Safety of ammonium formate (E 295) for all animal species

SCIENTIFIC OPINION ADOPTED: 18 March 2020 doi: 10.2903/j.efsa.2020.6076 Safety of ammonium formate (E 295) for all animal species EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), Vasileios Bampidis, Giovanna Azimonti, Maria de Lourdes Bastos, Henrik Christensen,
pez-Alonso, Birgit Dusemund, Maryline Kouba, Mojca Kos Durjava, Marta Lo
pez Puente, Francesca Marcon, Baltasar Mayo, Alena Pechova
, Mariana Petkova, Secundino Lo Fernando Ramos, Yolanda Sanz, Roberto Edoardo Villa, Ruud Woutersen, Gabriele Aquilina, €rgen Gropp, Carlo Nebbia and Matteo Lorenzo Innocenti Georges Bories, Ju Abstract Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety of ammonium formate for all animal species. In 2015, the FEEDAP Panel delivered an opinion on the safety and efficacy of ammonium formate, calcium formate and sodium formate. In that opinion, the Panel considered the unavoidable presence of formamide, as a contaminant of ammonium formate, of concern for developmental toxicity for reproduction animals and for carcinogenicity for non-food-producing animals. Regarding the safety for the consumer, the Panel concluded that: the use of the additive in dairy animals and laying poultry may raise concerns due to the potential exposure of consumers to formamide. In the current submission, the applicant proposed to reduce the maximum content of ammonium formate in feed to 2,000 mg formic acid equivalent/kg feed from the previously proposed 12,000 mg/kg for pigs and 10,000 mg/kg for all other animal species. Based on the calculation of the maximum safe concentration of formamide in feed, the FEEDAP Panel cannot conclude on the safety of ammonium formate in complete feed for laying hens and sows, since the calculate maximum concentration of formamide in feed (11.5 mg formamide/kg) exceed the maximum safe concentration in feed for these species (5.6 mg formamide/kg for laying hens and 9.9 mg formamide/kg for sows). Based on the results of a residue study in eggs, the use of ammonium formate in animal nutrition at a maximum content of 2,000 mg formic acid equivalent/kg complete feed would not result in concerns on the safety for the consumer. © 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority. Keywords: Ammonium formate, formamide, technological additive, safety for the target species, safety for the consumer Requestor: European Commission Question number: EFSA-Q-2018-00341 Correspondence: [email protected] www.efsa.europa.eu/efsajournal EFSA Journal 2020;18(4):6076 Ammonium formate for all animal species Panel members: Giovanna Azimonti, Vasileios Bampidis Maria de Lourdes Bastos, Henrik Christensen,
pez-Alonso, Secundino Lo
pez Puente, Birgit Dusemund, Mojca Kos Durjava, Maryline Kouba, Marta Lo
Francesca Marcon, Baltasar Mayo, Alena Pechova, Mariana Petkova, Fernando Ramos, Yolanda Sanz, Roberto Edoardo Villa and Ruud Woutersen. Suggested citation: EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), Bampidis V, Azimonti G, Bastos ML, Christensen H, Dusemund B, Kouba M, Kos
pez-Alonso M, Lo
pez Puente S, Marcon F, Mayo B, Pechova
A, Petkova M, Ramos F, Sanz Durjava M, Lo Y, Villa RE, Woutersen R, Aquilina G, Bories G, Gropp J, Nebbia C and Innocenti ML, 2020. Scientific Opinion on the safety of ammonium formate (E 295) for all animal species. EFSA Journal 2020;18 (4):6076, 12 pp. https://doi.org/10.2903/j.efsa.2020.6076 ISSN: 1831-4732 © 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority. This is an open access article under the terms of the Creative Commons Attribution-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited and no modifications or adaptations are made. The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. www.efsa.europa.eu/efsajournal 2 EFSA Journal 2020;18(4):6076 Ammonium formate for all animal species Table of Contents Abstract................................................................................................................................................... 1. Introduction................................................................................................................................ Background and Terms of Reference as provided by the requestor.................................................. 1.1. Additional information.................................................................................................................. 1.2. 2. Data and methodologies .............................................................................................................. Data........................................................................................................................................... 2.1. Methodologies............................................................................................................................. 