Bibliography Tag: biomonitoring

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.


Abou et al., 2020

Abou Ghayda R, Sergeyev O, Burns JS, Williams PL, Lee MM, Korrick SA, Smigulina L, Dikov Y, Hauser R, Mínguez-Alarcón L; “Russian Children’s Study. Peripubertal serum concentrations of organochlorine pesticides and semen parameters in Russian young men.” Environment International. 2020 Nov;144:106085. DOI:10.1016/j.envint.2020.106085.


Background: Epidemiologic literature on the relation of organochlorine pesticides (OCPs) with semen quality among adult men has been inconclusive, and no studies have prospectively explored the association between peripubertal serum OCPs and semen parameters in young men.

Objective: To evaluate prospective associations of peripubertal serum concentrations of hexachlorobenzene (HCB), β-hexachlorocylohexane (β-HCH), and p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE) with semen parameters among young Russian men.

Methods: This prospective cohort study included 152 young men who enrolled in the Russian Children’s Study (2003-2005) at age 8-9 years and were followed annually until young adulthood. HCB, β-HCH, and p,p’-DDE concentrations were measured at the CDC by mass spectrometry in serum collected at enrollment. Between 18 and 23 years, semen samples (n = 298) were provided for analysis of volume, concentration, and progressive motility; we also calculated total sperm count and total progressive motile count. Linear mixed models were used to examine the longitudinal associations of quartiles of serum HCB, β-HCH and p,p’-DDE with semen parameters, adjusting for total serum lipids, body mass index, smoking, abstinence time and baseline dietary macronutrient intake.

Results: Lipid-adjusted medians (IQR) for serum HCB, βHCH and p,ṕ-DDE, respectively, were 150 ng/g lipid (102-243), 172 ng/g lipid (120-257) and 275 ng/g lipid (190-465). In adjusted models, we observed lower ejaculated volume with higher serum concentrations of HCB and βHCH, along with reduced progressive motility with higher concentrations of βHCH andp,ṕ-DDE. Men in the highest quartile of serum HCB had a mean (95% Confidence Interval, CI) ejaculated volume of 2.25 mL (1.89, 2.60), as compared to those in the lowest quartile with a mean (95% CI) of 2.97 mL (2.46, 3.49) (p = 0.03). Also, men in the highest quartile of serum p,ṕ-DDE had a mean (95% CI) progressive motility of 51.1% (48.6, 53.7), as compared to those in the lowest quartile with a mean (95% CI) of 55.1% (51.7, 58.5) (p = 0.07).

Conclusion: In this longitudinal Russian cohort study, peripubertal serum concentrations of selected OCPs were associated with lower ejaculated volume and progressive motility highlighting the importance of the peripubertal window when evaluating chemical exposures in relation to semen quality. FULL TEXT

Ledda et al., 2021

Ledda C, Cannizzaro E, Cinà D, Filetti V, Vitale E, Paravizzini G, Di Naso C, Iavicoli I, Rapisarda V. “Oxidative stress and DNA damage in agricultural workers after exposure to pesticides.” Journal of Occupational Medicine and Toxicology. 2021 Jan 7;16(1):1. DOI: 10.1186/s12995-020-00290-z.


BACKGROUND: Recent epidemiological studies on workers describe that exposure to pesticides can induce oxidative stress by increased production of free radicals that can accumulate in the cell and damage biological macromolecules, for example, RNA, DNA, DNA repair proteins and other proteins and/or modify antioxidant defense mechanisms, as well as detoxification and scavenger enzymes. This study aimed to assess oxidative stress and DNA damage among workers exposed to pesticides.

METHODS: For this purpose, 52 pesticide exposed workers and 52 organic farmers were enrolled. They were assessed: the pesticide exposure, thiobarbituric acid reactive substances (TBARS), total glutathione (TG), oxidized glutathione levels (GSSG), and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), levels.

RESULTS: Correlation between pesticide exposure was positively associated with high TBARS and 8-oxodG levels (p < 0.001). A negative association was founded with TG and GSSG and pesticide exposure.

CONCLUSIONS: The present investigation results seem to indicate a mild augment in oxidative stress associated with pesticide exposure, followed by an adaptive response to increase the antioxidant defenses to prevent sustained oxidative adverse effects stress. 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

Mnif et al., 2011

Mnif W, Hassine AI, Bouaziz A, Bartegi A, Thomas O, Roig B. “Effect of endocrine disruptor pesticides: a review.” International Journal of Environmental Research and Public Health. 2011 Jun;8(6):2265-303. DOI: 10.3390/ijerph8062265.

