s are being accepted for the 3nd Annual Shanghai Symposium on Chemical and Pharmaceutical Structure Analysis (CPSA Shanghai 2012). Please visit the CPSA Shanghai website at www.cpsa-shanghai. com for submission information. • Abstracts must be received by March 31, 2012 • Maximum length is 350 words A sample abstract is available at www.cpsa-shanghai.com as a guide for format. Please visit the conference website for more information! CPSA Shanghai Correspondence In the USA Dr. Mike Lee Management & Correspondence Milestone Development Services Attn: CPSA Shanghai P.O. Box 178 Newtown, PA 18940-0178 Email: info@milestonedevelopment.com Fax: +1 267-757-0463 Ms. Carla Marshall-Waggett Marketing & Communications New Objective, Inc. 2 Constitution Way Woburn, MA 01801 USA Email: carla.marshall-waggett@newobjective.com SHANGHAI 2012 In Shanghai Mr. Frank Fung Event Services Manager MICE Partners Consulting Co., Ltd. Room 602, Building 22 No. 1177 Wanzhen Road Shanghai 201824 E-mail: frank.fung@mice-partners.com Tel: +86-21-69189215/52179515 Fax: +86-21-69189215 Mobile: +86-13817660578 CPSA is User Friendly! CPSA attracts sponsors, thought leaders, and participants who are dedicated to the spirit of cooperation to achieve common goals. Imagination needed. CPSA Shanghai Where Technology and Solutions Meet Where East Meets West

(Danish EPA report on the environmental and health risks posed by heavy metals in jewellery) The SCHER adopted this opinion by written procedure on 22 February 2010 2 About the Scientific Committees Three independent non-food Scientific Committees provide the Commission with the scientific advice it needs when preparing policy and proposals relating to consumer safety, public health and the environment. The Committees also draw the Commission's attention to the new or emerging problems which may pose an actual or potential threat. SCHER Opinions on risks related to pollutants in the environmental media and other biological and physical factors or changing physical conditions which may have a negative impact on health and the environment, for example in relation to air quality, waters, waste and soils, as well as on life cycle environmental assessment. It shall also address health and safety issues related to the toxicity and eco-toxicity of biocides. It may also address questions relating to examination of the toxicity and eco-toxicity of chemical, biochemical and biological compounds whose use may have harmful consequences for human health and the environment. In addition, the Committee will address questions relating to methodological aspect of the assessment of health and environmental risks of chemicals, including mixtures of chemicals, as necessary for providing sound and consistent advice in its own areas of competence as well as in order to contribute to the relevant issues in close cooperation with other European agencies. The opinions of the Scientific Committees present the views of the independent scientists who are members of the committees. They do not necessarily reflect the views of the European Commission. The opinions are published by the European Commission in their original language only. ACKNOWLEDGMENTS Members of the working group are acknowledged for their valuable contribution to this opinion. The members of the working group are: All Declarations of working group members are available at the following webpage:

The Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (the Panel) is asked to advise the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Panel is requested to consider the Joint FAO/WHO Expert Committee on Food Additives (the JECFA) evaluations of flavouring substances assessed since 2000, and to decide whether no further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. These flavouring substances are listed in the Register, which was adopted by Commission Decision 1999/217 EC and its consecutive amendments.The present consideration concerns 22 pyridine, pyrrole and quinoline derivatives evaluated by the JECFA (63rd meeting) and will be considered in relation to the European Food Safety Authority (EFSA) evaluation of pyridine, pyrrole, indole and quinoline derivatives evaluated in the Flavouring Group Evaluation 24, Revision 1 (FGE.24Rev1).The Panel concluded that the 22 substances in the JECFA flavouring group of pyridine, pyrrole and quinoline derivatives are structurally related to the group of pyridine, pyrrole, indole and quinoline derivatives evaluated by EFSA in FGE.24Rev1.The Panel agrees with the application of the Procedure as performed by the JECFA for five of the 22 substances: methyl nicotinate [FL-no: 14.071], indole [FL-no: 14.007] and 3-methylindole [FLno: 14.004] were evaluated on the A-side of the Procedure as they were anticipated to be metabolised to innocuous products. 