Bibliography Tag: biomonitoring

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

Freisthler et al., 2022

Freisthler, Marlaina S., Robbins, C. Rebecca, Benbrook, Charles M., Young, Heather A., Haas, David M., Winchester, Paul D., & Perry, Melissa J.; “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;” Environmental Health, 2022, 21(1); DOI: 10.1186/s12940-021-00815-x.


BACKGROUND: 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 mug/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).


Buckley et al., 2022

Jessie P. Buckley, Jordan R. Kuiper, Deborah H. Bennett, Emily S. Barrett, Tracy Bastain, Carrie V. Breton, Sridhar Chinthakindi, Anne L. Dunlop, Shohreh F. Farzan, Julie B. Herbstman, Margaret R. Karagas, Carmen J. Marsit, John D. Meeker, Rachel Morello-Frosch, Thomas G. O’Connor, Megan E. Romano, Susan Schantz, Rebecca J. Schmidt, Deborah J. Watkins, Hongkai Zhu, Edo D. Pellizzari, Kurunthachalam Kannan, and Tracey J. Woodruff. “Exposure to Contemporary and Emerging Chemicals in Commerce among Pregnant Women in the United States: The Environmental influences on Child Health Outcome (ECHO) Program.” Environmental Science & Technology (2022) 56 (10), 6560-6573 DOI: 10.1021/acs.est.1c08942.
Prenatal chemical exposures can influence maternal and child health; however, few industrial chemicals are routinely biomonitored. We assessed an extensive panel of contemporary and emerging chemicals in 171 pregnant women across the United States (U.S.) and Puerto Rico in the Environmental influences on Child Health Outcomes (ECHO) Program. We simultaneously measured urinary concentrations of 89 analytes (103 total chemicals representing 73 parent compounds) in nine chemical groups: bactericides, benzophenones, bisphenols, fungicides and herbicides, insecticides, organophosphate esters (OPEs), parabens, phthalates/alternative plasticizers, and polycyclic aromatic hydrocarbons (PAHs). We estimated associations of creatinine-adjusted concentrations with sociodemographic and specimen characteristics. Among our diverse prenatal population (60% non-Hispanic Black or Hispanic), we detected 73 of 89 analytes in ≥1 participant and 36 in >50% of participants. Five analytes not currently included in the U.S. biomonitoring were detected in ≥90% of samples: benzophenone-1, thiamethoxam, mono-2-(propyl-6-carboxy-hexyl) phthalate, monocarboxy isooctyl phthalate, and monohydroxy-iso-decyl phthalate. Many analyte concentrations were higher among women of Hispanic ethnicity compared to those of non-Hispanic White women. Concentrations of certain chemicals decreased with the calendar year, whereas concentrations of their replacements increased. Our largest study to date identified widespread exposures to prevalent and understudied chemicals in a diverse sample of pregnant women in the U.S.


Nomura et al., 2022

Nomura, H., Hamada, R., Wada, K., Saito, I., Nishihara, N., Kitahara, Y., Watanabe, S., Nakane, K., Nagata, C., Kondo, T., Kamijima, M., Ueyama, J.; “Temporal trend and cross-sectional characterization of urinary concentrations of glyphosate in Japanese children from 2006 to 2015;” International Journal of Hygiene and Environmental Health, 2022, 242, 113963; DOI:10.1016/j.ijheh.2022.113963.


Background Over the past two decades, domestic shipments of glyphosate (Gly), in the form of an ionic salt, have been increasing steadily in Japan. This increase has raising concerns about the effects of chemical exposure on children. The International Agency for Research on Cancer classified Gly as a “probably carcinogenic to humans (Group 2A)” in 2015. The purpose of the current study was to analyze Gly in urine samples of Japanese children to determine temporal changes, seasonal changes, and gender differences.

