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.

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.

Differences in tissue distribution of HBCD alpha and gamma between adult and developing mice.

Hexabromocyclododecane (HBCD) is a mixture of three stereoisomers alpha (α), beta (ß), and gamma (γ). γ-HBCD dominates the mixture (∼70%), and despite α-HBCD's minor contribution to global HBCD production and usage (∼10%), it is the dominant congener found in most biotic samples worldwide. Evidence of toxicity and lack of stereoisomer studies drives the importance of understanding HBCD toxicokinetics in potentially susceptible populations. The majority of public health concern has focused on hazardous effects resulting from exposure of infants and young children to HBCD due to reports on adverse developmental effects in rodent studies, in combination with human exposure estimates suggesting that nursing infants and young children have the highest exposure to HBCD. This study was designed to investigate differences in the disposition of both γ-HBCD and α-HBCD in infantile mice reported to be susceptible to the HBCD commercial mixture. The tissue distribution of α-[(14)C]HBCD- and γ-[(14)C]HBCD-derived radioactivity was monitored in C57BL/6 mice following a single oral dose of either compound (3 mg/kg) after direct gavage at postnatal day 10. Mice were held up to 7 days in shoebox cages after which pups were sacrificed, tissue collected, and internal dosimetry was measured. Developing mice exposed to α-HBCD had an overall higher body burden than γ-HBCD at every time point measured; at 4 days postexposure, they retained 22% of the α-HBCD administered dose, whereas pups exposed to γ-HBCD retained 10%. Total body burden in infantile mice after exposure to γ-HBCD was increased 10-fold as compared with adults. Similarly, after exposure to α-HBCD, infantile mice contained 2.5-fold higher levels than adult. These differences lead to higher concentrations of the HBCD diastereomers at target tissues during critical windows of development. The results indicate that the toxicokinetics of the two HBCD diastereomers differ between developing and adult mice; whereas distribution patterns are similar, concentrations of each HBCD diastereomer's-derived radioactivity are higher in the pup's liver, fat, kidney, brain, blood, muscle, and lungs than in the adult's. This study suggests that developmental stage may be a risk factor for the harmful effects of α-HBCD and γ-HBCD, when developing animals may be more sensitive to effects and have increased body burden.

Polybrominated diphenyl ethers in U.S. Meat and poultry from two statistically designed surveys showing trends and levels from 2002 to 2008.

Polybrominated diphenyl ether (PBDE) body burdens in the general U.S. population have been linked to the consumption of red meat and poultry. Exposure estimates have also indicated that meat products are a major contributor to PBDE dietary intake. To establish solid estimates of PBDE concentrations in domestic meat and poultry, samples from two statistically designed surveys of U.S. meat and poultry were analyzed for PBDEs. The two surveys were conducted in 2002-2003 and 2007-2008, between which times the manufacturing of penta-BDE and octa-BDE formulations had ceased in the United States (December 2004). Thus, the data provided an opportunity to observe prevalence and concentration trends that may have occurred during this time frame and to compare the mean PBDE levels among the meat and poultry industries. On the basis of composite samples, the average sum of the seven most prevalent PBDEs (BDE-28, -47, -99, -100, -153, -154, and -183) decreased by >60% from 1.95 ng/g lipid in 2002-2003 to 0.72 ng/g lipid in 2007-2008 for meat and poultry. PBDEs measured in individual samples in 2008 showed that beef samples had the lowest PBDE levels followed by hogs and chickens and then by turkeys. The PBDE congener pattern was the same for both surveys and resembled the penta-BDE formulation with BDE-47 and -99 accounting for 30 and 40% of the total, respectively. On the basis of the data from the two surveys, it appears that PBDE levels in U.S. meat and poultry have declined since manufacturing ceased; however, exposure pathways of PBDEs to livestock are still not known.

Toxicokinetics of the flame retardant hexabromocyclododecane alpha: effect of dose, timing, route, repeated exposure, and metabolism.

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 (ß), 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.

Metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in chickens.

