Provisional Tolerable Weekly Intakes

The term acceptable is used widely to describe safe levels of intake and is apphed for chemicals to be used in food production such as, e.g., food additives, pesticides, and veterinary dmgs. The term tolerable is applied for chemicals unavoidably present in a media such as contaminants in, e.g., drinking water and food. The term PTWI (Provisional Tolerable Weekly Intake) is generally used for contaminants that may accumulate in the body, and the weekly designation is used to stress the importance of limiting intake over a period of time for such substances. The tolerable intake is similar in definition and intent to terms such as Reference Dose and Reference Concentration (RfD/RfC), which are widely used by, e.g., the US-EPA. For some substances, notably pesticides, the ARID (Acute Reference Dose), is also established, often from shorter-term studies than those that would support the ADI. The ARfD is defined as the amount of a substance in food that can be consumed in the course of a day or at a single meal with no adverse effects. 

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 at the No Observed Adverse Effect Level (NOAEL). The NOAEL is used as the basis for setting human safety standards for contaminants, Provisional Tolerable Weekly Intakes (PTWIs) or Tolerable Daily Intakes (TDIs).1... 

The outputs from risk assessment will normally include information about the relationship between dose and risk and estimates of levels of doses and thus risks in the population. For contaminants that have a toxicological threshold the Provisional Tolerable Weekly Intake (PTWI) might be defined and the number of consumers who have the potential to exceed this level of intake quantified. If a PTWI cannot be established (such as for genotoxic carcinogens) then it may be possible to quantify the proportion of a population exposed to a given level of risk by using QRA methods. If QRA methods cannot be applied then a qualitative assessment can be made such as to reduce intake levels to as low as is reasonably practicable. In either case it is the function of risk management to identify an optimal course of action to minimise the risk to consumers. 

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. 

Lombardy on 231 breast milk samples taken on the third or fourth day after delivery showed extremely different concentration values for Pb (17.1 + 31.8 pg l-1, range 2-216 pgl-1) and Cd (1.7 + 2.4 pgl-1, range 1-20 pgl-1). Some 9.5 percent of breast-feds on day 6 of breast-feeding ingested quantities of Pb higher than the Provisional Tolerable Weekly Intake (PTWI) (25 pg kg-1) [14]. 

Organization (WHO) recommends limits for the safe intake of chemical elements. The limit for Hg is 300 pg per week of which a maximum of 200 pg is Me-Hg [11]. In April 2004 the European Food Safety Authority (EFSA) published new limits for Me-Hg. On the one hand, a Provisional Tolerable Weekly Intake (PTWI) of 1.6 pg kg-1 body weight is given on the other hand, a significantly lower intake limit of 0.7 pg kg-1 body weight per week from a previous evaluation by the United States National Research Council (USNRC) is established [12]. 

The guideline value for mercury is conservative because it is based on the provisional tolerable weekly intake (PTWI) for methylmercury, which is more toxic than mercury. Monitoring would normally only be justified if mercury were known to be present due to unusual circumstances, such as an industrial or mining discharge. 

For contaminants and naturally occurring toxicants, levels corresponding to tolerable intakes such as the provisional maximum tolerable daily intake (PMTDI) or provisional tolerable weekly intake (PTWI) are established when there is an identifiable no-observed-effect level, that is, a threshold of effect can be assumed based on available data. When a noobserved-effect level cannot be identified, the Committee provides other advice, such as identification of the food(s) that contributes most to intake. This allows for targeted management actions in order to decrease exposure. 

The joint expert committee for food additives and contaminants revised the Provisional Tolerable Weekly Intake for methylmercury, recommending that it be reduced to l.fipgkg body weight per week in order to sufficiently protect the developing fetus. 

ADIs for food additives and veterinary drugs and provisional tolerable weekly intakes (PTWIs) for contaminants are proposed by the WHO experts. 

Km Michaelis constant PTWI Provisional tolerable weekly intake... 

Daily intake of Pb in humans is estimated to range from 20 mg to 400 mg per person. The FAO/WHO Expert Committee established a Provisional Tolerable Weekly Intake (PTWI) of 3000 mg, corresponding to ca. 500 mg/d. Only a half of this amount appears to be safe for children. About 5 to 15% of ingested Pb is absorbed. This amounts to 15 to 25 mg/d and represents two thirds of the total absorbed lead. By contrast, about 20 to 40% of the inhaled Pb is absorbed, amounting to about 8 mg/d, or one third of the total absorbed lead. 

