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. Lipophilic dioxins are retained in the body for a longer period than previously estimated. Victims suffered from characteristic skin manifestations associated with non-specific systemic symptoms, neurological symptoms, and respiratory symptoms. The severe symptoms seen in the initial phase subsequently faded, but recently, improvements have scarcely been observed. The Yusho Group has been researching treatments for this condition. Several clinical trials with chelating agents or dietary fibers aimed at accelerating the excretion of compounds. While some treatments increased dioxin excretion, none provided satisfactory symptom relief. Concurrently, various phytochemicals and herbal extracts have been found to possess biological activities that suppress dioxin-induced toxicity via aryl hydrocarbon receptor or activate the antioxidant nuclear factor-erythroid 2-related factor-2 (NRF2) signal pathway, making them promising therapeutic candidates. Here, we summarize the current status of yusho and findings of clinical trials for yusho patients and discuss the treatment prospects.
We conducted congener-specific analysis of non-dioxin-like polychlorinated biphenyls (non-dioxin-like PCBs) in blood collected in February 2004 from 127 elderly residents living in Nakagawa Town, Fukuoka Prefecture, Japan. The present study is one of the few studies in which 56 non-dioxin-like PCBs congeners were measured in human blood. Of the 127 elderly residents, 51 were men (mean: 68.1 years) and 76 were women (mean: 68.1 years). Among 197 non-dioxin-like PCB congeners, 56 were identified in the blood of elderly residents. The arithmetic mean total concentrations of 56 non-dioxin-like PCBs congeners in the blood of elderly men and women in Nakagawa Town were 419 (median: 378) and 363 (median: 323)ngg(-1)lipid, respectively, and the concentrations were in the range of 172-1102 and 119-1226ngg(-1)lipid, respectively, indicating that the total concentrations in elderly men are significantly higher than those in elderly women. The contamination of non-dioxin-like PCBs in the blood of elderly men and women in Fukuoka Prefecture was found to have decreased compared to past levels. The ratios of hexachlorinated biphenyls (hexaCBs) to the total concentrations of 56 non-dioxin-like PCBs congeners in the blood of elderly men and women were 44.6% and 45.6%, respectively, which was particularly high compared with those of other congeners. 2,2',4,4',5,5'-HexaCB (#153) among hexaCBs congeners, the most abundant congener in the blood of elderly men and women, contributed approximately 23.0% and 23.5% to the total concentrations of 56 non-dioxin-like PCBs congeners, respectively. Furthermore, 2,2',3,4,4',5'-hexaCB (#138), 2,3,3',4',5,6-hexaCB (#163)/2,3,3',4',5',6-hexaCB (#164), 2,2',3,4,4',5,5'-heptaCB (#180), and 2,2',3,4,4',5,6'-heptaCB (#182)/2,2',3,4',5,5',6-heptaCB (#187) also showed high ratios to the total concentrations of 56 non-dioxin-like PCBs congeners detected in the blood of elderly men and women. A statistical examination of the relationship between the total concentrations of 56 non-dioxin-like PCBs congeners in blood and the age of elderly residents who were over 60 years indicated statistically significant correlations between the total concentrations of these PCBs congeners and the age of elderly women. However, similar correlations were not observed in elderly men. The results of the present study have indicated the current levels of non-dioxin-like PCBs in the blood of elderly men and women in Fukuoka Prefecture, Japan and can be used as baseline data for those over age 60. 相似文献
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 paired samples of blood and breast milk collected from 60 mothers in Sapporo City, Hokkaido Prefecture, Japan. The present study is one of the few studies in which PCDDs, PCDFs, and dioxin-like PCBs have been measured in blood and breast milk collected from 60 same mothers. Of these 60 mothers, 30 were primipara (mean: 30.1 years, median: 28.0 years) and 30 were multipara (mean: 32.2 years, median: 32.5 years). The arithmetic mean TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in blood and breast milk of the primiparous mothers were 9.0, 3.3, 5.7, and 0.4 pg TEQ g(-1) lipid, respectively, and 5.2, 2.2, 4.5, and 0.4 pg TEQ g(-1) lipid, respectively, with the total TEQ concentrations of these dioxin-like compounds being 9.3-42.9 (mean: 18.4, median: 17.3) and 7.0-41.1 (mean: 12.3, median: 11.4) pg TEQ g(-1) lipid, respectively. In the case of multiparous mothers, the arithmetic mean TEQ concentrations of these dioxin-like compounds in blood and breast milk were 7.1, 2.7, 5.3, and 0.4 pg TEQ g(-1) lipid, respectively, and 3.9, 1.7, 3.8, and 0.4 pg TEQ g(-1) lipid, respectively, with the total TEQ concentrations being 3.4-28.1 (mean: 15.5, median: 13.9) and 2.7-20.0 (mean: 9.8, median: 9.2)pg TEQ g(-1) lipid, respectively. The total TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in blood and breast milk of primiparous mothers in Sapporo City appeared to be generally lower than those recently surveyed