Polybrominated diphenyl ethers (PBDEs) are an important class of persistent, organic pollutant that, based on previous studies in rodents, are poorly metabolized and bioaccumulate in lipophilic stores of the body. Because humans typically consume the fat and skin of chicken, a single (14)C-radiolabeled dose (2.7 mg/kg; 5.64 mumol/kg) of the most common PBDE in the environment, that is, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), was administered to determine its metabolic disposition in male broiler chickens. Orally dosed BDE-47 was readily absorbed from the gut of chickens and was estimated to be 73% bioavailable. Cumulative tissue retention at 72 h was 60.2% of the dose. BDE-47 was deposited preferentially in lipophilic tissues, and the decreasing rank order of concentration on a wet weight basis was adipose tissue, skin, gastrointestinal tract, lung, carcass, muscle, liver, and kidney. When concentrations were adjusted for lipid content, the levels of BDE-47 in the principal edible tissues in chicken, that is, adipose tissue, skin, liver, and white and dark meat, were very similar to one another. Excretion of unbound metabolites in excreta was <1% of the dose, but bound radioactivity was a major component of excreta at >12% of the dose. Alkaline hydrolysis of bound material yielded a hydroxylated tetrabromo metabolite. The metabolic pathway of BDE-47 in chicken included mono-oxidation, mono-oxidation/debromination, and debromination. The present results suggest that trimming the fat and skin from chicken would substantially reduce human exposure to PBDEs during the consumption of chicken.

Biomonitoring polybrominated diphenyl ethers in human milk as a function of environment, dietary intake, and demographics in New Hampshire.

Human milk is a valuable biological specimen for biomonitoring lipid-soluble polybrominated diphenyl ethers (PBDEs). The purpose of this study was to determine the levels of PBDEs in human milk from New Hampshire and to examine potential relationships between PBDE levels in human milk and stage of lactation, maternal characteristics, living environment and dietary intake. Forty women provided up to three human milk samples at the end of their first, second and third month of breastfeeding for evaluation of day-to-day and month-to-month variation in PBDE levels. Participants completed four questionnaires, which provided maternal, living environment, and diet information. The sigma PBDE concentrations in human milk over the 3-month collection period ranged from 6.5 to 166.7 ng g(-1) lipid. The median for the 3-month period was 29.7 ng g(-1). BDE-47 was the predominant congener, however, BDE-153 predominated in 20% of the participants' samples. Day-to-day variation in sigma PBDEs was negligible; there was no significant difference in mean PBDE levels from month-to-month. Positive associations were seen between BDE-153 and age, postpartum saturated fat consumption, and the home model. There was a negative association between PBDE levels and fruit consumption during the third trimester. Our results indicate that PBDE levels in human milk from New Hampshire are within the range that has been reported in the US, and levels are stable during the first 3-months of lactation. Our findings revealed a higher predominance pattern with BDE-153 compared to other studies, and indicate that PBDE levels are influenced by diet and the home environment.

Cytochrome P4501A1 is required for vascular dysfunction and hypertension induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

National Health and Nutrition Examination Survey data show an association between hypertension and exposure to dioxin-like halogenated aromatic hydrocarbons (HAHs). Furthermore, chronic exposure of mice to the prototypical HAH, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), induces reactive oxygen species (ROS), endothelial dysfunction, and hypertension. Because TCDD induces cytochrome P4501A1 (CYP1A1) and CYP1A1 can increase ROS, we tested the hypothesis that TCDD-induced endothelial dysfunction and hypertension are mediated by CYP1A1. CYP1A1 wild-type (WT) and knockout (KO) mice were fed one control or TCDD-containing pill (180 ng TCDD/kg, 5 days/week) for 35 days (n = 10-14/genotype/treatment). Blood pressure was monitored by radiotelemetry, and liver TCDD concentration, CYP1A1 induction, ROS, and aortic reactivity were measured at 35 days. TCDD accumulated to similar levels in livers of both genotypes. TCDD induced CYP1A1 in endothelium of aorta and mesentery without detectable expression in the vessel wall. TCDD also induced superoxide anion production, measured by NADPH-dependent lucigenin luminescence, in aorta, heart, and kidney of CYP1A1 WT mice but not KO mice. In contrast, TCDD induced hydrogen peroxide, measured by amplex red assay, to similar levels in aorta of CYP1A1 WT and KO mice but not in heart or kidney. TCDD reduced acetylcholine-dependent vasorelaxation in aortic rings of CYP1A1 WT mice but not in KO mice. Finally, TCDD steadily increased blood pressure after 15 days, which plateaued after 25 days (+20 mmHg) in CYP1A1 WT mice but failed to alter blood pressure in KO mice. These results demonstrate that CYP1A1 is required for TCDD-induced cardiovascular superoxide anion production, endothelial dysfunction, and hypertension.

