Bioaccumulation of organochlorine compounds in large, threatened elasmobranchs off northern New South Wales, Australia.

Persistent organic pollutants (POPs) include polychlorinated biphenyls (PCBs) dichlorodiphenyltrichloroethane (DDT) and hexachlorobenzene (HCB), which are resistant to biodegradation and therefore accumulate in the marine environment. In Australia, POPs occur in high concentrations primarily in costal water near farming regions and urban centres. From contaminated sediments and biota, POPs are transferred and biomagnified in larger marine organisms. We quantified POPs concentrations in 57 individuals from ten species of sharks and rays caught in bather-protection gillnets deployed off northern New South Wales, Australia. Polychlorinated biphenyls, DDTs and HCB were detected in all species. For some individuals, concentrations were at levels known to have deleterious sub-lethal effects. Overall, the POP concentrations analysed in this study were comparable to those in similar species from more polluted regions, and may have negative impacts on longer-term health. Future research is warranted to investigate spatio-temporal patterns of species-specific contaminant loads and their implications.

A novel model to characterize postnatal exposure to lipophilic environmental toxicants and application in the study of hexachlorobenzene and infant growth.

BACKGROUND: Infants are exposed to persistent environmental contaminants through breast milk, yet studies assessing the health effects of postnatal exposure are lacking. Existing postnatal exposure assessment is either too simple (lactation exposure model, LEM) or requires complex physiologically-based pharmacokinetic (PBPK) models. OBJECTIVES: We present equations for postnatal exposure calculations. We applied these equations to study the effect of hexachlorobenzene (HCB) on infant growth in the two first years of life. METHODS: HCB was measured in breast milk samples in 449 mother-child pairs participating in the Norwegian birth cohort study HUMIS. We used these concentrations, mother's weight, height and age, together with child's weight at 8 age points, and proportion of milk consumed each month, to calculate HCB concentrations in the infant over age. We then estimated the association between HCB and infant growth using a linear mixed model. RESULTS: Children exposed to HCB via mother's milk reached concentrations 1-5 times higher than the mother. HCB was associated with lower weight gain in the first 2years (-33g per unit HCB and month, 95% CI: -38, -27 at 6months). Associations were stronger during the first 3months (-57g per unit HCB and month, 95% CI: -67, -49 at 1month), indicating a critical window of effect. Our equations gave more precise estimates than the LEM. CONCLUSION: Our equations for postnatal exposure of lipophilic environmental toxicants give better results than the LEM and are easier to implement than the complex PBPK models. HCB exposure, especially during the first three months of life, has a negative effect on infant growth up to 2years.

Historical intake and elimination of polychlorinated biphenyls and organochlorine pesticides by the Australian population reconstructed from biomonitoring data.

Quantifying the competing rates of intake and elimination of persistent organic pollutants (POPs) in the human body is necessary to understand the levels and trends of POPs at a population level. In this paper we reconstruct the historical intake and elimination of ten polychlorinated biphenyls (PCBs) and five organochlorine pesticides (OCPs) from Australian biomonitoring data by fitting a population-level pharmacokinetic (PK) model. Our analysis exploits two sets of cross-sectional biomonitoring data for PCBs and OCPs in pooled blood serum samples from the Australian population that were collected in 2003 and 2009. The modeled adult reference intakes in 1975 for PCB congeners ranged from 0.89 to 24.5ng/kgbw/day, lower than the daily intakes of OCPs ranging from 73 to 970ng/kgbw/day. Modeled intake rates are declining with half-times from 1.1 to 1.3years for PCB congeners and 0.83 to 0.97years for OCPs. The shortest modeled intrinsic human elimination half-life among the compounds studied here is 6.4years for hexachlorobenzene, and the longest is 30years for PCB-74. Our results indicate that it is feasible to reconstruct intakes and to estimate intrinsic human elimination half-lives using the population-level PK model and biomonitoring data only. Our modeled intrinsic human elimination half-lives are in good agreement with values from a similar study carried out for the population of the United Kingdom, and are generally longer than reported values from other industrialized countries in the Northern Hemisphere.

Evaluating the neurotoxic effects of lactational exposure to persistent organic pollutants (POPs) in Spanish children.

