The Health Effects of Glyphosate Exposure During Pregnancy in the Midwest

The Health Effects of Glyphosate Exposure During Pregnancy in the Midwest

Introduction

Glyphosate is one of the world’s most widely applied non-selective herbicide used to kill a wide variety of plants including “annual and perennial grasses, broadleaf weeds, trees and shrubs.” 17 In the early 1970s, Monsanto, an American agrochemical and agricultural biotechnology corporation, patented the glyphosate molecule as an active ingredient. 18 In 1974, the Environmental Protection Agency (EPA) officially registered glyphosate to the consumer market. 18 Regarding mechanisms, glyphosate herbicide inhibits 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase, “a key enzyme in the shikimic acid pathway, which is involved in the synthesis of the aromatic amino acids.” 13 As a result, EPSP inhibition depletes the aromatic amino acids essential for protein synthesis. 13

A major public health concern with widespread usage of glyphosate is that glyphosate residues can be found in the “environment, major food crops and consumed food items.” 17 Residues escape into the environment through numerous exposure pathways, harming members of surrounding communities, especially pregnant women and their fetuses. Moreover, public health studies provided evidence that exposure to glyphosate increases risks in fetal developments, most notably, by shortening gestational lengths during pregnancy. Another importance for public health studies focused on glyphosate exposure is potential long-term effects. In 2016, Dewayne Johnson, a groundskeeper who regularly utilized glyphosate, filed a lawsuit against Monsanto and their Roundup glyphosate product. Johnson claimed that two-year exposure to Roundup resulted in his diagnosis of Non-Hodgkin Lymphoma. 2

A targeted location for public health studies concerning glyphosate is the Midwest, specifically in Central Indiana. Central Indiana’s economy is centered around corn and soybean agriculture which depend on glyphosate. Furthermore, as a whole, the Midwest heavily relies on the application of glyphosate; in 2016, 188.7 million pounds of glyphosate were applied in this region. 10

This paper aims to understand the health risks of glyphosate exposure for vulnerable community members, specifically for pregnant women and their fetuses in the Midwest, and advocates for future steps to prevent glyphosate residues from infiltrating surrounding communities located near major agricultural facilities.

Exposures

Beginning with the scope of glyphosate exposure, glyphosate is most widely used on an industrial scale, introducing public health risks for its users and for surrounding community members. In the Midwest, including “Illinois, Indiana, Iowa, Kansas, Missouri, Nebraska and North Dakota, these locations contributed to 65% of the nation’s total agriculture glyphosate usage on crops.” 10 Because of their occupational roles, farmers in the Midwest are one vulnerable group directly exposed to glyphosate. Specific populations indirectly differentially vulnerable include community members close to major agricultural developments. As a result, pregnant women are a vulnerable subgroup that have been the focal point of many public health studies.

Furthermore, glyphosate has a multitude of exposure pathways ranging from “dermal contact with consumer products, crops, foliage, or soils containing residues of this chemical, ingestion of plants, crops, foods, or waters containing residues of this chemical, to inhalation of mist or spray during the use of products containing this chemical.” 1, 17

Absorption of glyphosate is composed of inhalation exposure, oral exposure, and dermal exposure. 7 Inhalation is a minor route of exposure through mist, causing oral or nasal discomfort and throat irritation. A study among 48 farmers observed increased urinary glyphosate levels after application glyphosate containing products, which reinforces evidence that inhaled glyphosate can be absorbed. 7 Oral exposure is another toxicokinetic pathway for ingested glyphosate in humans. Glyphosate in serum and urine samples were detected in the gastrointestinal tract from individuals who had ingested glyphosate containing products. 7 Lastly, dermal exposure to glyphosate causes photo-contact dermatitis and eye exposure causes conjunctivitis and corneal injury. 19

Toxicology

Toxicology studies of glyphosate originated from oral studies focused on laboratory animals’ exposure to technical grade glyphosate. Human toxicological exposures to glyphosate are studied through glyphosate herbicides and through glyphosate residues in selected foods.

