Safety evaluation of phosphodiesterase produced from Penicillium citrinum: summary of toxicological data.
The toxicity of Enzyme RP-1, an enzyme preparation used to hydrolyze yeast RNA to produce flavor enhancers for use in the food industry, was evaluated in a series of studies. A 5-week dietary toxicity study in Wistar rats was conducted in which animals received Enzyme RP-1 in feed at concentrations of 0, 500, 2000, or 8000 mg/kg body wt/day. A 13-week dietary toxicity study in Sprague-Dawley rats was conducted in which animals received RP-1 concentrate at 0, 0.125, 0.5, or 2% in their diets. At the highest dose levels in both studies, submandibular glands in the oral cavity were enlarged, an effect attributed to protease activity of the enzyme preparation. The no-observed-effect level in rats in the 13-week study was 0.5%, equivalent to 317 mg/kg body wt/day for males and 346 mg/kg body wt/day for females. Based on estimated dietary exposure to the enzyme preparation, the margin of exposure is estimated to be greater than 38,000. Lack of genotoxic potential was demonstrated by an in vitro reverse mutation assay in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 and in Escherichia coli strain WP2uvr and by an in vitro chromosome aberration test in CHL/IU cells derived from fibroblasts from the lungs of Chinese hamsters. Finally, the particular strain of Penicillium citrinum, the fungal strain used to prepare Enzyme RP-1, was shown to have low pathogenicity upon a single injection into the tail vein of rats of viable spores at doses up to 2.8x10(5) colony-forming units per animal. The results of these studies demonstrate that the enzyme preparation may be considered safe to workers and consumers when employed in the production of flavor enhancers from yeast.
Safety Assessment Department, Amano Pharmaceutical Co., Ltd., Kunotsubo, Nishiharu-cho, Nishikasugai-gun, Aichi-ken, 481-8543, Japan.
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Kondo
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Nishimura
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Tanaka
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Flood
D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004722:Endoribonucleases / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D029968:Escherichia coli Proteins; D005260:Female; D005421:Flavoring Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D019649:Food Industry; D008297:Male; D010407:Penicillium / Q000201:enzymology*; D016337:RNA, Catalytic / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D043262:Ribonuclease P
D029968:Escherichia coli Proteins; D005421:Flavoring Agents; D016337:RNA, Catalytic; D004722:Endoribonucleases; D043262:Ribonuclease P; C470865:ribonuclease P, E coli