An optimized ibuprofen dosing scheme for preterm neonates with patent ductus arteriosus, based on a population pharmacokinetic and pharmacodynamic study.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Ibuprofen is a nonsteroidal anti-inflammatory agent that induces closure of the patent ductus arteriosus in neonates. Few studies of ibuprofen pharmacokinetics have been performed and were limited to small groups of preterm infants, showing a large intersubject variability and an increase in clearance with either postnatal or gestational age. WHAT THIS STUDY ADDS: A population pharmacokinetic study was performed on 66 neonates to characterize the concentration-time courses of ibuprofen. Ibuprofen clearance significantly increased from postnatal age day 1 to day 8, but not with gestational age. A relationship was shown between ibuprofen area under the curve (AUC) and patent ductus arteriosus closure rate, and an effective threshold AUC was evidenced. Dosing schemes were proposed as a function of postnatal age, to achieve this AUC and to improve the efficacy of treatment for patent ductus arteriosus in neonates. AIMS To describe ibuprofen pharmacokinetics in preterm neonates with patent ductus arteriosus (PDA) and to establish relationships between doses, plasma concentrations and ibuprofen efficacy and safety. METHODS: Sixty-six neonates were treated with median daily doses of 10, 5 and 5 mg kg(-1) of ibuprofen-lysine by intravenous infusion on 3 consecutive days. A population pharmacokinetic model was developed with NONMEM. Bayesian individual pharmacokinetic estimates were used to calculate areas under the curve (AUC) and to simulate doses. A logistic regression was performed on PDA closure. RESULTS: Ibuprofen pharmacokinetics were described by a one-compartment model with linear elimination. Mean population pharmacokinetic estimates with corresponding intersubject variabilities (%) were: elimination clearance CL = 9.49 ml h(-1) (62%) and volume of distribution V = 375 ml (72%). Ibuprofen CL significantly increased with postnatal age (PNA): CL = 9.49*(PNA/96.3)(1.49). AUC after the first dose (AUC1D), the sum of AUC after the three doses (AUC3D) and gestational age were significantly higher in 57 neonates with closing PDA than in nine neonates without PDA closure (P = 0.02). PDA closure was observed in 50% of the neonates when AUC1D < 600 mg l(-1) h (or AUC3D < 900 mg l(-1) h) and in 91% when AUC1D > 600 mg l(-1) h (or AUC3D > 900 mg l(-1) h) (P = 0.006). No correlation between AUC and side-effects could be demonstrated. CONCLUSIONS: To achieve these optimal AUCs, irrespective of gestational age, three administrations at 24 h intervals are recommended of 10, 5, 5 mg kg(-1) for neonates younger than 70 h, 14, 7, 7 mg kg(-1) for neonates between 70 and 108 h and 18, 9, 9 mg kg(-1) for neonates between 108 and 180 h.

The Belgian PCB/dioxin crisis-8 years later An overview.

In January 1999, 50kg polychlorinated biphenyls (PCBs) contaminated with 1g dioxins were accidentally added to a stock of recycled fat used for the production of 500tonnes animal feed in Belgium. Although signs of poultry poisoning were noticed by February 1999, the extent of the contamination was publicly announced only in May 1999, when it appeared that more than 2500 poultry and pig farms could have been involved. This has resulted in a major food crisis, known worldwide as the "Belgian PCB/dioxin crisis". The crisis was resolved by the implementation of a large food monitoring program for the seven PCB markers (PCBs 28, 52, 101, 118, 138, 153 and 180). When PCB concentrations exceeded the tolerance levels of 100, 200 or 1000ng/g fat for milk, meat or animal feed, respectively, the 17 toxic polychlorinated dibenzodioxins and furans (PCDD/Fs) congeners were also determined. By December 1999, more than 55,000 PCB and 500 dioxin analyses were already done by Belgian and international laboratories. The highest concentrations of PCBs and dioxins and the highest percentage of affected animals were found in poultry. Several important consequences of the food crisis were: (1) the introduction in 1999 of norms for PCBs in feedstuffs and food in Belgium followed by the introduction in 2002 of European harmonized norms for PCDD/Fs in animal feed and food of animal origin; (2) the systematic national monitoring of food of animal origin; and (3) the creation of the Federal Agency for Food Safety in Belgium. The human health risk following this major incident was assessed with contradictory results. It was suggested that, since only a limited proportion of the food chain was contaminated, it is unlikely that adverse effects were inflicted in the Belgian population. However, another assessment suggests that neurotoxic and behavioural effects in neonates, together with an increase in the number of cancers, may be observed.

