A probabilistic effect assessment model for hazardous substances at the workplace

Investigation of the state of the science on combined actions of chemicals in food through dissimilar modes of action and proposal for science‐based approach for performing related cumulative risk assessment

“…Hattis and colleagues have compiled a large database of individual studies, which investigated differences in effectrelated observations or toxicokinetic parameters in humans (Hattis et al 1999a;Hattis et al 1999b;Hattis and Anderson 1999). As a first attempt to use such data to put extrapolations on a sound footing, the database was utilized by Schneider et al to derive distributions to be used in a probabilistic model for effect assessment (Schneider et al 2006). For the data sets about differences in effect-related doses in adults retrieved from the Hattis database these distributions describe the ratios between the group mean effective dose and the dose causing the effect in a specified (low) quantile of the examined population.…”

“…The following ratios of the medians of distributions were obtained by Schneider et al from the Hattis-database (Schneider et al 2006):…”

Re: Ritter, Leonard, Totman, Céline, Krishnan, Kannan, Carrier, Richard, Vézina, Anne, Morisset, Veronique. (2007). Deriving uncertainty factors for threshold chemical contaminants in drinking water.Journal of Toxicology and Environmental Health, Part B, 10:527–557

“…Probabilistic models may serve as an aid in the process of combining all factors (similar to Schneider et al, 2006) and should also include probabilistic quantification of exposure.…”

“…1907/2006 The scientific community has struggled for some time, and continues to struggle, with the most appropriate means by which to utilize data derived from laboratory studies in experimental animals for estimating human health risks from exposure to potentially toxic chemicals-either as direct additives or as avoidable and unavoidable contaminants.…”

Dispelling urban myths about default uncertainty factors in chemical risk assessment – sufficient protection against mixture effects?

“…A critical evaluation of these choices should consider whether the distribution was based on data as opposed to a theoretical distribution, whether these data were derived from humans or animals only, and whether adjustment for allometric scaling was included. The only analysis that would meet these requirements is that of [106] for which we calculated that the default uncertainty factor of 100 would be exceeded by 15-20% of chemicals if a safe level for human were to be extrapolated from experimental data in the rat (Table 6). When considering that sensitive subgroups and multimodal distributions of inter-individual sensitivity have not been taken into account in those analyses, an unwavering belief in the undue conservativeness of the default uncertainty factor appears ill-founded Table 6.…”