title: Safety evaluation of nuclease P1 from Penicillium citrinum.
abstract: Nuclease P1 has been widely used in the food industry to enhance or create flavor. One commercial source of this enzyme is Penicillium citrinum, an anamorphic mesophilic fungus with a long history of safe use in Europe and Asia as a fermentation organism used in the production of ribonucleases. Given the intended use in food for human consumption, and noting its potential presence at trace levels in finished products, a series of safety studies including an in vitro Ames and chromosome aberration assay, an in vivo rat erythrocyte micronucleus assay and a 90-day oral toxicity study in rats were conducted. No mutagenic activity was observed in the Ames assay. Equivocal activity in the chromosome aberration assay was not replicated in the micronucleus assay at doses of up to 1007 mg total organic solids (TOS)/kg body weight (bw)/day. Following oral administration of nuclease P1 at dosages of 10.1, 101 or 1007 mg TOS/kg bw/day to Sprague-Dawley rats, no adverse effects on any study parameter were observed. The no-observed-adverse-effect level was considered to be 1007 mg TOS/kg bw/day. The results of the genotoxicity studies and subchronic rat study support the safe use in food production of nuclease P1 produced from P. citrinum.
authors.affiliation: Shin Nihon Chemical Co., Ltd., 19-10 Showa-cho, Anjyo, Aichi 446-0063, Japan. Electronic address: nokado@snc-enzymes.co.jp.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Okado
authors.affiliation: Biosafety Research Center, Foods, Drugs, and Pesticides, 582-2, Shioshinden, Iwata, Shizuoka 437-1213, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Biosafety Research Center, Foods, Drugs, and Pesticides, 582-2, Shioshinden, Iwata, Shizuoka 437-1213, Japan.
authors.forename: Fukutaro
authors.initials: F
authors.lastname: Mizuhashi
authors.affiliation: Intertek Scientific and Regulatory Consultancy, 2233 Argentia Road, Suite 201, Mississauga, Ontario L5N 2X7, Canada.
authors.forename: Barry S
authors.initials: BS
authors.lastname: Lynch
authors.affiliation: Intertek Scientific and Regulatory Consultancy, 2233 Argentia Road, Suite 201, Mississauga, Ontario L5N 2X7, Canada.
authors.forename: Trung D
authors.initials: TD
authors.lastname: Vo
authors.affiliation: Intertek Scientific and Regulatory Consultancy, 2233 Argentia Road, Suite 201, Mississauga, Ontario L5N 2X7, Canada.
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Roberts
mesh_terms: D000818:Animals; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005260:Female; D005656:Fungal Proteins / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D010407:Penicillium / Q000201:enzymology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D005656:Fungal Proteins; C526100:Nuclease P1, Penicillium citrinum; D015719:Single-Strand Specific DNA and RNA Endonucleases
keywords: Food; Genotoxicity; Nuclease P1; Penicillium citrinum; Safety; Subchronic toxicity