Exposure to Environmental Contaminants and Lung Function in Adolescents-Is There a Link?

Dioxins (polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDF)), polychlorinated biphenyls (PCBs), and brominated flame retardants (BDEs) are well known toxic environmental contaminants. Their possible role in the incidence of respiratory disease is not yet well understood. Previous studies showed a negative effect on lung function in relation to prenatal and lactational dioxin exposure in pre-pubertal children. Effects of BDE exposure on the lung function have not previously been evaluated. As part of a longitudinal cohort study, the effects of perinatal dioxin (PCDD/F) exposure and serum PCDD/F, dl-PCB, and BDE levels on lung function in adolescents were assessed using spirometry, a body box, and diffusion measurements. Thirty-three children (born between 1986 and 1991) consented to the current follow-up study. Prenatal, lactational, and current dioxin, PCB, and BDE concentrations were determined using GC-MS. No relationship was seen between prenatal and lactational dioxin exposure, nor with current PCB body burden, and lung function. Indications of increasing airway obstruction were seen in relation to increasing current BDE exposure. This is a novel finding and certainly warrants further research.

Alterations in the programming of energy metabolism in adolescents with background exposure to dioxins, dl-PCBs and PBDEs.

OBJECTIVES: Dioxins and PCBs are highly toxic and persistent environmental pollutants that are measurable in humans worldwide. These persistent organic pollutants are associated with a higher incidence of diabetes mellitus. We hypothesise that perinatal (background) exposure to industrial pollutants like dioxins also influences body mass development and energy metabolism in later life. STUDY DESIGN: In The Netherlands, the perinatal exposure (prenatal exposure and postnatal lactational intake) to dioxins has been studied prospectively since 1987. Fasting glucose, insulin, HbA1c and leptin were analysed in 33 children of the original cohort of 60. BMI, glucose:insulin and BMI:leptin ratios were calculated. Prenatal exposure, lactational intake and current serum levels of dioxins (PCDD/F), dl-PCBs and PBDE concentrations were determined using (HR)GC-MS. RESULTS: Prenatal dioxin (PCDD/F) exposure was positively correlated to the glucose:insulin ratio (p = 0.024) and negatively correlated to the fasting insulin concentration (p = 0.017) in adolescence. Postnatal lactational PCDD/F intake was also negatively correlated to fasting insulin concentration (p = 0.028). Current serum levels of PCDD/Fs and total TEQ (dl-PCBs+PCDD/Fs) were positively correlated to the fasting serum glucose concentration (p = 0.015 and p = 0.037, respectively).No metabolic effects were seen in association with current serum levels of PBDEs. A positive correlation between the insulin and leptin concentrations (p = 0.034) was observed. No effects were found on leptin levels, BMI:leptin ratio, HbA1c levels or BMI. DISCUSSION/CONCLUSION: This study indicates that prenatal and lactational exposure influences glucose metabolism in adolescents, presumably through a negative effect on insulin secretion by pancreatic beta cells. Additionally, the very low recent background exposure to dioxins in puberty possibly has an effect on the glucose level.

PCDD/F-isomers signature - Effect of metal chlorides and oxides.

A recent paper presented the results from de novo tests, involving 11 distinct catalytic systems (oxides and chlorides of Cd, Cr, Cu, Ni, and Zn, as well as a blank sample). Their PCDD and PCDF formation activity was shown. This paper further assesses their isomer signature, with special emphasis on those congeners associated with chlorophenol precursor routes, and on 2,3,7,8- and 1,9-substituted congeners. Each metal catalyst generates a significantly different signature, also affected by the presence or absence of oxygen in the reaction atmosphere. Oxide and chloride catalysts supply distinctive signatures, suggesting singly weighted pathways. Quite a large number of data was handled, so that throughout this analysis special attention was given to testing and developing an appropriate methodology, allowing appropriate correlation analysis and statistical data treatment. The large tables resulting relate to the 11 catalytic systems, studied at 3 levels of oxygen concentration, with 94 PCDD/F-congeners considered individually. They constitute an extensive reference data bank for confronting novel experimental data with this vast data set.

PCDD/F catalysis by metal chlorides and oxides.

