In vitro modeling of the post-ingestion mobilization and bioaccessibility of pesticides sorbed to soil and house dust.

Soils and dusts can act as sinks for semivolatile lipophilic organic compounds and children ingest relatively large amounts of both soils and dusts. Following intake, sorbed chemicals may desorb (mobilize) and become available for intestinal absorption (bioaccessible). When chemicals are not degraded in the digestive tract, mobilization can approximate bioaccessibility. Alternatively, when gastrointestinal degradation of mobilized chemicals does occur, it can be useful to separate mobilization from bioaccessibility. In this study we used synthetic digestive fluids in a sequential, three-compartment (saliva, gastric, and intestinal) in vitro assay to construct mobilization and bioaccessibility models for 16 pesticides (log Kow 2.5-6.8) sorbed to 32 characterized soils and house dusts. To address the potential loss of mobilized pesticides due to absorption, the assays were repeated using a solid phase sorbent (tenax) added to the digestive fluid immediately after addition of the intestinal fluid components. We found that pesticide mobilization was predicted by pesticide log Kow and the carbon content of the soils and dusts. Pesticide loss measurably reduced the bioaccessibility of most pesticides, and bioaccessibility was largely predicted by log Kow and pesticide loss rate constants. Introduction of the sink increased mobilization by x̄ = 4 ± 6% (soil) and x̄ = 9 ± 7% (dust) while bioaccessibility increases were x̄ = 41 ± 21% (soil) and x̄ = 24 ± 12% (dust). The physicochemical properties of the soils, dusts, and pesticides used in this study successfully predicted the in vitro mobilization and bioaccessibility of the pesticides. This suggests that modeling of pesticide mobilization and bioaccessibility could reduce uncertainty in exposure and risk assessments.

In vitro modeling of the post-ingestion bioaccessibility of per- and polyfluoroalkyl substances sorbed to soil and house dust.

Per- and polyfluoroalkyl substances (PFAS) are regularly found in soils and dusts, both of which can be consumed by children at relatively high amounts. However, there is little data available to model the bioaccessibility of PFAS in soils and dusts when consumed or to describe how the physiochemical properties of PFAS and soils/dusts might affect bioaccessibility of these chemicals. Because bioaccessibility is an important consideration in estimating absorbed dose for exposure and risk assessments, in the current study, in vitro assays were used to determine bioaccessibility of 14 PFAS in 33 sets of soils and dusts. Bioaccessibility assays were conducted with and without a sink, which was used to account for the removal of PFAS due to their movement across the human intestine. Multiple linear regression with backward elimination showed that a segmented model using PFAS chain length, number of branches, and percent total organic carbon explained 78.0%-88.9% of the variability in PFAS bioaccessibility. In general, PFAS had significantly greater bioaccessibility in soils relative to dusts and the addition of a sink increased bioaccessibility in the test system by as much as 10.8% for soils and 20.3% for dusts. The results from this study indicate that PFAS bioaccessibility in soils and dusts can be predicted using a limited set of physical chemical characteristics and could be used to inform risk assessment models.

Is food type important for in vitro post ingestion bioaccessibility models of polychlorinated biphenyls sorbed to soil?

