Proceedings of Mocrinis II. 18 October 2017 Brussels

Transcription

1 Proceedings of Mocrinis II 18 October 2017 Brussels

2 Content MOCRINIS II Workshop 18 October 2017 Foreword by Hans Ketelslegers p 4 Session: Mineral Oil and Wax Definitions, Uses, Regulations p 6 Session: Manufacture of Mineral Oil and Wax - Composition and Specifications p 8 Session: Current case studies MOSH & MOAH paradigm in food contact lubrication p 12 Session: MOAH Technical and toxicological challenges: an industry perspective p 14 Session: Bioaccumulation, what is it all about? p 18 Session: MOSH Toxicology Considerations: Hepatic Granulomas p 20 Session: Mapping Exposure to hydrocarbons: Intended and not intended uses p 22 Session: Hydrocarbon: Waxes: The MOSH that are no MOSH p 24 Reproduction permitted with due acknowledgement Concawe Brussels 3

3 Hans Ketelslegers Science Executive, Concawe Mineral oils are safe for human health? Only the fact that there were strong discussions between experts on the punctuation needed at the end of this sentence, which is the title of this Concawe Mineral Oils Q&A brochure, shows how sensitive this topic is and explains the urgency for the second MOCRINIS workshop of which the proceedings are provided in this current publication. Almost 5 years ago now, Concawe organized a two day workshop to bring together delegates from a range of industry sectors, as well as European and national regulators, to discuss Mineral Oil CRoss INdustry ISsues (MOCRINIS). The outcome of this workshop provided opportunities for future work to address the identified outstanding topics and concerns. Fast forward a couple of years, and a lot of work has been done in the meantime leading to new insights on mineral oil issues which should help to answer the question whether the punctuation referred to above needs to be a question mark or not. The MOCRINIS II workshop, which took place on 18 October 2017 in Brussels, had the goal to achieve a better understanding of mineral oils between stakeholders representing manufacturers, downstream users, regulatory agencies, industry associations and also research institutes and academia. A better understanding of mineral oils means that in order to address the potential human health risks, which are claimed to be associated with exposure to mineral oils, a thorough understanding of the manufacturing processes, analytical methods to identify specific molecules, product specifications 4

4 Foreword and uses is critical. Once a clear understanding is achieved here, the potential effects on human health can be evaluated in light of specific product applications and uses to assess the safety of mineral oils. All these aspects have been covered in the MOCRNIS II workshop, and are summarized separately in the next chapters. I d like to take the opportunity to thank all the presenters in the workshop, who authored the chapters in this publication, and the organizing committee (Concawe STF-33/MOCRINIS Task Force, chaired by Juan-Carlos Carrillo, and the Concawe Communications team managed by Alain Mathuren and effectively led by Marine Teixidor) for their great contributions to the success of MOCRINIS II. And you, participant to the workshop and/or reader of this publication, for the fruitful discussions during the workshop and to keep the debate going with more information coming soon from follow up work of MOCRINIS II - which should increase the overall confidence and general alignment that the punctuation has transformed from a question mark (?) into a dot (.), and will further evolve into an exclamation mark (!) by the time of the next MOCRINIS workshop, on which there was unanimous agreement between all involved stakeholders that it should follow rather soon. Hence: I hope to see you at MOCRINIS III in Hans 5

