Dietary Risk - HH-RA.org

Bibliography Tag: dietary risk

Benbrook, 2019

Benbrook, Charles M., “How did the US EPA and IARC reach diametrically opposed conclusions on the genotoxicity of glyphosate-based herbicides?,” Environmental Sciences Europe, 2019, 31(1), DOI:10.1186/s12302-018-0184-7.

ABSTRACT:

BACKGROUND: The US EPA considers glyphosate as “not likely to be carcinogenic to humans.” The International Agency for Research on Cancer (IARC) has classified glyphosate as “probably carcinogenic to humans (Group 2A).” EPA asserts that there is no convincing evidence that “glyphosate induces mutations in vivo via the oral route.” IARC concludes there is “strong evidence” that exposure to glyphosate is genotoxic through at least two mechanisms known to be associated with human carcinogens (DNA damage, oxidative stress). Why and how did EPA and IARC reach such different conclusions?

RESULTS: A total of 52 genotoxicity assays done by registrants were cited by the EPA in its 2016 evaluation of technical glyphosate, and another 52 assays appeared in the public literature. Of these, one regulatory assay (2%) and 35 published assays (67%) reported positive evidence of a genotoxic response. In the case of formulated, glyphosatebased herbicides (GBHs), 43 regulatory assays were cited by EPA, plus 65 assays published in peer-reviewed journals. Of these, none of the regulatory, and 49 published assays (75%) reported evidence of a genotoxic response following exposure to a GBH. IARC considered a total of 118 genotoxicity assays in six core tables on glyphosate technical, GBHs, and aminomethylphosphonic acid (AMPA), glyphosate’s primary metabolite. EPA’s analysis encompassed 51 of these 118 assays (43%). In addition, IARC analyzed another 81 assays exploring other possible genotoxic mechanisms (mostly related to sex hormones and oxidative stress), of which 62 (77%) reported positive results. IARC placed considerable weight on three positive GBH studies in exposed human populations, whereas EPA placed little or no weight on them.

CONCLUSIONS: EPA and IARC reached diametrically opposed conclusions on glyphosate genotoxicity for three primary reasons: (1) in the core tables compiled by EPA and IARC, the EPA relied mostly on registrant-commissioned, unpublished regulatory studies, 99% of which were negative, while IARC relied mostly on peer-reviewed studies of which 70% were positive (83 of 118); (2) EPA’s evaluation was largely based on data from studies on technical glyphosate, whereas IARC’s review placed heavy weight on the results of formulated GBH and AMPA assays; (3) EPA’s evaluation was focused on typical, general population dietary exposures assuming legal, food-crop uses, and did not take into account, nor address generally higher occupational exposures and risks. IARC’s assessment encompassed data from typical dietary, occupational, and elevated exposure scenarios. More research is needed on real-world exposures to the chemicals within formulated GBHs and the biological fate and consequences of such exposures. FULL TEXT

Mills et al., 2017

Paul J. Mills, PhD, Izabela Kania-Korwel, PhD, John Fagan, PhD, Linda K.McEvoy, PhD, Gail A. Laughlin, PhD, Elizabeth Barrett-Connor, MD, “Excretion of the Herbicide Glyphosate in Older Adults Between 1993 and 2016,” October 24, 2017, Journal of the American Medical Association, 318:16, DOI:10.1001/jama.2017.11726.

ABSTRACT:

The herbicide Roundup is sprayed onto genetically modified crops and applied as a desiccant to most small non–genetically modified grains. Use of this herbicide has increased since 1994 when genetically modified crops were introduced in the United States. Glyphosate, the primary ingredient in the herbicide, is found in these crops at harvest. Environmental exposure through dietary intake of these crops has potential adverse health effects and can be assessed by measuring urinary excretion. We measured excretion levels of glyphosate and its metabolite aminomethylphosphonic acid (AMPA) in participants fromthe Rancho Bernardo Study (RBS) of Healthy Aging. Mean glyphosate and AMPA levels and the proportion of samples with detectable levels increased over time. FULL TEXT

EPA, 1992b

Environmental Protection Agency, December 15, 1992, “Dietary Exposure Analysis for Glyphosate in Support of the Reregistration Eligibility Document,” Office of Pesticides and Toxic Substances.