throughout the greater area of Japan. Significant correlations were observed between age and the total TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in the blood of primiparae and multiparae, and significant correlations were also observed between age and the total TEQ concentrations of these dioxin-like compounds in the breast milk of primiparae and multiparae. The total TEQ concentrations of PCDDs, PCDFs, and dioxin-like PCBs in the blood of primiparous mothers showed a close correlation to those in their breast milk and also showed good correlations between the total TEQ concentrations of these dioxin-like compounds in the blood of multiparous mothers and those in their breast milk. The result of a comparison of the arithmetic mean concentrations of each congener of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in blood and breast milk indicated that the transfer of octachlorodibenzo-p-dioxin (OCDD) from the blood to the breast milk was lower than those of other congeners. In contrast, among mono-ortho PCBs congeners, the arithmetic mean concentrations of 2,3',4,4',5-pentachlorobiphenyl (PentaCB) (#118) and 2,3,3',4,4'-PentaCB (#105) in the breast milk were slightly higher than those in the blood, which suggested that breast-fed infants may be at higher risk from mono-ortho PCBs. 相似文献
We conducted a congener-specific analysis of non-dioxin-like polychlorinated biphenyls (non-dioxin-like PCBs) in blood collected between July 2002 and July 2004 from 195 pregnant women living in Sapporo City of Hokkaido Prefecture, Japan. The present study is one of the few studies in which full congener concentrations of non-dioxin-like PCBs have been measured in the blood of pregnant women. Of the 195 pregnant women, 101 were primipara (mean: 28.8 years, median: 28.0 years) and 94 were multipara (mean: 32.3 years, median: 33.0 years). Among the 197 non-dioxin-like PCB congeners, 58 congeners were identified in the blood of pregnant women. The arithmetic mean total concentrations of 58 non-dioxin-like PCB congeners in the blood of primiparous and multiparous mothers in Sapporo City were 42.2-329.3 (mean: 114.5, median: 98.6) and 31.5-258.0 (mean: 100.3, median: 91.4)ngg(-1)lipid, respectively. The results show that the contamination of non-dioxin-like PCBs in the blood of women has decreased compared to past levels in other domestic areas, in which the subject age was similar to that in this study. The results of the present study indicate that current levels of non-dioxin-like PCBs in the blood of Japanese women and can be used as baseline data for future temporal trends. The sums of the ratios of the concentrations of hexaCBs and heptaCBs to the total concentrations of 58 non-dioxin-like PCB congeners in the blood of primiparous and multiparous mothers were 78.5% and 77.7%, respectively. The hexaCBs ratios in the blood of primiparous and multiparous mothers were 45.4% and 44.7%, respectively. HexaCB-153 among hexaCBs congeners, the most abundant congener in the blood of primiparous and multiparous mothers, contributed approximately 22.0% and 21.8% to the total concentrations of 58 non-dioxin-like PCBs congeners that were measured in the blood, respectively. Among the non-dioxin-like PCB congeners measured in the present study, hexaCB-138, heptaCB-170, heptaCB-180, and heptaCB-182/heptaCB-187 also showed high ratios to total concentrations of 58 non-dioxin-like PCB congeners detected in the blood of primiparous and multiparous mothers. With regard to the relationship between the total concentrations of 58 non-dioxin-like PCB congeners in maternal blood and the number of deliveries or the age of primiparous and multifarious mothers, the total levels of these PCB congeners tended to decreases with increases in the number of deliveries and significantly increased with increasing maternal age in both groups. Furthermore, significant correlations were observed between the total concentrations of these PCB congeners in blood and the age of primiparae and multiparae. The concentrations of hexaCB-153 in the blood of primiparous and multiparous mothers showed a close correlation to the total concentrations of these PCBs, suggesting that hexaCB-153 could be an indicator of total concentrations of non-dioxin-like PCB congeners in the blood of pregnant women. 相似文献
Compound-specific isotope analysis (CSIA) can be used to examine the source and transformation processes of organic pollutants in the environment. We performed a carbon stable isotope analysis of polychlorinated biphenyl (PCB) congeners in the PCB heat-transfer medium (heat medium) and the original Kanechlor-400 (KC-400, a commercial brand of PCBs) involved in the Yusho incident. The main purpose is to investigate whether isotope fractionation occurred in the rice oil deodorization process that caused the incident. The carbon isotope ratios (δ13C values) of the targeted PCB congeners ranged from ? 29.39 to ? 27.00‰ in the heat medium and from ? 28.77 to ? 