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See detailApplication of Bayesian Population Physiologically Based Pharmacokinetic (PBPK) Modeling and Markov Chain Monte Carlo Simulations to Pesticide Kinetics Studies in Protected Marine Mammals: DDT, DDE, and DDD in Harbor Porpoises
Weijs, Liesbeth; Yang, Raymond S.H.; Das, Krishna ULg et al

in Environmental Science & Technology (2013), 47

Physiologically based pharmacokinetic (PBPK) modeling in marine mammals is a challenge because of the lack of parameter information and the ban on exposure experiments. To minimize uncertainty and ... [more ▼]

Physiologically based pharmacokinetic (PBPK) modeling in marine mammals is a challenge because of the lack of parameter information and the ban on exposure experiments. To minimize uncertainty and variability, parameter estimation methods are required for the development of reliable PBPK models. The present study is the first to develop PBPK models for the lifetime bioaccumulation of p,p′-DDT, p,p′-DDE, and p,p′- DDD in harbor porpoises. In addition, this study is also the first to apply the Bayesian approach executed with Markov chain Monte Carlo simulations using two data sets of harbor porpoises from the Black and North Seas. Parameters from the literature were used as priors for the first “model update” using the Black Sea data set, the resulting posterior parameters were then used as priors for the second “model update” using the North Sea data set. As such, PBPK models with parameters specific for harbor porpoises could be strengthened with more robust probability distributions. As the science and biomonitoring effort progress in this area, more data sets will become available to further strengthen and update the parameters in the PBPK models for harbor porpoises as a species anywhere in the world. Further, such an approach could very well be extended to other protected marine mammals. [less ▲]

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See detailA review of dietary and non-dietary exposure to bisphenol-A.
Geens, Tinne; Aerts, Dominique; Berthot, Carl et al

in Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (2012), 50(10), 3725-40

Due to the large number of applications of bisphenol-A (BPA), the human exposure routes are multiple. We aimed to review shortly the food and non-food sources of BPA, and to evaluate their contribution to ... [more ▼]

Due to the large number of applications of bisphenol-A (BPA), the human exposure routes are multiple. We aimed to review shortly the food and non-food sources of BPA, and to evaluate their contribution to the human exposure. Food sources discussed here include epoxy resins, polycarbonate and other applications, such as paperboard and polyvinylchloride materials. Among the non-food sources, exposures through dust, thermal paper, dental materials, and medical devices were summarized. Based on the available data for these exposure sources, it was concluded that the exposure to BPA from non-food sources is generally lower than that from exposure from food by at least one order of magnitude for most studied subgroups. The use of urinary concentrations from biomonitoring studies was evaluated and the back-calculation of BPA intake seems reliable for the overall exposure assessment. In general, the total exposure to BPA is several orders of magnitude lower than the current tolerable daily intake of 50 mug/kg bw/day. Finally, the paper concludes with some critical remarks and recommendations on future human exposure studies to BPA. [less ▲]

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See detailUse of Physiologically Based Pharmacokinetic (PBPK) Models in Marine Mammal Toxicology
Weijs, Liesbeth; Yang, Raymond S.H.; Das, Krishna ULg et al

in Kawaguchi, M.; Misaki, K.; Sato, H. (Eds.) et al Interdisciplinary Studies on Environmental Chemistry—Environmental Pollution and Ecotoxicology (2012)

Physiologically based pharmacokinetic (PBPK) models are mathematical models that are largely based upon the physiological characteristics of the species and the biochemical properties of the chemical of ... [more ▼]

