Safety evaluation of certain mycotoxins in food - Food and

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Safety evaluation of certain mycotoxins in food - Food and

Transcript Of Safety evaluation of certain mycotoxins in food - Food and

WHO FOOD ADDITIVES SERIES 47

Safety evaluation of certain mycotoxins in food

FAQ FOOD AND NUTRITION
PAPER
74

WORLD HEALTH ORGANIZATION

FOOD AND
AGRICULTURE ORGANIZATION
OF THE UNITED NATIONS

IPCS
International Programme on Chemical Safety World Health Organization - Geneva

WHO FOOD.
ADDITIVES SERIES: 47

Safety evaluation of certain mycotoxins in food
Prepared by the Fifty-sixth meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECJFA)

FAO FOOD AND NUTRITION
PAPER 74

World Health Organization, Geneva, 2001
IPCS-International Programme on Chemical Safety

Food and Agriculture Organization of the United Nations
2001

This publication is a contribution to the International Programme on Chemical Safety.
The International Programme on Chemical Safety (IPCS), established in 1980, is a joint venture of the United Nations Environment Programme (UNEP), the International Labour Organisation (ILO), and the World Health Organization (WHO). The overall objectives of the IPCS are to establish tl1e scientific basis for .assessing the risk to human health and the environment from exposure to chemicals, through international peer-review processes, as a prerequisite for the promotion of chemical safety, and to provide technical assistance in strengthening national capacities for the sound management of chemicals.
The Inter-Organization Programme for the Sound Management of Chemicals (IOMC) was established in 1995 by UNEP, ILO, the Food and Agriculture Organization of the United Nations, WHO, the United Nations Industrial Development Organization, and the Organisation for Economic Co-operation and Development (Participating Organizations), following recommendations made by the 1992 United Nations Conference on Environment and Development to strengthen cooperation and increase coordination in the field of chemical safety. The purpose of the IOMC is to promote coordination of the policies and activities pursued by the Participating Organ·izations, jointly or separately, to achieve the sound management of chemicals in relation to human health and the environment.
Health & Environment International, Ltd, by agreement with WHO, performed independent literature searches on some of the substances on which data are summarized in this document in order to ensure that all relevant toxicological and related information was reviewed.
WHO ISBN 92 4 166047 3 FAO ISBN 92 5 104664 15

CONTENTS

Preface.........................................................................................................

v

Aflatoxin M1 ..................................................................... _............................. Fumonisins .. ................................................................................................

1 103

Ochratoxin A ... .... .. ......... ... .. ..... .. ... ... ... ..... ..... .......... .. .... ... ... .... ... ... .. .... .. ....... 281

Trichothecenes ... .................................................... ..................................... 417

Deoxynivalenol ....................................................................................... 419

T-2 and HT-2 .......................................................................................... 557

Annexes .........................................................-.............................................. 681 Annex 1 Reports and other documents resulting from previous meetings of the Joint FAO/WHO Expert Committee on Food Additives............................... 683 Annex 2 Abbreviations used in the monographs ... .. ..... .... .. ..... .. ... . 693 Annex 3 Participants in the fifty-sixth meeting of the Joint FAO/WHO Expert Committee on Food Additives ... ... ... ... .. .. ......... .... ..... ............ ... .. .. .. ....... .... 697

Corrigenda

701

PREFACE
The monographs contained in this volume were prepared at the fifty-sixth meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), which met at WHO Headquarters in Geneva, Switzerland, 6-15 February 2001. These monographs summarize the data on selected mycotoxins reviewed by the Committee.
The fifty-sixth report of JECFA will be published by the World Health Organization in the WHO Technical Report Series. Reports and other documents resulting from previous meetings of JECFA are listed in Annex 1. Abbreviations used in the monographs are listed in Annex 2. The participants in the meeting are listed in Annex 3 of the present publication.
JECFA serves as a scientific advisory body to FAO, WHO, their Member States, and the Codex Alimentarius Commission, primarily through the Codex Committee on Food Additives and Contaminants and the Codex Committee on Residues of Veterinary Drugs in Foods, regarding the safety of food additives, residues of veterinary drugs, naturally occurring toxicants, and contaminants in food. Committees accomplish this task by preparing reports of their meetings and publishing specifications or residue monographs and toxicological monographs on substances that they have considered.
The monographs contained in this volume are based on working papers that were prepared by working groups before the meeting. A special acknowledgement is given at the beginning of each monograph to those who prepared these working papers. The monographs were edited by E. Heseltine, Lajarthe, 24290 St Leonsur-Vezere, France.
The preparation and editing of the monographs included in this volume were made possible through the technical and financial contributions of the Participating Organizations of the International Programme on Chemical Safety (IPCS), which supports the activities of JECFA.
The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the organizations participating in the IPCS concerning the legal status of any country, territory, city, or area or its authorities, or concerning the delimitation of its frontiers or boundaries. The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by those organizations in preference to others of a similar nature that are not mentioned.
Any comments or new information on the biological or toxicological properties of the compounds evaluated in this publication should be addressed to: Joint WHO Secretary of the Joint FAO/WHO Expert Committee on Food Additives, International Programme on Chemical Safety, World Health Organization, Avenue Appia, 1211 Geneva 27, Switzerland.
-v -

