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.

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.

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%).

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.

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.

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.

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.

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 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.

Feathers as a nondestructive biomonitor for persistent organic pollutants.

Keratinous tissues of mammals and humans, such as hair, have been used to determine the exposure to polychlorinated biphenyls (PCBs) and organochlorine pesticides. In the present study, we investigated the accumulation of persistent organic pollutants (POPs; PCBs, p,p'-DDT, p,p'-dichlorodiphenyldichloroethane [DDD], p,p'-dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB], oxychlordane, trans-nonachlor, polybrominated diphenyl ethers, and polybrominated biphenyls [PBBs]) in feathers of the great tit (Parus major). The accumulation of POPs in feathers and fat samples of 27 adult great tits collected in April 2000 and December 2002 was compared with regard to possible temporal and spatial differences. Polybrominated diphenyl ethers, PBBs, trans-nonachlor, and HCB could not be quantified in feathers. Most PCB congeners and DDTs (p,p'-DDE, p,p'-DDD, and p,p'-DDT) could be determined in feathers, although concentrations in feathers were markedly lower (sigmaPCB concentration range, 28.2-87.1 ng/g) than concentrations in fat (sigmaPCB concentration range, 1244-10074 ng/g). Feathers had relatively higher levels of low-chlorinated PCBs (tetra- and pentachlorinated biphenyls) and p,p'-DDD compared to levels in fat, presumably reflecting levels in blood. Persistent organic pollutant concentrations did not increase with the age of the feather, suggesting that exogenous or aerial depositions of POPs onto the feather surface had no, or only minimal, influence on levels in feathers. For almost all compounds studied, POPs in feathers and fat were significantly positively correlated in samples collected during the breeding season but not in samples collected during the winter. This temporal difference may have been caused by seasonal changes in lipid reserves. Although further research is required, feathers appear to be a promising new, nondestructive biomonitor for PCBs and DDTs in avian wildlife.

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.

Distribution of methyl sulfone metabolites of polychlorinated biphenyls and p,p'-DDE in human tissues.

We determined methylsulfonyl metabolites of chlorinated biphenyls (MeSO2-CBs) and 1,1-bis(4-chlorophenyl)-2,2-dichloroethene (p,p'-DDE) in human adipose, liver, brain, and lung tissues obtained from 11 Belgian individuals (9-62 years of age). The total concentration of MeSO2-CBs (lipid weight basis) decreased in the following order: liver (mean, 9.30 ng/g; range, 1.68-27.03 ng/g lipid) > lung [mean, 2.72 ng/g; range, not detected (ND) to 11.54 ng/g lipid] > adipose tissue (mean, 1.57 ng/g; range, 0.33-4.33 ng/g lipid) > brain (mean, 0.24 ng/g; range, ND-0.56 ng/g lipid). The profiles of MeSO2-CBs and MeSO2-DDE in each tissue were similar for all 11 subjects. In adipose, brain, and lung tissues, 4'-MeSO2-CB87, 4'-MeSO2-CB101, and 3-MeSO2-CB149 (except brain) occurred at higher concentrations than did other MeSO2-CBs. However, 3'-MeSO2-CB132 was by far the most abundant congener in liver, contributing on average to approximately 60% of the sum of MeSO2-CBs. The concentrations of 3-MeSO2-DDE in different tissues were at the same or lower levels than the total concentrations of MeSO2-CBs. This study suggests that the distribution patterns of MeSO2-CBs and MeSO2-DDE in humans differ between liver and other tissues. Moreover, these profiles differ from those found in other mammals, such as polar bears, porpoises, and otters.

A reassessment of the nomenclature of polychlorinated biphenyl (PCB) metabolites.

