SCF Opinion on Food Additive E952

The Scientific Committee on Food (SCF) reviewed the toxicity of cyclamates in 2000.

The new epidemiological data revealed no indications of harmful effects on human reproduction parameters of either cyclamate used as food additive or of workplace exposure to cyclohexylamine, though the latter study was considered difficult to interpret.

The Committee noted that no in vitro studies to compare the relative sensitivity of human, monkey and rat testicular tissue to cyclohexylamine were performed but acknowledged the difficulties in performing such studies. The Committee now no longer requires such studies.

After considering all the data available on conversion of cyclamate to cyclohexylamine in humans, including the new data provided, the Committee concluded that the uncertainties with respect to the conversion rate in humans could be eliminated but that the 18.9% conversion rate used for establishing the temporary ADI of 0-11 mg/kg bw is no longer appropriate. There are large inter-individual variations observed in conversion rates and a lack of knowledge about the minimal time span of exposure to cyclohexylamine that might result in testicular damage. The Committee therefore concluded that the maximum observed individual overall conversion of cyclamate to cyclohexylamine and absorption of the latter would be 85%. This would be more appropriate for calculating an ADI. Since a maximum conversion figure would be utilised, a reduced safety factor should be applied for interindividual differences (see below).

The Committee concluded that a full ADI for cyclamate could now be established. Taking a NOAEL of 100 mg/kg bw for cyclohexylamine, allowing for the difference in molecular weight between cyclamic acid and cyclohexylamine, using an 85% overall conversion rate for ingested cyclamate, and applying a 32-fold safety factor (see Annex), a full ADI of 0-7 mg/kg bw, expressed as cyclamic acid, for cyclamic acid and its sodium and calcium salts was established by the Committee.