[Analysis of residual nature of dioxins in blood of Yusho patients and controls in relation to the Yusho oil and food as respective exposure routes].

In this study, we examined the dioxin levels and congener distributions in blood samples of Yusho patients and normal control subjects, especially in relation to the respective exposure routes. Remarkable differences were observed between the blood of Yusho patients and general population in terms of both congener distributions and concentration levels. Cumulative dioxin intake for Yusho patients was estimated using the mean Yusho oil consumption and congener-specific dioxin contamination data for Yusho oil; for control subjects, it was estimated from food consumption and dioxin congener contamination data. Estimated total intake of dioxins was 2.44 microg-TEQ for control subjects and 357 microg-TEQ for Yusho patients, respectively. The total intake of some congeners such as 2,3,4,7,8-PeCDF and 1,2,3,4,7,8-HxCDF for Yusho patients was more than 100 times higher than those of control subjects. The congener distribution of PCB and PCDD in the blood of control subjects was similar to those of the food. In the case of Yusho patients, however, the congener distribution did not resemble those of either the food or the causal Kanemi rice oil, nor did not match that of control subjects' blood. Selective metabolizing of congeners was suggested to have occurred in the Yusho patients. In a 2001 fiscal year survey, the concentration ratio of TEQ between Yusho and normal subjects was 4.5. However, the level of 2,3,4,7,8-PeCDF, thought to be the congener that had the closest relation to various symptoms of the Yusho patients, was ten times or more in Yusho patients than in controls. It is suggested that further examinations should be conducted in the future to follow up this survey monitoring the blood levels of toxic congeners in Yusho patients.

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.

Immunologic effects of perinatal exposure to dioxins, PCBs and organochlorine pesticides in Japanese infants.

Effects of perinatal exposure to dioxins, PCBs and organochlorine pesticides on lymphocyte subsets were investigated in the peripheral blood from 101 Japanese infants with approximately 10 months of age. Perinatal exposure to these organochlorine compounds were estimated by their contamination levels in the breast milk of the mothers. Lymphocyte subsets such as CD16+, HLA-DR+, CD4+, CD4+8+, CD8+, CD3+ and CD20+ cells in peripheral venous blood were assessed in a subgroup of 92 infants. Greater exposures to HCE, chlordane and dioxins were significantly associated with the increase in the percentages of CD8+ and CD3+ T lymphocytes and CD4+/CD8+ T cell ratios, respectively. In addition, higher HCH exposure was also associated with a decrease in the percentage of HLA-DR+ T lymphocytes. Furthermore effects of dioxins, DDT and PCBs on the percentage of CD16+ T lymphocyte were more pronounced by the combined exposure of dioxins and PCBs or by the combined exposure of DDT and PCBs. Effects of HCE on the percentages of CD8+ T lymphocyte were also more pronounced by the combined exposure of HCE and chlordane. In conclusion, our study suggests that greater exposures to dioxins, PCBs and organochlorine pesticides determined in this study (except dieldrin) influence the immune system of Japanese infant, although the clinical significance of these changes is uncertain.

[Follow-up survey of dioxins in the blood of Yusho patients (in 2001)].

Follow-up survey of the blood concentration of polychlorinated dibezo-p-dioxin (PCDDs), polychlorinated dibenzofuran (PCDFs), Non-ortho-coplaner PCBs (Non-Co-PCB), and Mono-ortho-coplaner PCBs (Mo-Co-PCB) in Yusho patients is very important for their health control. We determined the blood concentration of these dioxin-like isomers in 78 blood samples collected in 2001 using by a high-resolution gas chromatograph/high-resolution mass spectrometer (HRGC/HRMS) equipped with a solvent-cut large volume injection system (SCLV). The accelerated solvent extraction (ASE) method was employed for the treatment of blood samples. The method employed here can allow a reduced amount of blood collecting from Yusho patients compared with the conventional method. In typical Yusho patients (Group A of PCB pattern), the mean TEQ concentrations of PCDDs, PCDFs, Non-Co-PCBs, and Mono-Co-PCBs in blood collected in 2001 were 36, 260, 9.3, and 64 pg-TEQ/g lipid, respectively. As well, the toxic contribution of PCDDs, PCDFs, Non-Co-PCBs, and Mono-Co-PCBs in typical Yusho patients (Group A of PCB pattern) were 10, 70, 3, and 17% of the total TEQ value, respectively. The toxic contribution rate of PCDFs TEQ was still at high levels in relation to total TEQ in typical Yusho patients as mention above. The Yusho patients showing B pattern also had the same A pattern contribution rate. In the patients of group C, however, the mean blood levels of dioxin TEQ in 2001 was two times those of the normal controls determined in 2000 in Fukuoka prefecture. As well, the contribution rates were similar to those of normal subjects, although some patients in this group showed a high toxic contribution rate of PCDFs TEQ in relation to total TEQ. Thirty-three years had passed since the Yusho accident, and the total blood concentrations of PCDFs in the blood of Yusho patients were still higher than those of normal subjects. Among the different groups of PCB patterns, the concentration of 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF and 1,2,3,6,7,8-HxCDF showed significant differences. These findings indicate that these isomers are not metabolized in the human body since traces of them continued to be detected in these patients since they had been contaminated by the rice oil in the original incident.

