Bibliography Tag: routes of exposure

Milesi et al., 2021

Milesi, M. M., Lorenz, V., Durando, M., Rossetti, M. F., & Varayoud, J. “Glyphosate Herbicide: Reproductive Outcomes and Multigenerational Effects.” Frontiers in Endocrinology, 12. 2021; DOI:10.3389/fendo.2021.672532.


Glyphosate base herbicides (GBHs) are the most widely applied pesticides in the world and are mainly used in association with GBH-tolerant crop varieties. Indiscriminate and negligent use of GBHs has promoted the emergence of glyphosate resistant weeds, and consequently the rise in the use of these herbicides. Glyphosate, the active ingredient of all GBHs, is combined with other chemicals known as co-formulants that enhance the herbicide action. Nowadays, the safety of glyphosate and its formulations remain to be a controversial issue, as evidence is not conclusive whether the adverse effects are caused by GBH or glyphosate, and little is known about the contribution of co-formulants to the toxicity of herbicides. Currently, alarmingly increased levels of glyphosate have been detected in different environmental matrixes and in foodstuff, becoming an issue of social concern. Some in vitro and in vivo studies have shown that glyphosate and its formulations exhibit estrogen-like properties, and growing evidence has indicated they may disrupt normal endocrine function, with adverse consequences for reproductive health. Moreover, multigenerational effects have been reported and epigenetic mechanisms have been proved to be involved in the alterations induced by the herbicide. In this review, we provide an overview of: i) the routes and levels of human exposure to GBHs, ii) the potential estrogenic effects of glyphosate and GBHs in cell culture and animal models, iii) their long-term effects on female fertility and mechanisms of action, and iv) the consequences on health of successive generations. FULL TEXT

Benbrook et al., 2021

Benbrook, Charles, Kegley, Susan, & Baker, Brian; “Organic Farming Lessens Reliance on Pesticides and Promotes Public Health by Lowering Dietary Risks;” Agronomy, 2021, 11(7); DOI: 10.3390/agronomy11071266.


Organic agriculture is a production system that relies on prevention, ecological processes, biodiversity, mechanical processes, and natural cycles to control pests and maintain productivity. Pesticide use is generally limited or absent in organic agroecosystems, in contrast with non-organic (conventional) production systems that primarily rely on pesticides for crop protection. Significant differences in pesticide use between the two production systems markedly alter the relative dietary exposure and risk levels and the environmental impacts of pesticides. Data are presented on pesticide use on organic and non-organic farms for all crops and selected horticultural crops. The relative dietary risks that are posed by organic and non-organic food, with a focus on fresh produce, are also presented and compared. The results support the notion that organic farms apply pesticides far less intensively than conventional farms, in part because, over time on well-managed organic farms, pest pressure falls when compared to the levels on nearby conventional farms growing the same crops. Biopesticides are the predominant pesticides used in organic production, which work by a non-toxic mode of action, and pose minimal risks to human health and the environment. Consequently, eating organic food, especially fruits and vegetables, can largely eliminate the risks posed by pesticide dietary exposure. We recommend ways to lower the pesticide risks by increased adoption of organic farming practices and highlight options along organic food supply chains to further reduce pesticide use, exposures, and adverse worker and environmental impacts. 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

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

Blair et al., 1985

Blair, A., Malker, H., Cantor, K. P., Burmeister, L., & Wiklund, K.; “Cancer among farmers. A review;” Scandinavian Journal of Work, Environment, & Health, 1985, 11(6), 397-407; DOI: 10.5271/sjweh.2208.


During the performance of routine tasks farmers may come in contact with a variety of substances, including pesticides, solvents, oils and fuels, dusts, paints, welding fumes, zoonotic viruses, microbes, and fungi. Because some of these substances are known or suspected carcinogens, the epidemiologic literature regarding cancer risks concerning farmers has been reviewed. Farmers had consistent deficits for cancers of the colon, rectum, liver, and nose. The deficits for cancer of the lung and bladder were particularly striking, presumably due to less frequent use of tobacco among farmers than among people in many other occupational groups. Malignancies frequently showing excesses among farmers included Hodgkin’s disease, leukemia, non-Hodgkin’s lymphoma, multiple myeloma, and cancers of the lip, stomach, prostate, skin (nonmelanotic), brain, and connective tissues. The etiologic factors that may contribute to these excesses in the agricultural environment have not been identified. Detailed, analytic epidemiologic studies that incorporate environmental and biochemical monitoring are needed to clarify these associations. FULL TEXT

Macfarlane et al., 2013

Macfarlane, E., Carey, R., Keegel, T., El-Zaemay, S., & Fritschi, L.; “Dermal exposure associated with occupational end use of pesticides and the role of protective measures;” Safety and Health at Work, 2013, 4(3), 136-141; DOI: 10.1016/


BACKGROUND: Occupational end users of pesticides may experience bodily absorption of the pesticide products they use, risking possible health effects. The purpose of this paper is to provide a guide for researchers, practitioners, and policy makers working in the field of agricultural health or other areas where occupational end use of pesticides and exposure issues are of interest.

METHODS: This paper characterizes the health effects of pesticide exposure, jobs associated with pesticide use, pesticide-related tasks, absorption of pesticides through the skin, and the use of personal protective equipment (PPE) for reducing exposure.

CONCLUSIONS: Although international and national efforts to reduce pesticide exposure through regulatory means should continue, it is difficult in the agricultural sector to implement engineering or system controls. It is clear that use of PPE does reduce dermal pesticide exposure but compliance among the majority of occupationally exposed pesticide end users appears to be poor. More research is needed on higher-order controls to reduce pesticide exposure and to understand the reasons for poor compliance with PPE and identify effective training methods.


