Historical Evolution and Development of the Threshold (TTC) of Toxicological Concern

doi:10.7506/spkx1002-6630-201307072

Abstract

Abstract: The threshold of toxicological concern (TTC) is a concept that refers to the establishment of a level of exposure for all chemicals, below which there would be no appreciable risk to human health. The TTC method has been applied for nearly half a century since it was proposed, and has experienced a continuous improvement and development process. The establishment, development and improvement of TTC method were discussed. TTC method was originally developed to determine the threshold of safety in food materials. Since then, the non-carcinogenic oral toxicity endpoint of no significant effect level (NOEL) was analyzed to develop a structural class-based multi-scale TTC which was then adopted by Food Additives of FAO/World Health Organization (FAO/WHO) Joint Expert Committee (JECFA) and the European Food Safety Authority (EFSA) with development and improvement. The TTC approach is in wide application to assess the risk of chemicals at low exposure levels, which avoids multiple unnecessary, overly detailed studies, as well as a wide range of toxicological experiments. The TTC method also provides a feasible way for the risk assessment of chemical substances that the amount is very low but lack of a complete toxicity data.

Key words: threshold of toxicological concern (TTC), risk assessment, food safety

CLC Number:

TS201.6

ZHU Zhou-hai，ZENG Wan-li，GUAN Ying，GAO Qian，LI Xue-mei，MIAO Ming-ming，YAO Jian-hua*. Historical Evolution and Development of the Threshold (TTC) of Toxicological Concern[J]. FOOD SCIENCE, 2013, 34(7): 340-344.

