Safety evaluation of certain food additives - ipcs inchem

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STEVIOL GLYCOSIDES (addendum) 203 glucose tolerance and 96.1 ± 2.2 kg for subjects with diabetes. The study was compliant with ICH ethics guidelines and Good Clinical Practice guidelines. Participants received either rebaudioside A (97.4% rebaudioside A, remaining content other steviol glycosides) or placebo on two separate occasions, 1 week apart. Doses were randomly assigned, with individuals receiving 500 mg, 750 mg or 1000 mg rebaudioside A or placebo; all individuals received one dose of rebaudioside A and one placebo dose. Based on the mean body weight of the test subjects at the beginning of the study, the mean doses of rebaudioside A were 6.4, 9.5 and 12.7 mg/kg bw (2.1, 3.1 and 4.2 mg/kg bw expressed as steviol) for subjects with normal glucose tolerance and 5.2, 7.8 and 10.4 mg/kg bw (1.7, 2.6 and 3.4 mg/kg bw expressed as steviol) for those with type 2 diabetes mellitus. Blood pressure, diet, physical activity, vital signs and adverse events were recorded at each clinic visit. Blood samples were taken 30, 60, 90, 120, 150, 180, 210 and 240 min after the start of each dose period in all subjects and 270, 300, 330 and 360 min after the start of each dose period in those with normal glucose tolerance. Blood samples were analysed for glucose, insulin, C-peptide and glucagon. No statistically significant differences were found with any parameter at any dose in the test and control groups in either of the subgroups. The authors concluded that 1000 mg of rebaudioside A (equivalent to 329 mg steviol) did not have adverse effects on blood pressure or glucose homeostasis in healthy individuals or individuals with type 2 diabetes mellitus (Maki et al., 2007). A randomized double-blind placebo-controlled parallel group trial was carried out in 100 healthy subjects with normal blood pressure (21 males and 79 females aged 18–73 years). The study was compliant with ICH ethics guidelines. One group received 1000 mg rebaudioside A/day (97.4% purity, equivalent to 4.6 mg/kg bw per day expressed as steviol, based on the mean body weight of the test subjects), and the other group received a placebo. All subjects consumed four capsules daily, two with breakfast and two with the evening meal, for 4 weeks. Vital signs and adverse events were recorded at each clinic visit, along with changes in the laboratory assessments. Blood pressure was recorded at screening and weekly during dosing, and assessments were taken when seated, supine and standing. Twenty-four-hour ambulatory measurements were also taken in weeks 0 and 4. Two individuals in the placebo group withdrew from the study during dosing, but their reasons were unrelated to the treatment. Sixteen subjects receiving the test compound experienced one or more adverse events, compared with 18 in the placebo group. Only one event in the placebo group was classified as a serious adverse event, and one event in each group was considered to be severe in intensity. These events included back pain, headache, rhinitis and upper respiratory tract infection. All events in the test compound group were considered to be unrelated or unlikely to be related to the treatment, and one event in the placebo group (pruritis) was considered to be possibly related to the placebo used. There was no evidence of any adverse effects of treatment from the haematology, biochemistry or urinalysis. At week 0, there were no significant differences between groups in the changes from pre-meal to post-meal values in seated, supine or standing blood pressures (systolic, diastolic or mean arterial pressure) or heart rate. At week 4, there were small post-meal increases in some of the blood pressure parameters in the rebaudioside A group, compared with small decreases in the
204 STEVIOL GLYCOSIDES (addendum) placebo group. The overall treatment effect (change from week 0) was statistically significantly different from placebo for supine and standing diastolic blood pressure and mean arterial pressure, but this was not considered to be clinically meaningful (Wheeler, 2007b; Maki et al., 2008a). An additional pre-specified analysis to address the questions raised by the Committee at its sixty-third meeting focused on the subgroup of 20 control and 28 test subjects (dose adjusted for mean body weight of subgroup = 4.7 mg/kg bw per day expressed as steviol) with baseline systolic blood pressure below the sexspecific medians (baseline
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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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254 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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ALKOXY-SUBSTITUTED ALLYLBENZENES 35
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FURAN-SUBSTITUTED ALIPHATIC HYDROCA
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HYDROXY- AND ALKOXY-SUBSTITUTED BEN
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MISCELLANEOUS NITROGEN-CONTAINING S
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580 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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