Physiologically based pharmacokinetic (PBPK) models are mathematical models that are largely based upon the physiological characteristics of the species and the biochemical properties of the chemical of interest. They quantitatively describe and predict the kinetics of pollutants inside the body and can be of major importance for risk assessment of chemicals in marine mammals. PBPK models which consist of five compartments (liver, blubber, kidney, brain, and the rest of the body) were made for selected polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in order to address the bioaccumulation of these compounds in tissues of harbour porpoises (Phocoena phocoena). Harbour porpoises have relatively long life spans, are common cetaceans in the North Sea, a heavily polluted area, and are known to be very sensitive to pollution. Models developed for all compounds (some PCBs and PBDEs) were evaluated using existing datasets from the literature and from analyses performed by GC-MS, the latter being obtained from stranded porpoises in the Black Sea and the North Sea over a period of 18 years (1990–2008) to assess spatial and temporal trends in bioaccumulation of the respective PCBs and PBDEs. We demonstrate that PBPK models are a feasible computational approach that can be used as a non-destructive tool for predicting the chemical pollution status of the marine mammals. [less ▲]

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See detailComputational toxicology: Physiologically based pharmacokinetic models (PBPK) for lifetime exposure and bioaccumulation of polybrominated dephenyl ethers (PBDEs) in marine mammals
Weijs, Liesbeth; Covaci, Adrian; Yang, Raymond S H et al

in Environmental Pollution (2012)

Due to migration of harbour porpoises towards more polluted areas like the North Sea and their sensitivity towards pollution, there is a need for proper conservation measures for this species. As a ... [more ▼]

Due to migration of harbour porpoises towards more polluted areas like the North Sea and their sensitivity towards pollution, there is a need for proper conservation measures for this species. As a consequence, knowledge about the pollutant’s kinetics is required. The present study is the first to investigate the kinetics of PBDEs in marine mammals using PBPK modeling as a non-destructive tool for describing the chemical’s kinetics in a protected animal species. The models were developed and parameterized using data from the literature and Black Sea harbour porpoises through computer opti- mization. The predictability of these models in time was assessed by reverse dosimetry modeling using data from North Sea porpoises (1990e2008). From these predictions, PBDE 99 levels were found to decrease the fastest, followed by PBDE 153, 47 and 100. Results show that the PBPK models can be applied for harbour porpoises from different regions and also simulate time trends. [less ▲]

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See detailPotential effects of blood contaminants on immune responses in harbour seals (Phoca vitulina)
Dupont, Aurélie ULg; Weijs, Liesbeth; Siebert, Ursula et al

Poster (2011, August 23)

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See detailThe harbor seal and the harbor porpoise from the North Sea: review of their ecotoxicological status based on stranded and free-ranging individuals and potential threaths to the population
Das, Krishna ULg; Weijs, Liesbeth; Habran, Sarah ULg et al

Conference (2011, May)

The harbor seal (Phoca vitulina) and the harbor porpoise (Phocoena phocoena) from the North Sea have experienced major fluctuations these last decades due to habitat loss, prey fluctuation and pollution ... [more ▼]

The harbor seal (Phoca vitulina) and the harbor porpoise (Phocoena phocoena) from the North Sea have experienced major fluctuations these last decades due to habitat loss, prey fluctuation and pollution of the marine environment. Recently, development of monitoring programs and non-invasive sampling techniques, including seal catches in Germany allowed blood sampling together with measurements of blubber thickness, body mass, sex and body length. This approach is complementary to the study of stranded and by-caught individuals sampled during necropsies. Essential (Se, Zn, Cu, Fe) and non-essential elements (T-Hg, MeHg, Cd, Pb), perfluorinated organochemicals (PFCs) polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) were measured in blubber and in blood (for selected compounds) of stranded, by-caught and free-ranging individuals from Belgian and German coasts. In contrast to Cd and Pb, hepatic T-Hg can reach concentrations as high as 2.1 μg.g-1 dry weight but depended on several factors including position in the trophic chain (inferred from δ13C and δ15N values), age group and the body mass. This level has been shown to generate in vitro toxicity on harbor seal lymphocytes. Organic compound analysis (PFCs, PCBs, PBDEs) revealed widespread dispersion of contaminants in the marine environment with higher concentrations in seals compared to porpoises in agreement with the higher trophic position of the harbor seal. However, metabolization of these compounds differed between the two species, as revealed by the higher contribution of the persistent BDE-47 and lower chlorinated and non-persistent congeners (e.g. CB 52, CB95) in tissues of harbor porpoises. T-Hg, PFCs, PCBs and PBDEs were detected in calves confirming maternal transfer to offspring. These pollutants are strongly suspected to affect the immune and endocrine systems as well as vitamin A metabolism and this raises concern about exposure-related health effects, especially in younger individuals. [less ▲]

