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1. [UL-7,8-ring [sup 14]C]-1,2,7,8-tetrachlorodibenzo-p-dioxin (1278-TCDD) was administered orally to a ruminating Holstein bull calf (43.6 kg; 1.2 mg kg[sup -1] body weight). Urine and faeces were collected daily for 96 h, while blood was sampled at multiple time points. Tissues were removed for combustion analysis. 2. Each tissue contained < 0.6% of the dose at 96h. Tissues with highest levels of 1278-TCDD, as a percentage of administered dose, were the large and small intestine, rumen, liver and carcass. 3. Urinary excretion accounted for 10.6% of the dose, and faecal excretion accounted for 81.6% of the administered dose. The major urinary and faecal metabolites were isolated and characterized by mass spectrometry and [sup 1]H-NMR. 4. Plasma levels of [sup 14]C peaked at 24 h, and decreased to near background at 96 h. Detectable plasma levels of 1278-TCDD were observed by 2 h. 5. A hydroxylated metabolite of 1278-TCDD was detected in calf plasma, which has the potential to interfere with thyroid hormone homeostasis. [ABSTRACT FROM AUTHOR]

Hexabromocyclododecane (HBCD) is a brominated flame retardant (BFR) labeled by the Stockholm Convention as a persistent organic pollutant (POP) and exists primarily as three stereoisomers, i.e. α-, β-, and γ. One of the major routes of human exposure to HBCD is dust found in homes, offices, and cars and dust may be the most important route of HBCD exposure in young children. A study was conducted to determine the oral bioavailability of HBCD from household dust in rats over a 21-d feeding period relative to HBCD bioavailability from a corn oil matrix. Twenty-four hours after the last exposure, rats were sacrificed, and various tissues were collected. HBCD diastereomers were detected in adipose, blood, and liver of both dose groups, suggesting HBCD is bioavailable from both oil and dust. β-HBCD concentrations were below the limit of detection in all tissues, but α-HBCD was detected in the brain of oil-dose rats and in adipose and liver of both dose groups. γ-HBCD was the dominant diastereomer in adipose, blood, and liver samples regardless of dosing matrix. Except for γ-HBCD in muscle of the oil-dosed group, muscle did not contain measurable HBCDs. Adipose tissue accumulated HBCD to a greater extent than muscle or liver, having bioaccumulation factors greater than 1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Abstract: Perfluorooctanoic acid (PFOA) is used as a surfactant in consumer and industrial products and is frequently found in biosolids from wastewater treatment plants. When present in biosolids applied to croplands, PFOA can contaminate feed and fodder used by livestock, but the extent of PFOA transfer from soil to plants is not well characterized. A single dose of radiocarbon (14C)-tagged PFOA was applied to unplanted soil or soil containing growing alfalfa. PFOA transport through unplanted soil and uptake by alfalfa was monitored over a 10-week study period. Radiocarbon was initially measured in roots, stems, and leaves 7 days after [14C]-PFOA application to soil. PFOA accumulation was greatest in leaves during the 10-week sampling. By week 10, PFOA migration through unplanted soil had reached a depth of 22.8 ± 2.5 cm. In contrast, PFOA migrated to 7.5 ± 2.5 cm in soil containing alfalfa plants. The greatest predictor of PFOA concentration in alfalfa leaves was PFOA concentration in the top 5 cm of soil; PFOA concentrations at lower depths were not correlated with alfalfa PFOA concentrations. PFOA transport through soil may be slowed by the presence of forage; however, PFOA accumulation in edible portions of forage plants may increase food animal exposure to PFOA residues., (Published 2022 by the International Association for Food Protection. Not subject to U.S. Copyright.)

Abstract: Perfluorooctanoic acid (PFOA) is a perfluorinated alkyl substance used as a surfactant in a wide variety of industrial and consumer products. Over the past decade, concern has increased over the presence of PFOA in biosolids from wastewater treatment plants used as fertilizer on agricultural lands because of the potential for PFOA to enter the food chain. In this study, the uptake of 14C-PFOA from soil by alfalfa and 14C-PFOA bioavailability from consumption of this alfalfa was evaluated in Sprague-Dawley rats. Alfalfa leaves accumulated 14C-PFOA up to 4 to 5 μg/g of dry leaf, approximately 10 times higher than accumulation in the stem. Alfalfa was ground for feeding to 15 female Sprague-Dawley rats (175 to 200 g). Animals within metabolism cages were fed 10 g of feed (6 g of alfalfa plus 4 g of ground rat chow) twice daily for 14 days (equivalent to 50 μg of 14C-PFOA per kg per day). At the end of the feeding period, three rats were euthanized for sample collection on each of withdrawal days 0, 3, 7, 11, and 14. During the feeding and withdrawal phases, urine and feces were collected daily. At necropsy, blood, liver, kidney, adipose, muscle, skin, brain, heart, adrenal glands, spleen, lungs, and thymus were removed and assayed for 14C-PFOA by combustion and liquid scintillation counting. Rats had eliminated 72.8% ± 3.4% of the total dose via urine at 14 days, but urinary radioactivity fell below the level of detection by day 3 of the withdrawal period. Fecal elimination was 6.5% ± 1.2% of the dose and fell below the level of detection by day 2 of the withdrawal period. The rapid and high elimination via urine indicates that a majority of the dose was absorbed. The uptake of 14C-PFOA into alfalfa was low from soil with a high organic concentration; however, 14C-PFOA was highly bioavailable from the alfalfa when used as a feed component for rats. This study provides data for regulators investigating 14C-PFOA bioavailability and disposition in animals or animal products exposed to contaminated feed., (Published 2021 by the International Association for Food Protection. Not subject to U.S. Copyright.)

