| 1. |
- Ekman, Eva, et al.
(författare)
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Determination of 5-hydroxythiabendazole in human urine as a biomarker of exposure to thiabendazole using LC/MS/MS.
- 2014
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Ingår i: Journal of Chromatography. B. - : Elsevier BV. - 1873-376X .- 1570-0232. ; 973, s. 61-67
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Tidskriftsartikel (refereegranskat)abstract
- Thiabendazole (TBZ) is widely used as a pre-planting and post-harvest agricultural fungicide and as an anthelminthic in humans and animals. TBZ is of toxicological concern, since adverse effects including nephrogenic, hepatogenic, teratogenic and neurological effects have been reported in mammals. Occupational exposure can occur among agricultural workers and the general public may be environmentally exposed to TBZ through the diet. The metabolite 5-hydroxythiabendazole (5-OH-TBZ) was chosen as biomarker of exposure to TBZ and a LC/MS/MS method for the quantification of 5-OH-TBZ in human urine was developed. The method includes enzyme hydrolysis, as 5-OH-TBZ is conjugated to glucuronide and sulphate in urine. Sample through put was optimised using 96-well plates for sample handling as well as for solid phase extraction (SPE). The method has excellent, within-run, between-run and between-batch precision between 4 and 9%. The limit of detection (LOD) of 0.05 and a limit of quantification (LOQ) of 0.13ng 5-OH-TBZ/mL urine enable detection in environmentally exposed populations. When applying the method in a general Swedish population, 52% had levels above LOD. The method was also applied in one oral and one dermal human experimental exposure study in two individuals. After oral exposure, the excretion of 5-OH-TBZ in urine was described by a two-compartment model and both the first rapid and the second slower elimination phase followed first-order kinetics, with estimated elimination half-life of 2h and 9-12h. The recoveries in urine were between 21 and 24% of the dose. Dermal exposure was described by a one compartment model and followed first order kinetics, with estimated elimination half-life of 9-18h. The recovery in urine was 1% of the administrated dose of TBZ. Although these studies are limited to two individuals, the data provide new basic information regarding the toxicokinetics of TBZ after oral and dermal exposure.
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| 2. |
- Faniband, Moosa, et al.
(författare)
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Biomarkers of Exposure to Pyrimethanil After Controlled Human Experiments
- 2019
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Ingår i: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 1945-2403 .- 0146-4760. ; 43:4, s. 277-283
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Tidskriftsartikel (refereegranskat)abstract
- Pyrimethanil (PYM) is a fungicide used pre- and post-harvest on many crops. It has a low acute toxicity but is of toxicological concern because of its antiandrogenic properties. The aim of the current work was to investigate some metabolism and estimate elimination kinetics of PYM in humans after experimental oral and dermal exposure. A liquid chromatography triple quadrupole mass spectrometry (LC-MS-MS) method was developed and validated for the analysis of PYM and its metabolite 4-hydroxypyrimethanil (OH-PYM) in human urine. The method was applied to analyze urine obtained from two volunteers experimentally exposed to PYM. The elimination of OH-PYM seemed to follow first-order kinetics and a two-phase excretion. After the oral exposure, the elimination half-life of OH-PYM in the rapid phase was 5 and 3 h for the female and male volunteer, respectively. In the slower phase, it was 15 h in both volunteers. After the dermal exposure, the half-life in the rapid phase was 8 h in both volunteers. In the slower phase, it was 30 and 20 h, respectively. About 80% of the oral dose was recovered as urinary OH-PYM in both volunteers. The dermal dose recovered as urinary OH-PYM was 9.4% and 19%, in the female and male volunteer, respectively. OH-PYM was mainly found as a conjugate of sulfonate and glucuronic acid. No free PYM was found. The analytical method showed good within-run, between-run and between-batch precision with a coefficient of variation between 6% and 12%. A limit of detection of 0.1 ng/mL and a limit of quantification of 0.4 ng/mL were achieved for both the analytes. The method was applied to biomonitor PYM exposure in populations in Sweden. OH-PYM was detected in nearly 50% and 96% of samples from the environmentally and occupationally exposed populations, respectively.
