Bibliography Tag: analytical methods

Kutz et al., 1992

Kutz, F. W., Cook, B. T., Carter-Pokras, O. D., Brody, D., & Murphy, R. S.; “Selected pesticide residues and metabolites in urine from a survey of the U.S. general population;” Journal of Toxicology and Environmental Health, 1992, 37(2), 277-291; DOI: 10.1080/15287399209531670.


Residues of toxic chemicals in human tissues and fluids can be important indicators of exposure. Urine collected from a subsample of the second National Health and Nutrition Examination Survey was analyzed for organochlorine, organophosphorus, and chlorophenoxy pesticides or their metabolites. Urine concentration was also measured. The most frequently occurring residue in urine was pentachlorophenol (PCP), found in quantifiable concentrations in 71.6% of the general population with an estimated geometric mean level of 6.3 ng/ml. Percent quantifiable levels of PCP were found to be highest among males. Quantifiable concentrations of 3,5,6-trichloro-2-pyridinol (5.8%), 2,4,5-trichlorophenol (3.4%), para-nitrophenol (2.4%), dicamba (1.4%), malathion dicarboxylic acid (0.5%), malathion alpha-monocarboxylic acid (1.1%), and 2,4-D (0.3%) were found, but at much lower frequencies. No quantifiable levels of 2,4,5-T or silvex were found. Preliminary analyses showed an apparent relationship between residue concentration and two measures of urine concentration (osmolality and creatinine). A large segment of the general population of the United States experienced exposure to certain pesticides, including some considered biodegradable, during the years 1976-1980. FULL TEXT

Bienvenu et al., 2021

Bienvenu, J. F., Belanger, P., Gaudreau, E., Provencher, G., & Fleury, N.; “Determination of glyphosate, glufosinate and their major metabolites in urine by the UPLC-MS/MS method applicable to biomonitoring and epidemiological studies;” Analytical and Bioanalytical Chemistry, 2021; DOI: 10.1007/s00216-021-03194-x.


The preoccupation concerning glyphosate (GLYP) has rapidly grown over recent years, and the availability of genetically modified crops that are resistant to GLYP or glufosinate (GLUF) has increased the use of these herbicides. The debate surrounding the carcinogenicity of GLYP has raised interest and the desire to gain information on the level of exposure of the population. GLYP and aminomethylphosphonic acid (AMPA) are commonly simultaneously analysed. GLUF is sometimes also monitored, but its major metabolite, 3-[hydroxy(methyl)phosphinoyl]propionic acid (3MPPA), is rarely present in the method. Using a pentafluorobenzyl derivative to extract the analytes from human urine, we present a method that contains four important analytes to monitor human exposure to GLYP and GLUF. The use of the flash freeze technique speeds up the extraction process and requires less organic solvent than conventional liquid-liquid extraction. The limits of detection in the low mug/L range enable the use of this method for epidemiological studies. The results obtained for 35 volunteers from the Quebec City area are presented with the results from multiple interlaboratory comparisons (G-EQUAS, HBM4EU and OSEQAS). This methodology is currently being used in the Maternal-Infant Research on Environmental Chemicals (MIREC-ENDO) study and in the Canadian Health Measures Survey (CHMS).


Bakke et al., 2009

Bakke, B., De Roos, A. J., Barr, D. B., Stewart, P. A., Blair, A., Freeman, L. B., Lynch, C. F., Allen, R. H., Alavanja, M. C., & Vermeulen, R.; “Exposure to atrazine and selected non-persistent pesticides among corn farmers during a growing season;” Journal of Exposure Science & Environmental Epidemiology, 2009, 19(6), 544-554; DOI: 10.1038/jes.2008.53.


