Association of maternal serum concentration of hydroxylated polychlorinated biphenyls with maternal and neonatal thyroid hormones: The Hokkaido birth cohort study.

Background: Evidence on the toxicity of hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) for thyroid hormones (TH) is limited, and the underlying mechanism remains unknown.

Objectives: We aimed to investigate the effects of environmental prenatal exposure to OH-PCBs and maternal and neonatal TH levels, taking the maternal-fetal TH transfer into account.

Methods: In this prospective birth cohort (the "Hokkaido study") we included 222 mother-neonate pairs.

Current state of yusho and prospects for therapeutic strategies.

The mass food poisoning incident yusho occurred in Japan in 1968. It was caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls and various dioxins and dioxin-like compounds including polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDFs). Notably, PCDFs were found to contribute to approximately 65% of the total toxicity equivalent in the blood of yusho patients.

Gender-specific association of exposure to non-dioxin-like polychlorinated biphenyls during pregnancy with methylation levels of H19 and long interspersed nuclear element-1 in cord blood in the Hokkaido study.

Background: Associations between prenatal exposure to polychlorinated biphenyls (PCBs) and reduced birth-size, and between DNA methylation of insulin-like growth factor-2 (IGF-2), H19 locus, and long interspersed nuclear element-1 (LINE-1) and reduced birth-size are well established. To date, however, studies on the associations between prenatal exposure to PCBs and alterations in methylation of IGF-2, H19, and LINE-1 are lacking. Thus, in this study, we examined these associations with infant-gender stratification.

Dioxin-metabolizing genes in relation to effects of prenatal dioxin levels and reduced birth size: The Hokkaido study.

Objectives: We investigated the effects of maternal polymorphisms in 3 genes encoding dioxin-metabolizing enzymes in relation to prenatal dioxin levels on infant birth size in Japan.

Methods: We examined the relationship between dioxin exposure and birth size in relation to the polymorphisms in the genes encoding aromatic hydrocarbon receptor (AHR [G>A, Arg554Lys]), cytochrome P450 (CYP) 1A1 (T6235C), and glutathione S-transferase mu 1 (GSTM1; Non-null/null) in 421 participants using multiple linear regression models.

Results: In mothers carrying the GSTM1 null genotype, a ten-fold increase in total dioxin toxic equivalency was correlated with a decrease in birth weight of -345g (95% confidence interval: -584, -105).

Effect of colestimide on the concentrations of polychlorinated dibenzo-p-dioxins, polychlorinated dizenzofurans, and polychlorinated biphenyls in blood of Yusho patients.

Background: Oral colestimide was reported to lower the concentration of PCDDs, PCDFs, and PCB in the blood of humans. A pilot study showed that the arithmetic mean total TEQ concentrations of PCDDs, PCDFs, and PCBs in the blood of subjects after the trial decreased approximately 20 % compared to pre-trial levels, suggesting that colestimide could decrease human dioxin levels. We designed the current clinical trial study based on this information.

A Study on Polychlorinated Biphenyls Specifically--Accumulated in Blood of Yusho Patients Collected from Medical Check-Ups in 2012.

In this study, we analyzed polychlorinated biphenyls (PCBs) in the blood of Yusho patients collected from medical check-ups, which were conducted in 2012. The results show that 65 PCB isomers, not including non-ortho PCBs, were detected in the blood samples, and the total concentration was 620 ng g(-1) lipid. This value was comparable to the concentration in blood samples collected in 2005, and indicated that PCB concentrations in Yusho patients remained unchanged from 2005 to 2012.

[The Distribution of Dioxin Concentrations in the Blood of Yusho Patients].

In 1968, the contamination of cooking oil by heat-degraded polychlorinated biphenyls (PCBs) caused a case of mass poisoning, the so-called Yusho incident. The cause of Yusho disease is thought to be ingested toxic substances, including not only PCBs but also polychlorinated dibenzofuran (PCDFs) in Kanemi rice oil. We previously measured dioxins concentrations in the blood of 854 Yusho patients by annual medical examination from 2001 to 2013.

Effects of in utero exposure to polychlorinated biphenyls, methylmercury, and polyunsaturated fatty acids on birth size.