5 Laurent Jouanneau Global Specialties Product Line Advisor, ExxonMobil White mineral oils (HRBOs) are colorless, highly refined mineral oils derived from non-carcinogenic Lubricating Base Oils (LBOs). Technical white oils are HRBOs that meet requirements of US FDA 21 CFR (b) for color an UV-DMSO limits by to not comply with pharmacopeia monograph purity. They are mainly used to formulate food grade lubricants, textile oils, petroleum jellies, or as rubber extender oils. Pharmaceutical/medicinal/food grade white oils (paraffinum liquidum) are derived from technical white oils and by a second refining step, either hydrotreatment or acid treatment They comply with purity requirements of pharmacopeia monographs (EU or US) or FDA (US), thanks to their extremely low levels of aromatics (1-2 ring highly alkylated structures, typically ~0.1%). They are mainly used in pharmaceutical, cosmetic and food contact (e.g. as extender oils in plastics or elastomers) applications. The main purity tests used are: 1. UV-DMSO: used in Pharmacopeias (EU/US) and FDA (US, food-contact) to track remaining Polyaromatic compounds. 2. Readily Carbonisable Substances: tracks aromatics and impurities. UV-DMSO test is also the key purity test used on food-grade wax and petroleum jellies, in order to control suitability to use these products in food contact, pharmaceutical and cosmetic applications. As far as regulations are concerned, while pharmaceutical and cosmetic applications are well covered by the Pharmacopeia monographs that are consistent between Europe and the US (with the exception of microcrystalline wax for which no specific monograph currently exists in EU), the European regulations for food contact applications need further harmonization. Food related applications need to distinguish between: Uses as food additives (non-food substances intentionally added to modify a property of the food): EU food directive does not allow any mineral oil, but does list microcrystalline wax in its acceptable list (under E905 additive). Uses as processing aid (non-food substances intentionally used during the processing, resulting in the presence of non-intentional residues in the foodstuff): 6

6 Mineral Oil and Wax Definitions, Uses, Regulations Processing aids are not covered in a EU Directive, so national legislations apply. In the US, FDA 21 CFR (white mineral oils) and 21 CFR (paraffins) defines and regulates both food additives and processing aids. Food contact materials (materials, like plastic, glass, cardboard, that can come into contact with food): the EU Plastics directive (EU 10/2011) is the main harmonized directive in this category that defines suitable quality level for wax and for mineral oils that can be used as raw materials. In this plastics Directive, a further improvement should be the clarification of the level of purity actually required. For other food contact materials that may incorporate some wax or mineral oil, harmonized directives still need to be developed. In the US, uses in Food contact materials and applications are defined and regulated by FDA 21CFR (mineral oils) and 21CFR (wax). Lubricants with incidental food contact: no existing regulation in EU, so that US regulation (21 CFR ) and registration ( H1 ) are often referred to. In addition to the specifications and regulations, that set the definitions, characteristics and limits to control the chemical composition of mineral oils and wax, strong Quality Assurance processes and procedures, defined at industry or company levels, control the absence of contamination during refinery transfers, loading and packaging. This ensures the product delivered to customers is similar to the one produced by suppliers in their plants. In conclusion: Industry regulations and product specifications tightly control mineral oil and wax composition. To ensure performance in application and no safety concern for consumers. Purity of these products used in pharmaceutical, cosmetics and food contact applications are controlled mainly by UV-DMSO Tests (that are used to track remaining Polycyclic Aromatic Compounds (PAC)) and adequate Quality Assurance procedures. Total aromatics content (that could be measured by a so called MOAH test) is not a correct safety indicator. Development of harmonized EU regulations needs to be pursued, if possible with consistent EU vs US regulations. 7