1-Furfurylpyrrole [FL-no: 13.134] and 2-pyridine methanethiol [FL-no: 14.030] were the only two substances evaluated through the B-side of the Procedure as the substances were not anticipated to be metabolised to innocuous products by the JECFA.The Panel concluded, in line with the conclusions for 2-methylquinoline, 4-methylquinoline and 4-butylquinoline [FL-no: 14.138, 14.002 and 14.094] in FGE. 24Rev1, that 6-methylquinoline [FL-no: 14.042] should not be evaluated through the Procedure due to concern with respect to genotoxicity in vitro.For the remaining 16 substances the Panel, in contrast to the JECFA, did not anticipate that they will be metabolised to innocuous products and accordingly concluded that they should be evaluated along the B-side.For pyrrole and the five pyrrole derivatives and for isoquinoline [FL-no: 13.134, 14.001, 14.041, 14.045, 14.046, 14.047 and 14.068] No Observed Adverse Effect Levels (NOAELs) could not be derived as such or for structurally related substances. Accordingly, additional toxicological data are required for these seven substances. For 10 substances [FL-no: 14.038, 14.039, 14.058, 14.059, 14.060, 14.061, 14.065, 14.066, 14.072 and 14.164] NOAELs could be derived to provide adequate margins of safety at the estimated level of intakes as flavouring substance.For four substances [FL-no: 14.045, 14.058, 14.059 and 14.164] the JECFA evaluation is based on Maximised Survey-derived Daily Intake (MSDI) derived from production figures only from the USA. EU production figures are needed in order to finalise the evaluation of these substances.For all 21 substances evaluated through the Procedure use levels are needed to calculate the modified Theoretical Added Maximum Daily Intake (mTAMDI) in order to identify those flavouring substances that need more refined exposure assessment and to finalise the evaluation.In order to determine whether the conclusion for the 22 JECFA evaluated substances can be applied to the materials of commerce, it is necessary to consider the available specifications:Adequate specifications including complete purity criteria and identity tests are available for 16 of the 22 JECFA evaluated substances. For six substances [FL-no: 13.134, 14.007, 14.030, 14.038, 14.045, and 14.046] data on solubility in water is missing.Thus, for 10 substances [FL-no: 13.134, 14.001, 14.041, 14.045, 14.046, 14.047, 14.058, 14.059, 14.068 and 14.164] the Panel has reservations (no European production volumes available, preventing them from being evaluated using the Procedure and/or additional toxicological data are required). For one substance, 6-methylquinoline [FL-no: 14.042], the Panel concluded that the Procedure should not be applied until adequate genotoxicity data become available. For the remaining 11 of the 22 JECFA evaluated pyridine, pyrrole and quinoline derivatives [FL-no: 14.004, 14.007, 14.030, 14.038, 14.039, 14.060, 14.061, 14.065, 14.066, 14.071 and 14.072] the Panel agrees with the JECFA conclusion "no safety concern at estimated levels of intake as flavouring substances" based on the MSDI approach.

The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (the Panel) is asked to advise the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Scientific Panel is asked to evaluate three flavouring substances in the Flavouring Group Evaluation 04 (FGE. 04), using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. These three flavouring substances belong to chemical group 2, Annex I of the Commission Regulation (EC) No 1565/2000.FGE. 04 deals with one branched-chain aliphatic aldehyde, one branched-chain aliphatic acid and one ester of a branched-chain alcohol.All three flavouring substances possess a chiral centre. The stereoisomeric composition has not been specified for any of the substances. Developmental and metabolism studies for 2-ethylhexanoic acid have demonstrated different biological activities for the two enantiomers of the substance.All the three flavouring substances belong to structural class II according to the decision tree approach presented by Cramer et. al. (1978). All the three substances have been reported to occur naturally in a wide range of food items.In its evaluation, the Panel as a default used the Maximised Survey-derived Daily Intake (MSDI) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Panel examined the information provided by the European Flavour Industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate the intake by regular consumers of products flavoured at the use level reported by the Industry, especially in those cases where the annual production values were reported to be small. In consequence, the Panel had reservations about the data on use and use levels provided and the intake estimates obtained by the MSDI approach.In the absence of more precise information that would enable the Panel to make a more realistic estimate of the intakes of the flavouring substances, the Panel has decided also to perform an estimate of the daily intakes per person using a modified Theoretical Added Maximum Daily Intake (mTAMDI) approach based on the normal use levels reported by Industry. In those cases where the mTAMDI approach indicated that the intake of a flavouring substance might exceed its corresponding threshold of concern, the Panel decided not to carry out a formal safety assessment using the Procedure. In these cases the Panel requires more precise data on use and use levels.According to the default MSDI approach, the three flavouring substances in this group have estimated European daily per capita intakes from use as flavouring substances ranging from 0.0012 to 0.24 microgram, which are below the threshold of concern value for a structural class II substance of 540 microgram/person/day.The available data on genotoxicity of the three flavouring substances in this group do not preclude their evaluation through the Procedure.From the metabolism data