Reactionmass of octan-2-yl prop-2-enoate and octan-3-yl prop-2-enoate and octan-4-yl prop-2-enoate

Genetic toxicity: in vivo

Administrative data

Endpoint:

genetic toxicity in vivo, other

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING

A dubious result was obtained in the chromosomal aberration study conducted with the source substance (IOA) where a response indicating a possible interaction with DNA was only identified at a single, cytotoxic (50%) dose level with a 48 hour exposure without metabolic activation. All other dose levels, exposure lengths and metabolic activation combinations were negative for clastogenicity.

In general, substances containing acrylate functional groups have been documented to exert a cytotoxic, non-genotoxic mechanism of action in in vitro genotoxicity/mutageniciy assays. This is illustrated in the review article "A review of the genotoxic, mutagenic, and carcinogenic potentials of several lower acrylates" (Suh et al., 2018) which highlights positive responses with a variety of lower molecular weight acrylates solely at cytotoxic doses. In cases where a positive response was observed in an in vitro chromosome aberration study, follow-up in vivo testing was negative, supporting the cytotoxicity rather than genotoxicity mechanism of action. The authors concluded: "Toxicokinetic data demonstrate that these acrylates are metabolized rapidly by carboxylesterase hydrolysis and conjugation with glutathione. Overall, the genotoxicity and mutagenicity data support a cytotoxic, non-genotoxic mechanism for these acrylates." (Suh et al., 2018)

Additionally, higher molecular weight acrylates like EC 947-818-2 (REACH registered, dossier submitter is the owner of EC 947-818-2 data) were found to be negative in a bacterial reverse mutation assay, chromosome aberration study and mouse lymphoma assay further supporting the non-genotoxic effects for acrylates.

Against this background and in conformity with ECHA's principle of avoiding unnecessary animal testing, it is considered unnecessary to perform an in vivo genotoxicity/mutagenicity study.

Supporting References:

Suh, M, Proctor, D, Chappell, G, Rager, J, Thompson, C, Borghoff, S, Finch, L, Ellis-Hutchings, R, Wiench, K (2018) A review of the genotoxic, mutagenic, and carcinogenic potential os several lower acrylates. Toxicology 402-403:50-67.

REACH Registration of EC 947-818-2.

Materials and methods

Test material

Test material information

1

Reference substance name:

Reactionmass of octan-2-yl prop-2-enoate and octan-3-yl prop-2-enoate and octan-4-yl prop-2-enoate

EC Number:

947-155-9

Molecular formula:

C11H20O2

IUPAC Name:

Reactionmass of octan-2-yl prop-2-enoate and octan-3-yl prop-2-enoate and octan-4-yl prop-2-enoate

Test material form:

liquid