7 Laurent Jouanneau Global Specialties Product Line Advisor, ExxonMobil Mineral oils can be split between Lube Base Oils (LBOs), mainly used in the formulation of finished lubricants, and HRBOs, also called white mineral oils. Highly Refined Base Oils (HRBOs), are made of medicinal or pharmaceutical white oils, very pure products used in particular in pharmaceutical, cosmetics and food-contact applications, and of Technical white oils, that do not meet pharmacopeia purity level but can be used in food grade lubricants, rubber extender oils, textile oils, and petroleum jellies. Paraffin waxes are made from mainly n-alkanes, long straight chains of saturated hydrocarbons, separated from mineral oils during the solvent dewaxing process. They are solid at ambient temperature, and vary in consistency from mostly brittle and hard to sometimes soft and plastic. Mineral oils and wax originate from crude oils but typically account for less than 10% of total production in refineries. Crude oils are a complex matrix of naturally occurring hydrocarbons that can be mainly grouped in 3 families: paraffinics (alkanes), naphthenics (cyclo-alkanes), and aromatics. These various types of hydrocarbons have diverse and well-known performance characteristics and toxicological properties. Refining will select the desired molecules to set the final chemical composition (and properties) of the mineral oils: Distillation separates molecules by boiling range, and determines the boiling/carbon/molecular weight range of the final oil. Solvent extraction or hydrocracking or hydrogenation determines the total aromatics content and removes most of Polycyclic Aromatic Compounds (PACs) down to IP346<3%. It is a critical step to ensure mineral oils and wax are non-carcinogenic. It is key to remember that what is important for toxicological properties is the level of polyaromatic compounds, not the total amount of aromatic molecules. Solvent or iso-catalytic dewaxing removes or converts solid waxy hydrocarbons (n-paraffins and some isoparaffins) from mineral oil. Solvent Dewaxing also creates Wax as a co-product. Hydrocracking or moderate hydrotreatment or Acid Treatment removes most aromatics (to typically 0.5-5% level), and polyaromatics to below ppm level, and produces Technical White Oils. Severe hydrogenation or Acid Treatment removes nearly all remaining aromatics (to ~0.1% level), and brings polyaromatics to ppb level or below; It produces 8

8 Manufacture of Mineral Oil and Wax - Composition and Specifications Medicinal/pharmaceutical White Oils After its creation by separation from the oil, slack wax can be further refined to ensure higher purity and allow use in more demanding applications 1. Solvent deoiling produces paraffin wax and petrolatum with less than 1% remaining oil content 2. Hydrogenation or clay treatment removes additional polyaromatic and polar Compounds, to reach purity level suitable for pharmaceutical, cosmetic, and food contact applications of food grade wax and microcrystalline wax. Petroleum jellies, also called vaselines, are a blend of paraffin wax, microcrystalline wax and mineral oil, that can go through a purification step depending on purity of raw materials, and on the application (e.g. food contact, pharmaceutics). A set of specifications has been developed to tightly control mineral oil composition, ensure performance in intended application, and absence of Health and Safety concern. These specification tests are simple and quick to be run on each production batch: Volatility or Flash point control adequate initial boiling point. Viscosity or GC distillation control carbon range and average molecular weight. Pour point or solid paraffin test ensure removal of solid n-paraffins. CaCpCn by ASTM D2140 or density or viscosity Index control right aromatic vs naphthenic vs paraffinic hydrocarbons balance. Aromatics % by ASTM D2007 or Aromatics ppm in White oil by direct UV test relate to remaining total aromatics content. PAC in mineral oils by IP 346 ensures products are not carcinogenic, and low level of PAC in white oil, wax and petroleum jelly is controlled by UV DMSO test. Also, synthetic wax or oils can be obtained using the Fischer Tropsch process (also called Gas To Liquids process), plus a final purification step by hydrogenation for some food contact or cosmetic applications. 9

9 In conclusion: Refining selects the molecules from the crude oil in a controlled manner to set the final chemical composition (and properties) of the mineral oil and wax Removal of undesirable molecules obtained through various refining units Product Specifications tightly control mineral oil and wax composition White mineral oils, wax and petroleum jellies: removal of PAC to level suitable for the application is controlled by UV-DMSO test. Total aromatics content (like could be measured by a so called MOAH test) is not a correct safety indicator. to ensure performance in application and no safety concern for consumer tests shall be simple and quick to be run on each production batch PACs are removed at desired level Absence of carcinogenicity is controlled by IP346 <3.0% and known refining history Mineral base oils: Total aromatics can be in the 0-50% range, but PAC % are only a very small part of these total Aromatic hydrocarbons. 10