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| 3. |
- Faniband, Moosa H., et al.
(författare)
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Human experimental exposure to glyphosate and biomonitoring of young Swedish adults
- 2021
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Ingår i: International Journal of Hygiene and Environmental Health. - : Elsevier BV. - 1438-4639. ; 231
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Tidskriftsartikel (refereegranskat)abstract
- Glyphosate (GLY), N-(phosphonomethyl) glycine, is the most widely used herbicide in the world. It is a broad-spectrum herbicide, also used in crop desiccation. Agricultural workers may be occupationally exposed and general populations may be exposed to GLY mainly through diet. We studied the kinetics of GLY by measuring the parent compound and its metabolite aminomethylphosphonic acid (AMPA) in urine samples of three volunteers after an experimental oral exposure. We further examined GLY exposure by measuring GLY and AMPA in spot urine samples of 197 young adults in the general population in Scania, southern Sweden. Urine samples were analyzed using LC-MS/MS. In the experimental exposure, three healthy volunteers received an oral dose equivalent to 50% of the ADI for GLY. Urinary samples were collected up to 100 h after the exposure. The excretion of GLY to urine seemed to follow first-order kinetics and a two-phase excretion. The excretion half-life of GLY (density adjusted) was 6–9 h in the rapid phase and 18–33 h in the slower phase. The total dose recovered as unchanged GLY in the urine samples of volunteers was 1–6%. The metabolite AMPA was found to be 0.01–0.04% of the total dose of GLY. In the population of young adults, the median concentration was below 0.1 μg/L and a maximum concentration being 3.39 μg/L (density adjusted). AMPA was generally detected in lower concentrations (maximum = 0.99 μg/L). A moderate correlation (Spearman's ρ = 0.56) was observed between GLY and AMPA concentrations. Overall, the results may suggest that GLY and AMPA partly originate from separate exposures and that unchanged GLY is a more suitable biomarker of exposure.
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| 4. |
- Faniband, Moosa, et al.
(författare)
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Human biological monitoring of suspected endocrine-disrupting compounds.
- 2014
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Ingår i: Asian Journal of Andrology. - 1008-682X. ; 16:1, s. 5-16
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Forskningsöversikt (refereegranskat)abstract
- Endocrine-disrupting compounds are exogenous agents that interfere with the natural hormones of the body. Human biological monitoring is a powerful method for monitoring exposure to endocrine disrupting compounds. In this review, we describe human biological monitoring systems for different groups of endocrine disrupting compounds, polychlorinated biphenyls, brominated flame retardants, phthalates, alkylphenols, pesticides, metals, perfluronated compounds, parabens, ultraviolet filters, and organic solvents. The aspects discussed are origin to exposure, metabolism, matrices to analyse, analytical determination methods, determinants, and time trends.
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| 5. |
- Faniband, Moosa
(författare)
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Human Exposure Biomarkers of Some Commonly Used Pesticides
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The use of pesticides has caused pollution of surface and groundwater, soil and air across the world. Many pesticides cause health effects in humans. General populations are exposed to some degree and diet is reported to be a main source of exposure. It is important to study exposure and exposure-effect relationships in occupational groups and in general populations. For such studies, good methods to monitor exposure, such as human biomonitoring are needed. However, for many pesticides, there is a lack of knowledge on exposure biomarkers and analytical methods to measure exposure. Thus, there is a need for validated biomarkers of exposure and analytical methods.In this thesis, new methods were developed and validated to analyze the fungicides thiabendazole (TBZ), imazalil (IMZ) and pyrimethanil (PYM) and their exposure biomarkers in urine using LC-MS/MS. Further, an LC-MS/MS method for analysis of glyphosate (GLY) and one of its metabolite in urine was established. The analytical methods were sensitive enough to measure a wide range of concentrations of exposure biomarkers in populations and showed good precisions.Human experimental exposures (oral and/or dermal) with TBZ, IMZ, PYM and GLY were performed with 2-3 volunteers to investigate basic toxicokinetics. The excretion of biomarkers in urine was rapid with short half-lives for all the four pesticides. The biomarkers of IMZ, TBZ and PYM were found conjugated with glucuronides and sulfates. The concentrations of biomarkers varied quantitatively with the degree of exposure.The analytical methods were applied to biomonitor the exposure in occupationally exposed groups and in general populations. The measured biomarkers in population groups in Sweden reflect concentrations which seem to be far below the excreted concentrations after an intake of a dose equivalent to a dose half or equal to the ADIs. The diet of the general population could be a possible source of exposure. The measured exposure biomarkers of IMZ in greenhouse workers and of PYM in orchardists were higher than the general population and reflected concentrations that were sometimes close to those following an exposure at a dose half or equal to the ADIs. In conclusion, the analytical methods performed well and can be applied in biomonitoring studies. The identified biomarkers of all four pesticides were related to the exposures and the human experiments facilitated validation of the biomarkers. The short urinary excretion half-lives require a well-planned sampling strategy.
