Clearance of PCDD/Fs via the gastrointestinal tract in occupationally exposed persons.

A digestive tract mass balance was performed on six men with high body burdens of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). Intake via food was measured by analyzing duplicate portions of the food consumed by the volunteers and excretion via feces was determined by quantitative collection and analysis of the feces. Blood samples were taken to determine the current body burden. The results showed that the quantity of non-metabolized chemical excreted in the feces clearly exceeded the uptake via food for all of the 2,3,7,8-substituted PCDDs and some of the PCDFs, indicating a significant clearance across the gastrointestinal tract. The concentrations of these PCDD/F congeners in blood and feces were highly correlated (r > 0.8), demonstrating that the fecal PCDD/F content was determined by the body burden. The half lives in the test persons due to fecal clearance of non-metabolized chemical were estimated from the excretion rate and the current body burden and ranged between 10 years (Cl8DD) and 33 years (2,3,4,7,8-Cl5DF). These were compared with the overall contaminant half-lives due to all clearance processes which were calculated from the body burden and the decrease in blood concentrations measured over several years. The fecal clearance of non-metabolized PCDD/F contributed on average between 37% (2,3,7,8-Cl4DD) and 90% (Cl8DD) to the total elimination. This indicates that the gastrointestinal pathway plays a decisive role in the clearance of most 2,3,7,8-subsituted PCDD/F congeners.     

Polychlorinated biphenyl distribution and faecal excretion in rats fed wheat bran

Polychlorinated biphenyls (PCBs) are abundant and persistent environmental contaminants, which tend to accumulate through the food chain. Because of the toxic potential of these compounds, body burden should be kept as low as possible e.g. by taking dietary measures. In the present report, the effect of wheat bran consumption on absorption of dietary PCBs as well as on excretion of previously absorbed PCBs was investigated in rats. Moreover, the accumulation of 7 reference PCB congeners in liver and abdominal adipose tissue was studied. Faecal excretion of dietary PCBs was significantly higher in rats fed wheat bran compared to its placebo. As a result, apparent PCB digestibility was diminished, but not enough to significantly affect PCB accumulation in liver and abdominal adipose tissue. Furthermore, excretion of previously absorbed PCBs following switching of the rats to a control diet without added PCBs was enhanced by wheat bran fibre intake, although to a much lesser extent than excretion of PCBs originating directly from the diet. Consequently, stimulation of PCB clearance from liver and abdominal adipose tissue due to wheat bran consumption was not detectable. Although no preferential absorption of PCB congeners was observed, PCB patterns in tissues obviously differed from the dietary PCB pattern. This was mainly due to PCBs 52 and 101, which were metabolised in the body. Moreover, reduced levels of PCB 138 were found in liver, while PCB 28 and 138 were predominantly present in adipose tissue. The experiment also demonstrated that PCB redistribution from the liver to the adipose tissue occurs.     

Effects of dietary wheat bran on absorption and accumulation of PCBs in rats

Polychlorinated biphenyls (PCBs) are toxic environmental contaminants, which tend to accumulate in the food chain. Since dietary intake is the most important exposure route, PCB body burden may be affected by taking proper dietary measures. In the present study, diets were supplemented with either wheat bran or its cellulose based placebo in order to study the effect of bran consumption on the absorption of dietary PCBs and the excretion of initially stored PCBs. During the period of PCB intake, faecal PCB excretion was elevated by consumption of wheat bran as compared to the placebo. Hence, apparent faecal PCB digestibilities as well as PCB retentions in the whole body were lower in the wheat bran consuming rats. After ending PCB consumption, dietary wheat bran had only a minor effect on faecal PCB output while accumulation in the body was not affected. When PCBs were consumed for a longer time, a small but significant reduction of apparent faecal PCB digestibility was found. However, PCB content in the body kept increasing while PCB retention as percent of intake remained almost constant. Furthermore, differences among individual PCB congeners in metabolic susceptibility and hydrophobic characteristics had an impact on their accumulation in the body.     

Identification of the major urinary and fecal metabolites of 3,5-dinitrobenzamide in chickens and rats

Colostomized chickens given oral doses of 3,5-dinitrobenzamide (nitromide) cleared nitromide predominantly through the urine (58% of dose) and feces (21% of dose). Rats cleared 52% of nitromide via urinary excretion and 44% via feces. Major urinary metabolites for both chickens and rats include: 3-amino-5-nitrobenzamide, 3-acetamido-5-nitrobenzamide, 3-acetamide-5-aminobenzamide, and 3,5-diacetamidobenzamide. The major fecal metabolite in chickens was 3-acetamido-5-nitrobenzamide (67% of fecal 14C) and 3-acetamido-5-aminobenzamide in rats (approximately 50%).     

