Dose-response assessment acceptable daily intake

There are of course many mathematically complex ways to perform a risk assessment, but first key questions about the biological data must be resolved. The most sensitive endpoint must be defined along with relevant toxicity and dose-response data. A standard risk assessment approach that is often used is the so-called divide by 10 rule . Dividing the dose by 10 applies a safety factor to ensure that even the most sensitive individuals are protected. Animal studies are typically used to establish a dose-response curve and the most sensitive endpoint. From the dose-response curve a NOAEL dose or no observed adverse effect level is derived. This is the dose at which there appears to be no adverse effects in the animal studies at a particular endpoint, which could be cancer, liver damage, or a neuro-behavioral effect. This dose is then divided by 10 if the animal data are in any way thought to be inadequate. For example, there may be a great deal of variability, or there were adverse effects at the lowest dose, or there were only tests of short-term exposure to the chemical. An additional factor of 10 is used when extrapolating from animals to humans. Last, a factor of 10 is used to account for variability in the human population or to account for sensitive individuals such as children or the elderly. The final number is the reference dose (RfD) or acceptable daily intake (ADI). This process is summarized below. 

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... 

Health organizations throughout the world utilize a safe dose concept in the dose-response assessment of noncancer toxicity. This safe dose has often been referred to by different names, such as acceptable daily intake (ADI), tolerable daily intake (TDI) or tolerable concentration (TC), minimal risk level (MRL), reference dose (RfD), and reference concentration (RfC). The approaches used by various health organizations share many of the same underlying assumptions, judgments on critical effect, and choices of uncertainty (or safety) factors. 

The health assessment chapters of these documents contain the available dose-response data from animal experiments and human epidemiology studies for the chemical or class of chemicals of concern. By assessing the risks associated with various doses, acceptable daily intakes (ADIs - for systemic toxicants) or risk-specific doses (for carcinogens) were derived. These levels were divided by appropriate exposure assumptions (e.g., estimated average water consumption) to derive a criterion. 

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