[Toxic effects of PCB/PCDF to human observed in Yusho and other poisonings].

Yusho PCB poisoning occurred in 1968, when the human environment had been polluted with PCBs and related compounds. The causal rice oil was contaminated with large amounts of PCBs and PCDFs by accidental leakage at the rice oil producing Kanemi Company on February 7-15, 1968. Much less concentrations of PCBs were identified in the rice oil produced and shipped from the Company before and after the critical days. Concentration trend of PCBs and TEQ in human body were examined for 40 years from 1968 to present. Concentrations in the blood of heavily exposed Yusho patients and normal Japanese were PCBs : 80 and 1.5 microg/g-fat, and TEQ : 60 and 0.1 ng/g-fat, respectively, in 1969, and decreased to PCBs : 1 and 0.2 microg/g-fat, and TEQ : 0.5 and 0.02 ng/g-fat, respectively, in 2007. PCBs and PCDFs have been persistently retained in human body for 40 years. Serious cases of Yusho and Yucheng having very high PCB, PCDF concentrations in blood have suffered from severe chloracne, pigmentation, eye discharge and others at the first stage and recovered very slowly with a lapse of several years. However, their hormone mediated signs and symptoms, such as high triglyceride and thyroxin levels in serum, disorder of immunoglobulin, goiter, decrease of sperm mobility, disorder of teeth and joints conditions, decrease of IQ score in children, headache and numbness, etc, are persisting for more than 30 years. The residents in East Slovakia who have been exposed to PCBs wasted from a PCB factory and have about 3 times higher blood PCB concentrations than the controls, have suffered from disorder of FT4 and T3 levels in serum, disorder of thyroid grand and thymus, dental defects in enamel developmental, hearing impairment at low frequency tone, tendency to diabetes and others. Residents in the Great Lakes area, USA, whose blood PCB levels are estimated to be higher than other places, have shown disorder of thyroid, T4, TSH levels, endometriosis, joint disorder, and low IQ score in children. The levels of PCBs and PCDFs in the blood of Yusho patients and Controls are compared to the normal levels of estradiol, testosterone and thyroxin. In the blood of Yusho patients, concentrations of single congeners of PCB118, PCB153, PCB156 and PentaCDF are high enough to disturb the hormonal effects. Blood PCB concentrations in normal Japanese are higher than the FT3 and FT4 levels, indicating hormonal disturbance will be easily produced. PCBs are metabolized to produce HO-PCBs, which bind to TTR and retain in blood medium. Blood HO-PCB concentrations in Yusho patients and normal persons are higher than the FT3, FT4 levels in serum. Therefore, the hormonal effects of thyroxin will be disturbed in Yusho and normal persons. As HO-PCB will be easily transferred to fetus through placenta, fetus development will be possible to be disturbed. In Yusho and other cases, PCBs and TEQ (PentaCDF, PCB118 etc) were ingested together and the strong enzyme inducers of PentaCDF and others have metabolized PCBs to HO-PCBs, which have retained in the blood. Complex reactions of PCDFs, PCBs and HO-PCBs have disturbed the hormonal effects and the induced symptoms and diseases would have been caused.

[Trend of PCB/PCDF concentrations in the blood of Yusho patients for 38 years after the incidence].

Concentrations of 2,3',4,4',5-pentaCB (PCB118), 2,2',4,4',5,5'-hexaCB (PCB153), 2,3,3',4, 4',5-hexaCB (PCB156) and total PCB congeners (PCBs) in the blood of Yusho patients, surveyed by the annual medical examination in Fukuoka Prefecture, have been gradually decreased from 1974 (7 ppb) to 2006 (3 ppb). The patients are classified into 3 types of Yusho, namely, Yusho A: having typical Yusho gas chromatogram (GC) pattern, Yusho B: between Yusho A and Yusho C, and Yusho C: having GC pattern similar to those of Controls. The concentrations of PCB153, PCB156 and PCBs in the blood of Yusho A were higher than those of Yusho B and Yusho C in order. However, the concentrations of PCB118 in the blood of Yusho A were lower than those of Yusho B and Yusho C in order. Simple correlation coefficients between the concentrations of PCB118, PCB153, PCB156 and PCBs in the blood of Yusho patients and their ages at the blood sampling were examined from 1974 to 2006. The significant correlations were rather rare among them from 1974 to 1991, increasing number to 2000, and finally almost all to 2006, as observed in the blood of Fukuoka Controls in 1999 in which all the correlations are significant. However, the correlation coefficients between the concentrations of PCB118 and PCB156 in the blood of Yusho patients have been insignificant throughout from 1974 to 2006 with a few exceptions. By the use of the data of 3 Taiwan Yucheng patients and 5 Fukuoka Yusho patients, chronological concentrations of PCB118, PCB153, PCB156, 2,3,4,7,8-pentaCDF (23478F) and 1,2,3,4,7,8-hexaCDF (123478F) in the blood of Yusho patients were figured out from the outbreak of the poisoning to the present for 38 years. Very high concentrations of PCBs (20-90 ppb) and PCDFs (100-500 ppt) just after the onset were gradually decreased to 0.04-1.3 ppb of PCBs and 0.3-5 ppt of PCDFs in 2005 with the biological half-lives of 3.84, 6.31, 7.24, 4.98 and 4. 30 years, respectively. The particular declining mode of the PCB congeners during 38 years and the correlation coefficients between the concentrations of PCB118, PCB153, PCB156, 23478F and 123478F in the blood of Yusho patients indicated that PCB118 concentrations have been decreased by the coexisting PCB156, 23478F and others which have very strong enzyme inducing activities and the PCB118 has been metabolized by the enzyme inducers to hydroxyl-PCBs which firmly bind to transthyretin (thyroxin transport protein) in the blood and disturb the hormonal effects.

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.

[Peculiar remaining of some PCB congeners in the patients with Yusho for more than 30 years].

Concentrations of polychlorinated biphenyl (PCB) congeners, hexachlorobenzene (HCB) and dichloro dichlorophenyl ethylen (DDE) in the blood of Yusho patients (n = 28) were statistically compared with those in the blood of Fukuoka residents (n = 151). The PCB concentrations in the blood of Yusho patients were higher than those of Fukuoka controls and concentration ratios of Yusho/Control were various depending on PCB congeners, being 1.6 on 2,3',4,4',5-pentaCB (# 118), 17.5 on 2,3,3',4,4',5-hexaCB (# 156) and 5.4 on total PCBs. Correlation coefficients between age and concentrations of 7 PCB congeners, HCB and DDE in the blood of Fukuoka residents were significantly positive each other (p < 0.001), while in Yusho patients, the correlation coefficients were positive but various depending on the congeners. However, correlation coefficient between PCB # 118 and PCB # 156 in the Yusho patients was remarkably low, indicating their peculiar accumulative properties in Yusho patients. The concentration of PCB # 118 had been markedly decreased after the ingestion of PCBs and would be metabolized to hydroxylated PCB, which might cause estrogen disturbance in the Yusho patients.