To assess potential lethal dosages of glyphosate, a noncancer health effects assessment was conducted on rats following oral exposure to glyphosate. The dosages, measured in mg/kg/day, in which evident effects were found in animals, ranged from a dosage of 175 mg/kg/day to 3,000-3,500 mg/kg/day. 17 The rats were exposed to glyphosate for three durations; acute, less than 14 days, intermediate 15 to 364 days, and chronic, more than 365 days. 17 The symptoms ranged from acute symptoms including diarrhea, to chronic symptoms including decreased pH of urine and increased serum liver enzymes. 17 Increased liver weight and increased serum markers of liver effects were “observed in rats administered glyphosate technical for 13 weeks at ≥1,678 mg/kg/day.” 17 Increased specific gravity of urine and decreased urinary pH were “observed in male rats that were administered glyphosate technical for 2 years at 940 mg/kg/day.” 17

Furthermore, biomarkers have also been utilized to assess exposure and effect. Biomarkers of exposure are “chemical metabolites measured in the body or after excretion from the body to determine different characteristics of an organism's exposure.” 16 Glyphosate and the metabolite, aminomethlyphosphonic acid (AMPA), can be measured in both blood and urine. However, most absorbed glyphosate is rapidly excreted as a parent compound. Meaningful quantification of exposure would “require analysis of blood and/or urine within hours following exposure.” 17

Regarding human toxicological exposures to glyphosate, Professor Sophie Richard analyzed the differential effects of glyphosate on Human Placental Cells and Aromatase. Richard concluded that glyphosate is “toxic to human placental JEG3 cells within 18 hours with concentrations lower than those found with agricultural use.” 14 Richard proceeded to assess the relationship between the effects of glyphosate on aromatase, an enzyme responsible for estrogen synthesis. After 18 hours of incubation in 0.04% of Roundup, “aromatase activity was inhibited because of decreased mRNA levels, reducing aromatase gene expression.” 14 Both placental cells and estrogen synthesis are essential during the stages of pregnancy. The placenta protects the fetus against “certain xenobiotic molecules, infections and maternal diseases.” 14 Furthermore, corpus luteum in the maternal ovaries “synthesizes estrogen to prevent rejection of the developing embryo and enables the provision of essential nutrients for the embryo’s growth.” 14

Moreover, the EPA identified the EPA's Reference Dose for glyphosate as 2 milligrams per kilogram of body weight. For an average adult weighing 70 kilograms, the total reference dose is 140 milligrams a day. 5 On June 26, 2017, Office of Environmental Health Hazard Assessment (OEHHA) issued a proposed amendment to California's No Significant Risk Level (NSRL). The NSRL is the “exposure of the amount of chemical in a product would result in no more than one case of cancer out of every 100,000 individuals who were exposed to the chemical over a 70-year time period.” 6 However, OEHHA identified a NSRL of 1.1 milligrams per day for glyphosate. 7 This discrepancy in glyphosate exposure values is alarming and draws attention to human exposures, in particular for epidemiological studies focused on pregnant women and their fetuses.

Epidemiology

Glyphosate epidemiology studies have primary targeted the distribution and determinants of glyphosate in pregnant women living within proximity of major agricultural developments in the Midwest. The epidemiology study design for the “Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study” focused on 77 pregnant women from ages 18 to 40. Participants were recruited from an “obstetrician at a private obstetrical practice in Central Indiana from June 2015 to June 2016.” 12 Researchers designed a “prospective birth-cohort study to test the hypothesis that glyphosate can be directly measured in the urine of most pregnant women from their diet and that higher glyphosate levels in pregnancy will correlate with adverse fetal outcomes.” 12

93% of the pregnant women had “glyphosate levels above the limit of detection (0.1 ng/mL).” 12 Pregnant women who lived in rural areas had significantly higher urinary glyphosate levels compared to pregnant women who lived in suburban areas. Furthermore, the majority of participants were not farmers and thus did not have direct exposure through applying glyphosate on agricultural crops. Thus, this finding suggests the “inhalation of contaminated air or dust may represent another exposure pathway for higher urine glyphosate levels in rural areas.” 12 Likewise, researchers did not detect any glyphosate residues in the drinking water, eliminating drinking water as a possible glyphosate exposure pathway for the Indiana birth cohort. Moreover, researchers found no correlation between glyphosate urine levels and fetal growth indicators such as birth weight percentile and head circumference. However, higher glyphosate urine levels were significantly correlated with shortened gestational lengths. The Central Indiana study is an essential study because “this is the first US study designed to measure prenatal glyphosate exposure in pregnant women to determine its association with adverse fetal developmental risk.” 12

