Acceptable Daily Intake estimation

ADI = acceptable daily intake, estimate of amount of a substance in food or drinking water, expressed as mg/kg body weight, that can be ingested daily over a lifetime without appreciable risk (weight of standard human = 60 kg) bw = body weight. 

Acceptable Daily Intake (ADI) An estimate similar in concept to the RfD, but derived using a less strictly defined methodology. RfDs have replaced ADIs as the USEPA s (Agency) preferred values for use in evaluating potential noiicarcinogenic health effects resulting from exposure to a chemical. 

NOAEL (no-observed-adverse-effect level) is defined as the highest dose at which no adverse effects are observed in the most susceptible animal species. The NOAEL is used as a basis for setting human safety standards for acceptable daily intakes (ADIs), taking into account uncertainty factors for extrapolation from animals to humans and inter-individual variabilities of humans. The adequacy of any margin of safety or margin of exposure must consider the nature and quality of the available hazard identification and dose-response data and the reliability and relevance of the exposure estimations. In some cases, no adverse endpoint can be identified such as for many naturally occurring compounds that are widespread in foods. In that case, an ADI Not Specified is assigned. ... 

An estimate for the lowest level of toxicological concern for human exposure to a chemical is developed by dividing the appropriate NOAEL by the uncertainty factor. Historically, this estimate has been termed the acceptable daily intake (or ADI) although it has been replaced by what EPA calls the reference dose (or RfD). Both ADIs and RfDs are expressed in terms of the amount of chemical exposure per amount of body weight per day. 

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) ... 

Renwick, A.G. 1995. The use of an additional safety or uncertainty factor for nature of toxicity in the estimation of acceptable daily intake and tolerable daily intake values. Regul. Toxicol. Pharmacol. 27 3-20. 

Since food laws in most countries regulate the use of intense sweeteners, analytical control for the presence and levels of sweeteners in food is essential. According to the FAO/ WHO Joint Expert Committee on Food Additives (JECFA) it is also important to know the level of additives in food products in order to estimate the actual consumption by the population. This information will show the average intake in relation to the acceptable daily intake (ADI) over a period of time. Based on this knowledge, regulatory authorities can propose regulations to ensure intakes below... 

The estimation of the Actual Daily Exposure assuming a person consumes a large portion of food. If this one-day exposure exceeds the Acceptable Daily Intake, then this use of the pesticide could be denied. 

The risk to health from chemicals in food can be assessed by comparing estimates of dietary exposure with recommended safe levels of exposure. For most metals and other elements, these are the Provisional Tolerable Weekly Intakes (PTWIs) and the Provisional Tolerable Daily Intakes (PTDIs) recommended by the Joint Expert Committee on Food Additives of the Food and Agricultural Organisation of the United Nations and the World Health Organisation International Programme on Chemical Safety (JECFA). The European Commission s Scientific Committee on Food has established other relevant safe levels. These are Acceptable Daily Intakes (ADIs) for chemicals added to food, and Tolerable Daily Intakes (TDIs) for chemical contaminants. The use of the term tolerable implies permissibility rather than acceptability. All the above recommendations are estimates of the amount of substance that can be ingested over a lifetime without appreciable risk, expressed on a daily or weekly basis as appropriate. 

The dietary intake of OCPs is considered the main source of exposure for the general population in Australia and in many other countries. Estimates of dietary intakes of OCPs from AMBS are summarised in Tables 17.3 and 17.4 for the years 1971 to 1996. The initial survey in 1970 estimated that excessive intakes of dieldrin and HCB could occur in the diets of 15 18 year old males. Dieldrin and HCB had estimated daily intakes from 0.4 to 1.8 (0.1) and 0.7 to 1.4 (0.6) pg kg-1 bw, respectively. For comparison the accepted daily intake (ADI) at the time is shown in parenthesis (NHMRC, 1971). By 1976, the estimated daily intake of dieldrin remained relatively high, particularly for infants (e.g. 0.1 pg kg-1 bw), while HCB residues in foods were too low to estimate a dietary intake. 

The estimate of the exposure in this example is 0.34 pg/kg body weight per day (see Appendix 1). Normally, this value is communicated with an estimate of toxicity or together with toxicology-based target values, such as, for example, reference dose (RfD) or acceptable daily intake (ADI). 

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. 

Toxicity. The estimated minimum lethal dose is 7 g. The maximum permissible atmospheric concentration is lOmg/m and the maximum acceptable daily intake is 300 pg/kg. Di-chlorophenoxyacetic acid is very irritating to the eyes, nose, and throat. 

Toxicity. The minimum lethal dose is about 30 ml. Formic acid is dangerously caustic to the skin. The maximum permissible atmospheric concentration is 5 ppm or 9 mg/m the estimated acceptable daily intake is up to 3 mg/kg. 

Toxicity. Lindane is not highly toxic when applied externally in the concentrations usually employed (0.1 to 1%), but when ingested it may cause convulsions dusts may irritate the nose and throat when used in a confined space. Blood concentrations greater than 0.02 pg/ml have been associated with toxic effects. The estimated minimum oral lethal dose is 200 mg/kg and the maximum permissible atmospheric concentration is 0.5 mg/m. Toxic doses or long term exposure may cause liver necrosis. The maximum acceptable daily intake is lOfig/kg. 

Toxicity. Methylene chloride is widely used in paint strippers and several non-fatal and fatal cases of accidental inhalation have been reported. The maximum permissible atmospheric concentration is 200 ppm and the temporary estimated acceptable daily intake is up to 500 pg/kg. 

Dourson, M.L., R.C. Hertzberg, R. Hartung, and K. Blackburn. 1985. Novel methods for the estimation of acceptable daily intake. Toxicol. Ind. Health 1 23-41. 

Acceptable daily intake (ADI) an estimate of the daily intake of a food additive over a lifetime that is considered to be without appreciable health risk. It is... 

While the assessment may show several effects, from the information gained it should be possible to establish a threshold dose for the most sensitive relevant effect in the animals. From this the no observed adverse effect level (NOAEL) can be estimated and used to determine the acceptable daily intake (ADI). 

The use of the terms upper bound and worst-case refer to the expectations that this approach is likely to be highly conservative and will not underestimate potential risk. These terms are not meant to connote that statistical analysis to estimate error bounds would be performed, or that additional safety factors (traditional for extrapolation to acceptable daily intake values for non-carcinogens) would be incorporated into the extrapolation. 

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