2.2. 3. Assessment................................................................................................................................. 3.1. Conditions of use ........................................................................................................................ 3.2. Safety ........................................................................................................................................ 3.2.1. Toxicological profile of formamide................................................................................................. 3.2.2. Safety for the target species ........................................................................................................ 3.2.3. Safety for the consumer .............................................................................................................. 3.2.3.1. Residue study ............................................................................................................................. 3.2.3.2. Consumer exposure..................................................................................................................... 3.2.3.3. Conclusions on the safety for the consumer .................................................................................. 4. Conclusions................................................................................................................................. Documentation as provided to EFSA/Chronology............................................................................ 5. References............................................................................................................................................... Abbreviations ........................................................................................................................................... Appendix A – Calculation of consumer exposure with FACE model................................................................ www.efsa.europa.eu/efsajournal 3 1 4 4 4 5 5 5 5 5 5 5 6 7 7 8 8 8 8 8 9 10 EFSA Journal 2020;18(4):6076 Ammonium formate for all animal species 1. Introduction 1.1. Background and Terms of Reference as provided by the requestor Regulation (EC) No 1831/20031 establishes the rules governing the Community authorisation of additives for use in animal nutrition and in particular, Article 9 defines the terms of such authorisation by the Commission. The applicant, Nutreco Nederland B.V. Trade,2 is seeking a Community authorization for Ammonium formate (E295) as a feed additive for all animal species. (Table 1) Table 1: Description of the substances Category of additive Technological additive Functional group of additive Description preservatives Ammonium formate (E295) Target animal category Applicant All animal species Nutreco Nederland B.V. Trade Type of request New opinion On 05 May 2015, the Panel on Additives and Products or Substances used in Animal Feed of the European Food Safety Authority (“Authority”), in its opinion3 on the safety and efficacy of the product when used as a technological additive for all animal species, could not conclude on the safety of ammonium formate for target species and consumers. The Commission gave the possibility to the applicant to submit complementary information in order to complete the assessment and to allow a revision of the Authority’s opinion. The new data have been received on 09 April 2018. In view of the above, the Commission asks the Authority to deliver a new opinion on ammonium formate as a preservative for all animal species based on the additional data submitted by the applicant. 1.2. Additional information Ammonium formate (E 295) is presently listed in the EU Register of Feed Additives as technological additives (functional group: preservatives) for use in feed for all animal species without time limit, and it is subject to re-evaluation.4 Ammonium formate is authorised in food legislation as food packaging additive (E 295, Directive 2007/42/EC5) for use in ‘ingredients for manufacturing’ intended to come in contact with food. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) issued two opinions on ammonium formate (JECFA, 1974, 1998) allocating an acceptable daily intake (ADI) of 0–3 mg/kg/body weight (bw) per day. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) adopted in 2015 two opinions3,6 on ammonium formate as technological additives for all animal species (EFSA FEEDAP Panel, 2015a,b). In those opinions, the FEEDAP Panel could not conclude on the safety of the additive for reproducing and non-food producing animals, and for the consumer. The applicant has submitted new information to support the safety of ammonium formate as a preservative in feedingstuffs for all animal species. 