2016 WHO FAO Glyphosate Evaluation

glyphosate IARC WHO

Is the exclusion of a wide body of scientific evidence that demonstrates that glyphosate and its formulations cause long term (chronic) harmful effects at environmentally relevant levels by the WHO FAO JMPR panel a contravention of Constitution of the World Health Organisation?  Particularly when the arm of the World Health Organisation that deals with cancer (IARC) sets the standard for twenty-first century scientific knowledge of carcinogenesis and disease development - drawing information from a wide range of studies that includes consideration of full formulation toxicity?

On 16th May the Joint Meeting of the Food and Agriculture Organisation of the United Nations (FAO) Panel of Experts on Pesticide Residues in Food and the Environment and the World Health Organization (WHO) Core Assessment Group on Pesticide Residues (JMPR) released a summary report for glyphosate, diazinon and malathion. The FAO JMPR Page is here

The constitutions requires that these agencies place health as a priority:

Constitution of the World Health Organisation. 

Chapter I – OBJECTIVE Article 1
The objective of the World Health Organization (hereinafter called the Organization) shall be the attainment by all peoples of the highest possible level of health.

Food & Agriculture Organisation:

'Our mandate is to support members in their efforts to ensure that people have regular access to enough high-quality food.'

Yet it appears that the World Health Organisation (WHO) and Food and Agriculture Organisation (FAO) Joint Meeting on Pesticides Residues (JMPR) 2016 evaluation utilises antiquated guidelines and old scientific studies while neglecting to consider new scientific methods for understand toxicity at low exposures.

A 2015 scientist consensus statement advised

'Regulatory estimates of tolerable daily intakes for glyphosate in the United States and European Union are based on outdated science.'[1]

The 2016 WHO FAO evaluation for glyphosate, diazinon and malathion was released in May 2016. In relation to the glyphosate studies, it appears to draw from old data, exclude new science, and avoids providing references for scientific studies.

Current available JMPR 16 May summary noted:  Meeting reaffirmed the group ADI for the sum of glyphosate and its metabolites of 0–1 mg/kg body weight on the basis of effects on the salivary gland.'    http://www.who.int/foodsafety/jmprsummary2016.pdf

Detailed information is in the more comprehensive FAO Plant Production and Protection Paper 227, Pesticide residues in food 2016 REPORT 2016, ISSN 2070-2515.  http://www.fao.org/3/a-i5693e.pdf

Problems with the FAO/WHO JMPR panel 2016 Special Session evaluations: Outdated science & unpublished studies

1. Exposure levels for the world population - daily glyphosate acceptable daily intake (ADI) for life - stays the same from the 2004 toxicological evaluation.  

The 2016 panel retained the 2004 ADI ADI at 1mg per kg bodyweight per day. 

The Meeting reaffirmed the group ADI for the sum of glyphosate, AMPA, N-acetyl-glyphosate and N-acetyl-AMPA of 0–1 mg/kg bw on the basis of the NOAEL of 100 mg/kg bw per day for effects on the salivary gland in a long-term study of toxicity and carcinogenicity in rats and application of a safety factor of 100.  Page. 24

Unless otherwise confirmed, it would appear that the 'salivary gland study' may be an unpublished twenty-three year old Cheminova paid study from 1993. 

Atkinson, C., Strutt, A.V., Henderson, W., Finch, J. & Hudson, P. (1993b) Glyphosate: 104 week combined chronic feeding/oncogenicity study in rats with 52 week interim kill (results after 104 weeks.). 

Pesticide residues in food – 2004    Joint FAO/WHO Meeting on Pesticide Residues  EVALUATIONS  2004  Part II—Toxicological Pages 127-129.  Long-term studies of toxicity and carcinogenicity

  • Target/critical effect:  Reduced body weights, loose stools, liver (toxicity), salivary glands (organ weight, histology), eye (cataracts, lens fibre degeneration)
  • Lowest relevant NOAEL: 100 mg/kg bw per day (2 years; rat) Carcinogenicity. Not carcinogenic in rats; could not exclude possibility of carcinogenicity in mice at very high doses

It would seem the JMPR are relying on old data. This has the effect of maintaining permitted population daily exposures (ADI, RfD). The result of this, is to maintain permitted current levels of glyphosate applications to staple food crops, including cereals, oilseeds, sugar, peas and lentils.

