烟味原产品安全性科学意见 AM 01 – 2012 更新.pdf

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1、 EFSA Journal 2012;10(2):2580 Suggested citation: EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on the safety of smoke flavour Primary Product AM 01 - 2012 Update. EFSA Journal 2012;10(2):2580. 18 pp. doi:10.2903/j.efsa.2012.2580. Available

2、online: www.efsa.europa.eu/efsajournal European Food Safety Authority, 2012 SCIENTIFIC OPINION Scientific opinion on the safety of smoke flavouring Primary Product AM 01 2012 Update1 EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF)2,3 European Food Safety Authorit

3、y (EFSA), Parma, Italy This opinion, published on 07 March, replaces the earlier version published on 22 February 2012 4 ABSTRACT The EFSA CEF Panel updated the safety assessment of the smoke flavouring Primary Product AM 01. After the opinion of 2010 the Panel received new data i.e. new use levels,

4、 chemical data and a new in vivo Comet assay. In 2010, the Panel concluded that the genotoxic potential of this Primary Product could not be ruled out given the limitations in the data set. Also the margins of safety for this Primary Product were considered insufficient and the proposed use levels w

5、ere considered of safety concern. In the new in vivo Comet assay the Primary Product did not induce statistically significant increases in DNA strand breaks at any of the tested doses in the liver or in the duodenum cells. The Panel concluded that based on the available data there is no concern with

6、 respect to genotoxicity for the Primary Product. The chemical data provided demonstrate that the material tested in the Comet assay is representative of the Primary Product evaluated by EFSA in 2010. No additional data were provided in order to mitigate the issue associated with the large degree of

7、 batch-to-batch variability and chemical stability during shelf life described for the Primary Product in the opinion of 2010. Based on newly submitted use levels, the margins of safety are 104-114 (total dietary exposure) and 109-179 (use in traditionally smoke foods only) depending on the exposure

8、 scenario used. Given that these margins of safety are based on a 90-day toxicity study, and given the absence of data on 1 On request from the European Commission, Question No EFSA-Q-2011-01019, adopted on 02 February 2012. 2 Panel members: Iona Pratt, Ulla Beckman Sundh, Mona-Lise Binderup, Leon B

9、rimer, Laurence Castle, Karl-Heinz Engel, Roland Franz, Nathalie Gontard, Trine Husy, Rainer Grtler, Klaus-Dieter Jany, Catherine Leclercq, Jean-Claude Lhuguenot, Wim C. Mennes, Maria Rosaria Milana, Kettil Svensson, Fidel Toldr, Detlef Wlfle. Correspondence: cefefsa.europa.eu 3 Acknowledgement: The

10、 Panel wishes to thank the members of the Working Group on Flavourings: Ulla Beckman Sundh, Leon Brimer, Wilfried Bursch, Angelo Carere, Karl-Heinz Engel, Henrik Frandsen, Rainer Grtler, Frances Hill, Trine Husy, Catherine Leclercq, Wim Mennes, Gerard Mulder, Gerrit Speijers and Harriet Wallin for t

11、he preparatory work on this scientific opinion and EFSA staff: Davide Arcella, Anna F. Castoldi, Andrea Terron and Anne Theobald for the support provided to this scientific opinion. 4 Editorial changes have been made. These changes do not affect the overall conclusions of this Opinion. To avoid conf

12、usion the original version has been removed from the website. Smoke flavouring Primary Product AM 01 - 2012 Update 2 EFSA Journal 2012;10(2):2580 reproduction, developmental toxicity and of long term studies, it is concluded that the uses and use levels of Primary Product would require a larger marg

13、in of safety. The Panel concluded that the proposed use of the Primary Product at the uses and use levels specified is of safety concern. European Food Safety Authority, 2012 KEY WORDS Smoke flavouring, Primary Product, AM 01 Smoke flavouring Primary Product AM 01 - 2012 Update 3 EFSA Journal 2012;1

14、0(2):2580 SUMMARY Following a request from the European Commission (EC), the Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) of the European Food Safety Authority (EFSA) re-evaluated the safety of the smoke flavouring Primary Product AM 01 based on new data (new use l

15、evels, chemical data and a new in vivo Comet assay ) submitted by the applicant in accordance with Regulation (EC) No 2065/2003 of the European Parliament and the Council on smoke flavourings intended for use in or on foods. The other information required for the evaluation of the Primary Product AM

16、 01, in accordance with the Guidance document (EFSA, 2005), is available in the previous opinion published on 8 January 2010 (EFSA, 2010). The applicant did not submit new general data on the batch-to-batch variability and chemical composition during the shelf life of the Primary Product AM 01. Howe

