Self-reported and urinary biomarker-based measures of exposure to glyphosate and mancozeb and sleep problems among smallholder farmers in Uganda.

Objective: We aim to showcase the impact of applying eight different self-reported and urinary biomarker-based exposure measures for glyphosate and mancozeb on the association with sleep problems in a study among 253 smallholder farmers in Uganda.

Methods: The questionnaire-based exposure measures included: (1) the number of application days of any pesticide in the last 7 days (never, 1-2; >2 days) and six glyphosate and mancozeb-specific measures: (2) application status over the last 12 months (yes/no), (3) recent application status (never, last 7 days and last 12 months), (4) the number of application days last 12 months, (5) average exposure-intensity scores (EIS) and (6) EIS-weighted number of application days in last 12 months. Based on 384 repeated urinary biomarker concentrations of ethylene thiourea (ETU) and glyphosate from 84 farmers, we also estimated (7) average biomarker concentrations for all 253 farmers.

Factors influencing occupational exposure to pyrethroids and glyphosate: An analysis of urinary biomarkers in Malaysia, Uganda and the United Kingdom.

Background: Long-term exposure to pesticides is often assessed using semi-quantitative models. To improve these models, a better understanding of how occupational factors determine exposure (e.g.

FAIR environmental and health registry (FAIREHR)- supporting the science to policy interface and life science research, development and innovation.

The environmental impact on health is an inevitable by-product of human activity. Environmental health sciences is a multidisciplinary field addressing complex issues on how people are exposed to hazardous chemicals that can potentially affect adversely the health of present and future generations. Exposure sciences and environmental epidemiology are becoming increasingly data-driven and their efficiency and effectiveness can significantly improve by implementing the FAIR (findable, accessible, interoperable, reusable) principles for scientific data management and stewardship.

Development, testing, parameterisation, and calibration of a human PBK model for the plasticiser, di (2-ethylhexyl) adipate (DEHA) using , and human biomonitoring data.

A physiologically based biokinetic model for di (2-ethylhexyl) adipate (DEHA) based on a refined model for di-(2-propylheptyl) phthalate (DPHP) was developed to interpret the metabolism and biokinetics of DEHA following a single oral dosage of 50 mg to two male and two female volunteers. The model was parameterized using and methods such as, measured intrinsic hepatic clearance scaled from to and algorithmically predicted parameters such as plasma unbound fraction and tissue:blood partition coefficients (PCs). Calibration of the DEHA model was achieved using concentrations of specific downstream metabolites of DEHA excreted in urine.

Development, testing, parameterisation, and calibration of a human PBPK model for the plasticiser, di-(2-ethylhexyl) terephthalate (DEHTP) using , and human biomonitoring data.

A physiologically based pharmacokinetic model for di-(2-ethylhexyl) terephthalate (DEHTP) based on a refined model for di-(2-propylheptyl) phthalate (DPHP) was developed to interpret the metabolism and biokinetics of DEHTP following a single oral dose of 50 mg to three male volunteers. and methods were used to generate parameters for the model. For example, measured intrinsic hepatic clearance scaled from to and plasma unbound fraction and tissue:blood partition coefficients (PCs) were predicted algorithmically.

Development, Testing, Parameterisation and Calibration of a Human PBPK Model for the Plasticiser, Di-(2-propylheptyl) Phthalate (DPHP) Using in Silico, and Human Biomonitoring Data.

A physiologically based pharmacokinetic model for Di-(2-propylheptyl) phthalate (DPHP) was developed to interpret the biokinetics in humans after single oral doses. The model was parameterized with and in silico derived parameters and uncertainty and sensitivity analysis was used during the model development process to assess structure, biological plausibility and behaviour prior to simulation and analysis of human biological monitoring data. To provide possible explanations for some of the counter-intuitive behaviour of the biological monitoring data the model included a simple lymphatic uptake process for DPHP and enterohepatic recirculation (EHR) for DPHP and the mono ester metabolite mono-(2-propylheptyl) phthalate (MPHP).

Development, Testing, Parameterization, and Calibration of a Human Physiologically Based Pharmacokinetic Model for the Plasticizer, Hexamoll Diisononyl-Cyclohexane-1, 2-Dicarboxylate Using , , and Human Biomonitoring Data.