Moreover, high rate of detection of glyphosate in the Central Indiana study is comparable to detection rates in a congruent glyphosate study conducted in Iowa. The study focused on “47 fathers, 48 mothers and 117 children of Iowa farm and non-farm households who were recruited to participate in a study investigating take-home pesticide exposure.” 4 Similar to the Central Indiana epidemiology methodology, researchers collected two urine sample from each participant and additionally collected “dust samples from various rooms from each household to analyze for atrazine, metolachlor, glyphosate and chlorpyrifos or their metabolites.” 4 Both studies had comparable detection rates as the reported detection rate in the Iowa study “where the frequencies of glyphosate detection in farm, non-farm, father, mother, and children were reported between 65% and 88%.” 4

The Central Indiana epidemiology study reinforces the suggestion that “pesticide exposure in pregnancy may be correlated with gestational length, as well as adverse fetal growth.” 12 The importance of this study is that shortened gestational lengths can lead to life-long adverse health consequences for fetal offspring, most notably reducing lifetime cognitive achievements.

Risk Assessment

In order to conduct a more comprehensive risk assessment of glyphosate, data gaps first must be addressed. One general limitation for current glyphosate studies is that oral studies in animals indicate that “glyphosate technical toxicity is expressed only at oral dose levels many times higher than levels allowed as residues in food products.” 17 Thus, drawing statistical connections between animal studies and human exposure to glyphosate must accurately reflect parameters such as body weight and exposure amount. Regarding the Central Indiana study, many limitations imply the need for further toxicological and epidemiology studies to address data gaps. The birth cohort was “small, and of limited racial, age, and geographic diversity and…limited the ability to generalize these findings to a more diverse population.” 12 Since the majority of participants were Caucasian, other factors such as race can have “significant effects on gestational length and birth weight and additional data from ethnically diverse groups would be required before our findings could be generalized.” 12

In terms of current governmental regulation, the U.S Food and Drug Administration (FDA) has important roles in monitoring glyphosate residues. The FDA’s role is “to ensure that pesticide chemical residues on or in domestic and imported foods do not exceed the limits established by the EPA.” 11 The FDA has recently developed a streamlined selective residue method (SRM) to test for glyphosate residues. From 2016 to 2017, the FDA began “preliminary testing of samples of soybeans, corn, milk, and eggs for glyphosate residues.” 11 Of the 879 corn, soybean, milk, and egg samples tested for glyphosate, “approximately 59% of the corn and soy samples tested positive for residues of glyphosate, but all were below the tolerance levels set by the EPA.” 11 The tolerance levels for glyphosate residues range from 0.1 ppm (parts per million) for corn to 20 ppm for seed soybeans. 3 Though the residues of glyphosate were tested to be below the tolerance levels set by the EPA, to ensure continuous risk management and safety for consumers, the FDA must conduct standard routine assessments of glyphosate residues on a greater range of agricultural crops and ensure testing results are publicly available and easily accessible.

However, one major barrier in risk management is that the EPA “continues to find that there are no risks to public health when glyphosate is used in accordance with its current label and that glyphosate is not a carcinogen.” 18 Instead, the EPA has chosen to focus on ecological risks by “proposing management measures to help farmers target pesticide sprays on the intended pest, protect pollinators, and reduce the problem of weeds becoming resistant to glyphosate.” 18 However, in March 2015, the International Agency for Research on Cancer (IARC) classified glyphosate as “probably carcinogenic to humans.” 9  The discrepancy in findings between two major governmental organizations implies the need for more glyphosate studies to definitively conclude whether glyphosate is truly carcinogenic.

However, there are various preventive practices that community members can adopt in their lifestyles to reduce personal exposure to glyphosate. Individuals can purchase certified organic food, as glyphosate is prohibited on some organic crops, or they can eat locally grown whole foods. 14 Consuming local food reduces the risk of products being contaminated with conventional ingredients exposed to glyphosate along the supply chain. 14 For individuals living within close proximity to major agricultural developments that utilize glyphosate, it is important to reduce personal exposure by taking precautionary safety measures such as wearing long-sleeved plants and shirts or breathing masks. However, it is important to acknowledge the environmental injustice congruent with reducing personal exposure to glyphosate. Not every individual can afford to eat locally sourced organic foods or have the time to research which food crops have the lowest and highest exposures to glyphosate. Furthermore, reducing outside exposure time is not applicable to community members who are required to physically work in the agricultural fields where glyphosate is applied. The personal risk assessments are merely potential recommendations, but major systematic government policies must be enforced to reduce the risk for glyphosate residue contamination on surrounding community members.

