Human food safety acceptable daily intake

For many substances the body s own mechanisms for de-toxification and repair mean that low doses of some chemicals can be tolerated without experiencing any adverse effects. However, once a certain threshold has been exceeded then the degree of adverse effect is related to the dose. The highest dose at which no adverse effects are observed in the most susceptible animal species is identified as the No Observed Adverse Effect Level (NOAEL). The NOAEL is used as the basis for setting human safety standards for food additive Acceptable Daily Intakes (ADIs)4... 

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. ... 

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... 

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... 

The NOEL is used in setting exposure limits such as the Acceptable Daily Intake (ADI) for chemicals such as food additives or Threshold Limit Values (TLV) for industrial chemicals, usually with a 100-fold or sometimes greater safety factor to take account of species differences in response and human variability in response ... 

In 1954, the Food and Drug Administration published a paper that defined the basis for the acceptable daily intake (ADI). The ADI was a threshold for intake of a chemical for a large population, below which there should be no significant toxic risks. The paper not only defined a procedure for the ADI, but also described the use of safety factors and how animal data could be used to estimate risk to humans. A no effect level was determined from animal studies and a safety factor of 100 was used to establish a safe level. Tolerances for chemical additives and pesticides were calculated, comparing the safe level to the residue concentration of these chemicals in crops (e.g., wheat) and that crop s contribution to the individual s daily diet. 

In the case of harmful substances taken in by human beings through food or contact with articles of daily use , a value is determined for the quantity of the substance that is considered safe or tolerable when taken in daily. This accepted daily intake (ADI) is derived from animal experiments. The highest dose found to be without effects in the experiments (no observed effect level (NOEL)) is divided by a safety factor that depends on the extent of the data available and the nature of the effect ... 

In addition to the concerns relating to occupational exposure described above, the use of quinoxalines (see list in Table 1.4) in food-producing species is associated with food safety concerns. The genotoxic and carcinogenic nature of carbadox and its metabolites and the presence of relatively persistent residues in edible tissues of pigs treated with carbadox resulted in the JECFA not allocating an acceptable daily intake (ADI). In the case of olaquindox, the JECEA concluded that the substance is potentially genotoxic and that the toxicity of its metabolites is inadequately understood. For these reasons, the JECFA was unable to determine the amount of residues in food that did not cause an appreciable risk to human health, and thus MRLs were not established for these compounds by the CAC (see Chapter 3 for further discussion). Details... 

Acceptable daily intake (ADI) The amount of a food additive that can be ingested daily in the diet without appreciable risk, determined on the basis of all facts known at the time. Without appreciable risk refers to the practical certainty that injury will not result, even after a lifetime of experience. The ADI is a practical approach to determining the safety of food additives and is a means of achieving some uniformity of approach in regulatory control. It serves to ensure that the actual human intake of a substance is well below toxic levels. In the United States, ADIs are determined by the U.S. Food and Drug Administration (FDA). 

For the reasons outlined earlier, effective control and regulation of the use of these preservatives in foods is very important to ensure consumer safety. The EFSA has established an acceptable daily intake (ADI) of nitrite, that is, the amount that can be ingested without adverse effects on human health (EFSA, 2003). The ADI of nitrite in a daily diet is up to 0.07 mg of nitrite per kg of body weight per day (equivalent to 3.6 mg/day for a person weighing 60 kg). Because some nitrate from food is converted to nitrite in our body, there is also an ADI for the amount of nitrate we eat. The acceptable daily limit of nitrate is up to 3.7 mg/kg of body weight per day (equivalent to 219 mg/day for a person weighing 60 kg), (FAO/WHO, 2003a,b,c lARC/WHO, 2010). 

Safety assessment of preservatives, as for other food additives, is based on reviews of all available toxicological data, including observations in humans and in animal models. From the available data, a maximum level of an additive that has no demonstrable toxic effect is determined. This is called the no observed adverse effect level (NOAEL) and is used to determine the acceptable daily intake (ADI). The ADI refers to the amount of a food additive that can be taken daily in the diet, over a lifetime span, without any negative effect on health. Food additive legislation adopted by the European Union is included in several European Parliament and Council Directives (Directives 95/2/EC and 2006/52/ EC, which have been replaced by the Regulation (EC) 1333/2008 in 2011). 

The scientific committees mentioned earlier assess the safety for consumers of foods derived from animals treated with coccidiostats by assessing the available data from studies of the pharmacokinetics (including metabolism and residue depletion) in the target species and laboratory animals, toxicological studies and any available observations in exposed humans. Consumer safety is expressed numerically as an acceptable daily intake (ADI) and legal limits applied to concentrations of residues permitted in foods are established as a... 

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