Acceptable Daily Intakes risk evaluation

Toxicologists tend to focus their attention primarily on c.xtrapolations from cancer bioassays. However, tlicrc is also a need to evaluate the risks of lower doses to see how they affect the various organs and systems in the body. Many scientific papers focused on tlic use of a safety factor or uncertainty factor approach, since all adverse effects other than cancer and mutation-based dcvclopmcnUil effects are believed to have a tlu cshold i.e., a dose below which no adverse effect should occur. Several researchers have discussed various approaches to setting acceptable daily intakes or exposure limits for developmental and reproductive toxicants. It is Uiought Uiat an acceptable limit of exposure could be determined using cancer models, but today tliey arc considered inappropriate because of tlircsholds. ... 

The most recently reported UK results on surveillance for veterinary drug residues in meat and animal products show that traces of these compounds can, and sometimes do, arise in food. As all of these compounds are biologically potent in order to be effective in use, it is necessary to ensure that any residual activity in a food product does not present a risk to the consumer. The use of veterinary medicines inevitably leads to the presence of trace residues in food and the purpose of toxicological safety evaluation is to determine at what concentration the residues of a particular compound becomes a cause for concern with regard to human health. Thus, dose-response relationships have to be established and used to determine the concentration of a dmg at which the risks to human health become acceptable and are outweighed by the benefits from the use of the drug. This is in essence the process involved in the setting of Acceptable Daily Intakes (ADIs) and... 

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. 

Acceptable Daily Intake (ADI) The ADI of a chemical is the estimate of the amount of a substance in food and/or drinking water, expressed on a body weight basis, that can be ingested daily over a lifetime without appreciable health risk to the consumer on the basis of all of the known facts at the time of the evaluation. It is usually expressed in mg of the chemical per kg of body weight (EAO/WHO, 1997). 

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... 

JECFA has also evaluated modified celluloses. In 1990 JECFA allocated a group ADI (Accepted Daily Intake) not specified to seven modified cellulose derivatives including ethyl cellulose indicating the low risk potential of these substances. 

The main purpose of the toxicity tests just described is to provide a data base that can be used to evaluate the hazard and assess the risk associated with the use of a pesticide. In practice the no observable effect level (NOEL) found in the most sensitive animal species tested in chronic studies is used. To extrapolate a safe dose for human consumption, a safety factor of 100 is usually used. For example, if the NOEL in the most sensitive animal species e.g. the dog from the chronic feeding study, was 10 mg/kg of body weight, then the acceptable daily intake (ADI) for man would be... 

JECEA is an independent expert committee established (and jointly administered) by the FAO and the WHO in 1956 to evaluate the safety of food additives. Uie work has since expanded to include the evaluation of the safety of contaminants, naturally occurring toxicants and residues of veterinary drugs in food. JECFA serves as the risk assessor for the Codex Committee on Residues of Veterinary Drugs in Foods (CCRVDF), establishing an acceptable daily intake (ADI) for a veterinary drug when sufficient information is available, recommending maximum residue limits (MRLs) for consideration by... 

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