2. Ignoring 21st century science: Scope was restricted to the active ingredient.

It is understood that the adjuvants are frequently toxic - yet while regulatory agencies acknowledge increasing evidence, they resist allowing for cumulative and synergistic toxicity in risk assessment - despite the fact that the population is exposed to full formulation mixtures, and mixtures of various formulations of insecticides, fungicides, herbicides and growth promotants that may be applied to a single food crop. 

A wide range of science demonstrates that the full formulation is more toxic than the active ingredient. By ignoring this fact the WHO and FAO JMPR committee fail to evaluate glyphosate and its co-formulants safely. The constitution of the WHO prioritises ' the highest possible level of health.'

For decades, the chemical industry have discussed formulations in terms of 'acid equivalents' - different formulations will express different toxicity dependent on the ingredients in the formulation. It is not enough to say that it is only the active ingredient that may cause adverse effects.

The 2015 IARC Working Group on glyphosate included full formulation studies because it is commonly accepted that formulation mixtures exhibit synergies and can therefore be more toxic than the active ingredient.

As a leading authority on carcinogenesis and cancer the IARC establishes a level of scientific rigor in understanding toxicity that responsible regulators including the FAO & WHO should adopt, in order to be relevant and authoritative.

Agricultural manuals reflect this and discuss 'acid equivalents,' as formulation ingredients may result in less of the 'active ingredient' (in this case, glyphosate) in the end formulation. 

A Consensus Statement on glyphosate published in 2015 noted:- 

‘The distinction in regulatory review and decision processes between ‘active’ and ‘inert’ ingredients has no toxicological justification, given increasing evidence that several so-called ‘inert’ adjuvants are toxic in their own right.’ [1]

It appears the outdated guidelines and protocols which insist on 'active ingredient' assessment only are outdated and do not reflect modern scientific understanding.

3. Ignoring 21st century science: Environmentally relevant exposures not considered

Codex Alimentarius increased permitted levels of glyphosate on crops in 2006 after the 2004 evaluations and crop residue trials to allow for pre-harvest desiccation.  A US EPA screening report reveals significantly high residues across food crops. 

Maximum residue levels (MRLs) on food crops are obtained from trials on crops to assess levels of pesticide residue. Once the crop levels are agreed on they are formalised as MRLs within, for example, Codex Alimentarius and the US Code of Federal Regulations (Title 40 Protection of Environment) .

As toxicological evaluations to assess whether a pesticides causes adverse harm to health are not conducted at environmentally relevant levels - there is no requirement for MRLs to be adjusted for health reasons. MRLs are set much lower than the industry paid studies regulators use to assess cancer, reproductive toxicity etc. 

An increasing range of studies are demonstrating harm from pesticides at the environmentally relevant levels (for example, parts per billion) but conventionally regulators only use studies selected and supplied by the industry concerned with the active chemical in question.

As a result the JMPR summary declares there is no risk from food. 

Testing reveals that glyphosate is present in the population, and at higher levels in children: 'In the urine tests, glyphosate was detected at an average level of 3.096 parts per billion (PPB) with children having the highest levels with an average of 3.586 PPB.'  

European politicians excreted glyphosate in urine at surprisingly high doses. Where previously it was assumed only farm workers and spray applicators had constant exposure, it is now understood that city dwellers are exposed via food. It appears a substantive contribution to exposures may come from pre-harvest treatments, which were increased in 2006.

It is well known that glyphosate is increasingly present in groundwater. Maintenance of current exposure rates and hence crop application rates by definition will result in continued increases in groundwater and drinking water sources. Risk assessment within the World Health Organisation is yet to address the potential downstream effects of increased residues of glyphosate, its formulations - and the increasing synergies of various pesticide formulations in groundwater at environmentally relevant levels.