Model fly ash (MFA) samples were composed of silica, sodium chloride, and activated carbon, and doped with metal (0.1 wt% Cu, Cr, Ni, Zn and Cd) chloride or oxide. Each sample was de novo tested at 350 °C for 1 h, in a flow of gas (N2, N2 + 10% O2, +21% O2 or +10% H2) to investigate the effect of metal catalyst and gas composition on PCDD/F formation. Total PCDD/F yield rises rapidly with oxygen content, while the addition of hydrogen inhibits the formation and chlorination of PCDD/F. The amount of PCDD on average rises linearly with the oxygen concentration, while that of PCDF follows a reaction order of about 1/2; thus the PCDF to PCDD ratio drops when more oxygen becomes available. Some samples do not follow this trend. Chlorides are much more active than oxides, yet there are marked differences between individual metals. Principal component analysis (PCA) was applied to study the signatures from all samples, showing their unique specificity and diversity. Each catalyst shows a different signature within its individual homologue groups, demonstrating that these signatures are not thermodynamically controlled. Average congener patterns do not vary considerably with oxygen content changing from oxidising (air) to reducing (nitrogen, hydrogen).

Iron and copper catalysis of PCDD/F formation.

The formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) was explored during de novo tests designed to compare the catalytic activity of copper (II) chloride (CuCl2) with that of iron (III) oxide (Fe2O3) and to test some synergistic effect between these two catalytic compounds. Both copper chloride (CuCl2) and iron oxide (Fe2O3) were earlier proposed as catalysts to explain the PCDD/F emissions from, e.g. municipal solid waste incineration (MSWI). In addition, haematite (Fe2O3) is the main iron ore and could be responsible for the typical iron ore sintering plant fingerprint. A total of nine model fly ash (MFA) samples were prepared by mixing and grinding of sodium chloride (NaCl), activated carbon and a powder matrix of silica (SiO2) with the selected metal compound(s). The conditions of these de novo tests were 1 h in duration, 350 °C in a flow of synthetic combustion gas (10 vol.% oxygen in nitrogen). The effect of Fe-Cu catalyst concentration on yield and distribution pattern of PCDD/F was systematically explored; three strongly differing ratios of [Fe]:[Cu] were considered (1:1, 10:1 and 100:1) to study the potential interactions of Fe2O3 and CuCl2 suggested earlier. The results show some slight rise of PCDD/F formed with raising iron concentration from 0 to 10.1 wt% (no Cu added; 0.1 wt% Cu), as well as strong surging of both amount and average chlorination level of PCDD/F when rising amounts of copper (0 to 1.1 wt%) are introduced. The resulting fingerprints are compared with those from sintering and from MSWI.

Formation of dioxins on NiO and NiCl2 at different oxygen concentrations.

Model fly ash (MFA) containing activated carbon (AC) as source of carbon, NaCl as source of chlorine and either NiO or NiCl2 as de novo catalyst, was heated for 1h at 350 °C in a carrier gas flow composed of N2 containing 0, 6, 10, and 21 vol.% O2, to study the formation of PCDD/Fs (dioxins) and its dependence on oxygen. The formation of PCDD/Fs with NiCl2 was stronger by about two orders of magnitude than with NiO and the difference augmented with rising oxygen concentration. The thermodynamics of the NiO-NiCl2 system were represented, X-ray absorption near edge structural (XANES) spectroscopy allowed to probe the state of oxidation of the nickel catalyst in the MFA and individual metal species were distinguished using the LCF (Linear combination fitting) technique: thus three supplemental nickel compounds (Ni2O3, Ni(OH)2, and Ni) were found in the fly ash. Principal Component Analysis (PCA) indicates that both Ni2O3 and NiCl2 probably played an important role in the formation of PCDD/Fs.

Thyroid hormone metabolism and environmental chemical exposure.

