Toxicokinetics of dioxins and other organochlorine compounds in Japanese people: Association with hepatic CYP1A2 expression levels

Concentrations of persistent organochlorine compounds (OCs) including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) in the liver and adipose tissue of Japanese cadavers were measured, and their toxicokinetics were examined in association with hepatic cytochrome P450 (CYP) 1A protein expression levels. Total 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) were 66 ± 74 and 65 ± 57 pg/g lipid weight (mean ± S.D.) in the liver and adipose tissue, respectively. Total PCBs (sum of 62 congeners targeted), p,p′-dichlorodiphenyl-dichloroethylene (p,p′-DDE) and β-hexachlorocyclohexane (β-HCH) were detected at concentrations over 1 μg/g lipid in both tissues of some specimens. For most of the dioxin-like congeners, total PCBs, p,p′-DDE, oxychlordane, α- and β-HCH, hexachlorobenzene (HCB), and tris(4-chlorophenyl)methane (TCPMe), age-dependent increases in concentrations were found in the adipose tissue of males. No such age-dependent trend was observed in the liver, suggesting that there are different mechanisms underlying the hepatic concentrations of OCs. Immunoblot analyses indicated detectable expression of hepatic CYP1A2 protein, whereas no CYP1A1 protein was detected. The CYP1A2 expression levels were positively correlated with concentrations (on wet weight basis) of 2,3,4,7,8-P₅CDF, the dominant TEQ-contributed congeners in the liver, indicating the induction of this CYP. Hepatic CYP1A2 protein levels were strongly correlated with the liver to adipose concentration (L/A) ratios of PCDD/F congeners with more than 5 chlorine atoms. Together with higher concentrations of the congeners in the liver than in the adipose tissue, the observation on L/A ratios of highly chlorinated PCDD/Fs suggests that induced hepatic CYP1A2 protein is involved in their sequestration in this human population, as observed in model animals (rodents). Nonetheless, the magnitude of hepatic sequestration (L/A ratio) of PCDD/Fs in this human population was lower than in other mammals and birds, reported previously. This study emphasizes the fact that toxicokinetics of some OCs can be affected at least partly by CYP1A2 protein levels in humans. For the extrapolation of their toxicokinetics from model animals to humans, knowledge on the induction and sequestration potencies of CYP1A is necessary.     

Maternal exposure to high levels of dioxins in relation to birth weight in women affected by Yusho disease

Background

Studies on the association of maternal exposure to polychlorinated dibenzo-p-dioxin (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) with decreased birth weight in humans have produced conflicting results. In Japan in 1968, an accidental human exposure to rice oil contaminated with PCDDs, PCDFs, and PCBs, led to the development of Yusho disease.

Objective

The Yusho cohort was used to evaluate the effect of maternal exposure to PCDDs, PCDFs, and PCBs on birth weight.

Methods

Blood samples, obtained from 101 Yusho women (190 births) who gave birth after exposure, were analyzed for congeners of seven PCDDs, ten PCDFs, and four non-ortho PCBs.

Results

Total PCDD TEQ (adjusted beta = − 161.9 g; 95% CI, −265.3 to − 58.6), total PCDF TEQ (adjusted beta = − 105.9 g; 95% CI, −179.5 to − 32.2), and total non-ortho PCBs (adjusted beta = − 178.4 g; 95% CI, −318.3 to − 38.5) levels were inversely associated with birth weight. Significant inverse associations with birth weight were also found for total PCDD TEQ, total PCDF TEQ, and total non-ortho PCB TEQ levels among male, but not female, infants. Significant inverse associations with birth weight were also found for nine congeners among all infants; the adjusted beta coefficients were largest for 1,2,3,6,7,8-HxCDD and smallest for 2,3,4,7,8-PeCDF.

Conclusion

In the setting of exposure to high levels of dioxins, maternal blood levels of PCDDs, PCDFs and PCBs are associated with lower birth weight in Yusho patients. The association exhibited gender-specific differences, as male infants are more susceptible than females to growth restriction induced by in utero dioxin exposures.     