Metabolism, tissue disposition, and excretion of 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) in male Sprague-Dawley rats

A single oral dose of [14C] 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) was administered to conventional and bile-duct cannulated male Sprague-Dawley rats. Tissue disposition, excretion and metabolism was determined. BTBPE is a low-volume brominated flame retardant used in resins or plastics, and toxicity data in peer-reviewed journals is extremely limited. BTBPE was fairly insoluble in lipophilic solutions, which made dose preparation difficult. The great majority of 14C (>94%) was excreted in the feces of both groups of rats at 72 h, and tissue retention was minimal. Lipophilic tissues contained the highest concentrations of BTBPE, e.g. thymus, adipose tissue, adrenals, lung, and skin. Metabolites were excreted in the urine, bile and feces, but at a very low level. Fecal metabolites were characterized as monohydroxylated, monohydroxylated with debromination, dihydroxylated/debrominated on a single aromatic ring, monohydroxylated on each aromatic ring with accompanying debromination, and cleavage on either side of the ether linkage to yield tribromophenol and tribromophenoxyethanol. Despite a limited quantity of stable metabolites extractable in the feces, non-extractable 14C levels were relatively high (39% of the 0-24 h fecal 14C), which suggested that BTBPE could be metabolically activated in the rat and covalently bound to fecal proteins and/or lipids. It was concluded that limited absorption and metabolism of BTBPE would occur by ingestion in mammals.     

Modeling the exposure of children and adults via diet to chemicals in the environment with crop-specific models

Exposure to chemicals via diet is a major uptake pathway for many compounds but is often estimated in a rather generic way. We use a new model framework (NMF) with crop-specific models to predict the dietary intake by 4-5-year-old children and 14-75-year-old women of three environmental compounds from their background concentrations in soil and air. Calculated daily intakes of benzo(a)pyrene and 2,3,7,8-TCDD are in good agreement with measured results from diet studies. The major source of both compounds in human diet is deposition from air. Inhalation of air and ingestion of soil play a minor role. Children take up more than twice the amount than adults per kg bodyweight, due to higher consumption per kg bodyweight. Contrary, the methods for indirect human exposure suggested in the Technical Guidance Document (TGD) for chemical risk assessment in the EU lead to overprediction, due to unrealistic consumption data and a false root model.     

Absorption of decabromodiphenyl ether and other organohalogen chemicals by grey seals (Halichoerus grypus)

An input-output balance study was performed for polybrominated diphenyl ethers, polychlorinated biphenyls and some organochlorine pesticides on three captive, juvenile grey seals (Halichoerus grypus). The animals were fed a diet of herring for six months, during the last three months of which this study was performed. A supplement of decabromodiphenyl ether was included in the diet during the second month of the study. Consistently high absorption (>89%) was observed for all of the chemicals studied, whereas work on other animals has generally shown high (>80%) net absorption at log K(OW) < approximately 6, dropping towards higher log K(OW), and very low absorption of decabromodiphenyl ether. The half-life of decabromodiphenyl ether in blood was estimated to be between 8.5 and 13 days. Measurable concentrations of decabromodiphenyl ether were detected in seal blubber at the end of the study, indicating that this chemical can be stored in adipose and may bioaccumulate. Current understanding of the mechanism of absorption of organohalogen chemicals and the potential for accumulation of decabromodiphenyl ether will need reassessing in the light of these results.     

Dimension reduction and source identification for multispecies groundwater contamination

Assessment of chemical contamination at large industrial complexes with long and sometimes unknown histories of operation represents a challenging environmental problem. The spatial and temporal complexity of the contaminant may be due to changes in production processes, differences in the chemical transport, and the physical heterogeneity of the soil and aquifer materials. Traditional mapping techniques are of limited value for sites where dozens of chemicals with diverse transport characteristics may be scattered over large spatial areas without documentation of disposal histories. In this context, a site with a long and largely undocumented disposal history of shallow groundwater contamination is examined using principal component analysis (PCA). The dominant chemical groups and chemical "modes" at the site were identified. PCA results indicate that five primary and three transition chemical groups can be identified in the space of the first three eigenvectors of the correlation matrix, which account for 61% of the total variance of the data. These groups represent a significant reduction in the dimension of the original data (116 chemicals). It is shown that each group represents a class of chemicals with similar chemo-dynamic properties and/or environmental response. Finally, the groups are mapped back onto the site map to infer delineation of contaminant source areas for each class of compounds. The approach serves as a preliminary step in subsurface characterization, and a data reduction strategy for source identification, subsurface modeling and remediation planning.     