27.05‰ in the original KC-400. No significant differences were found in the δ13C values, suggesting carbon isotope fractionation did not occur for the targeted PCB congeners in the heat medium when deodorization of rice oil occurred at temperatures above 200 °C. Furthermore, we also conducted a congener-specific analysis of 64 PCB congeners found in the heat medium and rice oil contaminated by it. The total PCB congener concentrations were 503 mg/g in the heat medium and 81 μg/g in the rice oil. The concentrations of the highly chlorinated congeners were significantly lower in the heat medium than in the original KC-400, and the compositional ratios of the lowly chlorinated congeners were relatively lower in the rice oil than in the heat medium. These results suggest that the PCB congener patterns gradually changed from that of the original KC-400 in the deodorization process and subsequent contamination into the rice oil. Thus, a combination of CSIA and congener-specific analysis is a new approach for investigating the changing PCB congener profiles in samples from the Yusho incident. 相似文献
We measured the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), non-ortho coplanar polychlorinated biphenyls (non-ortho PCBs), and mono-ortho coplanar polychlorinated biphenyls (mono-ortho PCBs) in blood collected between 2002 and 2004 from 195 pregnant women living in Sapporo City of Hokkaido Prefecture, Japan. The present study is one of the few studies in which PCDDs, PCDFs, and dioxin-like PCBs have been measured in the blood of pregnant women. Of the 195 pregnant women, 101 were primipara (mean: 28.8 years) and 94 were multipara (mean: 32.4 years). The arithmetic mean total TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs of primiparous and multiparous mothers in Sapporo City were 17.4 (median: 15.7) and 14.0 (median: 13.9)pgTEQ/glipid, respectively, and the concentrations were in the range of 6.6-43.4 and 3.4-28.2pgTEQ/glipid, respectively. In regard to the relationship between the total TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in maternal blood and the number of deliveries or age of primiparous and multiparius mothers, the levels of these dioxin-like compounds tended to decrease with increases in the number of deliveries and significantly increased with increasing maternal age in both groups. Furthermore, significant correlations were observed between the total TEQ concentrations of these dioxin-like compounds and the age of primiparae and multiparae. The total TEQ concentration of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs measured in 195 pregnant women has decreased compared to past levels in Japan for the last several decades. The results of the present study have indicated that dioxin contamination in the blood of young women in Japan is continuing to decrease. 相似文献
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 2.7-20 (mean: 8.6, median: 8.5) pg TEQ g−1 lipid, respectively. The sums of the concentrations of 56 non-dioxin-like PCB congeners that were measured in the subjects’ blood and breast milk were 16-326 (mean: 107, median: 100) and 12-252 (mean: 73, median: 67) ng g−1 lipid, respectively. The partitioning ratios of individual congeners of PCDDs, PCDFs, dioxin-like PCBs, and non-dioxin-like PCBs from blood to breast milk in secundiparas were almost the same as those of primiparas that have been recently reported, suggesting that the partitioning ratios of these compounds from maternal blood to breast milk in women is little affected by delivery. Furthermore, the partition of PCB congeners with chlorine at the 2-, 3-, 4′-, and 5-positions or the 2-, 4-, 4′-, and 5-positions of the biphenyl ring from the blood to the breast milk tended to occur at a higher level than that of other congeners. In particular, the levels of tetraCB-74 and hexaCB-146 in the breast milk for both primiparous and secundiparous mothers were slightly higher than those in the blood. 相似文献
In what has become known as the Yusho incident, thousands of people in western Japan were poisoned by the accidental ingestion of rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds. In this study, we investigated the accumulation patterns of 69 PCB congeners in the blood of Yusho patients in comparison with those of non-exposed controls. The blood samples were collected at medical check-ups in 2004 and 2005. To compare the patterns of PCB congeners, we calculated the concentration ratio of each congener relative to the 2,2′,4,4′,5,5′-hexaCB (CB153) concentration. The concentration ratios of tetra- and penta-chlorinated congeners in the blood of Yusho patients were significantly lower than those of controls. To examine the cytochrome P450 (CYP)-dependent metabolic potential of the 2,3′,4,4′5-pentaCB (CB118), CB153, and 2,3,3′,4,4′5-hexaCB (CB156) congeners, we conducted PCB-CYP (CYP1A1, CYP1A2, CYP2A6, and CYP2B6) docking simulation by in silico analysis. The docking models showed that human CYP1A1, CYP2A6, and CYP2B6 isozymes have the potential to metabolize CB118 and CB153. On the other hand, it was inferred that CB156 is difficult to be metabolized by these four CYP isozymes. These results indicate that CYP1 and CYP2 isozymes may be involved in the characteristic accumulation patterns of PCB congeners in the blood of Yusho patients. 相似文献