Development and validation of prediction models for blood concentrations of dioxins and PCBs using dietary intakes

BackgroundDioxins and PCBs accumulate in the food chain and might exert toxic effects in animals and humans. In large epidemiologic studies, exposure estimates of these compounds based on analyses of biological material might not be available or affordable.ObjectivesTo develop and then validate models for predicting concentrations of dioxins and PCBs in blood using a comprehensive food frequency questionnaire and blood concentrations.MethodsPrediction models were built on data from one study (n = 195), and validated in an independent study group (n = 66). We used linear regression to develop predictive models for dioxins and PCBs, both sums of congeners and 33 single congeners (7 and 10 polychlorinated dibenzo-p-dioxins and furans (PCDDs/PCDFs), 12 dioxin-like polychlorinated biphenyls (PCBs: 4 non-ortho and 8 mono-ortho), sum of all the 29 dioxin-like compounds (total TEQ) and sum of 4 non dioxin-like PCBs (∑ CB-101, 138, 153, 183 = PCB₄). We used the blood concentration and dietary intake of each of the above as dependent and independent variables, while sex, parity, age, place of living, smoking status, energy intake and education were covariates. We validated the models in a new study population comparing the predicted blood concentrations with the measured blood concentrations using correlation coefficients and Weighted Kappa (К_W) as measures of agreement, considering К_W > 0.40 as successful prediction.ResultsThe models explained 78% (sum dioxin-like compounds), 76% (PCDDs), 76% (PCDFs), 74% (no-PCBs), 69% (mo-PCBs), 68% (PCB₄) and 63% (CB-153) of the variance. In addition to dietary intake, age and sex were the most important covariates.The predicted blood concentrations were highly correlated with the measured values, with r = 0.75 for dl-compounds 0.70 for PCB₄, (p < 0.001) and 0.66 (p < 0.001) for CB-153. К_W was 0.68 for sum dl-compounds 0.65 for both PCB₄ and CB-153. Out of 33 congeners 16 (13 dl-compounds and 3 ndl PCBs) had К_W > 0.40.ConclusionsThe models developed had high power to predict blood levels of dioxins and PCBs and to correctly rank subjects according to high or low exposure based on dietary intake and demographic information. These models underline the value of dietary intake data for use in investigations of associations between dioxin and PCB exposure and health outcomes in large epidemiological studies with limited biomaterial for chemical analysis.     

Temporal trends in concentrations and total serum burdens of organochlorine compounds from birth until adolescence and the role of breastfeeding

Introduction: The aims of the present study are to assess the temporal trends of organochlorine compounds (OCs) concentrations and total serum burdens from birth until adolescence and the influence of breastfeeding in these temporal trends. Methods: In 1997 two birth cohort studies were set up in Ribera d'Ebre (N = 102) and the island of Menorca (N = 482), Spain. Concentrations (ng/mL) of OCs [pentachlorobenzene (PeCB), four isomers of hexachlorocyclohexane (HCH), hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (4,4′-DDT), dichlorodiphenyldichloroethylene (4,4′-DDE) and seven polychlorobiphenyl congeners (Σ₇PCBs)] were measured in cord blood and at the age of 4 and 14 years. The total serum burdens (ng) of these compounds were estimated based on the total blood volume (mL) of children at the different ages. We compared median concentrations and total serum burdens of these OCs at the different time-points of follow-up between children of Ribera d'Ebre and Menorca and between breastfed and non-breastfed children. Results: From birth until adolescence concentrations of all OCs drastically reduced. These reductions were mainly derived from the dilution of OCs, associated to an increase in total blood volume of children at the age of 4 and 14 years. Despite the reduction in OCs concentrations, the total serum burdens of 4,4′-DDE and Σ₇PCBs, were higher in adolescents than at birth. Increases in OCs total serum burden occurred both in breastfed and non-breastfed children, but were significantly higher in the first. Conclusions: Even after decades of banning OCs production and use, current young generations in westernized countries are still bioaccumulating these compounds. Given the potential health effects of OCs, especial attention should be paid in the control of secondary emissions in the environment and in the control of food production and contamination. In countries with endemic malaria it is important to work towards effective alternatives to the use of DDT.     