Biliary secretion,retention and excretion of five 14C-labelled polychlorinated biphenyls in the rat

Five ¹⁴C-labelled polychlorinated biphenyls: 2,4′,5-trichlorobiphenyl, 2,2′,4,5′-tetrachlorobiphenyl, 2,2′,4,5,5′-pentachlorobiphenyl, 2,2′,3,4,4′-pentachlorobiphenyl and 2,2′,4,4′,5,5′-hexachlorobiphenyl were administered orally to bile-cannulated rats. The activity secreted in the bile, excreted in the feces and the urine was determined. Residues of radioactivity in certain tissues and the carcass were also measured.The trichlorobiphenyl showed the highest absorption (93.8%±5.4) from the gastrointestinal tract and biliary secretion of radioactivity (87.6%±6.1 of the dose). The hexachlorobiphenyl showed the lowest absorption and biliary secretion, 28.2%±1.4 and 18.6%±1.3, respectively. The urinary excretion was low and the radioactive residues in the eviscerated carcasses increased with the chlorine content of the biphenyls.     

Absorption of polychlorinated biphenyls, dibenzo-p-dioxins and dibenzofurans by breast-fed infants

The absorption of polychlorinated biphenyls, dibenzo-p-dioxins and dibenzofurans was studied in four breast-fed infants. The absorption was measured by comparing the estimated total intake and the excretion in faeces, during 48 hours, at three different time points; 1, 2 and 3 months post parta. The levels of the analysed compounds in the human milk are typical for Sweden, i.e 20 ppt toxic equivalents for the dibenzo-p-dioxins and dibenzofurans and for the polychlorinated biphenyls 16 ppt toxic equivalents. For most of the congeners the absorption is found to be over 95%. Higher excretion is noticed for heptachlorinated and octachlorinated dioxins.     

Cholestyramine enhances fecal elimination of pentachlorophenol in rhesus monkeys

The effect of cholestyramine in the daily diet upon the excretion of pentachlorophenol with the feces was studied in the rhesus monkey. The treatment increased fecal elimination of pentachlorophenol and/or metabolites up to 9- to 14-fold over a six-day period. At the same time urinary excretion was reduced 2- to 6-fold. The data suggest that cholestyramine interrupts the enterhepatic circulation of PCP and/or metabolites thus indicating its possible usefulness in preventing toxicity of PCP that otherwise may occur due to reabsorption of biliary PCP and/or metabolites.     

Uptake, distribution and elimination of monosodium methanearsonate following long term oral administration of the herbicide to sheep and goats

The rate and extent of accumulation and washout of arsenic, during daily oral administration of the herbicide monosodium methanearsonate (MSMA) were evaluated in Iranian dairy sheep and goats. Subjects received a dose of 10 mg of MSMA as arsenic per kg of body weight daily for 28 consecutive days. The total arsenic concentration in blood and milk was measured during and after the period of MSMA administration while arsenic in urine and feces was measured for 10 days following administration of last dosage of MSMA. Arsenic was accumulated slowly during 28 days of MSMA administration and steady states were essentially complete in sheep after 20 days and in goats following 25 days of MSMA administration. Blood arsenic concentration decreased rapidly after termination of MSMA administration. In both test animals, the half-lives of washout were smaller than accumulation. The concentration of arsenic in the urine and feces of both species did not increase significantly over controls and animals were free of arsenic relatively shortly after administration stopped. These data indicate that arsenic from MSMA is mainly absorbed from gastrointestinal tract and is not significantly accumulated in the body. Arsenic is eliminated from body by way of urine and feces with urinary excretion being the most important route.     

