食品中遗传毒性致癌物风险评估方法研究
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摘要
目的研究目前国际上食品中遗传毒性致癌物风险评估方法,为建立我国遗传毒性致癌物风险评估技术体系提供方法学支持。方法收集目前国际上食品中遗传毒性致癌物风险评估方法的科研文章和指南文件,梳理、对比各种方法的优缺点及其适用范围,研究其中可为我国风险评估借鉴和参考的内容。结果目前国际上对食品中遗传毒性致癌物进行风险评估的主要方法包括尽可能低作用水平(ALARA),毒理学关注阈值(TTC),低剂量外推和暴露限值(MOE)。尽管ALARA原则容易理解,但是它不能给出任何一个风险程度的指导,所以不能为制定现实的风险管理建议提供可靠的依据。在致癌剂量-反应关系数据缺乏或不足的情况下,若符合毒理学关注阈值适用范围,可以采用毒理学关注阈值的方法进行筛选评估。当来自动物试验的致癌数据可用时,可以采用暴露限值法,也可采用低剂量外推的方法,但推荐优先采用暴露限值法。结论我国应在充分参与国际遗传毒性物质风险评估相关工作的基础上,深入开展遗传毒性物质基础研究,尽快建立遗传毒性物质风险评估技术体系。
Objective To investigate the current risk assessment approaches on genotoxic carcinogens in food,so as to provide methodology support for the establishment of genotoxic carcinogens risk assessment system in China. Methods The current reviews and guidelines for risk assessment approaches on genotoxic carcinogens in foods were collected and the advantages and disadvantages as well as the applicability of different methods were analyzed and compared,the content that could be used or referred for risk assessment in China were investigated. Results Currently,risk assessment approaches for genotoxic carcinogens include as low as reasonably achievable( ALARA),threshold of toxicological concern( TTC),low dose extrapolation of data from rodent carcinogenicity bioassays,and margin of exposure( MOE). Although ALARA principle is easy to understand,it fails to provide any guidance on measurement of risk level and thus is unable to provide reliable evidence to make practical risk management suggestions. TTC approach,within its range of application,can be used for screening assessment when there was lack of dose-response data. When there were sufficient dose-response data from animal studies,both MOE and low dose extrapolation approaches can be applied,yet MOE approach was preferred.Conclusion China should actively participate in international risk assessment for genotoxic carcinogens in food,develop in-depth scientific research into genotoxic carcinogens,and establish technical system for risk assessment of genotoxic carcinogens in food as soon as possible.
Objective To investigate the current risk assessment approaches on genotoxic carcinogens in food,so as to provide methodology support for the establishment of genotoxic carcinogens risk assessment system in China. Methods The current reviews and guidelines for risk assessment approaches on genotoxic carcinogens in foods were collected and the advantages and disadvantages as well as the applicability of different methods were analyzed and compared,the content that could be used or referred for risk assessment in China were investigated. Results Currently,risk assessment approaches for genotoxic carcinogens include as low as reasonably achievable( ALARA),threshold of toxicological concern( TTC),low dose extrapolation of data from rodent carcinogenicity bioassays,and margin of exposure( MOE). Although ALARA principle is easy to understand,it fails to provide any guidance on measurement of risk level and thus is unable to provide reliable evidence to make practical risk management suggestions. TTC approach,within its range of application,can be used for screening assessment when there was lack of dose-response data. When there were sufficient dose-response data from animal studies,both MOE and low dose extrapolation approaches can be applied,yet MOE approach was preferred.Conclusion China should actively participate in international risk assessment for genotoxic carcinogens in food,develop in-depth scientific research into genotoxic carcinogens,and establish technical system for risk assessment of genotoxic carcinogens in food as soon as possible.
引文
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[15]U.S.Environmental Protection Agency.Guidelines for carcinogen risk assessment[Z].2005.
[16]European Chemicals Agency.Guidance on information requirements and chemical safety assessment Chapter R.8:Characterisation of dose[concentration]-response for human health[Z].2012.