Persistent organic pollutants in breast milk of mothers residing around an open dumping site in Kolkata,India: Specific dioxin-like PCB levels and fish as a potential source

Concentrations of persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs) and organochlorine pesticides were measured in human breast milk collected from mothers residing near an open dumping site and a reference site in Kolkata, India during 2004–2005. POPs were detected in all the human milk samples analyzed, suggesting that residents of Kolkata are widely exposed to these contaminants. Concentrations of dioxin-like PCBs in the samples from the dumping site were significantly higher than in the reference site samples, whereas no such difference was found for PCDDs and PCDFs. In addition, significantly higher concentrations of total PCBs were also observed in the samples from the dumping site than the reference site. Interestingly, concentrations of total and dioxin-like PCBs in the breast milk of mothers from the dumping site significantly increased with the number of years of residence near the dumping site. These results indicate that significant pollution sources of PCBs are present in the dumping site of Kolkata and the residents living around are exposed to relatively higher levels of PCBs. When the residue levels of dioxins and related compounds in fish collected from ponds near the Kolkata dumping site and the reference site were measured, it was found that dioxin-like PCB and TEQ levels in fish from the dumping site were notably higher than those from the reference site. This result indicates that fish is a potential source of PCBs for residents living near the Kolkata dumping site.     

Correcting serum concentrations of organochlorine compounds by lipids: Alternatives to the organochlorine/total lipids ratio

IntroductionWhen studying the effects of organochlorine compounds (OCs) on human health it is common to correct serum concentrations of OC by total lipids (TL). However, the relationship between serum OCs and serum TL is far from established in many diseases, including several cancers. Our aim was to analyze the relationship between serum OC and TL in patients with pancreatic ductal adenocarcinoma (PDA), and to explore several alternatives to perform the OC lipid correction.MethodsIncident cases of PDA were interviewed and had blood drawn soon around hospital admission (n = 144). Serum concentrations of OCs were analysed by high-resolution gas chromatography with electron-capture detection.ResultsMost patients with high TL had moderate or low concentrations of OCs. By contrast, the variability of OC values among patients with normal TL was large. Correlations were of a similar magnitude between OC and TL and between OC and total cholesterol; while these correlations were weak (all Spearman's ρ < 0.3 and R² < 0.11), no OC were significantly correlated with triglycerides. Although all alternatives to the OC/TL linear ratio were statistically significant for at least one OC, their R² was always below 10%.ConclusionsIn patients with severe diseases as PDA, linear correction of OC by TL as commonly performed in epidemiologic studies may be inappropriate. Results contribute to the scant literature on the rationale to correct serum concentrations of OC by lipids. They suggest that it is unwarranted to routinely correct OC by TL, offer ways to assess such need, and present alternatives as no TL correction, correction by total cholesterol only or use of different statistical models.     

Dioxin and dioxin-like PCB profiles in the serum of industrial and municipal waste incinerator workers in Korea

To assess occupational exposure, we determined the concentrations of PCDD/Fs and PCBs in human serum samples from 26 incinerator workers (10 industrial waste and 16 municipal solid waste incinerator workers), 38 residents near the facilities and 7 inhabitants (as control subjects) living over 10 km away from any incinerator facilities in Korea. The mean TEQ_WHO levels of PCDD/Fs in the industrial and MSWI workers were 41.57 and 9.86 pg TEQ_WHO g^? 1 lipid, respectively. For the residents, the mean TEQ_WHO was 13.47 pg TEQ_WHO g^? 1 lipid (residents near IWI, MSWI, and control subjects: 17.64, 13.31, and 6.91 pg TEQ_WHO g^? 1 lipid). Higher levels of certain PCDD/F congeners, mainly PCDFs, were detected in the serum of industrial incinerator workers in comparison to the levels measured in the residents. Significant differences were observed for PCDFs, the major compounds were OCDF, 1,2,3,4,6,7,8-HpCDF, and the minor components 1,2,3,4,7,8-HxCDF, 1,2,3,6,7,8-HxCDF, and 2,3,4,6,7,8-HxCDF (p < 0.01). The PCDD/F congener patterns and concentrations measured in the 71 serum samples examined suggest that the industrial incinerator workers were exposed to PCDD/Fs in the workplace, possibly through inhalation and/or skin contact. In contrast, the levels and congener patterns of PCBs measured were similar in all subjects, indicating that workers from the incinerator facilities examined were not subjected to additional exposure to these compounds.     