Polybrominated diphenyl ethers (PBDEs) levels in environmental matrices have generally declined following their phaseout as flame retardants. The objective of this study was to determine the absorption, distribution, metabolism, and excretion of three persistent PBDEs in laying hens and their transfer into eggs. Laying hens (n = 4 per congener) received a single oral dose of BDE-99, -153, or -209 and eggs and excreta were collected daily for 7 days, then tissues were collected and analysed. Cumulative BDE-209 excretion was 93% of dose, and bioavailability was approximately 17%. Lesser amounts of BDE-99 (41%) and -153 (26%) were excreted with bioavailabilities of 87% and 79%, respectively. Phenolic metabolites were observed in excreta extracts from BDE-99 dosed birds. Cumulative transfers based on bioavailability of BDE-99, -153, and -209 to eggs were 17%, 34%, and 15%, respectively. Egg residues were primarily present in yolk (12.3%, 23.5%, and 2.1% of the total dose for BDE-99, -153, and -209, respectively). Adipose, skin, ova, intestine, and thigh muscle contained the highest levels of radioactive tissue residues. These studies demonstrate movement of PBDE residues into edible tissues and eggs of laying hens.

Polybrominated dibenzo-p-dioxins (PBDDs) and mixed bromo/chloro dibenzo-p-dioxins (PXDDs) are persistent organic pollutants that can possess the same toxicity as their fully chlorinated analogs (PCDDs) and have been identified in the same matrices. Herein a general synthetic methodology is described to produce multiple congeners of PBDDs and PXDDs with varying degrees of halogenation and substitution patterns for use as analytical and/or internal standards, and for absorption, disposition, metabolism, and excretion (ADME) studies. The syntheses of PBDDs and PXDDs were accomplished by condensing a common precursor, 4,5-dibromo catechol, with variable precursors, i.e., polychlorinated 1-chloro-2-nitrobenzenes or polybrominated 1-fluoro-2-nitrobenzenes, to introduce a desired number of halogens and specific substitution patterns. Initial attempts to synthesize PBDDs and PXDDs were performed in potassium carbonate with DMSO at 145-150 °C. PXDDs syntheses resulted in formation of the desired products at >90% purity but attempts at higher brominated PBDDs syntheses resulted in dehalogenated by-products. To preclude by-product formation, additional syntheses for some PBDDs were conducted by refluxing the precursors in acetonitrile, which resulted in pure products at higher yield. Six PXDDs ranging from four to six halogens were synthesized (20-84% yield), of which three contained the halogen substitution pattern of 2,3,7,8. Five PBDDs ranging from four to six bromines were produced in 23-83% yield, three of which were toxic. Using the initial DMSO method, [ 14 C]-1,3,7,8-tetrabromodibenzo-p-dioxin (0.26 μCi/μmol; 11% overall yield) was synthesized from commercially available [ 14 C]-phenol to allow an ADME study to be conducted., (Published by Elsevier Ltd.)

Although livestock manure, such as from swine (Sus scrofa domestica), have high capacity to introduce endocrine-disrupting free estrogens into the environment, the frequency of estrogen detections from reconnaissance studies suggest that these compounds are ubiquitous in the environment, perhaps resulting from historic manure inputs (e.g. cattle grazing residues, undocumented historic manure applications) or uncontrolled natural sources. Compared to free estrogens, conjugates of estrogens are innocuous but have greater mobility in the environment. Estrogen conjugates can also hydrolyze to re-form the potent free estrogens. The objective of this study was to identify the transport of free and conjugated estrogens to subsurface tile drains and groundwater beneath fields treated with swine manure slurry. Three field treatments were established, two receiving swine lagoon manure slurry and one with none. Manure slurry was injected into soils at a shallow depth (∼8 cm) and water samples from tile drains and shallow wells were sampled periodically for three years. Glucuronide and sulfate conjugates of 17β-estradiol (E2) and estrone (E1) were the only estrogen compounds detected in the tile drains (total detects = 31; 5% detection frequency; conc. range = 3.9-23.1 ng L -1 ), indicating the important role conjugates played in the mobility of estrogens. Free estrogens and estrogen conjugates were more frequently detected in the wells compared to the tile drains (total detects = 70; 11% detection frequency; conc. range = 4.0-1.6 × 10 3  ng L -1 ). No correlations were found between estrogen compound detections and dissolved or colloidal organic carbon (OC) fractions or other water quality parameters. Estrogenic compounds were detected beneath both manure treated and non-treated plots; furthermore, the total potential estrogenic equivalents (i.e. estrogenicity of hydrolyzed conjugates + free estrogens) were similar between treated and non-treated plots., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We performed Bentall procedure on a 65-year-old male patient. Cardiopulmonary bypass was initiated via cannulation of the aneurysmatic segment of the aorta. Distal anastomosis was performed with the open technique under deep hypothermic circulatory arrest at 18°C. We performed arterial recannulation through the anastomosis with a new technique, and cardiopulmonary bypass was reestablished. Cardiopulmonary bypass was terminated after rewarming and de-airing phases, and decannulation was performed without any problems. By this technique, the patient had no additional incisions for arterial cannulation, and there were no additional cannulation sutures left on the patient's arterial tree or the valved conduit.

