Irritation/Sensitization
Acrylic acid is corrosive to the skin and eye, while the esters are strong to moderate irritants. Esters exhibit a low but definable potential for dermal sensitization, while acrylic acid is not considered a sensitizer. If inhaled, the vapor of acrylic acid or the esters can also cause irritation to the mucous membranes of the respiratory tract.
Excerpt from ARTF Category Justification - The variable part of the category approach is the length or configuration of the side chain of the parent ester and the alcohol metabolite, as well as their impacts on physico-chemical properties and subsequent properties. Despite these variations, the available data support the similarity in skin sensitisation potency for all the acrylate esters within the category. MA, EA, nBA and 2EHA are skin sensitisers based on the LLNA, whereas AA is a non-sensitiser. Skin sensitisation potency of acrylate esters involves reaction with tissue nucleophiles via Michael addition on the electrophilic C of the a,β-unsaturated carboxyl group (Freidig et al., 1999; Greim et al., 1995; McCarthy et al., 1994; cited in Borak et al., 2011). The prototype for such reactions is conjugation with GSH, which occurs spontaneously and enzymatically, leading to formation of thioethers and mercapturic acids. Increased urinary excretion of thioethers and depletion of hepatocyte GSH have been documented following in vivo and in vitro exposures to acrylate esters (Delbressine et al., 1981; Elovaara et al., 1983; cited in Borak et al., 2011). The electrophilic reactivity of low-molecular-weight molecules, as reflected by their interactions with GSH and other nucleophiles, is an important aspect of their ability to act as sensitizers (Enoch et al., 2008, 2009, 2010; Roberts et al., 2007, 2008; Smith and Hotchkiss, 2001; cited in Borak et al., 2001). In skin sensitisation studies, a key early step in the process leading to sensitisation is the formation of covalent adducts with a carrier protein, thereby forming an antigenic hapten-protein complex (Natsch and Emter, 2008; Roberts et al., 2008; Roberts and Aptula, 2008; Smith and Hotchkiss, 2001; cited in Borak et al., 2011). The difference in the skin sensitisation potency between the acrylate esters and AA are due to the presence or absence of C=C double bond in their structures. Indeed, all the acrylate esters within the category are classified for skin sensitisation Category 1 (EU harmonised classification). A comparison of the LLNA results for acrylate esters within the category does not suggest a clear correlation between the side chain length and the level of skin sensitisation potency. However, the EC3 values are all within the range to warrant the skin sensitisation Category 1B (weak sensitisers). There is a data gap for skin sensitisation for iBA and tBA, which is assessed by a category-based read-across from a reliable Local Lymph Node Assay of nBA (LLNA; OECD Guideline 429; 2006). Overall, the read-across approach is applied with a high level of confidence.
In RAAF nomenclature, the read-across approach for this endpoint is described in scenario 4 (different compounds have qualitatively similar properties) and governed by AE 4.2 and 4.3 (common underlying mechanism, qualitative and quantitative aspects). Here, a common underlying mechanism is a direct electrophilic reaction of the intact ester.
For more information, see Category Justifcation Document for use under EU REACH.