Comparison between "Yusho" patients and healthy Japanese in contamination level of dioxins and related chemicals and frequency of sister chromatid exchanges

Highly toxic organochlorine chemicals such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and coplanar polychlorinated biphenyls (CoPCBs) were determined in the peripheral blood and sebum from the face of 16 "Yusho" patients of about 27 yr after the outbreak of Yusho accident, and 39 healthy Japanese people. The mean total toxic equivalent (TEQ) levels of PCDDs, PCDFs and CoPCBs in the blood were still about seven times higher in Yusho patients than in healthy Japanese at the age of 45 yr and more. The sebum excretion of these chemicals seemed proportional to their blood levels in Yusho patients. These toxic chemicals, however, did not enhance frequencies of sister chromatid exchanges (SCEs) in the control and 7,8-benzoflavone (ANF) treated cultures in Yusho patients. Hence, no significant difference was observed in the mean SCE rates between the Yusho patients and general Japanese people of more than 45 yr of age. In this study, the number of Yusho patients examined is limited, so further large-scale investigations are needed to get more conclusive results concerning the genotoxic potency such as SCE induction.     

Effects of donor age and contamination level of dioxins and related chemicals on frequency of sister chromatid exchanges in human lymphocytes cultured in vitro

Frequencies of sister chromatid exchanges (SCEs) of human lymphocytes in control (DMSO treated) and 7,8-benzoflavone (ANF) treated cultures were measured in 39 healthy Japanese people and examined in connection with donor age. Both the control (baseline) and ANF induced SCE rates were significantly enhanced with age and highly positive correlation was observed between them. Therefore, in vivo aging seemed to have some effects on the frequencies of SCEs in human lymphocytes cultured in vitro. Concentrations of PCDDs, PCDFs and Co-PCBs in the blood and sebum of face were determined in the same Japanese subjects. Significantly positive correlation was observed between the blood and sebum in their total TEQ levels. Hence, PCDDs, PCDFs and Co-PCBs, which have been contaminating human bodies, are considered proportionally excreted from the sebum of face or body. Their total TEQ concentrations were also meaningfully increased with donor age in the sebum of face as well as in the blood. Either the baseline or ANF induced SCE frequencies was not enhanced with the total TEQ levels in the blood. Therefore, background levels of their contamination seem not to affect the SCE rates of the lymphocytes in the control and ANF treated cultures.     

Comparison of the concentrations of polychlorinated biphenyls and dioxins in mothers affected by the Yusho incident and their children

Accumulated maternal dioxins are passed onto the fetus and neonate via the placenta and maternal milk. In Japan in 1968, an accidental human exposure to rice oil contaminated with polychlorinated biphenyls (PCBs) and other dioxin-related compounds, such as polychlorinated dibenzofurans (PCDFs), led to development of Yusho oil disease. We investigated differences in blood dioxin concentrations in mother-children pairs affected by the Yusho incident. From 2002 to 2008, blood samples were collected from 26 pairs of Yusho mothers and their children (19 mothers, 26 children). Specific congeners of seven polychlorinated dibenzo-p-dioxins (PCDDs), ten PCDFs, and four non-ortho PCBs were analyzed. The children had significantly lower TEQ concentrations of PCDDs, PCDFs, and coplanar PCBs compared to their mothers. The mother-child difference in blood concentrations varied with the congeners; the largest for 2,3,4,7,8-pentaCDF and the smallest for 1,2,3,4,6,7,8-heptaCDD. The level for 2,3,4,7,8-pentaCDF, which characterizes Yusho oil disease, was approximately 17-30 times higher in the mothers than in the general population, whereas there were no significant differences between children in the formula-fed group and the general population. In contrast, the mean level for 2,3,4,7,8-pentaCDF in the breast-fed group was approximately 1.5 times, (range 0.5-6.5 times) higher than that in the general population. Over 30 years after the Yusho incident, the mean blood dioxin levels in the offspring were only a fraction of the levels in their mothers. This is more consistent with exposure via breast milk than via transplacental transfer in the Yusho incident.     