Downstream effects may include increased rates of chronic disease including cancer, endocrine disruption, reduced antibiotic effectiveness, reduced IQ and neurological harm. 

Regulators and risk assessment agencies have traditionally downplayed the risk of glyphosate entering groundwater and drinking water sources. It is now understood this this is assumption is incorrect. The Consensus Statement noted:

Studies have shown that soil sorption and degradation of glyphosate exhibit great variation depending on soil physical, chemical, and biological properties. The risk of long-term, incremental buildup of glyphosate contamination in soil, surface water, and groundwater is therefore driven by highly site-specific factors, and as a result, is difficult to predict and costly to monitor.[1]

Much of the current protocols and guidelines have been followed by the JMPR for decades - they appear sufficient to exclude twenty first century published data that a chemical under evaluation causes harm at very low levels. Simply put, the JMPR does not consider toxicity at environmentally relevant levels.

This needs confirmation, as scientific reviews must normally disclose the authors of the data that they review, contrary to normal procedure, this the JMPR does not appear to have done so at time of writing.

The older studies apparently used by the JMPR in this evaluation consider levels much higher than those present in food and water.

The Committee downplay the long term absorption and exposure aspects and appear to rely on decades old science. Furthermore, many old industry paid studies are used: for example, the claim that ‘Less than 1% of the administered dose was retained in tissues 168 hours post-administration.’ Appears to be from a 1988 unpublished study produced in a Monsanto laboratory and used in the 2004 evaluations:

Ridley, W.P. & Mirly, K. (1988) The metabolism of glyphosate in Sprague-Dawley rats. Part I. Excretion and tissue distribution of glyphosate and its metabolites following intravenous and oral administration. Unpublished report, study No. 86139, project No. ML-86-438, dated March 1988, from Monsanto Environmental Health Laboratory, St. Louis, Missouri, USA. Submitted to WHO by Monsanto Int. Services SA, Brussels, Belgium

The complexity and potential for adverse harm from low levels exposures are not addressed by the JMPR in the 2016 paper, yet are recognised by scientists:

‘Unless and until regulatory agencies incorporate modern endocrinologic principles into their risk assessment paradigms, they will continue to provide false assurances of “safety” and fail to recognize the actual health risks posed by chronic low-level exposure to an increasing number of chemicals found in commonly used products.'[2]

3. Ignoring 21st century science: Chronic toxicity - 'pretend' studied......

In 2004 (the last FAO WHO glyphosate evaluation) the JMPR declared glyphosate was fully excreted.

It is evident that this is now, not the case.  Science understands that due to extensive applications on staple food crops and animal feed, the population receives chronic low dose exposures from conception onwards and that babies are born pre-polluted. Non-agricultural and agricultural populations are exposed.

Studies demonstrate risk from chronic (long term) toxicity is of profound concern. Due to the demonstrated accumulation in food and urine we have evidence of low level exposures. The JMPR panel criteria that establishes the ADI does not address chronic toxicity at environmentally relevant exposures.

The longest studies held with risk assessment agencies are at 24 months - in rat years, that is 60 years. If long term studies were to accurately depict lifetime exposure, they would continue till 36 months, 90 years. This would make research even more expensive, but the challenge is that when tumours are detected at 24 months, these private studies frequently dismiss the tumour due to historical data, not considered related to the active ingredient - yet these studies cannot be peer reviewed nor subject to replication. 

For example. the JMPR advised that the overall NOAEL for systemic toxicity in rats was 100 mg/kg bw per day, and the overall LOAEL was 300 mg/kg bw per day.

chemicals children babies sick

3. Ignoring 21st century science: Pregnancies and infants ignored. 

In every instance, children are exposed to higher levels than adults. The JMPR do not consider toxicity studies that would apply to an infant under 15kg. This is unaccounted for.  In reproductive studies supplied for risk assessment, the rodent is not dosed in the first trimester. As the WHO says 'children are not little adults' - they are more vulnerable.