of the three flavouring substances and the structurally related substance it is not possible to conclude that the metabolites are innocuous.The toxicity of the flavouring substances in the present group as well as the structurally related substance has been well studied. A No Observed Adverse Effect Level (NOAEL) of 50 mg/kg body weight (bw) per day has been established based on a valid carcinogenicity study in rats. Also in rats, a valid developmental study provided a NOAEL of 100 mg/kg bw/day.It is considered that on the basis of the default MSDI approach these three flavouring substances would not give rise to safety concerns at levels of intake arising from their use as flavouring substances.When the estimated intakes were based on the mTAMDI approach they ranged from 1600 to 3900 microgram/person/day for the three flavouring substances from structural class II, which are above the threshold of concern for structural class II of 540 microgram/person/day.Thus, for the three substances allocated to structural class II, the intakes, estimated on the basis of the mTAMDI approach, exceed the relevant threshold for the structural class. Therefore, more reliable exposure data are required. On the basis of such additional data, these flavouring substances should be reconsidered using the Procedure. Subsequently, additional data might become necessary.In order to determine whether this evaluation could be applied to the materials of commerce, it is necessary to consider the available specifications:Specifications including complete purity criteria and identity tests for the materials of commerce have been provided for the three flavouring substances. Information on stereoisomerism is missing for all three substances. Thus, the evaluation of the three substances [FL-no: 05.147, 08.078 and 09.381], cannot be finalised pending further information on specifications.

The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (the Panel) is asked to advise the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Scientific Panel is asked to evaluate 58 flavouring substances in the Flavouring Group Evaluation 10, Revision 1 (FGE.10Rev1), using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. These 58 flavouring substances belong to chemical groups 9, 13 and 30, Annex I of the Commission Regulation (EC) No 1565/2000.The 58 flavouring substances are alcohols, aldehydes, acetals, carboxylic acids and esters containing additional oxygenated functional groups and lactones.Thirty-five of the 58 flavouring substances possess one or more chiral centres and six can exist as geometrical isomers due to the presence and the position of a double bond. For eight of these substances [FL-no: 06.088, 06.095, 06.135, 09.565, 09.916, 10.038, 10.040 and 10.168] the stereoisomeric composition/composition of mixture has not been specified.Fifty-one of the flavouring substances belong to structural class I, six of the substances belong to structural class II and one substance belongs to structural class III according to the decision tree approach presented by Cramer et al. (1978).Forty-eight of the flavouring substances in the present group have been reported to occur naturally in a wide range of food items.In its evaluation, the Panel as a default used the Maximised Survey-derived Daily Intake (MSDI) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Panel examined the information provided by the European Flavour Industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate the intake by regular consumers of products flavoured at the use level reported by the Industry, especially in those cases where the annual production values were reported to be small. In consequence, the Panel had reservations about the data on use and use levels provided and the intake estimates obtained by the MSDI approach.In the absence of more precise information that would enable the Panel to make a more realistic estimate of the intakes of the flavouring substances, the Panel has decided also to perform an estimate of the daily intakes per person using a modified Theoretical Added Maximum Daily Intake (mTAMDI) approach based on the normal use levels reported by the Industry. In those cases where the mTAMDI approach indicated that the intake of a flavouring substance might exceed its corresponding threshold of concern, the Panel decided not to carry out a formal safety assessment using the Procedure. In these cases the Panel requires more precise data on use and use levels.According to the default MSDI approach, the 58 flavouring substances in this group to which the Procedure has been applied have intakes in Europe from 0.0012 to 12 microgram/capita/day, which are below the thresholds of concern value for structural class I, II and III substances of 1800, 540 and 90 microgram/person/day, respectively.The combined estimated daily per capita intake as flavourings of the 51 candidate substances assigned to structural class I is 42 microgram, which does not exceed the threshold of concern for a substance belonging to structural class I of 1800 microgram/person/day. Likewise, the combined estimated daily per capita intake as flavouring of the six candidate substances assigned to structural class II is 1.2 microgram, which does not exceed the threshold of concern for a substance belonging to structural class II of 540 microgram/person/day.On the basis