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In Vitro Bioactivity in ToxCast Assays for Fruit and Vegetable Juices (TDS)
Citation:
Wetmore, B., M. Black, E. Berg, M. Polokoff, K. Houck, R. Judson, R. Thomas, AND M. Anderson. In Vitro Bioactivity in ToxCast Assays for Fruit and Vegetable Juices (TDS). Presented at ToxCast Data Summit, RTP, NC, September 29 - 30, 2014. https://doi.org/10.23645/epacomptox.5197186
Impact/Purpose:
Poster for ToxCast Data Summit
Description:
The ToxCast and Tox21 programs have generated in vitro screening data for over 1000 chemicals to aid in hazard identification and setting chemical testing priorities. These data, together with in vitro pharmacokinetic data, are used to infer possible toxic responses and external concentrations required to elicit these effects. There is only limited experience in evaluating dose-response for natural products in these assays. In this study, juices were extracted from 30 organically grown fruits and vegetables. These juices were screened in concentration-response format across primary human cell and co-culture assays (BioMAP systems) to compare juice bioactivities against those of ToxCast chemicals and reference compounds. Extensive bioactivities were observed across the BioMAP Diversity 8 Panel, with juices eliciting 4-fold more LEC (i.e., lowest effective concentration) hits than ToxCast chemicals. Unsupervised similarity searches against the BioMAP reference compound database identified similarities between several juices and therapeutic and/or industrial chemicals. Broccoli displayed significant similarity to mitomycin C and the fungicide mancozeb; kale and sweet potatoes displayed similarities to JAK3 and JAK1/2 kinase inhibitors, respectively. To relate in vitro concentrations to administered dose, the filtered juice yield per g item was used with the plasma volume of a 75 kg adult to approximate % juice present in systemic circulation after eating, assuming complete uptake and no first-pass metabolism. This value was used as a surrogate for target tissue concentration. To achieve tissue concentrations equivalent to the concentration at which apples elicited LECs in 10% of the assays, one-half cup (or 0.06 kg) apples would need to be consumed. Alternately, assuming a daily exposure to fludioxonil at maximal residue levels across over 20 commonly consumed fruits and vegetables (~3 mg/kg produce), one would need to consume 4.5 kg apples to achieve the fludioxonil oral equivalent (0.18 mg/kg body weight/day) associated with the in vitro 10% LEC hit rate concentration. It is important to note that the bioactivities observed do not necessarily lead to adverse effects. These data provide context for assessing the in vivo relevance of in vitro concentration-response and bioactivity data generated in ToxCast. This abstract does not necessarily reflect EPA policy.
