According to Article 32 of Regulation (EC) No 1333/2008, all food additives permitted before 20 January 2009 should be subject to a new risk assessment by the European Food Safety Authority (EFSA). The program for the re-evaluation of approved food additives has been set up by Commission Regulation (EU) No 257/2010 of 25 March 2010.
In November 2009 EFSA launched a public call for data on miscellaneous waxes permitted as food additives in the EU. The public call for data ended in March 2010 and only limited toxicological data on montan acid esters (E 912) were provided which would not enable EFSA to conclude on the safety of its use as a food additive. The data provided to EFSA and otherwise obtained through literature searches have been evaluated by the ANS Panel and major data gaps have been identified in relation to the following endpoints:
– No data on toxicokinetics are available,
– No data on reproductive and developmental toxicity are available,
– The available data on short-term and subchronic toxicity and genotoxicity are limited,
– The available data on chronic toxicity and carcinogenicity are limited, with important deficiencies in the available studies [i.e. limitations as regards haematology and urinanalyses (absence of comparison between treated animals and controls); very limited number of organs evaluated histopathologically].
It is also noted that the data requested by the Scientific Committee for Food (SCF) in the late 1990s (i.e. chromosomal aberration study in vitro, reproduction and teratogenicity studies, description of the material, including impurities, absence of PAHs and/or a specification) have never been submitted.
In order to ensure an effective re-evaluation of montan acid esters (E 912), it is important that EFSA acquires from interested parties all data requested below which are needed for the re-evaluation of the food additive (wax) montan acid esters (E 912). These data might already exist or might need to be generated.
The purpose of this call for data is to offer all interested parties and stakeholders the opportunity to provide to EFSA the sought data on montan acid esters (E 912), if necessary generating them through commissioning new studies. The data required are in accordance with the Guidance on submission of food additive evaluations by the SCF and are outlined in more detail below.
Interested parties and stakeholders should submit the requested data or provide information that they have commissioned the relevant studies before 1 June 2012. If the necessary data have not been made available but new studies have been commissioned to obtain the sought data, EFSA will set a new deadline for the submission of these data which will be communicated to the parties commissioning the studies and published on EFSA’s website.
In case neither the necessary data nor a commitment to generate the sought data through new studies are provided to EFSA by 1 June 2012, EFSA will base its re-evaluation of montan acid esters (E 912) on the information available at that date.
EFSA kindly asks governments, interested organisations, universities, research institutions, companies and other interested parties to submit the data as mentioned below on montan acid esters (E 912) and with reference to the 2001 SCF guidance on submissions for food additive evaluations.
– Usages and use levels of montan acid esters (E 912) when used as a food additive.
– Data on migration of montan acid esters (E 912) into the foods.
– Information on absorption, distribution, metabolism and excretion of montan acid esters (E 912) and based on this information support for the assumption that the experimental animal models used in the toxicity studies are representative for the human situation.
– The nature and fate of the fermentation products of montan acid esters (E 912) formed in the intestinal tract.
– Studies on the subchronic toxicity, genotoxicity, chronic toxicity, carcinogenicity, reproductive and developmental toxicity of montan acid esters (E 912), or a scientific rationale to justify that any of these studies would not be necessary for the risk assessment.
If some of these data do not exist and there is no scientific rationale to justify that they are not necessary for the risk assessment, new studies might need to be commissioned. In this case, the following tiered approach could be considered instead of the more extensive approach defined in the SCF 2001 guidance on food additives:
If negligible absorption of montan acid esters (E 912) and their intestinal (e.g. microflora or chemical) breakdown products is demonstrated, at least the following toxicity study should be carried out as a first step.
- A subchronic toxicity study should normally be conducted for a period of at least 90 days (OECD TG 408) in rodents, modified to include assessment of some additional parameters described in the more recent guideline on repeated-dose 28-day oral toxicity study in rodents (OECD TG 407).
Depending on the effects observed, additional studies might be necessary.
In case of non-negligible absorption of montan acid esters (E 912) or their intestinal (e.g. microflora or chemical) breakdown products, in addition to the subchronic toxicity described under Tier 1, the following tests are suggested to be conducted.
- An in vivo micronucleus test for the endpoint genotoxicity.
- Studies on chronic toxicity (12 months) and carcinogenicity in the rat, either as separate studies (OECD TGs 452 and 451, respectively) or the combined study (OECD TG 453).
- Studies for reproductive and developmental toxicity comprising a prenatal developmental toxicity study (OECD TG 414) in the rabbit and an Extended One-Generation Reproduction Toxicity Study (EOGRTS) (OECD TG 443). A multi-generation study, instead of an EOGRTS, is acceptable, provided that sufficient information on possible neurotoxicity and immunotoxicity is made available.
The content of montan acid esters (E 912) in the test preparation should be clearly specified. It should also be indicated whether the material tested is in accordance with the specifications for montan acid esters (E 912) as defined in Directive 2008/84/EC. The tests should be carried out according to the principles of Good Laboratory Practice (GLP) described in Directives 2004/9/EC and 2004/10/EC and accompanied by a statement of GLP compliance.
Process of the call for data
The data mentioned above or the information that the corresponding studies have been commissioned and new data will be generated needs to be submitted to EFSA electronically by 1 June 2012 at the latest.
Based on the timeframe of the commissioned studies the new deadline for submission of these data will be communicated by EFSA to the parties commissioning the studies and generating the data and published on EFSA’s website.
The interested parties are invited to contact EFSA for further clarification if required.
Confidentiality and unpublished data
Specific issues relating to confidentiality of the data provided should be discussed between the owners and EFSA on the basis of the justifications provided by the data owners. In application of Article 8.4 of Regulation 257/2010, following a proposal from EFSA, the Commission will decide after consulting the interested business operator and/or the other interested parties which information may remain confidential and shall notify EFSA and the Member States accordingly.
Please send all electronic correspondence, including enquiries to: foodadditives [at] efsa.europa.eu
Hard copies can also be sent to the address below:
Food Ingredients and Packaging Unit, Food Additives
European Food Safety Authority
Via Carlo Magno 1/a
 Regulation (EC) No 1333/2008 of the European Parliament and of the Council of 16 December 2008 on food additives.
 Commission Regulation (EU) No 257/2010 of 25 March 2010 setting up a program for the re-evaluation of approved food additives.
 Call for scientific data on miscellaneous waxes permitted as food additives in the EU.
 Guidance on submission of food additive evaluations by the Scientific Committee on Food, 2001.
 OECD Guidance 408. Repeated dose 90-day oral toxicity study in rodents.
 OECD Guidance 407. Repeated dose 28-day oral toxicity study in rodents.
 OECD Guideline 452. Chronic toxicity studies.
 OECD Guideline 451. Carcinogenicity studies.
 OECD Guideline 453. Combined chronic toxicity/carcinogenicity studies.
 OECD Guideline 414.Prenatal developmental toxicity study.
 OECD Guideline 443. Extended one-generation reproductive toxicity study.
 Commission Directive 2008/84/EC of 27 August 2008 laying down specific purity criteria on food additives other than colours and sweeteners. OJ L 253, 20.9.2008, p. 1.
 Directive 2004/9/EC of the European Parliament and of the Council of 11 February 2004 on the inspection and verification of good laboratory practice (GLP) OJ L 50, 20.2.2004, p. 28–43.
 Directive 2004/10/EC of The European Parliament and of the Council of 11 February 2004 on the harmonisation of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their applications for tests on chemical substances OJ L 50, 20.2.2004, p. 28–43.