of the data available it is concluded that there is no indication that the flavouring substances in the present Flavouring Group Evaluation possess genotoxic potential. However, the Panel reconsidered the fact that 1-hydroxypropan-2-one [FL-no: 07.169] is an endogenous metabolite of acetone. Acetone is endogenously formed from the degradation of body fat/fatty acids and occurs in the blood of healthy humans not exposed to external sources of acetone in amounts of approximately 4-12 mg/person corresponding to 0.7 to 2 mg/l blood. Under these conditions, the majority of the acetone in blood would be metabolised to 1-hydroxypropan-2-one, which is rapidly further metabolised to endogenous compounds (methylglyoxal, pyruvate and glucose) in the methylglyoxal pathway. The estimated exposure of 0.22 microgram/capita/day is considerably lower than that resulting from the metabolism of acetone and would not significantly add to the internal exposure to 1-hydroxypropan-2-one in the body and would not perturb the normal catabolism of the compound to innocuous endogenous products. The Panel therefore decided that further genotoxicity data are not required and that the substance could be taken through the Procedure.It can be anticipated that, at the estimated levels of intake as flavouring substances, 55 of the alcohols, aldehydes, acetals, carboxylic acids and esters with an additional oxygenated functional group and aliphatic lactones included in the present FGE are generally hydrolysed and completely metabolised to innocuous products, many of which are endogenous in humans. For three of the flavouring substances it cannot be concluded that they are metabolised to innocuous products. Adequate margins of safety could be established for these three substances in step B4 of the Procedure.It was noted that where toxicity data were available they were consistent with the conclusions in the present Flavouring Group Evaluation using the Procedure.It was considered that on the basis of the default MSDI approach the 58 flavouring substances, to which the Procedure have been applied, would not give rise to safety concerns at the estimated levels of intake arising from their use as flavouring substances.The mTAMDI for the 51 flavouring substances in structural class I range from 1600 to 5100 microgram/person/day. For 49 of these substances the mTAMDI is above the threshold of concern of 1800 microgram/person/day. The mTAMDI of the five substances assigned to structural class II, and for which use levels information is available, range from 3800 to 3900 microgram/person/day, which is above the threshold of concern of 540 microgram/person/day. For the one substance from structural class III the mTAMDI is 4100, which is above the threshold of 90 microgram/person/day.Thus, for 55 flavouring substances further information is required. This would include more reliable intake data and then, if required, additional toxicological data. For one substance [FL-no: 06.135] no use levels have been provided for the food categories as listed in Commission Regulation (EC) No 1565/2000. Two of the flavouring substances, which have mTAMDI intake estimates below the threshold of concern for their structural class, are also expected to be metabolised to innocuous products.In order to determine whether this evaluation could be applied to the materials of commerce, it is necessary to consider the available specifications:Specifications including complete purity criteria and identity tests for the materials of commerce have been provided for 50 flavouring substances. For eight substances [FL-no: 06.088, 06.095, 06.135, 09.565, 09.916, 10.038, 10.040 and 10.168] information on composition of mixture and/or stereoisomerism is missing. For two substances [FL-no: 06.088 and 06.095] identity tests are missing. Thus, the final evaluation of the materials of commerce cannot be performed for these eight substances pending further information.For the remaining 50 flavouring substances [FL-no: 02.132, 02.198, 02.242, 05.149, 06.090, 06.097, 06.102, 07.169, 08.053, 08.082, 08.090, 08.103, 09.333, 09.345 -09.354, 09.360, 09.502, 09.558, 09.580, 09.590, 09.601, 09.626, 09.629, 09.633, 09.634, 09.644, 09.683, 09.815, 09.824, 09.832, 09.833, 09.862, 09.874, 10.039, 10.045, 10.047 - 10.049, 10.052, 10.055, 10.058 and 10.068] the Panel concluded that they would present no safety concern at their estimated levels of intake based on the MSDI approach.

The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (the Panel) is asked to advise the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Panel is asked to evaluate two flavouring substances in the Flavouring Group Evaluation 49 (FGE. 49), using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. These two flavouring substances belong to chemical group 30, Annex I of the Commission Regulation (EC) No 1565/2000.The two flavouring substances, caffeine [FL-no: 16.016] and theobromine [FL-no: 16.032], cannot be evaluated using the Procedure as information on production volumes in order to calculate an Maximised Survey-Derived Daily Intake (MSDI) has not been submitted. Furthermore, data on normal and maximum use levels are also lacking. The Panel is also aware that further toxicological data have been published on caffeine since the review by the SCF in 2003. These will also need to be taken into account.