Ambient ionization mass spectrometric methods including desorption electrospray ionization (DESI) and atmospheric solid analysis probe (ASAP) have great potential for applications requiring real-time screening of target molecules in complex matrixes. Such techniques can also rapidly produce repeatable semiquantitative data, with minimal sample preparation, relative to liquid chromatography-mass spectrometry (LC-MS). In this study, a commercial ASAP probe was used to conduct both ASAP-MS and modified DESI (MDESI) MS analyses. We conducted real-time qualitative and semiquantitative analysis of the leanness-enhancing agent zilpaterol in incurred sheep urine, kidney, muscle, liver, and lung samples using ASAP-MS and MDESI MS. Using ASAP, limits of detection (LOD) and quantitation (LOQ) in urine were 1.1 and 3.7 ng/mL, respectively, while for MDESI MS they were 1.3 and 4.4 ng/mL, respectively. The LODs for tissues were 0.1-0.4 ng/g using ASAP, and 0.2-0.6 ng/g with MDESI MS. The LOQs of the tissues in ASAP were 0.4-1.2 ng/g and 0.5-2.1 ng/g in MDESI MS. Trace levels of zilpaterol were accurately analyzed in urine and tissues of sheep treated with dietary zilpaterol HCl. The correlation coefficient ( R 2 ) between semiquantitative ASAP-MS and MDESI MS results of urine samples was 0.872. The data from ASAP and MDESI MS were validated using LC-MS/MS; urinary zilpaterol concentrations ≥5.0 ng/mL or tissue zilpaterol concentrations ≥1.5 ng/g were detected by ASAP and MDESI MS, respectively, 100% of the time. Forty samples could be analyzed in triplicate, directly from biological matrixes in under an hour.

The distribution of 12 environmental contaminants or metabolites with diverse polarities (2,2',4,4',5-pentabromodiphenyl ether; bisphenol A; estrone; glyphosate; β-hexabromocyclododecane; imidacloprid; 2,3',4,4',5-pentachlorobiphenyl; 3'-methylsulfone 2,2',4,5,5'-pentachlorobiphenyl; 1,2,7,8-tetrachlorodibenzo- p -dioxin; 2-hydroxy-1,3,7,8-tetrachlorodibenzo- p -dioxin; tetrabromobisphenol A; and triclocarban) among skim milk, fat, curd, whey, whey retentate, and whey permeate was characterized. Analysis of these compounds along with 15 drugs previously studied provided a robust linear model predicting the distribution between skim and fat and the chemical's lipophilicity (log P , r 2 = 0.71; log D , r 2 = 0.79). Similarly, distribution between curd and whey was correlated with lipophilicity (log P , r 2 = 0.63; log D , r 2 = 0.73). Phenolic compounds had less predictable distribution patterns based on their lipophilicities. Within the whey fraction, chemicals with greater lipophilicity are associated with whey proteins more than hydrophilic chemicals. The resultant model could help predict the potential distribution of chemical contaminants among milk products in cow milk, if present., Competing Interests: The authors declare no competing financial interest.

Metabolism, environmental fate, and low concentration food residue studies would be facilitated by the use of radiolabeled test articles that can be readily quantified within complex matrices. However, radiochemical approaches for such studies require high specific activities to allow analytical detection of correspondingly low masses of test article. The synthesis of high specific activity (>50 μCi/μmol) [ 14 C]-radiolabeled phenylbutazone presents a challenge using existing methodology, mainly due to the low solvent volumes required and vigorous refluxing needed to close the pyrazolidinedione ring. Herein, we report on the significant modification of an existing method that allows the synthesis of low masses of high specific activity (>50 μCi/μmol) [ 14 C]-phenylbutazone under mild conditions with simple purification and high yield. The closure of the pyrazolidinedione ring of 1,2-diphenyl-3,5-pyrazolidinedione was accomplished as a first step with unlabeled 1,2-diphenylhydrazine and diethyl malonate in 32% yield under gram-scale conditions, which avoided the challenges of low solvent use and vigorous refluxing. Low mass of high specific activity n-[1- 14 C]-butyl bromide was then added via a nucleophilic substitution reaction as a final step. Yields ranged from 65% to 92% during multiple synthetic attempts with unlabeled butyl bromide and were greatly influenced by reaction stoichiometry and the selection of base., (Published 2017. This article is a U.S. Government work and is in the public domain in the USA.)

