A review of the genotoxic, mutagenic, and carcinogenic potentials of several lower acrylates

Abstract

Lower alkyl acrylate monomers include methyl-, ethyl-, n-butyl-, and 2-ethylhexyl acrylate. These acrylates are used in the manufacture of acrylic polymers and copolymers for plastics, food packaging, adhesives, and cosmetic formulations. Although there is limited potential for human environmental exposure, occupational exposure can occur via inhalation and dermal contact. Recently, new genotoxicity data have been generated, along with in silico and in vitro read-cross analyses, for these acrylates. The availability of high-throughput screening (HTS) data through the ToxCast™/Tox21 databases allows for consideration of computational toxicology and organization of these data according to the ten key characteristics of carcinogens. Therefore, we conducted a comprehensive review to evaluate the mechanistic, toxicokinetic, animal, and human data, including HTS data, for characterizing the potential carcinogenicity, mutagenicity, and genotoxicity of these acrylates. Toxicokinetic data demonstrate that these acrylates are metabolized rapidly by carboxylesterase hydrolysis and conjugation with glutathione. HTS data demonstrated an overall lack of bioactivity in cancer-related pathways. Overall, the genotoxicity and mutagenicity data support a cytotoxic, non-genotoxic mechanism for these acrylates. Cancer bioassay studies conducted by the oral, dermal, and inhalation routes in animal models with these acrylates did not show any increase in tumor incidence, with two exceptions. At high doses, and secondary to chronic site-of-contact irritation and corrosion, rodent forestomach tumors were induced by oral gavage dosing with ethyl acrylate, and skin tumors were observed following chronic dermal dosing with 2-ethylhexyl acrylate in C3H/HeJ inbred mice (a strain with deficiencies in wound healing), but not in the outbred NMRI strain. For both dermal and forestomach cancers, tumorigenesis is secondary to high doses and long-term tissue damage, shown to be reversible. With evidence that these chemicals are not genotoxic, and that they cause forestomach and dermal tumors through chronic irritation and regenerative proliferation mechanisms, these acrylates are unlikely to pose a human cancer hazard.

Radiation-Induced Graft Immobilization (RIGI): Covalent Binding of Non-Vinyl Compounds on Polymer Membranes

“…Advantages include a high density of functiona groups due to side-chain formation [42]. Disadvantages include the restriction to polymer izable monomers, mostly vinyl compounds such as acrylates, allyls, and styrenics [27 Many of these substances are known to have environmental [43] and aquatic toxicity [44 cytotoxicity [45], and allergenic properties [46], requiring additional purification steps t remove the unreacted monomer.…”

Engineering a naturally-derived adhesive and conductive cardiopatch

“…While different alternatives such as medical grade cyanoacrylates [32] and other bioadhesives [33][34][35] have been developed to adhere these patches on the heart, many of these approaches are associated with cytotoxicity and high stiffness (e.g cyanoacrylates), low adhesion and structural stability (e.g. fibrin-based bioadhesives), as well as failure to provide a biomimetic environment that allows for tissue regeneration [12,[36][37][38]. Therefore, there is an unmet need for engineering highly biocompatible and electroconductive fibrous scaffolds, which can adhere strongly to the myocardium to facilitate biointegration without the need for suturing.…”

Recapitulating Tumorigenesis in vitro: Opportunities and Challenges of 3D Bioprinting

“…It has also spawned a billion-dollar industry that supports the increasing demands for speed, capacity, and cost-effective screening of vast libraries of compounds ( Pereira and Williams, 2007 ). The accessibility of HTS data merged with the ToxCast TM /Tox21 databases allows for elucidative toxicological considerations seen below ( Suh et al, 2018 ).…”