ABSTRACT: Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air). For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health. FULL TEXT

Silver et al., 2021

Silver, M. K., Fernandez, J., Tang, J., McDade, A., Sabino, J., Rosario, Z., Velez Vega, C., Alshawabkeh, A., Cordero, J. F., & Meeker, J. D.; “Prenatal Exposure to Glyphosate and Its Environmental Degradate, Aminomethylphosphonic Acid (AMPA), and Preterm Birth: A Nested Case-Control Study in the PROTECT Cohort (Puerto Rico);” Environmental Health Perspectives, 2021, 129(5), 57011; DOI: 10.1289/EHP7295.


BACKGROUND: Glyphosate (GLY) is the most heavily used herbicide in the world. Despite nearly ubiquitous exposure, few studies have examined prenatal GLY exposure and potentially adverse pregnancy outcomes. Preterm birth (PTB) is a risk factor for neonatal mortality and adverse health effects in childhood.

OBJECTIVES: We examined prenatal exposure to GLY and a highly persistent environmental degradate of GLY, aminomethylphosphonic acid (AMPA), and odds of PTB in a nested case-control study within the ongoing Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort in northern Puerto Rico.

METHODS: GLY and AMPA in urine samples collected at 18+/-2 (Visit 1) and 26+/-2 (Visit 3) wk gestation (53 cases/194 randomly selected controls) were measured using gas chromatography tandem mass spectrometry. Multivariable logistic regression was used to estimate associations with PTB (delivery <37wk completed gestation).

RESULTS: Detection rates in controls were 77.4% and 77.5% for GLY and 52.8% and 47.7% for AMPA, and geometric means (geometric standard deviations) were 0.44 (2.50) and 0.41 (2.56) mug/L for GLY and 0.25 (3.06) and 0.20 (2.87) mug/L for AMPA, for Visits 1 and 3, respectively. PTB was significantly associated with specific gravity-corrected urinary GLY and AMPA at Visit 3, whereas associations with levels at Visit 1 and the Visits 1-3 average were largely null or inconsistent. Adjusted odds ratios (ORs) for an interquartile range increase in exposure at Visit 3 were 1.35 (95% CI: 0.99, 1.83) and 1.67 (95% CI: 1.26, 2.20) for GLY and AMPA, respectively. ORs for Visit 1 and the visit average were closer to the null.

DISCUSSION: Urine GLY and AMPA levels in samples collected near the 26th week of pregnancy were associated with increased odds of PTB in this modestly sized nested case-control study. Given the widespread use of GLY, multiple potential sources of AMPA, and AMPA’s persistence in the environment, as well as the potential for long-term adverse health effects in preterm infants, further investigation in other populations is warranted.


Geer et al., 2004

Geer, L. A., Cardello, N., Dellarco, M. J., Leighton, T. J., Zendzian, R. P., Roberts, J. D., & Buckley, T. J.; “Comparative analysis of passive dosimetry and biomonitoring for assessing chlorpyrifos exposure in pesticide workers;” Annals of Occupational Hygeine, 2004, 48(8), 683-695; DOI: 10.1093/annhyg/meh056.


Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the US Environmental Protection Agency (EPA) has the authority to regulate the use of pesticides to prevent unreasonable adverse human health effects associated with pesticide exposure. Accordingly, the EPA requires pesticide registrants to perform studies evaluating the potential for pesticide handler exposure. Data from five such studies that included exposure measurements based on both external measurements and biological monitoring were used to examine methods of assessment, routes and determinants of exposure and dose to the pesticide chlorpyrifos. Eighty workers across four job classes were included: mixer/loaders (M/L, n = 24), mixer/loader/applicators (M/L/A, n = 37), applicators (A, n = 9) and re-entry scouts (RS, n = 10). Results showed that doses were highly variable and differed by job class (P < 0.05) with median total (inhalation and dermal combined) exposure-derived absorbed doses (EDADtot) of 129, 88, 85 and 45 microg/application for A, M/L/A, M/L and RS, respectively. Doses derived from the measurement of 3,5,6-trichloro- 2-pyridinol (3,5,6-TCP) in urine were similar in magnitude but differed in rank with median values of 275, 189, 122 and 97 microg/application for A, M/L, RS, and M/L/A, respectively. The relative contribution of dermal to inhalation exposure was examined by their ratio. The median ratios of exposure-derived absorbed dermal dose (EDADderm) (assuming 3% absorption) to exposure-derived absorbed inhalation dose (EDADinh) (assuming 100% absorption) across job classes were 1.7, 1.5, 0.44 and 0.18 for RS, M/L, A and M/L/A, respectively, with an overall median of 0.6. For 34 of 77 workers (44%), this ratio exceeded 1.0, indicating the significance of the dermal exposure pathway. Different dermal absorption factor (DAF) assumptions were examined by comparing EDADtot to the biomarker-derived absorbed dose (BDAD) as a ratio where EDADtot was calculated assuming a DAF of 1, 3 and 10%. Median ratios of 0.45, 0.71 and 1.28, respectively, were determined suggesting the DAF is within the range of 3-10%. A simple linear regression of urinary 3,5,6-TCP against EDADtot indicates a positive association explaining 29% of the variability in the 3,5,6-TCP derived estimate of dose. A multiple linear regression model including the variables EDADderm, EDADinh and application type explained 46% of the variability (R2 = 0.46) in the urinary dose estimate. EDADderm was marginally significant (P = 0.066) while EDADinh was not (P = 0.57). The EDADderm regression coefficient (0.0007) exceeded the coefficient for EDADinh (0.00002) by a factor of 35. This study demonstrates the value of the pesticide registrant database for the purpose of evaluating pesticide worker exposure. It highlights the significance of the dermal exposure pathway, and identifies the need for methods and research to close the gap between external and internal exposure measures. FULL TEXT

