Kondo M, Nishimura S, Tanaka N, Flood M
Safety Assessment Department, Amano Pharmaceutical Co., Ltd., Kunotsubo, Nishiharu-cho, Nishikasugai-gun, Aichi-ken, 481-8543, Japan.
Regul Toxicol Pharmacol. 2001 Feb;33(1):2-11. doi: 10.1006/rtph.2000.1434.
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.
酶制剂RP - 1用于水解酵母RNA以生产食品工业中使用的风味增强剂，在一系列研究中对其毒性进行了评估。在Wistar大鼠中进行了一项为期5周的饮食毒性研究，动物在饲料中摄入浓度为0、500、2000或8000 mg/kg体重/天的酶制剂RP - 1。在Sprague - Dawley大鼠中进行了一项为期13周的饮食毒性研究，动物在其饮食中摄入0、0.125、0.5或2%的RP - 1浓缩物。在两项研究的最高剂量水平下，口腔中的下颌下腺肿大，这种效应归因于酶制剂的蛋白酶活性。13周研究中大鼠的无观察到效应水平为0.5%，相当于雄性为317 mg/kg体重/天，雌性为346 mg/kg体重/天。根据对酶制剂估计的饮食暴露量，暴露边际估计大于38,000。在鼠伤寒沙门氏菌菌株TA98、TA100、TA1535和TA1537以及大肠杆菌菌株WP2uvr中进行的体外反向突变试验，以及在中国仓鼠肺成纤维细胞衍生的CHL/IU细胞中进行的体外染色体畸变试验，均证明该酶制剂没有遗传毒性潜力。最后，用于制备酶制剂RP - 1的真菌菌株桔青霉的特定菌株，在以每只动物高达2.8×10(5)菌落形成单位的活孢子单次尾静脉注射到大鼠体内时，显示出低致病性。这些研究结果表明，当该酶制剂用于从酵母生产风味增强剂时，可认为对工人和消费者是安全的。