Temporal trends of polychlorinated dibenzo-p-dioxins and dibenzofurans and dioxin-like polychlorinated biphenyls in mothers' milk from Sweden, 1972–2011

Temporal trends of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in mothers' milk are still quite rare. Data are particularly scarce when it comes to concentrations from the last decade, 2000 and onwards. The aims of the present study were to assess temporal trends of PCDD, PCDF and DL-PCB in mothers' milk from Stockholm, 1972–2011 and to compare the results with previous analysis of some of the older samples.The samples were analyzed by high resolution GC/MS and results were statistically evaluated for the periods, 1972–2011 and 2002–2011. The rate of which ∑PCDDs, ∑DL-PCBs and the ∑TEQ are decreasing (on pg/g fat WHO-TEQ2005) is higher in the last decade compared to the 40 year period, 1972–2011. A similar trend is indicated, but not confirmed, for ∑TEQ of PCDFs, probably due to too many PCDF congeners below LOQ in the period 2002–2011. Concentrations of ∑PCDDs, ∑PCDFs, ∑DLPCBs and ∑TEQ, all expressed as pg/g fat on TEQ-WHO2005-basis, show a statistically significant decline over time, 5.8–6.8% per year, 1972–2011. The last ten years the annual declines for ∑PCDDs, ∑DL-PCBs and ∑TEQ are 9.2–11% and for ∑PCDF, 5.4%. Congener specific trend analysis, 2002–2001, of PCDDs and DL-PCBs showed the same pattern, while the PCDF congeners showed no such general trend. The results from the re-analysis showed good agreement with slightly lower ∑TEQ1998 pg/g fat concentrations in six out of seven samples and mean difference of 13% in ∑TEQ1998. The study shows that time series can be elongated from previous studies, as long as the sample population remains the same.     

Relative effect potency estimates of dioxin-like activity for dioxins,furans, and dioxin-like PCBs in adults based on cytochrome P450 1A1 and 1B1 gene expression in blood

BackgroundIn the risk assessment of PCDDs, PCDFs, and dioxin-like (DL) PCBs, regulatory authorities support the use of the toxic equivalency factor (TEF)-scheme derived from a heterogeneous data set of the relative effect potency (REPs) estimates.ObjectivesWe sought to determine REPs for dioxin-like compounds (DLCs) using expression of cytochrome P450 (CYP) 1A1 and 1B1 mRNA in human peripheral blood mononuclear cells representing two different pathways.MethodsWe used a sex and age adjusted regression-based approach comparing the strength of association between each DLC and the cytochrome P450 (CYP) 1A1 and 1B1 mRNA expression in 320 adults residing in an organochlorine-polluted area of eastern Slovakia.ResultsWe calculated REPs based on CYP1A1 expression for 4 PCDDs, 8 PCDFs, and 1 PCB congener, and based on CYP1B1 expression for 5 PCDFs and 11 PCB congeners. REPs from CYP1A1 correlated with REPs previously derived from thyroid volume (ρ = 0.85; p < 0.001) and serum FT4 (ρ = 0.77; p = 0.009). The 13 log REPs from CYP1A1 correlated with log WHO-TEFs (r = 0.63; p = 0.015) and 11 log PCB REPs with PCB consensus toxicity factors (CTFs) for compounds with WHO-TEFs (r = 0.80; p = 0.003). The complete set of derived 56 log REPs correlated with the log CTFs (r = 0.77; p = 0.001) and log WHO-TEFs (r = 0.81; p < 0.001).ConclusionsREPs calculated from thyroid and cytochrome P450 endpoints realistically reflect human exposure scenarios because they are based on human chronic and low-dose exposures. While the CYP 1A1 seems more suitable for toxicity evaluation of PCDD/Fs, the CYP 1B1 is more apt for PCDFs and PCBs and reflects different pathways.     