The aim was to develop quantitative estimates of farmers’ pesticide exposure to atrazine and to provide an overview of background levels of selected non-persistent pesticides among corn farmers in a longitudinal molecular epidemiologic study. The study population consisted of 30 Agricultural Health Study farmers from Iowa and 10 non-farming controls. Farmers completed daily and weekly diaries from March to November in 2002 and 2003 on pesticide use and other exposure determinants. Urine samples were collected at 10 time points relative to atrazine application and other farming activities. Pesticide exposure was assessed using urinary metabolites and diaries. The analytical limit of detection (LOD) ranged between 0.1 and 0.2 microg/l for all pesticide analytes except for isazaphos (1.5 microg/l) and diazinon (0.7 microg/l). Farmers had higher geometric mean urinary atrazine mercapturate (AZM) values than controls during planting (1.1 vs <LOD microg/g creatinine; P<0.05). AZM levels among farmers were significantly related to the amount of atrazine applied (P=0.015). Interestingly, farmers had a larger proportion of samples above the LOD than controls even after exclusion of observations with an atrazine application within 7 days before urine collection (38% vs 6%, P<0.0001). A similar pattern was observed for 2,4-D and acetochlor (92% vs 47%, P<0.0001 and 45% vs 4%, P<0.0001, respectively). Urinary AZM levels in farmers were largely driven by recent application of atrazine. Therefore, the amount of atrazine applied is likely to provide valid surrogates of atrazine exposure in epidemiologic studies. Elevated background levels of non-persistent pesticides, especially 2,4-D, indicate importance in epidemiologic studies of capturing pesticide exposures that might not be directly related to the actual application.


Aylward et al., 2010

Aylward, Lesa L., Morgan, Marsha K., Arbuckle, Tye E., Barr, Dana B., Burns, Carol J., Alexander, Bruce H., & Hays, Sean M.; “Biomonitoring data for 2,4-dichlorophenoxyacetic acid in the United States and Canada: Interpretation in a public health risk assessment context using biomonitoring equivalents;” Environmental Health Perspectives, 2010, 118, 177-181; DOI: 10.1289/ehp.0900970.


BACKGROUND: Several extensive studies of exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) using urinary concentrations in samples from the general population, farm applicators, and farm family members are now available. Reference doses (RfDs) exist for 2,4-D, and Biomonitoring Equivalents (BEs; concentrations in urine or plasma that are consistent with those RfDs) for 2,4-D have recently been derived and published.

OBJECTIVE: We reviewed the available biomonitoring data for 2,4-D from the United States and Canada and compared them with BE values to draw conclusions regarding the margin of safety for 2,4-D exposures within each population group.

DATA SOURCES: Data on urinary 2,4-D excretion in general and target populations from recent published studies are tabulated and the derivation of BE values for 2,4-D summarized.

DATA SYNTHESIS: The biomonitoring data indicate margins of safety (ratio of BE value to biomarker concentration) of approximately 200 at the central tendency and 50 at the extremes in the general population. Median exposures for applicators and their family members during periods of use appear to be well within acute exposure guidance values.

CONCLUSIONS: Biomonitoring data from these studies indicate that current exposures to 2,4-D are below applicable exposure guidance values. This review demonstrates the value of biomonitoring data in assessing population exposures in the context of existing risk assessments using the BE approach. Risk managers can use this approach to integrate the available biomonitoring data into an overall assessment of current risk management practices for 2,4-D.



Benbrook and Benbrook, 2021

Benbrook, Charles, & Benbrook, Rachel (2021). “A minimum data set for tracking changes in pesticide use.” In R. Mesnage & J. Zaller (Eds.), Herbicides: Elsevier and RTI Press.