Use of selected chemical markers in combination with a multiple regression model to assess the contribution of domesticated animal sources of fecal pollution in the environment

Human and animal wastes are major sources of environmental pollution. Reliable methods of identifying waste sources are necessary to specify the types and locations of measures that best prevent and mitigate pollution. This investigation demonstrates the use of chemical markers (fecal sterols and bile acids) to identify selected sources of fecal pollution in the environment. Fecal sterols and bile acids were determined for pig, horse, cow, and chicken feces (10-26 feces samples for each animal). Concentrations of major fecal sterols (coprostanol, epicoprostanol, cholesterol, cholestanol, stigmastanol, and stigmasterol) and bile acids (lithocholic acid, deoxycholic acid, cholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and hyodeoxycholic acid) were determined using a gas chromatography and mass spectrometer (GC-MS) technique. The fecal sterol and bile acid concentration data were used to estimate parameters of a multiple linear regression model for fecal source identification. The regression model was calibrated using 75% of the available data validated against the remaining 25% of the data points in a jackknife process that was repeated 15 times. The regression results were very favorable in the validation data set, with an overall coefficient of determination between predicted and actual fecal source of 0.971. To check the potential of the proposed model, it was applied on a set of simulated runoff data in predicting the specific animal sources. Almost 100% accuracy was obtained between the actual and predicted fecal sources. While additional work using polluted water (as opposed to fresh fecal samples) as well as multiple pollution sources are needed, results of this study clearly indicate the potential of this model to be useful in identifying the individual sources of fecal pollution.     

Enhancement in fecal excretion of dioxin isomer in mice by several dietary fibers

The effect of increased nutrients (protein, lipid, vitamins and minerals) on dioxin-induced toxic manifestations such as immune suppression, hepatic hypertrophy, splenic atrophy and enzyme induction was investigated in mice after oral administration of 1,2,3,4,7,8-HxCDD (HxCDD) as one of a representative compound of dioxin isomers. Consequently, it appeared that increased minerals and vitamins in the diet prevented immune suppression by HxCDD. In addition, to clarify the additive effect of nutrients and the ability to hasten the excretion of dioxins by dietary fiber, the adsorbing of dioxins by 16 dietary fibers was investigated by in vitro experiment. Among 16 dietary fibers, locust bean gum, pectin, alginic acid, guar gum, chitin and cellulose were effective in binding dioxin isomers. These dietary fibers also enhanced the fecal excretion of HxCDD in mice.     

Uptake,distribution and elimination of monosodium methanearsonate following long term oral administration of the herbicide to sheep and goats

Abstract

The rate and extent of accumulation and washout of arsenic, during daily oral administration of the herbicide monosodium methanearsonate (MSMA) were evaluated in Iranian dairy sheep and goats. Subjects received a dose of 10 mg of MSMA as arsenic per kg of body weight daily for 28 consecutive days. The total arsenic concentration in blood and milk was measured during and after the period of MSMA administration while arsenic in urine and feces was measured for 10 days following administration of last dosage of MSMA.

Arsenic was accumulated slowly during 28 days of MSMA administration and steady states were essentially complete in sheep after 20 days and in goats following 25 days of MSMA administration. Blood arsenic concentration decreased rapidly after termination of MSMA administration. In both test animals, the half‐lives of washout were smaller than accumulation. The concentration of arsenic in the urine and feces of both species did not increase significantly over controls and animals were free of arsenic relatively shortly after administration stopped.

These data indicate that arsenic from MSMA is mainly absorbed from gastrointestinal tract and is not significantly accumulated in the body. Arsenic is eliminated from body by way of urine and feces with urinary excretion being the most important route.     

Correlations between experimental and predicted equilibrium distribution coefficient of chlorobenzene and chlorophenol compounds in soil-water systems using partial solubility parameters

Many pesticides are degraded to become chlorinated aromatic compounds in soils. Equilibrium distribution of chlorobenzene and chlorophenol compounds in soil-water systems of Yangmingshan loam, Pingcheng silty clay loam and Annei silty loam was studied with the integral distribution equilibrium equation involving the partial solubility parameters of the chemicals. If the adsorption of chemicals on soils is partitioning in soil organic matter surrounding the soil mineral particles, the absorption constant (Kd) of a chemical in soil-water system could be stated as the distribution coefficient (or partition constant, Koc) of the chemical in the two adjunct immiscible phases--water and soil organic matter. The distribution coefficient (Koc) of chemicals calculated from the integral distribution equilibrium equation agrees well with the experimental adsorption coefficient (Kd, or experimental Koc) of chemicals determined in this study, for all the three different types of soils in water according to multiple-regression analysis. Reference data of Karger or Tijssen are employed to estimate the Koc for both polar and non-polar chemicals. The integral distribution equilibrium equation can exactly describe the distribution behavior of nonionic compound of chlorobenzenes and chlorophenols in soil-water systems.     