Meuling et al., 2005

Meuling, W. J., Ravensberg, L. C., Roza, L., & van Hemmen, J. J.; “Dermal absorption of chlorpyrifos in human volunteers;” International Archives of Occupational and Environmental Health, 2005, 78(1), 44-50; DOI: 10.1007/s00420-004-0558-6.


OBJECTIVE: The methods and results are described of a study on the dermal absorption of chlorpyrifos (CPF) in humans established via urinary excretion of the metabolite 3,5,6-trichloro-2-pyridinol (TCP).

METHODS: Two dermal, single, doses of CPF were applied in two study groups (A and B) each comprising three apparently healthy male volunteers who gave their written informed consent. The clinical part of the study was conducted in compliance with the ICH Guideline and the EC principles of good clinical practice (GCP). An approximately 0.5 ml dilution of CPF in ethanol was applied to an area of approximately 100 cm(2) of the volar aspect of the forearm, resulting in doses of either 5 mg (A) or 15 mg (B) of CPF per study subject. Duration of dermal exposure was 4 h, after which the non-absorbed fraction was washed off. The following samples were collected at pre-determined intervals for the determination of either CPF or its metabolite TCP: dosing solutions, wash-off fractions and urine samples collected up to 120 h after dosing.

RESULTS: A relatively large fraction of CPF (42%-67% of the applied dose) was washed off from the exposed skin area. Application of either 5 mg (A) or 15 mg CPF (B) resulted in the total urinary excretion of 131.8 microg (A) or 115.6 microg (B) of TCP 120 h after dosing. This indicated that 4.3% of the applied dose has been absorbed (A), while in group (B) no significant increase in urinary TCP (115.6 microg) was established. The latter indicates that an increase in the dermal dose at a fixed area does not increase absorption, which suggests that the percutaneous penetration rate was constant. Further, it was observed that the clearance of CPF by the body was not completed within 120 h, suggesting that CPF or TCP was retained by the skin and/or accumulated in the body. A mean elimination half-life of 41 h was established.

CONCLUSION: The results show that daily occupational exposure to CPF may result in accumulation of CPF and/or its metabolites, possibly resulting in adverse effects. FULL TEXT


Calafat, 2012

Calafat, A. M.; “The U.S. National Health and Nutrition Examination Survey and human exposure to environmental chemicals;” International Journal of Hygiene and Environmental Health, 2012, 215(2), 99-101; DOI: 10.1016/j.ijheh.2011.08.014.


Researchers are increasingly interested in using human biomonitoring – the measurement of chemicals, their metabolites or specific reaction products in biological specimens/body fluids – for investigating exposure to environmental chemicals. General population human biomonitoring programs are useful for investigating human exposure to environmental chemicals and an important tool for integrating environment and health. One of these programs, the National Health and Nutrition Examination Survey (NHANES), conducted in the United States is designed to collect data on the health and nutritional status of the noninstitutionalized, civilian U.S. population. NHANES includes a physical examination, collecting a detailed medical history, and collecting biological specimens (i.e., blood and urine). These biological specimens can be used to assess exposure to environmental chemicals. NHANES human biomonitoring data can be used to establish reference ranges for selected chemicals, provide exposure data for risk assessment, and monitor exposure trends. FULL TEXT