Joint FAO/WHO Meeting on Pesticide Residues
FAO PLANT PRODUCTION AND PROTECTION PAPER 223
Pesticide residues in food 2015
(acamedia cache of this report)
Format edited by J. Gruber
USE OF JMPR REPORTS AND EVALUATIONS BY REGISTRATION AUTHORITIES
Most of the summaries and evaluations contained in this report are based on unpublished proprietary data submitted for use by JMPR in making its assessments. A registration authority should not grant a registration on the basis of an evaluation unless it has first received authorization for such use from the owner of the data submitted for the JMPR review or has received the data on which the summaries are based, either from the owner of the data or from a second party that has obtained permission from the owner of the data for this purpose.
IARC published a summary of the findings on glyphosate in The Lancet Oncology1 and the glyphosate monograph was published on 29 July 20152 and provided to the task force on that date. The summary and monograph included a classification of Group 2A, probably carcinogenic to humans, for glyphosate. This classification was based on:
- limited evidence of carcinogenicity in humans – A positive association was observed for non-Hodgkin lymphoma.
- sufficient evidence of carcinogenicity in experimental animals, supported by mechanistic evidence of genotoxicity and oxidative stress.
JMPR most recently evaluated glyphosate in 2004 and 2011.
- The 2004 evaluation (in acamedia cache)
- found no evidence of carcinogenicity in long-term studies in mice and rats, and
- negative results were obtained in an adequate range of genotoxicity studies performed in compliance with current test guidelines.
- The 2011 evaluation covered only the metabolites N-acetyl-glyphosate and N-acetyl- aminomethylphosphonic acid in genetically modified plants and is therefore not relevant to this exercise on the carcinogenicity of the parent compound, glyphosate.
- The primary purpose of this task was to compare publications cited by IARC (2015) with those cited by JMPR (2004) and to identify those epidemiological, rodent bioassay, genotoxicity and other mechanistic studies that were not considered by JMPR in its assessment of the carcinogenic risk posed by exposure to glyphosate.
- In addition, the task force considered references cited in a report by EFSA (2014)3 which was released in April 2014 for public consultation and will be finalized and published before the end of 2015.
- No comparison of references cited by the proposed re-evaluation decision PRVD2015-01 on glyphosate from the Pest Management Regulatory Agency (PMRA) of Health Canada (April 2015)4 was included in this assessment, because the IARC monograph was made available only on 29 July 2015 and there was no time within the mandate of the task force to make this comparison.
- Any relevant study (e.g. those cited by PMRA) not identified in the current analysis because of the limited time frame should be considered in the proposed re-evaluation by JMPR.
The original reference list that IARC submitted to the task force in May 2015 included 403 studies. In the published IARC monograph (July 2015), only 263 studies were reported. The original list shared with JMPR consisted of all references “included” in the HAWC Literature Search tool (a collaborative workspace for conducting risk assessments for human) plus all references cited in the preliminary drafts. Therefore, IARC characterized the list as the literature “considered” by the IARC Working Group. The difference between the number of references included in the original list and the number of references included in the final monograph can be mainly attributed to the fact that not all identified literature must be cited in Sections 1 (epidemiology) and 4 (mechanistic and other studies).
Glyphosate References on Epidemiological Studies
40 references for epidemiological studies were cross-checked between the relevant JMPR, IARC and EFSA publications:
- There were 3 studies cited by IARC (2015) and 3 studies cited by EFSA (2014) that were also available to and evaluated by JMPR (2004).
- There were 28 studies cited by IARC (2015) that were not available to or evaluated by JMPR (2004).
- There were 30 studies cited by EFSA (2014) that were not available to or evaluated by JMPR (2004). These studies have not yet been published by the study owner, but should be submitted by the Glyphosate Task Force for consideration by JMPR.
Glyphosate References on Rodent Cancer Bioassays
15 references for carcinogenicity studies in rodents were cross-checked between the relevant JMPR, IARC and EFSA publications:
- There were 2 reports cited by IARC (2015) that were also available to and evaluated by JMPR (2004).
- There were 5 reports cited by IARC (2015) that were not available to or evaluated by JMPR (2004).
- There were 6 reports cited in the EFSA (2014) assessment that were not available to or evaluated by JMPR (2004) or IARC (2015), but were reviewed in the publication of Greim et al. (2015)5 These studies have not yet been published by the study owner, but should be submitted by the Glyphosate Task Force for consideration by JMPR.
Glyphosate References on Genotoxicity Studies
Active Substance Glyphosate
There were 99 references on the genotoxicity of glyphosate, but these could not be fully cross- checked between the relevant JMPR, IARC and EFSA publications. The task force also conducted a literature search for genotoxicity references published after the IARC (2015) review:
- here were three studies cited by IARC (2015) that were also available to and evaluated by JMPR (2004). One of the three references is a review article.
- There were 49 studies cited by IARC (2015) that were not available to or evaluated by JMPR (2004).
- There were four recently published studies identified by the task force that were not evaluated by JMPR (2004).
- There were 30 studies cited by EFSA (2014) that were not available to or evaluated by IARC (2015) or JMPR (2004). These studies have not yet been published by the study owner, but should be submitted by the Glyphosate Task Force for consideration by JMPR.
Glyphosate-containing Formulations and AMPA
There were many references relating to genotoxicity studies on glyphosate-containing formulations or aminomethylphosphonic acid (AMPA), but these could not be cross-checked between the relevant JMPR, IARC and EFSA publications within the available time frame.
Glyphosate References on Oxidative Stress and Other Mechanistic Studies
The IARC monograph includes mechanistic studies and other relevant data that might be of importance for a re-evaluation of toxicity end-points other than carcinogenicity.
In light of the studies identified in the publications by IARC (2015) and EFSA (2014) that were not considered by JMPR (2004), as well as the additional genotoxicity studies identified by the task force, it is recommended that JMPR discuss and consider the re-evaluation of the active substance glyphosate. In particular:
- It is recommended that Section 4.2.1 of the IARC monograph on genetic and related effects be carefully considered within the re-evaluation by JMPR, if the studies are performed with the active substance glyphosate, glyphosate-containing formulations and/or AMPA.
- It is recommended that the studies evaluated by IARC in Chapter 4 of the monograph, especially those on toxicokinetic data, receptor-mediated mechanisms, inflammation and immunomodulation, and cell proliferation and death, be considered in a full JMPR re-evaluation.
- Guyton KZ et al., on behalf of the International Agency for Research on Cancer Monograph Working Group, IARC, Lyon, France (2015). Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate. Lancet Oncol. 16(5):490–1.
- IARC (2015). Glyphosate (in acamedia chache). In: Some organophosphate insecticides and herbicides: diazinon, glyphosate, malathion, parathion, and tetrachlorvinphos. Lyon: International Agency for Research on Cancer (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 112; accessed 28 September 2015).
- The studies cited in this report, which have not yet been published, should be submitted by the European Glyphosate Task Force (a consortium of companies joining resources and efforts in order to renew the European glyphosate registration with a joint submission) for the proposed re-evaluation of glyphosate by JMPR.
- Summary available here (in acamedia cache).
- 1 Greim H, Saltmiras D, Mostert V, Strupp C (2015). Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies. Crit Rev Toxicol. 45(3):185–208.
Version: 4 February 2016
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