The 2016 Report advises: The lowest NOAEL for embryo and fetal toxicity was 300 mg/kg bw per day, based on delayed ossification and an increased incidence of fetuses with skeletal anomalies observed at 1000 mg/kg bw per day.

It appears that, without providing a reference, that the 2016 JMPR are again relying on old data – Pages 139-140 of the 2004 evaluations provide the same information, citing the study authors:

Brooker, A.J., John, D.M., Anderson, A. & Dawe, I.S. (1991b) The effect of glyphosate on pregnancy of the rat (incorporates preliminary investigation). GLP yes. Unpublished report No. CHV 43 & 41/90716, dated 14 October 1991, from Huntingdon Research Centre Ltd., Huntingdon, England. Submitted to WHO by Cheminova A/S, Lemvig, Denmark.

Internationally, twenty first century science clearly demonstrates the increased vulnerability of the developing infant – yet the JMPR rely on twentieth century unpublished science to arrive at a NOAEL for the developing baby.

New science points to the adverse effects cause by low level neonatal chemical exposures that can contribute to carcinogenesis via endocrine disruption and epigenetic influences.

This 1993 paper demonstrates that potential for adverse harm from chemicals at low levels has been known for over twenty years:

‘low level exposure to endocrine disrupting chemicals (EDCs) especially during early development, lead to both transient and permanent changes to endocrine systems. This results in impaired reproduction, thyroid function, and metabolism, and increased incidence and progression of hormone-sensitive cancers’. [3]

Yet the studies considered by the JMPR are a narrow range of chemical industry studies, rather than a wide section of published and peer reviewed studies that today would indicate that agencies and regulators should move with caution in permitting chemical exposures on staple food crops.

4. Ignoring 21st century science: Hormone damaging? Epigenetic effects? 

In the WHO FAO data call out there was no request for studies concerning endocrine disruption - the public literature indicates that glyphosate is likely an endocrine disruptor (EDC). 

Page 22 of the Report states:- 

‘Glyphosate was tested in a range of validated in vivo and in vitro assays for its potential to interact with the endocrine system. The studies that the Meeting considered adequate for the evaluation clearly demonstrate that there is no interaction with estrogen or androgen receptor pathways or thyroid pathways.’

Yet there are no references to elucidate as to which studies were reviewed.

The IARC made allowances that when it comes to the endocrine system, low doses may exert greater effects than higher doses, therefore linear dose response curves cannot be assumed.

Yet current risk assessment will dismiss a response at a lower dose that does not consistently increase at a higher dose. 

‘When the potential for non-linear dose-response relationships is combined with the possibility of synergism between and amongst low doses of mixtures of individual chemicals in the environment, it appears plausible that chemicals that are not individually carcinogenic may be capable of producing carcinogenic synergies that would be missed using current risk assessment practices.’ [4]

It is understood that glyphosate can adversely affect hormones at 0.1PPB.   

5. Conflicts of interest - with the JMPR panel

2016 May JMPR panel of experts 2016 September JMPR expert bios. 

The Guardian reported May 2016, in 'UN/WHO panel in conflict of interest row over glyphosate cancer risk:

'Professor Alan Boobis, who chaired the UN’s joint FAO/WHO meeting on glyphosate, also works as the vice-president of the International Life Science Institute (ILSI) Europe. The co-chair of the sessions was Professor Angelo Moretto, a board member of ILSI’s Health and Environmental Services Institute, and of its Risk21 steering group too, which Boobis also co-chairs.'

The Centre for Media and Democracy's SourceWatch advises:

International Life Sciences Institute (ILSI) is a Washington-D.C. based lobby group funded by food, chemical and drug companies. Primarily it acts on behalf of the global food manufacturing industry, but it also includes operations involved with agriculture and genetic modification; pesticides and pharmaceuticals; confectionery; and even with such dubious consumables as cigarettes.

SourceWatch notes that ILSI has over 400 companies listed as members, including Dow Agrosciences/Dow Chemical , Monsanto, DuPont and Bayer AG.

ILSI has valuable 'insider' status at WHO governing body meetings and the chairmanship of Professors Boobis and Moretto may inevitably facilitate close industry relationships.