Method First-morning urine samples were obtained from 50 Japanese children (4–6-year-old) in October of 2006, 2011, and 2015 (total = 150) to investigate the temporal trends in urinary Gly concentrations. Additionally, first-morning urine samples were collected from 3-year-old children in August–September of 2012 (summer; n = 42) and in February of 2013 (winter; n = 42) to investigate the seasonal and gender differences, and the correlations between urinary Gly concentrations and insecticide exposure biomarkers. Urine samples were analyzed to measure for Gly using a liquid chromatography with tandem mass spectrometry (LC-MS/MS).

Results Detectable Gly concentrations were found in 41% of the 234 children. The 75th percentile and maximum concentrations of urinary Gly were 0.20 and 1.33 μg/L, respectively. The urinary Gly concentration in 2015 was significantly higher than in 2006, suggesting that the Gly exposure levels have been increasing. No seasonal or gender-specific differences in urinary Gly concentrations were observed, and no correlation with insecticide exposure biomarkers was found.

Conclusion This study revealed that Gly exposure trends show an increase between 2006 and 2015, and that season and gender were not the exposure-determining factors. Overall, urinary concentrations of Gly were comparable with studies from other countries.


Lesseur et al., 2022

Corina Lesseur, Khyatiben V. Pathak, Patrick Pirrotte, Melissa N. Martinez, Kelly K. Ferguson, Emily S. Barrett, Ruby H.N. Nguyen, Sheela Sathyanarayana, Daniele Mandrioli, Shanna H. Swan, Jia Chen; “Urinary glyphosate concentration in pregnant women in relation to length of gestation;” Environmental Research, 2022, 203, 0013-9351; DOI:10.1016/j.envres.2021.111811.


Human exposure to glyphosate-based herbicides (GBH) is increasing rapidly worldwide. Most existing studies on health effects of glyphosate have focused on occupational settings and cancer outcomes and few have examined this common exposure in relation to the health of pregnant women and newborns in the general population. We investigated associations between prenatal glyphosate exposure and length of gestation in The Infant Development and the Environment Study (TIDES), a multi-center US pregnancy cohort. Glyphosate and its primary degradation product [aminomethylphosphonic acid (AMPA)] were measured in urine samples collected during the second trimester from 163 pregnant women: 69 preterm births (<37 weeks) and 94 term births, the latter randomly selected as a subset of TIDES term births. We examined the relationship between exposure and length of gestation using multivariable logistic regression models (dichotomous outcome; term versus preterm) and with weighted time-to-event Cox proportional hazards models (gestational age in days). We conducted these analyses in the overall sample and secondarily, restricted to women with spontaneous deliveries (n = 90). Glyphosate and AMPA were detected in most urine samples (>94 %). A shortened gestational length was associated with maternal glyphosate (hazard ratio (HR): 1.31, 95 % confidence interval (CI) 1.00–1.71) and AMPA (HR: 1.32, 95%CI: 1.00–1.73) only among spontaneous deliveries using adjusted Cox proportional hazards models. In binary analysis, glyphosate and AMPA were not associated with preterm birth risk (<37 weeks). Our results indicate widespread exposure to glyphosate in the general population which may impact reproductive health by shortening length of gestation. Given the increasing exposure to GBHs and the public health burden of preterm delivery, larger confirmatory studies are needed, especially in vulnerable populations such as pregnant women and newborns. FULL TEXT

Rempelos et al., 2022

Rempelos L, Wang J, Barański M, Watson A, Volakakis N, Hoppe HW, Kühn-Velten WN, Hadall C, Hasanaliyeva G, Chatzidimitriou E, Magistrali A, Davis H, Vigar V, Średnicka-Tober D, Rushton S, Iversen PO, Seal CJ, Leifert C.; “Diet and food type affect urinary pesticide residue excretion profiles in healthy individuals: results of a randomized controlled dietary intervention trial;” American Journal of Clinical Nutrition, 2022, 9;115(2),364-377; DOI: 10.1093/ajcn/nqab308.