The distributions of eight drugs (acetaminophen, acetylsalicylic acid/salicylic acid, ciprofloxacin, clarithromycin, flunixin, phenylbutazone, praziquantel, and thiamphenicol) were determined in milk products (skim milk, milk fat, curd, whey, and whey protein) and used to expand a previous model (from 7 drugs to 15 drugs) for predicting drug distribution. Phenylbutazone and praziquantel were found to distribute with the lipid and curd phases (≥50%). Flunixin distribution was lower but similar in direction (12% in milk fat, 39% in curd). Acetaminophen, ciprofloxacin, and praziquantel preferentially associated with casein proteins, whereas thiamphenicol and clarithromycin associated preferentially to whey proteins. Regression analyses for log [milk fat]/[skim milk] and log [curd]/[whey] had r 2 values of 0.63 and 0.67, respectively, with p of <0.001 for 15 drugs (7 previously tested and 8 currently tested). The robustness of the distribution model was enhanced by doubling the number of drugs originally tested.

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants whose use has contaminated foods and caused subsequent human exposures. To address the issue of possible human exposure, samples from a 2012-13 US meat and poultry (beef, pork, chicken, turkey) study were analysed for seven PBDEs. The mean summed concentrations of the seven BDE congeners (ΣPBDE) from beef, pork, chicken and turkey were 0.40, 0.36, 0.19, and 0.76 ng g -1 lipid weight (lw). The range of ΣPBDEs for all meat classes was 0.01-15.78 ng g -1 lw. A comparison of this study with a 2007-08 study revealed a decline in the median ΣPBDEs for all four meat classes, a reduction of 25.9% to 70.0%, with pork, chicken and turkey PBDE residues being statistically lower relative to the 2007-08 study. BDEs 47 and 99 contributed the most to the ΣPBDE concentrations, indicating likely animal exposures to the penta-BDE formulation. Based on the reported data an estimate of US consumer daily intake of PBDEs from meat and poultry was 6.42 ng day -1 .

17β-Estradiol (E2), a natural, endocrine-disrupting, steroid hormone, is excreted by all vertebrates and can enter the environment from domestic animal and wildlife wastes. Multiple field studies using livestock manures as E2 sources suggest significant background concentrations of E2 (e.g., wildlife sources, hydrolysis of E2 conjugates, previous inputs). To accurately understand field fate and transport processes of E2, it is necessary to address the issue of background detections. In this study, two fluorinated and three brominated surrogate compounds of E2 were synthesized and compared to native E2 using soil/water batch experiments and for estrogenic activity. Analytical difficulties presented by the two fluorinated congeners deemed these compounds to be unsuitable surrogates of E2, and further assessment was abandoned. However, the brominated congeners proved promising, with log( ) values that fell within the range previously reported for E2. Batch studies yielded similar relative aqueous concentrations and linear sorption isotherms across time for E2 and 2-bromo-17β-estradiol; however, the relative aqueous concentrations and linear sorption isotherms of 4-bromo-17β-estradiol and 2,4-dibromo-17β-estradiol were different from E2 but similar to one another. All three brominated congeners possessed estrogenic activity by E-Screen assay, albeit three orders of magnitude less than native E2, putatively due to steric interference introduced by the large bromine atom on the phenolic ring, the group that mediates interaction with the estrogen receptor. The data suggest that 2-bromo-17β-estradiol may serve as a suitable surrogate for E2 in planned field scale tracer studies designed to distinguish between antecedent and de novo inputs., (Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)

It is important to understand the partitioning of drugs in processed milk and milk products, when drugs are present in raw milk, in order to estimate the potential consumer exposure. Radioisotopically labeled erythromycin, ivermectin, ketoprofen, oxytetracycline, penicillin G, sulfadimethoxine, and thiabendazole were used to evaluate the distribution of animal drugs among rennet curd, whey, and protein fractions from skim cow milk. Our previous work reported the distribution of these same drugs between skim and fat fractions of milk. Drug distribution between curd and whey was significantly correlated (R 2 = 0.70) to the drug's lipophilicity (log P), with improved correlation using log D (R 2 = 0.95). Distribution of drugs was concentration independent over the range tested (20-2000 nM). With the exception of thiabendazole and ivermectin, more drug was associated with whey protein than casein on a nmol/g protein basis (oxytetracycline experiment not performed). These results provide insights into the distribution of animal drug residues, if present in cow milk, among milk fractions, with possible extrapolation to milk products.