The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (the Panel) is asked to advise the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular the Scientific Panel is requested to consider the Joint FAO/WHO Expert Committee on Food Additives (the JECFA) evaluations of flavouring substances assessed since 2000, and to decide whether no further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. These flavouring substances are listed in the Register, which was adopted by Commission Decision 1999/217/EC and its consecutive amendments.The present consideration concerns a group of six monocyclic secondary alcohols, ketones and related esters evaluated by the JECFA (63rd meeting) and will be considered in relation to the European Food Safety Authority (EFSA) evaluation of 15 monocyclic secondary alcohols, ketones and related esters in the Flavouring Group Evaluation 9, Revision 1 (FGE. 09Rev1)The Panel agrees with the application of the Procedure as performed by the JECFA for four out of the six monocyclic secondary alcohols, ketones and related esters [FL- no: 02.224, 02.246, 02.254 and 09.521]. However, for three substances [FL- no: 02.224, 02.246 and 02.254] no European production figures were available and consequently no European exposure estimates could be calculated. Accordingly, the safety in use could not be assessed using the Procedure for these three substances. For [FL- no: 07.110 and 07.111], the Panel concluded that in line with cyclotetradeca none [FL- no: 07.207] evaluated in FGE. 09Rev1, that the substances could not be anticipated to be metabolised to innocuous products and were therefore evaluated via the B- side of the EFSA Procedure. As no adequate No Observed Adverse Effects Level (NOAEL) were available for those substances additional data were required for [FL- no: 07.110 and 07.111].For three substances [FL- no: 02.224, 02.246 and 02.254] the JECFA evaluation is only based on MSDI values derived from production figures from the USA. EU production figures are needed in order to finalise the evaluation of these substances.For all six substances evaluated through the Procedure use levels are needed to calculate the mTAMDIs in order to identify those flavouring substances that need more refined exposure assessments and to finalise the evaluation.In order to determine whether the conclusion for the six JECFA evaluated substances can be applied to the materials of commerce, it is necessary to consider the available specifications:Specfications are available for the five materials of commerce. Information on stereoisomerism is lacking for [FL- no: 09.521].Thus, for the six JECFA evaluated monocyclic secondary alcohols, ketones and related esters the Panel has reservations. For [FL- no: 02.224, 02.246 and 02.254] there is no European production volume available, preventing evaluation of the substances through the Procedure. For [FL- no: 09.521] information on stereoisomerism is missing. For [FL- no: 07.110 and 07.111] additional toxicity data are required.

The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food is asked to advise the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Scientific Panel is asked to evaluate one flavouring substance, vinylbenzene [FL-no: 01.015], in the Flavouring Group Evaluation FGE. 29, using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. This flavouring substance belongs to chemical group 31, Annex I of the Commission Regulation EC) No 1565/2000.Vinylbenzene [FL-no: 01.015] is currently being assessed under the EC programme on risk assessment of existing substances Council Regulation EEC) No 793/93). A draft Risk Assessment Report RAR) on the substance draft dated November 2007) is currently being considered by the Scientific Committee on Health and Environmental Risks SCHER)*. The evaluation of vinylbenzene as a flavouring substance is therefore postponed pending the publication of the final RAR on vinylbenzene.

The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (the Panel) is asked to advise the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Panel is requested to consider the Joint FAO/WHO Expert Committee on Food Additives (the JECFA) evaluations of flavouring substances assessed since 2000, and to decide whether no further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. These flavouring substances are listed in the Register, which was adopted by Commission Decision 1999/217/EC and its consecutive amendments.The present consideration deals with 24 aliphatic, alicyclic and aromatic hydrocarbons evaluated by the JECFA at their 63rd meeting.The Panel concluded that the 24 substances in the JECFA flavouring are structurally related to the group of 32 aliphatic and aromatic hydrocarbons evaluated by the European Food Safety Authority (EFSA) in the Flavouring Group Evaluation 25 (FGE.25).The Panel agrees with the application of the Procedure as performed by the JECFA for eight of the 24 substances considered in this FGE [FL-no: 01.002, 01.005, 01.006, 01.016, 01.019, 01.020, 01.045 and 01.077].Two substances [FL-no: 01.011 and 01.013] are genotoxic in vitro and there are unresolved problems with potential carcinogenicity and therefore the Panel concluded that they cannot be taken through the Procedure.For the following 14 substances [FL-no: 01.003, 01.004, 01.007, 01.008, 01.009, 01.010, 01.014, 01.017, 01.018, 01.024, 01.026, 01.029, 01.040 and 01.061] it cannot be concluded that they are metabolised to innocuous substances and therefore their evaluation must proceed along the B-side of the Procedure. For one substance, myrcene [FL-no: 01.008] in subgroup II, acyclic alkenes, the intake based on the Maximised Survey-derived Daily Intake (MSDI) exceeds the threshold for the structural class (7100 mu g/capita/day) and accordingly additional data must be available for the substance or a structurally related substance. For another substance, 1-isopropenyl-4-methylbenzene [FL-no: 01.010] from subgroup IVe: alkyl substituted benzene hydrocarbons, a No Observed Adverse Effect Level (NOAEL) was available giving an adequate margin of safety compared to the estimated level of intake. For 