Regulatory Toxicology and Pharmacology 41 (2005) 66–72 www.elsevier.com/locate/yrtph 0273-2300/$ - see front matter  2004 Elsevier Inc. All rights reserved. doi:10.1016/j.yrtph.2004.09.004 Potato glycoalkaloids and adverse eVects in humans: an ascending dose study Tjeert T. Mensinga a,d,¤ , Adrienne J.A.M. Sips b , Cathy J.M. Rompelberg b , Klaas van Twillert c , Jan Meulenbelt a,d , Hester J. van den Top c , Hans P. van Egmond c a National Poisons Control Centre, National Institute for Public Health and the Environment, The Netherlands b Centre for Substances and Integrated Risk Assessment, National Institute for Public Health and the Environment, The Netherlands c Laboratory for Residue Analysis, National Institute for Public Health and the Environment, The Netherlands d Intensive Care 1 and Clinical Toxicology, University Medical Centre Utrecht, Utrecht, The Netherlands Received 15 June 2004 Available online 10 December 2004 Abstract Glycoalkaloids in potatoes may induce gastro-intestinal and systemic eVects, by cell membrane disruption and acetylcholinester- ase inhibition, respectively. The present single dose study was designed to evaluate the toxicity and pharmacokinetics of orally administered potato glycoalkaloids (-chaconine and -solanine). It is the Wrst published human volunteer study were pharmacoki- netic data were obtained for more than 24 h post-dose. Subjects (2–3 per treatment) received one of the following six treatments: (1– 3) solutions with total glycoalkaloid (TGA) doses of 0.30, 0.50 or 0.70 mg/kg body weight (BW), or (4–6) mashed potatoes with TGA doses of 0.95, 1.10 or 1.25 mg/kg BW. The mashed potatoes had a TGA concentration of nearly 200 mg/kg fresh weight (the presently recognised upper limit of safety). None of these treatments induced acute systemic eVects. One subject who received the highest dose of TGA (1.25 mg/kg BW) became nauseous and started vomiting about 4 h post-dose, possibly due to local glycoalkaloid toxicity (although the dosis is lower than generally reported in the literature to cause gastro-intestinal disturbances). Most relevant, the clearance of glycoalkaloids usually takes more than 24 h, which implicates that the toxicants may accumulate in case of daily consumption.  2004 Elsevier Inc. All rights reserved. Keywords: Glycoalkaloids; Chaconine; Solanine; Human; Pharmacokinetics; Potato; Public health 1. Introduction Potatoes (Solanum tuberosum) contain glycoalka- loids (GAs), a class of natural toxicants. The two major GAs are -chaconine and -solanine (Fig. 1), comprising 95% of all GAs. Both are glycosylated (trisaccharide) derivatives of the aglycone solanidine, a steroid alkaloid. Produced in bioactive parts of the plant (Xowers, young leaves, sprouts, and tubers), these substances protect the plant against fungi, insect pests and herbivores (Jadhav et al., 1981; Morris and Lee, 1984). GAs appear to have two toxic actions, one on cell membranes and another on acetylcholinesterase (Morris and Lee, 1984). The toxicity on membranes leads to cell disruption, thought to be caused by the formation of destabilising complexes of the lipophilic moiety of the GAs with cho- lesterol in membranes (Keukens et al., 1992). Recent cell culture and experimental animal studies have shown that GAs may adversely aVect intestinal permeability (Patel et al., 2002). As a consequence, for humans with for instance chronic inXammatory bowel disease, exposure to higher TGA concentrations might cause persistence * Corresponding author. Fax: +31 30 254 1511. E-mail address: tjeert.mensinga@rivm.nl (T.T. Mensinga).