1 2 3 4 5 6 Regulation (EC) No 1831/2003 of the European Parliament and of the Council of 22 September 2003 on additives for use in animal nutrition. OJ L 268, 18.10.2003, p. 29. Nutreco Nederland B.V. Trade, Stationsstraat 77 3811 MH Amersfoort, Netherlands. The opinion linked to the previous dossier (related to EFSA-Q-2011-00424) is available on the EFSA website: https://efsa.online library.wiley.com/doi/pdf/10.2903/j.efsa.2015.4056 FEED dossier reference: FAD-2018-0016. Commission Directive 2007/42/EC of 29 June 2007 relating to materials and articles made of regenerated cellulose film intended to come into contact with foodstuffs. The opinion linked to the previous dossier (related to EFSA-Q-2013-00755) is available on the EFSA website: https://efsa.online library.wiley.com/doi/epdf/10.2903/j.efsa.2015.4113 www.efsa.europa.eu/efsajournal 4 EFSA Journal 2020;18(4):6076 Ammonium formate for all animal species 2. Data and methodologies 2.1. Data The present assessment is based on data submitted by the applicant in the form of additional information4 to previous applications on the same product.7 2.2. Methodologies The approach followed by the FEEDAP Panel to assess the safety of ammonium formate is in line with the principles laid down in Regulation (EC) No 429/20088 and the relevant guidance documents: Guidance on technological additives (EFSA FEEDAP Panel, 2012), Guidance for the preparation of dossiers for the re-evaluation of certain additives already authorised under Directive 70/524/EEC (EFSA, 2008), Guidance on the assessment of the safety of feed additives for the target species (EFSA FEEDAP Panel, 2017a) and Guidance on the assessment of the safety of feed additives for the consumer (EFSA FEEDAP Panel, 2017b). 3. Assessment The additive under assessment is ammonium formate, intended to be used as a technological additive (functional group: preservatives) in feed for all animal species. The additive was fully characterised in the previous opinion on the safety and efficacy of formic acid, ammonium formate and sodium formate as technological additive for all animal species (EFSA FEEDAP Panel, 2015a). In its previous opinion (EFSA FEEDAP Panel, 2015a), the Panel concluded that ‘the presence of formamide (a developmental toxicant) in ammonium formate additives is a concern. Even if the concentration of formamide in the additive is restricted to a maximum of 0.3%, as proposed, this is considered insufficient to guarantee the protection of reproduction animals. There is also evidence from animal studies of a carcinogenic potential of formamide which is an argument for avoiding the use of ammonium formate-containing additives in non-food-producing animals’. Regarding the safety for the consumer, the Panel concluded that: ‘although the use of ammonium formate in growing/fattening animals would not raise any safety concern for the consumer, its use in dairy animals and laying poultry may raise concerns due to the potential exposure of consumers to formamide’. The applicant has provided new arguments to support the safety of the additive for the target species and new data on the presence of residues of formamide in eggs. In addition, they proposed a modification in the conditions of use, reducing the maximum ammonium formate content in complete feedingstuffs to 2,000 mg (formic acid equivalent)/kg for all animal species, from the original 12,000 mg/kg for pigs and 10,000 mg/kg for all the other species. 3.1. Conditions of use The applicant is proposing to modify the original conditions of use of the additive as follow: a) The additive is intended to be used as a preservative in feedingstuffs for all animal species except for dairy ruminants and non-food-producing animals. b) The maximum proposed content in complete feedingstuff is 2,000 mg (formic acid equivalent)/kg. 3.2. Safety 3.2.1. Toxicological profile of formamide In its former opinion (EFSA FEEDAP Panel, 2015a), the FEEDAP Panel identified a concern for the presence of the unavoidable contaminant formamide, because of its reproductive and potential carcinogenic properties. In particular, three studies (Leuscher, 1974; NTP, 2001; George et al., 2000a) were already evaluated in the previous assessment (EFSA FEEDAP Panel, 2015a). 