Polychlorinated Biphenyl Concentrations and Estimated Intakes in Fish Oil Supplements on the Japanese Market.

Polychlorinated biphenyls (PCBs) are synthetic organic contaminants that are widespread in the environment. There are 209 PCB congeners. Fish oil produced from marine fish is widely used as a health supplement. PCB contamination of fish oil is of concern. We determined the concentrations of all 209 PCB congeners in commercially available fish oil supplements from Japan and estimated PCB intakes for humans consuming the supplements. We determined the concentrations of non-dioxin-like PCBs separately. The total PCB concentrations in 37 fish oil supplements purchased in Japan were 0.024-19 ng/g whole weight, and the non-dioxin-like PCB concentration range was also 0.024-19 ng/g whole weight. The total PCB intakes calculated for a 50 kg human consuming the supplements were 0.039-51 ng/day (0.00078-1.0 ng/(kg body weight per day)) and the non-dioxin-like PCB intake range was also 0.039-51 ng/day (0.00078-1.0 ng/(kg body weight per day)). The total PCB intakes were much lower than the tolerable daily intake of 20 ng/(kg body weight per day) recommended by the WHO. The results indicated that PCBs in the fish oil supplements pose acceptable risks to humans consuming the fish oil supplements daily.

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. This method is effective at determining the concentrations of PCDDs, PCDFs, Co-PCBs and OH-PCBs from the same sample without special treatment of the sample. The concentration of OH-PCBs in the blood of Yusho patients was examined using this method. The major OH-PCB metabolites were 4-OH-CB187 (54-906 pg/g-wet), 4-OH-CB146 + 3-OH-CB153 (32-527 pg/g-wet), 4-OH-CB109 (ND-229 pg/g-wet) and 4'-OH-CB172 (ND-143 pg/g-wet). The total OH-PCBs ranged from 95 to 1740 pg/g-wet.

Dioxin concentration in the blood of patients collected during medical check-up for Yusho in 2004-2005.

We measured the concentrations of polychlorinated dizenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and non-ortho coplanar polychlorinated biphenyls (non-ortho PCBs) in blood collected from 242 Yusho patients and 74 Yusho-suspected persons in 2004 and 237 Yusho patients and 114 Yusho-suspected persons in 2005. The sums of toxic equivalents (TEQ) concentrations of PCDDs, PCDFs, and non-ortho PCBs in the blood of Yusho patients in 2004 and 2005 were 126.1 and 124.2 pg TEQ/g lipid, respectively, and the concentrations were 3.4 and 3.3 times higher than those of normal controls that had been previously reported, respectively. Those of the Yusho-suspected persons were about 0.8 and 1.0 times higher than those of normal controls, respectively. Although the TEQ concentrations of PCDDs and non-ortho PCBs among Yusho patients, Yusho-suspected persons, and normal controls were nearly the same, the PCDFs levels of Yusho patients were about 9.8 and 9.5 times higher than those of normal controls in 2004 and 2005, respectively. The concentration of 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PeCDF), which was the highest among PCDFs congeners for Yusho patients, was about 10. 6 and 10.2 times higher than that of the normal controls in 2004 and 2005, respectively. In the case of Yusho-suspected persons, the concentrations were 0.9 and 1.4 times higher than those of normal controls, respectively. However, some of the Yusho-suspected persons showed a high concentration of 2,3,4,7,8-PeCDF that was approximately 15 times greater than concentrations in normal controls. Of 74 Yusho-suspected persons measured in 2004, 7 persons were officially registered as Yusho patients based on the "New Diagnostic Criteria" that officially became the diagnostic criteria for Yusho exposure on September 29, 2004, which included a concentration of 2,3,4,7,8-PeCDF in the blood, and in 2005, 14 persons of 114 Yusho-suspected persons were officially registered as Yusho patients.

[Congener specific determination of PCBs in human blood using gel permeation chromatography (GPC) and high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS)].

We studied the progressive analytical method for polychlorinated biphenyls (PCBs) in blood samples collected from Yusho patients. This study established a systematic procedure for determining both "total concentration of PCBs and their profiles" and "concentrations of mono-ortho PCBs as dioxin-like compounds", providing a significant index for diagnosis. The method we developed consists of a rapid clean-up using gel permeation chromatography (GPC) and sensitive identification with high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS). This method provides identification of all of PCB congeners typically detected in human blood samples, especially it is worth noting that nine significant congeners on Yusho diagnosis (IUPAC #105, #114, #118, #123, #153, #156, #157, #167, #189) were detected from a five-gram blood sample. Using the present method, we analyzed sixty-six individual blood samples collected during the annual Yusho inspection in the 2004, and could identified sixty-eight PCB isomers in all samples. As a result, ten patients were classified into pattern A, the typical Yusho pattern. The mean total PCB concentration of pattern A subjects was 2.95 ppb, while that of control subjects was 0.77 ppb, at whole blood basis respectively.

Follow-up survey of dioxin concentrations in the blood of Yusho patients in 2002-2003.

We measured the concentrations of polychlorinated dizenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and non-ortho-coplanar polychlorinated biphenyls (Co-PCBs) in blood collected from 279 Yusho patients and 92 Yusho-suspected persons living in Japan in 2002, 269 Yusho patients and 74 Yusho-suspected persons living in Japan in 2003 and 128 normal controls living in Fukuoka Prefecture, and compared with the concentrations of these compounds among the groups. The total TEQ concentrations of PCDDs, PCDFs, and Co-PCBs in the blood of Yusho patients were 3.6 times and 3.3 times higher than those in the normal controls in 2002 and 2003, respectively. In the case of Yusho-suspected persons, the concentrations were 1.1 times and 1.0 times higher in 2002 and 2003, respectively. Among the TEQ concentrations of PCDDs, PCDFs, and Co-PCBs, the concentrations of PCDFs in the blood of Yusho patients were 10.3 times and 9.4 times higher than those of the normal controls in 2002 and 2003, respectively, whereas the concentrations of PCDDs and Co-PCBs in blood were identical in Yusho patients, Yusho-suspected persons and normal controls. Yusho patients indicated the highest concentrations ratio of PCDFs to the total TEQ concentrations. Moreover, of the PCDFs congeners for Yusho patients, the concentrations of 2,3,4,7,8-PeCDF were about 11.0 times and 10.1 times higher in 2002 and 2003 than those in normal controls. These results indicated that Yusho patients have a much higher concentration of 2,3,4,7,8-PeCDF in their blood than do unaffected persons even though over 34 years have passed since the outbreak of Yusho.

[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.

[Equality as Yusho diagnosis indices between blood PCB constitution data from using a conventional analytical method and a PCB isomer specific analytical method].

This paper reports that we can replace a conventional PCB analytical method with an isomer specific analytical method in Yusho diagnosis. The authors analysed 109 blood samples from people who had the 2002 annual inspection for Kanemi rice oil poisoning using both methods. The data from these methods were compared and proved to be almost the same in the so-called "PCB pattern" which has been adopted as a Yusho diagnosis index since early 1970s.

Increasing effect of nori on the fecal excretion of dioxin by rats.

The effects of nori (Porphyra yezoensis), a kind of red alga, on the gastrointestinal absorption and reabsorption of 17 types of dioxin were investigated in male Wistar rats. The rats were fed with 4 g of the control diet or 4 g of the nori diet containing a standard dioxin solution (233 ngTEQ/kg of body weight) for five consecutive days. In the group fed with the 10% nori diet, the fecal excretion of dioxin from days 1 to 5 was higher (p<0.01) than that of the control group by 5.5-fold for 2,3,7,8-TCDD, 6.6-fold for 1,2,3,7,8-pentaCDD, and 6.0-fold for 2,3,4,7,8-pentaCDF. In another experiment, the rats were fed with 4 g of the control diet containing a standard dioxin solution (2991 ngTEQ/kg of body weight) on the first day of the experiment and then given the control diet for 7 consecutive days, before being given either the control diet or the nori diet for 28 consecutive days more. In the group fed with the 10% Nori diet, the fecal excretion of dioxin during the period from days 8 to 35 was higher (p<0.01 or p<0.05) than that of the control group by 2.4-fold for 2,3,7,8-TCDD, 2.3-fold for 1,2,3,7,8-pentaCDD, and 2.4-fold for 2,3,4,7,8-pentaCDF. These results suggest that the administration of nori prevented dioxin from being efficiently absorbed and reabsorbed from the gastrointestinal tract, and might be useful for protecting humans exposed to dioxin from ill effects.