The feed additive ractopamine hydrochloride was fortified at four concentrations into batch vials containing soils that differed in both biological activity and organic matter (OM). Sampling of the liquid layer for 14days demonstrated that ractopamine rapidly dissipated from the liquid layer. Less than 20% of the fortified dose remained in the liquid layer after 4hr, and recoveries of dosed ractopamine ranged from 8 to 18% in the liquid layer at 336hr. Sorption to soil was the major fate for ractopamine in soil:water systems, i.e., 42%-51% of the dose at 14days. The major portion of the sorbed fraction was comprised of non-extractables; a smaller fraction of the sorbed dose was extracted into water and acetone, portions which would be potentially mobile in the environment. Partitioning coefficients for all soils suggested strong sorption of ractopamine to soil which is governed by hydrophobic interactions and cation exchange complexes within the soil OM. Ractopamine degradation was observed, but to mostly non-polar compounds which had a higher potential than ractopamine to sorb to soil. The formation of volatiles was also suggested. Therefore, despite rapid and extensive soil sorption, these studies indicated a portion of ractopamine, present in manures used to fertilize soils, may be mobile in the environment via water-borne events., (Copyright © 2016. Published by Elsevier B.V.)

Seven animal drugs [penicillin G (PENG), sulfadimethoxine (SDMX), oxytetracycline (OTET), erythromycin (ERY), ketoprofen (KETO), thiabendazole (THIA), and ivermectin (IVR)] were used to evaluate the drug distribution between milk fat and skim milk fractions of cow milk. More than 90% of the radioactivity was distributed into the skim milk fraction for ERY, KETO, OTET, PENG, and SDMX, approximately 80% for THIA, and 13% for IVR. The distribution of drug between milk fat and skim milk fractions was significantly correlated to the drug's lipophilicity (partition coefficient, log P, or distribution coefficient, log D, which includes ionization). Data were fit with linear mixed effects models; the best fit was obtained within this data set with log D versus observed drug distribution ratios. These candidate empirical models serve for assisting to predict the distribution and concentration of these drugs in a variety of milk and milk products.

Male Sprague-Dawley rats were dosed orally with 3 mg/kg of one of three hexabromocyclododecane (HBCD) diastereomers. Each diastereomer was well absorbed (73-83%), and distributed preferentially to lipophilic tissues. Feces were the major route of excretion; cumulatively accounting for 42% of dose for α-HBCD, 59% for ß-HBCD, and 53% for γ-HBCD. Urine was also an important route of HBCD excretion, accounting for 13% of dose for α-HBCD, 30% for ß-HBCD, and 21% for γ-HBCD. Total metabolism of HBCD diastereomers followed the rank order ß > γ > α, and was >65% of that administered. The metabolites formed were distinct in male rats: α-HBCD did not debrominate or stereoisomerize, but formed two hydroxylated metabolites; ß- and γ-HBCD were both extensively metabolized via pathways of stereoisomerization, oxidation, dehydrogenation, reductive debromination, and ring opening. ß-HBCD was biotransformed to two mercapturic acid pathway metabolites. The metabolites of ß- and γ-HBCD were largely distinct, and could possibly be used as markers of exposure. These isomer-specific data suggest that α-HBCD would be the most dominant HBCD diastereomer in biological tissues because it was metabolized to the lowest degree and also accumulated from the stereoisomerization of the β- and γ- diastereomers.

