Registration Dossier

Diss Factsheets

Environmental fate & pathways

Endpoint summary

Administrative data

Description of key information

Additional information

Isooctyl acrylate (IOA) is a UVCB material. In an HPLC study designed to estimate the octanol-water partition coefficient, nine peaks having a range of partition coefficients of 4.0 to 5.0 were reported, with major peaks (those contributing ≥5% of total peak area) having a range of 4.5-4.7. The constituents of IOA therefore have partition coefficients in the range of chemicals having a potential to bioaccumulate. No experimental studies of bioconcentration of IOA have been done. In a QSAR analysis using Catalogic software v.5.10.9, BCF values ranging from 120 to 940 were predicted. The BCF base-line model within Catalogic software functions by first converting log Kow to a baseline bioconcentration value. This baseline BCF sets an upper limit for bioconcentration without consideration of in vivo transformations or other factors; it is therefore overly conservative with respect to bioconcentration. The baseline BCF is then adjusted by adding factors for metabolism, a conformation-based calculation of molecular size, water solubility, and presence of phenolic or acidic moieties (the last two factors are not relevant to IOA). The impact of these corrections is to reduce calculated BCF from the baseline level to one more in keeping with the structure’s reactivity and physicochemical characteristics.  The accuracy of the correction depends on the model’s ability to assess the factors for the chemical of interest. With respect to IOA, the correction for in vivo transformations is based on predicted metabolic pathways for acrylate esters that proceed by one or two processes: epoxidation of the 2,3-unsaturated bond of the acrylate moiety for all acrylate esters, and hydroxylation of the branched carbon atom of the alcohol moiety in the case of terminally-branched esters. Both of these transitions are at fairly low probabilities (P-to metabolise ca. 0.3). The proposed pathway is incomplete. An extensive amount of research exists in the literature on the metabolism of acrylate esters by mammalian enzymatic systems, both in vivo and in vitro. The most favorable reaction pathways are by hydrolases, forming acrylic acid and the corresponding alcohol, and by Michael 1,4-addition to glutathione and other protein sulfhydryls, ultimately forming N-acetylcysteine (mercapturic acid) conjugates. None of the metabolites possess a hydroxyl group which would indicate that the unsaturated bond had been converted into an epoxide(1,2). Further, while the model does not consider hydrolysis of acrylate esters, it contains a specific hydrolytic transformation form ethacrylate esters at a high probability (P=0.985) of reaction. The training set for the log BCF model includes 2-ethylhexyl methacrylate (2-EHMA), which is the methacrylate analogue of a major component of IOA. The observed BCF for 2-EHMA is 37.2, while the predicted value is 29.1. Metabolism, as expected, is via ester hydrolysis and is nearly complete. As noted, hydrolysis of acrylate esters is not considered by the model. Therefore, the QSAR provides an extremely conservative estimate of bioconcentration potential for IOA. Nevertheless, predicted BCF values remain less than 1000.

As noted, metabolism of acrylate esters in mammals is well studied. Acrylate esters are readily absorbed by the gastrointestinal mucosa and respiratory tract of mammals. In inhalation exposure, 50-65% of the dose was absorbed by the upper respiratory tract rather than the lungs(1). Uptake of acrylates by aquatic organisms is likely to be at least as efficient as respiratory exposure in mammals. Metabolism of acrylates by mammals is extremely rapid. Initial transformation of acrylates occurs via two pathways, hydrolysis of the ester bond or addition of the acrylic moiety to gluthatione(1). However, experiments with ethyl acrylate and butyl acrylate(2) and methyl acrylate, methyl methacrylate and methyl crotonate(3) suggest that glutathione addition contributes less significantly to overall metabolism with either increasing steric hindrance at the olefinic center or with increasing molecular weight. The hydrolysis products, acrylic acid and an alcohol, are metabolized by normal cellular metabolism. Metabolism of acrylate esters is extensive and rapid. In a radiometric study, approximately 60% of the total oral dose of ethyl acrylates was recovered, mostly as carbon dioxide, within 8 hours.(1) Approximately 50% of absorbed ethyl acrylate was hydrolyzed by esterases within the nasal mucosa before entering the general circulation.(1) The remaining intact ethyl acrylate is hydrolyzed by esterase activity distributed throughout the body. Isolated rat liver homogenates were able to hydrolyze ethyl acrylate with an estimated half-life of two seconds (estimated from Km and Vmax values); lung homogenates had similar Km and Vmax values(4). While toxicity studies of acrylate esters in fish have been conducted, we could find no corresponding studies regarding acrylate metabolism in fish. In general, mammals tend to have a metabolic capacity/rate one order of magnitude higher than fish(5). Given the rapidity with which mammals detoxify and eliminate acrylate esters, metabolism in fish is likely to control bioaccumulation. Therefore, due to predicted rapid detoxification and elimination, it should be unnecessary to conduct additional bioconcentration tests with fish.

1)   J.E. McLaughlin, R.C. Baldwin, and J.M. Smith. Ethyl acrylate health affects assessment. In, Health Effect Assessments of the Basic Acrylates, T.R. Tyler, S. R. Murphy, E. K. Hunt,eds. CRC Press, 1993.


2)   I. Linhart, M. Vosmanská and J. Šmejkal. Biotransformation of acrylates. Excretion of mercapturic acids and changes in urinary carboxylic acid profile in rat dosed with ethyl and 1-butyl acrylate. Xenobiotica 1994, Vol. 24, No. 10, pp. 1043-1052


3)   L. P. C. Delbressine, F. Seutter-Berlage, and E. Seutter. Identification of urinary mercapturic acids formed from acrylate, methacrylate and crotonate in the rat. Xenobiotica, 1981, Vol. 11, No. 4, pp. 241-247


4)   C.B. Frederick, D.W. Potter, M.Chang-Mateu, and M.E. Andersen. A physiologically based pharmacokinetic and pharmacodynamic model to describe the oral dosing of rats with ethyl acrylate and its implications for risk assessment. Toxicol. Appl. Pharmacol. 1992 Vol. 114, pp. 246-260.


5)   European Chemicals Agency. 2008. Guidance on information requirements and chemical safety assessment: Chapter R.7c: Endpoint specific guidance