Characterisation and toxicological assessment of Neutral Methacrylate Copolymer for GRAS evaluation.

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).

Characterisation and toxicological behaviour of Basic Methacrylate Copolymer for GRAS evaluation.

Basic Methacrylate Copolymer is a fully polymerised cationic copolymer with taste-masking and moisture protection properties. It is used as a pharmaceutical excipient and has potential use as a glazing/coating agent to solid food supplements. This article describes available information on the safety of the substance. Oral administration of radiolabelled copolymer to rats showed the major route of excretion to be via the faeces. Minor absorption may occur at <0.02%. Safety studies revealed no adverse toxicity following repeated administration at up to 2000 mg/kg/day in a sub-chronic study in the rat or 750 mg/kg/day in a sub-acute study in the dog. No reproductive toxicity occurred at up to 1000 mg/kg/day in the rat. The substance shows no evidence of genotoxicity, has low acute toxicity and no irritation or sensitisation potential. As per the FDA approach an ADI of 20 mg/kg bw can be concluded. Daily exposure from use as a food additive is estimated as up to 11.7 mg/kg bw in adults and 13.3 mg/kg bw in children. In view of the high molecular weight of the substance, its lack of absorption and its low toxicity profile, the ADI is deemed adequate.