Toxicokinetics of the flame retardant hexabromocyclododecane gamma: effect of dose, timing, route, repeated exposure, and metabolism.

Hexabromocyclododecane-gamma (γ-HBCD) is the predominate diastereoisomer in the commercial HBCD mixture used as a flame retardant in a wide variety of consumer products. Three main diastereoisomers, alpha (α), beta (ß), and gamma (γ), comprise the mixture. Despite the γ-diastereoisomer being the major diastereoisomer in the mixture and environmental samples, the α-diastereoisomer predominates human tissue and wildlife. This study was conducted to characterize absorption, distribution, metabolism, and excretion parameters of γ-HBCD with respect to dose and time following a single acute exposure and repeated exposure in adult female C57BL/6 mice. Results suggest that 85% of the administered dose (3 mg/kg) was absorbed after po exposure. Disposition was dose independent and did not significantly change after 10 days of exposure. Liver was the major depot (< 0.3% of dose) 4 days after treatment followed by blood, fat, and then brain. γ-HBCD was rapidly metabolized and eliminated in the urine and feces. For the first time, in vivo stereoisomerization was observed of the γ-diastereoisomer to the ß-diastereoisomer in liver and brain tissues and to the α- and ß-diastereoisomer in fat and feces. Polar metabolites in the blood and urine were a major factor in determining the initial whole-body half-life (1 day) after a single po exposure. Elimination, both whole-body and from individual tissues, was biphasic. Initial half-lives were approximately 1 day, whereas terminal half-lives were up to 4 days, suggesting limited potential for γ-diastereoisomer bioaccumulation. The toxicokinetic behavior reported here has important implications for the extrapolation of toxicological studies of the commercial HBCD mixture to the assessment of risk.

Effect of nitroethane, dimethyl-2-nitroglutarate and 2-nitro-methyl-propionate on ruminal methane production and hydrogen balance in vitro.

Ruminal methanogenesis is considered a digestive inefficiency that results in the loss of 2-12% of the host's gross energy intake and contributes nearly 20% to the United States annual CH(4) emissions. Presently, the effects of the known CH(4) inhibitor, nitroethane, and two synthetic nitrocompounds, dimethyl-2-nitroglutarate and 2-nitro-methyl-propionate, on ruminal CH(4) production and fermentation were evaluated in vitro. After 24 h incubation at 39 degrees C under 100% CO(2), ruminal fluid cultures treated with 2.97 or 11.88 mumol ml(-1) of the respective nitrocompounds produced > 92% less CH(4) (P < 0.05) than non-treated controls. Quantification of fermentation end-products produced and H(2) balance estimates indicate that fermentation efficiencies were not compromised by the nitro-treatments.

Hypertension, cardiac hypertrophy, and impaired vascular relaxation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin are associated with increased superoxide.

The mechanisms by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases the incidence of human cardiovascular disease are not known. We investigated the degree to which cardiovascular disease develops in mice following subchronic TCDD exposure. Adult male C57BL/6 mice were dosed with vehicle or 300 ng TCDD/kg by oral gavage three times per week for 60 days. Blood pressure was recorded by radiotelemetry and aortic endothelial function was assessed by acetylcholine-induced vasorelaxation. Mean arterial pressure of TCDD-exposed mice was increased significantly by day 4 and between days 7-10, 25-35, and 45-60 with two periods of normalization on days 11-24 and days 36-39. Consistent with a prolonged period of systemic hypertension, heart weight was increased and was associated with concentric left ventricular hypertrophy. Significant increases in superoxide production also were observed in the kidney, heart, and aorta of TCDD-exposed mice. Furthermore, increased aortic superoxide resulted in endothelial dysfunction as demonstrated by significant impairment of acetylcholine-induced vasorelaxation in TCDD-exposed mice, which was restored by tempol, a superoxide dismutase (SOD) mimetic. Our model is the first to definitely demonstrate that sustained AhR activation by TCDD increases blood pressure and induces cardiac hypertrophy, which may be mediated, in part, by increased superoxide.