AFLATOXIN M1

First draft prepared by

S.H. Henry1, T. Whitaker2, I. Rabbani2, J. Bowers2, D. Park2, W. Price2, F. X. Bosch3, J. Pennington4, P. Verger5, T. Yoshizawa6, H. van Egmonc/7,
M.A Jonker7, R. Coker8

1Food and Drug Administration, Washington DC, USA 2Agricultural Research Service, Department of Agriculture, Raleigh,
North Carolina, USA 3/nstitute Catalan d' Onco/ogia, L'Hospitalet de/ Llobregat, Barcelona, Spain;
4National Institutes of Health, Bethesda, Maryland, USA; 5/nstitut National de Recherche Agronome, Paris, France;
6 Kagawa University, Kagawa, Japan; 7National Institute of Public Health and Environmental Protection,
Bilthoven, The Netherlands; BNatural Resources Institute, University of Greenwich, Kent,
United Kingdom

Explanation ... ..... .. ... ............. ... .... .... .... .. ... .. .. .. .. .. ... ... .. .. .... .. ... .. .. .. ... .. .

2

Biological data ..................................................:..........................

3

Chemical structure .... ... .. ... ........ .... .. ..... .. ... ..... .. .. .... .... ..... ... ... .... ..

3

Biochemical aspects ................... .. ..... ... .... .. .. ..... ..... ......... .. ...

3

Biotransformation .... .. ... ... ... .... .... .. .. .... .. .. .. .. .. .. ..... .. .. .. ... ..

3

Effects of oltipraz and ethoxyquin ... .. .. ......... ... ..... ..........

6

Toxicological studies .... .. .. .. .. .... .... .. .... .. .. ... ... .. ... .. ...... ... .... ... ..

9

Acute toxicity .... ....... ..... .. .. .. .... .. ................................ ......

9

Long-term studies of toxicity and carcinogenicity...........

9

Genotoxicity ... ..... ... .. .. .... ... .. .. .. .. .. .. .... .. .. ... .. .. .. .. .. .. .. .. .. ...... .. ... 10

Special studies ... .. .. .. .. .. .. .. .. .... .. ..... ... ..... .. ... .. .. .......... .. ... .. .. .. .

11

Observations in domestic animals and veterinary toxicology ... ..

13

Observations in humans ................................. .. .... .. .. .... .. .. .. .... ....

15

Correlation studies ............... .. ..... .. .. .. .. .. .. .. ............................ 17

Case-control and cohort studies .. ......... .. .. .. .. .... ...... .............

17

Metabolic epidemiological studies .. .. .... .. .. ... .. ...... .. ....... .... .. ..

19

Intervention studies with vaccination against hepatitis B virus 21

Intervention studies with with oltipraz ................................... 22

Other studies .... ... .... .. ... .. .. .. ..... .. ..... .. .. .. .... .. .. .. .. .. .. .. .. ..... .. ... ..

23

Studies of P53 as a marker of intake of aflatoxin ...... ... .. .... ..

23

Analytical methods .......................................................:.................... 26

Screening tests ..... ...... .. .. ....... .. .... .. .. ..... ....... .. .. .. .. .. ......... .. .. ........ 26

Quantitative methods .......... .. ............... ... ..................... ............... 27

Analytical quality assurance........................................................