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See detailThyroid endocrine disruption in situ and in vivo experiments reveals compensatory mechanisms
Schnitzler, Joseph ULg; Celis, Niko; Klaren, Peter et al

Conference (2011, May)

We compared effects of in situ and in vivo exposure of EDC on teleost thyroid system in order to get a complete picture of the putative interactions. A 120-day experimental exposure was designed in ... [more ▼]

We compared effects of in situ and in vivo exposure of EDC on teleost thyroid system in order to get a complete picture of the putative interactions. A 120-day experimental exposure was designed in combination to in situ measurements of persistent organic pollutants in 87 wild sea bass (Dicentrarchus labrax) form European estuaries. Seventy-five individuals were exposed to doses of PCB (0.3 to 1.0 µg Σ7PCBs per g food pellets) that reflects the persistent organic pollution to which the European sea bass population could conceivably be exposed. We applied a series of recommended measurement endpoints in these studies. The centrally controlled thyroidal secretion of T4 was monitored adequately from the muscular T4 levels and from thyroid histological appearance. Muscular T3 levels and enzymatic deiodinase and sulfatase activities in liver were measured. Observations made in experimental exposure to environmental relevant doses of PCB were consistent with those made in our field study. In both studies the muscular T4 levels were unaffected and no multivariate relationship with contaminant exposure could be revealed. Measurements of follicular diameter and epithelial cell heights showed no significant differences. Our findings revealed an increase of the hepatic T4ORD activity by higher chlorinated PCB congeners and DDTs. In both studies, we observed a general decrease the thyroid hormone conjugation by sulfatases that increases their solubility and facilitates their excretion. The muscular T3 levels were well preserved. These changes likely represent compensatory responses to disrupting effects that might otherwise have depressed T3 levels. This approach permitted us to interpret the causes and implications of alterations of the teleost thyroid system. [less ▲]

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See detailThyroid hormone disrupting chemicals in sea bass (Dicentrarchus labrax) from European coasts
Schnitzler, Joseph ULg; Michel, Loïc ULg; Klaren, Peter et al

Conference (2011, February 25)

Polychlorinated biphenyls (PCBs) and organochlorine pesticides like Dichloro-Diphenyl-Trichloroethane (DDTs), Hexachlorocyclohexanes (HCHs), aldrin, dieldrin and trace elements (Cd, Cu, Se, Pb, Zn and Hg ... [more ▼]

Polychlorinated biphenyls (PCBs) and organochlorine pesticides like Dichloro-Diphenyl-Trichloroethane (DDTs), Hexachlorocyclohexanes (HCHs), aldrin, dieldrin and trace elements (Cd, Cu, Se, Pb, Zn and Hg) were analysed in the muscle of sea bass (Dicentrarchus labrax) sampled in coastal regions near several important European river mouths (Gironde, Charente, Loire, Seine and Scheldt). These potential endocrine disrupting chemicals were present in European coastal waters. Even if their concentrations were well below the Maximum Residue Limits set by the governments, they induced alterations of the endocrine system. We established correlations between contaminant concentrations and effects on the thyroid system in sea bass. The contaminants induced modifications of the metabolic pathways of thyroid hormones and enhanced thyroid hormone synthesis. The activity of T4 Outer Ring Deiodinase was increased, that leads to an intensified conversion of thyroxine (T4) to its more biologically active form triiodothyronine (T3). Meanwhile, the activity of T4 sulfatation was reduced, that leads to a lowered biliary excretion of thyroid hormones. The modified metabolic pathways of the thyroid hormones can be interpreted as a tool to homeostatically maintain the thyroid hormone status. Of all tested compounds, the higher chlorinated PCBs seemed to be the most implicated in this perturbation. The nature of thyroid hormone synthesis, signalling and regulation is highly conserved among vertebrates. Although we cannot extrapolate thyroid toxicity data directly from one species to another, these environmental factors may well affect thyroid function in other species, including humans. [less ▲]

