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Risk Assessment of Pulegone in Foods Based on Benchmark Dose-Response Modeling
Verena Voigt1,2, Heike Franke1, Dirk W Lachenmeier2
1Postgraduate Study of Toxicology and Environmental Protection, Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig, Härtelstrasse 16-18, 04107 Leipzig, Germany.
Abstract:
This study presents a new risk assessment of pulegone, a substance classified as possibly carcinogenic to humans (Group 2B) by the WHO International Agency for Research on Cancer (IARC). The analysis used data from a two-year carcinogenicity studies in rats and mice conducted by the National Toxicology Program (NTP) in 2011. Because of the absence of a no-observed adverse effect level (NOAEL) in these studies, the benchmark dose (BMD) approach was employed as an alternative risk assessment method. The lowest BMD lower confidence level (BMDL) of 4.8 mg/kg b.w./day among the eight endpoints served as the point of departure for calculating an acceptable daily intake (ADI) of 48 μg/kg b.w./day. This new ADI is significantly lower than the previously established tolerable daily intake of 0.1 mg/kg b.w./day set in 1997. The analysis also considered various genotoxicity studies, which indicate that pulegone's effects follow a nongenotoxic, thresholded mechanism. The estimated intake levels of pulegone in the European Union and USA were below the newly calculated ADI, suggesting a low health risk based on current consumption patterns.
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