Observational studies have linked pesticide exposure to various diseases, whereas organic food consumption has been associated with positive health outcomes. Organic farming standards prohibit the use of most pesticides, and organic food consumption may therefore reduce pesticide exposure.


To determine the effects of diet (Western compared with Mediterranean) and food type (conventional compared with organic) and sex on urinary pesticide residue excretion (UPRE), as well as associations between specific diet components and UPRE.


In this 2-wk, randomized dietary intervention trial, healthy adults were randomly allocated to an intervention (n = 13) or conventional (n = 14) group. Whereas participants in the intervention group consumed a Mediterranean diet (MedDiet) made entirely from organic foods, the conventional group consumed a MedDiet made entirely from conventional foods. Both groups consumed habitual Western diets made from conventional foods before and after the 2-wk intervention period. The primary outcome was UPRE. In addition, we assessed diet composition and pesticide residue profiles in foods eaten. Participants were aware of group assignment, but the study assessors were not.


During the intervention period, total UPRE was 91% lower with organic (mean 17 μg/d; 95% CI: 15, 19) than with conventional (mean 180 μg/d; 95% CI: 153, 208) food consumption (P < 0.0001). In the conventional group, switching from the habitual Western diet to the MedDiet increased insecticide excretion from 7 to 25 μg/d (P < 0.0001), organophosphate excretion from 5 to 19 μg/d (P < 0.0001), and pyrethroid residue excretion from 2.0 to 4.5 μg/d (P < 0.0001). Small but significant effects of sex were detected for chlormequat, herbicide, and total pesticide residue excretion.


Changing from a habitual Western diet to a MedDiet was associated with increased insecticide, organophosphate, and pyrethroid exposure, whereas organic food consumption reduced exposure to all groups of synthetic chemical pesticides. This may explain the positive health outcomes linked to organic food consumption in observational studies.


Schütze et al. 2021

Andre Schütze, Pilar Morales-Agudelo, Meghan Vidal, Antonia M. Calafat, Maria Ospina.; “Quantification of glyphosate and other organophosphorus compounds in human urine via ion chromatography isotope dilution tandem mass spectrometry;” Chemosphere, 2021, 274; DOI: 10.1016/j.chemosphere.2020.129427.


Organophosphorus pesticides are the most used pesticides in the United States. Most organophosphorus pesticides are composed of a phosphate (or phosphorothioate or phosphorodithioate) moiety and a variable organic group. Organophosphorus pesticides are scrutinized by regulatory bodies and agencies because of their toxicity or suspected carcinogenicity. Upon exposure, organophosphorus pesticides and their metabolites eliminate in urine; these urinary biomarkers are useful to evaluate human exposure. We developed a method using stable isotope dilution, ion chromatography tandem mass spectrometry for quantification in urine of 6 O,O-dialkylphosphates, metabolites of organophosphorus insecticides, and glyphosate, the most used herbicide in the United States. With simple and minimal sample preparation, the analytical method is selective and sensitive (limits of detection are 0.2-0.8 μg/L), accurate (>85%) and precise (relative standard deviation <20%), depending on the analyte. To assess the suitability of the method in real exposure scenarios, we analyzed samples collected anonymously from subjects with suspected exposure to pesticides (n = 40) or who had been on an organic diet (n = 50). We detected glyphosate in 80% of subjects reporting an organic diet and in 78% of those with suspected glyphosate exposure; concentrations ranged from <0.2 to 28.6 μg/L. Median concentrations were 0.39 μg/L for the organic diet group and 0.40 μg/L for individuals with suspected exposure. Interestingly, interquartile ranges were considerably higher among those reporting pesticide exposure (0.63 μg/L) than those consuming organic diets (0.42 μg/L). These data suggest that the method meets typical validation benchmark values and is sensitive to investigate background exposures in the general population. FULL TEXT

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.