13 substances no applicable NOAEL is available for the substance itself or on a structurally related compound and therefore further data are required.For three substances [FL-no: 01.024, 01.029 and 01.040] the JECFA evaluation is only based on Maximised Survey-derived Daily Intake (MSDI) derived from production figures from the USA. EU production figures are needed in order to finalise the evaluation of these substances.For all substances evaluated through the Procedure use levels are needed to calculate the modified Theoretical Added Maximum Daily Intake (mTAMDI) in order to identify those flavouring substances that need more refined exposure assessment and to finalise the evaluation.In order to determine whether the conclusion for the 24 JECFA evaluated substances can be applied to the materials of commerce, it is necessary to consider the available specifications:Adequate specifications including complete purity criteria and identity tests are available for 10 of the 24 JECFA evaluated substances. For two substances [FL-no: 01.018 and 01.061] information on the isomeric composition is lacking and for 14 substances [FL-no: 01.004, 01.007, 01.008, 01.009, 01.017, 01.018, 01.019, 01.020, 01.024, 01.026, 01.029, 01.040, 01.045 and 01.061] further information on the composition of the mixture is requested.Thus, for 14 substances [FL-no: 01.004, 01.007, 01.008, 01.009, 01.017, 01.018, 01.019, 01.020, 01.024, 01.026, 01.029, 01.040, 01.045 and 01.061] the Panel has reservations (no European production volumes available, preventing them from being evaluated using the Procedure, and/or missing information on stereoisomerism/composition of mixture). For two of the 24 JECFA evaluated substances the Procedure could not be applied [FL-no: 01.011 and 01.013] based on concern with respect to genotoxicity and carcinogenicity. For 13 of the 24 JECFA evaluated aliphatic, alicyclic and aromatic hydrocarbons [FL-no: 01.003, 01.004, 01.007, 01.008, 01.009, 01.014, 01.017, 01.018, 01.024, 01.026, 01.029, 01.040 and 01.061] additional toxicity data are requested. For the remaining six substances [FL- no: 01.002, 01.005, 01.006, 01.010, 01.016 and 01.077] the Panel agrees with the JECFA conclusion "no safety concern at estimated levels of intake as flavouring substances" based on the MSDI approach.

The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (the Panel) is asked to advise the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Panel is asked to evaluate 13 flavouring substances in the Flavouring Group Evaluation 14, Revision 1 (FGE. 14Rev1), using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. These 13 flavouring substances belong to chemical group 15 and 22, Annex I of the Commission Regulation (EC) No 1565/2000.The present Flavouring Group Evaluation (FGE) deals with eight phenethyl alcohol derivatives (alcohol, esters and acetals), one phenylacetic acid, one phenethyl aldehyde derivative and three phenylacetals.Three of the 13 flavouring substances possess a chiral centre and two flavouring substances possess three chiral centres. For two of the substances the stereoisomeric composition has not been specified. The substances have been evaluated irrespective of their chirality. One of the substances can exist as geometrical isomers due to the presence and position of the double bond, but the geometrical isomeric form is given by the name.Twelve of the 13 flavouring substances are classified into structural class I and one flavouring substance is classified into structural class II according to the decision tree approach presented by Cramer et al. (1978).Ten of the substances have been reported to occur naturally in a wide range of food items.In its evaluation, the Panel as a default used the Maximised Survey-derived Daily Intake (MSDI) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Panel examined the information provided by the European Flavour Industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate the intake by regular consumers of products flavoured at the use level reported by the industry, especially in those cases where the annual production values were reported to be small. In consequence, the Panel had reservations about the data on use and use levels provided and the intake estimates obtained by the MSDI approach.In the absence of more precise information that would enable the Panel to make a more realistic estimate of the intakes of the flavouring substances, the Panel has decided also to perform an estimate of the daily intakes per person using a modified Theoretical Added Maximum Daily Intake (mTAMDI) approach based on the normal use levels reported by Industry. In those cases where the mTAMDI approach indicated that the intake of a flavouring substance might exceed its corresponding threshold of concern, the Panel decided not to carry out a formal safety assessment using the Procedure. In these cases the Panel requires more precise data on use and use levels.According to the default MSDI approach, the 13 flavouring substances have intakes in Europe from 0.0012 to 33 microgram/capita/day, which are well below the threshold of concern for structural class I of 1800 microgram/person/day and for structural class II of 540 microgram/person/day.All 13 flavouring substances are expected to be metabolised to innocuous substances.Overall, the genotoxicity data available are not sufficient to evaluate the genotoxicity adequately. However, the data available on candidate and supporting substances do not give rise to concern with respect to genotoxicity of the 13 candidate substances in this FGE. Consideration was given to ethanol and acetaldehyde, two potential hydrolysis products of the acetals [FL-no: 06.078 and 06.080]. Because of the natural occurrence in food and the endogenous formation in humans of considerably larger amounts of these compounds, their formation from hydrolysis of the acetals was not considered to be of safety concern with respect to genotoxicity at their estimated levels of intakes, based on the MSDI approach.It was noted that where toxicity data were available they were consistent with the conclusions in the present