Characterisation and toxicological assessment of Neutral Methacrylate Copolymer for GRAS evaluation

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• 作者：Johanna Eisele ; Geoff Haynes ; Knut Kreuzer ; Tiana Rosamilia
• 关键词：BCA ; bicinchoninic acid ; bw ; body weight ; CAS ; Chemical Abstract Service ; DMEM ; Dulbecco&rsquo ; s Modified Eagle&rsquo ; s Medium ; DMF ; drug master file ; DMSO ; dimethyl sulphoxide ; DNFCS ; Dutch National Food Consumption Survey ; EA ; ethyl acrylate ; EC ; European Council ; EFSA ; European Food Safety Authority ; GLP ; Good Laboratory Practice ; GPC ; gel permeation chromatography ; GRAS ; generally recognised as safe ; ICH ; International Conference on Harmonisation of technical requirements for registration of
• 刊名：Regulatory Toxicology and Pharmacology
• 出版年：December, 2013
• 年：2013
• 卷：67
• 期：3
• 页码：392-408
• 全文大小：842 K

文摘

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 鈥済enerally recognized as safe鈥?(GRAS).