Benbrook et al., 2021a
Benbrook, Charles, Perry, Melissa J., Belpoggi, Fiorella, Landrigan, Philip J., Perro, Michelle, Mandrioli, Daniele, Antoniou, Michael N., Winchester, Paul, & Mesnage, Robin; “Commentary: Novel strategies and new tools to curtail the health effects of pesticides;” Environmental Health, 2021, 20(1); DOI: 10.1186/s12940-021-00773-4.
BACKGROUND: Flaws in the science supporting pesticide risk assessment and regulation stand in the way of progress in mitigating the human health impacts of pesticides. Critical problems include the scope of regulatory testing protocols, the near-total focus on pure active ingredients rather than formulated products, lack of publicly accessible information on co-formulants, excessive reliance on industry-supported studies coupled with reticence to incorporate published results in the risk assessment process, and failure to take advantage of new scientific opportunities and advances, e.g. biomonitoring and “omics” technologies.
RECOMMENDED ACTIONS: Problems in pesticide risk assessment are identified and linked to study design, data, and methodological shortcomings. Steps and strategies are presented that have potential to deepen scientific knowledge of pesticide toxicity, exposures, and risks.
We propose four solutions:
(1) End near-sole reliance in regulatory decision-making on industry-supported studies by supporting and relying more heavily on independent science, especially for core toxicology studies. The cost of conducting core toxicology studies at labs not affiliated with or funded directly by pesticide registrants should be covered via fees paid by manufacturers to public agencies.
(2) Regulators should place more weight on mechanistic data and low-dose studies within the range of contemporary exposures.
(3) Regulators, public health agencies, and funders should increase the share of exposure-assessment resources that produce direct measures of concentrations in bodily fluids and tissues. Human biomonitoring is vital in order to quickly identify rising exposures among vulnerable populations including applicators, pregnant women, and children.
(4) Scientific tools across disciplines can accelerate progress in risk assessments if integrated more effectively. New genetic and metabolomic markers of adverse health impacts and heritable epigenetic impacts are emerging and should be included more routinely in risk assessment to effectively prevent disease.
CONCLUSIONS: Preventing adverse public health outcomes triggered or made worse by exposure to pesticides will require changes in policy and risk assessment procedures, more science free of industry influence, and innovative strategies that blend traditional methods with new tools and mechanistic insights.
Landrigan and Goldman, 2011
Landrigan, Philip J, & Goldman, Lynn R; “Children’s vulnerability to toxic chemicals: a challenge and opportunity to strengthen health and environmental policy;” Health Affairs, 2011, 30(5), 842-850; DOI: 10.1377/hlthaff.2011.0151.
A key policy breakthrough occurred nearly twenty years ago with the discovery that children are far more sensitive than adults to toxic chemicals in the environment. This finding led to the recognition that chemical exposures early in life are significant and preventable causes of disease in children and adults. We review this knowledge and recommend a new policy to regulate industrial and consumer chemicals that will protect the health of children and all Americans, prevent disease, and reduce health care costs. The linchpins of a new US chemical policy will be: first, a legally mandated requirement to test the toxicity of chemicals already in commerce, prioritizing chemicals in the widest use, and incorporating new assessment technologies; second, a tiered approach to premarket evaluation of new chemicals; and third, epidemiologic monitoring and focused health studies of exposed populations. FULL TEXT
Panzacchi et al., 2018
Panzacchi, S., Mandrioli, D., Manservisi, F., Bua, L., Falcioni, L., Spinaci, M., Galeati, G., Dinelli, G., Miglio, R., Mantovani, A., Lorenzetti, S., Hu, J., Chen, J., Perry, M. J., Landrigan, P. J., & Belpoggi, F. “The Ramazzini Institute 13-week study on glyphosate-based herbicides at human-equivalent dose in Sprague Dawley rats: study design and first in-life endpoints evaluation,” Environmental Health, 17(1), 52, 2018. doi:10.1186/s12940-018-0393-y.
BACKGROUND: Glyphosate-based herbicides (GBHs) are the most widely used pesticides worldwide, and glyphosate is the active ingredient of such herbicides, including the formulation known as Roundup. The massive and increasing use of GBHs results in not only the global burden of occupational exposures, but also increased exposure to the general population. The current pilot study represents the first phase of a long-term investigation of GBHs that we are conducting over the next 5 years. In this paper, we present the study design, the first evaluation of in vivo parameters and the determination of glyphosate and its major metabolite aminomethylphosphonic acid (AMPA) in urine.