Polychlorinated biphenyls (PCBs) are a widespread class of persistent organic chemicals that accumulate in the environment and humans and are associated with a broad spectrum of health effects. PCB biotransformation has been shown to lead to two classes of PCB metabolites that are present as contaminant residues in the tissues of selected biota: hydroxylated (HO) and methyl sulfone (MeSO2) PCBs. Although these two types of metabolites are related structures, different rules for abbreviation of both classes have emerged. It is important that a standardized nomenclature for the notation of PCB metabolites be universally agreed upon. We suggest that the full chemical name of the PCB metabolite and a shorthand notation should be adopted using the International Union of Pure and Applied Chemistry's chemical name/original Ballschmiter and Zell number of the parent congener, followed by the assignment of the phenyl ring position number of the MeSO2- or HO-substituent. This nomenclature provides a clear, unequivocal set of rules in naming and abbreviating the PCB metabolite structure. Furthermore, this unified PCB metabolite nomenclature approach can be extended to the naming and abbreviation of potential metabolites of structurally analogous contaminants such as HO-polybrominated biphenyls and HO-polybrominated diphenyl ethers.

Time trend investigation of PCBs, PBDEs, and organochlorine pesticides in selected n-3 polyunsaturated fatty acid rich dietary fish oil and vegetable oil supplements; nutritional relevance for human essential n-3 fatty acid requirements.

In addition to being used in the food and animal feed industry, fish oils have also been used traditionally as dietary supplements. Due to the presence of long-chain n-3 fatty acids, fish oils have therapeutic benefits in the prevention and treatment of cardiovascular, immunological, and arthritic diseases, as well as childhood deficiency diseases such as rickets, because of a high content of vitamin D. However, fish oils are also susceptible to contamination with lipophilic organic chemicals that are now ubiquitous contaminants of marine ecosystems. Many vegetable oils are sources of the shorter chain precursor forms of n-3 fatty acids, and in recent years the specialist dietary supplement market has expanded to include these oils in a variety of different formulations. This paper reports analytical results of selected contaminants, including polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers, for a range of commercially available n-3 fatty acid rich fish and vegetable oil dietary supplements. Using principal component analysis, the values are compared with historic samples to elucidate time trends in contamination profiles. Levels of contaminants are discussed in relation to the nutritional benefits to the consumer of long- and short-chain forms of n-3 fatty acids.

Levels of organohalogenated persistent pollutants in human milk from Kahramanmaras region, Turkey.

The levels of 1,1,1-trichloro-bis-2,2'-(4-chlorophenyl) ethane (p,p'-DDT) and its metabolites, hexachlorobenzene (HCB), hexachlorocyclohexane isomers (HCHs), chlordanes (trans- and cis-chlordane, oxychlordane and trans-nonachlor), 11 polychlorinated biphenyl (PCB) congeners, and 7 polybrominated diphenyl ether (PBDE) congeners were measured in 37 individual human milk samples from Kahramanmaras region, Turkey. Organochlorine pesticides were the major contaminants in the milk samples. p,p'-DDE and p,p'-DDT were detected in all samples, while beta-HCH had a detection frequency of 97%. The sum of the DDTs in human milk samples varied between 0.52 and 315.8 ng/g wet weight (ww) with a mean ratio between p,p'-DDE and p,p'-DDT equal to 31.1. p,p'-DDD could be measured only in six samples. beta-HCH was the most prevalent HCH isomer with a mean value of 2.08 ng/g ww. The mean concentration of gamma-HCH was 0.38 ng/g ww, while alpha-HCH was not detected in any sample. HCB is found in 95% of the milk samples with a mean concentration of 0.30 ng/g ww. The mean value for the sum of chlordanes was 0.39 ng/g ww, with oxychlordane and trans-nonachlor being the principal contributors. PCBs could be measured only in 8 out of 37 samples and their concentration ranged between <0.15 and 1.92 ng/g ww for the sum of PCBs. PCB profiles were dominated by congeners 153, 180 and 138. PBDEs were detected only in 3 out of 37 samples, with the highest value being 0.014 ng/g ww (0.40 ng/g lipid weight) and BDE 47 was the dominant congener. Although the number of samples is relatively low and they are not representative for the whole Turkish population, the results of the present study are important to provide additional data on the concentrations of persistent organochlorinated pollutants in Turkey and show as first the PBDE levels in Turkish population.

Distribution of organochlorine pesticides, polychlorinated biphenyls and alpha-HCH enantiomers in pork tissues.