Remediation of cadmium contamination in paddy soils by washing with chemicals: selection of washing chemicals

The efficiencies of neutral salts, strong acids, and chelates were tested for extracting cadmium (Cd) from three paddy soils. The higher the selectivity of the cations of the added neutral salts toward soil adsorption sites, the lower the pH in the extracts and the more soil Cd could be extracted. In addition, soil carbon and nitrogen contents and mineral composition were closely associated with the amount of Cd extracted. Calcium chloride and iron(III) chloride were selected as wash chemicals to restore Cd-contaminated paddy soils in situ. Washing with calcium chloride led to the formation of Cd chloride complexes, enhancing Cd extraction from the soils. The washing also substantially decreased soil levels of exchangeable and acid-soluble Cd, which are the major forms of bioavailable Cd for rice (Oryza sativa L.). The optimum conditions for in situ soil washing were also determined for calcium chloride.     

Recent trend of polychlorinated dibenzo-p-dioxins and their related compounds in the blood and sebum of Yusho and Yu Cheng patients

We investigated the levels of polychlorinated dibenzo-p-dioxins (PCDDs) and their related compounds in blood and sebum from Yusho and Yu-Cheng patients and findings compared with those of normal subjects. Concentrations of these compounds in blood and sebum still were obviously reflected the chemical concentration in the causal rice oil ingested 17 or 26 years since the outbreak. In addition, sebum form the body surface was the most useful sample for monitoring the amount of chemicals contaminating the human body.     

Concentration and distribution of dioxins and related compounds in human tissues

Polychlorinated dibenzo-p-dioxin, polychlorinated dibenzofuran and dioxin-like polychlorinated biphenyl concentrations in human blood, lung, liver, bile, pancreas, spleen, kidney and mesentery fat were determined to assess the concentrations and distribution of these chemicals in human tissues from 20 donors. The mean TEQ concentrations in blood, lung, liver, bile, spleen, pancreas, kidney and mesentery fat were 119, 178, 228, 50, 113, 163, 138 and 139 pg TEQ/g lipid, respectively. Parallel levels were seen in the blood, spleen, kidney and mesentery fat; in the lungs and pancreas, the levels were somewhat higher. Among the organ tissues samples, the highest concentration was observed in the liver and the lowest in the bile. Mean total-TEQ concentration of the liver was about 4.5 times higher than that of bile. Positive correlations were observed among the concentrations of dioxins in various tissues. However, the concentrations in bile were not correlated with any tissues. It is suggested that the distribution behavior of dioxin-like congeners in human tissues varies among tissues and the kinds of congeners ingested. To evaluate the relationship between the accumulation levels of dioxins and their pathophysiological significance or risk, data must be accumulated from a more extensive group of human samples.     

Dependence of GC-RRTs on the solvent-accessible surface area of dioxins and related compounds

The correlation between gas chromatograph relative retention times (GC-RRTs) of dioxins and related compounds, polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated naphthalenes (PCNs), and their solvent-accessible surface area (SAS) was analyzed for congeners and isomers. GC-RRTs were linearly dependent on SAS for congeners while there was little dependence for isomers. However, by using classification parameters, Nad-Cl, Nad-H, N1,9Cl, and NalphaCl, based on the substitution positions and patterns of chlorine and/or hydrogen atoms bound to the molecular skeleton, a linear relationship was found among isomers. Furthermore, the GC-RRTs of CDD, CDF, and CN isomers, which are planar, decreased despite increasing SAS, and this tendency was enhanced with the above classification. The retention behavior was explained in terms of the effective enhancement of molecular hydrophobicity caused by an increase in the number of adjacent chlorine pairs.     