To identify abiotic processes that govern the fate of a sulfate conjugated estrogen, 17β-estradiol-17-sulfate (E2-17S), soil batch experiments were conducted to investigate the dissipation, sorption, and degradation of radiolabeled E2-17S under sterilized conditions. The aqueous dissipation half-lives (DT50) for E2-17S ranged from 2.5 to 9.3h for the topsoil of high organic carbon (OC) content (1.29%), but E2-17S remained at ∼80% of applied dose in the low OC (0.26%) subsoil by 14 d. The non-linear sorption isotherms indicated limited sorption of E2-17S, and the concentration-dependent log KOC values were 2.20 and 2.45 for the topsoil and subsoil, respectively. Additionally, two types of hydroxyl E2-17S (OH-E2-17S and diOH-E2-17S) were found as major metabolites in the aqueous phase, which represented 9-25% and 6-7% of applied dose for the topsoil and subsoil at 14 d, respectively. Free estrogens, 17β-estradiol (E2) and estrone (E1), were detected from the sorbed phase of the soil-water systems., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Animal manure is the primary source of exogenous free estrogens in the environment, which are known endocrine-disrupting chemicals to disorder the reproduction system of organisms. Conjugated estrogens can act as precursors to free estrogens, which may increase the total estrogenicity in the environment. In this study, a comprehensive model was used to simultaneously simulate the coupled sorption and transformation of a sulfate estrogen conjugate, 17β-estradiol-17-sulfate (E2-17S), in various soil-water systems (non-sterile/sterile; topsoil/subsoil). The simulated processes included multiple transformation pathways (i.e. hydroxylation, hydrolysis, and oxidation) and mass transfer between the aqueous, reversibly sorbed, and irreversibly sorbed phases of all soils for E2-17S and its metabolites. The conceptual model was conceived based on a series of linear sorption and first-order transformation expressions. The model was inversely solved using finite difference to estimate process parameters. A global optimization method was applied for the inverse analysis along with variable model restrictions to estimate 36 parameters. The model provided a satisfactory simultaneous fit (R(2)adj=0.93 and d=0.87) of all the experimental data and reliable parameter estimates. This modeling study improved the understanding on fate and transport of estrogen conjugates under various soil-water conditions., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The dissolved (DF) and colloidal fractions (CF) of soil and manure play an important role in the environmental fate and transport of steroidal estrogens. The first objective of this study was to quantify the association of 17β-estradiol (E2) with the DF and CF isolated from (i) liquid swine manure (LSM), (ii) a soil:water mixture (soil), and (iii) a LSM:soil:water mixture (Soil+LSM). The appropriate CF and DF size fractions of the Soil, Soil+LSM, and LSM media were obtained by first filtering through a 0.45 μm filter, which provided the combined DF and CF (DF/CF). The DF/CF from the three media was spiked with carbon-14 ([(14)C]) radiolabeled E2 ([(14)C]-E2), and then ultrafiltered to isolate the CF (<0.45 μm and >1 kDa) from the DF (<1 kDa). The average recoveries of the [(14)C] associated with the DF were 67%-72%, 67%-79%, and 76%-78% for the Soil, Soil+LSM and LSM, respectively. For the CF that was retained on the 1 kDa filter, organic carbon and [(14)C]-E2 were dislodged with subsequent water rinses the Soil+LSM and LSM, but not the Soil. The second objective was to evaluate whether the E2 associated with the various fractions of the different media could still bind the estrogen receptor using an E2 receptor (17β-ER) competitor assay, which allowed E2 equivalent concentrations to be determined. The estrogen receptor assay results indicated that E2 present in the DF of the Soil and Soil+LSM solutions could still bind the estrogen receptor. Results from this study indicated that E2 preferentially associated with the DF of soil and manure, which may enhance its dissolved advective transport in surface and subsurface water. Furthermore, this study indicated that E2 associated with DF solutions in the environment could potentially induce endocrine responses through its interactions with estrogen receptor., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The fate of [C]17β-estradiol ([C]E2) was monitored for 42 d in triplicate 10-L anaerobic digesters. Total radioactive residues decreased rapidly in the liquid layer of the digesters and reached a steady-state value of 22 to 26% of the initial dose after 5 d. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry analyses of the liquid layer of the anaerobic digesters indicated a rapid degradation of E2 to estrone (E1), which readily adsorbed to the sludge layer subsequent to its formation. Estrone was the predominant steroid identified under anaerobic digestion in the liquid layer or sorbed to sludge at 42 d. Methane formation represented 11.1 ± 5.7% of the initial E2 fortification with 0.3 to 0.5% of the starting E2 mineralized to carbon dioxide. Maximum [C]methane production appeared between Days 4 and 7. An estimate of estrogenicity of the final product based on reported estrogen equivalents for E1 and E2 was 2% of the original in active digesters. Anaerobic digestion of swine waste has several management benefits; moreover, this study demonstrated that it reduces the potential of environmental release of estrogens, which are known endocrine disruptors., (Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)

In the environment, estrogen conjugates can be precursors to the endocrine-disrupting free estrogens, 17β-estradiol (E2) and estrone (E1). Compared to other estrogen conjugates, 17β-estradiol-17-sulfate (E2-17S) is detected at relatively high concentrations and frequencies in animal manure and surface runoff from fields receiving manure. To elucidate the lifecycle of manure-borne estrogens and their conjugates in the environment, the fate of radiolabelled E2-17S in agricultural soils was investigated using laboratory batch studies with soils of different organic carbon (OC) content (1.29% for topsoil versus 0.26% for subsoil). E2-17S was found relatively persistent in the aqueous phase throughout the duration of the 14 d experiment. The aqueous E2-17S persisted longer in the subsoil (half-lives (DT₅₀)=64-173 h) than the topsoil (DT₅₀=4.9-26 h), and the aqueous persistence of E2-17S depended on its initial concentration. The major transformation pathway was hydroxylation, yielding mono- and di-hydroxy-E2-17S (OH-E2-17S and diOH-E2-17S). Free estrogens, E2 and E1, were only observed in the sorbed phase of the soil at low concentrations (∼1% of applied dose), which demonstrated that deconjugation and subsequent oxidation had occurred. Although deconjugation was not a major pathway, E2-17S could be a precursor of free estrogens in the environment., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Estrogens, a potent group of endocrine disruptors toward aquatic species, are primarily excreted as conjugates from humans and animals. Radioassay-based approaches with detailed speciation have been frequently conducted for environmental-fate studies for pesticides; however, such techniques have not been exploited for reproductive hormones, and especially for hormone conjugates. This article describes a simple, robust, and high-mass-recovery approach to investigate the fate and transformation of a prototype estrogen conjugate, that is, 17β-estradiol-3-glucuronide (E2-3G), and its metabolites (free estrogens) in a laboratory soil and water matrix without the need for enzymatic cleavage and/or fluorescent derivatization. E2-3G and its metabolites were baseline resolved in a single run using high-performance liquid chromatography (HPLC) and quantified by liquid scintillation counting of the HPLC effluents. Transformation of E2-3G and the disposition of its metabolites--the free estrogens 17β-estradiol and estrone--into aqueous, sorbed, and gaseous phases, were adequately accounted for in a soil-water batch system. High mass balances ranging from 99.0% to 114.1% were obtained. Although the method gave lower sensitivity (parts per billion) than tandem mass spectrometer (parts per trillion), it offered sufficient chromatographic resolution and sensitivity to study the fate of labile estrogens in environmental matrices, using the concentration range of this study. An additional advantage of the approach was the relatively low cost of the instrumentation employed. The presented approach can be successfully applied to study the fate of conjugated hormones and their metabolites in the environment allowing simultaneous discernment of complex fate and transformation processes in soil, water, and gas.