FGE using the Procedure.It is considered that on the basis of the default MSDI approach these 13 substances would not give rise to safety concerns at levels of intake arising from their use as flavouring substances.When the estimated intakes were based on the mTAMDI approach they ranged from 1600 to 5700 microgram/person/day for the 12 flavouring substances from structural class I and for the candidate substance from structural class II the mTAMDI is 3900 microgram/person/day. Thus, the intakes were above the threshold of concern for structural class I of 1800 microgram/person/day and of 560 microgram/person/day for structural class II, except for one candidate substance [FL-no: 05.159] from class I. The one substance [FL-no: 05.159], which has an mTAMDI intake below the threshold of concern for structural class I, is also expected to be metabolised to innocuous products.Thus, the intakes, estimated on the basis of the mTAMDI, exceed the relevant threshold for the structural class to which the flavouring substance has been assigned for 12 of the 13 flavouring substances considered in this Opinion. Therefore, for these 12 substances [FL-no: 02.166, 06.078, 06.080, 08.108, 09.201, 09.620, 09.684, 09.685, 09.686, 09.756, 09.761 and 09.774] more reliable exposure data are required. On the basis of such additional data, these flavouring substances should be reconsidered along the steps of the Procedure. Following this procedure additional toxicological data might become necessary. In order to determine whether this evaluation of the 13 flavouring substances can be applied to the materials of commerce, it is necessary to consider the available specifications:Adequate specifications including complete purity criteria and identity tests for the materials of commerce have been provided for 12 of the 13 candidate substances. Identity test and information on chirality is missing for one substance [FL-no: 09.756]. Information on chirality is also missing for [FL-no: 08.108]. Thus, the final evaluation of the materials of commerce cannot be performed for two of the 13 substances [FL-no: 08.108 and 09.756], pending further information. The remaining 11 substances would present no safety concern at the levels of intake estimated on the basis of the MSDI approach.

SUMMARY The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (the Panel) is asked to advise the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular the Scientific Panel is requested to consider the Joint FAO/WHO Expert Committee on Food Additives (the JECFA) evaluations of flavouring substances assessed since 2000, and to decide whether any further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. These flavouring substances are listed in the Register, which was adopted by Commission Decision 1999/217/EC and its consecutive amendments. The present consideration concerns 16 miscellaneous nitrogen-containing substances evaluated by the JECFA (65 th meeting). The Panel concluded that no corresponding FGE is available. The Panel agrees with the application of the Procedure as performed by the JECFA for the 16 substances considered in this FGE. For three substances (FL-no: 14.014, 14.029 and 14.070) the JECFA evaluation is only based on Maximised Survey-derived Daily Intake MSDI values derived from production figures from the USA. EU production figures are needed in order to finalise the evaluation of these three substances. For four substances (FL-no: 12.025, 12.030, 13.039 and 13.115) evaluated through the JECFA Procedure intake data are available for the EU. For the remaining nine

The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (the Panel) is asked to advise the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular the Scientific Panel is requested to consider the Joint FAO/WHO Expert Committee on Food Additives (the JECFA) evaluations of flavouring substances assessed since 2000, and to decide whether no further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. These flavouring substances are listed in the Register, which was adopted by Commission Decision 1999/217/EC, and its consecutive amendments.The present consideration concerns a group of 15 bicyclic secondary alcohols, ketones and related esters evaluated by the JECFA (63rd meeting) and will be considered in relation to the European Food Safety Authority (EFSA) evaluation of four bicyclic secondary alcohols, ketones and related esters in the Flavouring Group Evaluation 47 (FGE.47).The Panel agrees with the application of the Procedure as performed by JECFA for the 15 bicyclic secondary alcohols, ketones and related esters. However, for two substances [FL-no: 09.153 and 09.319] the JECFA evaluation is only based on MSDI values derived from production figures from the USA. EU production figures are needed in order to finalise the evaluation of these substances.For all 15 substances evaluated through the Procedure use levels are needed to calculate the mTAMDIs in order to identify those flavouring substances that need more refined exposure assessments and to finalise the evaluation.In order to determine whether the conclusion for the 15 JECFA evaluated substances can be applied to the materials of commerce, it is necessary to consider the available specifications:Specifications are available for the 15 materials of commerce. Information on composition of mixture is lacking for eight substances [FL-no: 02.016, 02.038, 07.159, 09.017, 09.131, 09.153, 09.176 and 09.218].Thus, for nine of the 15 JECFA evaluated bicyclic secondary alcohols, ketones and related esters [FL-no: 02.016, 02.038, 07.159, 09.017, 09.131, 09.153, 09.176, 09.218 and 09.319] the Panel has reservations (no European production volumes available, preventing them from being evaluated using the Procedure, and/or information on the composition of mixture is lacking).For the remaining six of the 15 JECFA evaluated bicyclic secondary alcohols, ketones and related esters [FL-no: 02.059, 07.153, 09.082, 09.269, 09.456 and 09.457] the Panel agrees with the JECFA conclusion "no safety concern at estimated levels of intake as flavouring substances" based on the MSDI approach.