References

[1] WHO. Application of risk analysis to food standards issues [J]. Report of the Joint FAO/WHO Expert Consultation WHO, 1995,
[2] RENNEN M A, KOSTER S, KRUL C A, et al. Application of the threshold of toxicological concern (TTC) concept to the safety assessment of chemically complex food matrices [J]. Food Chem Toxicol, 2011, 49(4): 933-40.
[3] MUNRO I C, FORD R A, KENNEPOHL E, et al. Correlation of structural class with no-observed-effect levels: a proposal for establishing a threshold of concern [J]. Food Chem Toxicol, 1996, 34(9): 829-67.
[4] MUNRO I C, RAPPORTEUR. Safety assessment procedures for indirect food additives: An overview: Report of a workshop [J]. Regulatory Toxicology and Pharmacology, 1990, 12(1): 2-12.
[5] 龙再浩, 陈小青, 马中春. 危险度评价中的毒理学关注阈值原则 [J]. 癌变畸变突变, 2008, 01): 79-81.
[6] 袁家齐, 高仁君. 毒理关注阈值(TTC)方法在化学物质风险评估中的应用; [C]//中国毒理学会管理毒理学专业委员会学术研讨会暨换届大会, 中国北京, F, 2009.
[7] 高仁君, 袁家齐, 董晶. 毒理关注阈值(TTC)理论及其在风险评估中的应用; [C]//全国生化/工业与卫生毒理学学术会议, 中国辽宁大连, F, 2010.
[8] 郑明岚, 周少英, 刘学军, 等. 毒理学关注阈值(TTC)在化学物质风险评估中的应用 [J]. 卫生研究, 2010, 05): 639-42.
[9] 马宁, 李凤琴, 刘兆平. 食用香料风险评估方法与应用 [J]. 中国食品卫生杂志, 2011, 01): 41-5.
[10] FDA U. Food additives: Threshold of regulation for substances used in food-contact articles (final rule) [J]. Federal Register, 1995, 60(136): 36582-96.
[11] FDA U. Food additives; Threshold of regulation for substances used in food-contact articles [J]. Federal Register, 1993, 58(195): 52719-27.
[12] RULIS A M. Establishing a threshold of regulaion [M]//BONIN J J, STEVENSON D E. Risk Assessment in Setting National Priorities. New York; Plenum Press. 1989: 271-8.
[13] RULIS A M. De minimis and the threshold of regulation [M]//FELIX C W. Food protection technology. Chelsea, Michigan; Lewis Publishers Inc. 1986: 29-37.
[14] FRAWLEY J P. Scientific evidence and common sense as a basis for food-packaging regulations [J]. Food and Cosmetics Toxicology, 1967, 5(0): 293-308.
[15] KROES R, RENWICK A G, CHEESEMAN M, et al. Structure-based thresholds of toxicological concern (TTC): guidance for application to substances present at low levels in the diet [J]. Food Chem Toxicol, 2004, 42(1): 65-83.
[16] KROES R, GALLI C, MUNRO I, et al. Threshold of toxicological concern for chemical substances present in the diet: a practical tool for assessing the need for toxicity testing [J]. Food Chem Toxicol, 2000, 38(2-3): 255-312.
[17] JECFA. Evaluation of certain food additives and contaminants [M]. Forty-sixth report of the Joint FAO/WHO Expert Committee on Food Additives Geneva, 6-15 February 1996. WHO Technical Report Series, No. 868. Geneva. 1997.
[18] EFSA. SCIENTIFIC OPINION, Guidance on the data required for the risk assessment of flavourings to be used in or on foods [J]. EFSA Journal, 2010, 8(6): 1623.
[19] GOLD L S, SAWYER C B, MAGAW R, et al. A carcinogenic potency database of the standardized results of animal bioassays [J]. Environmental health perspectives, 1984, 58(9-319.
[20] GOLD L S, SLONE T H, BERNSTEIN L. Summary of carcinogenic potency and positivity for 492 rodent carcinogens in the carcinogenic potency database [J]. Environmental health perspectives, 1989, 79(259-72.
[21] MUNRO I C, KENNEPOHL E, KROES R. A procedure for the safety evaluation of flavouring substances. Joint FAO/WHO Expert Committee on Food Additives [J]. Food Chem Toxicol, 1999, 37(2-3): 207-32.
[22] FUNG V A, BARRETT J C, HUFF J. The carcinogenesis bioassay in perspective: application in identifying human cancer hazards [J]. Environmental health perspectives, 1995, 103(7-8): 680-3.
[23] CRAMER G M, FORD R A, HALL R L. Estimation of toxic hazard--a decision tree approach [J]. Food Cosmet Toxicol, 1978, 16(3): 255-76.
[24] JECFA. Evaluation of certain food additives and contaminants [M]. Forty-ninth report of the Joint FAO/WHO Expert Committee on Food Additives Rome, 17-26 June 1997. WHO Technical Report Series, No. 884. Geneva. 1999.
[25] JECFA. Evaluation of certain food additives and contaminants [M]. Sixty-fifth report of the Joint FAO/WHO Expert Committee on Food Additives. WHO Technical Report Series, No. 934. 2006.
[26] JECFA. Evaluation of certain food additives and contaminants [M]. Sixty-ninth report of the Joint FAO/WHO Expert Committee on Food Additives. WHO Technical Report Series, No. 952. 2009.
[27] WHO. Principles and Methods for the Risk Assessment of Chemicals in Food [M]. Geneva: World Health Organization, 2009.
[28] GOLD L S, MANLEY N B, SLONE T H, et al. Sixth plot of the carcinogenic potency database: results of animal bioassays published in the General Literature 1989 to 1990 and by the National Toxicology Program 1990 to 1993 [J]. Environmental health perspectives, 1995, 103 Suppl 8(3-122.
[29] 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.
[30] BARLOW S M, KOZIANOWSKI G, W RTZEN G, et al. Threshold of toxicological concern for chemical substances present in the diet [J]. Food and Chemical Toxicology, 2001, 39(9): 893-905.
[31] MUNRO I C, RENWICK A G, DANIELEWSKA-NIKIEL B. The Threshold of Toxicological Concern (TTC) in risk assessment [J]. Toxicology letters, 2008, 180(2): 151-6.
[32] KROES R, KLEINER J, RENWICK A. The threshold of toxicological concern concept in risk assessment [J]. Toxicological sciences : an official journal of the Society of Toxicology, 2005, 86(2): 226-30.
[33] EMEA. London: The European Medical Control Agency, Committee for Medicinal Products for Human Use, CPMP/ SWP/5199/02. EMEA/CHMP/QWP/251344/2006, 2006.
[34] ECHA. Guidance on information requirements and chemical safety assessment [J]. European Chemicals Agency, Chapter R7c: Endpoint specific guidance, 2008,
[35] KROES R, RENWICK A G, FERON V, et al. Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients [J]. Food Chem Toxicol, 2007, 45(12): 2533-62.