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See detailPOTENTIAL EFFECTS OF BLOOD CONTAMINANTS ON IMMUNE RESPONSES IN HARBOUR SEALS (PHOCA VITULINA)
Dupont, Aurélie ULg; Weijs, Liesbeth; Siebert, Ursula et al

in Organohalogen Compounds (2011), 73

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See detailFood interactions : effects on health, consumer perception and impact on agro-food industries “FOODINTER”.
Scippo, Marie-Louise ULg; Blust, Ronny; Boniver, Delphine et al

Report (2011)

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See detailThyroid dysfunction in sea bass (Dicentrarchus labrax): Underlying mechanisms and effects of polychlorinated biphenyls on thyroid hormone physiology and metabolism
Schnitzler, Joseph ULg; Celis, Niko; Klaren, Peter et al

in Aquatic Toxicology (2011), 105

The current study examines the effect of subchronic exposure to a mixture of Aroclor standards on thyroid hormone physiology and metabolism in juvenile sea bass. The contaminant mixture was formulated to ... [more ▼]

The current study examines the effect of subchronic exposure to a mixture of Aroclor standards on thyroid hormone physiology and metabolism in juvenile sea bass. The contaminant mixture was formulated to reflect the persistent organic pollution to which the European sea bass population could conceivably be exposed (0.3, 0.6 and 1.0 g 7PCBs per g food pellets) and higher (10 g 7PCBs per g food pellets). After 120 days of exposure, histomorphometry of thyroid tissue, muscular thyroid hormone concentration and activity of enzymes involved in metabolism of thyroid hormones were assessed. Mean concentrations of 8, 86, 142, 214 and 2279 ng g−1 ww ( 7 ICES PCB congeners) were determined after 120 days exposure. The results show that the effects of PCB exposures on the thyroid system are dose-dependent. Exposure to environmentally relevant doses of PCB (0.3–1.0 g 7PCBs per g food pellets) induced a larger variability of the follicle diameter and stimulated hepatic T4 outer ring deiodinase. Muscular thyroid hormone levels were preserved thanks to the PCB induced changes in T4 dynamics. At 10 times higher concentrations (10 g 7PCBs per g food pellets) an important depression of T3 and T4 levels could be observed which are apparently caused by degenerative histological changes in the thyroid tissue. [less ▲]

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See detailSTRATEGY FOR ASSESSING IMPACTS OF THYROID DISRUPTING CHEMICALS IN TELEOSTEANS
Schnitzler, Joseph ULg; Klaren, Peter; Celis, Niko et al

in Organohalogen Compounds (2011)

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See detailA non-invasive approach to study lifetime exposure and bioaccumulation of PCBs in protected marine mammals: PBPK modeling in harbor porpoises
Weijs, Liesbeth; Covaci, Adrian; Yang, Raymond S. H. et al

in Toxicology and Applied Pharmacology (2011), In Press, Corrected Proof

In the last decade, physiologically based pharmacokinetic (PBPK) models have increasingly been developed to explain the kinetics of environmental pollutants in wildlife. For marine mammals specifically ... [more ▼]