Concentrations of dioxins and related compounds in the blood of Fukuoka residents

Blood samples of 152 residents (male 75 and female 77) aged 20-60 years in Fukuoka, Japan, were analyzed for dioxin toxic compounds of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), non-ortho polychlorinated biphenyls (non-ortho PCBs) and mono-ortho polychlorinated biphenyls (mono-ortho PCBs) as well as 35 PCB congeners and 12 chlorinated pesticides by high-resolution gas chromatography/high-resolution mass spectrometry. Average concentrations of dioxin toxic equivalents (TEQ) from PCDDs, PCDFs, non-ortho PCBs, mono-ortho PCBs and their total in the blood of 152 residents were 10.28, 5.56, 7.75, 4.57 and 28.15 ppt in lipid, respectively. These total TEQ levels were comparable to the blood TEQ levels of normal Japanese (n=735). Lipid basis total TEQ levels progressively increased in the males from 17.1 ppt at age 20s to 47.5 ppt at age 50s and in the females from 19.5 ppt at age 20s to 54.5 ppt at age 50s. Dioxin toxic contribution of PCBs to total TEQ was increased from 31% at age 20s to 55% at age 50s. Average concentrations of total 35 PCBs and total 12 pesticides in the blood of 151 residents were 386 and 1079 ppb in lipid, respectively. Average concentrations (ppb in lipid) of total PCBs and total pesticides also progressively increased in the males from 213 and 444 at age 20s to 868 and 2140 at age 50s, respectively, and in the females from 199 and 588 at age 20s to 550 and 1977 at age 50s, respectively. The levels of TEQ, PCBs, hexachlorobenzene, beta-hexachlorocyclohexane, dieldrin, p,p'-dichlorodiphenyldichloroethylene, p,p'-dichlorodiphenyltrichloroethane, trans-nonachlor and cis-nonachlor were positively correlated with each other in most of the combinations, and the highest correlations (r>0.8) were observed between total TEQ and PCBs in both sexes.     

Blood levels of PCDDs,PCDFs, and coplanar PCBs in Yusho mothers and their descendants: Association with fetal Yusho disease

Maternal exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) may result in adverse health effects in their children. In Japan in 1968, an accidental human exposure to rice oil contaminated with PCDDs, PCDFs, and PCBs, led to the development of Yusho disease. Yusho mothers delivered descendants with low birth weights and hyperpigmented skin and mucosa, which are characteristic of fetal Yusho disease (FYD). The Yusho cohort was used to evaluate the effect of maternal exposure to PCDDs, PCDFs, and PCBs on the development of FYD. Blood samples, obtained from 64 Yusho mothers (117 descendants: 10 with FYD and 107 without FYD), were analyzed for congeners of seven PCDDs, 10 PCDFs, and four coplanar PCBs. We investigated the association between the maternal estimated blood levels of dioxins at delivery and the risk of fetal Yusho disease. We also studied the differences in dioxin blood levels in 24 mother–descendant pairs (5 with FYD and 19 without FYD). The estimated levels of total PCDD TEQ, total PCDF TEQ, total coplanar PCB TEQ, and total TEQ in the maternal blood at delivery were associated with significantly increased risk of FYD. The odds ratios, which present the risk of FYD for a 10-fold increase in blood dioxin, were largest for 1,2,3,6,7,8-HexaCDD (odds ratio = 28.6, 95% confidence interval = 1.67–489.9, p = 0.02). The levels of 1,2,3,6,7,8-HexaCDD in both the Yusho mothers and their descendants with FYD were higher than the levels in those without FYD. These findings suggest that 1,2,3,6,7,8-HexaCDD is the most important causative congener for the development of FYD.     

Effects of perfluoroalkyl acids on the function of the thyroid hormone and the aryl hydrocarbon receptor