17、ver, on the basis of the compositional data provided for the batch tested in the Comet assay (AM 01, CH 011210), the Panel considered this material to be representative of the Primary Product evaluated by EFSA in 2010. In the opinion published in 2010, the CEF Panel concluded that the genotoxic pote

18、ntial of the Primary Product AM 01 in vivo could not be ruled out, given the limitations in the dataset. In particular, one of the in vitro genotoxicity tests gave a positive result (positive in an in vitro assay for gene mutations at the hprt locus in V79 cells, only in the absence of metabolic act

19、ivation), whereas another test was regarded as inconclusive. The Panel deemed the then available in vivo Comet assay of limited validity because of some shortcomings with respect to the study design and reporting. In the same assessment the Panel also concluded that the margins of safety for this Pr

20、imary Product (ranging from 16 to 76, depending on the exposure scenario used) were insufficient and that its use at the proposed uses and use levels would be of safety concern. Such margins of safety were calculated on the basis of a no-observed-adverse-effect-level (NOAEL) of 250 mg/kg bw/day iden

21、tified from a 90-day toxicity study, and on dietary exposure estimates (normal or upper use levels) from all food sources (18 food categories) including traditionally smoked foods. Based on these EFSA conclusions, the applicant has performed a new in vivo Comet assay in the rat in compliance with GL

22、P principles and has submitted the results for evaluation by EFSA. As compared with the previous application, the applicant has modified the proposed maximum use levels of AM 01 for the 18 food categories as outlined in Commission Regulation (EC) No 1565/2000. Accordingly EFSA has updated its earlie

23、r exposure assessment for AM 01. The present opinion should be read in conjunction with the EFSA opinion of 2010, since this update only contains the new data provided by the applicant (chemical data, in vivo Comet assay and proposed reduced upper use levels) and their evaluation by the CEF Panel. T

24、he other (chemical and toxicological) information required for the evaluation of smoke flavourings is available in the previous opinion and is still considered to apply to this product. The chemical data provided demonstrate that the test material used in the new in vivo Comet assay done in 2011 is

25、representative of the Primary Product previously evaluated by EFSA (EFSA, 2010). No additional data were provided in order to mitigate the issue associated with the large degree of batch-to-batch variability and chemical stability during shelf life described for the Primary Product in the opinion of

26、 2010. The Primary Product AM01 was investigated in an in vivo Comet assay on liver and duodenum cells under alkaline conditions in male Wistar (Crl(WI)BR) rats (5 per group). Animals were treated by oral gavage twice with 2000 and 1000 mg/kg bw, with one sampling time of about 3 to 6 hours after th

27、e second treatment. The positive control 1,2-dimethylhydrazine was administered once at 10 or 20 mg/kg bw. Under the experimental conditions the test item did not induce statistically significant increases in DNA strand breaks at any of the tested doses in the liver or in the duodenum cells and was

28、considered not genotoxic in this assay. Smoke flavouring Primary Product AM 01 - 2012 Update 4 EFSA Journal 2012;10(2):2580 In order to estimate dietary exposure to the Primary Product AM 01, the CEF Panel used two different methodologies, namely the Smoke Theoretical Added Maximum Daily Intake (SMK

29、-TAMDI) and the smoke flavouring EPIC model (SMK-EPIC), developed by the Panel specifically for smoke flavourings. In both cases, dietary exposure estimates were calculated by assuming that the Primary Product AM 01 is present at the upper use levels provided by the applicant for the 18 food categor

30、ies as outlined in the Commission Regulation (EC) No 1565/2000. Normal use levels were not provided by the applicant. Depending on the exposure assessment model used, dietary exposures from all sources range from 2.2 to 2.4 mg/kg bw/day. When dietary exposure estimates are based on use of the Primar

31、y Product AM 01 in traditionally smoked foods only (upper use levels), these range from 1.4 to 2.3 mg/kg bw/day. Based on the data above, if the Primary Product AM 01 is present at the upper use levels provided by the applicant for the 18 food categories, the margins of safety for the intake estimat

32、es, as compared with the NOAEL of 250 mg/kg bw/day derived from the 90-day toxicity study in rats, amount to 104 and 114, respectively. When assuming the use of Primary Product AM 01 in traditionally smoked products only, the margins of safety would amount to 109 and 179, respectively for the intake

33、 estimates based on the upper use levels. However, given i) the fact that these margins of safety are based on a 90-day toxicity study, ii) the absence of data on reproduction and developmental toxicity and iii) the absence of long term studies, it is concluded that the uses and use levels of Primar

34、y Product AM 01 would require a larger margin of safety. Despite the increase in the margin of safety compared with the previous opinion, the Panel concluded that the proposed use of the Primary Product at the uses and use levels specified is of safety concern. To decide whether despite the low marg

