Acceptable daily intake , definition

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) ... 

Absorption, use for accumulating compounds from water, 206-207 Acceptable daily intake (ADI) calculation process, 702-703 definition, 701 p-dichlorobenzene, 705... 

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). 

Therefore, melamine appears to exert its effect via precipitation and chronic mechanical irritation. Since chronic irritation is a known promoting function, this is a likely hypothesis of the mechanism of toxicity. This hypothesis is further supported by the absence of carcinogenicity in doses below the dose which results in bladder calculi. The conclusions reached from this mechanism indicate that a threshold exists at the dose resulting in calculi and safe limits on exposure for melamine should be based upon the acceptable daily intake even though the compound by some definitions is a carcinogen. 

The reference dose (RfD) assumes there is a threshold of exposure below which a chemical does not produce a toxic effect because the body is able to detoxify and/or eliminate it. The reference dose is derived either from a no observed adverse effect level (NOAEL) or from a benchmark dose (BMD) determined in an animal toxicity study. The NOAEL or BMD is divided by at least two uncertainty factors or safety factors a factor of 10 to account for the uncertainty involved in extrapolating from animals to humans, and a second factor of 10 to account for variation in human sensitivity. If the animal toxicity data supporting the NOAEL or BMD are not definitive, a third safety factor of 10 is included. Thus, the RfD is set equal to the NOAEL or BMD divided by 100 alternatively, it is set equal to a number approximating the NOAEL or BMD divided by 1,000. The acceptable daily intake (ADI) is the same as the reference dose. The reference concentration (RfG) refers to the concentration of a pollutant in the air. It differs from the... 

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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