Threshold of no concern

Functional barrier A package construction or barrier layer which limits the extent of migration of a component from the package to the food or food simulant in amounts below a threshold value see threshold of no concern or migration limits. 

FDA s threshold of 1.5 fig/p/d is an example of the threshold of toxicological concern approach. Below this threshold level of consumer exposure, FDA does not consider specific testing necessary to identify compounds with significant carcinogenic potential. This threshold of regulation is not meant to be a level below which no chemicals could be harmful. FDA s threshold... 

The Cramer classification scheme can be used to make a threshold of toxicological concern (TTC) estimation. TTC is a concept that aims to establish a level of exposure for all chemicals below which there would be no appreciable risk to human health the threshold is based on a statistical analysis of the toxicological data from a broad range of different and/or structurally related chemicals and on the extrapolation of the underlying animal data to a no-effect dose considered to represent a negligible risk to human health. 

The substances in this group that have been evaluated at this meeting and at the fifty-third and sixty-first meetings are predicted to be metabolized by a variety of metabolic pathways. Because of the diverse structures, there are few common metabolites. Examples are 3-(methylthio)propionic acid (from Nos 476 and 468) and thioacetic acid (from Nos 482, 483, 485 and 491). The combined intakes of substances with a common metabolite were below the relevant threshold of toxicological concern (TTC) value. 

ILSI is publishing its proposals for Threshold of Toxicological Concern (ToTC), aimed at establishing a human exposure threshold below which no toxicity data would be necessary, avoiding the need to expend valuable resources, costs and time on developing safety materials and their uses, and ensure that they comply with national and international legislation. 

Fifteen flavorant compounds approved by the Flavor and Extract Manufacturers Association (FEMA) for the GRAS list have been found to be carcinogenic to laboratory animals. These inclnde benzyl acetate, cinnamyl anthranilate, ethyl aaylate, and pyridine [66]. Thongh the author of the smdy concludes that the levels of these compounds found in foods are below the thresholds of carcinogenic concern, no consideration was given to the effects of mixtures, which have been shown to indnce effects at lower concentration than individnal compoimds [50,67]. 

The choice of the solvent also has a profound influence on the observed sonochemistry. The effect of vapor pressure has already been mentioned. Other Hquid properties, such as surface tension and viscosity, wiU alter the threshold of cavitation, but this is generaUy a minor concern. The chemical reactivity of the solvent is often much more important. No solvent is inert under the high temperature conditions of cavitation (50). One may minimize this problem, however, by using robust solvents that have low vapor pressures so as to minimize their concentration in the vapor phase of the cavitation event. Alternatively, one may wish to take advantage of such secondary reactions, for example, by using halocarbons for sonochemical halogenations. With ultrasonic irradiations in water, the observed aqueous sonochemistry is dominated by secondary reactions of OH- and H- formed from the sonolysis of water vapor in the cavitation zone (51—53). 

National Ambient Air Quality Standards. Under the Clean Air Act, six criterion pollutants, ie, pollutants of special concern, have been estabhshed by the EPA sulfur oxides (SO ), particulates, carbon monoxide (CO), nitrogen oxides (NO ), o2one (photochemical oxidants), and lead. National Ambient Air QuaUty Standards (NAAQS) were developed by EPA based on threshold levels of air pollution below which no adverse effects could be experienced on human health or the environment. 

In general, it is difficult to determine whether there is an effect on the mean QT/QTc interval that is so small as to be of no clinical consequence. However, drugs that prolong the mean QT/QTc interval by around 5 ms or less do not appear to cause TdP. On that basis, the threshold level of regulatory concern is 5 ms. 

The last set of requirements in olfactometry is concerned with the differences between panel members. People vary widely in their sensitivity. A factor of a 100 between the thresholds of two subjects for the same substance is not uncommon. For a number of substances, specific anosmia s or specific hyposmia s are found. In such cases a person has no sensitivity at all or a very high threshold for the given substance, but normal sensitivity to other substances (1). This is an illustration of the fact that sensitivity to odours is specific rather than general. This is also demonstrated by Punter (2, 3) who determined the thresholds of 69 odorous substances for the same group of subjects and calculated the correlations between these thresholds (see figure 2). 

For every endpoint investigated, the risk assessment for new substances assigns one of four available conclusions (i) the substance is of no immediate concern and need not be considered again until further information is made available in accordance with the requirements of Directive 67/548/EEC, (ii) the substance is of concern and the Competent Authority wiU define information required to refine the assessment and request that it is supplied when the quantity of the substance placed on the market reaches the next supply threshold, (iii) the substance is of concern and the Competent Authority wiU request that defined information is supplied without further delay, and (iv) the substance is of concern and the Competent Authority will immediately make recommendations for risk reduction. 

Munro, l.C., R.A. Ford, E. Kennepohl, and J.G. Sprenger. 1996. Correlation of structural class with no-observed-effect levels A proposal for estabhshing a threshold of concern. Food Chem. Toxicol. 34 829-867. 

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