Safety evaluation of certain food additives
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- Điều hướng trang này:
- BRANCHING GLYCOSYLTRANSFERASE FROM RHODOTHERMUS OBAMENSIS 5
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Toxicological studies Bacillus subtilis is a non-pathogenic and non-toxigenic bacterium that has been utilized as a source of enzymes used in food for many years. Toxicological studies were performed with branching glycosyltransferase using a representative batch (PPY 27209), which was produced according to the procedure used for commercial production. The liquid enzyme preparation used in the toxicological studies was a mixture of three preparations from fermentation sub- batches. The final preparation (specific gravity 1.065 g/ml) had an activity of 89 200 branching enzyme units (BEU) per gram and a TOS value of 7.3%. 2.2.1 Acute toxicity No information was available. 2.2.2 Short-term studies of toxicity In a study conducted in accordance with Organisation for Economic Co- operation and Development (OECD) Test Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents) and Good Laboratory Practice (GLP) requirements, a 10-ml aqueous suspension of branching glycosyltransferase (batch PPY 27209, BRANCHING GLYCOSYLTRANSFERASE FROM RHODOTHERMUS OBAMENSIS 5 activity 89 200 BEU/g) was administered daily at 0, 77, 256 or 769 mg TOS/kg body weight (bw) by gavage to groups of 20 Wistar WU [Crl:WI(WU), outbred] rats (10 per sex) for 13 weeks. Stability testing of the prepared preparations at weeks 1, 6 and 13 indicated that the enzyme activity was similar to that predicted. The experimental parameters determined were clinical signs, body weight, food and water consumption, neurobehavioural testing (WHO/International Programme on Chemical Safety functional observational battery), ophthalmic end-points, haematological parameters, clinical chemical end-points, gross and microscopic appearance, and organ weights. Blood for haematology and clinical chemistry was collected during necropsy from male rats on day 91 of treatment and from female rats on day 92. Ophthalmoscopy was performed before treatment in all rats and then only in the control and high-dose groups during the last week of treatment. All other measurements were performed on day 91/92 only. No treatment-related effects were observed for mortality, clinical signs, body weight gain, food and water consumption, clinical chemistry, neurobehavioural effects or ophthalmic end-points. A small, but statistically significant, reduction in the mean corpuscular haemoglobin concentration, which was observed only in high- dose males, was considered to have no toxicological significance, because it was not corroborated by other related haematological parameters, such as packed cell volume and haemoglobin concentration. A reduction in absolute and relative weights of the epididymides in low-dose and mid-dose males was considered to be unrelated to treatment because of the absence of any effects at a 3-fold higher dose. The slightly increased relative liver weight (5%) and reduced absolute brain weight (4%) in high-dose males together with the absence of corresponding histopathological lesions identified in these organs were not considered to be toxicologically relevant. In both sexes, macroscopic pathology and histopathology were unaffected by treatment. Overall, it can be concluded that no toxicologically relevant effects were seen in this 13-week study of general toxicity in rats when branching glycosyl- transferase was administered daily by gavage at doses up to 769 mg TOS/kg bw per day. This dose, the highest dose tested, was therefore taken to be the no- observed-adverse-effect level (NOAEL) (Appel & Van den Hoven, 2008). 2.2.3 Long-term studies of toxicity and carcinogenicity No information was available. 2.2.4 Genotoxicity The results of two studies of genotoxicity with branching glycosyltransferase (batch PPY 27209) are summarized in Table 1 . The first study was conducted in accordance with OECD Test Guideline 471 (Bacterial Reverse Mutation Test), whereas the second complied with OECD Test Guideline 487 (In Vitro Mammalian Cell Micronucleus Test; draft). Both studies were certified for compliance with GLP and quality assurance. tải về 1.44 Mb. Chia sẻ với bạn bè của bạn:
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