Acute effects of a low-dose atropine/scopolamine mixture as a food contaminant in human volunteers
Article first published online: 9 AUG 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 33, Issue 9, pages 980–990, September 2013
How to Cite
Perharič, L., Juvan, K. A. and Stanovnik, L. (2013), Acute effects of a low-dose atropine/scopolamine mixture as a food contaminant in human volunteers. J. Appl. Toxicol., 33: 980–990. doi: 10.1002/jat.2797
- Issue published online: 23 JUL 2013
- Article first published online: 9 AUG 2012
- Manuscript Revised: 9 JUN 2012
- Manuscript Accepted: 9 JUN 2012
- Manuscript Received: 10 MAY 2012
- atropine/scopolamine mixture;
- low-dose exposure;
- 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.