METHODS: We exposed Sprague-Dawley (SD) rats orally via drinking water to a dose of glyphosate equivalent to the United States Acceptable Daily Intake (US ADI) of 1.75 mg/kg bw/day, defined as the chronic Reference Dose (cRfD) determined by the US EPA, starting from prenatal life, i.e. gestational day (GD) 6 of their mothers. One cohort was continuously dosed until sexual maturity (6-week cohort) and another cohort was continuously dosed until adulthood (13-week cohort). Here we present data on general toxicity and urinary concentrations of glyphosate and its major metabolite AMPA.
RESULTS: Survival, body weight, food and water consumption of the animals were not affected by the treatment with either glyphosate or Roundup. The concentration of both glyphosate and AMPA detected in the urine of SD rats treated with glyphosate were comparable to that observed in animals treated with Roundup, with an increase in relation to the duration of treatment. The majority of glyphosate was excreted unchanged. Urinary levels of the parent compound, glyphosate, were around 100-fold higher than the level of its metabolite, AMPA.
CONCLUSIONS: Glyphosate concentrations in urine showed that most part of the administered dose was excreted as unchanged parent compound upon glyphosate and Roundup exposure, with an increasing pattern of glyphosate excreted in urine in relation to the duration of treatment. The adjuvants and the other substances present in Roundup did not seem to exert a major effect on the absorption and excretion of glyphosate. Our results demonstrate that urinary glyphosate is a more relevant marker of exposure than AMPA in the rodent model. FULL TEXT
Landrigan and Belpoggi, 2018
Landrigan, P. J., and Belpoggi, F.,”The need for independent research on the health effects of glyphosate-based herbicides,” Environmental Health, 17(1), 51, 2018, doi:10.1186/s12940-018-0392-z.
BACKGROUND: Glyphosate, formulated as Roundup, is the world’s most widely used herbicide. Glyphosate is used extensively on genetically modified (GM) food crops designed to tolerate the herbicide, and global use is increasing rapidly. Two recent reviews of glyphosate’s health hazards report conflicting results. An independent review by the International Agency for Research on Cancer (IARC) found that glyphosate is a “probable human carcinogen”. A review by the European Food Safety Agency (EFSA) found no evidence of carcinogenic hazard. These differing findings have produced regulatory uncertainty.
REGULATORY ACTIONS: Reflecting this regulatory uncertainty, the European Commission on November 27 2017, extended authorization for glyphosate for another 5 years, while the European Parliament opposed this decision and issued a call that pesticide approvals be based on peer-reviewed studies by independent scientists rather than on the current system that relies on proprietary industry studies.
RAMAZZINI INSTITUTE RESPONSE: The Ramazzini Institute has initiated a pilot study of glyphosate’s health hazards that will be followed by an integrated experimental research project. This evaluation will be independent of industry support and entirely sponsored by worldwide crowdfunding. The aim of the Ramazzini Institute project is to explore comprehensively the effects of exposures to glyphosate-based herbicides at current real-world levels on several toxicological endpoints, including carcinogenicity, long-term toxicity, neurotoxicity, endocrine disrupting effects, prenatal developmental toxicity, the microbiome and multi-generational effects. FULL TEXT
Philip J. Landrigan, “Pesticides and Human Reproduction,” JAMA Internal Medicine, 2018, 178:1, DOI:10.1001/jamainternmed.2017.5092
Invited commentary by Managing Weeds for Healthy Kids science team member Dr. Landrigan reports that herbicide use has increased sharply, with glyphosate use up 250-fold from 1974 to 2014. And, “measurable levels of multiple pesticides are found in the bodies of nearly all Americans…and pesticides are capable of causing a wide range of asymptomatic effects at levels of exposure too low to produce overt signs and symptoms.” New theories suggest that long term exposure to pesticides cause this kind of subclinical toxicity. Dr. Landrigan reviews the known linkages, including in utero chlorpyrifos exposure leading to neurodevelopmental deficits, and reproductive injury including adverse birth outcomes and birth defects. He recommends: “We need to overcome the strident objections of the pesticide manufacturing industry, recognize the hidden costs of deregulation, and strengthen requirements for both premarket testing of new pesticides, as well as postmarketing surveillance of exposed populations— exactly as we do for another class of potent, biologically active molecules—drugs.” FULL TEXT
Landrigan and Benbrook, 2015
Phillip Landrigan and Charles Benbrook, “GMOs, Herbicides, and Public Health,” Commentary in New England Journal of Medicine, 2015, 373:8, DOI: 10.1056/NEJMp1505660.