Tissue distribution of polybrominated diphenyl ethers in male rats and implications for biomonitoring.

Polybrominated diphenyl ethers (PBDEs) are a class of widely used flame retardants which have been found to persist, bioaccumulate, and potentially affect development in animals. Exposure to PBDEs can be through both diet and the environment and is generally estimated by measuring PBDEs in blood, adipose tissue, muscle, or milk samples. Using rats as a model, we investigated tissue distribution of PBDEs after oral administration and evaluated a suitable matrix for body burden estimation. Male rats were administered dust or corn oil containing 8 or 6 microg PBDEs kg(-1) body wt, respectively, in the diet for 21 days (N=4 rats per treatment), and the concentration of 15 PBDEs were measured in various tissues, plasma, and feces. PBDEs were found in all tissues, including the brain, and showed no difference in distribution patterns between treatments for most PBDEs. Tri- to hexa-BDEs comprised >80% of the total PBDEs in the adipose, brain, kidney, lung, and residual carcass, but <40% in the liver and plasma. The ratio of the lipid-weight concentration of tri- to hexa-BDEs in adipose tissue, residual carcass, and plasma was 1:1:2. For the hepta- to nona-BDEs, lipid-weight concentrations increased from adipose tissue to residual carcass to plasma in the ratio 0.3:1:>4. BDE-209 was the dominant congener in the liver and plasma, but was not detected in the adipose tissue or carcass. In summary, the lower brominated congeners tended to distribute equally into lipids implying both adipose tissue and plasma would be suitable matrices for biomonitoring. Plasma was the best matrix for detection of the higher brominated congeners (especially BDE-209), although on a lipid-weight basis tended to overestimate the total body burdens.

Evaluation of automated direct sample introduction with comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry for the screening analysis of dioxins in fish oil.

An automated direct sample introduction technique coupled to comprehensive two-dimensional gas chromatography-time of flight mass spectrometry (DSI-GC x GC/TOF-MS) was applied for the development of a relatively fast and easy analytical screening method for 17 polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and 4 non-ortho polychlorinated biphenyls (PCBs) in fish oil. Comparison of instrumental performance between DSI-GC x GC/TOF-MS and the traditional gas chromatographic high resolution mass spectrometric (GC-HRMS) method showed good agreement of results for standard solutions analyzed in blind fashion. Relatively high tolerance of the DSI technique for lipids in the final extracts enabled a streamlined sample preparation procedure that only required gel permeation chromatography (GPC) and solid-phase extraction (SPE) cleanup with graphitized carbon black. The sample size for the method was 2g of cod liver oil, which achieved limits of quantitation (LOQs) of 0.019-7.8 pg/g toxic equivalent quotients for the individual PCDD/Fs. Lower detection limits can be achieved by using larger sample size and scaling up the sample preparation procedure, but this adds to the labor, time, solvent consumption, and expense of the approach. However, the streamlined method yielded 0.94 pg/g and 2.3 pg/g LOQs for 2,3,7,8-tetrachloro dibenzofuran (TCDF) and 3,3',4,4',5-pentachloro biphenyl (CB126), which were sufficiently low for regulatory monitoring of 2g samples. Therefore, instead of congener specific analysis, this streamlined analytical screening method for TCDF and CB126 has the potential to monitor fish oil contaminated with dioxin and dioxin-like PCBs at or above current food safety limits. Acceptable recoveries for nearly all analytes at three different spiking levels in fish oil samples were achieved with good repeatability.

Comparative absorption and bioaccumulation of polybrominated diphenyl ethers following ingestion via dust and oil in male rats.

