Toxicological assessment of Anionic Methacrylate Copolymer: I. Characterization, bioavailability and genotoxicity.
Anionic Methacrylate Copolymer (AMC) is a fully polymerized copolymer used in the pharmaceutical industry as an enteric/delayed-release coating to permit the pH-dependent release of active ingredients in the gastrointestinal tract from oral dosage forms. This function is of potential use for food supplements. Oral administration of radiolabeled copolymer to rats resulted in the detection of chemically unchanged copolymer in the feces, with negligible absorption (<0.1%). AMC is therefore determined not to be bioavailable. Within a genotoxicity test battery AMC did not show any evidence of genotoxicity in bacteria and mammalian cells. Furthermore, no genotoxic effects occurred in vivo within a micronucleus test. There would therefore appear to be no safety concerns under intended conditions of oral use for the discussed toxicological endpoints.
Evonik Nutrition & Care GmbH, Kirschenallee, 64293 Darmstadt, Federal Republic of Germany. Electronic address: Johanna.Eisele@evonik.com.
Johanna
J
Eisele
Haynes Safety Services Ltd, Oakridge, Quarry Lane, Gorsley, Ross-on-Wye, Herefordshire HR9 7SJ, England, UK. Electronic address: geoff.haynes@breatheconnect.com.
Geoff
G
Haynes
Evonik Nutrition & Care GmbH, Kirschenallee, 64293 Darmstadt, Federal Republic of Germany. Electronic address: Knut.Kreuzer@evonik.com.
Knut
K
Kreuzer
Evonik Nutrition & Care GmbH, Rodenbacher Chaussee 4, 63457 Hanau-Wolfgang, Federal Republic of Germany. Electronic address: Caroline.Hall@evonik.com.
Caroline
C
Hall
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D005243:Feces / Q000737:chemistry; D005260:Female; D065569:Gastrointestinal Absorption; D008297:Male; D008689:Methacrylates / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D016296:Mutagenesis; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D066007:Toxicokinetics
D005079:Excipients; D008689:Methacrylates; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer
Ames test; Anionic Methacrylate Copolymer; Chromosome aberration test; Coating agent; EUDRAGIT(®) FS; EUDRAGUARD(®); Food additive; Genotoxicity; Micronucleus assay; Mouse lymphoma assay