Perfluoroalkyl acids (PFAAs) are perfluorinated compounds that widely exist in the environment and can elicit adverse effects including endocrine disruption in humans and animals. This study investigated the effect of seven PFAAs on the thyroid hormone (TH) system assessing the proliferation of the 3,3′,5-triiodo-l-thryonine (T3)-dependent rat pituitary GH3 cells using the T-screen assay and the effect on the aryl hydrocarbon receptor (AhR) transactivation in the AhR-luciferase reporter gene bioassay. A dose-dependent impact on GH3 cells was observed in the range 1?×?10^?9–1?×?10^?4 M: seven PFAAs (perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), and perfluorododecanoic acid (PFDoA)) inhibited the GH3 cell growth, and four PFAAs (PFOS, PFHxS, PFNA, and PFUnA) antagonized the T3-induced GH3 cell proliferation. At the highest test concentration, PFHxS showed a further increase of the T3-induced GH3 growth. Among the seven tested PFAAs, only PFDoA and PFDA elicited an activating effect on the AhR. In conclusion, PFAAs possess in vitro endocrine-disrupting potential by interfering with TH and AhR functions, which need to be taken into consideration when assessing the impact on human health.     

Improved management of winter operations to limit subsurface contamination with degradable deicing chemicals in cold regions

This paper gives an overview of management considerations required for better control of deicing chemicals in the unsaturated zone at sites with winter maintenance operations in cold regions. Degradable organic deicing chemicals are the main focus. The importance of the heterogeneity of both the infiltration process, due to frozen ground and snow melt including the contact between the melting snow cover and the soil, and unsaturated flow is emphasised. In this paper, the applicability of geophysical methods for characterising soil heterogeneity is considered, aimed at modelling and monitoring changes in contamination. To deal with heterogeneity, a stochastic modelling framework may be appropriate, emphasizing the more robust spatial and temporal moments. Examples of a combination of different field techniques for measuring subsoil properties and monitoring contaminants and integration through transport modelling are provided by the SoilCAM project and previous work. Commonly, the results of flow and contaminant fate modelling are quite detailed and complex and require post-processing before communication and advising stakeholders. The managers’ perspectives with respect to monitoring strategies and challenges still unresolved have been analysed with basis in experience with research collaboration with one of the case study sites, Oslo airport, Gardermoen, Norway. Both scientific challenges of monitoring subsoil contaminants in cold regions and the effective interaction between investigators and management are illustrated.     

Effects of dioxins and polychlorinated biphenyls (PCBs) on thyroid function in infants born in Japan – the second report from research on environmental health

Dioxins (PCDD + PCDF) and polychlorinated biphenyl (PCB) are potentially hazardous compounds and have structural similarity to thyroid hormones. Our research group on “Dioxins and PCB in Human Milk” was organized in 1997 and has been active for the past three years. We collected breast milk from 80 mothers living in Tokyo, Saitama, Ishikawa and Osaka Prefecture in Japan at 5, 30, 150, 300 postpartum days and measured PCDDs, PCDFs and PCBs during 1998–1999. We added another 20 prefectures and cities during 1999–2000. Breast milk was obtained from 415 mothers at 30 postpartum days (breast-feeding group). Blood was taken from infants who were breast-fed at the age of 1 year for evaluation of thyroid and immune functions. Blood was also taken from 53 infants who were bottle-fed (bottle-feeding group) as a control. Serum T4, T3, FT4 and TSH levels in the breast-feeding (n=337) and bottle-feeding (n=53) groups were within normal ranges and were not significantly different between the two groups. Although there were a large geographic differences of dioxins and co-PCB content in breast milk, there were no differences in serum T4, T3, FT4, TSH levels and no significant correlation between the mean serum levels of TSH and TEQ in breast milk. There was a significant correlation between serum TSH at 1 year of age and that from blood on dried filter paper TSH at 5 days of age. We concluded that dioxin intake from breast milk in Japanese infants did not impair thyroid function. However, long-term effects remain to be evaluated.     

Fate of PCDF/PCB congeners and change of clinical symptoms in patients with Yusho PCB poisoning for 30 years

Two mass-food poisonings called Yusho and Yucheng occurred in Japan and Taiwan in 1968 and 1979, respectively. Blood samples from five Yusho patients and three Yucheng patients were collected several times from 1982 to 1998 and from 1980 to 1995, respectively, and analyzed for polychlorinated dibenzofurans (PCDF) and polychlorinated biphenyls (PCB) congeners. Fat base concentrations of 2,3,4,7,8-penta-CDF in the Yusho patients, which were responsible for about 70% of the dioxin toxicity, are estimated to be decreased from 60 ppb in 1969 to 800 ppt in 1997 with the median half-life of 2.9 years in the first 15 years after onset and 7.7 years in the next stage of 15 years. Typical Yusho symptoms of acneiform eruption, dermal pigmentation and increased eye discharge were very gradually recovered with lapse of several years. However, enzyme and/or hormone-mediated signs of high serum triglyceride, high serum thyroxin, immunoglobulin disorder and others are persistently maintained for 30 years.     