Fatal intoxication due to tramadol alone: case report and review of the literature.

Poisoning may also lead to both coma and multiple organ failure, also in youngsters without a known major medical history. As not all toxic agents are routinely screened when a poisoning is suspected, it is useful to consider less frequently encountered poisons in certain cases. We describe the occurrence of asystole and multiple organ failure which occurred in a young man after a suspected tramadol overdose. The tramadol concentration on admission in the ICU was indeed 8 microg/ml (mg/l), far above the therapeutic range. Subsequently, the patient developed severe acute liver failure, finally leading to death. Post-mortem toxicology did not reveal any other poison responsible for this unfavourable course as only very high serum and tissue tramadol and desmethyltramadol concentrations were found. Only a few fatal poisonings attributable to tramadol alone, as observed in our case, have been reported. An overview of these cases is presented.

Association of thyroid hormone concentrations with levels of organochlorine compounds in cord blood of neonates.

BACKGROUND: Thyroid hormones are important regulators of brain development. During critical periods of development, even transient disorders in thyroid hormone availability may lead to profound neurologic impairment. Animal experiments have shown that certain environmental pollutants, including heavy metals and organochlorine compounds such as polychlorinated biphenyls (PCBs) and dioxins, can interfere with thyroid hormone homeostasis. Whether these contaminants can affect circulating levels of thyroid hormones in humans is unclear, however, because the results of available studies are inconsistent. OBJECTIVES: The aim of the present study is to examine the possible relationships between concentrations of environmental pollutants and thyroid hormone levels in human umbilical cord blood. METHODS: We measured concentrations of environmental pollutants [including selected PCBs, dioxin-like compounds, hexachlorobenzene, p,p'-DDE (dichlorodiphenyldichloroethylene), cadmium, lead] and thyroid hormones in the cord blood of 198 neonates. RESULTS: A statistically significant inverse relationship between concentrations of organochlorine compounds and levels of both free triiodothyronine (fT3) and free thyroxine (fT4), but not thyroid-stimulating hormone, was observed. We found no association between concentrations of heavy metals and thyroid hormone levels. CONCLUSIONS: Our results suggest that environmental chemicals may affect the thyroid system of human neonates. Although the differences in fT3 and fT4 levels associated with the organochlorine compounds were within the normal range, the observed interferences may still have detrimental effects on the neurologic development of the individual children, given the importance of thyroid hormones in brain development.

Biomagnification of PBDEs in three small terrestrial food chains.

Eight polybrominated diphenyl ethers (PBDE) congeners (IUPAC nos. 28, 47, 99, 100, 153, 154, 183, and 209) were measured in passerines (great tits--Parus major), wood mice (Apodemus sylvaticus), and bank voles (Clethrionomys glareolus). These data were combined with previously obtained data on PBDEs in common buzzards (Buteo buteo), sparrowhawks (Accipiter nisus), and red fox (Vulpes vulpes). This enabled estimation of the biomagnification potential of PBDEs in the following three terrestrial food chains: great tit--sparrowhawk, small rodents--buzzard, and small rodents--fox. Biomagnification of BDE 209 could not be assessed because levels of this congener were below the LOQ in the prey species. All other congeners, except BDE 28, were biomagnified in both predatory bird species. Biomagnification of BDE 28 could not be observed from rodents to buzzard. Biomagnification factors (BMFs) were calculated as the ratio between the lipid-normalized concentrations in the predator and in the prey. BMFs ranged from 2 to 34 for the sum of PBDEs in predatory bird food chain. Although the fox is a top-predator, this is not reflected in the PBDE concentrations that were measured in its tissues. In the small rodent-fox food chain, no biomagnification could be observed. This observation is most likely related to the high metabolic capacity of the fox with regard to organohalogens and should be taken into account when selecting species for environmental monitoring purposes. Not all top-predators will give a representative reflection of the pollution of their habitat, but confounding factors, such as metabolism, can influence the results to a great extent and can therefore lead to misinterpretations.

