Safety evaluation of certain food additives - ipcs inchem

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HYDROXY- AND ALKOXY-SUBSTITUTED BENZYL DERIVATIVES (addendum) First draft prepared by Professor I.G. Sipes 1 and Ms E. Vavasour 2 1 College of Medicine, University of Arizona, Tucson, AZ, United States of America (USA) 2 Food Directorate, Health Canada, Ottawa, Ontario, Canada Evaluation .................................................................................. Introduction ......................................................................... Assessment of dietary exposure ......................................... Absorption, distribution, metabolism and elimination .......... Application of the Procedure for the Safety Evaluation of Flavouring Agents ........................................................... Consideration of combined intakes from use as flavouring agents ............................................................................. Consideration of secondary components ............................ Conclusion .......................................................................... Relevant background information .............................................. Explanation ......................................................................... Additional considerations on intake .................................... Biological data ..................................................................... Biochemical data: hydrolysis, absorption, distribution, metabolism and excretion ........................................ Toxicological studies ..................................................... Acute toxicity .......................................................... Short-term studies of toxicity .................................. Genotoxicity ............................................................ Reproductive/developmental toxicity studies ......... References ................................................................................ 1. EVALUATION 533 533 534 534 1.1 Introduction The Committee evaluated a group of six hydroxy- and alkoxy-substituted benzyl derivatives, including two vanillin acetals (Nos 1879 and 1882), one vanillin dimer (No. 1881), one alkoxy-hydroxylbenzaldehyde (No. 1878) and two alkoxybenzoyloxy derivatives (Nos 1880 and 1883). The evaluations were conducted according to the Procedure for the Safety Evaluation of Flavouring Agents (Figure 1, Introduction) (Annex 1, reference 131). None of these flavouring agents has previously been evaluated by the Committee. The Committee evaluated 46 other members of this group of flavouring agents at its fifty-seventh meeting (Annex 1, reference 154). In addition, ethyl vanillin - 533 - 540 540 541 541 541 541 542 542 542 543 543 543 544 545 548
534 HYDROXY- AND ALKOXY-SUBSTITUTED BENZYL DERIVATIVES (addendum) was evaluated at the eleventh meeting of the Committee (Annex 1, reference 14), and a conditional acceptable daily intake (ADI) 1 of 0–10 mg/kg body weight (bw) per day was assigned. At its thirty-fifth meeting (Annex 1, reference 88), the Committee converted the conditional ADI to a temporary ADI of 0–5 mg/kg bw per day. At its thirty-ninth meeting (Annex 1, reference 101), the Committee extended the temporary ADI of 0–5 mg/kg bw per day. At its forty-fourth meeting (Annex 1, reference 116), the Committee established an ADI of 0–3 mg/kg bw per day. Vanillin was evaluated at the eleventh meeting of the Committee and assigned an ADI of 0–10 mg/kg bw per day. Methyl salicylate was evaluated at the eleventh meeting of the Committee, and an ADI of 0–0.5 mg/kg bw per day was assigned. Piperonal was evaluated at the eleventh meeting of the Committee and assigned an ADI of 0–2.5 mg/kg bw per day. All other members of this group were evaluated by the Procedure and concluded to be of no safety concern based on current estimated levels of intake. Two of the six flavouring agents in this group are natural components of food (Nos 1878 and 1881). They have been detected in a variety of fruits, types of honey and alcoholic beverages, but quantitative data on natural occurrence were not available (Gatfield, 2006; Nijssen et al., 2007). 1.2 Assessment of dietary exposure The total annual production volume of the six hydroxy- and alkoxysubstituted benzyl derivatives is approximately 822 kg in Europe (European Flavour and Fragrance Association, 2005), 61 kg in the USA (Gavin et al., 2007) and 204 kg in Japan (Japan Flavor & Fragrance Materials Association, 2002). More than 99% of the annual production volume in Europe and Japan is accounted for by vanillin propylene glycol acetal (No. 1882). More than 85% of the annual production volume in the USA is accounted for by sodium 4-methoxybenzoyloxyacetate (No. 1880) and 4-methoxybenzoyloxyacetic acid (No. 1883). The daily per capita intake of each flavouring agent is reported in Table 1. Annual volumes of production of this group of flavouring agents are summarized in Table 2. 1.3 Absorption, distribution, metabolism and elimination The hydrolysis of aromatic acetals in simulated gastric juice and intestinal fluid supports the conclusion that the acetal functional group is hydrolysed before absorption in vivo. Both vanillin 3-(l-menthoxy)propane-1,2-diol acetal (No. 1879) and vanillin propylene glycol acetal (No. 1882) undergo hydrolysis under acidic conditions to form the corresponding alcohol and aldehyde, which will be rapidly metabolized and eliminated. The resulting hydroxy- and alkoxy-substituted derivatives are rapidly absorbed from the intestine, metabolized in the liver and excreted unchanged or as sulfate or glucuronide conjugates. Minor metabolic pathways include O-demethylation, reduction and/or decarboxylation. 1 “Conditional ADI”, which signifies an ADI with special considerations, is a term no longer used by the Joint FAO/WHO Expert Committee on Food Additives.
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WHO FOOD ADDITIVES SERIES: 60 Safet
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CONTENTS Preface ..................