Soils are sorbents for many organic compounds and children consume relatively large amounts of soil. To improve the estimated health risks from this exposure pathway, we examined the role of co-ingested foods in determining the post-ingestion bioaccessibility (mobilization) of 18 polychlorinated biphenyls (PCBs) sorbed to 10 characterized soils. The bioaccessibility test system (DIN 19738, 2004) was an in vitro, 3-compartment, digestive tract containing salts, protein, and bile. Each soil was fortified with PCBs, then, digestive fluids appropriate to each compartment, were added sequentially. Next, digestive fluid and soil were seperated and PCB concentrations in both media were measured. This complete test system was then reduced to assess contributions of individual endogenous digestive fluid constituents (water, salts, pancreatin, bile, and mucin) and representative foods: protein (bovine serum albumin (BSA)), sugar (glucose), and fat (oleic acid). Then, the influence of increasing concentrations of BSA, glucose, and oleic acid was evaluated (individually) complete test systems. In a subset of the samples, solid phase microextraction (SPME) was used to measure freely dissolved PCBs. Across all treatments, percent soil organic carbon was the most influential bioaccessibility determinant, accounting for ≥87% of the explained variation. When evaluated individually, pancreatin, mucin, BSA, bile, and oleic acid each effectively increased PCB bioaccessibility and reduced freely dissolved PCB concentrations. This suggests competitive sorption of PCBs by organic constituents of the digestive constituents. Without sink material, intra-PCB mobilization differences were observed as freely dissolved PCB concentrations inversely correlated (p < 0.05) with their respective log Kow's. When added to the complete digestive fluid, increasing oleic acid mass increased PCB bioaccessibility (p < 0.05), while adding more BSA or glucose did not (p > 0.05). This indicates that fat intake may be the sole consideration needed when modeling dietary contributions to bioaccessibility of soil sorbed PCBs.

The role of soil and house dust physicochemical properties in determining the post ingestion bioaccessibility of sorbed polychlorinated biphenyls.

Ingestion of soils and house dusts is an important pathway for children's exposure to sorbed organic pollutants such as polychlorinated biphenyls (PCBs). To reduce the uncertainty of the exposure estimates, it is important to understand the extent to which chemicals desorb and become bioaccessible following ingestion. In this study we use a three compartment in vitro digestive system to model the role of soil and house dust physicochemical properties on the post ingestion bioaccessibility of PCBs. Matched pairs (n = 37) of soil and dust were characterized for percent carbon and nitrogen, pH, moisture content, and particle size distribution. They were then fortified with a mixture of 18 PCBs and processed through the assay. The percent bioaccessibility of each PCB was calculated, then modeled using individual PCB log Kow values and the soil and dust properties. The bioaccessibility of the PCBs in soil (x̄ = 65 ±â€¯16%) was greater (p < 0.001) than that of the PCBs in house dust (x̄ = 36 ±â€¯14%). In the soil model, carbon was the sole statistically significant predictive (p ≤ 0.05) variable, while in house dust, both carbon and clay content were statistically significant (p ≤ 0.05) predictors.

Distribution, variability, and predictors of urinary bisphenol A levels in 50 North Carolina adults over a six-week monitoring period.

Bisphenol A (BPA) is commonly manufactured to make polycarbonate plastics and epoxy resins for use in consumer products and packaged goods. BPA has been found in several different types of environmental media (e.g., food, dust, and air). Many cross-sectional studies have frequently detected BPA concentrations in adult urine samples. However, limited data are available on the temporal variability and important predictors of urinary BPA concentrations in adults. In this work, the major objectives were to: 1) quantify BPA levels in duplicate-diet solid food, drinking water, hard floor surface wipe, and urine samples (first-morning void [FMV], bedtime, and 24-h) collected from adults over a six-week monitoring period; 2) determine the temporal variability of urinary BPA levels using concentration, specific gravity (SG) adjusted, creatinine (CR) adjusted, and excretion rate values, and; 3) examine associations between available study factors and urinary BPA concentrations. In 2009-2011, a convenience sample of 50 adults was recruited from residential settings in North Carolina. The participants completed diaries and collected samples during weeks 1, 2, and/or 6 of a six-week monitoring period. BPA was detected in 38%, 4%, and 99% of the solid food (n=775), drinking water (n=50), and surface wipe samples (n=138), respectively. Total BPA (free plus conjugated) was detected in 98% of the 2477 urine samples. Median urinary BPA levels were 2.07ng/mL, 2.20ng/mL-SG, 2.29ng/mg, and 2.31ng/min for concentration, SG-adjusted, CR-adjusted, and excretion rate values, respectively. The intraclass correlation coefficient (ICC) estimates for BPA showed poor reproducibility (≤0.35) for all urine sample types and methods over a day, week, and six weeks. CR-adjusted bedtime voids collected over six-weeks required the fewest, realistic number of samples (n=11) to obtain a reliable biomarker estimate (ICC=0.80). Results of linear mixed-effects models showed that sex, race, season, and CR-level were all significant predictors (p<0.05) of the adults' urinary BPA concentrations. BPA levels in the solid food and surface wipe samples did not contribute significantly to the participants' urinary BPA concentrations. However, a significant positive relationship was observed between solid food intake and urine-based estimates of BPA dose, when aggregated over 24-h periods. Ingestion of BPA via solid food explained only about 20% of the total dose (at the median of the dose distribution), suggesting that these adults were likely exposed to other major unknown (non-dietary) sources of BPA in their everyday environments.