A physiologically based pharmacokinetic model for Hexamoll diisononyl-cyclohexane-1, 2-dicarboxylate was developed to interpret the biokinetics in humans after single oral doses. The model was parameterized with and derived parameters and uncertainty and sensitivity analysis was used during the model development process to assess structure, biological plausibility and behavior prior to simulation and analysis of human biological monitoring data. The model provided good simulations of the urinary excretion (Curine) of two metabolites; cyclohexane-1,2-dicarboxylic acid mono hydroxyisononyl ester (OH-MINCH) and cyclohexane-1, 2-dicarboxylic acid mono carboxyisononyl ester (cx-MINCH) from the biotransformation of mono-isononyl-cyclohexane-1, 2-dicarboxylate (MINCH), the monoester metabolite of di-isononyl-cyclohexane-1,2-dicarboxylate.

Urinary Naphthol as a Biomarker of Exposure: Results from an Oral Exposure to Carbaryl and Workers Occupationally Exposed to Naphthalene.

Urinary naphthol is an established human biomarker used for assessing both occupational and environmental exposure. However, 1-naphthol is a metabolite of the insecticide carbaryl while both the 1- and 2-isomers are metabolites of naphthalene. Thus, urinary 1-naphthol levels will reflect combined exposure to both substances, particularly at environmental levels.

Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents' Exposure.

Penconazole is a widely used fungicide in the UK; however, to date, there have been no peer-reviewed publications reporting human metabolism, excretion or biological monitoring data. The objectives of this study were to i) develop a robust analytical method, ii) determine biomarker levels in volunteers exposed to penconazole, and, finally, to iii) measure the metabolites in samples collected as part of a large investigation of rural residents' exposure. An LC-MS/MS method was developed for penconazole and two oxidative metabolites.

Human volunteer studies investigating the potential for toxicokinetic interactions between the pesticides deltamethrin; pirimicarb and chlorpyrifos-methyl following oral exposure at the acceptable daily intake.

Human volunteer studies have been conducted by orally administering the pesticides deltamethrin (0.01 mg/kg/day) or pirimicarb (0.02 mg/kg/day) at the acceptable daily intake (ADI) together with chlorpyrifos-methyl (0.

Biological monitoring for exposure to pirimicarb: method development and a human oral dosing study.

This study has developed and validated an assay to quantify metabolites of the carbamate insecticide pirimicarb, whose residues are commonly found on a variety of food products, at levels that might be expected to arise from dietary exposure at or below the acceptable daily intake (ADI, 0.02mg/kg). A novel method for the determination of pirimicarb metabolites in human urine by liquid chromatography with mass spectrometry detection has been developed and validated.

Electron exchange in conformationally restricted donor-spacer-acceptor dyads: angle dependence and involvement of upper-lying excited States.

The rate constant for triplet energy transfer (k(TET)) has been measured in fluid solution for a series of mixed-metal Ru-Os bis(2,2':6',2''-terpyridine) complexes built around a tethered biphenyl-based spacer group. The length of the tether controls the central torsion angle for the spacer, which can be varied systematically from 37 to 130 degrees . At low temperature, but still in fluid solution, the spacer adopts the lowest-energy conformation and k(TET) shows a clear correlation with the torsion angle.

Competition between energy transfer and interligand electron transfer in porphyrin-osmium(II) bis(2,2':6',2' '-terpyridine) dyads.

Rapid intramolecular energy transfer occurs from a free-base porphyrin to an attached osmium(II) bis(2,2':6',2' '-terpyridine) complex, most likely by way of the Förster dipole-dipole mechanism. The initially formed metal-to-ligand, charge-transfer (MLCT) excited-singlet state localized on the metal complex undergoes very fast intersystem crossing to form the corresponding triplet excited state ((3)MLCT). This latter species transfers excitation energy to the (3)pi,pi* triplet state associated with the porphyrin moiety, such that the overall effect is to catalyze intersystem crossing for the porphyrin.

How the central torsion angle affects the rates of nonradiative decay in some geometrically restricted p-quaterphenyls.

A small series of p-quaterphenyl derivatives has been prepared in which the dihedral angle (phi) for the two central rings is constrained by dialkoxy spacers of varying length. The photophysical properties of these compounds remain comparable, but there is a clear correlation between the rate constants for nonradiative decay of both singlet and triplet excited states and phi in fluid solution. The rates tend toward a minimum as phi approaches 90 degrees .

Intramolecular excimer formation and delayed fluorescence in sterically constrained pyrene dimers.

The synthesis is described for a series of five molecular dyads comprising pyrene-based terminals covalently linked through a 1,3-disubstituted phenylene spacer. The extent of through-space communication between the pyrene units is modulated by steric interactions imposed by bulky moieties attached at the 6,8-positions of each pyrene unit. For the control compound, only hydrogen atoms occupy the 6,8 positions (DP1), whereas the remaining compounds incorporate ethynylene groups terminated with either triisopropylsilyl (DP2), 1-tert-butylbenzene (DP3), 2,6-di-tert-butylbenzene (DP4) or 1-tert-butyl-3,5-dimethylbenzene (DP5) units.

