Bibliography Tag: biomonitoring

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

Baker et al., 2019

Baker, S. E., Serafim, A. B., Morales-Agudelo, P., Vidal, M., Calafat, A. M., & Ospina, M.; “Quantification of DEET and neonicotinoid pesticide biomarkers in human urine by online solid-phase extraction high-performance liquid chromatography-tandem mass spectrometry;” Analytical and Bioanalytical Chemistry, 2019, 411(3), 669-678; DOI: 10.1007/s00216-018-1481-0.


Neonicotinoid insecticides are widely used replacements for organophosphate and carbamate insecticides, but the extent of human exposure is largely unknown. On the other hand, based on urinary concentrations of DEET metabolites, human exposure to N,N-diethyl-m-toluamide (DEET) appears to be widespread. We developed a fast online solid-phase extraction high-performance liquid chromatography-isotope dilution tandem mass spectrometry (HPLC-MS/MS) method to measure in 200 muL of human urine the concentrations of six neonicotinoid biomarkers (acetamiprid, N-desmethyl-acetamiprid, clothianidin, imidacloprid, 5-hydroxy-imidacloprid, thiacloprid), and two DEET biomarkers (3-diethyl-carbamoyl benzoic acid, 3-ethyl-carbamoyl benzoic acid). Limits of detection ranged from 0.01 to 0.1 mug/L, depending on the biomarker. Accuracy ranged from 91 to 116% and precision ranged from 3.7 to 10 %RSD. The presented method can be used to increase our understanding of exposure to neonicotinoid insecticides and DEET, and to evaluate the potential health effects from such exposures.  FULL TEXT

Kougias et al., 2020

Kougias, D. G., Miller, E., McEwen, A., Reamer, H., Kovochich, M., & Pierce, J.; “Risk Assessment of Glyphosate Exposures from Pilot Study with Simulated Heavy Residential Consumer Application of Roundup((R)) using a Margin of Safety (MOS) Approach;” Risk Analysis, 2020; DOI: 10.1111/risa.13646.


Due to the widespread application of glyphosate, a nonselective herbicide, to a variety of resistant food crops, the general population is exposed to glyphosate through dietary intake. Despite this, dietary exposures to glyphosate are considered low in comparison to application-related exposures. Although previous studies have evaluated exposure to horticultural and agricultural workers, to date only one study, which we recently conducted, has characterized exposure to glyphosate in consumers following heavy residential application of a glyphosate-containing herbicide in a residential yard and garden setting. In this previous study, we demonstrated that urinary glyphosate concentrations in these applicators were similar to or in some circumstances greater than those in occupational applicators, likely due to the nature of the simulation study, which ensured a heavy application protocol. However, it is unknown whether these urinary glyphosate concentrations in consumer applicators correspond to internal doses that may be of concern. Therefore, the purpose of this study is to provide a comprehensive risk assessment of glyphosate exposure in consumer applicators using a margin of safety approach. Here, we incorporated data collected from multiple spot urine samples across time from our previous study that assessed consumer exposure to glyphosate from Roundup((R)) application. Estimated internal doses, even with the use of conservative assumptions across unique approaches, were below internal doses estimated from established health-based guidance values. Overall, this study demonstrates that glyphosate exposure from even heavy consumer application of a commercially available glyphosate-containing herbicide does not appear to be a health concern. FULL TEXT

Yusa et al., 2015

Yusa, V., Millet, M., Coscolla, C., & Roca, M.; “Analytical methods for human biomonitoring of pesticides. A review;” Analytica Chimica Acta, 2015, 891, 15-31; DOI: 10.1016/j.aca.2015.05.032.


