Determining the Applicability of Threshold of Toxicological Concern Approaches to Substances Found in Foods

Figures & data

Table 1 A selection of TTC values proposed in the scientific literature

	Threshold value*
Chemical class	μg/d	μg/kg body wt per d
Various excluded substances^†
Cramer class I	1800	30
Cramer class II	540	9
Cramer class III	90	1.5
Organophosphates	18	0.3
Nongenotoxic compounds	1.5	0.025
Genotoxic compounds	0.15	0.0025
Data are adapted from Kroes et al. (2004) and Felter et al. (2009).
*For oral exposure, based on a body weight of 60 kg.
^†Various excluded substances are discussed in the text as well as in Table 3.
From Munro et al. (2008).

Figure 1 Summary of the three main conditions indicating that the TTC approach is inappropriate to the situation.

Table 2 Classes of chemicals to which the TTC approach does not apply, and reasons for exclusion

Excluded class	Reason(s) for exclusion
Aflatoxin-like compounds, N-nitroso compounds, Azoxy compounds	Highly potent genotoxic carcinogens
Steroids	Evidence for very high potency (by a nongenotoxic mechanism)
Polyhalogenated dioxins/dibenzo furans and dioxin-like polyhalogenated biphenyls	Wide species differences in biopersistence; toxicity data are available for some
Proteins	Not included in training databases; often associated with allergenic reactions
Metals	Not included in training databases; some show bioaccumulation potential; half-lives vary widely across species
Inorganic substances, high molecular weight substances (e.g., polymers), and other substances not in the training databases (e.g., nanomaterials and radioactives)	Not included in training databases
Based on Koster et al. (2011) and EFSA (2012).

Figure 2 Actions and decisions for evaluating the applicability of the TTC in response to detection of a low-level contaminant in food.

Table 3 Categories of chemicals found unexpectedly in food

Categories of chemicals found unexpectedly in food	Examples	Time of contamination
Environmental contaminants	Heavy metals, dioxins, brominated flame retardants	Production of raw materials
Natural toxins	Mycotoxins, paralytic shellfish toxins, cyanogenic glycosides	Production of raw materials, storage
Food processing–induced chemicals	Acrylamide, furan, nitrosamines	Production of raw materials
Agricultural chemical residue	DDT, dichlorvos, ciprofloxacin
Adapted from Shanklin (2009).

Kroes , R. , Renwick , A. G. , Cheeseman , M. , Kleiner , J. , Mengelsdorf , I. , Piersma , A. , Schilter , B. , Schlatter , J. , van Schothorst , F. , Vos , J. G. and Wurtzen , G. 2004 . Structure-based thresholds of toxicological concern-guidance for application to substances present at low levels in the diet . Food Chem. Toxicol. , 42 : 65 – 83 .

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Munro , I. C. , Renwick , A. G. and Danielewska-Nikiel , B. 2008 . The threshold of toxicological concern (TTC) in risk assessment . Toxicol. Lett. , 180 : 151 – 156 .

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Koster , S. , Boobis , A. R. , Cubberly , R. , Hollnagel , H. M. , Richling , E. , Wildemann , T. , Würtzen , G. and Galli , C. L. 2011 . Application of the TTC concept to unknown substances found in analysis of foods . Food Chem. Toxicol. , 49 : 1643 – 1660 .

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European Food Safety Authority . 2012 . Scientific Opinion on Exploring options for providing advice about possible human health risks based on the concept of Threshold of Toxicological Concern (TTC) Available from http://www.efsa.europa.eu/en/efsajournal/pub/2750.htm. Accessed November 2, 2012

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Shanklin , A. P. 2009 . Regulatory report. How FDA's “threshold of regulation” program works . Food Safety Magazine , Available from http://www.foodsafetymagazine.com/articleFF.asp?id=2719&sub=sub1. Accessed May 16, 2012

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