Tolerable intake definition

The term acceptable is used widely to describe safe levels of intake and is apphed for chemicals to be used in food production such as, e.g., food additives, pesticides, and veterinary dmgs. The term tolerable is applied for chemicals unavoidably present in a media such as contaminants in, e.g., drinking water and food. The term PTWI (Provisional Tolerable Weekly Intake) is generally used for contaminants that may accumulate in the body, and the weekly designation is used to stress the importance of limiting intake over a period of time for such substances. The tolerable intake is similar in definition and intent to terms such as Reference Dose and Reference Concentration (RfD/RfC), which are widely used by, e.g., the US-EPA. For some substances, notably pesticides, the ARID (Acute Reference Dose), is also established, often from shorter-term studies than those that would support the ADI. The ARfD is defined as the amount of a substance in food that can be consumed in the course of a day or at a single meal with no adverse effects. 

One of the most evident limitations in the NOAEL approach in the derivation of tolerable intakes is that it does not take into account the slope of the dose-response curve for the particular response of interest (Section 4.2.4). The NOAEL is by definition one of the doses tested, and apart from ensuring that the number and spacing of data points are adequate to provide a reasonable estimate of the NOAEL, all other data points are ignored. Although the NOAEL could be considered an estimate of the tme NAEL, the quality of the estimate cannot be assessed. For the dose-response relationship and precision in the NOAEL, consideration should therefore be given to the uncertainties in the NOAEL as the surrogate for the NAEL. 

Implicit from the definition of the tolerable intake, i.e., an estimate of the intake of a substance over a lifetime that is considered to be without appreciable health risk, arises the question What are the health implications of exceeding the tolerable intake This issue has been discussed at an ELSI (International Life Science Instimte) Europe Workshop on the Significance of Excursions of Intake above the Acceptable Daily Intake (ADI) in 1999. The following questions were asked (Larsen and Richold 1999, Larsen 2006) ... 

The guideline contains extensive lists of solvents of all three classes, with limits for each. Known toxicology data are given for each solvent, with definitions for parameters and methods of establishing exposure limits such as permitted daily exposure (PDE), no-observed-effect level (NOEL), lowest-observed-effect level (LOEL), tolerable daily intake (TDI), and acceptable daily intake (ADI). 

After these introductory remarks, I shall attempt to give you an account of the current recommendations of the World Health Organization in this field. In particular, I will stress the "safe" levels of intake based on concepts such as Acceptable and Admissible Daily Intake (ADI), respectively, for intentional food additives and pesticide residues in food Provisional Tolerable Weekly Intake (PTWI) for cumulative toxic metals figures for body burdens and the corresponding "safe" limits recommended for foodstuffs, including the relatively recent definition of irreducible limits to deal with the problem of trace contaminants in food. 

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