Biomonitoring of both currently-used and banned-persistent pesticides is a very useful tool for assessing human exposure to these chemicals. In this review, we present current approaches and recent advances in the analytical methods for determining the biomarkers of exposure to pesticides in the most commonly used specimens, such as blood, urine, and breast milk, and in emerging non-invasive matrices such as hair and meconium. We critically discuss the main applications for sample treatment, and the instrumental techniques currently used to determine the most relevant pesticide biomarkers. We finally look at the future trends in this field. FULL TEXT

Apel et al., 2020

Apel, P., Rousselle, C., Lange, R., Sissoko, F., Kolossa-Gehring, M., & Ougier, E.; “Human biomonitoring initiative (HBM4EU) – Strategy to derive human biomonitoring guidance values (HBM-GVs) for health risk assessment;” International Journal of Hygiene and Environmental Health, 2020, 230, 113622; DOI: 10.1016/j.ijheh.2020.113622.


The European Joint Program “HBM4EU” is a joint effort of 30 countries and the European Environment Agency, co-funded under the European Commission’s Horizon 2020 program, for advancing and implementing human biomonitoring (HBM) on a European scale and for providing scientific evidence for chemical policy making. One important outcome will be a Europe-wide improvement and harmonization of health risk assessment following the coordinated derivation or update of health-related guidance values referring to the internal body burden. These guidance values – named HBM guidance values or HBM-GVs – can directly be compared with HBM data. They are derived within HBM4EU for priority substances identified by the HBM4EU chemicals prioritization strategy based on existing needs to answer policy relevant questions as raised by national and EU policy makers. HBM-GVs refer to both the general population and occupationally exposed adults. Reports including the detailed reasoning for the values’ proposals are subjected to a consultation process within all partner countries of the consortium to reach a broad scientific consensus on the derivation approach and on the derived values. The final HBM-GVs should be applied first within the HBM4EU project, but may also be useful for regulators and risk assessors outside this project. The subsequent adoption of derived HBM-GVs at EU-level needs to be discussed and decided within the responsible EU bodies. Nevertheless, the establishment of HBM-GVs as part of HBM4EU is already a step forward in strengthening HBM-based policy efforts for public and occupational health. The strategy for deriving HBM-GVs which is based on already existing approaches from the German HBM Commission, the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) as well as from the US-based scientific consultant Summit Toxicology, the allocation of a level of confidence to the derived values, and the consultation process within the project are comprehensively described to enlighten the work accomplished under the HBM4EU initiative. FULL TEXT

Gillezeau et al., 2020

Gillezeau, C., Lieberman-Cribbin, W., & Taioli, E.; “Update on human exposure to glyphosate, with a complete review of exposure in children;” Environmental Health, 2020, 19(1), 115; DOI: 10.1186/s12940-020-00673-z.


BACKGROUND: Glyphosate, a commonly used pesticide, has been the topic of much debate. The effects of exposure to glyphosate remains a contentious topic. This paper provides an update to the existing literature regarding levels of glyphosate exposure in occupationally exposed individuals and focuses or reviewing all the available published literature regarding glyphosate exposure levels in children.

METHODS: A literature review was conducted and any articles reporting quantifiable exposure levels in humans published since January 2019 (the last published review on glyphosate exposure) were reviewed and data extracted and standardized.

RESULTS: A total of five new studies reporting exposure levels in humans were found including 578 subjects. Two of these studies focused on occupationally exposed individuals while three of them focused on glyphosate exposure levels in children. Given the sparse nature of the new data, previously identified studies on exposure to glyphosate in children were included in our analysis of children’s exposure. The lowest average level of glyphosate exposure reported was 0.28 μg/L and the highest average exposure levels reported was 4.04 μg/L.

CONCLUSION: The literature on glyphosate exposure levels, especially in children, remains limited. Without more data collected in a standardized way, parsing out the potential relationship between glyphosate exposure and disease will not be possible. FULL TEXT

Pellizzari et al., 2019

Pellizzari, E. D., Woodruff, T. J., Boyles, R. R., Kannan, K., Beamer, P. I., Buckley, J. P., Wang, A., Zhu, Y., & Bennett, D. H.; “Identifying and Prioritizing Chemicals with Uncertain Burden of Exposure: Opportunities for Biomonitoring and Health-Related Research;” Environmental Health Perspectives, 2019, 127(12), 126001; DOI: 10.1289/EHP5133.


