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Study on inter-ethnic human differences in bioactivation and detoxification of estragole using physiologically based
Jia Ning1, Jochem Louisse2, Bert Spenkelink2
1Division of Toxicology, Wageningen University, Stippeneng 4, 6708 WE, Wageningen, The Netherlands. jia.ning@wur.nl.
Archives of Toxicology
|March 31, 2017
Summary
Physiologically based kinetic (PBK) modeling reveals lower estragole cancer risk in Chinese populations compared to Caucasians. This difference is due to reduced metabolic activation, suggesting tailored risk assessments are crucial for diverse ethnic groups.
Area of Science:
- Toxicology
- Pharmacokinetics
- Risk Assessment
Background:
- Food safety assessments require ethnic-specific data, especially for chemicals like estragole.
- Understanding inter-ethnic differences in chemical metabolism is vital for accurate risk evaluation.
Purpose of the Study:
- To predict ethnic variations in estragole's metabolic bioactivation and detoxification using physiologically based kinetic (PBK) modeling.
- To assess the applicability of Caucasian-based safety assessments to the Chinese population.
Main Methods:
- Developed PBK models using in vitro hepatic metabolism data from Chinese and Caucasian liver fractions.
- Quantified estragole conversion to its ultimate carcinogenic metabolite, 1'-sulfooxyestragole.
- Evaluated detoxification pathways of 1'-hydroxyestragole.
Main Results:
- PBK models predicted a 4.5-fold lower conversion of estragole to 1'-sulfooxyestragole in Chinese subjects (0.02%) compared to Caucasians (0.09%) at realistic intake levels.
- Detoxification rates of 1'-hydroxyestragole were similar between the two ethnic groups.
- This suggests a potentially lower risk associated with estragole exposure in the Chinese population.
Conclusions:
- PBK modeling effectively identifies ethnic differences in chemical metabolism and sensitivity.
- Findings support the need for refined, ethnicity-specific risk assessments for food-borne genotoxic carcinogens like estragole.
- This approach enhances the precision of chemical safety evaluations for diverse populations.