone in the absence and presence of metabolic activation. The test item was tested to the predetermined maximum of 5000 µg per plate, at which concentration toxicity was encountered. In addition, the test item was tested up to and beyond its limits of solubility in the test system.

In Vitro Mammalian Chromosome Aberration Test: Alkenes, C11 -12 hydroformylation products, distn. residues was assessed for clastogenic potential in an in vitro mammalian chromosome aberration test in Chinese hamster ovary cells. This reliable (Klimisch 1; Klimisch 2 when used for read-across) and GLP compliant study was conducted according to OECD 473 guidelines. All the cultures treated with the test item had levels of structural aberrations within the 95% confidence limits for a negative response. An extra assessment of polyploidy was carried out on the cultures treated in the absence of S9 mix and harvested at 48 h. All the cultures treated with alkenes, C11-12, hydroformylation products, distn. residues had levels of polyploidy within the 95% confidence limits for a negative response. Consequently it can be concluded that alkenes, C11-12, hydroformylation products, distn. residues was not clastogenic when tested with Chinese hamster ovary cells in vitro.

 

Mouse Lymphoma Mutation Study: Alkenes, C11-12, hydroformylation products, distn. residues (CAS No. 90622-27-8) were assayed for mutagenic potential in the mouse lymphoma L5178Y cell line. Tests were conducted both in the absence and in the presence of a metabolic activator (S9 mix). The study was designed to be consistent with ICH Guidelines, OECD Guideline No. 476 and EC Directive 2000/32/EC B.17. No evidence of mutagenic activity was obtained with alkenes, C11-12, hydroformylation products, distn. residues in either the absence or the presence of S9 mix when the exposure period was 4 h. All such assays satisfied the criteria required to demonstrate that results had been obtained at a sufficiently toxic concentration of test item. It is therefore concluded that alkenes, C11-12, hydroformylation products, distn. residues is not mutagenic in mouse lymphoma L5178Y cells, in either the absence or the presence of S9 mix, when tested in acetone at concentrations extending into the toxic range.

No mutagenic potential was reported for Alkenes, C11-12, hydroformylation products, distn. residues in a range of in vitro genotoxicity studies conducted according to REACH annex VII or VIII requirements.

In Vivo

In accordance with REACH regulation Annex IX 8.4 column 2; 'Appropriate in vivo mutagenicity studies shall be considered in case of a positive result in any of the genotoxicity studies in Annex VII or VIII.' No positive findings have been reported across the range of REACH Annex VII or VIII in vitro genotoxicity studies for alkenes, C11-12, hydroformylation products, distn residues. Consequently there is no mandatory requirement any in vivo genotoxicity studies to be presented in this dossier.

 

On the basis of available in vitro data no genotoxic potential has been identified for alkenes, C11-12, hydroformylation products, distn. residues.


Short description of key information:
In vitro: 3 in vitro genotoxicity studies have been conducted with alkenes, C11-12, hydroformylation products, distn residues. In a reliable (Klimisch 1; Klimisch 2 when used for read-across) GLP compliant bacterial reverse mutation assay conducted according to OECD 471 guidelines, alkenes, C11-12, hydroformylation products, distn residues were reported to be negative for mutagenic activity

A reliable (Klimisch 1; Klimisch 2 when used for read-across) GLP compliant in vitro mammalian chromosome aberration test (Klimisch 1; Klimisch 2 when used for read-across) conducted according to OECD 473 guidelines reported that the test item, alkenes, C11-12, hydroformylation products, distn residues was not clastogenic.

Furthermore in a reliable (Klimisch 1; Klimisch 2 when used for read-across) GLP compliant mouse lymphoma mutation study alkenes, C11-12, hydroformylation products, distn residues were reported to be negative (with and without metabolic activation) for mutagenic activity.

In Vivo: In accordance with REACH regulation Annex IX 8.4 column 2;
'Appropriate in vivo mutagenicity studies shall be considered in case of a positive result in any of the genotoxicity studies in Annex VII or VIII.'
No positive findings have been reported across the range of REACH Annex VII or VIII in vitro genotoxicity studies for alkenes, C11-12, hydroformylation products, distn residues. Consequently there is no mandatory requirement any in vivo genotoxicity studies to be presented in this dossier.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The negative results reported inin vitrogenotoxicity assays do not warrant the classification of Alchisor CAL 145 as a substance with genotoxic potential.Consequently Alchisor CAL 145 is not classified as a genotoxin under the new Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.