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11 Andreas Adam International Sales Director, FRAGOL The lubricant industry is confronted with the demands of sensitive applications in the food, feed and pharmaceutical industry. These industries must meet the expectations of their customers and meet the demands put on their products by the local and European legislations. Consumer organisations add an additional dimension to this by alerting the public for perceived concerns around ingredients that are covered under current legislation or even exist in nature itself. Food is emotion. The main area where we must educate is around what products we actually refer to. Lubricants is a very generic term and here we can mean lubricant base oils as well as blended formulated products containing multiple additives and a mix of base oils designed to lubricate equipment. The mineral white oils (highly refined base oils), when used as a food additive or component in the food are referred to as category 3H by the original USDS nomenclature. These white oils in general, are intended to come into contact with food. White oils can also serve as an ingredient of a machine lubricant. Lubricants are blended products made of a wide selection of allowed oils (f.e. Mineral oil, poly alpha olefin, alkylnaphthalene, polyol ester, polyalkyl glycol etc.) where a number of selected additives are blended to make the final product for the lubrication of equipment. These components meet the FDA requirements and are considered safe when an incident might happen that was unforeseen and undetected for a short period. These lubricants carry the USDS nomenclature of H1 and are incidental food contact. These lubricants are not supposed to be in the final food! When food is analysed to contain MOSH and MOAH it will be important to establish where this is coming from and what type of MOSH and MOAH are involved. If a mineral oil was added to the food for the processing, then MOSH and MOAH will be found in the food, but since that mineral oil component was intended to be there it will be of the allowed type. It can well be that other MOSH and MOAH is found coming from unknown sources like environmental exposure or that it was a product from natural sources. As lubricant industry, we must be clear and consistent with our message and avoid marketing claims that confuse (e.g. MOSH and MOAH free), cannot be sustained or are misleading. There are still categories in use like H2 that originate 50 years ago from an era where different technology was available. These categories are obsolete and add to the confusion and should be discontinued. 12

12 Current case studies MOSH & MOAH paradigm in food contact lubrication Registration and certification: There are currently two companies doing product registration for H1 (lubricant) and 3H (food additives), NSF and INS. There is an ISO standard for lubricant blending facilities ISO21469 that adds the needed verification by certifying not only the components in use but also blending, traceability and documentation of the lubricants produced. An alignment of the interpretations between the USA and EU and within the EU national legislation regarding mineral oil will help global producers of foodstuffs assess the quality of globally sourced components sold in global markets 13

13 Juan Carlos Carrillo Senior Toxicologist Shell International Mineral oils are petroleum derived substances, produced through vacuum distillation at temperatures between ~300⁰C ~600⁰C. In order to be placed on the market these products must be non-carcinogenic. All refinement processes designed to eliminate carcinogenicity of mineral oils are based on the principle of elimination of the substance groups associated with carcinogenic activity, i.e. PACs, which include PAH (polycyclic aromatic hydrocarbons) and aromatics that may contain N or S in the ring structure. Traditionally the resulting product is tested for carcinogenicity using a bioassay. The golden standard has been the mouse skin painting assay. This assay is the most relevant to study the process of carcinogenesis and its relevance to human health because available data show that dermal studies are significantly more sensitive than those via the oral route. Mouse skin painting studies have also been important in understanding the toxicity of two types of mineral oil aromatic hydrocarbons (MOAH). The first type includes the 3-7 ring PACs associated with potential carcinogenic effects that are found in the ⁰C boiling range (at vacuum distillation). The second type, includes highly alkylated aromatic compounds (single or multi-ring systems, but predominantly 1-2 rings) which are not biologically active and thus non-carcinogenic. This shows that there are oils and related products which can have MOAH but are not carcinogenic due to their properties dictated by manufacturing; for example, there is a direct relationship between molecular weight (a function of boiling point) and MOAH content. The current industry standard to assess carcinogenicity of mineral oil is the IP346 method. It is a non-animal method capable to distinguish the two types of MOAH, and is validated against a large data base of mouse skin painting studies. This is the only existing analytical method that has biological significance and predictive value when assessing potential carcinogenicity of MOAH in mineral oils. Therefore, the IP346 is a clear reflection of refinement efficacy by providing an in-situ direct link between manufacturing conditions and biological activity of the tested sample. If the IP346 is < 3%, the material and its subsequent derivatives are not considered carcinogenic and they can be released for further processing to fulfil technical specifications and other regulatory requirements for sensitive applications in the pharma, cosmetics and food industry. In conclusion, the basics of mineral oil refinement, the toxicological data base and the historical developments that led to the establishment of IP346 and other regulatory tests must be properly understood. Based on this, PAC can be MOAH but not all MOAH is necessarily PAC. Thus, because MOAH is contextual, instead of focusing on what can be measured, we strongly advocate to rather measure what 14

14 MOAH Technical and toxicological challenges: an industry perspective needs to be focused on, i.e. 3-7 ring PACs. Applying the above-mentioned production and quality assurance processes ensures the safety of mineral oil compounds intentionally used in consumer goods like food, cosmetics and pharmaceutical products. 15

15 Atmospheric distillation Petroleum gases Naphta Kerosene Gasoils Heavy fuel oils Residue Vacuum distillation Extraction of 3-7 PAC or hydrocracking or hydrogenation Distillate aromatic extract FAIL PASS Slack-wax Dewaxing* Base oil Paraffin & microwax De-oiling Hydrotreatment/ acid treatment 1 Technical white oil Food grade wax & microwax Hydrogenation or clay treatment Hydrotreatment/ acid treatment 2 Pharmaceutical white oil 16

16 Refining operation Refining process Product Safety qualifier (PAC % content) Carbon# range selection Atmospheric and vacuum distillation Distillate or vacuum gas oil Carcinogenic: IP 346 3% Polycyclic Aromatic Compound (PAC) removal Solvent extraction and/or catalytic hydrotreatment Waxy hydrocarbons separation Solvent dewaxing or catalytic dewaxing Base oil and slack-wax Non-carcinogenic: IP 346 < 3% Purification Hydrogenation or acid/clay treatment Petroleum jelly manufacturing Blending and optional purification Technical white oil, white oil, paraffin wax and micro-crystalline wax Pharmacopeia tests White petroleum jelly and yellow petroleum jelly 17

17 Philippe Lemaire Senior Expert, Environmental Toxicologist. TOTAL Recent studies have found the presence of mineral oil in human tissues (Barp et al., 2014) and Barp, L., et al. (2017), authors have described this presence as being bioaccumulation of mineral oil in human body. However, it is important to understand that bioaccumulation is one of the components of bioconcentration (accumulation from environment: air, water, soil, ) which is the sum of biomagnification (accumulation from the trophic levels) and bioconcentration. Indeed, it is true that often the term bioaccumulation is used instead of bioconcentration. Bioconcentration of any substance is the net result of the input (from environment and from food) going into the body minus the output (excretion from the body) and what has been used for metabolism, energy, breeding, and so on. Usually three phases are recognised; the first one is the intake where the input is higher than metabolisation, the second one is the steady state where the input is equal to metabolisation and the third one is the output where the elimination is higher than intake. So when should we start talking about bioaccumulation? Unfortunately, there is no clear definition. Indeed, for human toxicology having a BioConcentration Factor (BCF) superior to 1 leads to think the substance could be bio accumulative. For instance, the level from which bioaccumulation is recognised is not the same according to the different existing regulations in different countries. Indeed, in the past (67/547/ CEE regulation) but also and still now OSPAR (Oslo Paris Convention) a substance is considered as possibly being bioaccumulative if the octanol/water coefficient (the so called Kow showing the lipophilicity of the substance in link with the carbon range, expressed as a logarithmic scale) is above 3 or if BCF ratio is more than 100. From now on with worldwide Global Harmonised System (GHS) a substance would be considered as bioaccumulative if Kow superior to 4 and/or BCF ratio is more than 500. For Persistent and Bioaccumulative and Toxic (PBT) substances, they are considered "bioaccumulative" if KoW is more than 5 and BCF ratio more than Usually Kow is the first screening criterion taken into account for a substance to be recognised as being potentially bioaccumulative (Kow superior to 3, 4 or 5). However, molecular length or molecular diameter of a substance should be deeply taken into consideration in order to understand if a substance can bioaccumulate or not. Substances with a high Kow that have reached a certain size will not be able to go through the cellular membrane and de facto will not bioaccumulate. However, for too large substances another phenomena called phagocytosis or picnocytosis by cell membranes can take place. Encapsulation and retention of these large substances does not necessarily mean bioaccumulation. 18

18 Bioaccumulation, what is it all about? According to their carbon range and molecular size, mineral oils have a Kow of more than 11 and are too large substances to cross the cell membrane and be bioaccumulative. Indeed, they can been found in tissues as observed in publications of Barp et al. (2014) Barp, L., et al. (2017) possibly as a result of phagocytosis. Moreover, if mineral oils would be bioaccumulative, increased concentration with age should have been found in human body and that was not the case. In order to become toxic a bioaccumulative substance must reach what is called the Critical Body Burden (CBB) which means a concentration high enough to have an adverse effect on any endpoint. CBB is the multiplication of the No Observed Adverse Effect Level (NOAEL) by the BCF. However, neither BCF has been determined for mineral oil nor NOAEL based on toxicity. In conclusion, mineral oils do not fulfil any criteria for bioaccumulation. Their carbon range and molecular size are too big to be bioaccumulative. No BCF has ever been measured in any organism and the CBB has never been reached and cannot be calculated (or shown) as BCF and NOAEL does not exist. Only the presence of mineral oil (not toxicity) has been observed which is emphasized by the fact there is no increment of concentration measured with age. 19

19 Marusia Popovech Senior Toxicologist, ExxonMobil Mineral hydrocarbons (MHC) are used in food, cosmetics, and pharmaceutical applications. Food-grade, high molecular weight, saturated MHC have generally been considered safe for intended uses based on an absence of evidence of human toxicity and a large body of evidence from toxicology data showing negligible systemic effects from long-term oral exposure. Subchronic feeding studies of MHC in Fischer 344 (F344) rats have shown a dose-related increase in histopathologic observations in some treatment groups. Observations include granulomas and microgranulomas in the liver, which appear to result from an inflammatory response. Not all MHC studied produced granuloma in F344 livers. Studies conducted in F344 rats with granulomatous findings are in marked contrast to the negative findings reported in numerous subchronic and chronic toxicity studies on MHC conducted in several animal models, including Sprague Dawley (SD) rats, Long-Evans rats and Beagle dogs. The underlying mechanisms for species/strain differences in response to MHC is unknown, but is hypothesized to result from differences in absorption, metabolism, and inflammatory response. As with naturally occurring saturated hydrocarbons, MHC are primarily absorbed in the small intestine and transported to the body through the lymphatic system. Numerous studies suggest strain-dependent differences in MHC absorption leading to higher circulating MHC levels in F344 rats, as compared to SD rats. MHC undergo oxidative metabolism in the liver and numerous studies suggest straindependent differences in MHC metabolism. SD rats appear to have a more efficient metabolism of saturated hydrocarbons and are less sensitive to MHC exposure as compared to F344 rats. This strain dependent difference in oxidative metabolism of hydrocarbons appears to be mediated through cytochrome P450 enzymes. Studies also suggest strain-dependent differences in inflammatory responses to MHC exposure. At similar target tissue concentrations of MHC, F344 rats exhibit inflammatory lesions, whereas no response is seen in SD rats. This may be due to differences with resident liver macrophages responsible for the secretion of vasoactive and toxic mediators involved in host defense mechanisms. Saturated hydrocarbons from MHC and natural plant sources are found in human livers, in lipogranulomas. Human hepatic lipogranulomas are benign, circumscribed lesions, containing lipid droplets in the center. They show no evidence of inflammation or fibrosis and have not been associated with adverse clinical effects. These findings are in contrast to the hepatic granulomas observed in F-344 rats. Human exposure 20

20 MOSH Toxicology Considerations: Hepatic Granulomas to MHC, under severe and abusive use exposures, do not result in F-344 rat-type epithelioid granulomas in the liver. The European Food Safety Authority (EFSA) reviewed the data on the incidence of human hepatic lipogranuloma and concluded that The current incidence is very low and do not appear to have any adverse consequences. It is unlikely that extrapolation of effects from F-344 rats are informative to human health risk assessments. 21

21 David Tennant Scientific Adviser, Food Chemical Risk Analysis Risk management measures to control mineral hydrocarbons presenting a potential risk to consumers need to be based on realistic and relevant estimates of exposure. Risk management also needs to reflect differences between hydrocarbons occurring in food as a result of intended uses, unintended uses and the presence of naturally occurring hydrocarbons in food. In 2004, Concawe and EWF reported the results from a project to determine realistic exposures to hydrocarbons in food 1. The project included a usage survey of food grade oils and waxes, information about concentrations of hydrocarbons in foods and an intake estimate based on UK adults and children. If the proportion of foods that might contain MOSH was taken into consideration, then intakes ranged up to 0.6 mg/kg bw/ day for children. In contrast potential intakes of hydrocarbons from natural sources, in particular natural waxes on fruit, could be as much as 2.5 mg/kg bw for children. The EFSA call for scientific data on mineral oil hydrocarbons in food in Invited data providers were to provide the range of carbon atoms and the maximum of the distribution curve. There were no recommendations on sampling strategy except to exclude known adulteration. This resulted in the EFSA Opinion on Mineral Oil Hydrocarbons in Food (2012) 3 being based on very broad definitions and including uncertainties associated with sampling. Many of the data came from one national enforcement laboratory where the selection of many samples was targeted and most of the data was pre Following the EFSA Opinion, in 2017 the European Commission published recommendations 4 on monitoring mineral oil hydrocarbons in food. The recommendations stated that where MOH are detected in food, Member States should carry out further investigations in the food business establishments in order to determine the possible source or sources. The current Concawe/EWF project on exposure mapping is designed to review available literature and consult with food industry to identify current MOH origins, usage, sources of exposure, and levels and frequencies of occurrence. The results will be uploaded into a searchable database that will allow tracking of hydrocarbons from origin to final foods. This will make it possible to establish current hydrocarbon use patterns, provide reliable occurrence data linked to hydrocarbon source: intended, unintended, natural 22

22 Mapping Exposure to hydrocarbons: Intended and not intended uses occurrence, etc. This will in turn provide a sound basis for realistic exposure modelling to support well informed risk management. 1 Tennant, D.R. (2004). The usage, occurrence and dietary intakes of white mineral oils and waxes in Europe. Food and Chemical Toxicology. Vol 42/3 pp EFSA (European Food Safety Authority), Specific requirements for chemical contaminant and food additive occurrence data submission. EFSA supporting publication 2015:EN pp. 3 EFSA Panel on Contaminants in the Food Chain (CONTAM); Scientific Opinion on Mineral Oil Hydrocarbons in Food. EFSA Journal 2012;10(6):2704. [185 pp.] doi: /j.efsa Commission Recommendation (EU) 2017/84 of 16 January 2017 on the monitoring of mineral oil hydrocarbons in food and in materials and articles intended to come into contact with food. OJ L 12/95,

23 Dirk F. Danneels Secretary General, European Wax Federation Abstract n-alkanes are substances that are not only important constituents of hydrocarbon waxes but they ubiquitously present on the surface of fruits, vegetables and plant materials in general. The recently published EFSA Eternal Scientific Report: Bioaccumulation and toxicity of mineral oil hydrocarbons in rats specificity of different subclasses of a broad mixture relevant for human dietary exposures (Cravedi et al. 2017) provides significant new information on the response of the Fischer (F-344) rats to n-alkanes. A first important finding of this study is the observation that also the animals in the control group, i.e. those that are not exposed to the hydrocarbon mixtures that are the subject of this study, show enhanced retention of n-alkanes of natural origin that are present in the feed. (Cravedi et al 2017 Table 1). Especially remarkable is the fact that the concentration of n-alkanes found in the rat livers is nine times higher than those in the fat tissue. This is completely opposite to the situation in human livers and rat species other than F- 344 where n-alkanes are essentially absent in livers. (Barp et al 2014 Fig 3.).This clearly indicates that something atypical is happening in the F-344 rats with respect to their capability to metabolize n-alkanes, including those of natural origin. A further comparison of the hydrocarbons found in human livers with those that typically constitute a wax leads indubitably to the following conclusions: Those hydrocarbons that are found to be retained preferentially in human livers are not present in waxes, and those hydrocarbons that waxes are composed of, are not see in human livers. (Cravedi et al 2017 Fig 52 and Biederman et al 2015 Fig. 6). Hence, waxes are confirmed to be fully and easy metabolizable substances in humans, a situation that is completely opposite to the situation of F-344 rats where significant retention of wax constituents, including n-alkanes, is observed. Therefore, waxes should not be seen as part of the MOSH concern that is essentially triggered by the retention of hydrocarbons by human tissues. Further experimental findings in the quoted EFSA External Scientific Report allow the elucidation of the mechanism by which n-alkanes lead to the inflammatory microgranulomas that have been exclusively found in the F-344 rat livers. The final disqualification of the F-344 rat strain as an appropriate model for assessing the human safety of waxes, and notably Low Melting Paraffin Wax (LMPW), has a number of direct and indirect consequences. First and foremost, it supports a petition requesting to allocate a new Specific Migration Limit (SML) for LMPW (FCM 93) in Annex 1 of the Plastics Regulation (EU) 10/2011. Currently, this SML is 0.05 mg/kg is based in a TIER 1 petition. Relying on the full toxicological data set, with the exclusion of those studies based on the F-344 rats, supports an SML higher than the 24

24 Hydrocarbon: Waxes: The MOSH that are no MOSH Overall Migration Limit (OML). Furthermore, it finishes the unqualified use of LMPW as a generic model for predicting potential adverse effects of MOSH. Hence, low viscosity oils need be assessed by their own experimentally established No Observed Adverse Effect Levels (NOAEL s) rather than by the 19 mg/kg b.w./day that was found for LMPW in the F-344 rats. Furthermore, also the margins of exposure (MOE s) that are calculated in the EFSA Opinion of 2012 and that are based on the use of 19 mg/kg b.w. day as the Reference Point need to be revised using relevant oil rather than wax data. References Barp, L., Kornauth, C., Wuerger, T., Rudas, M., Biedermann, L. Reiner, A., Concin, N., Grob, K Food and Chemical Toxicology, 72, Biedermann, M., Barp, L., Kornauth, C., Würger, T., Rudas, M., Reiner, A., Concin, N.,Grob, K Mineral oil in himan tissues, Part II: Characterization of the accumulated hydrocarbons by comprehensive two-dimensional gas chromatography. Science of the Total Environment , Cravedi, J-P.,Grob, K., Nygaard U.C. and Alexander, J., Bioaccumulation and toxicity of mineral oil hydrocarbons in rats-specificity of different subclasses of a broad mixture relevant for human dietary exposure. EFSA supporting publication 2017:EN-1090 EFSA (European Food Safety Agency), Scientific opinion on mineral oil hydrocarbons in food. EFSA Journal 10 (6): 2704,

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