7 8 FEED dossier reference: FAD-2018-0016 and FAD-2013-0036. Commission Regulation (EC) No 429/2008 of 25 April 2008 on detailed rules for the implementation of Regulation (EC) No 1831/2003 of the European Parliament and of the Council as regards the preparation and the presentation of applications and the assessment and the authorisation of feed additives. OJ L 133, 22.5.2008, p. 1. www.efsa.europa.eu/efsajournal 5 EFSA Journal 2020;18(4):6076 Ammonium formate for all animal species In the current dossier, the applicant did not provide any new toxicological data on formamide but proposed a new interpretation of the data already provided and evaluated in the EFSA opinion (EFSA FEEDAP Panel, 2015a). In the previous EFSA assessment (EFSA FEEDAP Panel, 2015a), a no observed adverse effect level (NOAEL) was identified for reproductive effects (maternal and embryo/fetotoxicity) in a study (Leuscher, 1974) in pregnant New Zealand White rabbits (N = 10/group) given formamide via gavage at 0, 34, 113 or 340 mg formamide/kg bw per day on gestation day 6 to 18. Mortality was increased (7/10) at the top exposure level, with clinical signs of toxicity in some animals at the lower dosage (113 mg formamide/kg bw per day), including inappetence and vaginal bleeding. Post-implantation losses were significantly increased at 113 mg/kg bw per day. Fetal weights were decreased and increased numbers of fetal variations were seen at 113 and 340 mg/kg bw per day. No teratogenic effects were observed. A NOAEL of 34 mg/kg bw per day was identified, based on maternal toxicity and embryotoxicity seen at doses equal or greater than 113 mg formamide/kg bw per day. In the current dossier, the applicant provided a different interpretation of the results of the available studies (Leuscher, 1974; NTP, 2001; George et al., 2000), expressing criticism towards the study in rabbits (Leuscher, 1974) selected by EFSA to derive the NOAEL for reproductive toxicity. This study was done before the issue of the Organisation for Economic Co-operation and Development (OECD) guidelines for reproductive and developmental studies. The applicant proposed instead to reconsider two more recent National Toxicology Program (NTP) studies, one performed in rabbits and another one in rats, already submitted in the original application and assessed by the FEEDAP Panel in the previous opinion. In the first study (NTP, 2001),9 female New Zealand White rabbits were dosed by gavage with formamide (35, 70 or 140 mg/kg bw per day) or its vehicle (deionised/distilled water) on GD 6 through 29. The study was conducted in a two-replicates design. Twenty-four naturally mated female rabbits (12 per replicate) were assigned to each group; mortality and other signs of toxicity (e.g. reduction body weight, feed intake, gravid uterine weight) were noted in does only at the highest dose, resulting in a maternal NOAEL of 70 mg/kg bw per day. In addition, formamide caused significant treatment-related developmental toxicity at 140 mg/kg per day, consisting of reduced mean live litter size and fetal body weight per litter. Consequently, the developmental toxicity NOAEL was also 70 mg/kg per day. In the second study (George et al., 2000), mated female rats were administered formamide via gavage at doses of 0, 50, 100 and 200 mg/kg bw per day on GD 6 through 19. No maternal mortality was observed throughout the experiment. The administration of the highest formamide dosage (200 mg/kg bw per day) resulted in the decrease of maternal body weight, weight gain and gravid uterine weight. Formamide did not affect prenatal viability or the incidence of fetal malformations or variations but decreased the average fetal body weight/litter at both 200 and 100 mg/kg/bw per day. The NOAEL for maternal toxicity in rats was 100 mg formamide/kg bw per day and the NOAEL for developmental toxicity was 50 mg formamide/kg bw/day. Taking into account the results of the above described studies, the applicant proposes to retain the value of 50 mg formamide/kg bw per day as the NOAEL for the developmental toxicity. The FEEDAP Panel considers that the three studies (Leuscher, 1974; NTP, 2001; George et al., 2000) were already evaluated in the previous assessment (EFSA FEEDAP Panel, 2015a) and that no new evidence on the toxicological profile of formamide has been provided by the applicant in the current application. The FEEDAP Panel further considers that the three studies remain valid and there is no ground for a modification of the conclusions previously reached. Consequently, the FEEDAP Panel concludes that the lowest NOAEL of 34 mg/kg bw per day, identified in the three studies, is still valid for formamide. 