Laborde et al., 2015
Laborde A, Tomasina F, Bianchi F, Bruné MN, Buka I, Comba P, Corra L, Cori L, Duffert CM, Harari R, Iavarone I, McDiarmid MA, Gray KA, Sly PD, Soares A, Suk WA, Landrigan PJ, “Children’s Health in Latin America: The Influence of Environmental Exposures,” Environmental Health Perspectives, 2015 Mar; 123(3), DOI: 10.1289/EHP.1408292.
BACKGROUND: Chronic diseases are increasing among children in Latin America.
OBJECTIVE AND METHODS: To examine environmental risk factors for chronic disease in Latin American children and to develop a strategic initiative for control of these exposures, the World Health Organization (WHO) including the Pan American Health Organization (PAHO), the Collegium Ramazzini, and Latin American scientists reviewed regional and relevant global data.
RESULTS: Industrial development and urbanization are proceeding rapidly in Latin America, and environmental pollution has become widespread. Environmental threats to children’s health include traditional hazards such as indoor air pollution and drinking-water contamination; the newer hazards of urban air pollution; toxic chemicals such as lead, asbestos, mercury, arsenic, and pesticides; hazardous and electronic waste; and climate change. The mix of traditional and modern hazards varies greatly across and within countries reflecting industrialization, urbanization, and socioeconomic forces.
CONCLUSIONS: To control environmental threats to children’s health in Latin America, WHO, including PAHO, will focus on the most highly prevalent and serious hazards—indoor and outdoor air pollution, water pollution, and toxic chemicals. Strategies for controlling these hazards include developing tracking data on regional trends in children’s environmental health (CEH), building a network of Collaborating Centres, promoting biomedical research in CEH, building regional capacity, supporting development of evidence-based prevention policies, studying the economic costs of chronic diseases in children, and developing platforms for dialogue with relevant stakeholders. FULL TEXT
John Peterson Myers, Michael N. Antoniou, Bruce Blumberg, Lynn Carroll, Theo Colborn, Lorne G. Everett, Michael Hansen, Philip J. Landrigan, Bruce P. Lanphear, Robin Mesnage, Laura N. Vandenberg, Frederick S. vom Saal, Wade V. Welshons and Charles M. Benbrook. “Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement,” Environmental Health, 2016, 15:19, DOI: 10.1186/s12940-016-0117-0.
The broad-spectrum herbicide glyphosate (common trade name “Roundup”) was first sold to farmers in 1974. Since the late 1970s, the volume of glyphosate-based herbicides (GBHs) applied has increased approximately 100-fold. Further increases in the volume applied are likely due to more and higher rates of application in response to the widespread emergence of glyphosate-resistant weeds and new, pre-harvest, dessicant use patterns. GBHs were developed to replace or reduce reliance on herbicides causing well-documented problems associated with drift and crop damage, slipping efficacy, and human health risks. Initial industry toxicity testing suggested that GBHs posed relatively low risks to non-target species, including mammals, leading regulatory authorities worldwide to set high acceptable exposure limits. To accommodate changes in GBH use patterns associated with genetically engineered, herbicide-tolerant crops, regulators have dramatically increased tolerance levels in maize, oilseed (soybeans and canola), and alfalfa crops and related livestock feeds. Animal and epidemiology studies published in the last decade, however, point to the need for a fresh look at glyphosate toxicity. Furthermore, the World Health Organization’s International Agency for Research on Cancer recently concluded that glyphosate is “probably carcinogenic to humans.” In response to changing GBH use patterns and advances in scientific understanding of their potential hazards, we have produced a Statement of Concern drawing on emerging science relevant to the safety of GBHs. Our Statement of Concern considers current published literature describing GBH uses, mechanisms of action, toxicity in laboratory animals, and epidemiological studies. It also examines the derivation of current human safety standards. We conclude that: (1) GBHs are the most heavily applied herbicide in the world and usage continues to rise; (2) Worldwide, GBHs often contaminate drinking water sources, precipitation, and air, especially in agricultural regions; (3) The half-life of glyphosate in water