Tissue localisation of tetra- and pentabromodiphenyl ether congeners (BDE-47, -85 and -99) in perinatal and adult C57BL mice

The distribution of polybrominated diphenyl ether (PBDE) congeners was followed in C57BL mice. The animals were subjected to whole-body autoradiography using (14)C-labelled 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',3,4,4'-pentabromodiphenyl ether (BDE-85) and 2,2',4,4',5-pentabromodiphenyl ether (BDE-99). Labelled BDE-85 and -99 were also used in quantitative studies on milk transfer and tissue concentrations during the neonatal period (12-15 days post partum), by use of liquid scintillation technique. The results show that in adult mice the studied PBDEs were effectively taken up, retained in fatty tissues and concentrated in some specific organs, i.e. the liver, adrenal cortex, ovary, lung and (initially) the brain. At longer post-injection time, the concentration in most tissues was considerably lower, and radioactivity was mainly found in fat depots and the liver. No significant difference in distribution between the three studied congeners was observed. Following maternal exposure, the foetal uptake was limited. On the other hand, during lactation a considerable fraction of the dose (about 20% of the studied penta-BDEs) given to the dam was transferred to the offspring. As in several cases the presently observed organ accumulation corresponds with earlier reports on PBDE effects in the same organs, the present results should be taken into consideration in the risk assessment of this compound group.     

Plasma PBDE and thyroxine levels in rats exposed to Bromkal or BDE-47

In experimental models, polybrominated diphenyl ethers (PBDEs), a group of brominated flame retardants, have caused effects in a number of biological end-points, including neurobehavioural effects, disturbances in thyroid and steroid hormone homeostasis, and other steroid-related effects. Almost exclusively, only external dose metrics (dose per body weight basis) have been studied in connection to the observed effects. In this study we report on new analyses of plasma PBDE levels in surplus samples from earlier studies on thyroid hormones (TH) in exposed rodents. Female, 7-week old Sprague-Dawley rats were given either Bromkal 70-5 DE (Study I; 18 or 36 mg/kg bw/day) or BDE-47 (Study II; 1, 6 or 18 mg/kg bw/day) daily by gavage for two weeks. At an external dose of 18 mg/kg bw/day significant TH effects (decreased plasma free thyroxin levels) were observed in both studies, corresponding to an internal (plasma) dose of 463 microg sumPBDE/g lipid (Study I) or 421 microg BDE-47/g lipid (Study II). If we compare the contribution of different BDE congeners to the total BDE level in rat plasma after Bromkal exposure (Study II), and in the Bromkal mixture itself, the most important congener in the Bromkal mixture were also found in plasma. However, the relative concentration of BDE-99 was lower, and that of BDE-153 was higher, than that of the mixture, indicating selectivity in uptake, metabolism and/or excretion of the individual BDE congeners. Explicitly, the possible in vivo conversion of BDE-99 to BDE-47, and of BDE-154 to BDE-153 could not be excluded. The internal dose in the present rat study could be compared to reported human serum doses of PBDE. Human serum/blood levels have a wide range, from 3 to 6 ng sumPBDE/g lipid in background samples from Europe, about 10 times higher in US sample, and up to 100 times higher (300-600 ng/g lipid) in upper-end levels in collected samples from USA. As a consequence, the margin between effects levels in the rat and exposure levels in man varies widely, with a quotient roughly from 1000 to 100,000. Generally, it could be expected that this margin is lower than if external dose metrics would be used. An even lower margin could be expected as recent studies have shown effects in offspring at lower doses than those giving effects in our studies. Lastly, it should be noted that humans are already exposed to a mixture of chemicals in daily life, a fact that complicates this kind of comparison.     

Emission Inventories of Carbon-containing Greenhouse Gases in China and Technological Measures for Their Abatement

The report summarizes surveys on carbon inventories and initiatives on sustainable carbon cycling taken by the Research Center for Eco-Environmental Sciences, where the authors work/worked. The first part of the report, which appeared in the preceding issue of this journal, deals with the concept of sustainable carbon cycling, the historic evolution of carbon cycling processes in China, carbon pool enhancement, value addition, carbon sequestration and carbon balance. This very paper, as the second part of the report, covers the results of carbon dynamics modeling, emission inventories of various carbon-containing greenhouse gases and their potential abatement measures.     

Changes in serum concentrations of polychlorinated biphenyls (PCBs), hydroxylated PCB metabolites and pentachlorophenol during pregnancy