The adverse effects of in utero exposure to polychlorinated biphenyls (PCBs) or methylmercury (MeHg), and the beneficial effects of nutrients from maternal fish intake might have opposing influences on fetal growth. In this study, we assessed the effects of in utero exposure to PCBs and MeHg on birth size in the Japanese population, which is known to have a high frequency of fish consumption. The concentrations of PCBs and polyunsaturated fatty acids in maternal blood, and the total mercury in hair (as a biomarker of MeHg exposure) were measured during pregnancy and at delivery.

Demographic, behavioral, dietary, and socioeconomic characteristics related to persistent organic pollutants and mercury levels in pregnant women in Japan.

Persistent organic pollutants and mercury are known environmental chemicals that have been found to be ubiquitous in not only the environment but also in humans, including women of reproductive age. The purpose of this study was to evaluate the association between personal lifestyle characteristics and environmental chemical levels during the perinatal period in the general Japanese population. This study targeted 322 pregnant women enrolled in the Hokkaido Study on Environment and Children's Health.

Concentration of hydroxylated polychlorinated biphenyls (OH-PCBs) in the blood of Yusho patients in 2010.

Hydroxylated polychlorinated biphenyls (OH-PCBs) are formed as major metabolites of PCBs by cytochrome P450 enzyme-mediated oxidation. It has been reported that their total concentration in serum samples of Yusho patients ranged from 390 to 1300 pg/g. We measured the concentration of OH-PCBs in blood collected from 183 Yusho patients living in Japan in 2010.

Improvement of measurement method for hydroxylated polychlorinated biphenyls (OH-PCBs) in blood samples using LC/MS/MS.

Hydroxylated polychlorinated biphenyls (OH-PCBs) are well known as metabolites of PCBs in the human body. We improved a measurement method for OH-PCBs in blood samples using LC/MS/MS. A new 2 microm particle column was used, and the analytical conditions for the LC/MS/MS measurements were optimized.

The changes in dioxin concentrations in the blood of Yusho patients from 2004 to 2010.

We measured the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) in blood collected from Yusho patients during medical health examinations performed from 2004 to 2010. Out of the 242 and 200 Yusho patients who received medical health examinations in 2004 and 2010, respectively, the concentrations of PCDDs, PCDFs, and PCBs in the blood of 136 patients were measured in both of those years. The concentrations of individual congeners of PCDDs, PCDFs, and PCBs in the blood of these 136 Yusho patients measured in 2004 were compared with those measured in 2010.

Development of a newly large-volume injection system for dioxin determinations in blood of Yusho patients.

We developed a more effective method to measure the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and non-ortho-coplanar polychlorinated biphenyls (non-ortho PCBs) in the blood of Yusho patients using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS) equipped with a newly large-volume injection system. The new injection system linked a LaviStoma system with a unique stomach-shaped inlet liner (SSIL) and a solvent-cut large-volume (SCLV) injection system. This approach made it possible to introduce volumes up to 200 microl into the HRGC/HRMS in comparison with the 20microl volume of the previously reported conventional SCLV method.

[Inter-laboratory crosscheck study of dioxins and PCBs in human blood samples].

We developed an analytical method for accurately determining the concentrations of dioxin and polychlorinated biphenyls(PCBs) in a blood volume of 5 g. Inter-laboratory crosscheck is available for maintaining the quality of dioxin and PCB analysis. We carried out the crosschecks of dioxin and PCB analysis in the blood with domestic analysis organizations.

Individuals' half-lives for 2,3,4,7,8-penta-chlorodibenzofuran (PeCDF) in blood: correlation with clinical manifestations and laboratory results in subjects with Yusho.

Background: In 1968, many people developed dioxin poisoning (Yusho) in Japan. Ingestion of 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PeCDF) was considered to be the cause of this poisoning. Although some patients had high concentrations of 2,3,4,7,8-PeCDF in their blood, individuals' half-lives of 2,3,4,7,8-PeCDF were long.

Genetic association of aromatic hydrocarbon receptor (AHR) and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) polymorphisms with dioxin blood concentrations among pregnant Japanese women.

Dioxins are metabolized by cytochrome P450, family 1 (CYP1) via the aromatic hydrocarbon receptor (AHR). We determined whether different blood dioxin concentrations are associated with polymorphisms in AHR (dbSNP ID: rs2066853), AHR repressor (AHRR; rs2292596), CYP1 subfamily A polypeptide 1 (CYP1A1; rs4646903 and rs1048963), CYP1 subfamily A polypeptide 2 (CYP1A2; rs762551), and CYP1 subfamily B polypeptide 1 (CYP1B1; rs1056836) in pregnant Japanese women. These six polymorphisms were detected in 421 healthy pregnant Japanese women.