The World Health Organization (WHO) has set a provisional tolerable weekly intake level for OTA at lOOng/Kg of body weight, taking its potentially carcinogenic effect into account (JEFCA, 2001). The tolerated maximum concentrations are based on a tolerable daily intake of 5 ng/(kg of body weight) suggested by the ED Scientific Committee on Food (Commission of the European Communities, 1998). CE... 

Provisional Tolerable Weekly Intake (PTWI) of Toxic Elements... 

Note PTWI = provisional tolerable weekly intake tins term refers to contaminants such as heavy metals ... 

Abbreviations EPA, Environmental Protection Agency ATSDR, Agency for Toxic Substances and Disease Registry FDA Food and Drug Administration NOAEL no-observed-adverse-effect level LOAEL, lowest-observed-adverse-effect level UF, uncertainty factor SF, safety factor RfD, reference dose (an amount of a substance that is anticipated to be without adverse health effects in humans, including sensitive populations, when ingested daily over a lifetime MRL, minimal risk level (an estimate of daily human exposure to a hazardous substance that is likely to be without an appreciable risk of adverse noncancer health effects over a specified route and duration of exposure) pTDI, provisional tolerable daily intake (maximum daily exposure level to a contaminant provisional meaning that it is considered temporary until more data are available, especially the completed Seychelles study) JECFA, Joint FAO/WHO Expert Conunittee on Food Additives pTWl, provisional tolerable weekly intake. 

To ascertain whether a general population is at risk or not, it is necessary to estimate the actual dietary intake of a toxic metal by comparison with provisional tolerable weekly intakes (PTWIs) [1]. This estimation is a measure of human exposure to pollutant and thus indispensable for risk assessment... 

In Greenlanders, the average weekly Cd intake for an individual was 1004 gg, which was considerably higher than that in uncontaminated areas, and also above the WHO Provisional Tolerable Weekly Intake (PTWI) of 7 gg kg body weight (Johansen 2000). 

The FAO/WHO provisional tolerable weekly intake (PTWI) of 15 pg As kg body weight for a 60-kg man, when translated to a daily basis, is 2.1 pg kg per day (FAO/WHO 1989). The above estimated figures thus result in a range of about 0.78 pg kg per day for the average Japanese to about 0.18 pgkg per day for the average US American. This is, even for outliers, well below the PTWI. 

PTWI (Provisional Tolerable Weekly Intake) A provisional estimate of the amount of a hazardous substance with cumulative properties in food or drinking water, expressed on a body-weight basis, that can be ingested weekly over a lifetime without appreciable health risk. 

PTWI, Provisionably tolerable weekly intake PMTDI, Provisionably maximum tolerable daily intake PDDR, Provisionably daily dietary requirement. 

PSA potentiometric stripping analysis PS-MS plasma source-mass spectrometry PTFE polytetrafluorethylene PTMI Provisional Tolerable Monthly Intake PTWI Provisional Tolerably Weekly Intake (WHO)... 

Pollutant (Average) weekly intake with the food Provisional tolerable weekly intake F.lfects/special features... 

Table 3 gives an overview of pollutants relevant to the soil and the potential risk to human beings constituted by them when they are taken in with the food. The stated values for provisional tolerable weekly intake correspond to the ADI but are based on a week instead of 1 day. 

In order to prevent any further increase of cadmium in agricultural soils likely to increase the dietary intake of future generations, the WHO recommended that airborne levels of cadmium in rural areas should be as low as possible and not exceed 5 ng/m and in urban or industrial areas levels should not exceed 10 ng/m (WHO, 1994). The provisional tolerably weekly intake (PTWI) for the total cadmium intake was set at 7 p.g/kg of body weight (WHO, 1989). A guideline value for cadmium in drinking water of 3 p.g/1 was established based on an allocation of 10% of the PTWI (WHO, 1993,1996). 

WHO and FAO establish the PTWI (Provisionally Tolerable Weekly Intake) for lead 25 p-g/kg body weight (WHO, 1993). 

Ochratoxin A was first evaluated by the Committee at its thirty-seventh meeting (Annex 1, reference 94). The key adverse effects noted involved toxicity to the kidney. The Committee established a provisional tolerable weekly intake (PTWI) of 112 ng/kg body weight (bw), on the basis of deterioration of renal function in pigs, for which the lowest-observed-effect level (LOEL) was 8 pg/kg bw per day, and application of a safety factor of 500. At that time, the Committee recommended that further studies be conducted to elucidate the role of ochratoxin A in causing nephropathy in pigs, the mode of action of ochratoxin A as a kidney carcinogen in rodents and the possible role of ochratoxin A in human disease. 

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