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

Abstract

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.

Scientific Opinion on Tropane alkaloids in food and feed

“…Perharič et al (2013a) examined the effects of a mixture of atropine and (-)-scopolamine hydrochloride added to buckwheat-based meal in a double-blind study involving 20 healthy adult males (18-28 years). The volunteers were exposed to control or four doses of atropine and (-)-scopolamine according to a cross-over protocol with a period of at least two weeks between the different meals.…”

“…Perharič et al (2013a) estimated the ingested doses of atropine and (-)-scopolamine, taking into account the breakdown during cooking, and expressed the total dose as atropine (Table 13). The CONTAM Panel noted that atropine is a racemic mixture of (+)-and (-)-hyoscyamine, and that only the (-) enatiomer has anticholinergic activity.…”

“…According to self-reporting, a student experienced immediately after the ingestion of 2 cups of tea prepared from 7-10 g of leaves of D. stramonium dry mouth, blurred vision, tachycardia, urinary retention and hallucination (Dieckhöfer et al, 1971). Perharič et al (2013a) examined the effects of a mixture of atropine and (-)-scopolamine hydrochloride added to buckwheat-based meal in a double-blind study involving 20 healthy adult males (18-28 years). The volunteers were exposed to control or four doses of atropine and (-)-scopolamine according to a cross-over protocol with a period of at least two weeks between the different meals.…”

Simultaneous quantification of three tropane alkaloids in goji berries by cleanup of the graphene/hexagonal boron nitride hybrids and ultra‐high‐performance liquid chromatography tandem mass spectrometry

“…Overdose of atropine gives rise to seizures, pupil dilatation, disturbance of vision, and arrhythmias [7]. According to European Food Safety Authority opinion [8], more attention must be paid to the content of atropine and scopolamine in food, such as tea [9], cereal products [10], and food products [11]. European Union regulation 2016/239 stated that the LOQ for atropine and scopolamine should be preferably less than 5.0 µg/kg and not more than 10.0 µg/kg for the agricultural raw materials, ingredients, supplements food and herbal teas, and should preferably be lower than 2.0 µg/kg for finished foods and 1.0 µg/kg for cereal-based foods for infants and young children.…”

Simultaneous quantification of atropine and scopolamine in infusions of herbal tea and Solanaceae plant material by matrix‐assisted laser desorption/ionization time‐of‐flight (tandem) mass spectrometry

“…The minimal toxic dose reported for Atr is 100 μg/kg body weight (bw) and for Scp 14 μg/kg bw . Perharic et al determined the acute reference dose (ARfD) for each TA to be 0.01 μg/kg bw . The ARfD defines an estimate of residual amounts in food the daily oral intake of which does not cause an appreciable health risk of deleterious effects in humans during their lifetime.…”