Blood levels of dioxins,furans, dioxin-like PCBs,and TEQs in general populations: A review, 1989–2010

A comprehensive worldwide literature review of blood levels of dioxins and dioxin-like compounds in non-exposed adult general populations was performed. The studies published in 1989–2010 reporting information on polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), non-ortho-PCBs (nPCBs), mono-ortho-PCBs (mPCBs) levels and Toxic Equivalencies (TEQs, a summary weighted measure of their combined toxicity) were reviewed. TEQs were calculated using as standard the most recent WHO 2005 reevaluation of Toxic Equivalency Factors (TEFs). Weighted multiple regression analyses adjusted for year, subject's age, type of sample analyzed, method used for values below detection limit, and central tendency measure used were performed for each congener and standardized TEQs (log-transformed). We identified 187 studies regarding 29,687 subjects of 26 countries. Year of blood collection ranged from 1985 to 2008. The studies reporting congener levels 161. In adjusted analyses, European countries showed higher levels of most dioxin-like congeners and TEQs. A strong positive association of subjects' age with most congeners and with TEQ values was found, confirming previous findings. Significant decreases over time (1985–2008) were documented for PCCDs, PCDFs, and TEQs including their contributions. No significant decrease was found for non-ortho-PCBs, notably PCB 126. Only some mono-ortho-PCBs showed clear significant declines. Accordingly, TEQs including only PCB contribution did not decrease over time. In interpreting these findings, it should be considered that for dioxin-like PCBs the analysis period was shorter (17 years), since these compounds were first measured in 1992.     

Unexpected high PCB and total DDT levels in the breeding population of red kite (Milvus milvus) from Doñana National Park, south-western Spain

This study provides information on the current status of contamination by organochlorines (DDTs, PCBs, PCDDs and PCDFs) in the declining red kite (Milvus milvus L.) population breeding in the Do?ana National Park (DNP), south-western Spain. Analyses were performed in addled eggs collected between 1999 and 2001. DDE concentrations ranged from 0.1 to 33.5 microg/g ww, representing more than 86% of the total DDTs. Of the samples studied, 50% showed DDE levels above those associated with reproductive impairment in other raptor species. Concentrations of ortho PCBs (average 36.8 microg/g ww+/-37.7) in 50% of the eggs were much higher than levels reported to cause reduced hatching success, embryo mortality, and deformities in birds (>20 microg/g ww). It is remarkable that average ortho PCB and DDE concentrations showed an increase of one order of magnitude compared to previous data for the species during the 80s. Total PCDD/Fs showed levels in the low pg/g range (7.2-42 pg/g ww), having PCDDs and PCDFs similar contributions in most samples. Total mean TEQs were 238 pg/g (ww), being the range 7.02-667 pg/g (ww). Spatial variation within DNP was observed for PCBs, DDTs, as well as for TEQs. Since some eggs exceeded the NOEL (67%) and LOEL (33%) reported for other raptor species, we would expect the red kite to experience detrimental effects to dioxin-like toxicity. Our results suggest that organochlorine contaminants should be regarded as an element of concern in the population under study, in addition to other conservation problems already reported. Further investigations should be undertaken to identify potential sources of these chemicals in DNP, and to find out if organochlorine contamination is present in other predator species in the area, as well as their potential health effects on individuals and/or populations.     