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| 6. |
- Faniband, Moosa, et al.
(författare)
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LC-MS-MS Analysis of Urinary Biomarkers of Imazalil Following Experimental Exposures.
- 2015
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Ingår i: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 1945-2403 .- 0146-4760. ; 39:9, s. 691-697
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Tidskriftsartikel (refereegranskat)abstract
- Imazalil (IMZ) is a fungicide used in the cultivation of vegetables, such as cucumbers, in green houses or post-harvest on fruit to avoid spoilage due to fungal growth. Agricultural workers can be occupationally exposed to IMZ and the general public indirectly by the diet. The purpose of this study was to develop and validate an LC-MS-MS method for the analysis of IMZ in human urine. The method used electrospray ionization and selected reaction monitoring in the positive mode. Excellent linearity was observed in the range 0.5-100 ng/mL. The limit of detection of the method was 0.2 ng/mL, and the limit of quantitation 0.8 ng/mL. The method showed good within-run, between-run and between-batch precision, with a coefficient of variation <15%. The method was applied to analyze urine samples obtained from two human volunteers following experimental oral and dermal exposure. The excretion of IMZ seemed to follow a two-compartment model and first-order kinetics. In the oral exposure, the elimination half-life of IMZ in the rapid excretion phase was 2.6 and 1.9 h for the female and the male volunteer, respectively. In the slower excretion phase, it was 7.6 and 13 h, respectively. In the dermal exposure, the excretion seemed to follow a single-compartment model and first-order kinetics. The elimination half-life was 10 and 6.6 h for the female and the male volunteer, respectively. Although the study is limited to two volunteers, some information on basic toxicokinetics and metabolism of IMZ in humans is presented.
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| 7. |
- Liljedahl, Emelie Rietz, et al.
(författare)
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Filaggrin polymorphisms and the uptake of chemicals through the skin—a human experimental study
- 2021
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Ingår i: Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 129:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The filaggrin protein is important for skin barrier structure and function. Loss-of-function (null) mutations in the filaggrin gene FLG may increase dermal absorption of chemicals. OBJECTIVE: The objective of the study was to clarify if dermal absorption of chemicals differs depending on FLG genotype. METHOD: We performed a quantitative real-time polymerase chain reaction (qPCR)-based genetic screen for loss-of-function mutations (FLG null) in 432 volunteers from the general population in southern Sweden and identified 28 FLG null carriers. In a dermal exposure experiment, we exposed 23 FLG null and 31 wild-type (wt) carriers to three organic compounds common in the environment: the polycyclic aromatic hydrocarbon pyrene, the pesticide pyrimethanil, and the ultraviolet-light absorber oxybenzone. We then used liquid-chromatography mass-spectrometry to measure the concentrations of these chemicals or their metabolites in the subjects’ urine over 48 h following exposure. Furthermore, we used long-range PCR to measure FLG repeat copy number variants (CNV), and we performed population toxicokinetic analysis. RESULTS: Lag times for the uptake and dermal absorption rate of the chemicals differed significantly between FLG null and wt carriers with low (20–22 repeats) and high FLG CNV (23–24 repeats). We found a dose-dependent effect on chemical absorption with increasing lag times by increasing CNV for both pyrimethanil and pyrene, and decreasing area under the urinary excretion rate curve (AUCð0–40hÞ ) with increasing CNV for pyrimethanil. FLG null carriers excreted 18% and 110% more metabolite (estimated by AUCð0–40hÞ ) for pyrimethanil than wt carriers with low and high CNV, respectively. CONCLUSION: We conclude that FLG genotype influences the dermal absorption of some common chemicals. Overall, FLG null carriers were the most susceptible, with the shortest lag time and highest rate constants for skin absorption, and higher fractions of the applied dose excreted. Furthermore, our results indicate that low FLG CNV resulted in increased dermal absorption of chemicals. https://doi.org/10.1289/EHP7310.