The metabolism of α- and γ-hexabromocyclododecane (HBCD) was investigated in adult C57BL/6 female mice. α- or γ-[(14)C]HBCD (3 mg/kg bw) was orally administered with subsequent urine and feces collection for 4 consecutive days; a separate group of mice was dosed and sacrificed 3 h postexposure to investigate tissue metabolite levels. Extractable and nonextractable HBCD metabolites were quantitated in liver, blood, fat, brain, bile, urine, and feces and characterized by LC/MS (ESI-). Metabolites identified were distinct between the two stereoisomers. In mice exposed to α-HBCD, four hydroxylated metabolites were detected in fecal extracts, and one of these metabolite isomers was consistently characterized in liver, brain, and adipose tissue extracts. In contrast, fecal extracts from mice exposed to γ-HBCD contained multiple isomers of monohydroxy-pentabromocyclododecene, dihydroxy-pentabromocyclododecene, and dihydroxy-pentabromocyclododecadiene, while in liver and adipose tissues extracts only a single monohydroxy-pentabromocyclododecane metabolite was observed. Both stereoisomers were transformed to metabolites which formed covalent bonds to proteins and/or lipids in the gut as suggested by high fecal nonextractables. The presence of tissue- and excreta-specific metabolic products after in vivo exposure to the two main HBCD stereoisomers supports previous toxicokinetic studies indicating that these two stereoisomers are biologically distinct. The distinct metabolic products identified in this study have the potential to aid in the identification of stereoisomer-specific HBCD exposures in future biomonitoring studies.

In the environment, conjugated estrogens are nontoxic but may hydrolyze to their potent unconjugated, 'free' forms. Compared to free estrogens, conjugated estrogens would be more mobile in the environment because of their higher water solubility. To identify the fate of a conjugated estrogen in natural agricultural soils, batch experiments were conducted with a (14)C labeled prototype conjugate, 17β-estradiol-3-glucuronide (E2-3G). Initially, aqueous dissipation was dominated by biological hydrolysis of E2-3G and its oxidized metabolite, estrone glucuronide (E1-3G), both of which were transformed into the free estrogens, 17β-estradiol (E2) and estrone (E1), respectively. Following hydrolysis, hydrophobic sorption interactions of E2 and E1 dominated. Depending on soil organic matter contents, dissolved E2-3G persisted from 1-14 d, which was much longer than what others reported for free estrogens (generally <24 h). Biodegradation rate constants of E2-3G were smaller in the subsoil (0.01-0.02 h(-1)) compared to topsoil (0.2-0.4 h(-1)). Field observations supported our laboratory findings where significant concentrations (425 ng L(-1)) of intact E2-3G were detected in groundwater (6.5-8.1 m deep) near a swine (Sus scrofa domesticus) farm. This study provides evidence that conjugate estrogens may be a significant source of free estrogens to surface water and groundwater.

The objective of the study was to determine the effects of repeated bouts of supramaximal exercise on plasma adiponectin, interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels in sedentary men. Fourteen healthy, nonsmoking, and sedentary men aged between 18.4 and 21.4 years participated in the study. All the subjects performed 5 Wingate tests (WTs) with 75 g per kilogram body weight load with 2-minute intervals between the tests. Blood samples were collected at preexercise, immediately after, 15 and 60 minutes after the fifth WT. Serum and plasma samples were stored at -80°C until the time of analysis for myoglobin, adiponectin, IL-6, and TNF-α. Plasma adiponectin levels decreased, whereas IL-6 levels increased postexercise compared with that preexercise. The TNF-α levels were not changed with supramaximal exercise. In conclusion, repeated bouts of supramaximal exercise cause an inflammatory response in exercised muscle and increase in plasma IL-6 levels and decrease in adiponectin concentrations.

The excreted estrogen rate of all livestock in the United States is estimated at 134 kg d. The influence of manure treatment on the fate of estrogens is critical in deciding the recycling of over 300 million dry tons of livestock produced annually. The effects of two common manure management practices, heated composting and ambient temperature decomposition, on the fate of 17β-estradiol in poultry litter were determined. A mixture of poultry litter, wood chips, and straw was amended with [C]17β-estradiol and allowed to undergo decomposition with a laboratory-scale heated composter (HC) or room temperature incubation (RTI) for 24 d. Radiolabel in the finished products was fractionated into water-extractable, acetone-extractable, nonextractable, and mineralized fractions. Total 17β-estradiol radioactive residues in the HC and RTI ( = 2) treatments were not different ( > 0.05), except that statistically less 17β-estradiol was mineralized to CO during HC than RTI (1.1 vs. 10.0% for HC and RTI, respectively). Estrone was the major degradation product in extracts of HC and RTI treatments as determined by liquid chromatography/mass spectrometry analyses. The nonextractable residues indicated no quantitative differences among the humins between the treatments. An estimated 3% of the fortified estrogenicity remained after HC treatment, and 15% of the fortified estrogenicity remained after RTI treatment. If reduction of water-removable, biologically active 17β-estradiol is the treatment goal, then HC treatment would be slightly preferred over ambient temperature degradation. However, unmanaged, ambient temperature litter piles are less costly and time consuming for food animal producers and result in greater mineralization and similar immobilization of estradiol., (by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)

