Acute effects of a low‐dose atropine/scopolamine mixture as a food contaminant in human volunteers

To verify the assumptions in our previous risk assessment of an atropine/scopolamine mixture in buckwheat flour, we performed a randomized, double‐blind, placebo‐controlled cross‐over study in 20 healthy, adult volunteers. The volunteers ingested a traditional Slovenian buckwheat meal, made of boiled buckwheat flour to which alkaloids were added. In addition to the placebo they ingested 0.12/0.10, 0.37/0.29, 1.22/0.95, 3.58/2.81 and 12.10/9.50 µg kg –1 body mass (BM) of the atropine/scopolamine mixture. The changes in body temperature, heart rate, salivary and sweat secretion, pupil size, near‐point vision and subjective symptoms were recorded regularly for 4 h after the ingestion. Decreased salivary and sweat secretion, increased heart rate and pupil size and reduced near‐point vision accompanied by characteristic subjective symptoms were observed at 12.10/9.50 µg kg –1 BM. At doses of 0.37/0.29 and 1.22/0.95 µg kg –1 BM, a significant decrease in the heart rate was noted, which we consider to be a critical effect of a low‐dose exposure to the atropine/scopolamine mixture. Although this did not have any clinical relevance in our subjects, it may have serious implications if it occurred in people with pre‐existent cardiac conditions or those on medications that may cause bradycardia. No significant changes in the observed end points were noted at 0.12/0.10 µg kg –1 BM. We estimate that the NOAEL (No Observed Adverse Effect Level) for the atropine/scopolamine mixture lies between the lower two administered doses. Applying the uncertainty factor of 10, we propose a new provisional Acute Reference Doses (ARfDs) of the mixture, i.e. 0.01 µg kg –1 BM for each alkaloid, and a further refinement using higher‐tier approaches. Copyright © 2012 John Wiley & Sons, Ltd.