A frequently asked but deceptively simple question often arises about pesticide use on a given farm or crop: Is pesticide use going up, down, or staying about the same? Where substantial changes in pesticide use are occurring, it is also important to understand the factors driving change. These might include more or fewer hectares planted, a change in the crop mix, a higher or lower percentage of hectares treated, or higher or lower rates of application and/or number of applications. Or, it might arise from a shift to other pesticides applied at a higher or lower rate and/or lessened or greater reliance on nonpesticidal strategies and integrated pest management (IPM). Questions about whether pesticide use is changing and why arise for a variety of reasons. Rising use typically increases farmer costs and cuts into profit margins. It generally raises the risk of adverse environmental and/or public health outcomes. It can accelerate the emergence and spread of organisms resistant to applied pesticides. If the need to spray more continues year after year for long enough, farming systems become unsustainable. Lessened reliance on and use of pesticides, on the other hand, are typically brought about and can only be sustained by incrementally more effective prevention-based biointensive IPM systems (bioIPM).1–3 Fewer pesticide applications and fewer pounds/kilograms of active ingredient applied reduce the impacts on nontarget organisms and provide space for beneficial organisms and biodiversity to flourish. Such systems reduce the odds of significant crop loss in years when conditions undermine the efficacy of control measures, leading to spikes in pest populations and the risk of economically meaningful loss of crop yield and/or quality. FULL TEXT

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.


Costello et al., 2009

Costello S, Cockburn M, Bronstein J, Zhang X, Ritz B; “Parkinson’s disease and residential exposure to maneb and paraquat from agricultural applications in the central valley of California.” American Journal of Epidemiology. 2009 Apr 15;169(8):919-26. DOI: 10.1093/aje/kwp006.
Evidence from animal and cell models suggests that pesticides cause a neurodegenerative process leading to Parkinson’s disease (PD). Human data are insufficient to support this claim for any specific pesticide, largely because of challenges in exposure assessment. The authors developed and validated an exposure assessment tool based on geographic information systems that integrated information from California Pesticide Use Reports and land-use maps to estimate historical exposure to agricultural pesticides in the residential environment. In 1998-2007, the authors enrolled 368 incident PD cases and 341 population controls from the Central Valley of California in a case-control study. They generated estimates for maneb and paraquat exposures incurred between 1974 and 1999. Exposure to both pesticides within 500 m of the home increased PD risk by 75% (95% confidence interval (CI): 1.13, 2.73). Persons aged < or =60 years at the time of diagnosis were at much higher risk when exposed to either maneb or paraquat alone (odds ratio = 2.27, 95% CI: 0.91, 5.70) or to both pesticides in combination (odds ratio = 4.17, 95% CI: 1.15, 15.16) in 1974-1989. This study provides evidence that exposure to a combination of maneb and paraquat increases PD risk, particularly in younger subjects and/or when exposure occurs at younger ages. FULL TEXT

Mesnage et al., 2021C

Mesnage R, Mazzacuva F, Caldwell A, Halket J, Antoniou MN. “Urinary excretion of herbicide co-formulants after oral exposure to roundup MON 52276 in rats.” Environmental Research. 2021 Jun;197:111103. DOI: 10.1016/j.envres.2021.111103.


The toxicity of surfactants, which are an integral component of glyphosate-formulated products is an underexplored and highly debated subject. Since biomonitoring human exposure to glyphosate co-formulants is considered as a public health priority, we developed and validated a high-resolution mass spectrometry method to measure the urinary excretion of surfactants present in Roundup MON 52276, the European Union (EU) representative formulation of glyphosate-based herbicides. Quantification was performed measuring the 5 most abundant compounds in the mixture. We validated the method and showed that it is highly accurate, precise and reproducible with a limit of detection of 0.0004 μg/mL. We used this method to estimate the oral absorption of MON 52276 surfactants in Sprague-Dawley rats exposed to three concentrations of MON 52276 via drinking water for 90 days. MON 52276 surfactants were readily detected in urine of rats administered with this commercial Roundup formulation starting from a low concentration corresponding to the EU glyphosate acceptable daily intake. Our results provide a first step towards the implementation of surfactant co-formulant biomonitoring in human populations. FULL TEXT

Lee et al., 2017

Lee KM, Park SY, Lee K, Oh SS, Ko SB. “Pesticide metabolite and oxidative stress in male farmers exposed to pesticide.” Annals of Occupational and Environmental Medicine. 2017 Feb 28;29:5, DOI: 10.1186/s40557-017-0162-3.


