2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced down-regulation of glucose transporting activities in mouse 3T3-L1 preadipocyte

The possibility that 3T3-L1 preadipocytes, while the level of its glucose uptake activity is relatively low, may offer a useful tool for studying the cause for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced "lipolytic response" was studied. It was established first, that TCDD causes reduction of glucose uptake, one of the hallmark events of the lipolytic process. Then the function of c-Src was investigated. The antisense c-src oligonucleotide decreased the inhibitory action of TCDD on glucose uptake activity in a sequence specific manner. Since antisense oligonucleotides are known to own their blocking effects to their ability to reduce translation of proteins, Western blotting analysis was performed to verify their effectiveness. As expected, the treatment of pre-adipocytes with antisense c-src oligonucleotide reduced c-Src in a sequence specific manner. The treatment of antisense c-src oligonucleotide alone was sufficient to diminish the inhibitory action of TCDD on glucose uptake activity in 3T3-L1 cells, indicating that c-Src is somehow involved in the action of TCDD. In a similar manner, the contribution of c-Fos was investigated using antisense c-fos oligonucleotide, since c-Fos is known to be one of the most affected proteins by c-Src activation among AP-1 members. The treatment of antisense c-fos oligonucleotide did not block the effect of TCDD on glucose uptake activity in 3T3-L1 cells. Therefore, it is unlikely that c-Fos is very important in the lipolytic signal transduction of TCDD mediated through c-Src. In order to determine the relationship between c-Src and c-Myc in the mitotic signal transduction pathway, the effect of antisense c-myc oligonucleotide was investigated. Basically the same result as antisense c-src oligonucleotide experiment was obtained thereby, suggesting the importance of c-Myc as well as c-Src in the signal transduction of TCDD. To show the effect of antisense c-myc oligonucleotide treatment, the level of c-Myc protein by Western blotting and electrophoretic gel-mobility shift assay was assessed. However, antisense c-myc oligonucleotide treatment increased the activity of c-Myc in a sequence specific manner. This may be the result of cellular compensatory response to the initial suppression of c-Myc by antisense treatment. The observation that antisense c-fos oligonucleotide could not block the effect of TCDD indicates that this preadipocyte model is different from the adipocyte differentiation model.     

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on serum insulin and glucose levels in the rabbit

Serum insulin and glucose were measured in young male rabbits after a single intraperitoneal dose of 1 or 50 micrograms/kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Serum insulin levels in the high dosed rabbits were significantly decreased between 15 min and 8 h post treatment, equivalent after 24 h, significantly elevated 48 h post treatment, and they were not different at 10 days post-treatment when compared to weight matched and pair-fed controls. At the low dose, rabbits showed no differences in serum insulin from controls. In the high dose group, serum glucose levels were generally not different between treated and control animals, though there was a transient hyperglycemia 1 h after treatment, and both treated groups became hypoglycemic after ten days. The results indicate that TCDD altered serum insulin levels which were not coupled to changes in serum glucose.     

A new structure-affinity relationship for TCDD receptor binding

We have investigated the capacity of various indoles to inhibit specific binding of [1,6-³H]2,3,7,8-tetrachlorodibenzo- -dioxin ([³H]TCDD) in rat liver cytosol, as analyzed by electrofocusing in polyacrylamide gels. Of these indoles, indolo[3,2- ]carbazole was the most active. The IC₅₀ value for TCDD receptor binding of indolo[3,2- ]carbazole as well as for 2,3,7,8-tetrachlorodibenzofuran was 3.6 nM. We have also studied the influence on binding exerted by introduction of some substituents on indolo[3,2- ]carbazole. Substitution with methyl groups at the 5 and 11 positions resulted in an increased affinity (IC₅₀ 1.2 nM) for the TCDD receptor as compared to the parent compound. Computer-supported molecular structure studies indicated that if the van der Waals radii of atoms are included, a rectangle of 6.8 × 13.7 Å may account for the binding of high-affinity ligands to the TCDD receptor.     