6. Conflicts of interest - data. 

The FAO released FAO Plant Production and Protection Paper 227, Pesticide residues in food 2016 REPORT 2016, ISSN 2070-2515.  This is a Summary Report - rather than a Toxicological Monograph. At time of writing (5 months after release) there are no references for the data nor advice regarding exactly which organisations or individuals selected and supplied the studies used. 

It appears that the World Health Organisation (WHO) and Food and Agriculture Organisation (FAO) Joint Meeting on Pesticides Residues (JMPR) appear to be using old unpublished industry selected and supplied studies to arrive at the recommended exposure levels for the world population. 

Traditionally the manufacturers (industry) carefully select and supply the critical data that supply the NOAELs that contribute to establishing the daily permitted expsoures (ADI or RfD). 

It is critical these studies are transparently available as the high ADI justifies ongoing glyphosate applications to food and feed crops and lack of testing in groundwater and retail food products.  Is the data widely sourced and published for peer review? 

Peer review enables scientists to look critical at data and ensure a study has been produced using good science - every good study must be replicable. The chemical industry avoids publishing data, instead they produce studies according to 'Good Laboratory Practice' and 'OECD guidelines' - fulfilling the requirements of these protocols and guidelines enable the chemical industry to avoid public disclosure of the studies. Yet these protocols and guidelines in many respects are not keeping up with twenty first century science and the increasing knowledge of how chemicals, and chemical mixtures affect humans (particularly baby humans) at surprisingly low levels.

The JMPR derive international levels of chemical exposure for glyphosate and glyphosate formulations to the human population from an extremely narrow range of private, industry produced single dosing studies and private 2 year chronic toxicity studies of the single active chemical glyphosate.

The current Summary Report appears demonstrate an increasingly opaque and outdated approach to risk assessment.

7. The JMPR brushes off the IARC genotoxicity and 'probable carcinogen' finding. 

Hazard based assessment looks at the inherent toxicity of a substance, while risk assessment is concerned with exposure, primarily concerning risk related to dietary exposure. The IARC conclusion is primarily hazard based assessment, but as it looked at current exposure levels, it also addressed risk. 

Typically, regulatory findings follow risk based assessment - yet we find there is a breakdown in what constitutes 'risk' in light of current scientific knowledge that is unravelling the complex mechanisms by which cancer establishes itself - and the significant influence of environmental factors in carcinogenesis.

While the IARC Monograph of course, focused on cancer, it is important to note it included  genotoxicity and oxidative stress as mechanisms for cancer. Regulators have minimised these effects in risk assessment and barely consider oxidative stress.

The JMPR 2016 has largely ignored the role of oxidative stress in cancer. Oxidative stress can facilitate genetic mutations or epigenetically regulate gene expression.

‘Cancer is a multistage process defined by at least three stages: initiation, promotion, and progression. Oxidative stress interacts with all three stages of this process.'

What is risk without understanding caution? 

Evident from the JMPR paper is the focus on particular antiquated unpublished studies to retain the exposure levels, and lack of scrutiny and transparent consideration of the wide range of studies in the publicly available scientific literature.

8. Requirement to future proof. Risk assessment only happens every fifteen years. 

JMPR periodic reviews are scheduled for every 15 years – due to the rare occasions on which pesticides are evaluated it would not be unreasonable to expect every effort to be undertaken to ensure best practice.

The 'business as usual' toxicological evaluation scenario that does not permit consideration of full formulation adverse harm - effectively pushes evaluations that may consider full formulation exposures into the far distant future.

http://www.fao.org/fileadmin/templates/agphome/documents/Pests_Pesticides/JMPR/FAO_manual2nded_Oct07.pdf

9. Probability - the Precautionary Principle - where a chemical is applied to staple food crops.

Unlike cancer from cigarettes, or even chronic disease arising from dietary choices - glyphosate based herbicides are applied to staple food crops - oilseeds, cereals (including oats and wheat), legumes - as well as on animal feed crops.