Household dust has been implicated as a major source of polybrominated diphenyl ether (PBDE) exposure in humans. This finding has important implications for young children, who tend to ingest more dust than adults and may be more susceptible to some of the putative developmental effects of PBDEs. Absorption parameters of PBDEs from ingested dust are unknown; therefore, the objectives of this study were to determine and to compare the uptake of PBDEs from either household dust (NIST Standard Reference Material 2585) or a corn oil solution. Male rats were administered dust or corn oil doses at 1 or 6 microg of PBDEs kg(-1) body wt in the diet for 21 days (n = 4 rats per group). The concentrations of 15 PBDEs were measured in adipose tissue and liver from each treatment group and showed that bioconcentration was congener dependent, but for the majority of congeners, the concentrations did not differ with either dose level or dose vehicle. Hepatic Cyp2b1 and 2b2 mRNA expression increased in rats receiving the higher PBDE doses, suggesting potential effects on metabolic activity. Retention of PBDEs in tissues ranged from <5% of the dose for BDE-209 to 70% for BDEs-47, 100, and 153 but generally did not differ between the high dust and high oil treatment groups. Excretion via the feces was significantly lower in the high oil dosed rats suggesting differences in absorption, excretion, and/or metabolism. The present study shows that PBDEs in dust are readily bioavailable and are biologically active, as indicated by increased transcription of hepatic enzymes.

In utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure: effects on fetal and adult cardiac gene expression and adult cardiac and renal morphology.

The mouse heart is a target of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during fetal development, and microarray analysis demonstrates significant changes in expression of cardiac genes involved in extracellular matrix (ECM) remodeling. We tested the hypothesis that developmental TCDD exposure would disrupt cardiac ECM expression and be associated with changes in cardiac morphology in adulthood. In one study, time-pregnant C57BL/6 mice were dosed with corn oil or 1.5, 3.0, or 6.0 microg TCDD/kg on gestation day (GD) 14.5 and sacrificed on GD 17.5, when changes in fetal cardiac mRNA expression were analyzed using quantitative PCR. TCDD induced mRNA expression of genes associated with ECM remodeling (matrix metalloproteinase 9 and 13, preproendothelin-1 [preproET-1]), cardiac hypertrophy (atrial natriuretic peptide, beta-myosin heavy chain, osteopontin), and aryl hydrocarbon receptor (AHR) activation (cytochrome P4501A1, AHR repressor). Further, all TCDD-induced changes required the AHR since gene expression was not altered in AHR knockout fetuses. In a second study, time-pregnant mice were treated with corn oil or 6.0 microg TCDD/kg on GD 14.5, and male offspring were assessed for changes in cardiac gene expression and cardiac and renal morphology at 3 months. All TCDD-induced changes in cardiac gene expression observed fetally, except for preproET-1, remained induced in the hearts of adult male offspring. Adult male offspring of TCDD-exposed dams also displayed cardiac hypertrophy, decreased plasma volume, and mild hydronephrosis. These results demonstrate that in utero and lactational TCDD exposures alter cardiac gene expression and cardiac and renal morphology in adulthood, which may increase the susceptibility to cardiovascular dysfunction.

Accumulation, whole-body depletion, and debromination of decabromodiphenyl ether in male sprague-dawley rats following dietary exposure.

Decabromodiphenyl ether (BDE-209) isthe major component in the flame-retardant formulation DecaBDE which is incorporated into numerous consumer goods ranging from upholsteries to electronics. Because of the high volume of DecaBDE produced, its presence in consumer products and the environment, and the finding of BDE-209 in the blood of exposed workers, the extent of bioavailability, persistence, and potential debromination are important issues. To measure the bioconcentration, distribution, reductive debromination, and whole-body half-lives of BDE-209 after multiple low doses in an animal model, we dosed rats with a commercial DecaBDE (0.3 microg/g of diet) for 21 days and measured tissue polybrominated diphenyl ether levels during a 21 day withdrawal period. BDE-209, three nona-BDEs, and four octa-BDEs accumulated in the rats and distributed proportionately throughout the body. Only 5% of the total BDE-209 dose was present as parent compound in the rats after 21 days of dosing and <4% in the feces, suggesting extensive metabolism. A nona-BDE (BDE-207) and two octa-BDEs (BDEs-201 and -197) appeared to form via meta-debromination(s) of BDE-209 to a minimal extent (1% of the total BDE-209 dose). The wholebody half-lives tended to increase with decreasing bromination; however, two octa-BDEs, presumably forming from debromination, increased in the rats after 21 days of withdrawal and demonstrated the potential for BDE-209 to form more persistent lipophilic compounds in vivo.