Portal absorption of 14C after ingestion of spiked milk with 14C-phenanthrene, 14C-benzo[a]pyrene or 14C-TCDD in growing pigs

Polycyclic aromatic hydrocarbons (PAHs) and dioxins are lipophilic organic pollutants occurring widely in the terrestrial environment. In order to study the PAHs and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) transfer in the food chain, pigs have been fed with milk mixed either with 14C-phenanthrene, with 14C-benzo[a]pyrene or with 14C-TCDD. The analysis of portal and arterial blood radioactivity showed that both PAHs and TCDD were absorbed with a maximum concentration at 4-6 h after milk ingestion. Then, the blood radioactivity decreased to reach background levels 24 h after milk ingestion. Furthermore, the portal and arterial blood radioactivities were higher for phenanthrene (even if the injected load was the lowest) than these of benzo[a]pyrene or these of TCDD, in agreement with their lipophilicity and water solubility difference. Main 14C absorption occurred during the 1-3 h time period after ingestion for 14C-phenanthrene and during the 3-6 h time period for 14C-benzo[a]pyrene and for 14C-TCDD. 14C portal absorption rate was high for 14C-phenanthrene (95%), it was close to 33% for 14C-benzo[a]pyrene and very low for 14C-TCDD (9%). These results indicate that the three studied molecules have a quite different behaviour during digestion and absorption. Phenanthrene is greatly absorbed and its absorption occurs via the blood system, whereas benzo[a]pyrene and TCDD are partly and weakly absorbed respectively. However these two molecules are mainly absorbed via the portal vein.     

Polyfluorinated chemicals in a spatially and temporally integrated food web in the Western Arctic

This study reports on an investigation of the presence of polyfluorinated chemicals in a spatially and temporally integrated set of biological samples representing an Arctic food web. Zooplankton, Arctic cod, and seal tissues from the western Canadian Arctic were analyzed for perfluoroalkyl sulfonates [PFAS], perfluorocarboxylates [PFCAs], and other polyfluorinated acids. Perfluorooctane sulfonate [PFOS] was found in all samples [0.20-34 ng/g] and in the highest concentrations. PFCAs from nine to 12 carbons were quantified in most of the samples [0.28-6.9 ng/g]. PFCAs with carbon chain lengths of eight or less were not detected. Likewise, 8-2 fluorotelomer acid [8-2 FTA] and 8-2 fluorotelomer unsaturated acid [8-2 FTUA], products of fluorotelomer environmental transformation, were not detected. 2H,2H,3H,3H, heptadecafluoro decanoic acid [7-3 Acid], an additional metabolite from fluorotelomer biological transformation, was detected only in seal liver tissue [0.5-2.5 ng/g]. The ratios of branched to linear PFOS isomers in fish and seal tissue were not similar and did not match that of technical PFOS as manufactured. No branched PFCA isomers were detected in any samples. It is concluded that differing pharmacokinetics complicate the use of branched to linear ratios of PFCAs in attributing their presence to a specific manufacturing process. A statistical analysis of the data revealed significant correlations between PFOS and the PFCAs detected as well as among the PFCAs themselves. The 7-3 Acid was not correlated with either PFCAs or PFAS, which suggests that it may have a different exposure pathway.     

Bioconcentration potential (BCP) of 2,3,7,8-Tetrachlorodibenzop-dioxin (2,3,7,8-TCDD) in terrestrial organisms including humans

The bioconcentration factors (BCFs) of 2,3,7,8-TCDD in adipose tissue of rats, beef cattle and monkeys have been calculated. The bioconcentration potential of TCDD in man was calculated by two indirect methods: 1) from daily intake of TCDD and its measured concentrations in adipose tissues and 2) from measured half-life and measured concentrations in body fat at steady state using a linear one compartment pharmacokinetic model. The BCFs in humans calculated by both methods are between 104 and 206, or 153, respectively.     