Conclusion

Though various epidemiological studies provide evidence between maternal glyphosate exposure and a shortened pregnancy gestational length and toxicological studies note lethal dosages of glyphosate, there must be further investigations that encompass a more geographically and racially diverse cohort and ethical studies focused on human exposure to glyphosate.

From the results in both the Central Indiana and Iowa, the high rate of detection of glyphosate draws major concerns for potential life-long adverse consequences, most notably the reduction in lifetime cognitive achievement for fetuses.  However, the major hinderance of implementing greater glyphosate residue risk assessment is the conflicting findings between the EPA and the IARC. Preventive long-term solutions must be properly assessed once and if glyphosate is unanimously concluded as a carcinogenic compound. Based on the results from current studies, the potential harmful effects on pregnant women can lead to generational effects for the development of their offspring and thus action must be taken now to ensure a safer and healthier future for the next generation.

Works Cited

1. Benbrook, Charles M. “Impacts of Genetically Engineered Crops on Pesticide Use in the U.S. the First Sixteen Years.” Environmental Sciences Europe 24, no. 1 (September 28, 2012): 24. https://doi.org/10.1186/2190-4715-24-24.
2. Bradberry, SM. Proudfoot AT. “Glyphosate Poisoning” National Poisons Information Service (Birmingham Centre) and West Midlands Poisons Unit, City Hospital, Birmingham, UK. Toxicological Reviews 23, no. 3 (2004): 159–67. https://doi.org/10.2165/00139709-200423030-00003.