The distribution of HCH isomers, DDT analogues and selected PCB congeners in pork organs collected from the same individuals raised in Romanian farms was investigated. Organochlorine pesticides (HCHs and DDTs) were the principal contaminants in all samples, while PCB concentrations were low, in accordance with previously reported concentrations from Romanian animal farms. The most part of the pollutant load in the body is retained in the adipose tissue, with HCHs ranging between 16 and 27.7 ng/g lipid and with higher concentrations of DDTs ranging between 65.9 and 334.5 ng/g lipid. The highest PCB levels (up to 32 ng/g lipid) were measured in lung and liver. The lipid-normalized concentrations in the brain were lower than in all other tissues due to the presence of the blood-brain barrier or due to a lower proportion of the neutral lipids such as triglycerides. The highest concentrations of DDTs were measured in muscle and fat, with p,p'-DDE being the principal contributor and with a variable contribution of p,p'-DDD and p,p'-DDT. In liver, p,p'-DDD has a higher contribution to the sum DDTs, while in all analyzed livers, the concentration of p,p'-DDT was very low. beta-HCH was the most persistent HCH isomer in all tissues, accounting for 40-97% of sum HCHs. For all animals, the highest concentrations of beta-HCH and HCHs were found in liver, while the lowest HCH concentrations were measured in brain and spinal marrow. Additionally, the distribution of alpha-HCH enantiomers in the tissues was discussed. In all samples (except 2 brain samples), (+) alpha-HCH was depleted and (-) alpha-HCH was enantioenriched. Enantiomeric ratios in brain were the highest measured values between all organs. For all studied animals, ERs increased in the order fat < muscle < liver < brain.

Patterns of PCBs and PCDD/PCDFs in chicken and pork fat following a Belgian food contamination incident.

A food contamination incident involving polychlorobiphenyls (PCBs) and PCDD/Fs occurred in 1999 in Belgium. On heavily affected farms, concentrations of PCBs in chicken or pork fat exceeded the Belgium tolerance limit of 200 ng/g lipid weight for the sum of seven marker PCBs. Analysis of contaminated samples showed that the patterns for PCB and PCDD/F congeners differed among feed, chicken fat and pork fat. Lower chlorinated PCBs and polychlorodibenzofurans (PCDFs) including those with high TEFs (PCBs 105, 118, 126 and 2,3,4,7,8-PeCDF) were shown to either bioaccumulate more in chicken fat or to be eliminated more readily in pork. This leads to the possibility that consumption of chicken would result in a higher TEQ human body burden than that from the same consumption of pork. In addition, PCDF congeners with non-2,3,7,8-substitution (e.g., 1,2,4,7,8-PeCDF) were present in chicken fat but absent in pork fat. Since the residue pattern in this commercial episode changes less in the avian species, these results reinforce the value of birds rather than mammals as markers of the source of contamination with persistent organochlorine pollutants.

Hair analysis: another approach for the assessment of human exposure to selected persistent organochlorine pollutants.

Hair analysis was used for the assessment of exposure to organochlorine pollutants in specimens from Greece, Romania and Belgium. A simple method (using 3 N HCI as incubation reagent, liquid-liquid extraction with hexane/ dichloromethane (DCM), alumina/acid silica clean-up and GC-ECD/GC-MS analysis) was used for screening of specimens. The highest organochlorine load (up to 148 ng/g hair for the sum of PCB, DDT and hexachlorocyclohexane (HCH) isomers) was found in samples from a group of Greek women with past occupational exposure to pesticides. DDTs were the main organochlorine pollutants in Greek samples (up to 70%), while in Belgian hair samples their contribution was reduced to 40%. PCB mean concentration was higher in Belgian specimens (up to 14 ng/g hair). Lindane (y-HCH) was the main HCH isomer found in the samples (up to 82% in the Greek samples). Contribution of p,p'-DDT to the sum of DDTs was higher in Greek samples and indicates recent exposure to technical DDT. Similar PCB 153/sum PCBs ratios were found for each of the three countries suggesting similar sources of pollution with PCBs (mainly dietary). Artificially coloured hair samples were found to have lower, but not statistically significant concentrations of organochlorine pollutants than the non-coloured hair.