TCDD alters PKC signaling pathways in developing neuronal cells in culture

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to induce neurodevelopmental deficits such as poor cognitive development and motor dysfunction. However, the mechanism of TCDD-mediated neurotoxicity remains unclear. Since PKC signaling is one of the most pivotal events involved in neuronal function and development, we analyzed the effects of TCDD on the PKC signaling pathway in cerebellar granule cells derived from PND-7 rat brain. Immunoblot analysis revealed the presence of PKC-alpha, betaII, delta, epsilon, lambda and iota in both cytosol and membrane fractions of cerebellar granule cells, but PKC-gamma was below the detectable level. TCDD induced a significant translocation of PKC-alpha, -betaII and -epsilon from cytosol to membrane fraction (p<0.05) and a marginal translocation of PKC-delta at high dose only (p<0.1). It also increased RACK-1, an adaptor protein for PKC, in a dose-dependent manner. Exposure to TCDD induced a dose-dependent increase of both [3H] PDBu binding and the intracellular calcium level. The results suggest that the selective PKC isozymes and RACK-1 are involved in TCDD-mediated signaling pathway and these proteins may be possible molecular targets in neuronal cells for TCDD exposure. Our study provides basic data to understand mechanism of TCDD-induced neurotoxicity with respect to PKC signaling pathway and a scientific basis for improving the health risk assessment of neurotoxicants by identifying intracellular target molecules in neuronal cells.     

Refinements on the age-dependent half-life model for estimating child body burdens of polychlorodibenzodioxins and dibenzofurans

We modified our prior age-dependent half-life model to characterize the range of child (ages 0-7) body burdens associated with dietary and environmental exposure to polychlorodibenzodioxins and furans (PCDD/Fs). Several exposure scenarios were evaluated. Infants were assumed to be either breast-fed or formula-fed from birth to 6 months of age. They then received intakes of PCDD/Fs through age 7 from foods based on weighted means estimates [JECFA, 2001. Joint FAO/WHO Committee on Food Additives. Fifty-seventh meeting, Rome, June 5-14 , 2001, pp. 24-40], and with or without exposures (ingestion and dermal) to urban residential soils at 1ppb TCDD toxic equivalents (TEQ). A one-compartment (adipose volume) toxicokinetic model for TCDD described by Kreuzer [Kreuzer, P.F., Csanady, Gy.A., et al., 1997. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and congeners in infants. A toxicokinetic model of human lifetime body burden by TCDD with special emphasis on its uptake by nutrition. Arch. Toxicol. 71, 383-400] was expanded to include the key non-TCDD congeners in human breast milk and adipose tissues, and two model parameter refinements were examined: (1) use of updated and more detailed age-correlated body fat mass data [CDC, 2000. Centers for Disease Control. CDC Growth Charts: United States. Advance Data from Vital and Health Statistics of the Centers for Disease Control and Prevention, National Center for Health Statistics, Number 314, December 2000]; (2) use of breast milk PCDD/F concentration data from sampling completed in 2000-2003 [Wittsiepe, J., Fürst, P., et al., 2004. PCDD/F and dioxin-like PCB in human blood and milk from German mothers. Organohalogen Compd. 66, 2865-2872]. The updated body fat mass data nearly halved the predicted peak body burden for breast-feeding and lowered the time-weighted average (TWA) body burdens from ages 0-7 by 30-40% for breast-fed and formula-fed infants. Combined use of the updated breast milk PCDD/F concentration and body fat mass data increased the contribution of breast-feeding but reduced TWA body burdens from diet and soil. We conclude that further refinements are needed, but reliance on these better data sets for body fat mass and breast milk PCDD/F concentration significantly improves the model's ability to accurately predict body burdens during early childhood.     