Solvent-dependent transformation of aflatoxin B1 in soil.

To date, all studies of aflatoxin B1 (AFB1) transformation in soil or in purified mineral systems have identified aflatoxins B2 (AFB2) and G2 (AFG2) as the primary transformation products. However, identification in these studies was made using thin layer chromatography which has relatively low resolution, and these studies did not identify a viable mechanism by which such transformations would occur. Further, the use of methanol as the solvent delivery vehicle in these studies may have contributed to formation of artifactual transformation products. In this study, we investigated the role of the solvent vehicle in the transformation of AFB1 in soil. To do this, we spiked soils with AFB1 dissolved in water (93:7, water/methanol) or methanol and used HPLC-UV and HPLC-MS to identify the transformation products. Contrasting previous published reports, we did not detect AFB2 or AFG2. In an aqueous-soil environment, we identified aflatoxin B2a (AFB2a) as the single major transformation product. We propose that AFB2a is formed from hydrolysis of AFB1 with the soil acting as an acid catalyst. Alternatively, when methanol was used, we identified methoxy aflatoxin species likely formed via acid-catalyzed addition of methanol to AFB1. These results suggest that where soil moisture is adequate, AFB1 is hydrolyzed to AFB2a and that reactive organic solvents should be avoided when replicating natural conditions to study the fate of AFB1 in soil.

Environmentally relevant pyrethroid mixtures: A study on the correlation of blood and brain concentrations of a mixture of pyrethroid insecticides to motor activity in the rat.

Human exposure to multiple pyrethroid insecticides may occur because of their broad use on crops and for residential pest control. To address the potential health risk from co-exposure to pyrethroids, it is important to understand their disposition and toxicity in target organs such as the brain, and surrogates such as the blood when administered as a mixture. The objective of this study was to assess the correlation between blood and brain concentrations of pyrethroids and neurobehavioral effects in the rat following an acute oral administration of the pyrethroids as a mixture. Male Long-Evans rats were administered a mixture of ß-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate and cis- and trans-permethrin in corn oil at seven dose levels. The pyrethroid with the highest percentage in the dosing solution was trans-permethrin (31% of total mixture dose) while deltamethrin and esfenvalerate had the lowest percentage (3%). Motor activity of the rats was then monitored for 1h. At 3.5h post-dosing, the animals were euthanized and blood and brain were collected. These tissues were extracted and analyzed for parent pyrethroid using HPLC-tandem mass spectrometry. Cypermethrin and cis-permethrin were the predominate pyrethroids detected in blood and brain, respectively, at all dosage levels. The relationship of total pyrethroid concentration between blood and brain was linear (r=0.93). The pyrethroids with the lowest fraction in blood were trans-permethrin and ß-cyfluthrin and in brain were deltamethrin and esfenvalerate. The relationship between motor activity of the treated rats and summed pyrethroid blood and brain concentration was described using a sigmoidal Emax model with the Effective Concentration50 being more sensitive for brain than blood. The data suggests summed pyrethroid rat blood concentration could be used as a surrogate for brain concentration as an aid to study the neurotoxic effects of pyrethroids administered as a mixture under the conditions used in this study.

Measurement of pyrethroids and their environmental degradation products in fresh fruits and vegetables using a modification of the quick easy cheap effective rugged safe (QuEChERS) method.

