pesticide residues in food 2016: special session of the

Exhibit 18

Case 3:16-md-02741-VC Document 2419-19 Filed 01/03/19 of 7

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PRODUCTIONAND PROTECTION

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ISSN 2070-2515227Pesticide residues in food 2016 –

Joint FAO/WHO Meeting on Pesticide Residues

FAO

Pesticide residuesin food 2016

REPORT2016

Special Session of the Joint FAO/WHO Meeting on Pesticide Residues

I5693E/1/05.16

8Biotecnología agrícola para países en desarrollo

FAO

Biotecnología agrícolapara países en desarrollo Resultados de un foro electrónico

ESTUDIO FAOINVESTIGACIÓNY TECNOLOGIA

En esta publicación se presenta un informe sobre las primeras seis conferencias mediante correo electrónico organizadas por el Foro electrónico de la FAO sobre la biotecnología en la alimentación y la agricultura,

celebradas entre marzo de 2000 y mayo de 2001. Todas las conferencias contaron con un moderador, duraron aproximadamente dos meses y se centraron en la biotecnología agrícola en los países en desarrollo. Las cuatro primeras conferencias trataron de la idoneidad para los países en desarrollo de las biotecnologías actualmente

disponibles en los sectores agrícola, pesquero, forestal y ganadero. Las otras dos conferencias trataron de las repercusiones de la biotecnología agrícola sobre el hambre y la seguridad alimentaria en los países en

desarrollo y las consecuencias de los derechos de propiedad intelectual en la alimentación y la agricultura en esos países.

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durable de lÕAfrique, dans le contexte des changements politiques et institutionnels, d mographiques, conomiques, technologiques et environnementaux. Sur la base dÕun examen de lÕimpact des facteurs de changement et des sc narios probables, il donne une indication de ce qui pourrait arriver dÕici ˆ 2020, si les

tendances actuelles persistent. Les priorit s et les strat gies permettant de renforcer la contribution du secteur forestier au bien- tre social sont galement tudi es.

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A Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues (JMPR) was held in Geneva, Switzerland, from 9 to 13 May 2016. The three pesticides evaluated at the meeting were placed on the agenda by the JMPR Secretariat following the recommendation of an electronic task force of the WHO Core Assessment Group that they be re-evaluated due to public health concerns identified by the

International Agency for Research on Cancer (IARC) and the availability of a significant number of new studies. During the meeting, the WHO Core Assessment Group was responsible for reviewing epidemiological, toxicological and related data in order to establish acceptable daily intakes (ADIs) and acute reference doses (ARfDs) of the pesticides for humans, where necessary. As no residue data

were requested, the FAO Expert was responsible for estimating the dietary exposures (both short-term and long-term) to the pesticides reveiewed and, on this basis, performed dietary risk assessments in relation to their ADIs or ARfDs. This report contains information on ADIs, ARfDs and general principles for the evaluation of pesticides. The recommendations of the Joint Meeting, including further research and information, are proposed for use by Member governments of the

respective agencies and other interested parties.


WORLD HEALTH ORGANIZATIONFOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS

Pesticide residues in food 2016Joint FAO/WHO Meetingon Pesticide Residues

Report of the special session of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Envi-ronment and the WHO Core Assessment Group on Pesticide Residues Geneva, Switzerland, 9–13 May 2016

Rome, 2016

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The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Food and Agriculture Organization of the United Nations (FAO) or of the World Health Organization (WHO) concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or products of manufacturers, whether or not these have been patented, does not imply that these are or have been endorsed or recommended by FAO or WHO in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by FAO and WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall FAO and WHO be liable for damages arising from its use. The views expressed herein are those of the authors and do not necessarily represent those of FAO or WHO. ISBN 978-92-5-109246-0 © FAO and WHO, 2016 FAO and WHO encourage the use, reproduction and dissemination of material in this information product. Except where otherwise indicated, material may be copied, downloaded and printed for private study, research and teaching purposes, provided that appropriate acknowledgement of FAO and WHO as the source and copyright holder is given and that FAO and WHO’s endorsement of users’ views, products or services is not implied in any way. All requests for translation and adaptation rights, and for resale and other commercial use rights should be made via www.fao.org/contact-us/licence-request or addressed to [email protected]. FAO information products are available on the FAO website (www.fao.org/publications) and can be purchased through

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iii

iii

TABLE OF CONTENTS

List of participants ................................................................................................................................ v

Abbreviations ..................................................................................................................................... vii

Use of JMPR reports and evaluations by registration authorities .................................................. ix

1. Introduction .............................................................................................................................. 1

1.1 Declaration of interests ....................................................................................................... 1

2. General considerations ............................................................................................................ 3