We studied pregnancy-related changes in serum concentrations of five polychlorinated biphenyls (PCBs, CB 118, CB 138, CB 153, CB 156, CB 180), three hydroxylated PCB metabolites (4-OH-CB107, 4-OH-CB146, 4-OH-CB187), and pentachlorophenol (PCP). Median serum lipid content increased 2-fold between early (weeks 9-13) and late pregnancy (weeks 35-36) (N = 10), whereas median PCB levels in serum lipids decreased 20-46%, suggesting a dilution of PCB concentrations in serum lipids. Nevertheless, strong positive intra-individual correlations (Spearman’s r = 0.61-0.99) were seen for PCBs during the whole study period. Thus, if samples have been collected within the same relative narrow time window during pregnancy, PCB results from one single sampling occasion can be used in assessment of relative differences in body burdens during the whole pregnancy period. Concentrations of OH-PCBs in blood serum tended to decline as pregnancy progressed, although among some women the concentrations increased at the end of pregnancy. Positive intra-individual correlations (r = 0.66-0.99) between OH-PCB concentrations were observed during the first and second trimester, whereas correlations with third trimester concentrations were more diverging (r = −0.70-0.85). No decline in PCP concentrations was observed during pregnancy and no significant correlations were found between concentrations at different sampling periods. Our results suggest that for both OH-PCBs and PCP, sampling has to be more specifically timed depending on the time period during pregnancy that is of interest. The differences in patterns of intra- and inter-individual variability of the studied compounds may be due to a combination of factors, including lipid solubility, persistence of the compounds, distribution in blood, metabolic formation, and pregnancy-related changes in body composition and physiological processes.     

Selective accumulation of chlorinated paraffins (C12 and C16) in the olfactory organ of rainbow trout

Three ¹⁴C-labelled polychloroalkanes (C₁₂ and C₁₆), representing low (23% Cl by weight), medium (51%), and highly (68%) chlorinated paraffin (CP) mixtures, were presented to rainbow trout via the water. The uptake in fat-rich tissues was positively correlated to the degree of chlorination of the preparations. Notably, all preparations gave rise to a high and selective uptake of radioactivity in the olfactory organ and gills. This selective radiolabelling may reflect a general ability of these organs to enrich xenobiotics from the surrounding water. The olfactory organ may be a hitherto unforseen target for toxic environmental pollutants in fish.     

Large variation in breast milk levels of organohalogenated compounds is dependent on mother's age, changes in body composition and exposures early in life

We identified factors that are important determinants of body burdens (breast milk levels) of polychlorinated biphenyls (PCBs), dioxins (polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs)) and polybrominated diphenyl ethers (PBDEs). PCBs, PCDD/Fs and PBDEs were analysed in breast milk from up to 325 first-time mothers in Uppsala, Sweden, who delivered between 1996 and 2006. Hierarchical clustering was used as a method for identification of groups of compounds with common sources of exposure and similar toxicokinetics. Based on correlations between levels of single compounds/congeners in breast milk, distinctly separated clusters were formed, strongly dependent on structural similarities of the organohalogen molecules. In a multiple regression model, levels of PCBs (except PCB 28), PCDD/Fs and BDE-153 were positively associated with age of the mother and weight loss after delivery and inversely associated with pre-pregnancy BMI (body mass index) and weight gain during pregnancy. Higher levels of mono-ortho PCB TEQ, non-ortho PCB TEQ and BDE-153 in milk were found among women with high physical activity. Women who were breastfed during infancy and grew up on the Baltic coast of Sweden, with high availability of contaminated fish from the Baltic sea, had higher levels of PCBs and PCDD/Fs in breast milk indicating that exposure early in life from breast milk and contaminated fish may still affect body burdens at the time of pregnancy. The importance of current consumption of fatty Baltic fish as a source of exposure was supported by the positive association with breast milk levels of mono-ortho PCB TEQ, PCDF TEQ and BDE-153. The results show that, in contrast to the lower brominated PBDE congeners, the hexa-brominated BDE-153 resembles the chlorinated compounds with regards to determinants in breast milk. This suggests that some of the PBDEs may have toxicokinetic properties and that are similar to the PCBs and PCDD/Fs. Our results show that a few simple advices to women regarding weight changes in connection with pregnancy and consumption of contaminated fatty fish during the whole lifetime may lower the levels of dioxins in breast milk by up to 60%.     

PCDD/F, PCB, PBDE, HBCD and chlorinated pesticides in a Swedish market basket from 2005--levels and dietary intake estimations

Based on consumption data statistics, food items from four regions in Sweden were sampled in a so-called market basket study. Food items from five food groups, i.e. fish, meat, dairy products, eggs and fat/oils, were analyzed for persistent organic pollutants (POPs) followed by per capita intake calculations. The highest levels of PCDD/F, PCB, PBDE, HBCD and chlorinated pesticides were found in the fish/fish products. The estimated market basket per capita intake of PCDD/F and dl-PCB was 0.7 pg WHO-TEQ kg bw⁻¹ d⁻¹ (TEFs from 1998). The intake of ∑PCB was estimated to 4.9 ng kg bw⁻¹ d⁻¹ and fish was found to be the major contributor with 64%. The intake of ∑PBDE was found to be 0.7 ng kg bw⁻¹ d⁻¹. Fish (38%) and dairy products (31%) were the largest contributors to the total PBDE intake. The intake of HBCD was estimated to 0.14 ng kg bw⁻¹ d⁻¹. HBCD mainly came from fish (65%), but also dairy products (24%) and meat (10%) contributed. Also regarding the chlorinated pesticides, fish was found to be the major contributor, with 51% of the ∑DDT coming from fish. The intake of ∑DDT, ∑HCH and HCB was 4.0, 1.0 and 1.1 ng kg bw⁻¹ d⁻¹, respectively. Most of the ∑HCH and HCB originate from dairy products (43% and 55%, respectively). This study shows that the levels, and intake, of different POPs from food of animal origin in the market basket of 2005 seem to have decreased since the market basket study in 1999.     

