title: Characterisation and toxicological assessment of Neutral Methacrylate Copolymer for GRAS evaluation.
abstract: Neutral Methacrylate Copolymer is a fully polymerised copolymer used in the pharmaceutical industry to permit pH-independent delayed release of active ingredients from oral dosage forms. This function has potential use with food supplements and this article describes available information on the safety of the substance. Oral administration of radiolabelled copolymer to rats resulted in the detection of chemically unchanged copolymer in the faeces, with negligible absorption. Safety studies revealed no adverse toxicity following repeated administration at doses of up to 2000 mg/kg bw/d in a sub-chronic study in rats or 250 mg/kg bw/d in a sub-chronic study in dogs. No reproductive toxicity occurred at up to 2000 mg/kg bw/d in rats or rabbits. The substance shows no evidence of genotoxicity, has low acute toxicity and no irritation or sensitisation potential. An ADI value of 20 mg/kg bw was concluded from two alternative approaches. Daily exposure from use in dietary supplements is estimated as up to 10.0 mg/kg bw in adults and 13.3 mg/kg bw in children. There would therefore appear to be no safety concerns under the intended conditions of use. The information provided is intended to support an evaluation that the substance may be "generally recognized as safe" (GRAS).
authors.affiliation: Evonik Industries AG, Kirschenallee, 64293 Darmstadt, Federal Republic of Germany. Electronic address: Johanna.Eisele@Evonik.com.
authors.forename: Johanna
authors.initials: J
authors.lastname: Eisele
authors.forename: Geoff
authors.initials: G
authors.lastname: Haynes
authors.forename: Knut
authors.initials: K
authors.lastname: Kreuzer
authors.forename: Tiana
authors.initials: T
authors.lastname: Rosamilia
mesh_terms: D000818:Animals; D003257:Consumer Product Safety; D004353:Drug Evaluation, Preclinical; D005079:Excipients / Q000737:chemistry / Q000633:toxicity*; D005503:Food Additives / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D008689:Methacrylates / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D008855:Microscopy, Electron, Scanning; D019055:No-Observed-Adverse-Effect Level; D011817:Rabbits; D051381:Rats; D013499:Surface Properties; D018675:Toxicity Tests / Q000379:methods
chemical_list: D005079:Excipients; D005503:Food Additives; D008689:Methacrylates; C492994:poly(ethyl acrylate-methyl methacrylate)
keywords: BCA; CAS; Chemical Abstract Service; Coating agent; DMEM; DMF; DMSO; DNFCS; Dulbecco’s Modified Eagle’s Medium; Dutch National Food Consumption Survey; EA; EC; EFSA; EUDRAGIT® NE; EUDRAGIT® NM; European Council; European Food Safety Authority; European Pharmacopoeia; Food additive; GLP; GPC; GRAS; Good Laboratory Practice; ICH; INCI; IUPAC; International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use; International Nomenclature for Cosmetic Ingredients; International Union of Pure and Applied Chemistry; JPE; Japanese Pharmaceutical Excipients; LD50; MMA; MNPCE; MOS; Mn; Mw; NMT; NOAEL; Neutral Methacrylate Copolymer; OECD; Organisation for Economic Co-operation and Development; PCE; Ph. Eur.; Polymer toxicity; RIVM; Rijksinstituut voor Volksgezondheid en Milieu; SCF; SEM; Safety; Scientific Committee on Food; TDI; TK; UK; US; USA; USP/NF; United Kingdom; United States; United States Pharmacopoeia/National Formulary; United States of America; average molecular weight by number; average molecular weight by weight; bicinchoninic acid; body weight; bw; dimethyl sulphoxide; drug master file; ethyl acrylate; gel permeation chromatography; generally recognised as safe; margin of safety; median lethal dose; methyl methacrylate; micronucleated polychromatic erythrocytes; no observed adverse effect level; not more than; polychromatic erythrocytes; scanning electron microscope; thymidine kinase locus; total daily intake