methyl acrylate; methyl propenoate

Endpoint summary

Additional information

Methyl acrylate is readily absorbed by the oral, dermal and inhalation routes and the major portion is rapidly (1) hydrolyzed by carboxyesterases to acrylic acid and methanol and/or (2) conjugated with glutathione. In vivo, greater than 90 % is excreted within 72 hours, primarily via the lungs (> 50 %) as CO₂, and kidneys (40-50 %) as products of methyl acrylate-glutathione conjugation. In vitro tests using rat liver microsomes, Methyl Acrylate hydrolyzed to form the metabolite acrylic acid (AA) with a half-life of less than 8.5 minutes.  In whole rat blood in vitro, MA quickly metabolized, shown by a significant and (nearly) complete loss of the parent acrylate. Based on the measured concentrations of the remaning parent acrylate, the half-life value for MA was less than 12 minutes in rat blood.  MA formed a single GSH conjugate in the presence of GST. 

Dermal absorption is somewhat slower and appears to follow irritation of the skin, possibly reflecting an initial de-esterification, with subsequent absorption of the acrylic acid formed.

Discussion on bioaccumulation potential result:

Methyl acrylate is rapidly absorbed by the oral and inhalation routes and distributed throughout the body. After oral or intraperitoneal administration, greater than 90 % is excreted within 72 hours, primarily via the lungs as carbon dioxide (> 50 %), and kidneys as products of glutathione conjugation reactions (10-50 %) (Delbressine 1981, Sapota 1988 & 1990, Seutter 1981). The predominant pathway of metabolism of methyl acrylate, by many tissues (including lung, liver, kidney and plasma) appears to be hydrolysis to acrylic acid and methanol, which is catalyzed by carboxyl esterase enzymes. Thus, under normal circumstances, a relatively small amount of the intact ester is absorbed into the blood through the lungs. The subsequent metabolism will follow that for acrylic acid, and involves metabolism to carbon dioxide via the propionate degradation pathway (acrylic acid --> 3-hydroxypropionic acid --> malonyl semialdehyde --> acetyl S CoA --> --> tricarboxylic acid cycle --> --> CO₂). Metabolism of methanol proceeds via a catalase peroxidative pathway or alcohol dehydrogenase pathway. Intact methyl acrylate, which reaches the blood, is detoxified by hydrolysis, as well as by conjugation (by Michael addition) with glutathione (GSH) to form thioethers. The conjugates are then converted to mercapturic acids and excreted in the urine. The main conjugate has been identified as N-acetyl-S-(2-carboxyethyl)cysteine. Inhibition of the hydrolytic pathway with carboxylase inhibitor results in increased metabolism via the GSH conjugation route (Silver 1981, Miller 1981). There is no evidence to suggest that the vinyl moiety undergoes epoxidation in vivo (Delbressine 1981).

Discussion on absorption rate:

Administration of 14C-methyl acrylate to the skin of guinea pigs under occlusive conditions led to severe irritation, i.e. edema and necrosis, confirmed histologically. The test compound penetrated slowly through epidermis and dermis. A large part of the labeled acrylate was retained in the dermis (Seutter and Rijntjes, 1981).

Autoradiography showed that metabolism of a locally administered dose was practically limited to the skin in the first 24 h; subsequently, labeled material was transported by the blood to the kidneys and concentrated in the bladder, whereas other organs showed a slowly rising concentration (Delbressine, 1979).