In the last decade, physiologically based pharmacokinetic (PBPK) models have increasingly been developed to explain the kinetics of environmental pollutants in wildlife. For marine mammals specifically, these models provide a new, non-destructive tool that enables the integration of biomonitoring activities and in vitro studies. The goals of the present study were firstly to develop PBPK models for several environmental relevant PCB congeners in harbor porpoises (Phocoena phocoena), a species that is sensitive to pollution because of its limited metabolic capacity for pollutant transformation. These models were tested using tissue data of porpoises from the Black Sea. Secondly, the predictive power of the models was investigated for time trends in the PCB concentrations in North Sea harbor porpoises between 1990 and 2008. Thirdly, attempts were made to assess metabolic capacities of harbor porpoises for the investigated PCBs. In general, results show that parameter values from other species (rodents, humans) are not always suitable in marine mammal models, most probably due to differences in physiology and exposure. The PCB 149 levels decrease the fastest in male harbor porpoises from the North Sea in a time period of 18†years, whereas the PCB 101 levels decrease the slowest. According to the models, metabolic breakdown of PCB 118 is probably of lesser importance compared to other elimination pathways. For PCB 101 and 149 however, the presence of their metabolites can be attributed to bioaccumulation of metabolites from the prey and to metabolic breakdown of the parent compounds in the harbor porpoises. [less ▲]

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See detailPCBs versus PBDEs: how similar compounds can behave differently in harbour porpoises
Weijs, Liesbeth; Yang, R. S. H.; Das, Krishna ULg et al

in Organohalogen Compounds (2011)

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See detailMaternal transfer of PCBs, PBDEs and their hydroxylated metabolites in grey seal (Halichoerus grypus) from the Isle of May, Scotland
Vanden Berghe, Marie; Weijs, Liesbeth; Habran, Sarah ULg et al

in Organohalogen Compounds (2011)

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See detailAnthropogenic and naturally-produced organobrominated compounds in marine mammals from Brazil
Dorneles, Paulo R; Lailson-Brito, José; Dirtu, Alin C et al

in Environment International (2010), 36(1), 60-67

Liver samples from 51 cetaceans, comprising 10 species, stranded between 1994 and 2006 in a highly industrialized and urbanized region in Southeast Brazil, were analyzed for polybrominated diphenyl ethers ... [more ▼]

Liver samples from 51 cetaceans, comprising 10 species, stranded between 1994 and 2006 in a highly industrialized and urbanized region in Southeast Brazil, were analyzed for polybrominated diphenyl ethers (PBDEs) and methoxylated-PBDEs (MeO-PBDEs). A concentration range of PBDEs (3-5960 ng/g lw) similar to that observed in Northern Hemisphere dolphins was found. MeO-PBDE concentrations in continental shelf (CS) dolphins from Brazil are among the highest detected to date in cetaceans (up to 250 µg/g lw). Higher [Sigma]MeO-PBDE concentrations were measured in CS and oceanic dolphins than in estuarine dolphins. The [Sigma]PBDE/[Sigma]MeO-PBDE ratio varied significantly ranging from a mean value of 7.12 to 0.08 and 0.01 for estuarine, CS and oceanic species, respectively. A positive correlation was observed between [Sigma]PBDE and year of stranding of male estuarine dolphins (Sotalia guianensis), which suggests temporal variation in the exposure. Placental transfer of organobrominated compounds was also evidenced in S. guianensis. [less ▲]

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See detailPersistent organic pollutants and methoxylated PBDEs in harbour porpoises from the North Sea from 1990 until 2008. Young wildlife at risk?
Weijs, Liesbeth; van Elk, Cornelis; Das, Krishna ULg et al

in Science of the Total Environment (2010), 409

n the European North Sea, harbour porpoises are top predators with relatively long life spans and a limited capacity for metabolic biotransformation of contaminants compared to some other marine mammal ... [more ▼]

n the European North Sea, harbour porpoises are top predators with relatively long life spans and a limited capacity for metabolic biotransformation of contaminants compared to some other marine mammal species. As such, they are exposed to a mixture of persistent pollutants, such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), DDT and metabolites (DDXs), hexachlorobenzene (HCB) and chlordanes (CHLs) that bioaccumulate in their tissues. We report here on the levels of persistent organic pollutants and of the naturally-produced methoxylated PBDEs (MeO-PBDEs) in blubber, liver and kidney of harbour porpoise neonates (n = 3), calves (n = 15), juveniles (n = 6) and adults (n = 4) of the southern North Sea. Concentrations of almost all contaminant classes decrease slightly in all age groups over the period 1990–2008. For some classes (e.g. PCBs and DDXs) however, levels seem to increase little in harbour porpoise calves. In all animals, blubber had the highest concentrations, followed by liver and kidney, whereas liver and kidney were the preferred tissues for several compounds, such as octa- and deca-PCBs. Our data suggest that harbour porpoises calves are exposed to higher or comparable concentrations of POPs and of MeO-PBDEs and somewhat different patterns of selected POPs than adults, potentially placing them, and the entire population, at a disproportionate risk for exposure-related health effects. [less ▲]

