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Item Association between increasing agricultural use of 2,4-D and population biomarkers of exposure: findings from the National Health and Nutrition Examination Survey, 2001-2014(BMC, 2022-02-10) Freisthler, Marlaina S.; Robbins, C. Rebecca; Benbrook, Charles M.; Young, Heather A.; Haas, David M.; Winchester, Paul D.; Perry, Melissa J.; Obstetrics and Gynecology, School of MedicineBackground: 2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most extensively used herbicides in the United States. In 2012, 2,4-D was the most widely used herbicide in non-agricultural settings and the fifth most heavily applied pesticide in the US agricultural sector. The objective of this study was to examine trends in 2,4-D urinary biomarker concentrations to determine whether increases in 2,4-D application in agriculture are associated with increases in biomonitoring levels of urine 2,4-D. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) with available urine 2,4-D biomarker measurements from survey cycles between 2001 and 2014 were utilized. Urine 2,4-D values were dichotomized using the highest limit of detection (LOD) across all cycles (0.40 μg/L or 0.4 ppb). Agricultural use of 2,4-D was estimated by compiling publicly available federal and private pesticide application data. Logistic regression models adjusted for confounders were fitted to evaluate the association between agricultural use of 2,4-D and urine 2,4-D level above the dichotomization threshold. Results: Of the 14,395 participants included in the study, 4681 (32.5%) had urine 2,4-D levels above the dichotomization threshold. The frequency of participants with high 2,4-D levels increased significantly (p < .0001), from a low of 17.1% in 2001-2002 to a high of 39.6% in 2011-2012. The adjusted odds of high urinary 2,4-D concentrations associated with 2,4-D agricultural use (per ten million pounds applied) was 2.268 (95% CI: 1.709, 3.009). Children ages 6-11 years (n = 2288) had 2.1 times higher odds of having high 2,4-D urinary concentrations compared to participants aged 20-59 years. Women of childbearing age (age 20-44 years) (n = 2172) had 1.85 times higher odds than men of the same age. Conclusions: Agricultural use of 2,4-D has increased substantially from a low point in 2002 and it is predicted to increase further in the coming decade. Because increasing use is likely to increase population level exposures, the associations seen here between 2,4-D crop application and biomonitoring levels require focused biomonitoring and epidemiological evaluation to determine the extent to which rising use and exposures cause adverse health outcomes among vulnerable populations (particularly children and women of childbearing age) and highly exposed individuals (farmers, other herbicide applicators, and their families).Item Behavioral Effects of the Mixture and the Single Compounds Carbendazim, Fipronil, and Sulfentrazone on Zebrafish (Danio rerio) Larvae(MDPI, 2024-05-25) Gomes, Samara da Silva; da Silva, Jadson Freitas; Padilha, Renata Meireles Oliveira; de Vasconcelos, João Victor Alves; Neto, Luís Gomes de Negreiros; Marrs, James A.; Cadena, Pabyton Gonçalves; Biology, School of SciencePesticides are often detected in freshwater, but their impact on the aquatic environment is commonly studied based on single compounds, underestimating the potential additive effects of these mixtures. Even at low concentrations, pesticides can negatively affect organisms, altering important behaviors that can have repercussions at the population level. This study used a multi-behavioral approach to evaluate the effects of zebrafish larvae exposure to carbendazim (C), fipronil (F), and sulfentrazone (S), individually and mixed. Five behavioral tests, thigmotaxis, touch sensitivity, optomotor response, bouncing ball test, and larval exploratory behavior, were performed to assess potential effects on anxiety, fear, and spatial and social interaction. Significant changes were observed in the performance of larvae exposed to all compounds and their mixtures. Among the single pesticides, exposure to S produced the most behavioral alterations, followed by F and C, respectively. A synergistic effect between the compounds was observed in the C + F group, which showed more behavioral effects than the groups exposed to pesticides individually. The use of behavioral tests to evaluate pesticide mixtures is important to standardize methods and associate behavioral changes with ecologically relevant events, thus creating a more realistic scenario for investigating the potential environmental impacts of these compounds.Item Commentary: Novel strategies and new tools to curtail the health effects of pesticides(Springer Nature, 2021-08-03) Benbrook, Charles; Perry, Melissa J.; Belpoggi, Fiorella; Landrigan, Philip J.; Perro, Michelle; Mandrioli, Daniele; Antoniou, Michael N.; Winchester, Paul; Mesnage, Robin; Pediatrics, School