Dietary PBDE intake: a market-basket study in Belgium.

A food market-basket, representative for the general Belgian population, containing various meat, fish and dairy food products, was assembled and analysed for its polybrominated diphenyl ether (PBDE) content. Additionally, fast food samples were also investigated. Based on the measured PBDE levels, an average daily dietary intake estimate of PBDEs was calculated. Of all foods analysed, fish had the highest average sum of PBDE levels (BDEs 28, 47, 99, 100, 153, 154, and 183; 460 pg/g ww), followed by dairy products and eggs (260 pg/g ww), fast food (86 pg/g ww) and meat products (70 pg/g ww). One fresh salmon filet had the highest total concentration of PBDEs (2360 pg/g ww), whereas levels in steak and chicken breast were the lowest of all foods analysed. BDE 209 was never found above LOQ in any food. PBDE intake calculations were based on the average daily food consumption in Belgium and were estimated between 23 and 48 ng/day of total PBDEs (lower and upper bound). This value is in accordance with what was previously reported for diets from geographical distinct areas, such as Canada, Finland, Spain, Sweden and the UK. Although it is only a minor constituent of the Belgian diet, fish is the major contributor to the total daily PBDE-intake (around 40%) due to the high PBDE levels in this type of food. Although low contaminated, meat products account for around 30% of the total dietary intake of PBDEs. Dairy products and eggs contribute to a lesser degree (less than 30%).

Distribution of polychlorinated biphenyls, organochlorine pesticides and polybrominated diphenyl ethers in human umbilical cord serum, maternal serum and milk from Wielkopolska region, Poland.

The levels of organochlorinated pesticides (OCPs): p,p'-DDT and its metabolites, hexachlorobenzene (HCB), hexachlorocyclohexane isomers (HCHs), chlordanes and their metabolites, and 18 polychlorinated biphenyl (PCB) congeners were measured in maternal serum, umbilical cord serum and human milk collected from 22 mothers living in the Wielkopolska region, Poland. Additionally, 11 polybrominated diphenyl ether (PBDE) congeners were measured in the human milk samples. p,p'-DDT and its major metabolite, p,p'-DDE, together with HCB, were found in all milk and serum samples. Median concentrations of p,p'-DDE in maternal serum, umbilical cord serum and milk were 343, 329 and 634ng/g lipid weight (lw). PCB congeners 138, 153 and 180 were the major congeners measured in all serum samples, while CB 170 was detected in 74% and 100% of umbilical cord and maternal serum, respectively. Except for CBs 74, 101 and 105, which had a detection frequency of 77%, 23% and 82%, respectively, all investigated PCB congeners were measured in all human milk samples. The median concentrations of sum PCBs in maternal serum, umbilical cord serum and milk were 79, 60 and 133 ng/g lw, respectively. A good correlation (Spearman R(S)>0.75, p<0.001) was found for major PCBs, p,p'-DDT and p,p'-DDE, between maternal and umbilical cord serum, while the correlation was weaker between milk and serum. The median of sum PBDEs in human milk was 2.0 ng/g lw (range 0.8 to 8.4), with BDE 47 being always the most abundant PBDE congener and, together with BDE 153, being present in all samples. In general, results found in the investigated group are at the low end of the concentration range measured in Europe.

Remarkable findings concerning PBDEs in the terrestrial top-predator red fox (Vulpes vulpes).