1. “Code of Federal Regulations 180.364 - Glyphosate; Tolerances for Residues. - Content Details - CFR-2010-Title40-Vol23-Sec180-364.” Accessed November 11, 2019. https://www.govinfo.gov/app/details/CFR-2010-title40-vol23/CFR-2010-title40-vol23-sec180-364
2. Curwin, Brian D., Misty J. Hein, Wayne T. Sanderson, Cynthia Striley, Dick Heederik, Hans Kromhout, Stephen J. Reynolds, and Michael C. Alavanja. “Urinary Pesticide Concentrations Among Children, Mothers and Fathers Living in Farm and Non-Farm Households in Iowa.” The Annals of Occupational Hygiene 51, no. 1 (January 1, 2007): 53–65. https://doi.org/10.1093/annhyg/mel062.
3. Environmental Working Group. “Calif. to Issue First Health Guideline for Carcinogenic Glyphosate.” Accessed November 11, 2019. https://www.ewg.org/research/california-proposes-safe-level-roundup-more-100-times-lower-epa-limit
4. Findlaw. “California Code, Health and Safety Code - HSC § 25249.10.” Accessed November 11, 2019. https://codes.findlaw.com/ca/health-and-safety-code/hsc-sect-25249-10.html.
5. Gillezeau, Christina, Maaike van Gerwen, Rachel M. Shaffer, Iemaan Rana, Luoping Zhang, Lianne Sheppard, and Emanuela Taioli. “The Evidence of Human Exposure to Glyphosate: A Review.” Environmental Health 18 (January 7, 2019). https://doi.org/10.1186/s12940-018-0435-5.
6. “Glyphosate General Fact Sheet.” NPIC National Pesticide Information Center. March 2019. Accessed November 11, 2019. http://npic.orst.edu/factsheets/glyphogen.html.
7. “International Agency for Research on Cancer World Health Organization Monograph on Glyphosate – IARC.” International Agency for Research on Cancer World Health Organization. Accessed November 11, 2019. https://www.iarc.fr/featured-news/media-centre-iarc-news-glyphosate/.
8. Midwest Center for Investigative. “By The Numbers: Glyphosate Use In The Midwest For Corn, Soybeans.” Accessed November 11, 2019 https://www.harvestpublicmedia.org/post/numbers-glyphosate-use-midwest-corn-soybeans.
9. Nutrition, Center for Food Safety and Applied. “Questions and Answers on Glyphosate.” FDA, September 13, 2019. http://www.fda.gov/food/pesticides/questions-and-answers-glyphosate.
10. Parvez, S., Gerona, R. R., Proctor, C., Friesen, M., Ashby, J. L., Reiter, J. L., … Winchester, P. D. (2018). Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study. Environmental health: a global access science source, 17(1), 23. doi:10.1186/s12940-018-0367-0
11. Resources, University of California, Division of Agriculture and Natural. “EPSP Synthase Inhibitors.” Accessed November 11, 2019. http://herbicidesymptoms.ipm.ucanr.edu/MO
12. Richard, Sophie et al. “Differential effects of glyphosate and roundup on human placental cells and aromatase.” Environmental health perspectives vol. 113,6 (2005): 716-20. doi:10.1289/ehp.7728. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1257596/
13. Rodale Institute. “How to Avoid Exposure to Glyphosate, the World’s Most Common Weedkiller,” February 11, 2019. https://rodaleinstitute.org/blog/how-to-avoid-exposure-to-glyphosate-the-worlds-most-common-weedkiller/.
14. Tarazona, J. V., Court-Marques, D., Tiramani, M., Reich, H., Pfeil, R., Istace, F., & Crivellente, F. (2017). Glyphosate toxicity and carcinogenicity: a review of the scientific basis of the European Union assessment and its differences with IARC. Archives of toxicology, 91(8), 2723–2743. doi:10.1007/s00204-017-1962-5
15. United States Department of Health and Human Services. “Toxicological Profile for Glyphosate.”ATSDR, 2019. Web. Accessed November 5, 2019. https://www.epa.gov/ingredients-used-pesticide-products/glyphosate
16. United States Environmental Protection Agency, Office of Chemical Safety and Pollution. “Environmental Protection Agency Releases Draft Risk Assessments for Glyphosate.” Announcements and Schedules. United States Environmental Protection Agency, December 18, 2017. https://www.epa.gov/pesticides/epa-releases-draft-risk-assessments-glyphosate
17. United States Environmental Protection Agency. Office of Chemical Safety and Pollution. “Glyphosate.” Overviews and Factsheets. United States Environmental Protection Agency, September 18, 2014. https://www.epa.gov/ingredients-used-pesticide-products/glyphosate.

Teleken JL, Gomes ECZ,

Marmentini C, Moi MB, Ribeiro RA, Balbo SL,

Amorim EMP, and Bonfleur ML. Glyphosate-

based herbicide exposure during pregnancy

and lactation malprograms the male

reproductive morphofunction in F1 offspring.

Journal of Developmental Origins of Health and

Disease

Teleken JL, Gomes ECZ,

Marmentini C, Moi MB, Ribeiro RA, Balbo SL,

Amorim EMP, and Bonfleur ML. Glyphosate-

based herbicide exposure during pregnancy

and lactation malprograms the male

reproductive morphofunction in F1 offspring.

Journal of Developmental Origins of Health and

Disease

Teleken JL, Gomes ECZ,

Marmentini C, Moi MB, Ribeiro RA, Balbo SL,

Amorim EMP, and Bonfleur ML. Glyphosate-

based herbicide exposure during pregnancy

and lactation malprograms the male

reproductive morphofunction in F1 offspring.

Journal of Developmental Origins of Health and

Disease

Teleken JL, Gomes ECZ,

Marmentini C, Moi MB, Ribeiro RA, Balbo SL,

Amorim EMP, and Bonfleur ML. Glyphosate-

based herbicide exposure during pregnancy

and lactation malprograms the male

reproductive morphofunction in F1 offspring.

Journal of Developmental Origins of Health and

Disease

Teleken JL, Gomes ECZ,

Marmentini C, Moi MB, Ribeiro RA, Balbo SL,

Amorim EMP, and Bonfleur ML. Glyphosate-

based herbicide exposure during pregnancy

and lactation malprograms the male

reproductive morphofunction in F1 offspring.

Journal of Developmental Origins of Health and

Disease

Glyphosate-based herbicide exposure during

pregnancy and lactation malprograms the male

reproductive morphofunction in F1 offspring