SUMMARY:

Memo provides a Dietary Risk Evaluation System for glyphosate as part of the reregistration process. This document confirms that EPA has changed the RfD to 2.0 mg/kg/day. FULL TEXT

EPA, 1989

Environmental Protection Agency, January 30, 1989, Memo on petition to increase glyphosate tolerances on soybeans, Office of Pesticides and Toxic Substances, Dietary Exposure Branch.

SUMMARY:

In this memo, the Dietary Exposure Branch recommends approving Monsanto’s petition to raise tolerances for soybeans to 20 ppm from 6 ppm, soybean straw from 15 to 200 ppm, and soybean hulls from 20 to 100 ppm. FULL TEXT

Donauer et al., 2016

Donauer, Stephanie, Mekibib Altaye, Yingying Xu, Heidi Sucharew, Paul Succop, Antonia M. Calafat, Jane C. Khoury, Bruce Lanphear, Kimberly Yolton, “An Observational Study to Evaluate Associations Between Low-Level Gestational Exposure to Organophosphate Pesticides and Cognition During Early Childhood,” American Journal of Epidemiology, 2016, 184:5.

ABSTRACT:

Prenatal exposure to organophosphate pesticides, which is ubiquitous, may be detrimental to neurological development. We examined 327 mother/infant pairs in Cincinnati, Ohio, between 2003 and 2006 to determine associations between prenatal exposure to organophosphate pesticides and neurodevelopment. Twice during pregnancy urinary concentrations of 6 common dialkylphosphates, nonspecific metabolites of organophosphate pesticides, were measured. Aggregate concentrations of diethylphosphates, dimethylphosphates, and total dialkylphosphates were calculated. Bayley Scales of Infant Development, Second Edition-Mental and Psychomotor Developmental indices were administered at ages 1, 2, and 3 years, the Clinical Evaluation of Language Fundamentals-Preschool, Second Edition, at age 4, and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, at age 5. Mothers with higher urinary total dialkylphosphate concentrations reported higher levels of socioeconomic status and increased fresh fruit and vegetable intake. We found no associations between prenatal exposure to organophosphate pesticides and cognition at 1-5 years of age. In our cohort, exposure to organophosphate pesticides during pregnancy was not associated with cognition during early childhood. It is possible that a higher socioeconomic status and healthier diet may protect the fetus from potential adverse associations with gestational organophosphate pesticide exposure, or that dietary exposure to the metabolites is innocuous and not an ideal measure of exposure to the parent compound.

Vogt et al., 2012

Vogt R, Cassady D, Frost J, Bennett DH, Hertz-Picciotto I, “An assessment of exposures to toxins through diet among California residents,” Environmental Health, 2012;11:83.

ABSTRACT:

BACKGROUND: In the absence of current cumulative dietary exposure assessments, this analysis was conducted to estimate exposure to multiple dietary contaminants for children, who are more vulnerable to toxic exposure than adults.

METHODS: We estimated exposure to multiple food contaminants based on dietary data from preschool-age children (2-4 years, n=207), schoolage children (5-7 years, n=157), parents of young children (n=446), and older adults (n=149). We compared exposure estimates for eleven toxic compounds (acrylamide, arsenic, lead, mercury, chlorpyrifos, permethrin, endosulfan, dieldrin, chlordane, DDE, and dioxin) based on selfreported food frequency data by age group. To determine if cancer and non-cancer benchmark levels were exceeded, chemical levels in food were derived from publicly available databases including the Total Diet Study.

RESULTS: Cancer benchmark levels were exceeded by all children (100%) for arsenic, dieldrin, DDE, and dioxins. Non-cancer benchmarks were exceeded by >95% of preschool-age children for acrylamide and by 10% of preschool-age children for mercury. Preschool-age children had significantly higher estimated intakes of 6 of 11 compounds compared to school-age children (p<0.0001 to p=0.02). Based on self-reported dietary data, the greatest exposure to pesticides from foods included in this analysis were tomatoes, peaches, apples, peppers, grapes, lettuce, broccoli, strawberries, spinach, dairy, pears, green beans, and celery.

