Exposure/potency index

In order to express the carcinogenic response or potency, a dose descriptor is used, for example the Tumorigenic Dose (TD). The TD is often set at a defined incidence, for example 5%, the TD5, defined as the dose (or concentration) associated with a 5% incidence of mmors. The dose descriptor can serve as the basis for development of an Exposure/Potency Index (EPl), which is the estimated daily human exposure divided by the TD. A calculated EPl of 10 for the TD5 represents a one million-fold difference between the human exposure and that at the lower end of the dose-response curve, on which the estimate of potency is based. 

The TEF approach normalizes exposures to common mechanism chemicals with different potencies to yield a total equivalent exposure (TEQ) to one of the chemicals, the index compound. TEFs are derived as the ratio of the POD of the index compound to that of each member in the group. The exposure to each chemical is then multiplied by the respective TEF value to express exposure in terms of the index compound. Summation of these values result in the total combined exposure (TEQ) expressed in terms of the index compound. 

The UK Pesticide Safety Directorate (PSD) has decided to use the TEF approach for assessment of combined risk from exposure to mixtures of acetyl cholinesterase inhibitors (organophosphate (OP) compounds and carbamates) (PSD 1999). Despite clear differences in the action of carbamates and OP compounds, the index compounds selected for all acetyl cholinesterase inhibitors were either aldicarb (carbamate) or chlorpyrifos (OP). The POD for determining relative potency was predetermined as the dose level that produced 20% inhibition of red blood cell cholinesterase in a 90-day dietary study in rats. 

Ames also uses the CPDB to create an index of the relative cancer risks humans face, given the potency of each chemical and the average human exposure (Ames, Magaw, and Gold 1987 Gold et al. 

Although one cannot say whether the ranked chemical exposures are likely to be of major or minor importance in human cancer, it is not prudent to focus attention on risks at the bottom of a ranking if the same methodology identifies numerous, common human exposures that pose much greater possible risks. Our rankings are based on the human exposure/rodent potency (HERP) index, which is the ratio between the average human exposure to a chemical and the dose that caused cancer in 50 percent of exposed rodents. 

In a regime of not knowing what to do the TVOC indicator was bom. The TVOC s mass/m3 was suggested as an indicator of exposure to a mixture of VOCs and of its potency to cause effects reviewed by IVtelhave (2000b, 2001). From the beginning it was underlined that this TVOC indicator is intended as an ad hoc tool meant for screening and for sensory irritation (i.e., non-adverse secondary causalities as described above). The indicator is based on the assumption that additivity can be used to calculate a summation index which indicates low risk of effects when below one. 

Component methods include those based on the assumption of response addition (e.g., addition of probabilistic cancer risks) or dose addition (e.g., relative potency factors (RPFs), hazard indexes (HI)). The advantages of component methods include an ability to utilize single chemical exposure and dose-response information to estimate a mixture risk and the flexibility to compare mixtures containing the same chemicals, but in different concentrations and proportions. 

The HI Approach For historical reasons seemingly based on data availability, the HI approach is the most often used approach, and it is traditionally applied to noncarcinogens. The hazard index is found by integratings the exposure level and the related toxicity into a single value with potency-weighted dose additions. The HI approach is simple to implement but somewhat limited in its scope, however, since it can underpredict or overpredict risk estimates. Initially... 

Risk Characterization. Once a quantitative exposure assessment has been made, Risk Assistant allows the user to automatically calculate lifetime excess cancer risk and/or a hazard index for toxic non-carcinogenic effects of chronic exposure for any agent included in the toxicity databases which currently include about 300 compounds. The appropriate hazard values (slope-potency factors and reference doses) for the relevant routes of exposure are automatically retrieved from the databases. The uncertainty calculations in the exposure assessment can also be retrieved to assess the range of risks associated with a given exposure situation. 

The analysis of bactericidal index values after a short time of drug exposure confirms the higher potency of hydrogels compared with that of ofloxacin (Fig. 22). 

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