3.2.2. Safety for the target species In the previous opinion (EFSA FEEDAP Panel 2015a), the FEEDAP Panel estimated the exposure of reproductive animals (sows, laying hens and dairy cows) to formamide considering the maximum content of ammonium formate of 12,000 mg/kg complete feed for pigs and 10,000 mg/kg complete feed for the other species, and the maximum concentration of 0.3% formamide in the additive. The resulting exposure corresponded to 2.1, 3.4 and 1.8 mg formamide/kg bw per day for sows, laying hens and dairy cows, respectively. The Panel concluded that ‘the difference between the potential 9 Technical dossier/Section III/Ref_III_15_NTP_2001. www.efsa.europa.eu/efsajournal 6 EFSA Journal 2020;18(4):6076 Ammonium formate for all animal species exposure and the NOAEL identified in the rabbit study is considered insufficient to guarantee the protection of reproduction animals’ (EFSA FEEDAP Panel, 2015a). The applicant does not support the application for the authorisation of the additive for lactating ruminants and non food-producing animals and asks to reduce the maximum inclusion level of ammonium formate in complete feed to 2,000 mg/kg (as formic acid equivalent), with a maximum content of formamide of 0.3% additive, will reduce the maximum formamide content in complete feed to 11.5 mg/kg. In order to calculate the maximum feed concentration of formamide which can be considered safe for the target species, the Panel used the approach described in the Guidance on safety for the target species (EFSA FEEDAP Panel, 2017a). The NOAEL of 34 mg/kg bw per day for formamide was used (see Section 3.2.1). Applying an uncertainty factor (UF) of 100 to the NOAEL, the maximum calculated safe concentration in feed for laying hens and sows would correspond to 5.6 and 9.9 mg/kg complete feed, respectively. Both values are below the calculated concentration of formamide in compete feed (11.5 mg/kg). Therefore, the FEEDAP Panel is not in the position to conclude on the safety of ammonium formate at a maximum concentration of 2,000 mg formic acid equivalent/kg complete feed for laying hens and sows. 3.2.3. Safety for the consumer In its previous opinion, the Panel raised concerns for the safety of consumers regarding the use of the additive in dairy animals and laying poultry due to the potential exposure of consumers to formamide. In the present submission, the applicant has provided a residue study in laying hens. 3.2.3.1. Residue study A study on the transfer of formamide from feed to eggs of laying hens was submitted. A total of 87 laying hens (Dekalb White, 77 weeks old) were distributed into five groups according to the experimental protocol described on Table 2. A standard laying hen feed was supplemented with ammonium formate at 0.5 times the maximum dose proposed for use (group 1: equivalent to 1,000 mg formic acid/kg) and at that dose (groups 2, 3, 4 and 5: 10,000 mg/kg). In these groups, ammonium formate was spiked with increasing doses of formamide and the analytically measured average values in feed were retained for transfer calculations of formamide. Table 2: Group number Experimental protocol of the residue studies in eggs Laying hens/pens (animals/ pen) Ammonium formate inclusion level (as formic acid equivalent, mg/kg feed) Formamide content in the Formamide spiked level additive % Analysed formamide concentration in feed (mg/kg)2 1 30, 10 (3) 1,000 0.3 0.5 91 7.3 2 30, 10 (3) 9, 3 (3) 10,000 0.3 59 66.3 10,000 1.2 20 9 208 4 9, 3 (3) 10,000 2.1 35 9 340 5 9, 3 (3) 10,000 3.0 50 9 542 3 1 Level corresponding to the level deriving from the use of the additive at the maximum recommended concentration of 2000 mg formic acid equivalent/kg complete feed. 2 Analytically determined average values. All animals were accustomed for 7 days to the control feed then were administered the formamide spiked feed from day 7 until day 40. Eggs were collected per pen per day at day 6 (pre-experimental period), day 37, day 38 and day 39, homogenised and kept at 20°C; the samples were analysed in duplicate. The analysis of the eggs indicated similar formamide concentrations after 31, 32 and 33 days of exposure, indicating that the metabolic steady-state was reached. A linear relationship was shown to www.efsa.europa.eu/efsajournal 7 EFSA Journal 2020;18(4):6076 Ammonium formate for all animal species occur between the formamide level in the feed and that measured in the eggs, with: formamide in eggs (mg/kg) = 0.0494 9 [formamide in feed (mg/kg)] + 0.4493 (R2 = 0.9606). On the basis of the linear regression equation between formamide in layer feed and formamide in eggs, it can be calculated that the expected amount of formamide in eggs will be 1.02 mg/kg at the maximum recommended level of 2,000 mg formic acid equivalents/kg of complete feed with maximum 0.3% formamide. Using the upper 95% confidence level of the regression, the expected concentration of formamide in eggs would be 1.32 mg/kg. The FEEDAP Panel notes that formamide concentrations in feed used to calculate the linear regression for formamide in feed and in eggs were not centred at the expected maximum inclusion level of formamide in feed. This value is 11.5 mg formamide/kg complete feed, the values used in the experiment and consequently in the regression analysis are between 7.3 and 542 mg/kg (see Table 2). However, the high R2 is considered to partially compensate this weakness. 