Dietary exposure levels to polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and non-ortho-polychlorinated biphenyls in US meat, poultry and siluriform fish from 2018 to 2019.

Daily dietary exposure estimates from beef, pork, chicken, turkey and siluriform fish were calculated using toxic equivalency (TEQ) data from the U.S. Department of Agriculture's survey of dioxins and dioxin-like compounds (DLCs) in the domestic meat supply and consumption data. Exposure estimates for the whole population and age groups were based on mean consumption of a commodity and mean or 90th percentile TEQ dioxin levels from the survey. Ratios of the exposure estimates to the U.S. EPA oral reference dose (RfD) of 0.7 pg TEQ/kg bw/day were calculated to determine if domestic meat might contribute materially to consumer exposure. In general, normal consumption of lean beef, pork, chicken and turkey will not cause exposures exceeding the RfD. Non-lean meats will have higher dioxin levels as dioxins accumulate in fat, therefore consumption of non-lean meat might cause higher exposure than compared to lean meat. However, on a mean basis, none of the exposure estimates for non-lean beef, pork, chicken or turkey exceeded the RfD for any of the age groups. For some age groups, especially toddlers, there are commodities such as non-lean beef in the 90th percentile of dioxin TEQs and siluriform fish that might exceed the RfD on occasion.

Bioavailability of non-aromatic brominated flame retardants in rats from dust and oil vehicles.

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-, ß-, 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. ß-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.

Plasma and Skin Per- and Polyfluoroalkyl Substance (PFAS) Levels in Dairy Cattle with Lifetime Exposures to PFAS-Contaminated Drinking Water and Feed.

Plasma and ear notch samples were removed from 164 Holstein cows and heifers, which had lifetime exposures to per- and polyfluoroalkyl substances (PFAS) through consumption of contaminated feed and water sources. A suite of nine PFAS including five perfluoroalkyl carboxylic acids (PFCA) and four perfluoroalkyl sulfonic acids (PFSA) was quantified in plasma and ear notch samples by liquid chromatography-mass spectrometry. Bioaccumulation of four- to nine-carbon PFCAs did not occur in plasma or skin, but PFSAs longer than four carbons accumulated in both plasma and skin. Exposure periods of at least 1 year were necessary for PFSAs to reach steady-state concentrations in plasma. Neither parity (P = 0.76) nor lactation status (P = 0.30) affected total PFSA concentrations in mature cow plasma. In contrast, lactation status greatly affected (P < 0.0001) total PFSA concentrations in ear notch samples. Skin samples could be used for biomonitoring purposes in instances when on-farm blood collection and plasma preparation are not practical.

Survey of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and non-ortho-polychlorinated biphenyls in U.S. meat, poultry, and siluriform fish from 2018-2019: toxic equivalency levels, temporal trends, and implications.

The U.S. Department of Agriculture (USDA) conducted a survey of domestic animal products including beef fat, pork fat, chicken fat, turkey fat, dairy cow fat, and siluriform fish muscle (i.e. catfish) to determine the current residue levels of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and non-ortho-polychlorinated biphenyls (no-PCBs). The following types of fat samples were analysed: beef from heifers and steers (referred to as "beef"), pork, chicken, turkey, dairy cow (referred to as "dairy cow"), and siluriform fish muscle, which includes catfish. The survey is conducted every 5 years. Fat samples for each slaughter class and siluriform fillets were collected from U.S. federally inspected slaughter facilities, processed, and analysed for 17 PCDD/Fs and 3 no-PCBs. Toxic equivalency concentrations were calculated using 2005 toxic equivalency factors and summed (sum-TEQ) for all slaughter classes. The sum-TEQs ranged from non-detect (nd) to 16.5 pg TEQ/g lipid. The median sum-TEQs, when nd = ½ LOD, for beef, pork, chicken, turkey, dairy cow, and siluriform fish were 0.48, 0.08, 0.07, 0.21, 0.38, and 0.62 pg TEQ/g lipid (wet weight for siluriform fish), respectively. A comparison of the current and previous surveys typically depicts a significant declining trend depending on the slaughter class (such as chicken and turkey), however, beef and pork fat median values slightly increased and decreased, respectively, but neither were significant compared to the previous survey. The congener patterns for some high concentration beef and pork fat samples suggested that pentachlorophenol treated wood continues to be a likely on-farm dioxin exposure source.

Perfluorooctanoic Acid Transport in Soil and Absorption and Distribution in Alfalfa (Medicago sativa).

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.

Absorption, distribution, metabolism, and excretion of three [14C]PBDE congeners in laying hens and transfer to eggs.

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.

Perfluorooctanoic Acid Uptake by Alfalfa (Medicago sativa) and Bioavailability in Sprague-Dawley Rats.

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.

Distribution of Chemical Residues among Fat, Skim, Curd, Whey, and Protein Fractions in Fortified, Pasteurized Milk.

The distribution of 12 environmental contaminants or metabolites with diverse polarities (2,2',4,4',5-pentabromodiphenyl ether; bisphenol A; estrone; glyphosate; ß-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.

