Body weight basis, estimating exposure

An important outcome of the JECFA evaluation is the establishment of an ADI for a food additive. The ADI is based on the available toxicological data and the no adverse effect level in the relevant species. JECFA defines the ADI as an estimate of the amount of a food additive, expressed on a body weight basis, that can be ingested daily over a lifetime without appreciable health risk (8). JECFA utilizes animal data to determine the ADI based on the highest no-observed-adverse-effect level (NOAEL), and a safety factor is applied to the NOAEL to provide a margin of safety when extrapolating animal data to humans. JECFA typically uses safety factors of 50, 100, or 200 in the determination of an ADI. The NOAEL is divided by the safety factor to calculate the ADI. The food additive is considered safe for its intended use if the human exposure does not exceed the ADI on a chronic basis. This type of information may potentially be used to help assess the safety of a pharmaceutical excipient that is also used as a food additive, based on a comparison of the ADI to the estimated daily intake of the excipient. 

Intake can be expressed either as a pollutant mass per unit time, as discussed above, or as a mass per kg of body weight per unit time. The latter expression facilitates comparison to health effects data, especially laboratory animal data, which are commonly reported in equivalent units. Similarly, depending on the route of exposure, intake may be estimated on an annual basis to address chronic effects, or on a smaller time scale for addressing acute effects including lethality, teratogenesis, reproductive and neurotoxic effects. 

Accumulation of 2,3,7,8-TCDD is reported in the liver of rats during lifetime exposure to diets containing 0.022 pg 2,3,7,8-TCDD/kg (Newton and Snyder 1978), or when administered orally at 0.01 pg/kg body weight once a week for 45 weeks (Cantoni et al. 1981). Liver residues of rats fed 2,3,7,8-TCDD were 0.54 pg/kg, or about 25 times dietary levels livers of rats dosed orally contained 1.05 pg/kg, or about 2.3 times the total dose received on a unit weight basis. Unlike toxicity, elimination rates of accumulated 2,3,7,8-TCDD were within a relatively narrow range. The estimated retention times of 2,3,7,8-TCDD in small laboratory mammals (rats, mice, guinea pigs, and... 

The animal to human extrapolation Involves an estimation of exposure equivalent to the body burden based on sig/food intake/— day, mg/kg of body weight/day, or sig/day interpolated from surface area. Traditionally species comparisons are made on a mg/kg dose basis, but this technique does not allow for differences in metabolism rate. Alternatively basing species extrapolations on body surface area affords such a correction. The use of ppm in the diet also reflects differences in metabolism rates. Dietary ppm may be converted to oig/kg/day by incorporation of food consumed per day and animal body weight. If compounds are metabolized (as most are) the use of ppm in the diet is probably superior. Furthermore its use will usually result in the most conservative estimates (13). 

The estimated average exposure to NDL-PCB contained in breast milk is up to two orders of magnitude higher for exclusively breastfed children, and is on average 1600 ng/kg body weight. Levels of population exposure to halogenated POPs are often determined on the basis of their concentrations in breast milk. The WHO study carried out in 2001/2002... 

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