Declining levels of PCB, HCB and p,p′-DDE in adipose tissue from food producing bovines and swine in Sweden 1991–2004

The official control programme for organochlorine (OC) contaminants in food producing animals in Sweden was used to study temporal and spatial trends of the polychlorinated biphenyl CB 153, hexachlorobenzene (HCB) and p,p′-DDE in adipose tissue from bovines and swine 1991–2004. Our results show that efforts to decrease OC contamination of animal feed and the environment have had a positive impact on the contamination of the animal production. OC concentrations declined significantly in almost all studied regions of Sweden. OC temporal trends were slower in bovines (6–8% per year) than in swine (10–12%). Power analyses showed that data from more than 10 years of sampling were needed for a detection of an annual OC level change of 5% in both species in the control programme, due to large within- and between-year variation in OC levels. CB 153 and p,p′-DDE levels were higher in southern than in northern Sweden. Levels decreased with age in milk cows, but not in young nulliparous cows (heifers) and bulls. Moreover, milk cows and bulls had significantly lower OC levels than heifers. Levels were not age-dependent among swine, but castrated male swine (barrows) had significantly lower OC levels than young female swine (gilts). Levels of the studied OCs are now in many cases below the LOQ of the analytical method used. Future time trend studies of these OCs thus depend on lowered LOQs in the control programme.     

Toxic effects of brominated flame retardants in man and in wildlife

Brominated flame retardants (BFRs) are ubiquitous industrial chemicals, and many of them are produced in large volumes. Due to this fact, several BFRs are found in quantifiable levels in wildlife, as well as in humans. However, we are still lacking information on the effects of BFR in wildlife and, especially, in man. This review summarises the biological effects of polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A (TBBPA) and derivates, hexabromocyclododecane (HBCD) and polybrominated biphenyls (PBBs), however excluding other aspects such as environmental levels. These BFR groups were selected because of a large volume production (PBDEs, TBBPA and derivates), and availability of some toxicity data in spite of much lower production volumes (HBCD and PBBs). In addition, the increase in levels of PBDEs in human (breast milk) and wildlife samples during later time made it especially interesting to include this BFR group. PBDES: The commercial PBDE products predominantly consist of so-called penta-, octa- and decabromodiphenyl ether products. Each product consists of a rather narrow range of congeners and is named after the dominating congener as regards the bromination pattern. Generally, the PentaBDEs seem to cause adverse effects at the comparably lowest dose, whereas much higher doses were needed for effects of the DecaBDEs. The critical effects of PentaBDEs are those on neurobehavioural development (from 0.6 mg/kg body weight) and, at somewhat higher dose, thyroid hormone levels in rats and mice, of OctaBDEs on fetal toxicity/teratogenicity in rats and rabbits (from 2 mg/kg body weight), and of DecaBDEs on thyroid, liver and kidney morphology in adult animals (from 80 mg/kg body weight). Carcinogenicity studies, only performed for DecaBDEs, show some effects at very high levels, and IARC (1990) evaluates DecaBDEs not classifiable as to its carcinogenicity to humans. TBBPA: The toxicity of TBBPA in the experimental in vivo studies is suggested to be low. In most reported studies, only doses in g/kg body weight were effective, but at least one study suggested renal effects at around 250 mg/kg body weight. Although difficult to include and interpret in a quantitative risk assessment, the in vitro effects on immunological and thyroid hormones, as well as binding to erythrocytes should be noted. Before a solid standpoint could be reached on TBBPA toxicity additional studies must be performed. This statement is even more valid regarding the TBBPA derivates, where there is an almost complete lack of toxicity data. HBCD: Also in the case of HBCD, relevant toxicity studies are lacking. Based on the present animal studies, a critical effect is seen in the liver and on thyroid hormones (LOAEL 100 mg/kg body weight/day). However, in a recent short paper behavioural effects in mice pups were observed already at 0.9 mg/kg body weight, and behavioural effects may be a sensitive endpoint for HBCD, as well as for other BFRs. PBBS: Due to the Michigan accident in 1973-1974, many toxicity studies on PBBs are available. The critical experimental effects are those on reproduction and carcinogenicity, and a NOAEL of 0.15 mg/kg body weight/day could be suggested based on the cancer effects. In man no unequivocal effects have been observed, although in some studies neurological and musculoskeletal symptoms were suggested. Based on the carcinogenic effects in animals, a human TDI of 0.15 microg/kg body weight has been presented.To conclude, the toxicity data are almost entirely based on experimental models. There are differences among the BFR groups, as well as within these groups, both regarding type of toxic effect and at what dose it appears. As BFRs will continue to appear both in industrial applications and, even if the production has ceased, in our environment, there is a continued need for effects studies on BFRs.