Pyrethroid insecticides are used extensively in agriculture, and they, as well as their environmental degradates, may remain as residues on foods such as fruits and vegetables. Since pyrethroid degradates can be identical to the urinary markers used in human biomonitoring, it is important to understand the contribution of these degradates when studying sources of human pyrethroid exposure. We modified the widely used Quick Easy Cheap Effective Rugged Safe (QuEChERS) method to measure several current-use pyrethroids (cis/trans-permethrin, cypermethrin, deltamethrin, esfenvalerate, bifenthrin, cyfluthrin, and cyhalothrin) and their environmental degradation products (3-PBA, cis/trans-DCCA, 4-F-3-PBA, DBCA, and MPA) in selected fresh fruits and vegetables. Using fortified samples, we determined extraction efficiencies from: tomatoes, oranges (whole, peeled, and rind), grapes, apples, bananas (peeled and rind only), onions, lettuce, green peppers, carrots and broccoli. For a subset of these food items (apples, grapes, tomatoes, lettuce and banana peel), we also established limits of detection (MDLs) and quantitation (MQLs). Each sample was homogenized (1kg) then spiked with the target pyrethroids and their degradation products. Sub-samples (15g) were extracted with acetonitrile, then salted out and partitioned with NaCl and MgSO4. The extract was divided and further cleaned using solid phase extraction (SPE) cartridges containing either graphitized non-porous carbon (pyrethroids) or C18 (degradation products). Sample analysis was via liquid chromatography/tandem mass spectrometry (LC-MS/MS). Considering the mean recoveries each of the 14 analytes in all 13 matrices: 42% of the recoveries were ≥90%, 70% were ≥80%, and 90% were ≥70%. All MDL's were less than 100ng/kg, except 3-PBA (132ng/kg, tomato), MPA (129ng/kg, tomato), and trans-permethrin (141ng/kg, banana peel). We then applied the method to non-spiked samples (subset of 5 for which the MDLs/MQLs had been determined) collected weekly for four weeks from local supermarkets. At least one pyrethroid was present in measureable concentrations in all matrices except banana peels. In contrast, the only degradation products detected were cis/trans-DCCA, in one lettuce sample.

Using paired soil and house dust samples in an in vitro assay to assess the post ingestion bioaccessibility of sorbed fipronil.

For children, ingestion of soils and house dusts can be an important exposure pathway for regulated organic compounds. Following ingestion, the extent to which compounds desorb and become bioaccessible is a critical determinant of systemic adsorption. We characterized the physicochemical properties of 37 soil and house dust pairs collected during a national survey of United States homes. For each sample, we measured the bioaccessibility of fipronil, a phenylpyrazole insecticide using an in vitro, three- compartment digestive system, then modeled the physicochemical predictors of fipronil bioaccessibility. The properties of the soils and dusts were not correlated and percent carbon was the only significant predictor of bioaccessibility for both soils (p<0.001) and dusts (p<0.001). The carbon content of the soils (3.1±2.4%) was lower than that of the dusts (18.6±6.9%) Due to the lower carbon content, soil sorbed fipronil was more bioaccessible than dust sorbed fipronil. However, the slope of the bioaccessibility carbon regression line was steeper for the soils than for the house dusts. This suggested that, for soils having carbon percentages greater than those in this study, fipronil bioaccessibility may be less than that of house dusts having equal carbon content.

Tissue time course and bioavailability of the pyrethroid insecticide bifenthrin in the Long-Evans rat.

