Reactionmass of dodecan-2-yl prop-2-enoate and dodecan-3-yl prop-2-enoate and dodecan-4-yl prop-2-enoate

Endpoint summary

Additional information

Bioconcentration testing is not a required test at this annual volume under REACH. Information on bioconcentration was developed for other regulatory regimes. In a feasibility study, MTDID 44430 could not be stably maintained using the static exposure system available to the contract research organization engaged for testing under GLP criteria. QSAR modeling using OASIS LMC Catalogic software gave estimated BCF values of 32 - 33. This QSAR has been validated and is applicable to the class of acrylates.

A substantial set of data on metabolism of acrylate esters exists in the mammalian toxicology literature. Acrylate esters readily cross the gastrointestinal mucosa, after which they are delivered directly to the liver. In addition, acrylate esters are readily absorbed by the mucosa of the respiratory tract of mammals. In inhalation exposure, 50-65% of an ethyl acrylate dose was absorbed by the upper respiratory tract rather than the lungs (1). Uptake of acrylates by the gills of aquatic organisms is likely to be at least as efficient as respiratory exposure in mammals.

Extensive uptake of acrylates by mammals is mitigated by favorable detoxification. Conversion of acrylates occurs via two pathways: by enzymatic hydrolysis of the ester bond (with the acid and alcohol catabolized by normal cellular pathways) or by Michael 1,4-addition of the acrylic moiety to gluthatione (GSH) and other protein sulfhydryls (with the GSH-adduct converted enzymatically to a mercapturic acid adduct for urinary excretion) (1,2). Of the two, the hydrolytic pathway is most likely for MTDID 44430. The contribution of the glutathione pathway to overall metabolism of butyl acrylate was less than with ethyl acrylate (1.6-3.6% v. 11%, respectively) (3) or with methyl acrylate (6.6% of an interperitoneal dose) (4). Only 2% of 2-ethylhexyl acrylate labelled on the vinyl carbons was recovered as thioethers in the first 5 hours post-treatment (5). Mercapturic adducts of methyl methacrylate (2-methylacrylate) were not observed at all unless carboxylesterases were first inhibited by tri-o-tolyl phosphate, and methyl crotonate (3-methylacrylate) formed mercapturates at an intermediate level (4). Taken together, the results suggest that the glutathione reaction contributes less significantly to overall detoxification for sterically-hindered acrylates, or for acrylates with increasing molecular weight.

Transformation of acrylate esters is extremely rapid. In the study of 2-ethylhexyl acrylate, 50% of radioactivity was recovery as exhaled carbon dioxide in the first 24 hours (5). In a radiometric study of ethyl acrylate, approximately 60% of the total oral dose was recovered, mostly as carbon dioxide, within 9 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 was 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, and lung homogenates had similar Km and Vmax values (2). The hydrolysis products, acrylic acid and an alcohol, are metabolized by normal cellular metabolism: the propionate cycle in the case of acrylic acid and beta-oxidation for the alcohol. In general, mammals tend to have a metabolic capacity/rate one order of magnitude higher than fish (6). However, given the rapidity with which mammals detoxify and eliminate acrylate esters, metabolism in fish is also likely to control bioaccumulation. Therefore, due to predicted rapid detoxification and elimination, it should be unnecessary to conduct additional bioconcentration tests with fish.

References:

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, 1994

2) C.B. Frederick, D.W. Potter, M. I. 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.

3) 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.

4) 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.

5) I. Gut, P. Vodička, M. Cikrt, A Sapota, I Kavan. Distribution and elimination of (14C)-2-ethylhexyl acrylate radioactivity in rats. Arch. Toxicol. 1988, Vol. 62, No. 5, pp. 346-50.

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