Bioavailability of cyanide after consumption of a single meal of foods containing high levels of cyanogenic glycosides: a crossover study in humans

Abstract

The acute toxicity of cyanide is determined by its peak levels reached in the body. Compared to the ingestion of free cyanide, lower peak levels may be expected after consumption of foods containing cyanogenic glycosides with the same equivalent dose of cyanide. This is due to possible delayed and/or incomplete release of cyanide from the cyanogenic glycosides depending on many factors. Data on bioavailability of cyanide after consumption of foods containing high levels of cyanogenic glycosides as presented herein were necessary to allow a meaningful risk assessment for these foods. A crossover study was carried out in 12 healthy adults who consumed persipan paste (equivalent total cyanide: 68 mg/kg), linseed (220 mg/kg), bitter apricot kernels (about 3250 mg/kg), and fresh cassava roots (76-150 mg/kg), with each "meal" containing equivalents of 6.8 mg cyanide. Cyanide levels were determined in whole blood using a GC-MS method with K(13)C(15)N as internal standard. Mean levels of cyanide at the different time points were highest after consumption of cassava (15.4 µM, after 37.5 min) and bitter apricot kernels (14.3 µM, after 20 min), followed by linseed (5.7 µM, after 40 min) and 100 g persipan (1.3 µM, after 105 min). The double dose of 13.6 mg cyanide eaten with 200 g persipan paste resulted in a mean peak level of 2.9 µM (after 150 min). An acute reference dose of 0.075 mg/kg body weight was derived being valid for a single application/meal of cyanides or hydrocyanic acid as well as of unprocessed foods with cyanogenic glycosides also containing the accompanying intact β-glucosidase. For some of these foods, this approach may be overly conservative due to delayed release of cyanide, as demonstrated for linseed. In case of missing or inactivated β-glucosidase, the hazard potential is much lower.

Keywords: Bioavailability; Bitter apricot kernels; Cassava; Cyanide; Cyanogenic glycosides; Linseed; Persipan.

Fig. 1

Chemical structures of the main cyanogenic glycosides in the foods investigated

Fig. 2

a Concentration–time curves of cyanide in whole blood after consumption of 100 g persipan paste, 30.9 g linseed, about 2.1 g bitter apricot kernels, and 76–150 g unprocessed cassava (equivalent dose of cyanide: 6.8 mg each). Individual curves of the 12 participants are displayed in grey; the curve of the means is displayed in black (bold). b Concentration–time curves of cyanide in whole blood after consumption 200 g persipan paste (equivalent dose of cyanide: 13.6 mg). Individual curves of the 12 participants are displayed in grey; the curve of the means is displayed in black (bold)

Fig. 3

Dose dependency of the concentration–time curves of cyanide in whole blood after ingestion of different amounts of linseed (7.5–100 g with a cyanide content of 220 mg/kg) by test person No. 5 (left side). On the right side, the peak levels are displayed versus the dose of linseed

Fig. 4

Dose dependency of the concentration–time curves of cyanide in whole blood after ingestion of different amounts of persipan paste (100, 200, and 400 g with a cyanide content of 68 mg/kg) by test person No. 5

Fig. 5

Concentration–time curves of cyanide in whole blood after ingestion of different foods, amygdalin, and linamarin by test person No. 5 (equivalent dose of cyanide: 6.8 mg each, n = 1 each)