Repeated Dose Toxicity
Acrylic acid and the acrylate esters demonstrate similar toxicity profiles in rats and mice via inhalation, dietary and/or dermal routes of administration in tests ranging from 28 days to 2 years.
No evidence of systemic toxicity was observed; effects seen in these studies are consistent with direct irritation effects.
Excerpt from ARTF Category Justification -The variable part of the category approach is the length and/or configuration of the side chain of the parent ester and the alcohol metabolite, as well as their impacts on physico-chemical properties and consequent biological properties. Despite these variations, the available data support a lack of systemic toxicity for all the category members across the tested species. The repeated dose toxicity studies are available for AA, MA, EA, nBA and 2EHA for the oral route. For the inhalation route, studies are available for all the category members except for iBA. The available repeated dose toxicity studies on the acrylate category members have dosing periods ranging from 28 days to 2 years. Results demonstrate similar effects in rats and mice via both the oral and inhalation routes. The most predominant effects are based on the irritant (local reactive) properties of this class of chemical, rather than on intrinsic potential to cause systemic toxicity. None of the studies available for the category members produced evidence of reproductive toxicity or carcinogenicity viewed as relevant to humans. These repeated dose toxicity studies have also reported a similar and common profile of target organs (i.e. a lack of systemic toxicity). Thus, the results of the collection of sub-chronic and chronic studies conducted on these substances are consistent and can be regarded as offering a true picture of repeated dose toxicity for the category. In order to fill the data-gap for iBA, a category based read-across is applied to the sub-chronic repeated dose toxicity studies available for oral and inhalation routes for nBA. Overall, the read-across approach is applied with a high level of confidence.
For this endpoint, the common primary metabolic pathway of the category members (i.e. common functional groups and rapid metabolism by ester cleavage leading to the common metabolite AA) is considered as the most relevant aspect of the category approach. Qualitatively, this aspect can be categorised as scenario 3 “(Bio) transformation to common compound(s)”, whereas AA is the toxicologically relevant metabolite for systemic effects.
For more information, see Category Justifcation Document for use under EU REACH.