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| 8. |
- Norén, Erika, et al.
(författare)
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Concentrations and temporal trends in pesticide biomarkers in urine of Swedish adolescents, 2000–2017
- 2020
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Ingår i: Journal of Exposure Science and Environmental Epidemiology. - : Springer Science and Business Media LLC. - 1559-0631 .- 1559-064X. ; 30:4, s. 756-767
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Tidskriftsartikel (refereegranskat)abstract
- Agricultural pesticides are extensively used for weed- and pest control, resulting in residues of these compounds in food. The general population is mainly exposed through dietary intake. Exposure to certain pesticides has been associated with adverse human health outcomes. Our aim was to assess urinary concentrations and temporal trends in the biomarkers of commonly used pesticides. Samples were collected from adolescents (n = 1060) in Scania, Sweden, from 2000 to 2017. Concentrations of 14 pesticide biomarkers were analyzed in urine using LC–MS/MS. Temporal trends in biomarker concentrations (ln-transformed) were evaluated using linear regression. Biomarkers of pyrethroids (3-PBA and DCCA), chlorpyrifos (TCPy), chlormequat (CCC), thiabendazole (OH-TBZ), and mancozeb (ETU) were detected in >90% of the population all sampling years. The biomarkers CCC and TCPy had the highest median concentrations (>0.8 µg/L), whereas the biomarkers of cyfluthrin (4F-3-PBA) and two pyrethroids (CFCA) had the lowest median concentrations (<0.02 µg/L). Increasing temporal trends were found for the biomarkers 3-PBA (3.7%/year), TCPy (1.7%/year) and biomarkers of pyrimethanil (11.9%/year) and tebuconazole (12.2%/year). Decreasing trends were found for CCC (–5.5%/year), OH-TBZ (−5.5%/year), and ETU (−3.9%/year). Our results suggest that Swedish adolescents are commonly exposed to pesticides in low concentrations (median concentrations <3.88 µg/L).
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| 9. |
- Norén, Erika, et al.
(författare)
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Tidstrender för urinhalter av bekämpningsmedelsrester hos unga män – Resultat från fyra undersökningar mellan 2000 - 2013
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The increased use of synthetic chemicals in society poses possible harmful risks for the environment and human health. There are difficulties in predicting and evaluating consequences and effects of long-time exposure of different chemicals. Biomonitoring is one way to observe the level of exposure in the human population.Agricultural pesticides are a widely used group of chemicals to which we are mainly exposed by occupation or by diet. Long-term exposure to pesticides might have a negative impact on human health, especially in children and foetuses, due to genotoxic, neurotoxic and endocrine disrupting characteristics of many pesticides.This study focuses on the exposure assessment of 14 different metabolites from about 20 pesticides in urinary samples. The pesticides and their biomarkers of exposure included in the analysis were the fungicides thiabendazole (OH-T), pyrimetanil (OH-P), tebuconazole (TEB-OH), mancozeb and several ethylenebisdithiocarbamates (ETU), propineb (PTU), the insecticides chlorpyrifos (TCP), some pyrethroid insecticides, which have the same corresponding biomarkers (3-PBA, DCCA), and some specific pyrethroid biomarkers (4F-3-PBA, CFCA), the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-methyl-4-chlorophenoxyacetic acid (MCPA) and the growth regulators chlormequat (CCC) and mepiquat (MQ). The samples were collected years 2000, 2004, 2009 and 2013 from young men in the enrolment for military service in the south of Sweden. The last year of measurement (2013) both young men and women in upper secondary school were included. All samples were analysed in 2016 with liquid chromatography-tandem mass spectrometry (LC/MS/MS). The emphasis of the statistical analysis was temporal trends between the years 2000 and 2013.The highest concentrations were found for TCP and CCC in all samples from all four years. In general, the concentrations were below the levels seen in previous studies of other Swedish populations.The only increasing trend near significance was that for TCP, although the increasing gradient was fairly low ( = 0,28). The concentrations of CCC decreased over the years, but not statistically significantly so. The biomarkers 3-PBA, 2,4-D, DCCA and MQ were detected above the limit of detection (LOD), but in fairly low concentrations in the majority of samples and without significant trends. The remaining residues were mainly below the LOD and could not be further statistically analysed.
