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2008
Conference Paper
Title
Influence of study parameters on TTC
Abstract
The Threshold of Toxicological Concern (TTC) concept established by Munro et al. provides generic exposure thresholds for groups of chemicals. Below the TTC no appreciable risk to human health is assumed. Thresholds for oral toxicity were defined by grouping food ingredients into three structural classes according to the Cramer decision-tree. In order to apply the Cramer classification to industrial chemicals and to study the influence of study duration, species and route on TTC, a comparison of the Munro database with RepDose (database on repeated dose toxicity) was performed. Both databases contain a similar number of chemicals, 95 are identical. NOELs/LOELs in both databases show a wide distribution in each Cramer-class. Median/mean analyses reveal that NOELs/LOELs in RepDose are lower than in Munro, also for the shared 95 substances. Means/medians decrease significantly from Cramer-class 1 to 3 in both databases the difference being higher in Munro than in RepDose. A comparison of subchronic, chronic and lifespan studies reveals a significant decrease of mean/median LOELs with study duration. Class 1 and 3 differ significantly for lifespan/subchronic studies in Munro and for all categories in RepDose. As seen before, the difference of Classes 1 and 3 does not exceed a factor of 5 in RepDose. The analysis of species gave similar results. Besides oral application, RepDose also contains inhalation studies. A preliminary analysis of LOELs/NOELs indicates, that inhalation studies will provide lower thresholds than oral application.