The EFSA was requested by the European Commission to assess the safety in use of the substance dioctadecyl disulphide and if the established specific migration limit (SML) of 3 mg/kg food is still valid on the basis of new information provided by industry.
The substance is used as an additive in plastics intended to come in contact with food and it was authorised in 2001 following an opinion by the Scientific Committee on Food (SCF) published in 1995. In that opinion a TDI of 0.05 mg/kg bw was allocated to the substance based on the results of a 90-day oral rat study of 1969 submitted by the industry. The Commission allocated an SML of 3 mg/kg food on the assumption that a person, weighing 60 kg, may consume daily up to 1 kg of food in contact with a food contact material containing the substance.
In 2010 the industry submitted new toxicological studies to the Commission with the question to be examined if the substance is accumulated in man.
The Commission asked the EFSA to review the information provided and advise on whether it raises issues regarding the safe use of the substance and to assess if the SML of 3 mg/kg food is still appropriate.
Data from two toxicokinetic studies in male rats suggest that dioctadecyl disulphide is poorly absorbed from the gastrointestinal tract.
The CEF Panel considers that there is no concern regarding the genotoxicity of dioctadecyl disulphide based on negative findings in five in vitro genotoxicity assays and one in vivo micronucleus assay.
Two 90-day toxicity studies in which dioctadecyl disulphide was administered orally to rats and beagle dogs could not be used for the derivation of a NOAEL/LOAEL due to the limited data reporting (rat study) and inadequate study design (dog study).
In two chronic studies deposits of dioctadecyl disulphide were observed in several organs (e.g. liver, adrenals, lymph nodes) in rats and dogs, together with treatment-related evidence of toxicity. An inverse dose:response relationship was however seen for both deposition of test material and organ changes evidencing toxicity . The Panel considered that due to absence of a positive dose-relationship for the observed effects and the presence of possible treatment-related effects at the lowest dose tested, the results of the study could not be used for the purposes of risk assessment of dioctadecyl disulphide.
In a reproduction/developmental toxicity study the NOAEL for reproductive toxicity was at the highest administered dose (approximately 1200 mg/kg bw/day).
The CEF Panel concluded that dioctadecyl disulphide is very poorly absorbed from the gastrointestinal tract, but is taken up to some extent as evidenced by the finding of insoluble test material in various organs in chronic studies in two species. The substance therefore has a potential for accumulation, and to result in toxicity. Due to uncertainties related to the dose-response relationship and the presence of possible treatment-related effects at the lowest dose tested in two species, the Panel could not derive a NOAEL for dioctadecyl disulphide from the available in vivo studies.
Therefore the CEF Panel does not concur with the TDI of 0.05 mg/kg/bw for dioctadecyl disulphide allocated by the SCF in 1995 and with the SML of 3 mg/kg food based on this TDI. However, considering the absence of genotoxicity, a limited daily intake of the substance up to 0.05 mg/person is unlikely to be a safety concern.