Although the brain continues developing in the postnatal period, epidemiological studies on the effects of postnatal exposure to neurotoxic POPs through breast-feeding remain mostly inconclusive. Failure to detect associations between postnatal exposure and health outcomes may stem from the limitations of commonly employed approaches to assess lactational exposure. The aim of the present study was to assess whether lactational exposure to polychlorinated biphenyl-153 (PCB-153), dichlorodiphenyldichloroethylene (DDE), or hexachlorobenzene (HCB) as estimated with a physiologically based pharmacokinetic (PBPK) model, is associated with decrements in mental and psychomotor development scores of the Bayley Scales of Infant Development (BSID) test in children aged around 14-months of a subsample (N=1175) of the Spanish INMA birth cohort, and to compare this with the effects of prenatal exposure. Although in the present study population PCB-153, DDE and HCB exposure increased within the first months of postnatal life, no associations were found between different periods of postnatal exposure to these compounds and mental or psychomotor scores. Increasing prenatal PCB-153 concentrations were associated with worse mental and psychomotor scores, although significance was only reached for psychomotor development (ß [95%CI]=-1.36 [-2.61, -0.11]). Indeed, the association between exposure and effects observed during prenatal life weakened gradually across periods of postnatal life. Results of the present study suggest that, although breastfeeding increases children's blood persistent organic pollutants (POPs) levels during postnatal life, deleterious effects of PCB-153 on neuropsychological development are mainly attributable to prenatal exposure.

Bioconcentration and intracellular storage of hexachlorobenzene in charophytes and their potential role in monitoring and remediation actions.

It has been hypothesized that highly hydrophobic substances (LogK(OW) > 5) including many persistent organic pollutants cannot overtake protective tissues and diffuse inside the body of plants due to steric hindrance or very slow diffusion. We investigated the bioaccumulation of hexachlorobenzene (HCB, LogK(OW) = 5.5) in a benthic charophycean macro-alga: Chara rudis. Chara species are a group of common freshwater algae with a complex body structure encompassing a protective layer of cortex cells surrounding large internode cells. The charophyte cell wall has many features in common with that of higher plants; therefore, they are useful models to investigate bioaccumulation mechanisms in general. We found that HCB diffused through the cortex and reached the cytoplam of internode cells. More than 90% of the HCB mass found in the organism was in the cortex and 10% in the internode cell cytoplasm. The cortex reached a pseudoequilibrium partitioning with water, and the bioconcentration factor was in the same range as that of lower aquatic organisms such as phytoplankton. Charophytes are therefore very efficient accumulators of hydrophobic compounds. Based on the structural and ecological features of charophytes, we speculated on their possible use as biomonitors and bioremediation tools.

Bioavailability assessment of hexachlorobenzene in soil as affected by wheat straw biochar.

Biochar incorporation with soil could increase sorption of organic contaminants, thereby reducing their bioavailability. In this study, the effects of wheat straw biochar on the sorption, dissipation and bioavailability of hexachlorobenzene (HCB), a typical persistent organic pollutant (POP), were investigated in laboratory experiments. We observed that HCB sorption by biochar was 42 times higher than that by soil and the sorption isotherm was linear for the concentration range studied. Biochar amendments reduced HCB dissipation, volatilization and earthworm (Eisenia foetida) uptake of HCB from soil. Hydroxypropyl-ß-cyclodextrin extraction correlated better with the earthworm bioassay than butanol extraction of HCB in biochar-amended soil. The results of both chemical extraction and earthworm bioassay indicate that biochar amendment of soil resulted in a rapid reduction in the bioavailability of HCB, even for the 0.1% biochar application rate. This suggested that wheat straw biochar could potentially be used in immobilizing POPs in contaminated sites.

Human and environmental biomonitoring of polychlorinated biphenyls and hexachlorobenzene in Saxony, Germany based on the German Environmental Specimen Bank.

The objective of the present study was to investigate the principle relationships between concentrations in human and environmental matrices of polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) in short distance comparable areas within Saxony, Germany by employing the data of the German Environmental Specimen Banking (ESB). Examples supporting this idea were presented by selecting data on blood plasma collected from students in University of Halle and pine shoots, egg matter of city pigeons, earthworm, and roe deer liver. Similar pattern for PCB 138 and PCB 180 was found for the human plasma and pine shoots samples during investigated years and the human data followed the corresponding environmental levels with some delay of approximately two years. However, PCB 153 that was the prevailing congener did not manifest this relationship. In addition, the correlation of the ratios of concentrations (human/environmental concentration) to some physicochemical constants such as molecular weight (MW), octanol-water partition coefficient (logK(ow)), Henry's law constant (K(H)), and sorption partition coefficient (logK(oc)) of HCB, PCB 138, PCB 153, and PCB 180 were studied. The resulted negative slopes with all constants in case of blood plasma/city pigeons egg matter pairs suggested that the accumulation of lipophilic compounds is more pronounced in pigeon eggs than in human blood.