Polychlorinated dioxins, furans, and biphenyls, and polybrominated diphenyl ethers in a U.S. meat market basket and estimates of dietary intake.

Persistent environmental contaminants including polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), non-ortho-polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) were analyzed in 65 meat samples collected from supermarkets across the U.S. in 2001. The samples included hamburger, sirloin steaks, pork chops, bacon, and whole chickens from nine different cities. The average PCDD/F/non-ortho-PCB toxic equivalency (TEQ) for all the samples was 0.55 pg/g of lipid (nd (nondetect) = DL (detection limit)/2) with a range from nondetectable to 3.21 pg/g of lipid. For PBDEs, eight congeners were routinely found in the meat samples with an average sum of 1.71 ng/g of lipid (nd = DL/2) and a range from nondetectable to 16.6 ng/g of lipid. While average TEQs were similar to recent values reported in Europe and Asia, the sums of PBDEs in chicken and pork were 3-20 times higher than levels reported in Spain and Japan for these foods. The presence of a few outliers raised the average PBDE sums and indicated that isolated sources of contamination may exist that, if identified, could be removed from the U.S. animal production chain. Using these TEQ and PBDE values and USDA food consumption data, the estimated dietary intake ranges from meat products were 5.3-16.0 pg TEQ and 14.9-44.7 ng of PBDEs/d or 0.1-0.3 pg TEQ and 0.3-0.5 (ng of PBDEs/kg of body mass)/d for an average individual, similar to intakes in other countries.

Laboratory and on-farm studies on the bioaccumulation and elimination of dioxins from a contaminated mineral supplement fed to dairy cows.

A dioxin-contaminated mineral supplement was used to study the bioaccumulation and elimination of dioxins in two dairy cows. The supplement was mixed into the total maintenance ration and fed to the cows for 40 days after which unfortified diets were fed for 40 additional days. Dioxins and coplanar polychlorinated biphenyls (PCBs) were measured twice a week in the milk and in selected tissues of the cows, one at death (day 10 of withdrawal) and one at slaughter (day 40 of withdrawal). The dioxins and PCBs were readily transferred into the milk, and at steady state, total toxic equivalents were concentrated 6-fold into the milk fat from the diet. Bioaccumulation was inversely related to chlorination number. The elimination of dioxins and PCBs in milk was biphasic. With the exception of 1,2,3,4,6,7,8-heptachlorodioxin and both octachlorinated congeners, dioxin and furan half-lives in milk were approximately 3-5 days for the alpha-phase and 35-50 days for the beta-phase. PCB-169 had a longer half-life: 11 (alpha) and 200 days (beta). When milk and feed samples from Minnesota farms that had used similar contaminated mineral supplements were analyzed, no elevated dioxin levels were found in milk. It appeared that although the dioxins from the mineral supplements have the potential to bioaccumulate, dilution into the total diet was sufficient to prevent a significant rise in the dioxin concentrations in the milk at these farms.

Analysis of mono- to deca-brominated diphenyl ethers in chickens at the part per billion level.

Polybrominated diphenyl ethers (PBDEs) are flame retardants which have been found to be increasing in the environment. Because of structural similarities to the polychlorinated biphenyls and concerns that PBDEs may be widespread, we have investigated their presence in a food source, namely chickens. A GC-MS method was developed to analyze mono- through deca-BDEs in chicken fat samples. The method utilized GC pressure programming and selected ion monitoring to quantitate PBDEs at the low part per billion level. Four 13C-labeled surrogates were used to determine recoveries; recoveries averaged from 76% to 114%. Thirteen chickens from the Southern US and a composite sample of chickens from North Dakota were analyzed by this method. The total concentrations of PBDEs on a whole weight basis ranged from 1.7 ppb in North Dakota chickens to 39.4 ppb in a chicken from Arkansas. On a lipid weight basis, these levels were lower than those generally found in fish and fish-eating mammals. The PBDE pattern was also different from other samples reported; penta-BDEs rather than tetra-BDEs were the most prominent congeners.