1. Pyrethroids are neurotoxic and parent pyrethroid appears to be toxic entity. This study evaluated the oral disposition and bioavailability of bifenthrin in the adult male Long-Evans rat. 2. In the disposition study, rats were administered bifenthrin (0.3 or 3 mg/kg) by oral gavage and serially sacrificed (0.25 h to 21 days). Blood, liver, brain and adipose tissue were removed. In the bioavailability study, blood was collected serially from jugular vein cannulated rats (0.25 to 24 h) following oral (0.3 or 3 mg/kg) or intravenous (0.3 mg/kg) administration of bifenthrin. Tissues were extracted and analyzed for bifenthrin by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). 3. Bifenthrin concentration in blood and liver peaked 1-2-h postoral administration and were approximately 90 ng/ml (or g) and 1000 ng/ml (or g) for both tissues at 0.3 and 3 mg/kg, respectively. Bifenthrin was rapidly cleared from both blood and liver. Brain concentrations peaked at 4-6 h and were lower than in blood at both doses (12 and 143 ng/g). Bifenthrin in adipose tissue peaked at the collected time points of 8 (157 ng/g) and 24 (1145 ng/g) h for the 0.3 and 3 mg/kg doses, respectively and was retained 21 days postoral administration. Following intravenous administration, the blood bifenthrin concentration decreased bi-exponentially, with a distribution half-life of 0.2 h and an elimination half-life of 8 h. Bifenthrin bioavailability was approximately 30%. These disposition and kinetic bifenthrin data may decrease uncertainties in the risk assessment for this pyrethroid insecticide.

Environmentally relevant mixing ratios in cumulative assessments: a study of the kinetics of pyrethroids and their ester cleavage metabolites in blood and brain; and the effect of a pyrethroid mixture on the motor activity of rats.

UNLABELLED: National surveys of United States households and child care centers have demonstrated that pyrethroids are widely distributed in indoor habited dwellings and this suggests that co-exposure to multiple pyrethroids occurs in nonoccupational settings. The purpose of this research was to use an environmentally relevant mixture of pyrethroids to assess their cumulative effect on motor activity and develop kinetic profiles for these pyrethroids and their hydrolytic metabolites in brain and blood of rats. Rats were dosed orally at one of two levels (1.5× or 5.0× the calculated dose that decreases rat motor activity by 30%) with a mixture of cypermethrin, deltamethrin, esfenvalerate, cis-/trans-permethrin, and ß-cyfluthrin in corn oil. At 1, 2, 4, 8, or 24h after dosing, the motor activity of each animal was assessed and the animals sacrificed. Concentrations of pyrethroids in brain and blood, and the following metabolites: cis-/trans-dichlorovinyl-dimethylcyclopropane-carboxylic acid, 3-phenoxybenzoic acid, 3-phenoxybenzyl alcohol, 4-fluoro-3-phenoxybenzoic acid, and cis-dibromovinyl-dimethylcyclopropane-carboxylic acid were determined using liquid chromatography tandem mass spectrometry (LC-MS/MS). Using this pyrethroid mixture in rats, the results suggest there is greater metabolism of trans-permethrin prior to entering the systemic circulatory system. All pyrethroids had tissue half-lives (t1/2) of less than 5h, excepting esfenvalerate in brain. At early time points, relative pyrethroid brain concentrations approximated their dose mixture proportions and a sigmoidal Emax model described the relationship between motor activity decrease and total pyrethroid brain concentration. In blood, the t1/2's of the cyclopropane metabolites were longer than the phenoxybenzoic metabolites. However, relative to their respective precursors, concentrations of the phenoxybenzoic acids were much higher than concentrations of the cyclopropane metabolites. Brain concentrations of all metabolites were low relative to blood concentrations. This implies limited metabolite penetration of the blood-brain barrier and little metabolite formation within the brain. IN CONCLUSION: toxicokinetic differences between the pyrethroids did not appear to be important determinants of their relative potency and their effect on motor activity was consistent with a pyrethroid dose additive model.

A pharmacokinetic model of cis- and trans-permethrin disposition in rats and humans with aggregate exposure application.