Effect of hexachlorobenzene on the specific binding of 2,3,7,8,-TCDD to the hepatic receptor

The ability of HCB to interact with the receptor was investigated and . HCB, up to 1.0 μM, was not a potent competitor for the specific binding of [³H]-TCDD (0.3 nM) to rat hepatic cytosol. Administration of HCB (3000 ppm in the diet) to rats for up to 7 days resulted in a decrease in the specific binding of [³H]-TCDD to hepatic cytosol, as compared to pair-fed control rats. These results suggest that HCB may be able to interact, either directly or indirectly, with the hepatic receptor .     

The impact of synthetic pyrethroid and organophosphate sheep dip formulations on microbial activity in soil

Sheep dip formulations containing organophosphates (OPs) or synthetic pyrethroids (SPs) have been widely used in UK, and their spreading onto land has been identified as the most practical disposal method. In this study, the impact of two sheep dip formulations on the microbial activity of a soil was investigated over a 35-d incubation. Microbial utilisation of [1-(14)C] glucose, uptake of (14)C-activity into the microbial biomass and microbial numbers (CFUs g(-1) soil) were investigated. In control soils and soils amended with 0.01% sheep dip, after 7d a larger proportion of added glucose was allocated to microbial biomass rather than respired to CO(2). No clear temporal trends were found in soils amended with 0.1% and 1% sheep dips. Both sheep dip formulations at 0.1% and 1% concentrations resulted in a significant increase in CFUs g(-1) soil and [1-(14)C] glucose mineralisation rates, as well as a decline in microbial uptake of [1-(14)C] glucose, compared to control and 0.01% SP- or OP-amended soils. This study suggests that the growth, activity, physiological status and/or structure of soil microbial community may be affected by sheep dips.     

Uptake and translocation of plutonium in two plant species using hydroponics

This study presents determinations of the uptake and translocation of Pu in Indian mustard (Brassica juncea) and sunflower (Helianthus annuus) from Pu contaminated solution media. The initial activity levels of Pu were 18.50 and 37.00 Bq ml(-1), for Pu-nitrate [239Pu(NO3)4] and for Pu-citrate [239Pu(C6H5O7)+] in nutrient solution. Plutonium-diethylenetriaminepentaacetic acid (DTPA: [239Pu-C14H23O10N3] solution was prepared by adding 0, 5, 10, and 50 microg of DTPA ml(-1) with 239Pu(NO3)4 in nutrient solution. Concentration ratios (CR, Pu concentration in dry plant material/Pu concentration in nutrient solution) and transport indices (Tl, Pu content in the shoot/Pu content in the whole plant) were calculated to evaluate Pu uptake and translocation. All experiments were conducted in hydroponic solution in an environmental growth chamber. Plutonium concentration in the plant tissue was increased with increased Pu contamination. Plant tissue Pu concentration for Pu-nitrate and Pu-citrate application was not correlated and may be dependent on plant species. For plants receiving Pu-DTPA, the Pu concentration was increased in the shoots but decreased in the roots resulting in a negative correlation between the Pu concentrations in the plant shoots and roots. The Pu concentration in shoots of Indian mustard was increased for application rates up to 10 microg DTPA ml(-1) and up to 5 microg DTPA ml(-1) for sunflower. Similar trends were observed for the CR of plants compared to the Pu concentration in the shoots and roots, whereas the Tl was increased with increasing DTPA concentration. Plutonium in shoots of Indian mustard was up to 10 times higher than that in shoots of sunflower. The Pu concentration in the apparent free space (AFS) of plant root tissue of sunflower was more affected by concentration of DTPA than that of Indian mustard.     