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PREFACE The monographs contained in
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ASPARAGINASE FROM ASPERGILLUS NIGER
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16 CALCIUM LIGNOSULFONATE (40-65) 1
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18 CALCIUM LIGNOSULFONATE (40-65) ~
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20 CALCIUM LIGNOSULFONATE (40-65) A
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22 CALCIUM LIGNOSULFONATE (40-65) c
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24 CALCIUM LIGNOSULFONATE (40-65) T
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28 CALCIUM LIGNOSULFONATE (40-65) i
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ETHYL LAUROYL ARGINATE First draft
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ETHYL LAUROYL ARGINATE 41 and Devel
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ETHYL LAUROYL ARGINATE 43 lauroyl a
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ETHYL LAUROYL ARGINATE 45 arginine.
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ETHYL LAUROYL ARGINATE 47 resulting
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ETHYL LAUROYL ARGINATE 49 Table 4.
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ETHYL LAUROYL ARGINATE 51 weight ch
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ETHYL LAUROYL ARGINATE 53 stomach l
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ETHYL LAUROYL ARGINATE 55 fibrosis
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ETHYL LAUROYL ARGINATE 57 Table 5 (
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ETHYL LAUROYL ARGINATE 59 first 4 d
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ETHYL LAUROYL ARGINATE 61 The gener
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ETHYL LAUROYL ARGINATE 63 treatment
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ETHYL LAUROYL ARGINATE 65 gestation
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ETHYL LAUROYL ARGINATE 67 Body weig
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ETHYL LAUROYL ARGINATE 69 Table 6.
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ETHYL LAUROYL ARGINATE 77 About 99%
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ETHYL LAUROYL ARGINATE 79 concentra
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ETHYL LAUROYL ARGINATE 81 theoretic
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ETHYL LAUROYL ARGINATE 83 Huntingdo
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PAPRIKA EXTRACT First draft prepare
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PAPRIKA EXTRACT 87 of capsanthin ra
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PAPRIKA EXTRACT 89 biochemical para
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PAPRIKA EXTRACT 91 Table 1. Sales o
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PAPRIKA EXTRACT 93 Table 2. Estimat
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PAPRIKA EXTRACT 95 The European Sci
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PAPRIKA EXTRACT 97 The potential di
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PAPRIKA EXTRACT 99 Hornero-Mendez,
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PAPRIKA EXTRACT 101 Appendix 1. Res
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PAPRIKA EXTRACT 103 Appendix 1. (co
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PAPRIKA EXTRACT 105 Appendix 1. (co
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108 PHOSPHOLIPASE C EXPRESSED IN PI
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PHYTOSTEROLS, PHYTOSTANOLS AND THEI
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166 POLYDIMETHYLSILOXANE (addendum)
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STEVIOL GLYCOSIDES (addendum) First
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STEVIOL GLYCOSIDES (addendum) 185 r
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STEVIOL GLYCOSIDES (addendum) 187 c
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STEVIOL GLYCOSIDES (addendum) 189 a
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STEVIOL GLYCOSIDES (addendum) 191 N
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STEVIOL GLYCOSIDES (addendum) 193 2
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STEVIOL GLYCOSIDES (addendum) 195 T
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STEVIOL GLYCOSIDES (addendum) 197 a
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STEVIOL GLYCOSIDES (addendum) 199 r
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STEVIOL GLYCOSIDES (addendum) 201 l
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STEVIOL GLYCOSIDES (addendum) 203 g
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STEVIOL GLYCOSIDES (addendum) 209 t
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STEVIOL GLYCOSIDES (addendum) 211 t
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STEVIOL GLYCOSIDES (addendum) 213 s
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STEVIOL GLYCOSIDES (addendum) 215 C
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STEVIOL GLYCOSIDES (addendum) 217 L
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STEVIOL GLYCOSIDES (addendum) 219 W
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222 SULFITES: ASSESSMENT OF DIETARY
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SAFETY EVALUATIONS OF GROUPS OF REL
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264 INTRODUCTION Figure 1. Procedur
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DIETARY EXPOSURE ASSESSMENT OF FLAV
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292 ALIPHATIC BRANCHED-CHAIN SATURA
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332 ALIPHATIC LINEAR ,-UNSATURATED
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ALKOXY-SUBSTITUTED ALLYLBENZENES PR
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FURAN-SUBSTITUTED ALIPHATIC HYDROCA
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584 SUBSTANCES STRUCTURALLY RELATED
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ANNEXES
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598 ANNEX 1 10. Specifications for
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600 ANNEX 1 No. 54, 1974; WHO Techn
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602 ANNEX 1 70. Evaluation of certa
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604 ANNEX 1 108. Toxicological eval
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606 ANNEX 1 148. Residues of some v
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608 ANNEX 1 188. Safety evaluation
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610 ANNEX 2 ECG electrocardiogram E
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612 ANNEX 2 SI stimulation index SU
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614 ANNEX 3 Ms J. Baines, Food Stan
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ANNEX 4 ACCEPTABLE DAILY INTAKES, O
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ANNEX 4 619 Food additive Specifica
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ANNEX 4 621 3. FLAVOURING AGENTS 3.
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ANNEX 4 623 Flavouring agent No. Sp
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ANNEX 4 625 Flavouring agent JECFA
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ANNEX 4 627 Actual production volum
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ANNEX 4 629 Flavouring agent No. Sp
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ANNEX 5 SUMMARY OF THE SAFETY EVALU
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ANNEX 5 633 Secondary components Co
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