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See detailOccurrence of anthropogenic and naturally-produced organohalogenated compounds in tissues of Black Sea harbour porpoises
Weijs, Liesbeth; Das, Krishna ULg; Neels, Hugo et al

in Marine Pollution Bulletin (2010), 60

Harbour porpoises are one of the three cetacean species inhabiting the Black Sea. This is the first study to report on polybrominated diphenyl ethers (PBDEs) and naturally-produced compounds, methoxylated ... [more ▼]

Harbour porpoises are one of the three cetacean species inhabiting the Black Sea. This is the first study to report on polybrominated diphenyl ethers (PBDEs) and naturally-produced compounds, methoxylated PBDEs (MeO-PBDEs) and polybrominated hexahydroxanthene derivatives (PBHDs), in tissues (kidney, brain, blubber, liver, muscle) of male harbour porpoises (11 adults, 9 juveniles) from the Black Sea. Lipid-normalized concentrations decreased from muscle > blubber > liver > kidney > brain for the sum of polychlorinated biphenyls (PCBs) and for the sum of PBDEs. Among the naturally-produced compounds, levels of PBHDs were higher than of MeO-PBDEs, with tri-BHD and 6-MeO-BDE 47 being the dominant compounds for both groups, respectively. Concentrations of naturally-produced compounds decreased from blubber to brain, similarly to the sum of DDT and metabolites (DDXs). Concentrations of DDXs were highest, followed by PCBs, HCB, PBHDs, PBDEs and MeO-PBDEs. Levels of PCBs and PBDEs in blubber were lower than concentrations reported for harbour porpoises from the North Sea, while concentrations of DDXs were higher. [less ▲]

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See detailPolychlorinated Biphenyls affect Histological Appearance of European sea bass (Dicentrarchus labrax) Thyroids
Schnitzler, Joseph ULg; Klaren, Peter; Celis, Niko et al

Conference (2010)

Polychlorobiphenyls (PCBs) are well-described endocrine disrupters and of particular interest are effects on thyroid function. We propose here a thorough approach to assess effects of these compounds on ... [more ▼]

Polychlorobiphenyls (PCBs) are well-described endocrine disrupters and of particular interest are effects on thyroid function. We propose here a thorough approach to assess effects of these compounds on the thyroid function of European sea bass (Dicentrarchus labrax). An experimental exposure of sea bass to commercial PCB mixtures has been designed to understand underlying toxicity mechanisms and effects on the thyroid system. After 120 days of exposure histological appearance of thyroid tissue was assessed by light and electron microscopy. The follicle area, perimeter, diameter, length and with of every follicle cross section were interactively measured. The shape of the follicles was described with three dimensionless shape descriptors: roundness, form factor and aspect ratio. The histomorphometrical analysis showed a greater heterogeneity of thyroid follicle diameter and especially higher epithelial cell heights in sea bass exposed to environmental relevant doses of PCB (from 0.3 to 0.9 μg g-1 [7 ICES PCB]). Ultrastructural histological investigations showed that the epithelial cells surrounding the bigger follicles present an higher accumulation of colloid droplets. This was interpreted to be the result of increased stimulation of follicular cells. No differences in shape could be identified among the different treatment groups The size of the follicles and the form of the follicular cells gives an indication of the secretary activity of the gland. These observations support the hypothesis that the contamination of PCB mixtures can induce a hyperactivity of the thyroid tissue. These observations were confirmed by measurements of muscular thyroid hormone concentrations and activity thyroid hormone metabolism. [less ▲]

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