Concentrations of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and polychlorinated biphenyls in blood and breast milk collected from pregnant women in Sapporo City, Japan.

We measured the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (PCBs), and non-dioxin-like PCBs in paired samples of blood and breast milk collected from 67 secundiparas in Sapporo City, Japan, and combined this data with those of the 30 secundiparas previously measured. The arithmetic mean total toxic equivalents (TEQ-WHO) concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in blood and breast milk of the 97 secundiparous subjects were 3.0-23 (mean: 13, median: 14) and 2.

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.

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.

[The difference between male and female dioxin concentrations in the blood of Yusho patients].

In 1968, the contamination of cooking oil by heat-degraded polychlorinated biphenyls (PCBs) caused a case of mass poisoning, the so-called Yusho incident. The cause of Yusho disease is thought to be ingested toxic substances, including not only PCBs but polychlorinated dibenzofuran (PCDFs) in Kanemi rice oil. Extensive studies have been performed since 1995 by the Yusho study group involving follow-up surveys of human blood concentrations of the casual compounds in Yusho patients as well as clinical trials of the acceleration of the excretion of these compounds in Yusho patients.

[Promotive excretion of causative agents of Yusho by fermented brown rice with Aspergillus oryze in Yusho patients].

Forty two years have passed since the outbreak of Kanemi rice oil poisoning, namely, Yusho in the western Japan. However, even now the Yusho patients have been still suffering from several objective and subjective symptoms. In order to improve or, if possible, to cure such symptoms, the most important therapeutic treatment is considered to actively excrete the causative agents, that is, polychlorinated dibenzofurans (PCDFs) from the bodies of the patients and to reduce their body burdens.

[Time serial changes in the concentrations of the related agents to fetal Yusho--dioxin-like PCBs and PCBs].

We determined dioxin-like polychlorinated biphenyls (PCBs) and PCBs in 6 preserved umbilical cords of fetal Yusho patients and in 11 preserved umbilical cords of Yusho suspected persons who were born to mothers with Yusho from 1970 to 2002, which were Yusho group. As a control, we also analyzed dioxin-like PCBs and PCBs in 15 preserved umbilical cords of babies who were born to healthy mothers, which was healthy group, in the same period of time. As a result, concentrations of three dioxin-like PCBs, that is, #156, #157 and #189 which were 6 to 20 times higher in fetal Yusho patients than in healthy babies were still 4 to 6 times greater in Yusho group than in healthy group about 20 years after the outbreak of Yusho, but could not recognize this characteristic anymore about 30 years after the outbreak.

[Time serial changes in the concentrations of the etiological agents of fetal Yusho--PCDDs and PCDFs].

We determined polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzo-p-dioxins (PCDDs) in 6 preserved umbilical cords of fetal Yusho patients and in 11 preserved umbilical cords of Yusho suspected persons who were born to mothers with Yusho from 1970 to 2002, which were Yusho group. As a control, we also analyzed PCDFs and PCDDs in 15 preserved umbilical cords of babies who were born to healthy mothers, which was healthy group, in the same period of time. As a result, 2,3,4,7,8-pentachlorodibenzofuran and 1,2,3,4,7,8-hexachlorodibenzofuran, true causal agents of fetal Yusho, were only determined in the umbilical cords of fetal Yusho patients, except for one umbilical cords of Yusho suspected persons.

[Relationship between half-lives of blood dioxins and possible metabolic mechanism].

Blood levels of dioxins in Yusho patients have been measured for 10 years. The purposes of this study were to determine the half-lives of dioxins on the basis of the data obtained from Yusho patients and to compare the half-lives of the compounds. Linear regression analysis was performed using the binary logarithmic value of each dioxin level as the dependent variable and the year of measurement as the independent variable.

Measurement method for hydroxylated polychlorinated biphenyls in the blood of Yusho patients by liquid chromatography-electrospray tandem mass spectrometry.

Hydroxylated polychlorinated biphenyls (OH-PCBs) are formed as major metabolites of PCBs by cytochrome P450 enzyme-mediated oxidation. It has been reported that their total concentration in serum samples of Yusho patients ranged from 390 to 1300 pg/g. We developed a measurement method for OH-PCBs in blood samples by LC/MS/MS.