(1-methyl-1,2-ethanediyl)bis[oxy(methyl-2,1-ethanediyl)] diacrylate

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Remarks:

Extensive review, compiling and assessing mutagenicity data of acrylate and methacrylate compounds in-vitro and in-vivo.

Data source

Reference

Reference Type:

publication

Title:

Mutagenicity assessment of acrylate and methacrylate compounds and implications for regulatory toxicology requirements

Author:

Johannsen FR, Vogt B, Waite M and Deskin R

Year:

2008

Bibliographic source:

Regul Toxicol Pharmacol 50 (3): 322-335

Materials and methods

Type of study / information:

Review

Principles of method if other than guideline:

Genotoxicity testing has been completed on many of the acrylates and methacrylates. In this paper, a summary of published mutagenicity results indicating that these compounds should be considered nonmutagenic in the whole animal is presented. The data clearly support the concept of a category for mutagenicity behavior for acrylates and methacrylates.

Test material

Test material information

Constituent 1

Reference substance name:

(1-methyl-1,2-ethanediyl)bis[oxy(methyl-2,1-ethanediyl)] diacrylate

EC Number:

256-032-2

EC Name:

(1-methyl-1,2-ethanediyl)bis[oxy(methyl-2,1-ethanediyl)] diacrylate

Cas Number:

42978-66-5

Molecular formula:

C15 H24 O6

IUPAC Name:

(1-methyl-1,2-ethanediyl)bis[oxy(methyl-2,1-ethanediyl)] diacrylate

Results and discussion

Any other information on results incl. tables

A substantial number of monofunctional and multifunctional acrylates and methacrylates have been tested using standard test methodology currently found in internationally accepted mutagenicity testing guidelines (OECD, 1997).

Acrylic acid, methacrylic acid and the vast majority of acrylates and methacrylates that have been tested are inactive in the bacterial reverse mutation assay, whether tested with or without metabolic activation in a series of standard Salmonella tester strains. An exception is GMA (glycidyl methacrylate), derived from glycidol which, as a member of the class of epoxides, is mutagenic in the bacterial reverse mutation assay (McCann et al., 1975). Positive responses reported with trimethylolpropane triacrylate (TMPTA) and trimethylolpropane trimethacrylate (TMPTMA) occurred in a single Salmonella tester strain (TA1535) only when a hamster liver metabolic activation system was used. Both were inactive in all Salmonella strains without metabolic activation and in TA1535 when a conventional rat liver metabolic activation system was used (NLM, 2006). While hamster liver homogenates are used to assess chemicals containing the azo moiety, no such structural alert is present in either of these chemicals. Thus, when compared to equivalent study designs used for other acrylates and methacrylates, TMPTA and TMPTMA should be considered inactive in the bacterial reverse mutation assay.

Results of mouse lymphoma testing on acrylic acid and monofunctional and multifunctional acrylates and methacrylates were as follows: Acrylic acid produced a positive response with and without metabolic activation. The response observed was considered relatively weak, in that less than tripling of the background mutation rate was reported. With the exception of iso-octyl acrylate, all acrylates and methacrylates tested were positive in the mouse lymphoma assay. With several of the acrylates, positive responses were characterized as modest (2- to 3-fold) mutational increases which occurred at cytotoxic dose levels where the Relative Total Growth (RTG) was less than 50% of control values.

A few short-term mammalian cell culture assays other than the mouse lymphoma assay have been used to identify the capability of several acrylates and methacrylates to affect gene mutational events. Two such assays which measure effects occurring at a particular gene (hgprt) locus have been used and include the Chinese Hamster ovary (CHO)/hgprt assay and the Chinese Hamster lung V79/hgprt assay. No evidence for induction of point mutations was observed in any of these tests in mammalian cell lines, although Schweikl and Schmaltz (1999) identified chromosomal effects in this system with triethylene glycol dimethacrylate (TEGDMA) and glycidyl methacrylate (Schweikl et al., 1998).

In vitro tests designed to either directly or indirectly measure chromosomal events involving chromosomal structure or number include the chromosomal aberration assay, using either Chinese Hamster ovary (CHO), Chinese hamster lung cells (CHL), human lymphocytes (HL) or even rat bone marrow cell cultures. Formation of micronuclei (presumably formed from broken or disjointed chromosomes) and a more indirect in vitro measure of chromosomal damage, the sister chromatid exchange (SCE) assay (signaling interference with the reciprocal interchanges of the two chromatid arms within a single chromosome) have also been used. Positive mutagenic responses were seen with acrylic acid itself and most other mono-and multifunctional acrylates and methacrylates tested for chromosome damage.

The results of two other in vitro assays, capable of broadly measuring cellular events affecting DNA, have also been reported. The unscheduled DNA synthesis assay in cultured mammalian cells is capable of measuring repair of DNA damage induced by a number of chemicals. The cell transformation assay, also conducted in mammalian cells, is designed to identify the earliest recognizable phenotype in the multi-step transformation process leading to neoplasia. For the few mono- and multifunctional acrylates tested in these assays, a consistent pattern of nonresponse was reported and results proved nongenotoxic (inactive) or equivocal.

There are results of in vivo tests available, either rat or mouse cytogenetics or mouse micronucleus assays which have been conducted with 18 acrylate and methacrylate esters and acrylic acid. Whether testing by the oral, dermal or inhalation exposure routes, no mutagenic response has been observed with acrylic acid or any of the mono- or multifunctional acrylates tested. With the exception of glycidyl methacrylate, which gave inconsistent responses when tested by two different dosing routes (IP and oral), the remaining mono- and multifunctional methacrylates were also inactive.