[Evaluation of bioavailability of hexachlorobenzene and pentachlorobenzene to rice roots in soils by accelerated solvent extraction].

A pot experiment was conducted in greenhouse in two types of soils, Hydragric Acrisols (Ac) and Gleyi-Stagnic Anthrosols (An). Three treatments as control and the additions of 1% and 2% organic fertilizer were designed in each type of soil. The objective of this study was to evaluate the accumulation abilities of hexachlorobenzene (HCB) and its predominant metabolite of pentachlorobenzene (PeCB) by rice roots, and to compare the correlation between HCB or PeCB concentrations in rice roots and in soils extracted by four extraction solvents (hexane/acetone = 3/1(V/V), ethanol, hexane, water) to evaluate the bioavailability of HCB and PeCB to rice roots. The results showed that the mean concentrations of HCB in rice roots for Ac and An were 364.1 and 306.0 ng/g, respectively, while PeCB were 12.7 and 28.7 ng/g, respectively, which was due to the higher degradation rates of HCB in An than in Ac. Both the applications of 1% and 2% organic fertilizer inhibited HCB degradation, so as to decrease PeCB concentrations in rice roots either in Ac or An. The orders of correlation coefficient of both HCB and PeCB concentrations in rice roots and in soils extracted by four extraction solvents were ethanol > hexane/acetone > hexane > water, which indicated that ethanol was the best extraction solvent of soils to evaluate the bioavailability of HCB and PeCB to rice roots. Only the HCB concentrations in soils extracted by ethanol were significantly positive correlated with the HCB concentrations in rice roots. And the PeCB concentrations in soils extracted by all solvents except for water were significantly positive correlated with the PeCB concentrations in rice roots. Our results suggested that it was feasible to evaluate the bioavailability of HCB and PeCB to rice roots using accelerated solvent extraction by choosing proper extraction solvent.

Biomonitoring equivalents for hexachlorobenzene.

Recent efforts worldwide have resulted in a growing database of measured concentrations of chemicals in blood and urine samples taken from the general population. However, few tools exist to assist in the interpretation of the measured values in a health risk context. Biomonitoring equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline. This study reviews available health-based exposure guidance values for hexachlorobenzene (HCB) from Health Canada, the United States Environmental Protection Agency (US EPA), the US Agency for Toxic Substances and Disease Registry (ATSDR) and World Health Organization (WHO). HCB liver tissue concentrations in chronic rodent bioassays and information on human elimination rates and tissue distribution of HCB were extrapolated to estimate serum lipid-adjusted HCB concentrations that are consistent with the exposure guidance values for HCB. Estimated serum lipid-adjusted HCB concentrations ranging from 16 to 250 ng/g lipid were consistent with non-cancer-based exposure guidance values from various agencies. Concentrations associated with cancer risk-specific doses at target risk levels of interest were also estimated. These BE values may be used as screening tools for evaluation of population biomonitoring data for HCB in a risk assessment context and can assist in prioritization of the potential need for additional risk assessment efforts for HCB relative to other chemicals.

Organohalogen compounds in human breast milk from mothers living in Payatas and Malate, the Philippines: levels, accumulation kinetics and infant health risk.

Human breast milk samples (n=33) from primipara and multipara mothers from Payatas a waste dump site, and Malate a reference site in the Phillipines were collected in 2004 and analyzed for eight organohalogen compounds, viz., PCBs, DDTs, CHLs, HCHs, HCB, TCPMe, PBDEs and HBCDs. DDTs and PCBs were predominant in all the samples. Overall mean concentrations of PBDEs found in our study were higher (7.5 ng/g lipid wt.) than those reported for Japan and many other Asian countries. Primipara mothers had significantly higher levels of DDTs, CHLs and HCHs than multipara mothers, but not PBDEs and HBCDs. A few individuals accumulated CHLs close to or even higher than the tolerable daily intake guidelines proposed by Health Canada.

Lymphatic and portal vein absorption of organochlorine compounds in rats.