32

Conclusions .. ...... .. ...... .. .. .. ... .. ... .. ...... ......... .. .. .... .. ............ .. .. ... .... 33

Sampling protocols ... .... .. ...... .. ..... .. .. ....... ... .. .. .. .. .. ... .. ..... .. .............. .. .. 34

Effects of processing ... .. .. .. ... ... .. ... .. ... .... .... .... ... .. .. .... .. ....... ... ..... ....... . 34

Fate of aflatoxin M1 during processing of milk............................

35

Degradation of aflatoxin M1 in milk .............................................

35

Levels and patterns of contamination of food commodities .. .. .. .. ... ... 36

Results of surveys....................................................................... 36

Distribution curves ... .... .. ....... .. ........... .. ........... .. ............. .. .. ... ...... 38

Annual variation .... .... .. ... ... .. ............. ....... ... .. .. .. .. .. .... .... ...... ..... ....

38

-1-

2

AFLATOXIN M1

Food consumption and dietary intake estimates ............................... 39

National and regional assessments of intake ............... .. .. .. ...... ..

41

Estimates of intake of aflatoxin M1 from milk..............................

47

Limitations of intake estimates....................................................

51

Prevention and control ......................................................................

52

Carry-over from feed to cows' milk ..... ...... ... ........... .......... ... .. ... ..

52

Control and prevention of carry-over ..... .... .......... .. .. .. .... ...... .. .. ...

53

Dose-response relationship and estimation of carcinogenic risk ... ..

56

Contribution of biochemical data to assessment of risk .. .. ... .. .... . 56

General modelling issues............................................................

58

Potency estimates....................................................................... 60

Comments ........... .... .. ....... .. ... .. .... .. .. .. ..... .......... .. .. ..... ....... .. .. .... ....... 65

Evaluation .......................... ... .. ......... .. ... .... ..... .. .. .... ... .. .. ........... .. .. ... 68

References ................................... ..... ................... ............................ 69

Appendix A. Results of surveys.........................................................

81

Appendix B. Concentrations in milk ......... ...... .. .. ..... .. ... ... .. .. ..... .... .. .. ..

95

Appendix C. Concentrations·m milk by regional diet .. ... .. .. .... .. .. ........ 100

1.

EXPLANATION

The Expert Committee was requested by the Codex Committee on Food Additives and Contaminants at its Thirty-second Session (Codex Alimentarius, 2000) to 'examine exposure to aflatoxin M1 and to conduct a quantitative risk assessment' to compare the consequences of setting the maximum level in milk at 0.05 and 0.5 µg/kg.
Aflatoxins can be produced by three species of Aspergillus-A. f/avus, A. parasiticus, and the rare A. nomius-which contaminate plants and plant products. A. flavus produces only B aflatoxins, while the other two species produce both B and G aflatoxins. Aflatoxins M1 and M2 are the hydroxylated metabolites of aflatoxins 8 1 and B2 and can be found in milk or milk products obtained from livestock that have ingested contaminated feed. The main sources of aflatoxins in feeds are peanut meal, maize and cottonseed meal.
Aflatoxins were evaluated by the Committee at its thirty-first, forty-sixth, and forty-ninth meetings (Annex 1, references 77, 122, and 131 ). At its forty-ninth meeting, the Committee considered estimates of the carcinogenic potency of aflatoxins and the potential risks associated with their intake. At that meeting, the Committee reviewed a wide range of studies conducted in animals and humans that provided qualitative and quantitative information on the hepatocarcinogenicity of aflatoxins. The Committee evaluated the potency of these contaminants, linked those potencies to estimates of intake, and discussed the potential impact of hypothetical standards on sample populations and their overall risk. In its evaluation, the Committee stated
that the carcinogenic potency of aflatoxin M1 in sensitive species is about one order of magnitude less than that of aflatoxin B1. In particular, the Committee noted that the carcinogenic potency of aflatoxin 8 1is substantially higher in carriers of hepatitis B virus (about 0.3 cancers per year per 100 000 persons per ng/kg bw per day), as determined by the presence in serum of the hepatitis B virus surface antigen (HBsAg+ individuals), than in HBsAg- individuals (about 0.01 cancers per year per 100 000 persons per ng/ kg bw per day). Populations with both a high prevalence of HBsAg+ and a high aflatoxin intake might benefit from reductions in aflatoxin intake. The Committee also noted that vaccination against hepatitis B virus would reduce the
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