In the present study, we have analyzed muscle, liver, and adipose tissue of 33 red foxes from Belgium for their content of polybrominated diphenyl ethers (PBDEs). Median sums of seven tri- to hepta-BDEs (BDE 28, BDE 47, BDE 99, BDE 100, BDE 153, BDE 154, and BDE 183) were 2.2, 2.4, and 3.4 ng/g lipid weight in adipose tissue, liver, and muscle, respectively. These levels were lower than those found in various species of voles and mice, the main prey species of the red fox. This is probably related to the high capacity of the foxes to metabolize and eliminate lower brominated congeners. BDE 209 generally dominated the PBDE congener profiles in the red fox samples. In samples containing BDE 209, this congener contributed, on the average, approximately 70% to the total PBDE content. BDE 209 was measured in concentrations as high as 760 ng/g lipid weight in the liver, but the detection frequency was not more than 40%. In animals with the highest BDE 209 levels, this congener was detected in muscle, liver, as well as in adipose tissue. Other abundant congeners were BDE 153 and BDE 47, which prevail in other terrestrial species. The particular PBDE congener profile observed in the red fox resembles that seen in grizzly bears from Canada, but differs from those previously reported for terrestrial avian species. Our data confirms unambiguously that BDE 209 does bioaccumulate in terrestrial top predators, such as the red fox.

Levels and distribution of polybrominated diphenyl ethers in various tissues of birds of prey.

In the present study, concentrations and tissue distribution of polybrominated diphenyl ethers (PBDEs; IUPAC # 28, 47, 99, 100, 153, 154, 183, and 209) were examined in brain, adipose tissue, liver, muscle, and serum of birds of prey. Median SigmaPBDE levels (BDE 28-183) in the tissues of sparrowhawks ranged from 360 to 1900 ng/g lipid weight (lw), which was in general one order of magnitude higher than in the tissues of common buzzards (26-130 ng/g lw). There were no differences in PBDE congener patterns between the various tissues within individuals of a certain species. Inter-species differences in PBDE patterns and in particular the percentage of BDE 99, 100 and 153 were, however, pronounced between sparrowhawk and common buzzard. BDE 209 was detected in nearly all serum and in some liver samples, but not in any other tissues. This observation suggests that exposure to BDE 209 is low or that this congener is poorly accumulated. Passive (lipid content related) diffusion could not completely describe the PBDE tissue distribution, e.g. the lowest PBDE-load was measured in brain, a fairly lipid rich tissue.

Nondestructive pollution exposure assessment in the European hedgehog (Erinaceus europaeus): III. Hair as an indicator of endogenous organochlorine compound concentrations.

Concentrations of organochlorine persistent pollutants were investigated in tissues of the European hedgehog (Erinaceus europaeus). Road kills and carcasses from wildlife rescue centers were used to characterize organochlorine compound tissue distribution and tissue profile dissimilarities (hair, liver, kidney, muscle, and adipose tissue). The most important contaminants were polychlorinated biphenyls (PCBs), chlordanes (CHLs), and DDTs, with median concentrations of 75, 5.1, and 1.4 ng/g liver wet weight, respectively. Median levels for the remaining compounds-hexachlorobenzene (HCB), hexachlorocyclohexanes (HCHs), and octachlorostyrene-were less than 0.5 ng/g liver wet weight. Compared to results with other mammalian wildlife, the present results indicate that hedgehogs may accumulate considerable concentrations of organochlorine compounds. Polychlorinated biphenyls and HCB preferably accumulated in liver and muscle tissue. Concentrations of DDTs and HCHs were highest in muscle tissue and hair, respectively. Octachlorostyrene and CHL levels were predominant in liver. The observed positive relationships between concentrations in hair and internal tissues for PCBs, DDTs, HCB, HCHs, and CHLs (0.49 < r < 0.91) and for several individual PCB, DDT, and CHL compounds (0.31 < r < 0.76) indicate the usefulness of hair as a biomonitoring tool of organochlorine compounds. Multivariate profile analyses revealed a higher dominance of less-persistent compounds (p,p'-DDT, alpha-HCH, and PCBs 95, 101, and 149) in hair compared to internal tissues. The present study demonstrates the suitability of hedgehog hair as a nondestructive biomonitoring tool regarding pollution with organochlorine compounds and the promising role of the hedgehog as a mammalian indicator species of pollution in terrestrial environments.

Levels and distribution of organochlorine pesticides, polychlorinated biphenyls and polybrominated diphenyl ethers in sediments and biota from the Danube Delta, Romania.

Concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs), such as dichlorodiphenyltrichloroethane (DDT) and analogues, hexachlorocyclohexanes (HCHs) and hexachlorobenzene (HCB), were measured in sediments and biota (invertebrates, 11 fish species and cormorant tissues) collected in 2001 from the Danube Delta, the biggest European wetland. DDTs were the predominant pollutants in all samples. A high variability in the concentrations of pollutants within the same species was observed and this was related to sampling location, age, length and sex. DDTs were also the main organohalogenated contaminants in cormorant muscle and liver, followed by PCBs, HCHs, HCB and PBDEs. The present levels of DDTs in cormorant tissues are lower than levels measured in cormorant eggs sampled from the Danube Delta in 1982 and 1997, respectively. The variance of delta15N for herbivores was much greater than for carnivores, while carp and bream showed higher delta15N signatures than expected, probably due to a higher dietary proportion of benthos, typically more delta15N enriched relative to pelagic biota.

Occurrence of organochlorine pesticides (OCPs) and their enantiomeric signatures, and concentrations of polybrominated diphenyl ethers (PBDEs) in the Adélie penguin food web, Antarctica.

Concentrations and enantiomeric signatures of organochlorine pesticides were determined in Antarctic krill, emerald rockcod and Adélie penguin from the Ross Sea, Antarctica. HCB and DDTs were prevalent contaminants in penguin eggs. The highest concentrations of SigmaHCHs (1.35 +/- 0.72 ng/g) were found in the rockcod muscle, where gamma-HCH (1.23 +/- 0.67 ng/g) was the principal isomer. The ratio gamma-HCH/alpha-HCH was evaluated. Enantioselective gas chromatography was used for the evaluation of enantiomeric fractions (EFs) for alpha-HCH and oxychlordane. An increase of 14% in the (+)alpha-HCH enantiomer was found from krill through penguin, suggesting the enantioselective biotransformation increased proportionately with trophic level. Polybrominated diphenyl ethers (PBDEs) were measured and their concentrations were 5.6 +/- 1.12, 5.81 +/- 2.32, 4.57 +/- 0.17 and 3.06 +/- 3.27 ng/g lipids in krill, rockcod muscle, rockcod homogenate and penguin eggs, respectively. The detection of BDE28, BDE47, BDE99 and BDE100 in Antarctic organisms confirmed their global transport and distribution; the detection of lower brominated congeners suggested a potential long-range transport.

Highly chlorinated toxic contaminants in pesticide-treated wooden art objects.

Although the contamination of wooden art objects with pesticides is well known, to the authors' knowledge no attempt has yet been made to investigate the eventual presence of other toxic compounds that have been produced during the degradation of pesticides or that may be present in the technical formulations. Here, the authors report on the presence of polychlorinated biphenyls (PCBs) and polychlorinated terphenyls (PCTs) in scrapings from wooden antique art objects, namely printing blocks, sculptures, and masks. These antiques belong to 2 fine art museums in Belgium--Antwerp's Ethnographic Museum and the Plantin-Moretus Museum. It is documented that these art objects were treated with pesticides in the 1950s. In addition, 2-heptachlorodibenzo-p-dioxin (HpCDD) isomers and octachlorodibenzo-p-dioxin (OCDD) were also identified. The presence of these toxic compounds in these antiques requires a better understanding of safety for the persons (conservators, museum employees, restorers, and visitors) coming in contact with these objects.

Hair as an indicator of endogenous tissue levels of brominated flame retardants in mammals.

Few data are available on brominated flame retardants (BFRs) in terrestrial mammalian wildlife. Moreover, the use of hair in nondestructive monitoring of BFRs in mammals or humans has not been investigated. In the present study, concentrations of polybrominated diphenyl ethers (PBDEs) and brominated biphenyl 153 (BB 153) were analyzed in tissues of the European hedgehog Erinaceus europaeus. Road kills and carcasses from wildlife rescue centers were used to investigate relationships between concentrations of BFRs in hair and internal tissues, BFR tissue distribution (hair, liver, kidney, muscle, and adipose tissue), and PBDE congener tissue pattern dissimilarities. Liver concentrations of PBDEs and BB 153 were in the ranges 1-1178 and 0-2.5 ng/g of liver wet weight, respectively. PBDEs were predominant in adipose tissue and liver, while accumulation of BB 153 was tissue independent. The less persistent compound BDE 99 was more dominant in hair than in internal tissues. We observed positive relationships between BFR levels in hair and internal tissues for sum PBDEs and BDE 47 (0.37 < r < 0.78). The present study demonstrated that hair is a suitable indicator of PBDE exposure in terrestrial mammals which can be used in nondestructive monitoring schemes.