Chlorinated dibenzo-p-dioxin and dibenzofuran levels in human adipose tissue and milk samples from the north and south of Vietnam

Although 2,3,7,8-TCDD has been found to be extremely toxic to a variety of laboratory aminals, human epidemiology studies, where exposure to 2,3,7,8-TCDD has been less well characterized than in animal toxicologic studies, have been less conclusive in characterizing the extent of toxicity. In order to determine whether the newly refined techniques of human adipose tissue biopsy including isomer specific and sensitive measurement of PCDDs and PCDFs might be able to assist in finding populations within the same country with high and low levels of dioxins, adipose tissue samples were taken and levels analyzed from the north and south of Vietnam. It seemed reasonable, based on previous work, that high levels of 2,3,7,8-TCDD might still be found in adipose tissue in selected patients living in areas sprayed with Agent Orange and other 2,3,7,8-TCDD containing herbicides, and that lower levels should be found in patients not exposed to 2,3,7,8-TCDD from herbicides or other sources, such as persons who had always resided in the north of Vietnam. Of 9 specimens from patients hospitalized in Hanoi who had never been south, none had detectable adipose tissue levels of 2,3,7,8-TCDD at a detection limit of 2 or 3 ppt on a wet weight basis. Of 15 specimens from Ho Chi Minh City hospitalized patients the mean of positive specimens (12 of 15) was 28 on a lipid basis. The mean of the positive values from the south is about 2 to 3 times higher than found in the North American Continent control patients where the mean is about 6–10 ppt and much higher than in the north of Vietnam. In the northern specimens, the levels were non-detectable with a sensitivity of between 2 and 3 ppt. Other PCDD and PCDF isomers not found in Agent Orange, the penta- through octachlorinated dibenzo-dioxins and dibenzofurans, were similar in isomer type and quantity in the south of Vietnam to what we previously reported in North America. Adipose tissue from the north of Vietnam contained the lowest levels of four through eight chlorinated dioxins and furans thus far reported. The initial data suggests that populations exist in the south of Vietnam with elevated levels of 2,3,7,8-TCDD at the present time, fourteen years after the last known 2,3,7,8-TCDD (Agent Orange) application, superimposed on a preexisting body burden of dioxins and dibenzofurans from sources other than Agent Orange such as technical grade pentachlorophenol or products of incineration contaminated with higher chlorinated PCDDs or PCDFs. In light of the recent finding that unexpected levels of PCDDs and PCDFs exist in the general adult population of industrialized countries, ca. 1,000 to 1,200 ppt, wet weight of total dioxin and furan isomers in adipose tissues, it seems reasonable that the extent of human toxicity of dioxins may be more readily characterized in Vietnam than in industrialized countries. Because 2,3,7,8-TCDD was applied in 1962–1970, although not yet cleaned up, the levels of 2,3,7,8-TCDD in the environment, the food chain, and in humans, would be expected to decrease with time. Therefore, if studies are not initiated in a timely fashion, the opportunity to better characterize the extent of the toxicity of TCDD to humans as well as the persistence of TCDD in the environment in Vietnam may be lost.     

Comparative metabolism of phenanthrene in the rat and guinea pig.

In the present study the biotransformation of phenanthrene in the rat and guinea pig was investigated. 14C-labelled phenanthrene was administered by gavage in corn oil to Sprague-Dawley rats (10 mg/kg b.w./day) and guinea pigs (10 mg/kg b.w./day). Urine and feces were separately collected for the determination of the radioactivity content, and pooled urine was used for the analysis of metabolites. Phenanthrene was metabolized by the rat and guinea pig to free hydroxylated phenanthrenes and their conjugates. The percentages of conjugates, expressed as the total urinary radioactivity, were 39% glucuronides, 24% sulfates and 18% cysteinylglycine for rats; and 39% glucuronides, 23% sulfates and 28% cysteinylglycine for guinea pigs. Enzymatic hydrolysis of glucuronides and sulfates resulted in the formation of free 1,2-, 3,4- and 9,10-dihydrodiols of phenanthrene and 1-, 2-, 3-, and 4-hydroxyphenanthrene in both species.     