of MedicineBackground: 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.Item An economic model of a genetic resistance commons: Effects of market structure applied to biotechnology in agriculture(Resources for the Future, 2003) Noonan, Douglas S.Genetic resistance resources represent an emerging class of environmental resources. These resources are the subject of increasing public interest, especially for resistance in agriculture and antibiotic use. This paper models genetic resistance resources as common-pool resources. The static model applies directly to the case of Bt corn, whose seeds are bioengineered to contain a pesticide. Firms produce an agricultural output, corn, using two inputs: Bt corn seeds and refuge areas. Production also depends on the common stock of environmental resistance. Seed use contributes to greater resistance, while refuge areas abate resistance. This costly form of abatement represents another (positive) externality, which allows for the optimal seed use to be greater than the competitive level. The use of seeds and refuge areas by other firms can be shown to be substitutes and compliments in production, respectively, for each firm. This simple model of externalities is complicated by introducing another important feature common to genetic resistance resources: monopoly supply in the biotechnology factor market. Monopoly provision of seeds, with imperfect price discrimination, leads the monopoly to act as a gatekeeper of the commons who tries to maximize its own rents rather than the rents from the resource. This divergence in interests leads to a deadweight loss as seed use is curtailed through higher monopoly prices. This equilibrium is compared to the competitive and the optimal cases. The way in which the resistance externality operates, through damaging others’ output or through affecting their marginal productivities, suggests whether the monopoly improves the efficiency of the seed market. Further consideration is given to the possibility that the monopoly determines the firms’ level of abatement. Assuming some enforcement mechanism, the monopoly chooses higher abatement levels to increase factor demand for seeds and increase its rents. The Under some plausible conditions, a monopoly supplier of the input that accesses the genetic resistance commons can be shown to actually improve welfare by mandating a higher level of care that also maximizes its profits. The distributional consequences of the different market structures are shown, noting how gains for the monopoly come at the expense of firms. In 2000, the EPA and Monsanto required purchasers of Bt corn to plant specific refuge areas in order to forestall resistance. This approach is readily extended to other cases, such as pesticides more generally or antibiotic use in the production of health services by households.Item Incipient resistance to an effective pesticide results from genetic adaptation and the canalization of gene expression(Wiley, 2020-12-14) Yin, Xiaoshen; Martinez, Alexander S.; Perkins, Abigail; Sparks, Morgan M.; Harder, Avril M.; Willoughby, Janna R.; Sepúlveda, Maria S.; Christie, Mark R.; Anatomy and Cell Biology, School of MedicineThe resistance of pest species to chemical controls has vast ecological, economic, and societal costs. In most cases, resistance is only detected after spreading throughout an entire population. Detecting resistance in its incipient stages, by comparison, provides time to implement preventative strategies. Incipient resistance can be detected by coupling standard toxicology assays with large-scale gene expression experiments. We apply this approach to a system where an invasive parasite, sea lamprey (Petromyzon marinus), has been treated with the highly effective pesticide 3-trifluoromethyl-4-nitrophenol (TFM) for 60 years. Toxicological experiments revealed that lamprey from treated populations did not have higher survival to TFM exposure than lamprey from untreated populations, demonstrating that full-fledged resistance has not yet evolved. In contrast, we find hundreds of genes differentially expressed in response to TFM in the population with the longest history of exposure, many of which relate to TFM's primary mode of action, the uncoupling of oxidative phosphorylation, and subsequent depletion of ATP. Three genes critical to oxidative phosphorylation, ATP5PB, PLCB1, and NDUFA9, were nearly fixed for alternative alleles in comparisons of SNPs between treated and untreated populations (FST > 5 SD from the mean). ATP5PB encodes subunit b of ATP synthase and an additional subunit, ATP5F1B, was canalized for high expression in treated populations, but remained plastic in response to TFM treatment in individuals from the untreated population. These combined genomic and transcriptomic results demonstrate that an adaptive, genetic response to TFM is likely driving incipient resistance in a damaging pest species.