3.2.3.2. Consumer exposure For the current assessment, the exposure of consumers has been calculated following the methodology described in the most recent Guidance on the safety of feed additives for consumers (EFSA FEEDAP Panel, 2017b) (for further details see Appendix A), using the residue data reported in the residue study (see Section 3.2.3.1). The exposure to formamide at the 95th percentile varied between 0.0017 mg/kg bw per day in the category ‘elderly’ and 0.0055 mg/kg bw per day in the category ‘other children’. The NOAEL identified for formamide (34 mg/kg bw and day) is by a factor of 20,000 and 6,200, respectively, higher than the estimated exposure of consumers. 3.2.3.3. Conclusions on the safety for the consumer Based on the above, the FEEDAP Panel concludes that use of ammonium formate in feed for laying hens at the maximum use level of 2,000 mg/kg complete feed would not raise concerns on the safety for the consumers. Considering the outcome of the previous opinion and the new data assessed above, the FEEDAP Panel concludes that use of ammonium formate in animal nutrition at the proposed conditions of use is safe for the consumers. 4. Conclusions The FEEDAP Panel cannot conclude on the safety of ammonium formate in complete feed for laying hens and sows, since the calculated maximum concentration of formamide in feed (11.5 mg formamide/kg) exceed the maximum safe concentration in feed for these species (5.6 mg formamide/kg for laying hens and 9.9 mg formamide/kg for sows). The use of ammonium formate in diets of laying hens at the maximum use level of 2000 mg/kg is considered safe for the consumers. Considering also the outcome of the previous opinion, the FEEDAP Panel concludes that use of ammonium formate in animal nutrition at the proposed conditions of use is safe for the consumers. 5. Documentation as provided to EFSA/Chronology Date Event 09/04/2018 02/05/2018 Dossier received by EFSA. Ammonium formate (E 295) submitted by Nutreco Reception mandate from the European Commission 22/05/2018 Application validated by EFSA – Start of the scientific assessment 18/03/2020 Opinion adopted by the FEEDAP Panel. End of the Scientific assessment References EFSA (European Food Safety Authority), 2008, revised in 2009. Guidance of the Scientific Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) for the preparation of dossiers for the re-evaluation of certain additives already authorised under Directive 70/524/EEC. EFSA Journal 2008;6(9):779, 9 pp. https:// doi.org/10.2903/j.efsa.2008.779 www.efsa.europa.eu/efsajournal 8 EFSA Journal 2020;18(4):6076 Ammonium formate for all animal species EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), 2012. Guidance for the preparation of dossiers for technological additives. EFSA Journal 2012;10(1):2528, 23 pp. https://doi. org/10.2903/j.efsa.2012.2528 EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), 2015a. Scientific Opinion on the safety and efficacy of ammonium formate, calcium formate and sodium formate when used as a technological additive for all animal species. EFSA Journal 2015;13(5):4056, 24 pp. https://efsa.onlinelibrary. wiley.com/doi/pdf/10.2903/j.efsa.2015.4056 EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), 2015b. Scientific Opinion on the safety and efficacy of formic acid, ammonium formate and sodium formate as feed hygiene agents for all animal species. EFSA Journal 2015;13(5):4113, 24 pp. https://efsa.onlinelibrary.wiley.com/doi/ epdf/10.2903/j.efsa.2015.4113 EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), Rychen G, Aquilina G, Azimonti G, Bampidis V, Bastos ML, Bories G, Chesson A, Cocconcelli PS, Flachowsky G, Gropp J,
pez-Alonso M, Lo
pez Puente S, Mantovani A, Mayo B, Ramos F, Saarela M, Villa RE, Kolar B, Kouba M, Lo Wallace RJ, Wester P, Anguita M, Galobart J, Innocenti ML and Martino L, 2017a. Guidance on the assessment of the safety of feed additives for the target species. EFSA Journal 2017;15(10):5021, 19 pp. https://doi.org/ 10.2903/j.efsa.2017.5021 EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), Rychen G, Aquilina G, Azimonti G, Bampidis V, Bastos ML, Bories G, Chesson A, Cocconcelli PS, Flachowsky G, Gropp J,
pez-Alonso M, Lo