Alexander et al., 2007

Alexander, B. H., Mandel, J. S., Baker, B. A., Burns, C. J., Bartels, M. J., Acquavella, J. F., & Gustin, C.; “Biomonitoring of 2,4-dichlorophenoxyacetic acid exposure and dose in farm families;” Environmental Health Perspectives, 2007, 115(3), 370-376; DOI: 10.1289/ehp.8869.


OBJECTIVE: We estimated 2,4-dichlorophenoxyacetic acid (2,4-D) exposure and systemic dose in farm family members following an application of 2,4-D on their farm.

METHODS: Farm families were recruited from licensed applicators in Minnesota and South Carolina. Eligible family members collected all urine during five 24-hr intervals, 1 day before through 3 days after an application of 2,4-D. Exposure profiles were characterized with 24-hr urine 2,4-D concentrations, which then were related to potential predictors of exposure. Systemic dose was estimated using the urine collections from the application day through the third day after application.

RESULTS: Median urine 2,4-D concentrations at baseline and day after application were 2.1 and 73.1 microg/L for applicators, below the limit of detection, and 1.2 microg/L for spouses, and 1.5 and 2.9 microg/L for children. The younger children (4-11 years of age) had higher median post-application concentrations than the older children (> or = 12 years of age) (6.5 vs. 1.9 microg/L). The geometric mean systemic doses (micrograms per kilogram body weight) were 2.46 (applicators), 0.8 (spouses), 0.22 (all children), 0.32 (children 4-11 years of age), and 0.12 (children > or = 12 years of age). Exposure to the spouses and children was primarily determined by direct contact with the application process and the number of acres treated. Multivariate models identified glove use, repairing equipment, and number of acres treated as predictors of exposure in the applicators.

CONCLUSIONS: We observed considerable heterogeneity of 2,4-D exposure among farm family members, primarily attributable to level of contact with the application process. Awareness of this variability and the actual magnitude of exposures are important for developing exposure and risk characterizations in 2,4-D-exposed agricultural populations.


Cosemans et al., 2021

Cosemans, C., Van Larebeke, N., Janssen, B. G., Martens, D. S., Baeyens, W., Bruckers, L., Den Hond, E., Coertjens, D., Nelen, V., Schoeters, G., Hoppe, H. W., Wolfs, E., Smeets, K., Nawrot, T. S., & Plusquin, M.; “Glyphosate and AMPA exposure in relation to markers of biological aging in an adult population-based study;” International Journal of Hygiene and Environmental Health, 2021, 240, 113895; DOI: 10.1016/j.ijheh.2021.113895.


BACKGROUND/AIM: Glyphosate, a broad-spectrum herbicide, and its main metabolite aminomethylphosphonic acid (AMPA) are persistent in the environment. Studies showed associations between glyphosate or AMPA exposure and several adverse cellular processes, including metabolic alterations and oxidative stress.

OBJECTIVE: To determine the association between glyphosate and AMPA exposure and biomarkers of biological aging.

METHODS: We examined glyphosate and AMPA exposure, mtDNA content and leukocyte telomere length in 181 adults, included in the third cycle of the Flemish Environment and Health Study (FLEHSIII). DNA was isolated from leukocytes and the relative mtDNA content and telomere length were determined using qPCR. Urinary glyphosate and AMPA concentrations were measured by Gas Chromatography-Tandem Mass Spectrometry (GC-MS-MS). We used multiple linear regression models to associate mtDNA content and leukocyte telomere length with glyphosate or AMPA exposure while adjusting for confounding variables.

RESULTS: A doubling in urinary AMPA concentration was associated with 5.19% (95% CI: 0.oth49 to 10.11; p = 0.03) longer leukocyte telomere length, while no association was observed with urinary glyphosate concentration. No association between mtDNA content and urinary glyphosate nor AMPA levels was observed.

CONCLUSIONS: This study showed that AMPA exposure may be associated with telomere biology in adults.