Permethrin is a broad-spectrum pyrethroid insecticide and among the most widely used insecticides in homes and crops. Managing the risks for pesticides such as permethrin depends on the ability to consider diverse exposure scenarios and their relative risks. Physiologically based pharmacokinetic models of delta methrin disposition were modified to describe permethrin kinetics in the rat and human. Unlike formulated deltamethrin which consists of a single stereoisomer, permethrin is formulated as a blend of cis- and trans-diastereomers. We assessed time courses for cis-permethrin and trans-permethrin in several tissues (brain, blood, liver, and fat) in the rat following oral administration of 1 and 10mg/kg permethrin (cis/trans: 40/60). Accurate simulation of permethrin in the rat suggests that a generic model structure is promising for modeling pyrethroids. Human in vitro data and appropriate anatomical information were used to develop a provisional model of permethrin disposition with structures for managing oral, dermal, and inhalation routes of exposure. The human permethrin model was used to evaluate dietary and residential exposures in the U.S. population as estimated by EPA's Stochastic Human Exposure and Dose Simulation model. Simulated cis- and trans-DCCA, metabolites of permethrin, were consistent with measured values in the National Health and Nutrition Examination Survey, indicating that the model holds promise for assessing population exposures and quantifying dose metrics.

Environmentally relevant mixtures in cumulative assessments: an acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids.

Due to extensive use, human exposure to multiple pyrethroid insecticides occurs frequently. Studies of pyrethroid neurotoxicity suggest a common mode of toxicity and that pyrethroids should be considered cumulatively to model risk. The objective of this work was to use a pyrethroid mixture that reflects human exposure to common pyrethroids to develop comparative toxicokinetic profiles in rats, and then model the relationship between brain concentration and motor activity. Data from a national survey of child care centers were used to make a mixture reflecting proportions of the most prevalent pyrethroids: permethrin, cypermethrin, ß-cyfluthrin, deltamethrin, and esfenvalerate. The mixture was administered orally at one of two concentrations (11.2 and 27.4 mg/kg) to adult male rats. At intervals from 1 to 24h, motor activity was assessed and the animals were sacrificed. Pyrethroid concentrations were measured in the blood, liver, fat, and brain. After controlling for dose, there were no differences in any tissue concentrations, except blood at the initial time point. Elimination half-lives for all pyrethroids in all tissues were < 7h. Brain concentrations of all pyrethroids (when cis- and trans-permethrin were pooled) at the initial time point were proportional to their relative doses. Decreases in motor activity indicated dose additivity, and the relationship between pyrethroid brain concentration and motor activity was described by a four-parameter sigmoidal E(max) model. This study links environmental data with toxicokinetic and neurobehavioral assays to support cumulative risk assessments of pyrethroid pesticides. The results support the additive model of pyrethroid effect on motor activity and suggest that variation in the neurotoxicity of individual pyrethroids is related to toxicodynamic rather than toxicokinetic differences.

Correlation of tissue concentrations of the pyrethroid bifenthrin with neurotoxicity in the rat.

The potential for human exposure to pyrethroid pesticides has prompted pharmacodynamic and pharmacokinetic research to better characterize risk. This work tested the hypothesis that blood and brain concentrations of the pyrethroid bifenthrin are predictive of neurotoxic effects. Adult male Long Evans rats received a single oral dose of bifenthrin dissolved in corn oil. Using figure-eight mazes, motor activity was measured for 1h at 4- and 7-h following exposure to bifenthrin (0-16mg/kg or 0-9mg/kg, respectively; n=4-8/group). Whole blood and brains were collected immediately following motor activity assays. Bifenthrin concentrations in blood and brain were quantified using HPLC/MS/MS. Bifenthrin exposure decreased motor activity from 20% to 70% in a dose-dependent manner at both time points. The relationship between motor activity data and administered dose, and blood and brain bifenthrin concentrations were described using a sigmoidal E(max) model. The relationships between motor activity and administered dose or blood concentrations were different between the 4- and 7-h time points. The relationship between motor activity and brain concentration was not significantly different between the two time points. These data suggest that momentary brain concentration of bifenthrin may be a more precise dose metric for predicting behavioral effects because the relationship between brain concentration and locomotor activity is independent of the time of exposure.

