Acceptable daily intake calculation process

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

Basically, these workers were attempting to determine the amounts of chemicals that the human body could ingest on a daily basis without undue risk and toxicity. In the process, they found that a level of acceptable daily intake could be calculated from the toxicity of the materials expressed as an LDS0. These data are widely available on material safety data sheets and other references on which toxicity data can be found. 

The UEL for reproductive and developmental toxicity is derived by applying uncertainty factors to the NOAEL, LOAEL, or BMDL. To calculate the UEL, the selected UF is divided into the NOAEL, LOAEL, or BMDL for the critical effect in the most appropriate or sensitive mammalian species. This approach is similar to the one used to derive the acute and chronic reference doses (RfD) or Acceptable Daily Intake (ADI) except that it is specific for reproductive and developmental effects and is derived specifically for the exposure duration of concern in the human. The evaluative process uses the UEL both to avoid the connotation that it is the RfD or reference concentration (RfC) value derived by EPA or the ADI derived for food additives by the Food and Drug Administration, both of which consider all types of noncancer toxicity data. Other approaches for more quantitative dose-response evaluations can be used when sufficient data are available. When more extensive data are available (for example, on pharmacokinetics, mechanisms, or biological markers of exposure and effect), one might use more sophisticated quantitative modeling approaches (e.g., a physiologically based pharmacokinetic or pharmacodynamic model) to estimate low levels of risk. Unfortunately, the data sets required for such modeling are rare. 

For chemicals such as food additives, food contaminants, and industrial chemicals the threshold, that is the dose at which toxic effects become apparent, is determined from the dose-response graph and used in the risk assessment process. The threshold value is used, together with safety factors, to determine the acceptable daily intake (ADI) of a food additive, or the tolerable daily intake (TDI) of a food contaminant, or the threshold limit value (TLV in the USA, or maximum exposure limit (MEL) in the UK), for an industrial chemical (see box for calculation). For a drug, information about the dose in animals below which there are no adverse effects will be necessary before human volunteers can be exposed in clinical trials. More extensive safety evaluation is carried out for drugs than for... 

ICH Q3C guides in determining, on a safety basis, acceptable residual solvent levels for intake by use of the term permitted daily exposure (PDE). This Guidance classifies residual solvents used in the synthesis and processing into four categories. The Guidance recommends that Class I solvents be avoided. These include benzene, carbon tetrachloride, 1,2-dichloromethane, 1,1-dichloroethane, and 1,1,1-trichloroethane. Table 2 is an example from the list of Class II solvents that should be limited because of their inherent toxicity either by calculation of concentration (PPM) or by PDE. 

---