35、ins of safety the use of Primary Product AM01 might be approved for traditionally smoked products, at use levels specified, to replace smoking, is outside the remit of the Panel. The Panel did not anticipate that smoke flavourings would be used in food specifically designed for infants (0-12 months)

36、 and young children (12-36 months). Therefore the safety of use of Primary Product AM 01 in such products was not assessed. Smoke flavouring Primary Product AM 01 - 2012 Update 5 EFSA Journal 2012;10(2):2580 TABLE OF CONTENTS Abstract . 1Key words . 2Summary . 3Table of contents . 5Background as pro

37、vided by the European Commission . 6Terms of reference as provided by the European Commission . 6Assessment . 71.Introduction . 71.1.Summary of the previous opinion on the safety of the smoke flavouring Primary Product AM 01 (EFSA, 2010) . 72.Technical data . 92.1.Identity of the Primary Product . 9

38、2.2.Chemical description of the Primary Product . 92.3.Identification and quantification of Primary Product constituents . 102.3.2Content of Polycyclic Aromatic Hydrocarbons (PAHs) . 113.Proposed use levels . 124.Dietary exposure assessment . 125.Toxicology . 135.1.Identity of the test material . 13

39、5.2.Genotoxicity . 136.Discussion . 14CONCLUSIONS AND RECOMMENDATIONS . 15DOCUMENTATION PROVIDED TO EFSA. 16Glossary / Abbreviations . 18Smoke flavouring Primary Product AM 01 - 2012 Update 6 EFSA Journal 2012;10(2):2580 BACKGROUND AS PROVIDED BY THE EUROPEAN COMMISSION The European Parliament and C

40、ouncil Regulation (EC) No 2065/20035 provides the basis for securing a high level of protection for human health and the interests of consumers in relation to smoke flavourings used or intended for use in or on foods. It furthermore lays down a procedure for the evaluation and authorisation of prima

41、ry smoke condensates and primary tar fractions and for the establishment of a list of primary smoke condensates and tar fractions to the exclusion of all others and their conditions of use. The European Food Safety Authority was asked to provide a scientific opinion on the safety of the product AM 0

42、1. In its opinion6 adopted on 26 November 2009 EFSA stated that a positive result was obtained in one of the in vitro genotoxicity tests, and another test was inconclusive. Furthermore, it was stated that an in vivo Comet assay should be considered of limited validity because of some shortcomings wi

43、th respect to the study design and reporting. Accordingly, the opinion concluded that the genotoxic potential in vivo of the Primary Product AM 01 can not be ruled out. Based on the conclusions drawn by EFSA the applicant has repeated the Comet assay study in order to address the shortcomings identi

44、fied in the opinion. TERMS OF REFERENCE AS PROVIDED BY THE EUROPEAN COMMISSION The European Commission requests the European Food Safety Authority to carry out a safety assessment of the smoke flavouring primary product AM 01 based on the repeated in vivo Comet assay submitted by the applicant in ac

45、cordance with Regulation (EC) No 2065/20035 of the European Parliament and the Council on smoke flavourings intended for use in or on foods. 5 Regulation (EC) No 2065/2003 of the European Parliament and of the Council of 10 November 2003 on smoke flavourings used or intended for use in or on foods.

46、OJ L 309, 26.11.2003, p. 1-8. 6 EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) . Scientific Opinion on Safety of smoke flavour - Primary Product AM 01 . EFSA Journal 2010; 8(1):1396. 22 pp. doi:10.2903/j.efsa.2009.1396. Available online: www.efsa.europa.eu/efsaj

47、ournal Smoke flavouring Primary Product AM 01 - 2012 Update 7 EFSA Journal 2012;10(2):2580 ASSESSMENT 1. Introduction The European Food Safety Authority (EFSA) has been asked by the European Commission (EC) to re-consider its safety assessment of the smoke flavouring Primary Product AM 01 based on e

48、valuation of a new Comet assay study submitted by the applicant in accordance with Regulation (EC) No 2065/20037 of the European Parliament and the Council on smoke flavourings intended for use in or on foods. In the opinion published by EFSA in 2010 on the safety of smoke flavour Primary Product AM

49、 01 (EFSA, 2010), the CEF Panel concluded that the genotoxic potential of the Primary Product AM 01 in vivo could not be ruled out, given the limitations in the dataset. In particular, one of the in vitro genotoxicity tests gave a positive result, whereas another test was regarded as inconclusive. T

50、he Panel deemed the then available in vivo Comet assay of limited validity because of some shortcomings with respect to the study design and reporting. The Panel calculated the margins of safety for this Primary Product on the basis of a no-observed-adverse-effect-level (NOAEL) of 250 mg/kg bw/day i