Research to develop a predicting system of mammalian subacute toxicity (3) construction of a predictive toxicokinetics model

A new predictive toxicokinetics model was developed to estimate subacute toxicity (target organs, severity, etc.) of non-congeneric industrial chemicals, where the chemical structures and physico-chemical properties are only available. Thus, a physiological pharmacokinetics model, which consists of blood, liver, kidney (these were experimentally found as major toxicological targets), muscle and fat compartments , was established to simulate the chemical concentrations in organs/tissues with pharmacokinetic parameters by means of Runge-Kutta-Gill algorithm. The pliarmacokinetic parameters, i.e. absorption rate, absorption ratio, hepatic extraction ratio of metabolism and renal clearance were calculated by using separately established Quantitative Structure-Pharmacokinetics Relationship equations. The developed predictive model was then applied to simulations of 43 non-congeneric industrial chemicals. The chemical concentrations in organs/tissues after single oral administration were simulated, and their maximum concentrations (Cmax's) and area tinder the concentration-time curves (AUC's) were calculated.Fast Inverse Laplace Transform was newly applied for the purpose of simulation of 28-day repeated dose toxicity.Simulated concentrations of 28 days repeated dose were, however, found to be the same as those of simple repetitions of a single administration per day because of the short half-lives of non-congeneric industrial chemicals.A comparison of subacute toxicity data with Cmax's and AUC's in a single dose scenario suggested that the organs/tissues with relatively high concentrations of tested chemical substances were the most sensitive targets within a chemical.Chemical concentrations in liver, for instance, were correlated with the severity of hepatotoxicity among the chemicals. It was also suggested that to improve and widen the present approach, data of metabolite and reactivity of non-congeneric industrial chemicals to organs/tissues, receptors, etc. should be incorporated into the model.     

Calibration and field performance of membrane-enclosed sorptive coating for integrative passive sampling of persistent organic pollutants in water

Membrane-enclosed sorptive coating (MESCO) is a miniaturised monitoring device that enables integrative passive sampling of persistent, hydrophobic organic pollutants in water. The system combines the passive sampling with solventless preconcentration of organic pollutants from water and subsequent desorption of analytes on-line into a chromatographic system. Exchange kinetics of chemicals between water and MESCO was studied at different flow rates of water, in order to characterize the effect of variable environmental conditions on the sampler performance, and to identify a method for in situ correction of the laboratory-derived calibration data. It was found that the desorption of chemicals from MESCO into water is isotropic to the absorption of the analytes onto the sampler under the same exposure conditions. This allows for the in situ calibration of the uptake of pollutants using elimination kinetics of performance reference compounds and more accurate estimates of target analyte concentrations. A field study was conducted to test the sampler performance alongside spot sampling. A good agreement of contaminant patterns and water concentrations was obtained by the two sampling techniques.     

Reactive transport modeling of processes controlling the distribution and natural attenuation of phenolic compounds in a deep sandstone aquifer

Reactive solute transport modeling was utilized to evaluate the potential for natural attenuation of a contaminant plume containing phenolic compounds at a chemical producer in the West Midlands, UK. The reactive transport simulations consider microbially mediated biodegradation of the phenolic compounds (phenols, cresols, and xylenols) by multiple electron acceptors. Inorganic reactions including hydrolysis, aqueous complexation, dissolution of primary minerals, formation of secondary mineral phases, and ion exchange are considered. One-dimensional (1D) and three-dimensional (3D) simulations were conducted. Mass balance calculations indicate that biodegradation in the saturated zone has degraded approximately 1-5% of the organic contaminant plume over a time period of 47 years. Simulations indicate that denitrification is the most significant degradation process, accounting for approximately 50% of the organic contaminant removal, followed by sulfate reduction and fermentation reactions, each contributing 15-20%. Aerobic respiration accounts for less than 10% of the observed contaminant removal in the saturated zone. Although concentrations of Fe(III) and Mn(IV) mineral phases are high in the aquifer sediment, reductive dissolution is limited, producing only 5% of the observed mass loss. Mass balance calculations suggest that no more than 20-25% of the observed total inorganic carbon (TIC) was generated from biodegradation reactions in the saturated zone. Simulations indicate that aerobic biodegradation in the unsaturated zone, before the contaminant entered the aquifer, may have produced the majority of the TIC observed in the plume. Because long-term degradation is limited to processes within the saturated zone, use of observed TIC concentrations to predict the future natural attenuation may overestimate contaminant degradation by a factor of 4-5.