The route of absorption of ingested compounds is a determinant of their distribution and metabolism. Portal vein absorption results in direct transport to the liver, where metabolism may take place before extrahepatic delivery. Lymphatic absorption can result in delivery of parent compound to nonhepatic tissues. Understanding the fate of an ingested compound requires determination of the importance of each of these routes. Portal vein absorption can be estimated from the difference in concentrations of an ingested compound between the portal vein and peripheral vessel blood. To make these estimations, one must make assumptions on the basis of estimates of flow rate and dilution. We report here methodology that allows a direct measurement of portal vein absorption that is independent of these assumptions. Mesenteric lymph was diverted from rats by cannulation. Portal blood was sampled after duodenal infusion of a bolus of compound of interest along with a portal absorption marker, 3-O-methylglucose. Since lymph was diverted, the appearance in portal blood was solely the result of portal absorption. Absorption was quantified by the areas under the curve for the compound and marker. Portal absorption was a function of the octanol/water partition coefficients for four organochlorine compounds: hexachlorobenzene, pentachlorophenol, DDT, and its metabolite 1,1,1-trichloro-2,2-bischlorophenylethylene.

Effects of aging and sediment composition on hexachlorobenzene desorption resistance compared to oral bioavailability in rats.

Studies were conducted to assess the effects of black carbon, clay type and aging (1-1.5yr) on desorption and bioavailability of hexachlorobenzene (HCB) in spiked artificial sediments. Tenax (a super sorbent)-mediated desorption was used to examine the effects of these parameters on the physicochemical availability of HCB. The Tenax-mediated desorption of HCB from the four aged artificial sediments exhibited biphasic kinetics. The fast desorbing fractions ranged from 64.8% to 22.3%, showing reductions of 4.0-18.9% compared with freshly-spiked sediments. Statistical analysis on the fast desorbing fractions showed that all three treatment effects (i.e., montmorillonite clay, black carbon content, and aging) were significant. Two sediments with higher black carbon content exhibited much greater aging effects (i.e., greater reduction in fast desorbing fraction) than the other two sediments without the addition of black carbon. For both freshly-spiked and aged sediments, the desorption resistant sediment-bound HCB (i.e., slow desorbing fraction) correlated reasonably well to previously reported rat fecal elimination of HCB, which is a measure of the non-bioavailable fraction of sediment-bound HCB. A similar correlation was also observed between fast desorbing fraction and previously reported accumulation of HCB in the rat body (carcass+skin). These observations suggest that physicochemical availability, as defined by the desorption of HCB from sediments, provides a reasonable prediction of the oral bioavailability of sediment-bound HCB to rats. These results showed that montmorillonite clay, black carbon and aging reduced physicochemical availability and ultimately bioavailability of sediment-bound HCB.

Determination of the dietary absorption efficiency of hexachlorobenzene with the channel catfish (Ictalurus punctatus).

This study was designed to experimentally measure the assimilation efficiency of hexachlorobenzene (HCB) in a warm-water, benthic-feeding fish species, the channel catfish (Ictalurus punctatus). Catfish were exposed to (14)C-radiolabeled HCB in catfish food over a 28-day exposure period, followed by a 14-day clearance period. Over the experimental period, the total (14)C residues were measured in fish tissue and a simple two-box kinetic model was applied to the data to simulate uptake and clearance dynamics. No detectable metabolism of HCB by catfish was found. A two-box kinetic model effectively modeled the uptake and clearance of (14)C-HCB in catfish, with a calculated assimilation efficiency of the chemical into the whole catfish of 67% (growth corrected). The growth-corrected pseudo first-order elimination half-life of (14)C-HCB from whole catfish was determined to be 29 days (k(2)=0.024 day(-1)).

Effect of organic carbon content, clay type, and aging on the oral bioavailability of hexachlorobenzene in rats.

Bioavailability of lipophilic chemicals is influenced by the physicochemical properties of soils/sediment such as particle size, pH, clay, and organic carbon content. The present study investigated the effects of sediment composition and aging on the oral bioavailability of hexachlorobenzene (HCB) in rats. Formulated sediments were prepared using various ratios of kaolinite and montmorillonite clay, sand, peat moss, and black carbon, spiked with (14)C-HCB, and orally administered to rats prior to and after one year of aging in dark at 10 degrees C. In the nonaged sediments there was a 21 to 45% reduction in the oral bioavailability of HCB when compared to the corn oil standard without any clear pattern of the impact of the sediment clay and/or organic carbon content. One year of aging resulted in statistically significant (p = 0.049) reduction in the oral bioavailability of HCB from the sediments compared to the corn oil standard and nonaged sediment indicating stronger interactions between HCB and sediment contents with aging. The mean reduction in oral bioavailability after one year of aging ranged from approximately 5 to 14% greater than that observed for nonaged sediments. The fecal elimination of the HCB-derived radioactivity from the one-year-aged sediments was much higher than the nonaged sediments, consistent with the lower absorption from the gastrointestinal tract due to lower desorption of HCB from the aged sediments. Increase in the fecal elimination and decrease in oral bioavailability of (14)C-HCB was related to the increase in clay and black carbon.