pez Puente S, Mantovani A, Mayo B, Ramos F, Saarela M, Villa RE, Kolar B, Kouba M, Lo Wallace RJ, Wester P, Anguita M, Dujardin B, Galobart J and Innocenti ML, 2017b. Guidance on the assessment of the safety of feed additives for the consumer. EFSA Journal 2017;15(10):5022, 17 pp. https://doi.org/10. 2903/j.efsa.2017.5022 George JD, Price CJ, Marr MC, Myers CB and Jahnke GD, 2000a. Evaluation of the developmental toxicity of formamide in Sprague-Dawley (CD) rats. Toxicological Science, 57, 284–291. George JD, Price CJ, Marr MC, Myers CB and Jahnke GD, 2000b. Evaluation of the developmental toxicity of formamide in Sprague-Dawley (CD) rats, Research Triangle Institute, North Carolina 27709-2194. Toxicological Sciences, 69, 165–174. JECFA (The Joint FAO/WHO Expert Committee on Food Additives), 1974. Toxicological evaluation of some food additives including anticaking agents, antimicrobials, antioxidants, emulsifiers, and thickening agents. FAO Nutrition Meetings Report Series, No. 53. http://www.inchem.org/documents/jecfa/jecmono/v05je09.htm JECFA (The Joint FAO/WHO Expert Committee on Food Additives), 1998. Safety evaluation of certain food additives and contaminants. Saturated aliphatic acyclic linear primary alcohols, alcohols, aldehydes and acids. WHO Food Additives Series, No. 40. Available online: http://www.inchem.org/documents/jecfa/jecmono/v040je 10.htm €chtige Kaninchen und den €fung des Einflusses von Formamid (Charge XXIII/245) auf das tra Leuscher F, 1974. Pru Foetus bei Verabreichung per Schludsonde. NTP, 2001. Final study report developmental toxicity evaluation of formamide (cas no. 75-12-7) administered by gavage to new zealand white rabbits on gestational days 6 throuGH 29, Research Triangle Institute, North Carolina 27709-2194, National Toxicology Program P.O. Box 12233 Research Triangle Park, NC 27709. Abbreviations ADI bw FEEDAP JECFA NOAEL NTP OECD RAC UF WHO acceptable daily intake body weight Panel on Additives and Products or Substances used in Animal Feed The Joint FAO/WHO Expert Committee on Food Additives no observed adverse effect level National Toxicology Program Organisation for Economic Co-operation and Development raw agricultural commodities uncertainty factor World Health Organization www.efsa.europa.eu/efsajournal 9 EFSA Journal 2020;18(4):6076 Ammonium formate for all animal species Appendix A – Calculation of consumer exposure with FACE model Methodology As described in the Guidance on the safety of feed additives for consumers (EFSA, FEEDAP Panel, 2017b), consumption data of edible tissues and products as derived from the EFSA Comprehensive European Food Consumption Database (Comprehensive Database) will be used to assess exposure to residues from the use of feed additives in different EU countries, age classes10 and special population groups. For each EU country and age class, only the latest survey available in the Comprehensive Database will be used. While the residue data reported for feed additives refer to organs and tissues (raw agricultural commodities (RAC)), the Comprehensive Database includes consumption data for foods as consumed. In order to match those consumption data with the available residue data for feed additives, the consumption data reported in the Comprehensive Database have been converted into RAC equivalents. For assessing the exposure to coccidiostats from their use in (non-reproductive) poultry, the following list of commodities is considered: meat, fat, liver, other offals (including kidney). Depending on the nature of the health-based guidance derived, either a chronic or acute exposure assessment may be required. For chronic exposure assessments, the total relevant residues will be combined for each individual with the average daily consumptions of the corresponding food commodities, and the resulting exposures per food will be summed in order to obtain total chronic exposure at individual level (standardised by using the individual body weight). The mean and the higher percentile (usually the 95th percentile) of the individual exposures will be subsequently calculated for each dietary survey (country) and each age class separately. As opposed to the chronic exposure assessments, acute exposure calculation will be carried out for each RAC value separately. The higher percentile (usually the 95th percentile) exposures based on the consuming days only will be calculated for each food commodity, dietary survey and age class separately. Detailed results on chronic exposure calculation Table A.1: Chronic dietary exposure per population class, country and survey (mg/kg bw per day) of consumers to formamide residues eggs of laying hens fed ammonium formate (containing 0.3% formamide) at