Microbial and physicochemical parameters associated with Legionella contamination in hot water recirculation systems

Hot water recirculation systems (HWRS) in hotels and nursing homes, which are common in countries such as Spain, have been related to outbreaks of legionellosis. To establish the relationships of microbial and physicochemical parameters, especially protozoa, with the occurrence of Legionella in HWRS, 231 samples from hotels and nursing homes were analysed for Legionella, protozoa, heterotrophic plate counts (HPC) at 22 and 37 °C, Pseudomonas, metals, temperature and others. Legionella pneumophila was the dominant species isolated, and 22 % were sg. 1. The sampling method became particularly important in order to define which factors were involved on the occurrence of Legionella. Results showed that the bacteria and the accompanying microbiota were more abundant in the first flush water whose temperature was lower. The bacteria occurred in those samples with high HPC and were inversely correlated with high temperatures. Multivariate regression showed that a concentration above 1?×?10⁵?CFU/100 mL of HPC at 37 °C, Fe above 0.095 ppm and the presence of protozoa increased significantly the risk of Legionella colonization, while univariant regression showed that the presence of Cu above 0.76 ppm and temperature above 55 °C diminished it. Therefore, to reduce the risk associated with Legionella occurrence in HWRS these parameters should be taken into consideration.     

Concentrations of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and non-ortho and mono-ortho polychlorinated biphenyls in blood of Yusho patients

We measured the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), non-ortho polychlorinated biphenyls (non-ortho PCBs) and mono-ortho polychlorinated biphenyls (mono-ortho PCBs) in blood collected from 279 Yusho patients living in Japan, 92 Yusho-suspected persons living in Japan and 127 normal controls living in Fukuoka Prefecture, and compared among the groups in terms the concentrations of these compounds. The total toxic equivalents (TEQ) concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in the bloods of Yusho patients and Yusho-suspected persons were 161.4 and 51.2 pg TEQ/g lipid, respectively and were about 3.5 and 1.1 times higher than those of normal controls, respectively. Although the TEQ concentrations of PCDDs, non-ortho PCBs, and mono-ortho PCBs among Yusho patients, Yusho-suspected persons and normal controls were nearly the same, the PCDFs levels of Yusho patients were significantly higher than those of Yusho-suspected persons and about 10.3 times higher than those of normal controls. In Yusho patients, PCDFs contributed about 65% to the total TEQ concentration. Among the PCDFs congeners for Yusho patients, the concentration of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) was about 11.3 times higher than that of normal controls. These findings indicated that Yusho patients even now, more than 34 years after the outbreak of Yusho, have much higher blood levels of 2,3,4,7,8-PeCDF in general than do unaffected persons.     

Quantitative analysis of perfluorinated chemicals in media for in vitro fertilization and related samples

The actual standard in vitro fertilization (IVF) protocol recommends an overnight gamete co-incubation. All of the culture media used for human IVF are supplemented with serum or albumin. In the present study, we determined the concentrations of perfluorinated chemicals (PFCs) in IVF media (IVFM) and related samples by liquid chromatography with tandem mass spectrometry (LC/MS/MS). The results indicated that the concentrations of PFOS and PFOA in the protein source were higher than those in the IVFM samples. Compared with human plasma concentrations of PFCs, PFCs in all of the IVFM samples, such as PFBS, PFHxS and PFOA, were either not detected or present at only trace levels, even when protein source was added. LC/MS/MS could be used to determine PFCs in IVFM samples in future studies of the effects of PFC exposure on intrauterine insemination.