Facile synthesis of high specific activity 4-[1-14 C]butyl-1,2-diphenylpyrazolidine-3,5-dione (phenylbutazone) using nucleophilic substitution.

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.

Distribution of Spiked Drugs between Milk Fat, Skim Milk, Whey, Curd, and Milk Protein Fractions: Expansion of Partitioning Models.

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 r2 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) in US meat and poultry: 2012-13 levels, trends and estimated consumer exposures.

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.

Survey of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and non-ortho-polychlorinated biphenyls in US meat and poultry, 2012-13: toxic equivalency levels, patterns, temporal trends and implications.

The US Department of Agriculture (USDA) conducts a statistically based survey of the domestic meat supply (beef, pork, chicken and turkey) to determine current levels of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and non-ortho-polychlorinated biphenyls (no-PCBs) every 5 years. Fat samples for each slaughter class were collected from US federally licensed slaughter facilities. The samples were processed and analysed for 17 PCDD/Fs and three no-PCBs. The sum of PCDD, PCDF and no-PCB toxic equivalencies (sum-TEQ) calculated using 2005 toxic-equivalency factors for all slaughter classes ranged from non-detect (n.d.) to 6.47 pg TEQ g-1 lipid. The median sum-TEQs, when n.d. = 0.5 LOD, for beef, pork, chicken and turkey were 0.66, 0.12, 0.13 and 0.34 pg TEQ g-1 lipid respectively. A comparison of the current survey with the previous three surveys shows a declining trend, with decreasing differences between medians; differences between the median sum-TEQs from 2007-08 and 2012-13 were -10%, -29%, -33% and -25% for beef, pork, chicken and turkey respectively. Several beef samples underwent further characterisation and congener patterns from these beef samples suggested pentachlorophenol treated wood as the likely exposure source. US consumer exposure to these compounds is relatively low and no slaughter class contributed more than 26% to the US Environmental Protection Agency (USEPA) chronic oral reference dose of 0.7 pg TEQ kg-1 bw day-1.

Distribution of Animal Drugs among Curd, Whey, and Milk Protein Fractions in Spiked Skim Milk and Whey.

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 (R2 = 0.70) to the drug's lipophilicity (log P), with improved correlation using log D (R2 = 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.

Distribution of Animal Drugs between Skim Milk and Milk Fat Fractions in Spiked Whole Milk: Understanding the Potential Impact on Commercial Milk Products.

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.

Perfluorooctane Sulfonate Plasma Half-Life Determination and Long-Term Tissue Distribution in Beef Cattle (Bos taurus).

Perfluorooctane sulfonate (PFOS) is used in consumer products as a surfactant and is found in industrial and consumer waste, which ends up in wastewater treatment plants (WWTPs). PFOS does not breakdown during WWTP processes and accumulates in the biosolids. Common practices include application of biosolids to pastures and croplands used for feed, and as a result, animals such as beef cattle are exposed to PFOS. To determine plasma and tissue depletion kinetics in cattle, 2 steers and 4 heifers were dosed with PFOS at 0.098 mg/kg body weight and 9.1 mg/kg, respectively. Plasma depletion half-lives for steers and heifers were 120 ± 4.1 and 106 ± 23.1 days, respectively. Specific tissue depletion half-lives ranged from 36 to 385 days for intraperitoneal fat, back fat, muscle, liver, bone, and kidney. These data indicate that PFOS in beef cattle has a sufficiently long depletion half-life to permit accumulation in edible tissues.

Depletion of penicillin G residues in heavy sows after intramuscular injection. Part II: application of kidney inhibition swab tests.

Sows (n = 126; 228 ± 30.1 kg) were administered daily IM doses of penicillin G procaine (33 000 IU/kg bw; 5× the label dose) for 3 consecutive days using three different administration patterns. Within treatment, six sows each were slaughtered on withdrawal day 5, 10, 15, 20, 25, 32, and 39. Tissues (injection site, kidney, liver, skeletal muscle) or body fluids (serum and urine) were screened for penicillin G using the KIS test, recently adopted by the USDA Food Safety and Inspection Service. The IM administration patterns had no discernible effect on penicillin G depletion. Residues were depleted more rapidly from liver and skeletal muscle and more slowly from kidney and urine. Kidney was the most sensitive and suitable tissue for detecting penicillin G residues on-site, with two positive results after a 39-day withdrawal period. Urine was the most suitable ante-mortem surrogate to predict the results of kidney tests.

Distribution and excretion of perfluorooctane sulfonate (PFOS) in beef cattle (Bos taurus).