Moore et al., 2014

Moore, C. A., Wilkinson, S. C., Blain, P. G., Dunn, M., Aust, G. A., & Williams, F. M.; “Percutaneous absorption and distribution of organophosphates (chlorpyrifos and dichlorvos) following dermal exposure and decontamination scenarios using in vitro human skin model;” Toxicology Letters, 2014, 229(1), 66-72; DOI: 10.1016/j.toxlet.2014.06.008.


To date, there has been little research investigating low-level human exposure to chemicals, and so the aim of this study was to examine the percutaneous penetration of organophosphates (dichlorvos and chlorpyrifos) using low-level exposure scenarios in vitro. Dermal absorption of chlorpyrifos applied in different vehicles was measured at 0, 4, 8 and 24 h, after dose application for 4 and 24 h exposure (finite dose, 500 ng/cm(2)) in isopropanol (IPA), isopropyl myristate (IPM) and propylene glycol (PG). Dichlorvos was applied to the skin for 24 h (infinite dose, 1 mg/cm(2) and 10 mg/cm(2); finite dose, 5 mug/cm(2)) using the same vehicles. Human skin was mounted in flow through diffusion cells with minimum essential medium eagle pH 7.4 (supplemented with 2% BSA) as receptor fluid. Following exposure, the skin surface dose was removed by tissue swabbing, the stratum corneum removed by sequential tape stripping, and the skin digested prior to scintillation counting (chlorpyrifos), or GC/MS analysis (dichlorvos). The dermal absorption of chlorpyrifos was the greatest following application in PG (19.5% of dose), when compared with absorption from the IPA and IPM vehicles (10.3% and 1.9% absorbed respectively). However, dichlorvos showed greater dermal absorption than chlorpyrifos from all vehicles used, with greatest absorption from the IPA vehicle (38.6% absorbed). Although dichlorvos exhibited a short lag time (0.6 h from IPA and IP vehicles, and 0.4 h from PG), chlorpyrifos displayed greater propensity to accumulate in the stratum corneum and epidermis/dermis. These results demonstrate that prompt skin surface decontamination would be required for both dichlorvos and chlorpyrifos (and chemicals with similar properties) in the event of skin contact. The magnitude of the skin reservoir formed with chlorpyrifos was time dependent, therefore, prompt decontamination of this and similar chemicals would be required to reduce delayed systemic absorption.

Kezic and Nielsen, 2009

Kezic, S., & Nielsen, J. B.; “Absorption of chemicals through compromised skin;” International Archives of Occupational and Environmental Health, 2009, 82(6), 677-688; DOI: 10.1007/s00420-009-0405-x.


Skin is an important route of entry for many chemicals in the work place. To assess systemic uptake of a chemical in contact with the skin, quantitative information on dermal absorption rates of chemicals is needed. Absorption rates are mainly obtained from studies performed with intact, healthy skin. At the work place, however, a compromised skin barrier, although not necessarily visible is common, e.g. due to physical and chemical damage. As reviewed in this article, there are several lines of evidence that reduced integrity of the skin barrier may increase dermal absorption of chemicals in the occupational setting. An impaired skin barrier might lead not only to enhanced absorption of a specific chemical, but also to entrance of larger molecules such as proteins and nanoparticles which normally are not able to penetrate intact skin. In addition to environmental influences, there is increasing evidence that some individuals have an intrinsically affected skin barrier which will facilitate entrance of chemicals into and through the skin making these persons more susceptible for local as well for systemic toxicity. This review addresses mechanisms of barrier alteration caused by the most common skin-damaging factors in the occupational settings and the consequences for dermal absorption of chemicals. Furthermore, this review emphasizes the importance of maintained barrier properties of the skin. FULL TEXT

Mahler et al., 2021

Mahler, B. J., Nowell, L. H., Sandstrom, M. W., Bradley, P. M., Romanok, K. M., Konrad, C. P., & Van Metre, P. C.; “Inclusion of Pesticide Transformation Products Is Key to Estimating Pesticide Exposures and Effects in Small U.S. Streams;” Environmental Science & Technology, 2021; DOI: 10.1021/acs.est.0c06625.


Improved analytical methods can quantify hundreds of pesticide transformation products (TPs), but understanding of TP occurrence and potential toxicity in aquatic ecosystems remains limited. We quantified 108 parent pesticides and 116 TPs in more than 3700 samples from 442 small streams in mostly urban basins across five major regions of the United States. TPs were detected nearly as frequently as parents (90 and 95% of streams, respectively); 102 TPs were detected at least once and 28 were detected in >20% samples in at least one region-TPs of 9 herbicides, 2 fungicides (chlorothalonil and thiophanate-methyl), and 1 insecticide (fipronil) were the most frequently detected. TPs occurred commonly during baseflow conditions, indicating chronic environmental TP exposures to aquatic organisms and the likely importance of groundwater as a TP source. Hazard quotients based on acute aquatic-life benchmarks for invertebrates and nonvascular plants and vertebrate-centric molecular endpoints (sublethal effects) quantify the range of the potential contribution of TPs to environmental risk and highlight several TP exposure-response data gaps. A precautionary approach using equimolar substitution of parent benchmarks or endpoints for missing TP benchmarks indicates that potential aquatic effects of pesticide TPs could be underestimated by an order of magnitude or more. FULL TEXT

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