The potential impact of environmental variation on the concentrations and ecological effects of pollutants in a marine avian top predator

Concentrations of organochlorine contaminants (OCs) and associations between OCs and fitness components were examined in great black-backed gulls (Larus marinus) in three colonies along the coast of northern Norway. In one of the colonies, data were collected in two subsequent seasons. Concentrations of four OCs (HCB, oxychlordane, DDE and PCB) were measured in blood (n=260) and fitness components (reproductive variables and adult return rate between breeding seasons) were recorded. In the first year, in two of the colonies, body condition and reproductive performance among the gulls were poor compared to the third colony, suggesting spatial variation in environmental conditions, especially food availability. However, in the third colony, body condition and reproductive performance were even better in the second season; i.e. environmental conditions varied temporally. OC residues were higher in the colonies where environmental conditions were poor, but much of this variation was explained by differences in body condition among colonies. Moreover, concurrent with improved body condition from one season to the next, the concentrations of OCs were halved. In the two colonies where environmental conditions were poor, female OC residues were negatively related to egg-laying date, egg size and nesting success, and in the colony where the concentrations of OC were highest, gulls with elevated DDE residues had low probability of returning between breeding seasons. In comparison, in the colony where environmental conditions were better in the first year, other types of adverse relationships between OCs and fitness components were found; i.e. chicks from females with high OC concentrations were in poor condition at hatching, suggesting maternal transfer of OCs to the eggs, and males with high OC residues had poor nesting success and chick survival, suggesting OC-mediated behavioural changes. With improved environmental conditions and lower OC concentrations in the second season, no significant adverse relationships between OCs and fitness components were found. This study thus suggests that there are complex interrelationships between both concentrations and ecological effects of OCs, and the environment, indicating that effects of OCs in nature may only be assessed after considering environmental variation.     

Concentrations of PCDD/PCDFs and PCBs in fish and seafood from the Catalan (Spain) market: estimated human intake

The concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) in samples from 14 fish and seafood species widely consumed by the population of Catalonia, Spain, were measured. These samples were randomly purchased independently of their geographical origin. The intake of PCDD/Fs and PCBs through consumption of these species was also estimated for various age and sex groups of this population. The highest and lowest levels of PCDD/Fs and dioxin-like PCBs (DL-PCBs) were found in red mullet and shrimp, respectively. For a standard adult man (70 kg body weight), the intake of PCDD/Fs plus DL-PCBs through consumption of fish and other seafood was estimated to be 38.0 pg WHO-TEQ/day. Tuna, hake, and sardine were the species with the highest contribution to this intake. The results of this study indicate that, in general terms, the dietary habits of the population of Catalonia (Spain) regarding fish and seafood consumption do not contribute remarkably to increase PCDD/F and DL-PCB intake.     

Reproductive performance and organochlorine pollutants in an Antarctic marine top predator: the south polar skua

Despite low levels of organochlorine contaminants (OCs) in Antarctic biota, some compounds may exceed the levels in equivalent Arctic species, and previous studies have found biochemical evidence of pollutant exposure in south polar skuas (Catharacta maccormicki), a common marine top predator in the region. In this study we examined relationships between fitness components (fecundity and adult return rate between breeding seasons) and concentrations of OCs in this species. In 65 nests, both males and females were caught, and using principal component analyses (PCA) we produced composite measurements (PC1 and PC2) of six highly correlated OCs measured in blood samples. Although the concentrations of OC were below those documented to have reproductive effects in other aquatic birds, we found that the eggs of females with high levels of OCs in the blood hatched later, and their chicks were in poorer condition at hatching, than females with low OC levels. Thus OCs may delay reproduction and reduce foetal growth in the skuas. However, there was no relationship between the parents' OC residues and the occurrence of non-viable eggs, although the proportion of nests containing non-viable eggs was high (47%). Moreover, there were no significant relationships between OCs and reproductive variables in males, even if males had higher OC levels than females, and no associations between OCs and adult return rate between breeding seasons.     