Tissue distribution, excretion, and metabolism of 1,2,7,8-tetrachlorodibenzo-p-dioxin in the rat

A tissue distribution, excretion, and metabolism study was conducted using a relatively non-toxic dioxin congener, i.e., 1,2,7,8-tetrachlorodibenzo-p-dioxin (1278-TCDD), to gain a better understanding of mammalian metabolism of dioxins. Conventional, bile duct cannulated, and germ free male rats were administered mg/kg quantities as a single oral dose. Elimination of 1278-TCDD was largely complete by 72 h. Distribution of [¹⁴C]1278-TCDD was low in all tissues examined. Metabolites were identified in urine, bile, and feces by negative ion FAB-MS and ¹H-NMR, or GC/MS. The major fecal metabolite was a NIH-shifted hydroxylated TCDD. The bile contained a glucuronide conjugate of this hydroxy TCDD, and a diglucuronide conjugate of a dihydroxy-triCDD. The major metabolites in urine were glucuronide and sulfate conjugates of 4,5-dichlorocatechol.     

Effects of reduced return activated sludge flows and volume on anaerobic zone performance for a septic wastewater biological phosphorus removal system.

Enhanced biological phosphorous removal (EBPR) performance was found to be adequate with reduced return-activated sludge (RAS) flows (50% of available RAS) to the anaerobic tank and smaller-than-typical anaerobic zone volume (1.08 hours hydraulic retention time [HRT]). Three identical parallel biological nutrient removal pilot plants were fed with strong, highly fermented (160 mg/L volatile fatty acids [VFAs]), domestic and industrial wastewater from a full-scale wastewater treatment facility. The pilot plants were operated at 100, 50, 40, and 25% RAS (percent of available RAS) flows to the anaerobic tank, with the remaining RAS to the anoxic tank. In addition, varying anaerobic HRT (1.08 and 1.5 hours) and increased hydraulic loading (35% increase) were examined. The study was divided into four phases, and the effect of these process variations on EBPR were studied by having one different variable between two identical systems. The most significant conclusion was that returning part of the RAS to the anaerobic zone did not decrease EBPR performance; instead, it changed the location of phosphorous release and uptake. Bringing less RAS to the anaerobic and more to the anoxic tank decreased anaerobic phosphorus release and increased anoxic phosphorus release (or decreased anoxic phosphorus uptake). Equally important is that, with VFA-rich influent wastewater, excessive anaerobic volume was shown to hurt overall phosphorus removal, even when it resulted in increased anaerobic phosphorus release.     

Removal of tetrafluoroborate ion from aqueous solution using magnesium-aluminum oxide produced by the thermal decomposition of a hydrotalcite-like compound

Magnesium-aluminum oxide (Mg-Al oxide) prepared by the thermal decomposition of a hydrotalcite-like compound was found to have potential for treating NaBF(4) wastewater. The Mg-Al oxide removed the BF(4)(-) and F(-) and H(3)BO(3) from the NaBF(4) solution. With increasing Mg-Al oxide quantity and time, the BF(4)(-) concentration decreased and the degree of BF(4)(-), F(-), and boron removal increased. The decrease in the BF(4)(-) concentration resulted from uptake by the Mg-Al oxide and not hydrolysis. The Mg-Al oxide took up F(-) from the solution preferentially. The Mg-Al oxide also converted the H(3)BO(3) in the aqueous solution into H(2)BO(3)(-), which it took up.     

In vitro EROD induction equivalency factors for the 10 PAHs generally monitored in risk assessment studies in The Netherlands