Perfluorooctane sulfonate (PFOS), a perfluoroalkyl surfactant used in many industrial products, is present in industrial wastes and in wastewater treatment plant biosolids. Biosolids are commonly applied to pastures and crops used for animal feed; consequently, PFOS may accumulate in the edible tissues of grazing animals or in animals exposed to contaminated feeds. There are no data on the absorption, distribution, and excretion of PFOS in beef cattle, so a 28-day study was conducted to determine these parameters for PFOS in three Lowline Angus steers given a single oral dose of PFOS at approximately 8 mg/kg body weight. PFOS concentrations were determined by liquid chromatography-tandem mass spectrometry in multiple tissue compartments. The major route of excretion was in the feces (11 ± 1.3% of the dose, mean ± standard deviation) with minimal PFOS elimination in urine (0.5 ± 0.07% of the dose). At day 28 the mean plasma concentration remained elevated at 52.6 ± 3.4 µg/mL, and it was estimated that 35.8 ± 4.3% of the dose was present in the plasma. Plasma half-lives could not be calculated due to multiple peaks caused by apparent redistributions from other tissues. These data indicate that after an acute exposure PFOS persists and accumulates in edible tissues. The largest PFOS body burdens were in the blood (∼36%), carcass remainder (5.7 ± 1.6%), and the muscle (4.3 ± 0.6%). It was concluded that PFOS would accumulate in edible tissues of beef, which could be a source of exposure for humans.

Absorption and excretion of 14C-perfluorooctanoic acid (PFOA) in Angus cattle (Bos taurus).

Perfluoroalkyl substances (PFASs), such as perfluorooctanoic acid (PFOA), are environmentally persistent industrial chemicals often found in biosolids. Application of these biosolids to pastures raises concern about the accumulation of PFOA in the edible tissues of food animals. Because data on the absorption, distribution, metabolism, and excretion (ADME) of PFOA in cattle were unavailable, a study was conducted to determine pharmacokinetic parameters following a single oral exposure (1 mg/kg body weight of (14)C-PFOA) in four Lowline Angus steers. Radiocarbon was quantified in blood, urine, and feces for 28 days and in tissues at the time of slaughter (28 days) by liquid scintillation counting (LSC) or by combustion analysis with LSC with confirmation by liquid chromatography-tandem mass spectrometry (LC-MS/MS). (14)C-PFOA was completely absorbed and excreted (100.7 ± 3.3% recovery) in the urine within 9 days of dosing. The plasma elimination half-life was 19.2 ± 3.3 h. No (14)C-PFOA-derived radioactivity was detected in edible tissues. Although PFOA was rapidly absorbed, it was also rapidly excreted by steers and did not persist in edible tissues, suggesting meat from cattle exposed to an acute dose of PFOA is unlikely to be a major source of exposure to humans.

Analysis of hydroxylated polybrominated diphenyl ether metabolites by liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry.

Hydroxylated polybrominated diphenyl ether (OH-PBDEs) metabolites have the potential to cause endocrine disruption as well as other health effects. Currently, gas chromatography/mass spectrometry (GC/MS) after derivatization is used for the analysis of OH-PBDEs. However, there is a need for the direct analysis of OH-PBDEs at relatively low concentrations in environmental and biological samples. Liquid chromatography with atmospheric pressure chemical ionization tandem mass spectrometry (LC/APCI-MS/MS) was evaluated for the analysis of nine OH-PBDEs, ranging from tri- to hexabrominated. Separation of the nine isomeric metabolites was achieved with reversed-phase liquid chromatography, followed by detection by APCI-MS in negative mode. Notably, a significant decrease in ionization was observed in 6-hydroxyl-substituted PBDE metabolites in the presence of an ortho-substituted bromine, relative to the other hydroxylated metabolites. This is probably due to the formation of dioxins in the source as a result of the high-temperature conditions, which prevented ionization by hydrogen abstraction. The MS/MS experiments also provided evidence of the neutral losses of HBr and Br(2), indicating the possible use of neutral loss scanning and selected reaction monitoring (SRM) for the screening of brominated metabolites in samples. The applicability of LC/APCI-MS/MS was demonstrated for the analysis of metabolites of BDEs 47 and 99 formed in human liver microsomes. The LC/APCI-MS/MS method was able to detect metabolites that had previously been identified by GC/MS following derivatization.

Human liver microsome-mediated metabolism of brominated diphenyl ethers 47, 99, and 153 and identification of their major metabolites.

While the metabolism and excretion of polybrominated diphenyl ethers (PBDEs) have been reported in rodents, PBDE metabolism in humans has only recently been investigated. In this present study, individual human liver microsomes were incubated for 120 min with radiolabeled and nonradiolabeled BDE 47, 99, or 153 to determine their relative degrees of metabolism and to identify the structures of metabolites formed. Radiolabeled samples were analyzed using high-performance liquid chromatography/radiochemical detection, while nonradiolabeled samples were analyzed with and without derivatization using gas chromatography/mass spectrometry. Results from radiolabeled incubations demonstrated that human liver microsomes metabolized BDEs 47 and 99 but not BDE 153. Differences in the extent of BDE metabolism by the three individual liver specimens used in the study were observed. BDE 47 metabolized to a dihydroxylated BDE 47 and 2,4-dibromophenol, while BDE 99 metabolized to a dihydroxylated BDE 99, 2,4,5-tribromophenol and 1,3-dibromobenzene. This study showed that BDEs 47 and 99 are metabolized by human liver microsomes with relatively large interindividual differences. Results of this study could provide one explanation for the high bioaccumulation rate of BDE 153 in humans.