CYANOGENIC GLYCOSIDES

Overview

Functional Class
Food Contaminant
NATURALLY_OCCURRING_TOXICANT

Evaluations

Evaluation year: 2011

Comments:
The Committee derived acute reference dose (ARfD) and PMTDI values for cyanogenic glycosides of 0.09 mg/kg bw of cyanide equivalents and 20 μg/kg bw/d, respectively. The ARfD value was derived from a benchmark dose lower confidence limit for 10% increased incidence (BMDL10) for fetal skeletal defects of 85 mg/kg bw from a developmental toxicity study conducted in hamsters with linamarin. A safety factor of 100 was applied to this BMDL10 value, and the resultant value of 0.9 mg/kg bw linamarin was converted to the equivalent value for cyanide of 90 μg/kg bw. The PMTDI was derived from a BMDL10 value of 1.9 mg/kg bw per day for decreased absolute cauda epididymis weights from a 13-week drinking water study conducted in male F344 rats with sodium cyanide and application of a 100-fold uncertainty factor. The Committee decided that it was not necessary to apply an additional uncertainty factor to account for the absence of a long-term study, considering the generally acute nature of cyanide toxicity and the sensitivity of the effect (i.e. the reduction of absolute cauda epididymis weight). Comparing the ARfD and PMTDI values to the available data for dietary exposure, dietary intake of cyanide from consumption of cassava (adults), apple juice (children), bitter apricot kernels, and ready-to-eat cassave chips/crisps all exceeded the ARfD of 90 μg/kg bw as cyanide equivalents by up to 10-fold, depending on the population group. There is also the potential to exceed the PMTDI of 20 μg/kg bw as cyanide for populations reliant on cassava as a staple food: between 1- and 3-fold in children and between 1- and 2-fold in adults. There is also a potential for those populations not reliant on cassava to exceed the PMTDI: between 1- and 5-fold for children and between 1- and 3-fold for adults.
Intake:
Estimated mean chronic dietary exposures to total HCN: 10 μg/kg bw/d (children) and 2–11 μg/kg bw/d (adults); 90th percentile total HCN: 10–40 μg/kg bw/d (children) and 10–12 μg/kg bw/d (adults). For all cassava chips at the ML of 10 mg/kg, acute dietary exposures to total HCN: maximum of 100 μg/kg bw/d (children) and 25 μg/kg bw/d (adults). Acute dietary exposures for large portion consumption of sweet cassava containing the Codex ML of HCN (50 mg/kg HCN): 150 μg/kg bw/d (adults) and 330 μg/kg bw/d (children). Exposure to total HCN from consumption of cassava flour containing the Codex ML of 10 mg/kg HCN: 30 μg/kg bw/d (adults) and 70 μg/kg bw/d (children). Chronic dietary exposures to HCN from consumption of sweet cassava and cassava flour containing HCN concentrations at their respective Codex ML values: 1-235 μg/kg bw/d and less than 0.1-14 μg/kg bw/d, respectively.
Tolerable Intake:
ARfD: 0.09 mg/kg bw cyanide equivalents; PMTDI: 20 μg/kg bw/d cyanide equivalents
Meeting:
74

Toxicological study

Pivotal Study:
For the ARfD (Frakes, Sharma & Willhite, 1985): A single linamarin dose of 0, 70, 100, 120 or 140 mg/kg bw was administered by oral gavage to pregnant hamsters on day 8 of gestation, with the fetuses removed on gestation day 15 and examined for internal and external malformations. Data were not reported by the study authors for individual litters; therefore, quantal data on a fetal basis were considered. For the PMTDI (NTP, 1993): Male F344 rats were exposed to sodium cyanide in drinking water at doses ranging from 1.4 to 12.5 mg/kg bw per day over 13 weeks.
Animal Specie:
Hamster (ARfD) & rat (PMTDI)
Effect:
Increased fetal skeletal defects (ARfD) & decreased absolute cauda epididymis weights
PMTDI:
20 µg/kg bw/d
Point of departure:
ARfD: 85 mg/kg bw/d of linamarin; PMTDI: 1.9 mg/kg bw/d sodium cyanide

Evaluation year: 1992

Comments:
The Committee recommended that guidelines be developed to provide reliable and sensitive methods for the analysis of these foodstuffs for hydrogen cyanide releasable from cyanogenic glycosides, in order to ensure that amounts in foods as consumed do not present a hazard. Because of a lack of quantitative toxicological and epidemiological information, a safe level of intake of cyanogenic glycosides could not be estimated. However, the Committee concluded that a level of up to 10 mg/kg hydrogen cyanide in the Codex Standard for Cassava Flour (CAC, 1991) is not associated with acute toxicity.
Tolerable Intake:
Not established
Meeting:
39
Tox Monograph: 

Evaluation year: 1981

Comments:
The Committee concluded that hydrocyanic acid and its salts should not be used as flavouring agents.
Meeting:
25
Tox Monograph: 
Specification: