Safety evaluation of crosslinked polyacrylic acid polymers (carbomer) as a new food additive
2021; Wiley; Volume: 19; Issue: 8 Linguagem: Inglês
10.2903/j.efsa.2021.6693
ISSN1831-4732
AutoresMaged Younes, Gabriele Aquilina, Karl–Heinz Engel, Paul Fowler, María José Frutos Fernández, Peter Fürst, Rainer Gürtler, Ursula Gundert‐Remy, Trine Husøy, Melania Manco, Wim Mennes, Sabina Passamonti, Peter Moldéus, Romina Shah, Ine Waalkens‐Berendsen, Detlef Wölfle, Matthew Wright, José Manuel Barat Baviera, Gisela H. Degen, Jean‐Charles Leblanc, Lieve Herman, Consuelo Civitella, Alessandra Giarola, Camilla Smeraldi, Alexandra Tard, Giorgia Vianello, Laurence Castle,
Tópico(s)Pesticide Residue Analysis and Safety
ResumoEFSA JournalVolume 19, Issue 8 e06693 Scientific OpinionOpen Access Safety evaluation of crosslinked polyacrylic acid polymers (carbomer) as a new food additive EFSA Panel on Food Additives and Flavourings (FAF), Corresponding Author EFSA Panel on Food Additives and Flavourings (FAF) fip@efsa.europa.eu Correspondence:fip@efsa.europa.euSearch for more papers by this authorMaged Younes, Maged YounesSearch for more papers by this authorGabriele Aquilina, Gabriele AquilinaSearch for more papers by this authorKarl-Heinz Engel, Karl-Heinz EngelSearch for more papers by this authorPaul Fowler, Paul FowlerSearch for more papers by this authorMaria Jose Frutos Fernandez, Maria Jose Frutos FernandezSearch for more papers by this authorPeter Fürst, Peter FürstSearch for more papers by this authorRainer Gürtler, Rainer GürtlerSearch for more papers by this authorUrsula Gundert-Remy, Ursula Gundert-RemySearch for more papers by this authorTrine Husøy, Trine HusøySearch for more papers by this authorMelania Manco, Melania MancoSearch for more papers by this authorWim Mennes, Wim MennesSearch for more papers by this authorSabina Passamonti, Sabina PassamontiSearch for more papers by this authorPeter Moldeus, Peter MoldeusSearch for more papers by this authorRomina Shah, Romina ShahSearch for more papers by this authorIne Waalkens-Berendsen, Ine Waalkens-BerendsenSearch for more papers by this authorDetlef Wölfle, Detlef WölfleSearch for more papers by this authorMatthew Wright, Matthew WrightSearch for more papers by this authorJosé Manuel Barat Baviera, José Manuel Barat BavieraSearch for more papers by this authorGisela Degen, Gisela DegenSearch for more papers by this authorJean-Charles Leblanc, Jean-Charles LeblancSearch for more papers by this authorLieve Herman, Lieve HermanSearch for more papers by this authorConsuelo Civitella, Consuelo CivitellaSearch for more papers by this authorAlessandra Giarola, Alessandra GiarolaSearch for more papers by this authorCamilla Smeraldi, Camilla SmeraldiSearch for more papers by this authorAlexandra Tard, Alexandra TardSearch for more papers by this authorGiorgia Vianello, Giorgia VianelloSearch for more papers by this authorLaurence Castle, Laurence CastleSearch for more papers by this author EFSA Panel on Food Additives and Flavourings (FAF), Corresponding Author EFSA Panel on Food Additives and Flavourings (FAF) fip@efsa.europa.eu Correspondence:fip@efsa.europa.euSearch for more papers by this authorMaged Younes, Maged YounesSearch for more papers by this authorGabriele Aquilina, Gabriele AquilinaSearch for more papers by this authorKarl-Heinz Engel, Karl-Heinz EngelSearch for more papers by this authorPaul Fowler, Paul FowlerSearch for more papers by this authorMaria Jose Frutos Fernandez, Maria Jose Frutos FernandezSearch for more papers by this authorPeter Fürst, Peter FürstSearch for more papers by this authorRainer Gürtler, Rainer GürtlerSearch for more papers by this authorUrsula Gundert-Remy, Ursula Gundert-RemySearch for more papers by this authorTrine Husøy, Trine HusøySearch for more papers by this authorMelania Manco, Melania MancoSearch for more papers by this authorWim Mennes, Wim MennesSearch for more papers by this authorSabina Passamonti, Sabina PassamontiSearch for more papers by this authorPeter Moldeus, Peter MoldeusSearch for more papers by this authorRomina Shah, Romina ShahSearch for more papers by this authorIne Waalkens-Berendsen, Ine Waalkens-BerendsenSearch for more papers by this authorDetlef Wölfle, Detlef WölfleSearch for more papers by this authorMatthew Wright, Matthew WrightSearch for more papers by this authorJosé Manuel Barat Baviera, José Manuel Barat BavieraSearch for more papers by this authorGisela Degen, Gisela DegenSearch for more papers by this authorJean-Charles Leblanc, Jean-Charles LeblancSearch for more papers by this authorLieve Herman, Lieve HermanSearch for more papers by this authorConsuelo Civitella, Consuelo CivitellaSearch for more papers by this authorAlessandra Giarola, Alessandra GiarolaSearch for more papers by this authorCamilla Smeraldi, Camilla SmeraldiSearch for more papers by this authorAlexandra Tard, Alexandra TardSearch for more papers by this authorGiorgia Vianello, Giorgia VianelloSearch for more papers by this authorLaurence Castle, Laurence CastleSearch for more papers by this author First published: 11 August 2021 https://doi.org/10.2903/j.efsa.2021.6693 Requestor: European Commission Question number: EFSA-Q-2020-00514 Panel members: Gabriele Aquilina, Laurence Castle, Karl-Heinz Engel, Paul Fowler, Maria Jose Frutos Fernandez, Peter Fürst, Rainer Gürtler, Ursula Gundert-Remy, Trine Husøy, Melania Manco, Wim Mennes, Sabina Passamonti, Peter Moldeus, Romina Shah, Ine Waalkens-Berendsen, Detlef Wölfle, Matthew Wright and Maged Younes. Note: The full opinion will be published in accordance with Article 12(3) of Regulation (EC) No 1331/2008 once the decision on confidentiality will be received from the European Commission. Declarations of interest: The declarations of interest of all scientific experts active in EFSA's work are available at https://ess.efsa.europa.eu/doi/doiweb/doisearch. Acknowledgements: The Panel wishes to thank the following for the support provided to this scientific output: Ana Campos Fernandes, Galvin Eyong and the members of the FAF WG Specifications of Food Additives. Adopted: 23 June 2021 AboutSectionsPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract The EFSA Panel on Food Additives and Flavourings (FAF) provides a scientific opinion on the safety of crosslinked polyacrylic acid polymers (carbomer) proposed for use as food additive in solid and liquid food supplements. Carbomer is formed from the monomer, acrylic acid, which is polymerised and crosslinked with allyl pentaerythritol (APE). The polymers are synthesised in ethyl acetate using ■■■■■ as free-radical polymerisation initiator. In vivo data showed no evidence for systemic availability or biotransformation of carbomer. Carbomer does not raise a concern regarding genotoxicity. Considering the available data set, the Panel derived an acceptable daily intake (ADI) of 190 mg/kg body weight (bw) per day based on a no observed adverse effect level (NOAEL) of 1,500 mg/kg bw per day from a sub-chronic 13-week study in rat, applying a compound specific uncertainty factor (UF) of 8. At the proposed maximum use levels, the exposure estimates ranged at the mean from 1.1 to 90.2 mg/kg bw per day and at the p95 from 12.5 to 237.4 mg/kg bw per day. At the proposed typical use level, the exposure estimates ranged at the mean from 0.7 to 60.2 mg/kg bw per day and at the p95 from 10.3 to 159.5 mg/kg bw per day. The Panel noted that the maximum proposed use levels would result in exposure estimates close to or above the ADI. The Panel also noted that level of exposure to carbomer from its proposed use is likely to be an overestimation. Taking a conservative approach, the Panel considered that exposure to carbomer would not give rise to a safety concern if the proposed maximum use level for solid food supplements is lowered to the typical use level reported by the applicant. Summary Following a request from the European Commission to the European Food Safety Authority (EFSA), the Panel on Food Additives and Flavourings (FAF) was asked to provide a scientific opinion on the safety of crosslinked polyacrylic acid polymers (carbomer) proposed for use as food additive in solid and liquid food supplements, in accordance with Regulation (EC) No 1331/2008 establishing a common authorisation procedure for food additives, food enzymes and food flavourings. The present evaluation is based on the data on crosslinked polyacrylic acid polymers (carbomer) in a newly submitted dossier and additional information submitted by the applicant during the assessment process in response to a request by EFSA. The proposed food additive 'carbomer' is formed from the monomer, acrylic acid, which is polymerised and crosslinked with allyl pentaerythritol (APE). The polymers are synthesised in ethyl acetate using ■■■■■ as free-radical polymerisation initiator. Two different grades of carbomer can be manufactured by varying the amount of the crosslinker used in the polymerisation reaction (i.e. sold under the trade names Carbopol® 974P NF Polymer, defined as 'highly crosslinked', and Carbopol® 971P NF Polymer, defined as 'lightly crosslinked') and a third grade of carbomer (Carbopol® 71G NF) can be obtained from Carbopol® 971P NF Polymer via dry granulation. The estimated average molecular weight of the three carbomer grades is over 3 × 109 Daltons (Da) but an amount of lower molecular weight fraction (LMWF) is present in the final product ■■■■■. The carbomer impurities profile was characterised by the applicant showing that they are substances carried over or originated from the starting materials, i.e. residual acrylic acid, residual ethyl acetate, unreacted APE or by-products from the polymerisation initiator. The anticipated dietary exposure estimates to the carbomer impurities using the specifications proposed by the applicant and/or the highest reported analytical levels were calculated by the Panel. For the residual acrylic acid, based on its estimated dietary exposure, the Panel considered that a lowering of the proposed maximum limit for the residual acrylic acid is recommended and it is technologically achievable as indicated by the analytical data provided. Carbomer showed no evidence for systemic availability or biotransformation in an in vivo study in rats dosed by gavage with three 14C-labelled poly(acrylic acid) of different average molecular weights and degrees of cross-linking. The toxicology data set comprised studies on sub-chronic toxicity (13-week dietary toxicity study in rats; 13-week dietary toxicity study in dogs) and the basic test battery for in vitro genotoxicity. Overall, the available biological and toxicological data were considered adequate to conclude on the safety of the proposed new food additive. From the sub-chronic 13-week toxicity study in rats, effects on body weight and body weight gain were observed as well as some minor effects in clinical chemistry parameters. The Panel considered that the decreases in body weight and body weight gain could be reflective of interactions between nutrients and carbomer resulting in nutrient malabsorption, which is considered as an undesirable effect. Therefore, the Panel identified a NOAEL of 1,513 mg/kg bw per day, the mid dose tested. In dogs, the NOAEL identified was of 1,642 mg/kg bw per day, the highest dose tested. Carbomer does not raise concern with respect to genotoxicity. Considering the available data set, the Panel derived an ADI of 190 mg/kg bw per day based on a NOAEL of 1,500 mg/kg bw per day from the sub-chronic 13-week toxicity study in rat, applying a compound specific UF of 8. To assess the dietary exposure to carbomer, the exposure was calculated based on the proposed maximum use levels considering only consumers of food supplements and the proposed typical use level (200,000 mg/kg) in the solid food supplement food category (FC 17.1). At the proposed maximum use levels, the exposure estimates ranged at the mean from 1.1 to 90.2 mg/kg bw per day and at the p95 from 12.5 to 237.4 mg/kg bw per day. At the proposed typical use level for FC 17.1, the exposure estimates ranged at the mean from 0.7 to 60.2 mg/kg bw per day and at the p95 from 10.3 to 159.5 mg/kg bw per day. The Panel noted that the estimated long-term exposures are very likely conservative, as the uncertainties identified resulted in an overestimation of the exposure to carbomer from its use as a food additive. On the other hand, it was noted that there may be additional exposure to carbomer from other uses e.g. pharmaceuticals. The Panel noted that the maximum proposed use levels in solid and liquid food supplements would result in exposure estimates close to or above the derived ADI of 190 mg/kg bw per day, with the highest p95 value being 240 mg/kg bw per day. The uncertainties identified indicated that level of exposure to carbomer from its proposed use as a food additive is likely to be an overestimation. Taking a conservative approach, the Panel concluded that exposure to carbomer would not give rise to a safety concern if the proposed maximum use level for the food supplements supplied in a solid form is lowered to the typical use level reported by the applicant. 1 Introduction The present scientific opinion deals with the safety evaluation of crosslinked polyacrylic acid polymers, known under the generic term 'carbomer', proposed as food additive for use in solid and liquid food supplements. 1.1 Background and Terms of Reference as provided by the requestor 1.1.1 Background The use of food additives is regulated under the European Parliament and Council Regulation (EC) No 1333/2008 on food additives.11 Regulation (EC) No 1333/2008 of the European Parliament and of the Council of 16 December 2008 on food additives. OJ L 354, 31.12.2008. Only food additives that are included in the Union list, in particular in Annex II to that regulation, may be placed on the market and used in foods under conditions of use specification therein. Moreover, food additives shall comply with the specifications as referred to in Article 14 of that Regulation and laid down in Commission Regulation (EU) No 231/201222 Commission Regulation (EU) No 231/2012 of 9 March 2012 laying down specifications for food additives listed in Annexes II and III to Regulation (EC) no 1333/2008 of the European Parliament and of the Council. OJ L 83, 22.3.2012. . An application has been introduced for the authorisation of the use of carbomer (cross-linked polyacrylic acid polymers) as a new food additive. Carbomer is intended for use in solid and liquid food supplements (i.e. food categories 17.1 and 17.2 of part E of Annex II to Regulation (EC) No 1333/2008). In solid food supplements it is intended for use at maximum level of 300,000 mg/kg for the controlled extended release of nutrients from the food supplement. In liquid food supplements it is intended for use at the maximum level of 30,000 mg/kg as thickener, emulsifier and stabiliser to develop semisolid and liquid oral formulations with a wide range of flow and rheological properties. 1.1.2 Terms of Reference The European Commission requests the European Food Safety Authority to perform a risk assessment and to provide a scientific opinion on the safety of the proposed use of carbomer as a food additive in solid and liquid food supplements, in accordance with Regulation (EC) No 1331/2008 establishing a common authorisation procedure for food additives, food enzymes and flavourings.33 Regulation (EC) No 1333/2008 of the European Parliament and of the Council of 16 December establishing a common authorisation procedure for food additives, food enzymes and food flavourings. OJ L 354, 31.12.2008. 1.2 Information on existing evaluations and authorisations Carbomers, defined as high molecular mass polymers of acrylic acid cross-linked with polyalkenyl ethers of sugars or polyalcohols with 56–68% of carboxylic acid groups (for the dried substance), are used in pharmaceutical products and recognised as excipients in the European Pharmacopoeia (European Pharmacopoeia 10.5, 2021). Carbomer (CAS No 9007-20-9; 9003-01-4; 76050-42-5; 9062-04-8; 9007-16-3; 9007-17-4) is included in the European Commission database for information on cosmetic substances and ingredients (CosIng, online). As a cosmetic ingredient, its functions are reported to be: emulsion stabiliser, gel formation and viscosity control. Carbomer (CAS No 9007-20-9) is also pre-registered under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation44 Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC. OJ L 396, 30.12.2006. and is listed in the inventory of substances likely to meet the Annex III criteria of the same Regulation as suspected hazardous to the aquatic environment and as a suspected skin irritant (ECHA, online a). With respect to acrylic acid, the constituent monomer of the polymer carbomer, a group specific migration limit (SML) of 6 mg/kg food, expressed as free acrylic acid, is established for acrylic acid along with 13 related substances (e.g. esters of acrylic acid) used as food contact substances by Commission Regulation (EU) No 10/2011 on plastic materials and articles intended to come into contact with food.55 Commission Regulation (EU) No 10/2011 on plastic materials and articles intended to come into contact with food. OJ L 12, 15.1.2011. 2 Data and methodologies 2.1 Data The applicant submitted a dossier to support the safety evaluation of the present application on crosslinked polyacrylic acid polymers, named as 'carbomer', proposed as a food additive for use in solid and liquid food supplements (Documentation provided to EFSA No. 1). Following a request from EFSA on 05 November 2020, additional data were provided by the applicant on 2 February 2021 (Documentation provided to EFSA No. 2). 2.2 Methodologies This opinion was formulated following the principles described in the EFSA Guidance of the Scientific Committee on transparency with regard to scientific aspects of risk assessment (EFSA Scientific Committee, 2009) and following the relevant existing Guidance documents from the EFSA Scientific Committee. The current 'Guidance for submission for food additive evaluation' (EFSA ANS Panel, 2012) has been followed by the FAF Panel for evaluating the present application. 3 Assessment 3.1 Technical data 3.1.1 Identity of the proposed food additive According to the applicant, the proposed food additive consists of crosslinked polyacrylic acid polymers, known as 'carbomer'. These polymers are formed from the monomer, acrylic acid, which is polymerised and crosslinked with allyl pentaerythritol (APE). The polymers are synthesised in ethyl acetate using ■■■■■ as free-radical polymerisation initiator (see Table 1). Table 1. Monomer, crosslinker and polymerisation initiator of carbomer Chemical structure Function and chemical name Monomeracrylic acid (2-propenoic acid), CAS: 79-10-7 Crosslinkerallyl pentaerythritol (CAS: 91648-24-7), mixture comprising of:■■■■■■■■■■, the structure shown)■■■■■ Polymerisation initiator■■■■■ The polymer was characterised by attenuated total reflective infra-red spectroscopy (ATR-IR) and by proton nuclear magnetic resonance spectroscopy (1H-NMR). The structural unit of carbomer, as provided by the applicant, is the following: Figure 1Open in figure viewerPowerPoint Carbomer structural unit m: number of monomer units; XM: crosslinker, p: number of crosslinker units, with m ≫ p. According to the applicant, each carbomer is a network structure of polymer chains interconnected by crosslinks. A representative figure illustrating a carbomer polymer with crosslinks is given in Figure 2. Figure 2Open in figure viewerPowerPoint Representative figure illustrating a carbomer polymer with crosslinks (in blue) The applicant indicated that three different grades of the carbomer are produced and sold under the trade names Carbopol® 974P NF Polymer, Carbopol® 971P NF Polymer and Carbopol® 71G NF Polymer. Specifically, two grades of carbomer can be manufactured by varying the amount of the crosslinker APE used in the polymerisation reaction (i.e. Carbopol® 974P NF Polymer, defined as 'highly crosslinked', and Carbopol® 971P NF Polymer, defined as 'lightly crosslinked') thus resulting in polymers with different viscosities. A third grade of carbomer (Carbopol® 71G NF Polymer) can be obtained from Carbopol® 971P NF Polymer via dry granulation to give a different particle size. According to the applicant, these different grades are chemically and toxicologically equivalent, all containing at least ■■■■■ of acrylic acid and less than ■■■■■ of crosslinker. Upon request for clarification from EFSA, the applicant explained that the amount of crosslinker used in the manufacture of 'lightly crosslinked' 971P NF and 71G NF polymers is ˜ ■■■■■ of the amount used for 'highly crosslinked' Carbopol 974P NF Polymer. For all three polymer grades, the manufacturing molar ratio of crosslinking agent relative to the acrylic acid monomer is ■■■■■. The applicant also explained that the degree of crosslinking affects the functional performance of the polymer. The degree of cross-linking affects the viscosity, the dissolution characteristics and the pore size of the polymer. ■■■■■ (Documentation provided to EFSA No. 1-2). Based on the information provided by the applicant, the estimated average molecular weight of the three carbomer grades is over 3 × 109 Daltons (Da), but an amount of lower molecular weight oligomer fraction (LMWF) is present in the final product (■■■■■). Analysis using ■■■■■, showing a series of oligomers increasing in steps of 72 mass units that is consistent with the repeat unit of -CH2-CH(COOH)- depicted in Figure 1. ■■■■■ (Documentation provided to EFSA No. 1-2). The impurities profile of carbomer was analysed by gas chromatography-mass spectrometry (GC-MS) for component identification and by gas chromatograph (GC) or high-performance liquid chromatography (HPLC) for quantification. In particular, the applicant differentiated between: 'specified impurities': such as acrylic acid (monomer) and ethyl acetate (solvent). According to the applicant, these impurities are controlled by the manufacturing process and limited by the proposed maximum limits as outlined in Table 2. 'unspecified impurities' derived from the starting materials: residual levels of unreacted cross linker APE. The applicant stated that the reaction conditions employed ensure an almost complete incorporation of the cross linker into the polymer backbone and that the manufacture ratio of APE/acrylic acid monomer is very low ■■■■■. The ■■■■■ APE components (see structures in Table 1) were reported as being typically ■■■■■ with lower levels of the ■■■■■ APE at typically ■■■■■. For the three batches of 'lightly crosslinked' and three batches of 'highly crosslinked' polymer analysed, the ■■■■■ component was in the range ■■■■■ and the ■■■■■ component was in the range ■■■■■. No data were provided for the ■■■■■ component (Documentation provided to EFSA No. 2). by-products from the polymerisation initiator ■■■■■: ■■■■■. The applicant indicated that ■■■■■ are typically present at levels of ■■■■■. ■■■■■ and controls on raw materials specifications and the manufacturing processes ensure a high degree of batch-to-batch consistency. ■■■■■ (Documentation provided to EFSA No. 2). Concerning the polymerisation initiator ■■■■■ itself, the Panel noted that the manufacturing process for carbomer involves heating during the polymerisation step and the drying step. Taking into account the short half-life of the thermally unstable initiator when heated,66 https://neochemical.ru/File/Akzo%20Data%20110407-Initiators%20for%20High%20Polymers.pdf the Panel considered there will be no residues of the initiator in the proposed food additive. Overall, for the 'unspecified impurities', the applicant stated that these are typically present at levels below ■■■■■ (Documentation provided to EFSA No. 1). The Panel noted that the analytical levels reported for ■■■■■, as indicated by the applicant. The anticipated dietary exposure estimates to the carbomer impurities ('specified' and 'unspecified' impurities and LMWF ■■■■■ using the specifications proposed by the applicant and/or the highest reported analytical levels are reported in Section 3.3.2. (Table 7). 3.1.2 Proposed specifications Specifications for the new food additive carbomer, as proposed by the applicant, are reported in Table 2. Table 2. Specifications proposed by the applicant for the new food additive carbomer (Documentation provided to EFSA No. 1) Common name Carbomer Trade names Carbopol® 974P NF Polymer, Carbopol® 971P NF Polymer, Carbopol® 71G NF Polymer Definition: Carbomers are defined as high-molecular mass polymers obtained by polymerisation of acrylic acid and crosslinking with alkenyl ethers of sugars or polyalcohols CAS nr. 9007-20-9 (primary CAS), 9003-01-4 (secondary CAS) Carboxylic acid content 56–68% (on dried substance) Acrylic acid Not more than 1,000 mg/kg Ethyl acetate Not more than 0.5% Loss on drying Not more than 2% Sulfated ashes Not more than 2.5% Viscosity (mP*s)25°Caa Brookfield RVT, 20 rpm, neutralised to pH 7.3–7.8. 