Frequency of SCEs in Japanese infants exposed to dioxins and PCBs through the breast milk.

Frequency of sister chromatid exchanges (SCEs), which has been considered an index to the synthetic and sharp genotoxic and clastogenic potencies, was examined by using the infant lymphocytes postnatal of around ten months, in order to evaluate the genotoxic or clastogenic potency of exposures to PCBs and dioxins through the breast milk. SCE frequency (mean +/- S.D.) as the control culture treated with the solvent, DMSO, alone (SCEcontrol) was 8.3 +/- 1.1/cell and that as the culture treated with 7,8-benzoflavone (SCEANF) was 11.9 +/- 1.5/cell. In addition, the difference between SCEANF and SCEcontrol, that is, delta SCEs was calculated 3.6 +/- 1.5/cell. The intake of PCBs (mean +/- S.D.) through the breast milk in these infants was 133 +/- 85 mg/kg body weight and that of dioxins 24 +/- 13 TEQ-ng/kg body weight. PCBs intake in the average was about 5,500 times greater than that of dioxins. We however, could not find any significant effect of PCBs on the frequencies of SCEs. Dioxins, on the contrary, showed a significant negative relationship to the frequency of delta SCEs. Therefore, exposure to dioxins through the breast milk seemed to elicit some genotoxic or clastogenic effects on Japanese general infants postnatal of around ten months.

Frequency of SCEs in Japanese infants lactationally exposed to organochlorone pesticides.

Changes in the frequency of sister chromatid exchanges (SCEs) in cultured mammalian cells have been considered as indices to the synthetic and sharp genotoxic and clastogenic potencies. Frequency of SCEs in cultured lymphocyte obtained from infants postnatal of around ten months was examined to evaluate the genotoxic or clastogenic potency of lactational exposures to some organochlorine pesticides such as HCHs, DDT and chlordane in this study. Frequency (median, min.-max.) of SCEs as the control culture treated with the solvent, DMSO, alone (SCE control) was 8.0/cell, 6.5-12.4/cell, that as the culture treated with 7,8-benzoflavone (SCEANF) was 11.8/cell, 9.1-15.6/cell and the difference between SCEANF and SCEcontrol, that is, delta SCEs was 3.9/cell, 0.2:7.2/cell. Lactational exposures (median, min.-max.) to the three organochlorine pesticides were as follows: HCHs; 341 mg/kg body weight, 43-1449 mg/kg body weight, DDT; 272 mg/kg body weight, 33-1361 mg/kg body weight and chlordane; 69 mg/kg body weight, 13-379 mg/kg body weight. The median exposure level to chlordane through the breast milk was one fourth to one fifth times lower than that to HCHs or DDT and probably due to such small amounts of it's intake, we could not find any correlation of chlordane with frequencies of SCEcontrol, SCEANF and delta SCEs in cultured lymphocytes of Japanese infants postnatal of about ten months. In the meantime, frequencies of SCEcontrol and SCEANF showed increasing and decreasing tendencies with the increasing exposure to DDT and also HCHs through the breast milk. In consequence, the frequency of delta SCEs was significantly lowered. Therefore, lactational exposure to DDT and HCHs seemed to elicit some genotoxic or clastogenic effects on Japanese general infants at ages of around the months. These compounds were also considered rather potent S-dependent clastogens than non-S-dependent ones. So, further detailed studies are needed not only to get conclusive findings but also from this viewpoint.