and soil is longer than previously recognized; (4) Glyphosate and its metabolites are widely present in the global soybean supply; (5) Human exposures to GBHs are rising; (6) Glyphosate is now authoritatively classified as a probable human carcinogen; (7) Regulatory estimates of tolerable daily intakes for glyphosate in the United States and European Union are based on outdated science. We offer a series of recommendations related to the need for new investments in epidemiological studies, biomonitoring, and toxicology studies that draw on the principles of endocrinology to determine whether the effects of GBHs are due to endocrine disrupting activities. We suggest that common commercial formulations of GBHs should be prioritized for inclusion in government-led toxicology testing programs such as the U.S. National Toxicology Program, as well as for biomonitoring as conducted by the U.S. Centers for Disease Control and Prevention. FULL TEXT
Portier et al., 2016
Christopher J Portier, Bruce K Armstrong, Bruce C Baguley, Xaver Baur, Igor Belyaev, Robert Bellé, Fiorella Belpoggi, Annibale Biggeri, Maarten C Bosland, Paolo Bruzzi, Lygia Therese Budnik, Merete D Bugge, Kathleen Burns, Gloria M Calaf, David O Carpenter, Hillary M Carpenter, Lizbeth López-Carrillo, Richard Clapp, Pierluigi Cocco, Dario Consonni, Pietro Comba, Elena Craft, Mohamed Aqiel Dalvie, Devra Davis, Paul A Demers, Anneclaire J De Roos, Jamie DeWitt, Francesco Forastiere, Jonathan H Freedman, Lin Fritschi, Caroline Gaus, Julia M Gohlke, Marcel Goldberg, Eberhard Greiser, Johnni Hansen, Lennart Hardell, Michael Hauptmann, Wei Huang, James Huff, Margaret O James, C W Jameson, Andreas Kortenkamp, Annette Kopp-Schneider, Hans Kromhout, Marcelo L Larramendy, Philip J Landrigan, Lawrence H Lash, Dariusz Leszczynski, Charles F Lynch, Corrado Magnani, Daniele Mandrioli, Francis L Martin, Enzo Merler, Paola Michelozzi, Lucia Miligi, Anthony B Miller, Dario Mirabelli, Franklin E Mirer, Saloshni Naidoo, Melissa J Perry, Maria Grazia Petronio, Roberta Pirastu, Ralph J Portier, Kenneth S Ramos, Larry W Robertson, Theresa Rodriguez, Martin Röösli, Matt K Ross, Deodutta Roy, Ivan Rusyn, Paulo Saldiva, Jennifer Sass, Kai Savolainen, Paul T J Scheepers, Consolato Sergi, Ellen K Silbergeld, Martyn T Smith, Bernard W Stewart, Patrice Sutton, Fabio Tateo, Benedetto Terracini, Heinz W Thielmann, David B Thomas, Harri Vainio, John E Vena, Paolo Vineis, Elisabete Weiderpass, Dennis D Weisenburger, Tracey J Woodruff, Takashi Yorifuji, Il Je Yu, Paola Zambon, Hajo Zeeb,Shu-Feng Zhou, “Differences in the carcinogenic evaluation of glyphosate between the International Agency for Research on Cancer (IARC) and the European Food Safety Authority (EFSA),” Journal of Epidemiology and Community Health, 2016, 0:0, DOI: 10.1136/JECH-2015-207005.
Vandenberg et al., 2017
Laura N Vandenberg, Bruce Blumberg, Michael N Antoniou, Charles M Benbrook, Lynn Carroll, Theo Colborn, Lorne G Everett, Michael Hansen, Philip J Landrigan, Bruce P Lanphear, Robin Mesnage, Frederick S vom Saal, Wade V Welshons, John Peterson Myers, “Is it time to reassess current safety standards for glyphosate-based herbicides?”, Journal of Epidemiology and Community Health, 2017, 0, DOI: 10.113/jech-2016-208463.
Use of glyphosate-based herbicides (GBHs) increased ∼100-fold from 1974 to 2014. Additional increases are expected due to widespread emergence of glyphosate-resistant weeds, increased application of GBHs, and preharvest uses of GBHs as desiccants. Current safety assessments rely heavily on studies conducted over 30 years ago. We have considered information on GBH use, exposures, mechanisms of action, toxicity and epidemiology. Human exposures to glyphosate are rising, and a number of in vitro and in vivo studies challenge the basis for the current safety assessment of glyphosate and GBHs. We conclude that current safety standards for GBHs are outdated and may fail to protect public health or the environment. To improve safety standards, the following are urgently needed: (1) human biomonitoring for glyphosate and its metabolites; (2) prioritisation of glyphosate and GBHs for hazard assessments, including toxicological studies that use state-of-the-art approaches; (3) epidemiological studies, especially of occupationally exposed agricultural workers, pregnant women and their children and (4) evaluations of GBHs in commercially used formulations, recognising that herbicide mixtures likely have effects that are not predicted by studying glyphosate alone. FULL TEXT