The occurrence of the manure-borne estrogen, 17β-estradiol (E2), was investigated in laboratory and field soils. In the laboratory, E2 was applied to soil to simulate concentrations found in swine (Sus scrofa domestica) manure (5000ngL(-1)). The aqueous-extracted E2 dissipated in the soil by 98% within 1h and was not significantly different from background concentrations (18ng L(-1)) for the duration of the experiment (64h). In the field study, soil cores were taken before and several dates after swine manure application. Equivalent porewater concentrations of water-extractable E2 were determined in 0.15-m increments down to the water table (0.70-2.00m deep). The average frequency of detection for 168 samples was 38% (average=40ng L(-1) porewater equivalents). Eleven days after manure application there was no significant effect on E2 detection frequency or concentration. However, E2 concentrations significantly increased by 6 months after manure application, and appeared to be related to precipitation. Concentrations then returned to original levels by 17 months after manure application. Manure did not have an immediate effect on E2 occurrence due to the capacity of the soil to rapidly sorb E2. However, it appears that soil may act as a long-term reservoir for E2 in the environment, which may be periodically released through desorption., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Alpha-hexabromocyclododecane (α-HBCD) is an emerging persistent organic pollutant present in the hexabromocyclododecane (HBCD) commercial mixture. HBCD is used as an additive flame retardant in a wide variety of household consumer products. Three main stereoisomers, alpha (α), beta (β), and gamma (γ), comprise roughly 10, 10, and 80% of the mixture, respectively. Despite its small contribution to HBCD global production and usage, α-HBCD is the major stereoisomer found in wildlife and human tissues including breast milk and blood in North America, European Union, and Asia. No mammalian or human data are currently available regarding the toxicokinetics of α-HBCD. This study was conducted in an effort to fully characterize the absorption, distribution, metabolism, and elimination of α-HBCD following a single and repeated exposure with respect to dose, time, and route of administration in female C57BL/6 mice. Results indicate that ∼90% of the administered dose (3 mg/kg) was absorbed after oral exposure. Disposition was (1) dictated by lipophilicity, as adipose, liver, muscle, and skin were major depots and (2) was dose dependent with nonlinear accumulation at higher doses. Elimination, both whole-body and from individual tissues, was biphasic. α-HBCD-derived radioactivity was excreted in the feces as parent and metabolites, whereas urine only contained metabolites. Presence of polar metabolites in the blood and urine were a major factor in determining the rapid initial whole-body half-life after a single oral exposure. Initial half-lives were ∼1-3 days and much longer terminal half-lives of 17 days were observed, suggesting the potential for α-HBCD bioaccumulation. A 10-day repeated study supports α-HBCD bioaccumulation potential. Stereoisomerization previously observed after exposure to γ-HBCD was not seen after exposure of α-HBCD. The toxicokinetic behavior reported here has important implications for the extrapolation of toxicological studies of the commercial HBCD mixture to the assessment of risk of α-HBCD which is the major stereoisomer found in wildlife and people.

17β-estradiol (E2) is a natural estrogenic hormone found in animal manure and urine, which may cause endocrine disruption in sensitive organisms. 17β-Estradiol has been widely detected in the environment, and animal agriculture may be an important source. The objectives of this study were to investigate the potential sources and/or spatial and temporal characteristics contributing to detections of E2 at the farm-scale. Soil cores, segmented into 0.15m increments, were taken down to the water table from four locations (three potential E2 sources and one control) at or around a swine (Sus scrofa domesticus) farm on five different dates between 2006 and 2007. Estradiol was quantified in the soil-water extracts using liquid chromatography-with tandem mass spectrometry (LC/MS/MS) analysis. Estradiol detections were widespread and found in 128 out of 345 extractions (37%). Concentrations ranged from 0 to 1910 ng L⁻¹ (porewater equivalents). A location that received field application of manure had significantly lower E2 concentrations compared to other locations. Also, the spring 2007 E2 concentrations were significantly higher than all other sample dates, perhaps related to climatic and hydrological events. Results suggested E2 was not directly related to manure sources, but was widespread in this environment. Where E2 was detected, highest concentrations favored the upper profile, while the greatest frequency of detections was in the lower profile and near the water table. Detections of E2 were associated with high organic mater contents in the upper profile and high sand contents in the lower profile. The study suggests that E2 is widespread in some soil environments, raising questions as to the source and mechanisms that facilitate its transport and mobility., (Copyright © 2010 Elsevier Ltd. All rights reserved.)