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| 10. |
- Tebby, Cleo, et al.
(författare)
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A generic PBTK model implemented in the MCRA platform : Predictive performance and uses in risk assessment of chemicals
- 2020
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915. ; 142
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Tidskriftsartikel (refereegranskat)abstract
- Physiologically-based toxicokinetic (PBTK) models are important tools for in vitro to in vivo or inter-species extrapolations in health risk assessment of foodborne and non-foodborne chemicals. Here we present a generic PBTK model implemented in the EuroMix toolbox, MCRA 9 and predict internal kinetics of nine chemicals (three endocrine disrupters, three liver steatosis inducers, and three developmental toxicants), in data-rich and data-poor conditions, when increasingly complex levels of parametrization are applied. At the first stage, only QSAR models were used to determine substance-specific parameters, then some parameter values were refined by estimates from substance-specific or high-throughput in vitro experiments. At the last stage, elimination or absorption parameters were calibrated based on available in vivo kinetic data. The results illustrate that parametrization plays a capital role in the output of the PBTK model, as it can change how chemicals are prioritized based on internal concentration factors. In data-poor situations, estimates can be far from observed values. In many cases of chronic exposure, the PBTK model can be summarized by an external to internal dose factor, and interspecies concentration factors can be used to perform interspecies extrapolation. We finally discuss the implementation and use of the model in the MCRA risk assessment platform.
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| 11. |
- van Wendel de Joode, Berna, et al.
(författare)
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Aerial Application of Mancozeb and Urinary Ethylene Thiourea (ETU) Concentrations among Pregnant Women in Costa Rica: The Infants' Environmental Health Study (ISA).
- 2014
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 122:12, s. 1321-1328
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mancozeb and its main metabolite ethylene thiourea (ETU) may alter thyroid function; thyroid hormones are essential for fetal brain development. In Costa Rica, mancozeb is aerially sprayed at large-scale banana plantations on a weekly basis. Objectives: (1) evaluate urinary ETU concentrations in pregnant women living nearby large-scale banana plantations; (2) compare their estimated daily intake (EDI) with established Reference Doses (RfDs); and (3) identify factors that predict their urinary ETU concentrations. Methods: We enrolled 451 pregnant women from Matina County, Costa Rica, with large-scale banana production. We visited 445 women up to three times during pregnancy to obtain urine samples (n = 872) and information on factors that possibly influence exposure. We determined urinary ETU concentrations using liquid chromatography mass spectrometry (LCMS). Results: Pregnant women's median urinary ETU concentrations were more than five times higher than reported for other general populations. Seventy-two percent of the women had EDIs above the RfD. Women who lived closest (1st quartile, < 48 meters) to banana plantations on average had a 45% (95% CI: 23, 72%) higher urinary ETU compared with women who lived farthest away (4th quartile, ≥ 565 meter). Compared with the other women, ETU was also higher in women who washed agricultural work clothes on day before sampling (11%; 95% CI; 4.9, 17%), worked in agriculture during pregnancy (19%; 95% CI: 9.3, 29), and immigrant women (6.2%; 95% CI: 1.0, 13%). Conclusions: The pregnant women's urinary ETU concentrations are of concern, and the principal source of exposure is likely to be aerial spraying of mancozeb. The factors predicting ETU provide insight into possibilities for exposure reduction.
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