Selective bioaccumulation of chlorinated pesticides and metabolites in Arctic seabirds.

Chlorinated pesticides and metabolites (CPs) were quantified in the seabird species: little auk (Alle alle), Brünnich's guillemot (Uria lomvia), black guillemot (Cepphus grylle) and black-legged kittiwake (Rissa tridactyla). The purpose was to evaluate avian accumulation of selected CPs based on their concentrations and relative patterns, their relation to dietary descriptors (stable isotopes of carbon and nitrogen), to enzymes involved in biotransformation, as well as CPs' accumulation potential relative to the recalcitrant polychlorinated biphenyl PCB-153. In all species, the CP pattern was dominated by p,p'-dichlorodiphenyltrichloroethane (DDE) and hexachlorbenzene (HCB). Except for HCB, concentrations were not related to trophic position. Most CPs were quantified in black guillemot, indicating a slower elimination compared to other seabird species. Brünnich's guillemot showed efficient elimination of chlordanes, whereas the opposite was found for little auk. Kittiwake showed higher accumulation of persistent CP and metabolites than auks, whereas accumulation of less recalcitrant CPs was low.

Toxicity of hexachlorobenzene and its transference from microalgae (Chlorella kessleri) to crabs (Chasmagnathus granulatus).

The aim of this work was to study the transference of hexachlorobenzene from a green alga (Chlorella kessleri) to an estuary crab (Chasmagnathus granulatus), and to analyze the toxic effects that the xenobiotic has on the latter. The effect of hexachlorobenzene uptake was evaluated measuring oxidative stress, Uroporphyrinogen decarboxylase activity and morphometric parameter alteration, and also performing a histological analysis of crab hepatopancreas. Results demonstrated that hexachlorobenzene enters the alga, is accumulated in it, and then transferred into the crab, causing a decrease in Uroporphyrinogen decarboxylase activity in both organisms. The high malondialdehyde levels detected in crab hepatopancreas after the toxic treatment suggested the existence of hexachlorobenzene-induced lipid peroxidation. Antioxidant defenses such as superoxide dismutase activity and reduced glutathione content fell below normal values on the fourth week of treatment. At the same time, the hepatosomatic index, used as a morphometric parameter, reduced 20% with respect to the control. The histological analysis revealed epithelium disorganization in hepatopancreas tubules, confirming the existence of structural damage caused by hexachlorobenzene.

An updated physiologically based pharmacokinetic model for hexachlorobenzene: incorporation of pathophysiological states following partial hepatectomy and hexachlorobenzene treatment.

Physiologically based pharmacokinetic (PBPK) modeling is generally used for describing xenobiotic disposition in animals and humans with normal physiological conditions. We describe here an updated PBPK model for hexachlorobenzene (HCB) in male F344 rats with the incorporation of pathophysiological conditions. Two more features contribute to the distinctness of this model from the earlier published versions. This model took erythrocyte binding into account, and a particular elimination process of HCB, the plasma-to-gastrointestinal (GI) lumen passive diffusion (i.e., exsorption), was incorporated. Our PBPK model was developed using data mined from multiple pharmacokinetic studies in the literature, and then modified to simulate HCB disposition under the conditions of our integrated pharmacokinetics/liver foci bioassay. This model included plasma, erythrocytes, liver, fat, rapidly and slowly perfused compartments, and GI lumen. To account for the distinct characteristics of HCB absorption, the GI lumen was split into an upper and a lower part. HCB was eliminated through liver metabolism and the exsorption process. The pathophysiological changes after partial hepatectomy, such as alterations in the liver and body weights and fat volume, were incorporated in our model. With adjustment of the transluminal diffusion-related parameters, the model adequately described the data from the literature and our bioassay. Our PBPK model simulation suggests that HCB absorption and exsorption processes depend on exposure conditions; different exposure conditions dictate different absorption and exsorption rates. This model forms a foundation for our further exploration of the quantitative relationship between HCB exposure and development of preneoplastic liver foci.