BACKGROUND: The objective of this study was to measure malondialdehyde (MDA) and isoprostane which has been used as an index of lipid injury, 8-hydroxy-2′-deoxyguanosine (8-OHdG), which has been used as an index of DNA damage, and dialkyl-phosphate (DAP), which has been used to quantify pesticide exposure, and to investigate the relationship between pesticide exposure and oxidative stress.

METHODS: This study was a cross-sectional study that evaluated 84 male farmers exposure to pesticide. In this study, 8-OHdG, isoprostane, and MDA were measured as oxidative stress indices, and dialkyl-phosphate (dimethylphosphate(DMP), diethylphosphate(DEP), dimethylthiophosphate(DMTP), and diethylthiophosphate (DETP)) excreted in the urine was also measured to evaluate pesticide exposure. A linear regression analysis was performed to investigate the relationship between pesticide metabolites, and oxidative stress biomarkers.

RESULTS: A Correlation analysis was performed for pesticide exposure month (PEI), cumulative exposure index (CEI), and DAP as well as the concentration of the oxidative stress biomarkers. The PEM significantly and positively correlated to the levels of 8-OHdG, isoprostane, CEI, and DMP. CEI showed a correlation to 8-OHdG and PEM. DMP, DEP, and DETP showed a positive correlation to 8-OHdG, isoprostane, and MDA. A correlation analysis was adjusted some demographic characteristics, such as age, smoking, drinking, and exercise to determine the relationship between pesticide exposure and oxidative stress. The 8-OHdG, isoprostane, and MDA levels were significantly related to the DMP (ß = 0.320), DEP (ß = 0.390), and DETP (ß = 0.082); DMP (ß = 0.396), DEP (ß = 0.508), and DETP (ß = 0.504); and DMP (ß = 0.432), DEP (ß = 0.508), and DETP (ß = 0.329) levels, respectively.

CONCLUSIONS: The concentration between oxidative stress biomarkers and the pesticide metabolite were a positive correlation. Indicators of oxidative stress was associated with a pesticide metabolite DMP, DEP, and DETP. Therefore, Pesticide exposure and oxidative stress were relevant. FULL TEXT

Syafrudin et al., 2021

Syafrudin M, Kristanti RA, Yuniarto A, Hadibarata T, Rhee J, Al-Onazi WA, Algarni TS, Almarri AH, Al-Mohaimeed AM. Pesticides in Drinking Water-A Review. International Journal of Environmental Research and Public Health. 2021 Jan 8;18(2):468. DOI: 10.3390/ijerph18020468.


The ubiquitous problem of pesticide in aquatic environment are receiving worldwide concern as pesticide tends to accumulate in the body of the aquatic organism and sediment soil, posing health risks to the human. Many pesticide formulations had introduced due to the rapid growth in the global pesticide market result from the wide use of pesticides in agricultural and non-agricultural sectors. The occurrence of pesticides in the water body is derived by the runoff from the agricultural field and industrial wastewater. Soluble pesticides were carried away by water molecules especially during the precipitation event by percolating downward into the soil layers and eventually reach surface waters and groundwater. Consequently, it degrades water quality and reduces the supply of clean water for potable water. Long-time exposure to the low concentration of pesticides had resulted in non-carcinogenic health risks. The conventional method of pesticide treatment processes encompasses coagulation-flocculation, adsorption, filtration and sedimentation, which rely on the phase transfer of pollutants. Those methods are often incurred with a relatively high operational cost and may cause secondary pollution such as sludge formation. Advanced oxidation processes (AOPs) are recognized as clean technologies for the treatment of water containing recalcitrant and bio-refractory pollutants such as pesticides. It has been adopted as recent water purification technology because of the thermodynamic viability and broad spectrum of applicability. This work provides a comprehensive review for occurrence of pesticide in the drinking water and its possible treatment. FULL TEXT