Scientific Opinion on the re-evaluation of hexamethylene tetramine (E 239) as a food additive

Hexamethylene tetramine (HMT) is a food additive, currently only permitted in EU for use in Provolone cheese. The maximum permitted level is 25 mg/kg residual amount, expressed as formaldehyde, the break down product of HMT under acidic conditions. HMT has been previously evaluated by the Joint Expert Committee on Food Additives (JECFA, 1974) who established an ADI of 0.15 mg/kg bw/day based on a reproductive study with a NOEL of 15 mg/kg bw/day. Due to the limitations in the database the Panel could not identify a critical study and therefore to derive an ADI. However, the Panel noted that the exposure to formaldehyde from HMT of high level consumers of Provolone cheese equalled 18 µg formaldehyde/kg bw/day in adults and could be as high as 87 µg formaldehyde/kg bw/day in children according to a theoretical conservative assumption that all ripened cheese consumed was Provolone cheese. Considering the estimated exposure from the very limited permitted use, the toxicological database on HMT, the data from use of HMT therapeutically, the available oral toxicity and toxicokinetic data of formaldehyde and the magnitude of the potential effect on intracellular formaldehyde levels arising from this use of HMT, the Panel concluded that the use of HMT in Provolone cheese at the MPL of 25 mg/kg residual amount, expressed as formaldehyde, would not be of safety concern. However the Panel considered that any increase in the permitted uses of HMT or increases in the MPL of 25 mg /kg residual amount, expressed as formaldehyde would need detailed assessment which might require new toxicity data as well as use levels and/or an evaluation of its impact on formaldehyde levels in vivo.