The dioxin-like PCB 77 but not the ortho-substituted PCB 153 interferes with chicken embryo thyroid hormone homeostasis and delays hatching.

The effects of the dioxin-like polychlorinated biphenyl (PCB) 77 and the ortho-substituted PCB 153 on thyroid hormone availability were investigated during the last week of embryonic development in chicken. High doses of these PCBs (1microg PCB 77 and 20microg PCB 153) were injected into chicken eggs at day 4 of incubation. Blood and tissue samples were collected from day 14 of incubation until 1 day after hatching. We did not observe influences of PCB 153 on thyroid hormone (TH) levels. Treatment with PCB 77, on the other hand, decreased plasma total T(4) concentrations but increased hepatic T(4) levels at day 14 of incubation. Later in development, at stages near the process of hatching, severe decreases of T(4) and T(3) levels were observed in the PCB 77 group, both in plasma and tissues. PCB 77 severely reduced the TH peak that normally coincides with the stage of internal pipping. This reduction was accompanied by a considerable delay in the moment of hatching. We conclude that the dioxin-like PCB 77, but not the ortho-substituted PCB 153, can decrease TH availability towards the end of embryonic development and hence disturb the process of hatching.

Levels of organochlorine pesticides, polychlorinated biphenyls and polybrominated diphenyl ethers in fish species from Kahramanmaras, Turkey.

The levels of organohalogenated contaminants, such as organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) were measured in four fish species (Acanthobrama marmid (kalashpa), Cyprinus carpio (carp), Chondrostoma regium (nose-carp), and Silurus glanis (wels)) from the Sir Dam Lake, Kahramanmaras, Turkey. These species were selected for their characteristic feeding behaviour and their importance to local human fish consumption. DDTs were the predominant organohalogenated contaminants in all species, with the p,p'-DDE contributing to more than 90% to the total DDTs. Other OCPs, such as hexachlorocyclohexane (HCH) isomers, chlordanes and hexachlorobenzene (HCB) were found at much lower levels in all five species. The levels of PCBs and PBDEs (on wet weight basis) were lower than in similar species from European or American freshwater systems. PBDE data were measured for the first time in fish species from Turkish environment. Lipid-based concentrations of OCPs, PCBs and PBDEs were higher in wels than in the other species and this was related to its piscivorous feeding mode and to its higher lipid content. Contrarily, concentrations of pollutants in nose-carp were the lowest, in agreement with its more herbivorous diet. A preferential accumulation in muscle compared to liver was observed for all OCPs, PCBs, and PBDEs in wels and carp, while in nose-carp, a preferential accumulation in liver was observed only for PBDEs, p,p'-DDT and PCBs. Racemic amounts for alpha-HCH were measured in all investigated muscle and liver samples, except for carp muscle.

Brominated flame retardants and organochlorine pollutants in eggs of little owls (Athene noctua) from Belgium.