Physiologically based pharmacokinetic modeling of deltamethrin: development of a rat and human diffusion-limited model.

Mirfazaelian et al. developed a physiologically based pharmacokinetic (PBPK) model for the pyrethroid pesticide deltamethrin in the rat. This model describes gastrointestinal (GI) tract absorption as a saturable process mediated by phase III efflux transporters which pump deltamethrin out of the intestinal enterocytes into the GI tract lumen, resulting in minimal net absorption at low concentrations and increasing absorption at higher concentrations. In the present study, the dose dependency in absorption of deltamethrin was examined in male Long Evans rats using po exposures predicted by the Mirfazaelian model to yield different po bioavailability values. No difference in the bioavailability from single po doses of 0.3 and 3.0 mg/kg deltamethrin was observed. Based on this finding, the Mirfazaelian PBPK model was modified to exclude a saturable absorption process. Other changes to the Mirfazaelian model included describing all tissue compartments with diffusion-limited kinetics and a single blood compartment. These changes improved model predictions of deltamethrin tissue concentration data from the present study and the literature. The rat model was then scaled to humans. The model predicted a twofold greater peak deltamethrin brain concentration and threefold greater area under the curve (AUC(0-48 h)) for humans following an po exposure of 1 mg/kg. Based on this model, humans would have greater distribution of deltamethrin to the brain for the same administered po dose compared to rats. The relative sensitivity to deltamethrin between rats and humans depends on both pharmacokinetic and pharmacodynamic differences. Species differences in the pharmacodynamic responses to deltamethrin between rats and humans remain uncharacterized.

In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms.

Species differences in the intrinsic clearance (CL(int)) and the enzymes involved in the metabolism of pyrethroid pesticides were examined in rat and human hepatic microsomes. The pyrethroids bifenthrin, S-bioallethrin, bioresmethrin, beta-cyfluthrin, cypermethrin, cis-permethrin, and trans-permethrin were incubated in rat and human hepatic microsomes in the presence or absence of NADPH. Metabolism was measured using a parent depletion approach. The CL(int) of the pyrethroids was 5- to 15-fold greater in rat relative to human microsomes except for trans-permethrin, which was approximately 45% greater in human microsomes. The metabolism of bifenthrin, S-bioallethrin, and cis-permethrin in rat and human hepatic microsomes was solely the result of oxidative processes. The metabolism of bioresmethrin and cypermethrin in human hepatic microsomes was solely the result of hydrolytic processes. Bioresmethrin and cypermethrin in rat hepatic microsomes and beta-cyfluthrin and trans-permethrin in microsomes from both species were metabolized by both oxidative and hydrolytic pathways. The metabolism of trans-permethrin was reduced when incubated with its diastereomer, cis-permethrin, in both rat and human hepatic microsomes. Rat cytochrome P450 (P450) isoforms that showed activity toward several pyrethroids included CYP1A1, CYP1A2, CYP2C6, CYP2C11, CYP3A1, and CYP3A2. Human P450 isoforms that showed activity toward multiple pyrethroids were CYP2C8, CYP2C9, CYP2C19, and CYP3A4. Species-specific differences in metabolism may result in variable detoxification of pyrethroids, which may in turn result in divergent neurotoxic outcomes. These species differences and isomer interactions in metabolism of pyrethroids should be considered when assessing the potential adverse health effects of pyrethroid pesticides.

Supercritical fluid extraction of aflatoxin B(1) from soil.

This research describes the development of a supercritical fluid extraction (SFE) method to recover aflatoxin B(1) from fortified soil. The effects of temperature, pressure, modifier (identity and percentage), and extraction type were assessed. Using the optimized SFE conditions, the mean recovery from air dried soil was 72%. The variables associated with changes in recovery of aflatoxin were co-solvents, static extraction, and temperature. Acetonitrile-2% acetic acid, used both in-cell and on-line, provided the most efficient recovery. The results indicate that desorption from the soil was the limiting factor in recovery and that the static phase was more important than the dynamic.