CONCLUSIONS: Dietary strategies to reduce exposure to toxic compounds for which cancer and non-cancer benchmarks are exceeded by children vary by compound. These strategies include consuming organically produced dairy and selected fruits and vegetables to reduce pesticide intake, consuming less animal foods (meat, dairy, and fish) to reduce intake of persistent organic pollutants and metals, and consuming lower quantities of chips, cereal, crackers, and other processed carbohydrate foods to reduce acrylamide intake.

FULL TEXT

Niemann et al., 2015

Niemann L, Sieke C, Pfeil R, Solecki R., “A critical review of glyphosate findings in human urine samples and comparison with the exposure of operators and consumers,” 2015, Journal of Consumer Protection and Food Safety, 10: 3-12, DOI: 10.1007/s00003-014-0927-3.

ABSTRACT: For active substances in plant protection products (PPP) with well defined urinary elimination, no potential for accumulation and virtually no metabolism, measuring of urine levels could be a powerful tool for human biomonitoring. Such data may provide reliable estimates of actual internal human exposure that can be compared to appropriate reference values, such as the ‘acceptable daily intake (ADI)’ or the ‘acceptable operator exposure level (AOEL)’. Traces of the active compound glyphosate were found in human urine samples, probably resulting either from occupational use for plant protection purposes or from dietary intake of residues. A critical review and comparison of data obtained in a total of seven studies from Europe and the US was performed. The conclusion can be drawn that no health concern was revealed because the resulting exposure estimates were by magnitudes lower than the ADI or the AOEL. The expected internal exposure was clearly below the worst-case predictions made in the evaluation of glyphosate as performed for the renewal of its approval within the European Union. However, differences in the extent of exposure with regard to the predominant occupational and dietary exposure routes and between Europe and North America became apparent. FULL TEXT

Jensen et al., 2016

Jensen PK, Wujcik CE, McGuire MK, McGuire MA, “Validation of reliable and selective methods for direct determination of glyphosate and aminomethylphosphonic acid in milk and urine using LC-MS/MS,” Journal of Environmental Science and Health – Part B, 2016, 51:4, DOI: 10.1080/03601234.2015.1120619.

ABSTRACT:

Simple high-throughput procedures were developed for the direct analysis of glyphosate [N-(phosphonomethyl)glycine] and aminomethylphosphonic acid (AMPA) in human and bovine milk and human urine matrices. Samples were extracted with an acidified aqueous solution on a high-speed shaker. Stable isotope labeled internal standards were added with the extraction solvent to ensure accurate tracking and quantitation. An additional cleanup procedure using partitioning with methylene chloride was required for milk matrices to minimize the presence of matrix components that can impact the longevity of the analytical column. Both analytes were analyzed directly, without derivatization, by liquid chromatography tandem mass spectrometry using two separate precursor-to-product transitions that ensure and confirm the accuracy of the measured results. Method performance was evaluated during validation through a series of assessments that included linearity, accuracy, precision, selectivity, ionization effects and carryover. Limits of quantitation (LOQ) were determined to be 0.1 and 10 µg/L (ppb) for urine and milk, respectively, for both glyphosate and AMPA. Mean recoveries for all matrices were within 89-107% at three separate fortification levels including the LOQ. Precision for replicates was ≤ 7.4% relative standard deviation (RSD) for milk and ≤ 11.4% RSD for urine across all fortification levels. All human and bovine milk samples used for selectivity and ionization effects assessments were free of any detectable levels of glyphosate and AMPA. Some of the human urine samples contained trace levels of glyphosate and AMPA, which were background subtracted for accuracy assessments. Ionization effects testing showed no significant biases from the matrix. A successful independent external validation was conducted using the more complicated milk matrices to demonstrate method transferability. FULL TEXT

Defarge et al., 2016

Defarge N, Takács E, Lozano VL, Mesnage R, Spiroux de Vendômois J, Séralini GE, Székács A, “Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels,” International Journal of Environmental Research and Public Health, 2016, 13:3.

ABSTRACT:

Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH), the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18-2000 times for co-formulants, 8-141 times for formulations), and not the declared active ingredient glyphosate (G) alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine-POEA and alkyl polyglucoside-APG) and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI) value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone. FULL TEXT

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