BACKGROUND: The National Institutes of Health’s Environmental influences on Child Health Outcomes (ECHO) initiative aims to understand the impact of environmental factors on childhood disease. Over 40,000 chemicals are approved for commercial use. The challenge is to prioritize chemicals for biomonitoring that may present health risk concerns.

OBJECTIVES: Our aim was to prioritize chemicals that may elicit child health effects of interest to ECHO but that have not been biomonitored nationwide and to identify gaps needing additional research.

METHODS: We searched databases and the literature for chemicals in environmental media and in consumer products that were potentially toxic. We selected chemicals that were not measured in the National Health and Nutrition Examination Survey. From over 700 chemicals, we chose 155 chemicals and created eight chemical panels. For each chemical, we compiled biomonitoring and toxicity data, U.S. Environmental Protection Agency exposure predictions, and annual production usage. We also applied predictive modeling to estimate toxicity. Using these data, we recommended chemicals either for biomonitoring, to be deferred pending additional data, or as low priority for biomonitoring.

RESULTS: For the 155 chemicals, 97 were measured in food or water, 67 in air or house dust, and 52 in biospecimens. We found in vivo endocrine, developmental, reproductive, and neurotoxic effects for 61, 74, 47, and 32 chemicals, respectively. Eighty-six had data from high-throughput in vitro assays. Positive results for endocrine, developmental, neurotoxicity, and obesity were observed for 32, 11, 35, and 60 chemicals, respectively. Predictive modeling results suggested 90% are toxicants. Biomarkers were reported for 76 chemicals. Thirty-six were recommended for biomonitoring, 108 deferred pending additional research, and 11 as low priority for biomonitoring.

DISCUSSION: The 108 deferred chemicals included those lacking biomonitoring methods or toxicity data, representing an opportunity for future research. Our evaluation was, in general, limited by the large number of unmeasured or untested chemicals.  FULL TEXT

Buckley et al., 2020

Buckley, J. P., Barrett, E. S., Beamer, P. I., Bennett, D. H., Bloom, M. S., Fennell, T. R., Fry, R. C., Funk, W. E., Hamra, G. B., Hecht, S. S., Kannan, K., Iyer, R., Karagas, M. R., Lyall, K., Parsons, P. J., Pellizzari, E. D., Signes-Pastor, A. J., Starling, A. P., Wang, A., Watkins, D. J., Zhang, M., Woodruff, T. J., & program collaborators for, Echo; “Opportunities for evaluating chemical exposures and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) Program;” Journal of exposure science & environmental epidemiology, 2020, 30(3), 397-419; DOI: 10.1038/s41370-020-0211-9.


The Environmental Influences on Child Health Outcomes (ECHO) Program will evaluate environmental factors affecting children’s health (perinatal, neurodevelopmental, obesity, respiratory, and positive health outcomes) by pooling cohorts composed of >50,000 children in the largest US study of its kind. Our objective was to identify opportunities for studying chemicals and child health using existing or future ECHO chemical exposure data. We described chemical-related information collected by ECHO cohorts and reviewed ECHO-relevant literature on exposure routes, sources, and environmental and human monitoring. Fifty-six ECHO cohorts have existing or planned chemical biomonitoring data for mothers or children. Environmental phenols/parabens, phthalates, metals/metalloids, and tobacco biomarkers are each being measured by ≥15 cohorts, predominantly during pregnancy and childhood, indicating ample opportunities to study child health outcomes. Cohorts are collecting questionnaire data on multiple exposure sources and conducting environmental monitoring including air, dust, and water sample collection that could be used for exposure assessment studies. To supplement existing chemical data, we recommend biomonitoring of emerging chemicals, nontargeted analysis to identify novel chemicals, and expanded measurement of chemicals in alternative biological matrices and dust samples. ECHO’s rich data and samples represent an unprecedented opportunity to accelerate environmental chemical research to improve the health of US children. FULL TEXT