2.1 General considerations on the evaluation of genotoxicity studies ...................................... 3

2.2 Methods for the evaluation of epidemiological evidence for risk assessment .................... 3

3. Evaluation of data for acceptable daily intake and acute reference dose for humans ..... 7

3.1 Diazinon (22) (T)** ............................................................................................................ 7

3.2 Glyphosate (158) (T)** ..................................................................................................... 19

3.3 Malathion (49) (T)** ........................................................................................................ 29

4. Recommendations .................................................................................................................. 43

Annex 1: Acceptable daily intakes and acute reference doses recorded by the May 2016 Meeting ...................................................................................................................... 45

Annex 2: Index of reports and evaluations of pesticides by the JMPR ............................... 47

Annex 3: International estimated daily intakes of pesticide residues .................................. 61

Annex 4: International estimates of short-term dietary intakes of pesticide residues ....... 91

Annex 5: Reports and other documents resulting from previous Joint Meetings of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues .......................... 101

T, toxicological evaluation

** Evaluated following the recommendation of an electronic task force of the WHO Core Assessment Group on Pesticide Residues that the compound be re-evaluated due to public health concerns identified by IARC and the availability of a significant number of new studies


Diazinon 13

13

diazinon use, but confidence intervals were wide, reflecting uncertainty in the risk estimates, and chance could not be excluded as an explanation for the findings. Overall, there was no convincing evidence of a positive association between NHL and exposure to diazinon.

A significantly increased risk of leukaemia in the highest exposure category (> 38.8 lifetime days of diazinon exposure; RR = 3.36; 95% CI = 1.08–10.49) and a significant exposure–response relationship were observed in the AHS. Findings for intensity-weighted lifetime exposure days demonstrated a similar pattern, but did not reach significance. Two other studies reported non-significantly elevated risks of leukaemia for high versus low diazinon use and ever versus never use of diazinon, with a non-significant dose–response relationship observed using days of use per year. Overall, there is weak evidence of a positive association between leukaemia and exposure to diazinon from the AHS only. It is noted that the number of diazinon-exposed cases was low or not reported in all three available studies.

A significant 60% excess risk of lung cancer in the highest exposure category (> 38.8 lifetime days of diazinon exposure) and a significant trend across exposure categories were observed in the AHS. Findings for intensity-weighted lifetime exposure days demonstrated a similar pattern, but did not reach significance. A separate analysis of ever use of diazinon versus never use from the AHS found no evidence of elevated risk of lung cancer among spouses of farmers/pesticide applicators; however, there were only 15 exposed cases. One other study reported a non-significant elevated risk of lung cancer for ever versus never use of diazinon (based on 17 exposed cases). Overall, there is weak evidence of a positive association between lung cancer and exposure to diazinon from the AHS cohort study only.

In view of the lack of genotoxicity and the absence of carcinogenicity in mice and rats and considering the available epidemiological data from occupational exposure, the Meeting concluded that diazinon is unlikely to pose a carcinogenic risk to humans via exposure from the diet.

The Meeting concluded that the existing database on diazinon was adequate to characterize the potential hazards to the general population, including fetuses, infants and children.

Toxicological evaluation

The Meeting identified inhibition of acetylcholinesterase activity as the most sensitive end-point after single or repeated doses of diazinon in all species. After considering all previously evaluated data and the new studies, the Meeting established an ADI of 0–0.003 mg/kg bw, based on the overall NOAEL of 0.3 mg/kg bw per day from all repeated-dose toxicity studies, and using a safety factor of 100. This ADI was supported by the NOAEL of 0.03 mg/kg bw per day, the highest dose tested, identified in repeated-dose studies that involved a limited number of male volunteers, with application of a safety factor of 10.

In 2006, the Meeting established an ADI of 0–0.005 mg/kg bw, based on the highest NOAEL of 0.5 mg/kg bw per day for inhibition of erythrocyte acetylcholinesterase activity at 1 mg/kg bw per day in a 92-day repeated-dose toxicity study in rats and using a safety factor of 100. In this study, the dietary concentrations of diazinon were converted to units of milligrams per kilogram body weight per day using a default conversion factor; the present Meeting considers this less reliable than the conversion using feed consumption data.

The Meeting reaffirmed the ARfD of 0.03 mg/kg bw established by the 2006 JMPR. This ARfD was based on the NOAEL of 2.5 mg/kg bw identified in studies of acute (neuro)toxicity in rats, and using a safety factor of 100. This ARfD was supported by the NOAEL of 0.21 mg/kg bw, the highest dose tested, identified in the study in which a limited number of male volunteers were given a single dose of diazinon, with application of a safety factor of 10.


pesticide residues in food 2016: special session of the

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