BACKGROUND: Polychlorinated dioxins and -furans (PCDD/Fs) and polychlorinated-biphenyls (PCBs) are environmental toxicants that have been proven to influence thyroid metabolism both in animal studies and in human beings. In recent years polybrominated diphenyl ethers (PBDEs) also have been found to have a negative influence on thyroid hormone metabolism. The lower brominated flame retardants are now banned in the EU, however higher brominated decabromo-diphenyl ether (DBDE) and the brominated flame retardant hexabromocyclododecane (HBCD) are not yet banned. They too can negatively influence thyroid hormone metabolism. An additional brominated flame retardant that is still in use is tetrabromobisphenol-A (TBBPA), which has also been shown to influence thyroid hormone metabolism.Influences of brominated flame retardants, PCDD/F's and dioxin like-PCBs (dl-PCB's) on thyroid hormone metabolism in adolescence in the Netherlands will be presented in this study and determined if there are reasons for concern to human health for these toxins. In the period 1987-1991, a cohort of mother-baby pairs was formed in order to detect abnormalities in relation to dioxin levels in the perinatal period. The study demonstrated that PCDD/Fs were found around the time of birth, suggesting a modulation of the setpoint of thyroid hormone metabolism with a higher 3,3', 5,5'tetrathyroxine (T4) levels and an increased thyroid stimulating hormone (TSH). While the same serum thyroid hormone tests (- TSH and T4) were again normal by 2 years of age and were still normal at 8-12 years, adolescence is a period with extra stress on thyroid hormone metabolism. Therefore we measured serum levels of TSH, T4, 3,3',5- triiodothyronine (T3), free T4 (FT4), antibodies and thyroxine-binding globulin (TBG) in our adolescent cohort. METHODS: Vena puncture was performed to obtain samples for the measurement of thyroid hormone metabolism related parameters and the current serum dioxin (PCDD/Fs), PCB and PBDE levels. RESULTS: The current levels of T3 were positively correlated to BDE-99. A positive trend with FT4 and BDE-99 was also seen, while a positive correlation with T3 and dl-PCB was also seen. No correlation with TBG was seen for any of the contaminants. Neither the prenatal nor the current PCDD/F levels showed a relationship with the thyroid parameters in this relatively small group. CONCLUSION: Once again the thyroid hormone metabolism (an increase in T3) seems to have been influenced by current background levels of common environmental contaminants: dl-PCBs and BDE-99. T3 is a product of target organs and abnormalities might indicate effects on hormone transporters and could cause pathology. While the influence on T3 levels may have been compensated, because the adolescents functioned normal at the time of the study period, it is questionable if this compensation is enough for all organs depending on thyroid hormones.

Sludge as dioxins suppressant in hospital waste incineration.

Nitrogen containing compounds such as ammonia, urea and amines can effectively inhibit the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). Sewage sludge accumulates both sulfur and nitrogen during wastewater treatment so it could be used to reduce PCDD/Fs formation. Indeed, it is observed in this study that the gas evolving from the sludge drying process can significantly suppress chlorobenzene (CBz) and PCDD/Fs formation from fly ash collected from a hospital waste incinerator. For instance, the reduction of hexachlorobenzene (HxCBz) and PCDD/Fs amount was 92.1% and 78.7%, respectively, when the drying gas evolving from 2g sludge flew through 2g fly ash. These tests were conducted in the frame of projects devoted to hospital waste incineration. The disposal technology for hospital waste (HW), developed in this institute, features rotary kiln pyrolysis combined with post-combustion followed by flue gas cleaning. Hence, some preliminary tests were devoted to investigate dioxins suppression by co-pyrolysis and co-combustion of polyvinyl chloride (PVC) and sludge in lab scale. More experimental research will be conducted to appropriately assess these effects of sludge on PCDD/Fs emissions during co-pyrolysis/combustion of HW and sludge.

Effects of dioxins, PCBs, and PBDEs on immunology and hematology in adolescents.

Dioxins and PCBs are environmental pollutants, proven to be immunotoxic. In the period 1987-1991 a cohort of mother-baby pairs was initiated to detect abnormalities in relation to dioxin levels in the mother's milk. At birth and at follow-up at 8-12 years, immunological and hematological effects were seen, prompting us to perform a new follow-up during adolescence. In addition, we assessed the immunological and hematological parameters in relation to current levels of PBDEs and PCBs. In the Netherlands, the pre- and postnatal exposure to dioxins have been studied prospectively since 1987. Venapuncture was performed to assess hematological (Hemoglobin, thrombocytes, thrombopoietin) and immunological (leukocytes, leukocyte differentiation) parameters and the current serum levels of dioxin, dioxinlike (dl)-PCBs and PBDEs. A decrease in the number of polymorphic neutrophils was found in adolescents with higher dl-PCBs in their serum (p = 0.021). No relation with total leukocytes, thrombocytes, hemoglobin, or thrombopoietin levels was seen. Similarly, we found no relation between prenatal, nor current dioxin levels and the hematological and the immunological parameters determined. The SigmaPBDEs were negatively associated with the number of lymphocytes (p = 0.01) and positively associated with the hemoglobin concentration (p = 0.003). These effects on the innate immunity by current levels of dl-PCBs and on the adaptive immunity by PBDEs are disconcerting, especially as the dl-PCB (0.04-7.8 WHOTEQ pg/g lipid, mean: 2.2 WHOTEQ pg/g lipid) and SigmaPBDE levels (mean 14.0 ng/g lipid, including one outlier with a sum of 73.6 ng/g lipid) were not high.

Delayed initiation of breast development in girls with higher prenatal dioxin exposure; a longitudinal cohort study.

