Provisional Tolerable Weekly Intake PTWI

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. 

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

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. 

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

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. 

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). 

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. 

A provisional tolerable weekly intake, PTWI, of lead was determined (by a Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives, JECFA) to be 0.025 mg/kg body weight in 2004 [11]. Also in 2004, the WHO s standard for lead in drinking water was 0.01 mg/L [11]. In addition as mentirmed in a 2007 WHO pubhcation, the WHO recommendation for the limit of lead in herbal medicines and products was 10 mg/kg [12]. 

After these introductory remarks, I shall attempt to give you an account of the current recommendations of the World Health Organization in this field. In particular, I will stress the "safe" levels of intake based on concepts such as Acceptable and Admissible Daily Intake (ADI), respectively, for intentional food additives and pesticide residues in food Provisional Tolerable Weekly Intake (PTWI) for cumulative toxic metals figures for body burdens and the corresponding "safe" limits recommended for foodstuffs, including the relatively recent definition of irreducible limits to deal with the problem of trace contaminants in food. 

Provisional tolerable weekly intake (PTWI) for aluminium, in Toxicological evaluation of current food additives and contaminants, WHO-FAO Expert Committee on Food Additives, Geneve, 1989, p. 113-154.. 

The toxicity of cadmium has been known for more than 150 years, as summarized recently by Nordberg [1] nevertheless, there is stiU an ongoing discussion on cadmium-induced toxicity at comparatively low exposure conditions. With respect to non-cancer endpoints, the European Food Safety Authority (EFSA) has lowered the Provisional Tolerable Weekly Intake (PTWI) of 7 pg/kg bw established previously by the Joint FAOAVHO Expert Committee on Food Additives to a TWI of 2.5 pg/kg bw based on cadmium-induced nephrotoxicity [2]. One other endpoint of toxicological concern on low exposure conditions of the general population... 

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