0.5 wt% mucilage, spindle #5 (674P and 71G) or #6 (971P); –: Not specified. Carbopol® 974P NF Carbopol® 971P NF Carbopol® 71G NF 29.400–39.400 4.000–11.000 Physical form Powder Powder Granules Pass through 40 mesh, % 425 μm – – 95 min Pass through 100 mesh, % 150 μm – – 10 max a Brookfield RVT, 20 rpm, neutralised to pH 7.3–7.8. 0.5 wt% mucilage, spindle #5 (674P and 71G) or #6 (971P); –: Not specified. According to publicly available information, applicable synonyms for Carbopol® 974P NF Polymer and Carbopol® 971P NF Polymer are: carbomer, carboxypolymethylene; for Carbopol® 71G NF Polymer are: carbomer homopolymer type A, carbomer homopolymer (Lubrizol pharmaceuticals, online77 https://www.lubrizol.com/Health/Pharmaceuticals/Excipients/Carbopol-Polymer-Products ). The Panel noted that analytical data performed on five batches, for each grade of carbomer, were provided to demonstrate that carbomer can be consistently manufactured within its proposed specifications. The applicant provided information about the analytical methods employed for each determination (for some of them, the related validation reports were made available). The applicant indicated that the proposed definition for the food additive is consistent with the European Pharmacopoeia monograph for carbomer. The Panel, however, noted that the European Pharmacopoeia monograph refers to a limit for benzene, a solvent medium which is not used in the manufacturing process of the proposed food additive described in the dossier submitted in support of the current evaluation (ethyl acetate is used instead) and that such definition does not specify the crosslinking agent (allyl pentaerythritol) and the polymerisation initiator ■■■■■. In addition, the Panel noted that depending on the crosslinker and polymerisation initiator used in the synthesis of carbomer, different impurities may result in the final product. Therefore, the Panel considered that the crosslinker, the polymerisation initiator and the polymerisation solvent used in the manufacturing of carbomer, proposed in the present application, should be specified in the definition. Also, the Panel observed that no specification limit value has been proposed by the applicant for either the starting amount (or proportion) of the crosslinker used in the polymerisation and/or its residual content in the proposed food additive. The applicant indicated that the total carboxylic acid group content is a key indicator of polymerisation and residual acrylic acid content provides confirmation that the reaction has gone to completion. Accordingly, inclusion of these two key manufacturing parameters for the EU specifications for the food additive was proposed by the applicant (see Table 2). The Panel noted that the reported residual levels of the monomer acrylic acid in five batches of each of the three carbomer grades were all listed as equal to 50 mg/kg. Based on such analytical results on the content of residual acrylic acid in the three grades of the proposed food additive, the Panel considered that lower values than the proposed maximum limit for the specification on residual acrylic acid (not more than 1,000 mg/kg) are technologically achievable. For the residual polymerisation solvent ethyl acetate, the applicant indicated that it occurs in the final product at levels in the range of 0.2–0.48%, i.e. within the limit proposed for the specification (not more than 0.5%). The reported levels were similar for the three grades of carbomer. The Panel noted that the proposed specification maximum value should be expressed as 'percentage w/w'. The Panel noted that an average MW value for carbomer is not indicated in the proposed specifications. Following clarifications reque
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