The majority of the world population cannot exercise a choice to buy organic - therefore the application of a chemical on staple food crops where the science is highly contentious - should mean that responsible regulators and agencies act with caution.

However where there is doubt, today, regulators and agencies do not appear to act with caution in the public interest. Where there is uncertainty they do not elect to remove the chemical from public exposures - instead they act with caution to retain chemical registration and maintain sales of the chemicals.

Actions of regulators to fail to account for full toxicity of a formulation, and to push aside modern advances in understanding cancer development undermines the trust of civil society, fails to adhere to primary purposes of acts which give them an obligation to prevent or manage risks to public health.

Much of this comes back to resourcing - regulatory risk assessment agencies do not have the money to conduct their own research to understand toxicity of chemicals in food and environment. Thus they are dependent on studies supplied directly from the relevant chemical industry and necessarily maintain close relationships with industry when evaluating chemicals.

(I don't think many scientists working in this environment, are happy about it.)

This leads to issues of transparency, and stagnation in scientific rigour as the chemical industry traditionally work with regulators to set and maintain guidelines and protocols that help derive 'weight of evidence' findings that work to ensure regulators select chemical industry studies over public domain, peer reviewed science (the OECD is a trade organisation, rather than a scientific organisation, after all).

Current risk assessment of chemicals, including glyphosate, reveals the deep fraying and decay that demonstrates the dis-ease between the founding constitutions and other legislation that these high profile agencies and regulators must act under - and the reality of actually who sets the agenda to establish and define toxicity, and what studies will actually be considered - for the world population.

This is not just a problem for the World Health Organisation and Food and Agriculture Organisation's JMPR. It is repeated in nearly every national government risk assessment agency.

Current risk assessment reflects the lack of resourcing of these agencies and hence ability to act independently from industry, and reflects the necessary close relationships with the chemical industry that prevent regulators and agencies from acting directly in the public interest and necessarily implementing public health measures that reflect twenty-first century scientific understanding.

 

References:

[1] Myers J P et al (2016). Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement. Environmental Health 15(19). DOI 10.1186/s12940-016-0117-0. 

[2] Myers et al 2009b. A Clash of Old and New Scientific Concepts in Toxicity.

[3] Colborn T, vom Saal FS, Soto AM. 1993. "Developmental effects of endocrine-disrupting chemicals in wildlife and humans". Environ. Health Perspect. 101 (5): 378–84.  doi:10.2307/3431890. 

[4] Goodson et al 2015. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment.

[5] D.A.Hanahan & R.A.Weinberg. Review: The Hallmarks of Cancer. Cell. Vol. 100, pp57–70, 2000 http://dx.doi.org/10.1016/S0092-8674(00)81683-9
Reuter et al 2010. Oxidative stress, inflammation, and cancer: How are they linked? Free Radical Biology and Medicine Vol. 49, 1 December 2010, Pp 1603–1616. http://dx.doi.org/10.1016/j.freeradbiomed.2010.09.006

 

 

WHAT IS THE JMPR? 

Content sourced from AGP - The Joint FAO/WHO Meeting on Pesticide Residues (JMPR)

'The current JMPR comprises the WHO Core Assessment Group and the FAO Panel of Experts on Pesticide Residues in Food and the Environment. The WHO Core Assessment Group is responsible for reviewing pesticide toxicological data and estimating Acceptable Daily Intakes (ADI), acute reference doses (ARfDs) and characterizes other toxicological criteria.

The FAO Panel is responsible for reviewing pesticide data residue and for estimating maximum residue levels, supervised trials median residue values (STMRs) and highest residues (HRs) in food and feed. The maximum residue levels are recommended to the Codex Committee on Pesticide Residues (CCPR) for consideration to be adopted by the Codex Alimentarius Commission (CAC) as CXLs.

The output of JMPR not only constitutes the essential basis for Codex MRLs for food and agricultural commodities circulating in international trade, its health-based guidance for pesticides (i.e. ADIs and ARfDs) and recommends maximum residue levels also benefit to the governments of the member countries and regions.'