OBJECTIVES: While many studies have assessed the health impacts of PCDD/Fs and PCBs on animals and humans, long-term consequences for especially adolescents, have not (yet) been well documented. This is certainly also true for the effects of PBDE exposure. As part of a longitudinal cohort study, now well into its second decade, effects of perinatal and current PCDD/F exposure, as well as current dl-PCB and PBDE exposures, on puberty, were assessed. STUDY DESIGN: Prenatal, lactational and current PCDD/F, dl-PCB and PBDE concentrations were determined using GC-MS. Pubertal development and growth were assessed by means of physical examination and the Tanner scale. 33 Children (born between 1986 and 1991) consented to the current follow-up study. Outcomes were evaluated using linear regression or the non parametric Spearman's correlation coefficient. RESULTS: A delay in initiation of breast development was found in girls (n = 18) with higher prenatal (p = 0.023) and lactational PCDD/F exposure (p = 0.048). The males revealed a negative trend with age at first ejaculation. For other endpoints on puberty and growth (pubic hair, axillary hair, genital stage, length, BMI, testicular volume, menarche) no significant relation was found with any of the measured compounds. DISCUSSION AND CONCLUSION: A relation between prenatal PCDD/F exposure and later initiation of breast development was seen. A Belgian study found a delay in breast development with higher current serum concentrations of dioxin-like compounds. The initiation of puberty is a complex process and it is yet not clear how dioxin-like compounds precisely affect this process prenatally. Further follow-up into adulthood is warranted, in order to detect the possibility of developing malignancies and fertility problems.

Perinatal dioxin exposure, cytochrome P-450 activity, liver functions and thyroid hormones at follow-up after 7-12 years.

OBJECTIVES: Prenatal and lactational exposure to Dutch "background" dioxin levels may cause health effects spanning many years. In addition, perinatal studies have shown a relationship between dioxin exposure and thyroid disturbance. To assess the later health effects of prenatal and lactational dioxin exposure on liver function we measured plasma ALAT and ASAT levels amongst our longitudinal cohort, as was done perinatally and at 2(1/2) years. The children underwent a caffeine loading test to determine CYP1A2 activity. To assess the later effects on thyroid function we measured plasma TSH and FT4. STUDY DESIGN: A longitudinal cohort of 37 healthy children (age 7-12, mean 8.2 years), with documented prenatal and lactational dioxin exposure, ingested 3mg caffeine/kg BW 6h prior to blood withdrawal. Paraxanthine/caffeine molar ratio, ALAT, ASAT, TSH and FT4 were determined in venous blood. RESULTS: Linear regression of ASAT and ALAT revealed no relation with prenatal and lactational dioxin exposure. No correlation was found between the paraxanthine/caffeine molar ratio and prenatal and lactational dioxin exposure. Linear regression of TSH and FT4 revealed no relation with prenatal and lactational dioxin exposure. CONCLUSION: This follow-up has shown a normalisation of previously abnormal ALAT and ASAT levels, indicating a transient effect. CYP1A2 activity, measured by means of a caffeine-loading test, revealed no correlation with the prenatal and lactational exposures. A normalisation of previously abnormal thyroid hormone homeostasis was seen, also possibly indicating a transient effect. This study provides new data on long-term follow-up after perinatal dioxin exposure to background levels of dioxins.

Evaluation of Organochlorine Compounds (PCDDs, PCDFs, PCBs and DDTs) in Two Raptor Species Inhabiting a Mediterranean Island in Spain (8 pp).