The ethoxy resorufin dealkylase (EROD) inducing potency of 10 polycyclic aromatic hydrocarbons (PAHs) is measured in the H4IIE in vitro bioassay and the results are compared to those reported in literature. The selected PAHs varied considerably in their potency to induce EROD activity. Anthracene (Ant) and phenanthrene (Phe) showed consistently no response. Naphthalene (Nap) showed no or a very weak response on EROD activity. Fluoranthene (Fla) and benzo[g,h,i]perylene (BghiP) showed weak responses at the highest doses. The other PAHs, including indeno[1,2,3-cd]pyrene (IP), benz[a]anthracene (BaA), benzo[a]pyrene (BaP), chrysene (Chr) and benzo[k]fluoranthene (BkF), showed full bell shaped dose-response curves. BaP EROD induction equivalency factors (BaP-1EF) were calculated and increased in the order Ant approximately Phe < Fla < Nap < BghiP < IP < BaA < BaP < Chr < BkF. Comparison of BaP-IEFs based on 50% effect concentration (EC50) or lowest effect concentration (LEC), yielded a significant relationship between both methods described by the equation log(BaPIEF(EC50) = 0.55 x log(BaPIEF(LEC)) + 0.07 (r2 = 0.913). BaP-IEFs as derived from our measurements and as reported in literature and measured in other in vitro assays deviated up to a factor of 17 among the different studies, but the potency rankings were comparable. For the PAH mixture as on average present in the human diet an overall tetrachlorodibenzo-p-dioxin (TCDD)-IEF of 1 x 10(-4) was estimated. The total PAH based TCDD induction equivalents (IEQ) intake then was calculated 300 pg/day, which is approximately 2 times higher then the PHAH based TCDD-EQ intake reported for humans.     

Partitioning of dioxins and dibenzofurans: Whole blood, blood plasma and adipose tissue

It has become relatively common to estimate human dioxin body burden and to document dioxin exposures by measuring dioxin and dibenzofuran congeners in adipose tissue, whole blood or blood plasma, and reporting these values on a lipid basis. It has not been determined whether these three types of specimens contain identical dioxin and dibenzofuran levels. This paper compares paired plasma and adipose tissue and paired whole blood and adipose tissue in analyses from two groups of patients. The first group consists of twenty U.S. veterans with paired plasma and adipose specimens. The second group consists of four German adults with whole blood compared to adipose tissue. Forty-eight analyses were performed. The results suggest that for some higher chlorinated compounds, such as OCDD, plasma lipid values may be higher than adipose lipid values, but whole blood lipid values for the higher as well as lower chlorinated PCDD/Fs may be relatively similar. On the other hand, the values for the lower chlorinated PCDD/Fs, such as TCDD, are similar in blood plasma, adipose tissue and whole blood. Total PCDD/F dioxin “toxic equivalents” are similar within each of the two series reported here, using the current “International Dioxin Toxic Equivalent” system.     

The disposition and metabolism of 1,3-dibromobenzene in the rat

The distribution, excretion and metabolism of 1,3-dibromobenzene following a single i.p. administration to rats 100 or 300 mg/kg was investigated using radiotracer [3H] and GC-MS technique. After 72 hours about 74 to 90% were excreted in urine. The highest radioactivity was observed in the liver, kidneys and fat tissue. Later on a steady decline of radioactivity was apparent in all investigated tissues except for blood cells and the sciatic nerve, where constant levels were noted. In urine the following substances were identified and quantified by GC peak areas: unchanged 1,3-DBB (18%), dibromophenols (34%), dibromothiophenols (28%), dibromothioanisole (1.8%), bromophenol (5.5%), bromohydroxythiophenols (5%), and bromohydroxythioanisole (7.5%).     

Effects of bisphenol A on energy balance and accumulation in brown adipose tissue in rats

Some environmental contaminants have the potential to affect humans or animals by mimicking the effects of hormones. Bisphenol A (BPA) is a weak estrogen agonist when tested using in vitro or in vivo bioassays. In addition to the well documented effects of estrogens on reproductive functions, ovarian hormones also have salient effects on mammalian energy balance and feeding behavior. In this study, we investigated the effects of BPA on body weight and food intake of ovariectomized adult female rats. Treatment with doses of 4 or 5 mg/day for 15 days resulted in a significant reduction of body weight gain with no reduction in food intake. A dose of 1 mg/day did not affect feeding or weight gain. BPA was detected in the blood, brain and adipose tissues of the BPA-treated animals but not in the vehicle control group. There was a preferential concentration of BPA in brown adipose tissue. These results indicate that BPA can affect energy balance and that brown adipose tissue may be a primary tissue into which BPA accumulates in mammals.