An apparent angle dependence for the nonradiative deactivation of excited triplet states of sterically constrained, binuclear ruthenium(II) bis(2,2':6',2' '-terpyridine) complexes.

The photophysical properties are reported for a series of binuclear ruthenium(II) bis(2,2':6',2"-terpyridine) complexes built around a geometrically constrained, biphenyl-based bridge. The luminescence quantum yield and lifetime increase progressively with decreasing temperature, but the derived rate constant for nonradiative decay of the lowest-energy triplet state depends on the length of a tethering strap attached at the 2,2'-positions of the biphenyl unit. Since the length of the strap determines the dihedral angle for the central C-C bond, the rate of nonradiative decay shows a pronounced dependence on angle.

Comparison of the photophysical properties of osmium(II) bis(2,2':6',2' '-terpyridine) and the corresponding ethynylated derivative.

The photophysical properties of osmium(II) bis(2,2':6',2' '-terpyridine) have been recorded over a wide temperature range. An emission band is observed and attributed to radiative decay of the lowest-energy metal-to-ligand, charge-transfer (MLCT) triplet state. This triplet is coupled to two other triplet states that lie at higher energy.

Intramolecular energy-transfer processes in a bis(porphyrin)-ruthenium(II) bis(2,2':6',2''-terpyridine) molecular array.

A molecular triad has been synthesized comprising two free-base porphyrin terminals linked to a central ruthenium(II) bis(2,2':6',2''-terpyridine) subunit via meso-phenylene groups. Illumination into the ruthenium(II) complex is accompanied by rapid intramolecular energy transfer from the metal-to-ligand, charge-transfer (MLCT) triplet to the lowest-energy pi-pi* triplet state localized on one of the porphyrin subunits. Transfer takes place from a vibrationally excited level which lowers the activation energy.

A strategy for the synthesis of metal bis(2,2':6',2' '-terpyridine)-terminated molecular dyads having controlled torsion angles at the central biphenyl linker.

The synthesis of a series of binuclear complexes comprising bis(2,2':6',2' '-terpyridine)ruthenium(II) and -osmium(II) centers connected via a geometrically constrained 4,4'-biphenyl bridge is described. These compounds have been prepared by a "synthesis-at-metal" approach as well as by the conventional method of synthesizing the ligand and subsequently attaching the metal center. A computational investigation into the behavior of the biphenyl-based bridges has been used to provide lowest-energy conformations and to estimate the degree of internal fluctuation about the mean torsion angle.

Temperature-induced switching of the mechanism for intramolecular energy transfer in a 2,2':6',2' '-Terpyridine-based Ru(II)-Os(II) trinuclear array.

The synthesis and photophysical properties of a linear 2,2':6',2' '-terpyridine-based trinuclear Ru(II)-Os(II) nanometer-sized array are described. This array comprises two bis(2,2':6',2' '-terpyridine) ruthenium(II) terminals connected via alkoxy-strapped 4,4'-diethynylated biphenylene units to a central bis(2,2':6',2' '-terpyridine) osmium(II) core. The mixed-metal linear array was prepared using the "synthesis at metal" approach, and the Ru(II)-Ru(II) separation is ca.

Orientational control of electronic coupling in mixed-valence, binuclear ruthenium(II)-bis(2,2':6',2' '-terpyridine) complexes.

A series of binuclear ruthenium(II)-bis(2,2':6',2' '-terpyridine) complexes has been prepared around a central biphenylene unit equipped with a strap of variable length. Partial oxidation forms the mixed-valence complex that displays both ligand-to-metal, charge-transfer, and intervalence charge-transfer (IVCT) transitions in the near-IR region. On the basis of Hush theory, the electronic coupling matrix element for interaction between the metal centers decreases with increasing length of the tethering strap.

Electron delocalization in a ruthenium(II) Bis(2,2':6',2' '-terpyridyl) complex.

Photophysical properties have been recorded for a ruthenium(II) bis(2,2':6',2' '-terpyridine) complex bearing a single ethynylene substituent. The target compound is weakly emissive in fluid solution at room temperature, but both the emission yield and lifetime increase dramatically as the temperature is lowered. As found for the unsubstituted parent complex, the full temperature dependence indicates that the lowest-energy triplet state couples to two higher-energy triplets and to the ground state.