Use of transplanted Zebra mussels (Dreissena polymorpha) to assess the bioavailability of microcontaminants in Flemish surface waters.

Zebra mussels (Dreissena polymorpha) were translocated in cages to 56 water bodies in Flanders (Belgium) during summer 2001. After six weeks, concentrations of polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), p,p'-DDE, and trace metals were measured in the transplanted mussels. It was investigated whether total dissolved water and sediment pollutant levels or bioaccumulation factors (BAFs) and biota-sediment accumulation factors (BSAFs) were predictive for mussel tissue levels. The sample sites covered a broad range both in terms of the type and concentration of the pollutants, and this was reflected in large differences in tissue concentrations of all pollutants among the sites. The highest pollutant levels in mussels were among the highest reported in the literature. For Cd and Zn levels up to 33 and 1994 microg/g dry wt. respectively were found. The lowest levels were comparable to those from uncontaminated sites in Europe and the U.S. For Cd and Zn respectively 51 and 75% of the variation in tissue levels was described. For both metals, dissolved and particulate metal contributed to the variation in accumulation. For other pollutants, relationships between tissue concentration and water or sediment concentration were weak or nonsignificant. Then the measured environmental factors (dissolved calcium, pH, oxygen, organic carbon and clay content in the sediment) were taken into account applying multiple regression analysis, and no increase in the described variation of pollutant accumulation was observed. The BAF and BSAF for all pollutants varied up to 1000-fold even after TOC-normalization. Clear negative relationships were found between BAFs/ BSAFs and environmental levels. However, even at constant environmental concentrations a 10- to 100-fold variation in BAFs/BSAFs was observed. This study illustrated the need for biological monitoring since neither environmental

Breastfeeding and concentrations of HCB and p,p'-DDE at the age of 1 year.

Exposure to organochlorine compounds (OCs) occurs both in utero and through breastfeeding. Levels of hexachlorobenzene (HCB) in the cord serum of newborns from a population located in the vicinity of an electrochemical factory in Spain are among the highest ever reported. We aimed to assess the degree of breast milk contamination in this population and the subsequent exposure of children to these chemicals through breastfeeding. A birth cohort including 92 mother-infant pairs (84% of all births in the study area) was recruited between 1997 and 1999 in five neighboring villages. OCs were measured in cord serum, colostrum, breast milk, and children's serum at 13 months of age. Concentrations of OCs were detected and quantified in all colostrum and milk samples. The concentrations in mature milk were lower than those encountered in colostrum. At 13 months of age the highest concentration of OC was found for dichlorodiphenyl dichloroethane (p,p'-DDE), in contrast to what these children presented at birth, where HCB was the highest compound. Those infants who were breastfed had higher concentrations at the age of 1 than those who were formula fed (2.13 ng/mL of HCB among formula feeders vs 4.26 among breast feeders, and 1.95 of p,p'-DDE vs 6.00 (P<0.05)). Long-term breastfeeding leads to a dose-response increase of the concentrations in children's serum during the first year of life.

Effects of yo-yo diet, caloric restriction, and olestra on tissue distribution of hexachlorobenzene.

Chlorinated hydrocarbons are lipophilic, toxic, and persistent in the environment and animal tissues. They enter the body in food and are stored in adipose tissue. Loss of body fat through caloric restriction mobilizes stored lipophilic xenobiotics and results in distribution to other tissues. We have studied the reversibility of this process in mice that followed a regimen of body weight cycling. Weight gain was followed by weight loss, a second gain, and a second loss ("yo-yo diet regimen"). We measured the distribution of orally gavaged [14C]hexachlorobenzene, which is sparingly metabolized. We found that weight cycling has different effects in different organs. Continued weight loss resulted in a threefold increase of 14C amount and concentration in the brain. After weight regain, 14C in the brain decreased but then increased again after a second weight loss. Weight loss resulted in an increase in the concentration of 14C in adipose tissue without changing the total amount in that tissue. Weight loss and regain resulted in an increase of 14C in the liver, which reflected an increase of fat in the liver. The regimen of weight gain and loss was repeated in mice gavaged with [14C]hexachlorobenzene, with one group receiving the nonabsorbable fat olestra in the diet. Combined dietary olestra and caloric restriction caused a 30-fold increase in the rate of excretion of 14C relative to an ad libitum diet or a reduced caloric diet alone. Distribution of 14C into the brain resulting from the restricted diet was reduced by 50% by dietary olestra.