Residues of brominated diphenylethers (PBDEs), organochlorinated pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in 40 eggs of little owls (Athene noctua), a terrestrial top predator from Belgium. The major organohalogens detected were PCBs (median 2,600 ng/g lipid, range 790-23 000 ng/g lipid). PCB 153,138/163, 170, 180 and 187 were the predominant congeners and constituted 71% of total sum PCBs. PBDEs were measurable in all samples, but their concentrations were much lower than for PCBs, with a range from 29-572 ng/g lipid (median 108 ng/g lipid). The most prevalent PBDE congeners in little owl egg samples were BDE 47, 99 and 153. This profile differs from the profile in marine bird species, for which BDE 47 was the dominant congener, indicating that terrestrial birds may be more exposed to higher brominated BDE congeners than marine birds. The fully brominated BDE 209 could be detected in one egg sample (17 ng/g lipid), suggesting that higher brominated BDEs may accumulate in terrestrial food chains. Brominated biphenyl (BB) 153 was determined in all egg samples, with levels ranging from 0.6 to 5.6 ng/g lipid (median 1.3 ng/g lipid). Additionally, hexabromocyclododecane (HBCD) could be identified and quantified in only two eggs at levels of 20 and 50 ng/g lipid. OCPs were present at low concentrations, suggesting a rather low contamination of the sampled environment with OCPs (median concentrations of sum DDTs: 826 ng/g lipid, sum chlordanes: 1,016 ng/g lipid, sum HCHs: 273 ng/g lipid). Hexachlorobenzene (HCB) and octachlorostyrene (OCS) were also found at low median levels of 134 and 3.4 ng/g lipid, respectively. Concentrations of most analytes were significantly higher in eggs collected from deserted nests in comparison to addled (unhatched) eggs, while eggshell thickness did not differ between deserted and addled eggs. No significant correlations were found between eggshell thickness and the analysed organohalogens.

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

Uptake and tissue-specific distribution of selected polychlorinated biphenyls in developing chicken embryos.

Fertilized chicken eggs were injected with high doses of individual polychlorinated biphenyl (PCB) congeners (0.5 microg of PCB 77, 9.8 microg of PCB 153, or 10.9 microg of PCB 180) before incubation to investigate the structure-specific uptake of these compounds by the embryo and their accumulation in brain and liver tissue. In accordance with earlier publications, a gradual uptake and accumulation of these compounds was observed during the last week of embryonic development. The PCB uptake and distribution to the specific tissues did not appear to be structure dependent. Wet-weight liver PCB concentrations (18, 266, and 278 ng/g at hatching for PCB 77, PCB 153, and PCB 180, respectively) were consistently two- to fourfold higher than carcass levels (7 ng/g of PCB 77, 117 ng/g of PCB 153, and 81 ng/g of PCB 180 at hatching). Whereas liver and carcass concentrations increased exponentially between day 13 of incubation and hatching, PCB levels in brain tissue remained unaltered (range, 0.6-1.0 ng/g of PCB 77 and 8-12 ng/g of PCB 153 and PCB 180 throughout the last week of incubation). Lipid analysis of the organs suggested that the lipid composition of brain may be an important factor explaining the low PCB accumulation in this tissue.

Polybrominated diphenyl ethers (PBDEs) in freshwater mussels and fish from Flanders, Belgium.

The levels and distribution of PBDEs in zebra mussels and several freshwater fish species (eel, carp and gibel carp) were investigated for different sites in Flanders, Belgium. In parallel, other organohalogenated contaminants, such as polychlorinated biphenyls (PCBs), p,p[prime or minute]-DDE and hexachlorobenzene (HCB) were also measured and their relationship with PBDEs was investigated. At most sites, individual PBDE congeners were present at detectable levels in mussel tissue, with the mean [summation operator]PBDE concentration ranging from 0.15 to 1.8 ng g(-1) wet weight (ww). The PCB concentrations in mussels ranged from 6.2 to 102 ng g(-1) ww. HCB and p,p[prime or minute]-DDE could be measured in mussels from most sites, mean values ranging from below the limit of quantification (LOQ) to 0.58 ng g(-1) ww and from 0.66 to 6.5 ng g(-1) ww, respectively. Except for one site (Blokkersdijk, Antwerp) where PBDEs were below the LOQ in carp muscle, all fish samples from other sites contained detectable PBDE levels, with the highest concentrations (14 +/- 14 ng g(-1) ww) being measured in eel liver from Watersportbaan (Ghent). The sampled sites covered a broad concentration range of organohalogenated pollutants with the highest values being consistently measured in eel liver. With few exceptions, all correlations between PBDEs and organochlorine pollutants for each species were low (r < 0.50) and most were statistically not significant (p > 0.05). This suggests that the exposure to contaminants arises from local sources possessing different signatures of PBDEs and organochlorine pollutants.