Hydroxylated PCB metabolites (OH-PCBs) in archived serum from 1950–60s California mothers: A pilot study

We are studying participants selected from the Child Health and Development Studies (CHDS), a longitudinal birth cohort of over 20,000 California pregnancies between 1959 and 1967, for associations between maternal body burden of organochlorine contaminants and thyroid function. We designed a pilot study using 30 samples selected among samples with high and low PCB concentrations to evaluate the feasibility of measuring OH-PCBs in the larger study population. GC-ECD and GC-NCI/MS were used to determine PCBs and OH-PCBs as methyl derivatives, respectively. Maternal serum levels of Σ₁₁PCBs and Σ₈OH-PCB metabolites varied from 0.74 to 7.99 ng/mL wet wt. with a median of 3.05 ng/mL, and from 0.12 to 0.98 ng/mL wet wt. with a median of 0.39 ng/mL, respectively. Average concentrations of Σ₈OH-PCB metabolites in the high PCB group were significantly higher than those in the low PCB group (p < 0.05). The levels of OH-PCB metabolites were dependent on PCB levels (r = 0.58, p < 0.05) but approximately an order of magnitude lower (p < 0.05). The average ratio of Σ₈OH-PCBs to Σ₁₁PCBs was 0.14 ± 0.08. The primary metabolite was 4-OH-CB187 followed by 4-OH-CB107. Both of these metabolites interfere with the thyroid system in in vitro, animal, and human studies. OH-PCBs were detectable in all archived sera analyzed, supporting the feasibility to measure OH-PCB metabolites in the entire cohort.     

Yusho and its latest findings—A review in studies conducted by the Yusho Group

The Yusho incident is an unprecedented mass food poisoning that occurred in Japan in 1968. It was caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds, such as polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). The victims of Yusho have suffered from characteristic skin manifestations associated with systemic, ophthalmological, and mucosal symptoms for a long period of time. The Study Group of Yusho (the Yusho Group) has been conducting annual medical check-ups on Yusho victims for more than 45 years. Since 2002, when concentrations of dioxins in the blood of Yusho patients started to be measured, the pharmacokinetics of dioxins, relationship between blood levels of dioxins and symptoms/signs in patients directly exposed to dioxins, and the adverse effects on the next generation have become dramatically clear. Herein we review recent findings of studies conducted by the Yusho Group to evaluate chronic dioxin-induced toxicity to the next generation as well as Yusho patients in comparison with a similar food mass poisoning, the Yucheng incident. Additionally, we summarized basic studies carried out by the Yusho Group to re-evaluate the mechanisms of dioxin toxicities in experimental models and various functions of the aryl hydrocarbon receptor (AhR), known as the dioxin receptor, pathway.     

Evidence for bismuth-207 in global fallout

Samples of lichen, moss, soil and air collected since 1961 in Greenland, Svalbard, Iceland, the Faroe Islands, Sweden and Denmark have been remeasured for γ-emitting radionuclides by Ge(Li) spectroscopy. The samples have shown the presence of ²⁰⁷Bi (physical half-life 38 years), a nuclide which has not been reported earlier in world-wide fallout. The concentrations of ²⁰⁷Bi have been compared with those of ⁶⁰Co, ¹²⁵Sb, and ¹³⁷Cs. From this comparison the production of ²⁰⁷Bi is estimated at 1 PBq. It is assumed that the ²⁰⁷Bi is created in thermonuclear tested explosions in general and that in particular the 55Mt detonation of 30 October 1961 at Novaya Zemlya may have produced this activation product.     