[17]European Food Safety Authority.Opinion of the Scientific Committee on a request from EFSA related to a harmonised approach for risk assessment of substances which are both genotoxic and carcinogenic[Z/OL].2005(2018-02-20).https://www.efsa.europa.eu/en/efsajournal/pub/282.
[18]IPCS.Environmental Health Criteria 240.Principles and methods for the risk assessment of chemicals in food[S/OL].ISBN:978 92 4 157240,2005(2018-02-20).http://www.who.int/foodsafety/publications/chemical-food/en/.
[19]Joint FAO/WHO Expert Committee on Food Additives.Summary and conclusions[C/OL].JECFA Sixty-fourth Meeting,Rome,2005(2018-02-20).http://www.fao.org/3/a-at877e.pdf.
[2]陈君石.食品安全风险评估概述[J].中国食品卫生杂志,2011,23(1):4-7.
[3]O'BRIEN J,RENWICK A G,CONSTABLE A,et al.Approaches to the risk assessment of genotoxic carcinogens in food:a critical appraisal[J].Food Chem Toxicol,2006,44(10):1613-1635.
[4]刘兆平,李凤琴,贾旭东.食品中化学物风险评估原则和方法[M].北京:人民卫生出版社,2012.
[5]EFSA Scientific Committee.Scientific opinion on genotoxicity testing strategies applicable to food and feed safety assessment[J].EFSA Journal,2011,9(9):2379.
[6]隋海霞,张磊,毛伟峰,等.毒理学关注阈值方法的建立及其在食品接触材料评估中的应用[J].中国食品卫生杂志,2012,24(2):109-113.
[7]EFSA(European Food Safety Authority),WHO(World Health Organization).Review of the threshold of toxicological concern(TTC)approach and development of new TTC decision tree[J].EFSA Supporting Publication,2016,13(3):50.
[8]CHEESEMAN M A,MACHUGA E J,BAILEY A B.A tiered approach to threshold of regulation[J].Food Chem Toxicol,1999,37(4):387-412.
[9]U.S.Environmental Protection Agency.Guidelines for carcinogen risk assessment[Z].Fed Reg,1986,51(185):33992-34003.
[10]U.S.Environmental Protection Agency.Guidelines for carcinogen risk assessment[Z].Fed Reg,1996,61(79):17960-18011.
[11]SANNER T,DYBING E,WILLEMS M I,et al.A simple method for quantitative risk assessment of non-threshold carcinogens based on the dose descriptor T25[J].Pharmacol Toxicol,2001,88(6):331-341.
[12]DYBING E,SANNER T,ROELFZEMA H,et al.T25:a simplified carcinogenic potency index:description of the system and study of correlations between carcinogenic potency and species/site specificity and mutagenicity[J].Pharmacol Toxicol,1997,80(6):272-279.
[13]U.S.Environmental Protection Agency.The use of the benchmark dose approach in health risk assessment:EPA/630/R-94/007[A].Washington DC,Risk Assessment Forum,1995.
[14]VAN LANDINGHAM C B,ALLEN B C,SHIPP A M,et al.Comparison of the EU T25 single point estimate method with benchmark dose response modeling for estimating potency of carcinogens[J].Risk Anal,2001,21(4):641-656.
[15]U.S.Environmental Protection Agency.Guidelines for carcinogen risk assessment[Z].2005.
[16]European Chemicals Agency.Guidance on information requirements and chemical safety assessment Chapter R.8:Characterisation of dose[concentration]-response for human health[Z].2012.
[17]European Food Safety Authority.Opinion of the Scientific Committee on a request from EFSA related to a harmonised approach for risk assessment of substances which are both genotoxic and carcinogenic[Z/OL].2005(2018-02-20).https://www.efsa.europa.eu/en/efsajournal/pub/282.
[18]IPCS.Environmental Health Criteria 240.Principles and methods for the risk assessment of chemicals in food[S/OL].ISBN:978 92 4 157240,2005(2018-02-20).http://www.who.int/foodsafety/publications/chemical-food/en/.
[19]Joint FAO/WHO Expert Committee on Food Additives.Summary and conclusions[C/OL].JECFA Sixty-fourth Meeting,Rome,2005(2018-02-20).http://www.fao.org/3/a-at877e.pdf.