The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (the Panel) is asked to advise the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Scientific Panel is asked to evaluate one flavouring substance in the Flavouring Group Evaluation 48 (FGE. 48), using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. This flavouring substance belongs to chemical group 33, Annex I of the Commission Regulation (EC) No 1565/2000.The present Flavouring Group Evaluation (FGE) deals with an amino substituted aromatic ketone, 2-aminoacetophenone [FL-no: 11.008].No geometrical or optical isomers exist for this flavouring substance. The flavouring substance has been assigned to structural class III.The flavouring substance has been reported to occur naturally in few food items.In its evaluation, the Panel, as a default, used the Maximised Survey-derived Daily Intake (MSDI) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Panel examined the information provided by the European Flavouring Industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate the intake by regular consumers of products flavoured at the use level reported by the Industry, especially in those cases where the annual production values were reported to be small. In consequence, the Panel had reservations about the data on use and use levels provided and the intake estimates obtained by the MSDI approach.In the absence of more precise information that would enable the Panel to make a more realistic estimate of the intakes of the flavouring substances, the Panel has decided also to perform an estimate of the daily intakes per person using a modified Theoretical Added Maximum Daily Intake (mTAMDI) approach based on the normal use levels reported by Industry. In those cases where the mTAMDI approach indicated that the intake of a flavouring substance might exceed its corresponding threshold of concern, the Panel decided not to carry out a formal safety assessment using the Procedure. In these cases the Panel requires more precise data on use and use levels.According to the default MSDI approach, the candidate substance has a daily per capita intake in Europe of 0.012 microgram, which is below the threshold of concern of 90 microgram/capita/day for a structural class III substance.The Panel considered that the candidate substance had a structural alert for genotoxicity despite the available negative genotoxicity tests on the candidate substance which are not considered to be of adequate quality to provide reassurance of a lack of genotoxic activity. Therefore, the Procedure could not be applied to the candidate substance, 2-aminoacetophenone [FL-no: 11.008] until adequate genotoxicity data become available. Furthermore, it cannot be anticipated that the candidate substance 2-aminoacetophenone [FL-no: 11.008] is metabolised to innocuous products.It was considered that on the basis of the default MSDI approach the substance would not give rise to safety concerns at the estimated levels of intake arising from its use as flavouring substance.When the estimated intake was based on the mTAMDI approach it was 1600 microgram/person/day for 2-aminoacetophenone, which is above the threshold of concern of 90 microgram/capita/day for a structural class III substance. Thus, the intake, estimated on the basis of the mTAMDI, exceed the relevant threshold for its structural class, to which the flavouring substance has been assigned. Therefore, for this substance more reliable exposure data are required. On the basis of such additional data, the flavouring substance should be reconsidered along the steps of the Procedure. Following this procedure additional toxicological data might become necessary.In order to determine whether this evaluation could be applied to the materials of commerce, it is necessary to consider the available specifications: Adequate specifications including complete purity criteria and identity tests for the material of commerce have been provided for the flavouring substance.Thus, in conclusion, for the flavouring substance, 2-aminoacetophenone [FL-no: 11.008] the Panel concluded that there was a possible genotoxic potential, and therefore the Procedure could not be applied to the candidate substance until adequate genotoxicity data become available.