the concentration of 2,000 mg formic acid equivalent/kg complete feed Number of subjects HRP(1) HRP description Bulgaria 523 0.00453 95th Infants Infants Denmark Finland 799 427 0.00100 0.00000 95th 95th Infants Infants Germany Italy 142 9 0.00116 0.00000 95th 50th Infants Toddlers United Kingdom Belgium 1,251 36 0.00292 0.00258 95th 90th Toddlers Toddlers Bulgaria Denmark 428 917 0.00516 0.00226 95th 95th Toddlers Toddlers Finland Germany 500 348 0.00178 0.00318 95th 95th Toddlers Toddlers Italy Netherlands 36 322 0.00295 0.00372 90th 95th Toddlers Toddlers Spain United Kingdom 17 1,314 0.00408 0.00401 75th 95th Toddlers United Kingdom 185 0.00355 95th Population class Survey’s country Infants 10 Infants: < 12 months old, toddlers: ≥ 12 months to < 36 months old, other children: ≥ 36 months to < 10 years old, adolescents: ≥ 10 years to < 18 years old, adults: ≥ 18 years to < 65 years old, elderly: ≥ 65 years to < 75 years old, and very elderly: ≥ 75 years old. www.efsa.europa.eu/efsajournal 10 EFSA Journal 2020;18(4):6076 Ammonium formate for all animal species Number of subjects HRP(1) HRP description Austria 128 0.00324 95th Other children Other children Belgium Bulgaria 625 433 0.00261 0.00476 95th 95th Other children Other children Czech Republic Denmark 389 298 0.00340 0.00225 95th 95th Other children Other children Finland France 750 482 0.00247 0.00315 95th 95th Other children Other children Germany Germany 293 835 0.00331 0.00337 95th 95th Other children Other children Greece Italy 838 193 0.00482 0.00395 95th 95th Other children Other children Latvia Netherlands 187 957 0.00287 0.00326 95th 95th Other children Other children Netherlands Spain 447 399 0.00284 0.00395 95th 95th Other children Other children Spain Sweden 156 1,473 0.00552 0.00228 95th 95th Other children Adolescents United Kingdom Austria 651 237 0.00269 0.00200 95th 95th Adolescents Adolescents Belgium Cyprus 576 303 0.00156 0.00128 95th 95th Adolescents Adolescents Czech Republic Denmark 298 377 0.00199 0.00107 95th 95th Adolescents Adolescents Finland France 306 973 0.00087 0.00168 95th 95th Adolescents Adolescents Germany Germany 393 1,011 0.00268 0.00141 95th 95th Adolescents Adolescents Italy Latvia 247 453 0.00224 0.00224 95th 95th Adolescents Adolescents Netherlands Spain 1,142 651 0.00170 0.00277 95th 95th Adolescents Adolescents Spain Spain 209 86 0.00355 0.00145 95th 95th Adolescents Adolescents Sweden United Kingdom 1,018 666 0.00144 0.00154 95th 95th Adults Adults Austria Belgium 308 1,292 0.00114 0.00124 95th 95th Adults Adults Czech Republic Denmark 1,666 1,739 0.00140 0.00090 95th 95th Adults Adults Finland France 1,295 2,276 0.00139 0.00117 95th 95th Adults Adults Germany Hungary 10,419 1,074 0.00132 0.00153 95th 95th Adults Adults Ireland Italy 1,274 2,313 0.00116 0.00151 95th 95th Adults Adults Latvia Netherlands 1,271 2,055 0.00194 0.00134 95th 95th Adults Adults Romania Spain 1,254 981 0.00181 0.00163 95th 95th Adults Spain 410 0.00165 95th Population class Survey’s country Other children www.efsa.europa.eu/efsajournal 11 EFSA Journal 2020;18(4):6076 Ammonium formate for all animal species Number of subjects HRP(1) HRP description Sweden 1,430 0.00183 95th Adults Elderly United Kingdom Austria 1,265 67 0.00124 0.00123 95th 95th Elderly Elderly Belgium Denmark 511 274 0.00112 0.00103 95th 95th Elderly Elderly Finland France 413 264 0.00109 0.00098 95th 95th Elderly Elderly Germany Hungary 2,006 206 0.00120 0.00129 95th 95th Elderly Elderly Ireland Italy 149 289 0.00133 0.00118 95th 95th Elderly Elderly Netherlands Netherlands 173 289 0.00110 0.00117 95th 95th Elderly Elderly Romania Sweden 83 295 0.00165 0.00170 95th 95th Elderly Very elderly United Kingdom Austria 166 25 0.00111 0.00075 95th 75th Very elderly Very elderly Belgium Denmark 704 12 0.00121 0.00069 95th 75th Very elderly Very elderly France Germany 84 490 0.00102 0.00124 95th 95th Very elderly Very elderly Hungary Ireland 80 77 0.00136 0.00124 95th 95th Very elderly Very elderly Italy Netherlands 228 450 0.00119 0.00110 95th 95th Very elderly Very elderly Romania Sweden 45 72 0.00132 0.00214 90th 95th Very elderly United Kingdom 139 0.00103 95th Population class Survey’s country Adults bw: body weight. (1): HRP: highest reliable percentile, i.e. the highest percentile that is considered statistically robust for combinations of dietary survey, age class and possibly raw primary commodity, considering that a minimum of 5, 12, 30 and 61 observations are respectively required to derive 50th, 75th and 90th and 95th percentile estimates. Estimates with less than 5 observations were not included in this table. www.efsa.europa.eu/efsajournal 12 EFSA Journal 2020;18(4):6076