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Botanical dietary supplements (BDS) are used around the world for many purported therapeutic properties. The selection of an authentic product and it's phytochemical characterization is critical to generate robust safety data. Because botanicals are complex mixtures with variable quality, identification of a representative product for testing has been challenging. Echinacea is used for its purported immune stimulant properties and was listed as the 2 nd top-selling BDS in 2018. However, there are limited safety data for Echinacea. Hence, the National Toxicology Program (NTP) has selected Echinacea for safety testing using rodent models. Here, we describe selection and comprehensive characterization of an Echinacea purpurea root extract to be used in the NTP testing program. Using non-targeted chemical analyses combined with chemometric analysis, a potential unfinished product (i.e., an extract that serves as source material for finished products) of Echinacea purpurea was selected. The product was then authenticated using chemical and DNA techniques and characterized, including the phytochemical composition. Among numerous constituents identified, caftaric acid, chicoric acid, chlorogenic acid and dodeca-2(E),4(E),8(Z),10(E/Z)-tetraenoic acid isobutylamide made up a small fraction of the extract. Based on these analyses, an approach is proposed for test article selection for Echinacea research which can be adapted to other botanicals.

2-Hydroxy-4-methoxybenzophenone (HMB) is a common ingredient in sunscreens and other personal care products and thus significant potential exists for human exposure. HMB was nominated to the National Toxicology Program (NTP) for testing due to its high exposure through consumer products and inadequate toxicological data at the time, which also included increasing concern for the potential effects of HMB on reproduction and development. HMB is metabolized to numerous metabolites in vivo and in vitro including 2,4-dihydroxybenzophenone (DHB), 2,3,4-trihydroxybenzophenone (THB) and 2,5-dihydroxy-4-methoxybenzophenone (2,5-DHMB) as well as their corresponding glucuronide and/or sulfate conjugates. In this study, we have developed and validated a liquid chromatography-tandem mass spectrometry method to quantitate free (unconjugated) HMB and DHB, and total (combined conjugated and unconjugated) HMB, DHB, THB and 2,5-DHMB. The method was successfully applied to quantitate these analytes in plasma from postnatal day 28 and 56 male and female Harlan Sprague Dawley rat pups following perinatal dietary exposure to 0 (control), 3,000, 10,000 and 30,000 ppm HMB beginning on gestational Day 6. All determined analyte concentrations increased with increasing dose and were significantly higher than the controls at both timepoints. All the total analytes were quantified in all plasma samples and total concentrations were considerably higher than free, suggesting extensive conjugation. Mean concentrations of total HMB and DHB were higher (~100-300-fold) than the free HMB and DHB concentrations, and total concentrations in plasma were approximately HMB≈DHB > 2,5-DHMB»THB. Free and total analyte plasma concentrations were not sex-dependent and in general, both free and total analytes were detected in the control samples. Comparison of our rat data, using the internal dose, with human data available in the literature suggests that the rat doses used in our studies were within 4-fold of the human dose.

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