Evaluation of background persistent organic pollutant levels in human from Taiwan: polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls

This study was intended to determine the background levels of PCDD/PCDFs and PCBs in the Taiwanese population and to investigate factors potentially related to PCDD/PCDF and PCB levels. The levels of seventeen PCDD/PCDFs in the 251 serum samples collected from the general population in Taiwan ranged from 4.92 to 26.7 pg WHO(1998)-TEQ/g lipid (median: 11.5) and those of the twelve dioxin-like PCBs ranged between 1.74 and 21.6 pg WHO(1998)-TEQ/g lipid (median: 6.14). Five factors, age, gender, region of residence, dietary status, and smoking status, showed statistically significant association with the TEQ level of PCDD/PCDFs. The TEQ level of PCBs was statistically associated with age only, but not with the other four factors. The trends observed between age and the levels of PCDD/PCDFs and PCBs were not parallel in young subjects (<30 years old) and old subjects (>30 years old). The levels of PCDD/PCDFs and PCBs increased by 0.16 and 0.03 WHO(1998)-TEQ/g lipid per year for subjects above the age of 30, but there was no evidence of any association between age and the levels for subjects below the age of 30 years. These factors should be considered when investigating relationships between background serum levels of persistent organic pollutants and parameters associated with exposure sources or health outcomes.     

Persistent environmental pollutants in eggs of aplomado falcons from Northern Chihuahua, Mexico, and south Texas, USA

The northern aplomado falcon (Falco femoralis septentrionalis) disappeared from south Texas in the 1940s. Due to great success in the release of captive-reared aplomado falcons in south Texas, there are currently more than 40 established nesting pairs in the region. Addled eggs from aplomado falcons nesting in northern Chihuahua and south Texas were analyzed to determine organochlorine (OC) and inorganic element contaminant burdens and their potential association with egg failures and effects on reproduction. Among the OCs, DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] was present at the highest concentrations (range 262-21487 ng/g wet weight) followed by polychlorinated biphenyls (PCBs, range 88-3274 ng/g ww). DDE was greater (P=0.03) in eggs from El Sueco (Chihuahua, Mexico) than in those from Matagorda Island (Texas, USA). DDE concentrations in eggs of aplomado falcons from El Sueco were elevated; however, reproductive success in the two Chihuahuan populations did not seem to be affected by DDE. DDE and metals in potential avian prey of the aplomado falcon from Matagorda Island were very low and below levels in the diet at which some negative effects might be expected. Except for mercury (Hg), metal concentrations in eggs were fairly low and were not different among locations in Chihuahua and south Texas. Hg was somewhat elevated and was greater (P<0.001) in Texas than in the Chihuahua locations. Periodic monitoring of Hg concentrations in addled eggs of aplomado falcons in south Texas is recommended to continue evaluating potential negative effects on their recovery.     

Background exposure to persistent organic pollutants predicts stroke in the elderly

Background exposure to persistent organic pollutants (POPs), lipophilic xenobiotics that accumulate mainly in adipose tissue, has recently emerged as a new risk factor for cardiovascular diseases. This prospective study was performed to evaluate if plasma concentrations of selected POPs predict incident stroke among the elderly. Twenty‐one POPs (including 16 polychlorinated biphenyl (PCB) congeners, 3 organochlorine (OC) pesticides, 1 brominated diphenyl ether (BDE), and 1 dioxin) were measured in plasma collected at baseline in 898 participants aged 70 years of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). Stroke diagnosis was validated by hospital records. During the five year follow-up, 35 subjects developed hospital-treated stroke. After adjusting for known stroke risk factors, most PCBs with 4, 5, or 6 chlorine atoms, p,p′-DDE, trans-nonachlor, and octachlorodibenzo-p-dioxin significantly predicted the risk of stroke. Across quartiles of summary measures of PCBs and OC pesticides, the adjusted ORs were 1.0, 0.8 (95% confidence interval: 0.2–2.5), 1.2 (0.4–3.4), and 2.1 (0.7–6.2) for PCBs and 1.0, 1.2 (0.3–4.2), 2.3 (0.7–6.9), and 3.0 (1.0–9.4) for OC pesticides (P for trend = 0.11 and 0.03, respectively). The adjusted ORs among participants ≥ 90th percentile of the summary measures were 5.5 (1.7–18.1) for PCBs and 4.0 (1.1–14.6) for OC pesticides; corresponding ORs for those ≥ 95th percentile were 7.8 (2.1–29.6) and 9.5 (2.3–38.9). Background exposure to POPs may play an important role in development or progression of stroke in the elderly.