UNLABELLED: -: DOI: http://dx.doi.org/10.1065/espr2006.01.015 BACKGROUND: Species that are at high levels of the food web have often been used as bioindicators to evaluate the presence of persistent contaminants in ecosystems. Most of these species are long-lived, so pollutant burdens may be integrated in some complex way over time. This makes them particularly sensitive to deleterious effects of Persistent Organic Pollutants (POPs). Birds have been suggested as useful organisms for monitoring pollutant levels. Traditionally such studies have been carried out with raptors such as osprey (Pandion haliaetus), peregrine falcon (Falco peregrinus), bald eagle (Haliaetus leucocephalus), etc. In this paper we present the results of a monitoring study conducted on two raptor species, osprey (Pandion haliaetus) and red kite (Milvus milvus), inhabiting a Mediterranean island (Menorca, Spain). These two species have different feeding habits; ospreys prey on fish and red kites feed on terrestrial species. This study constitutes a good opportunity to investigate if differences in feeding habits (aquatic vs. terrestrial) influences the contaminants pattern in two species inhabiting the same area. METHODS: The study was conducted in a non-destructive way, using only failed eggs, to avoid the damage of the population stability. Eggs were collected during the period 1994-2000. The contaminants examined were dichlorodiphenyltrichloroethanes (DDTs, including DDT and its main metabolite, DDE), polychlorinated biphenyls (PCBs), including ortho PCBs (PCBs with at least one Chlorine atom in the ortho position): #28, 52, 95, 101, 123+149, 118, 114, 153, 132+105, 138, 167, 156, 157, 180, 170, 189, 194; and non ortho PCBs (PCBs with no Chlorine atom in the ortho position): #77, 126, 169 and all the polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) with Chlorine atoms at the 2,3,7 and 8 position (2,3,7,8-substituted PCDDs and PCDFs). The analysis of organochlorine compounds was performed using a sample treatment based on a Solid Phase Matrix Dispersion procedure. Ortho PCBs and DDTs were determined by HRGC-µECD; non ortho PCBs and PCDD/Fs were determined by HRGC-HRMS. RESULTS AND DISCUSSION: The sum of the ortho PCB congeners analysed ranged from 0.94 to 15.03 µg/g wet weight (ww) for ospreys and from 1.0 to 11.2 µg/g ww for red kites. In both species, PCB congeners #153, #138 and #180 accounted about 75% to total ortho PCB concentrations. Regarding non ortho PCBs, for ospreys, concentrations ranged from 0.16 to 1.39 ng/g wet weight (ww) and for red kites from 0.12 to 0.51 ng/g ww, being congener #126 the most abundant. Concerning DDTs, concentration for ospreys ranged from 0.07 to 1.03 µg/g ww; and for red kites ranged from 0.90 to 2.10 µg/g ww, representing DDE more than 95% of the total DDTs, which proves a past use of DDT in the study area. Differences in contaminant levels between species are probably associated to feeding habits. The fish-eating species presents the highest PCB levels, whereas the terrestrial species exhibits the highest DDT levels. PCDD/Fs in ospreys were in the range 2.6-14.2 pg/g ww, while in red kites the range was slightly wider (22.2-43.2 pg/g ww), being PCDDs the major contributors in black kites. Ospreys had PCDDs similar to PCDF concentrations. PCDD/F profiles were mostly influenced by OCDD in both species. Non ortho PCBs were the major contributors to calculated Toxic Equivalent Quantity (TEQs) in both species. CONCLUSION: In both species studied, ortho-PCBs could represent a problem of concern since 57% of the eggs exhibited levels higher than 4 µg/g ww, reported as the level that could cause reduced hatchability, embryo mortality, and deformities in birds. RECOMMENDATIONS AND OUTLOOK: Results found in this study suggest that a more detailed study to clear up possible deleterious effects of PCBs on the bird populations studied here should be done.

Persistent hematologic and immunologic disturbances in 8-year-old Dutch children associated with perinatal dioxin exposure.

Perinatal exposure to Dutch "background" dioxin levels in 1990 was high, but comparable with that of other industrialized Western European countries. Exposure during the sensitive perinatal period may cause permanent disturbances. Therefore, we assessed the health status and various hematologic and immunologic parameters among our longitudinal cohort. A medical history was taken and venipuncture performed in a longitudinal cohort of 27 healthy 8-year-old children who had documented perinatal dioxin exposure. Linear regression revealed a decrease in allergy in relation to prenatal (p = 0.02) and postnatal (p = 0.03) dioxin exposure. Increases in CD4+ T-helper cells (p = 0.006) and in CD45RA+ cells (p = 0.02) were seen in relation to postnatal exposure. A persistently decreased platelet count (p = 0.04) and increased thrombopoietin concentration (p = 0.03) were seen in relation to postnatal exposure. This follow-up has shown a decrease in allergy, persistently decreased thrombocytes, increased thrombopoietin, and increased CD4+ T-helper and increased CD45RA+ cell counts. This study provides indications of effects at the stem cell level of perinatal dioxin exposure, persisting until minimally 8 years after birth.

Metals as Catalysts during the Formation and Decomposition of Chlorinated Dioxins and Furans in Incineration Processes.

Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are found on fly ash and in flue gas of municipal waste incinerators. Municipal waste incinerators seem to be the most important source for PCDDs and PCDFs emitted into the air during the last decades. PCDD/F formation takes place in the cooler zones (250 °C-450 °C) of a municipal waste incinerator, at the electrostatic precipitator. Copper is an important component of the fly ash that can catalyse the formation of PCDDs and PCDFs. Inhibition of the formation can be done by complexation of the metals (Cu) with EDTA or NTA.