Risk assessment acceptable daily intake

Data on the safety studies were submitted to international agencies like the Joint Expert Committee for Food Additives of the WHO and FAO (JECFA), and the Scientific Committee on Food (SCF) of the EC. Both committees endorsed acesulfame K as a food additive. Initial acceptance was based on an NOEL of 900mg/kg in dogs which were considered to be the most sensitive species. Therefore Acceptable Daily Intake (ADI) values of 0-9 mg/kg of body weight were allocated.8 9 Evidence that rats would be an appropriate model for risk assessment was the reason for JECFA to change the ADI to 0-15 mg/kg of body weight on the basis of a no-effect level of 1500-3000 mg/kg in rats.10 Countries allocating their own ADI values like the USA and Canada have come to the same conclusion. The SCF still retains its 0-9 mg/kg ADI.11... 

The risk assessment comprises an effect assessment (hazard identification and hazard characterization) and an exposure assessment. The principles for the effect assessment of the active substances are in principle similar to those for existing and new chemicals and are addressed in detail in Chapter 4. Based on the outcome of the effect assessment, an Acceptable Daily Intake (ADI) and an Acceptable Operator Exposure Level (AOEL) are derived, usually from the NOAEL by applying an overall assessment factor addressing differences between experimental effect assessment data (usually from animal studies) and the real human exposure situation, taking into account variability and uncertainty for further details the reader is referred to Chapter 5. As a part of the effect assessment, classification and labeling of the active substance according to the criteria laid down in Directive 67/548/EEC (EEC 1967) is also addressed (Section 2.4.1.8). 

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. 

Risk assessment The process by which the nature and magnitude of risks are identified Reference dose (RfD) or acceptable daily intake (ADI)... 

Some critical differences in risk assessment procedure lead to confusing situations on a worldwide basis. These differences are due to some very controversial areas of safety issues including the calculation of the acceptable daily intake (ADI), the assignment of the ADI to maximum residue limit (MRL)/tolerance, the validation of the analytical methods needed to regulate drug residues, and the fitness of legislation to toxicology. 

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. 

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... 

Interspecies and intraspecies UFs have been used in the development of safe or threshold exposure levels for chronic, noncancer toxicity by health organizations throughout the world. Examples include the acceptable daily intake (ADI) (Lu 1988 Truhaut 1991 Lu and Sielken 1991), the tolerable daily intake (TDI) or tolerable concentration (TC) (Meek et al. 1994 IPCS 1994), the minimal risk level (MRL) (Pohl and Abadin 1995), the reference dose (RfD) (Barnes and Dourson 1988 Dourson 1996), and the reference concentration (RfC) (EPA 1994 Jarabek et al. 1990). The importance of using distribution-based analyses to assess the degree of variability and uncertainty in risk assessments has been emphasized in recent trends in risk analysis. This will enable risk managers to make more informed decisions and... 

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... 

In this sense, safety factors, margin of safety, low dose extrapolations, etc. are not risk assessment tools, they are risk management tools. Thus while it has been noted in scientific experiments and observations that animal to animal variations are seldom greater than an order of magnitude and sensitivity from one species to another is usually within a factor of ten, the 1/100 safety factor for establishing acceptable daily intake (ADI) is not a risk assessment decision, it is a risk managerial decision with scientific input. 

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. 

In the present study we estimated whether the intake of dioxin and dibenzofuran contaminated breast milk presents a potential risk to the health of the nursing infants in these populations. This was performed using "virtually safe" or "acceptable daily intake" values which various governmental agencies in the United States currently employ in their risk assessments for these compounds. 

Methods for toxicological safety assessments are multiple and varied - some are more reliable than others, some more radical than others, but all are important. Their nature greatly depends on their endpoints, namely, the degree of practical safety they attempt to attain. Unfortunately, the true validity of these methods can only be assessed retrospectively, that is to say, by the record of cases of health impairment they were able to prevent over a reasonable period of time. Because of this and the uncertainty inherent in any extrapolation technique, the final products expressed in numerical form can only be considered as opinions. Some important toxicological opinions presented in numerical form are the LD50 the quantitative risk assessments, the threshold limit values (TLV), and the acceptable daily intakes (ADIs). 

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