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. 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.

     

Dual mechanochemical immobilization of heavy metals and decomposition of halogenated compounds in automobile shredder residue using a nano-sized metallic calcium reagent

Simultaneous immobilization of heavy metals and decomposition of halogenated organic compounds in different fractions of automobile shredder residue (ASR) were achieved with a nano-sized metallic calcium through a 60-min ball milling treatment. Heavy metal (HM) immobilization and chlorinated/brominated compound (CBC) decomposition efficiencies both reached 90–100 %, after ball milling with nanometallic calcium/calcium oxide (Ca/CaO) dispersion, regardless of ASR particle size (1.0, 0.45–1.0, and 0.250 mm). Concentrations of leachable HMs substantially decreased to a level lower than the regulatory standard limits (Co and Cd 0.3 mg L⁻¹; Cr 1.5 mg L⁻¹; Fe, Pb, and Zn 3.0 mg L⁻¹; Mn and Ni 1 mg L⁻¹) proposed by the Korean hazardous waste elution standard regulatory threshold. Scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS) element maps/spectra showed that while the amounts of HMs and CBCs detectable in ASR significantly decreased, the calcium mass percentage increased. X-ray powder diffraction (XRD) patterns indicate that the main fraction of enclosed/bound materials on ASR includes Ca-associated crystalline complexes that remarkably inhibit HM desorption and simultaneously transform dangerous CBCs into harmless compounds. The use of a nanometallic Ca/CaO mixture in a mechanochemical process to treat hazardous ASR (dry conditions) is an innovative approach to remediate cross-contaminated residues with heavy metals and halogenated compounds.

     

High immobilization of soil cesium using ball milling with nano-metallic Ca/CaO/NaH2PO4: implications for the remediation of radioactive soils

This report shows that cesium can be immobilized in soils with an efficiency of 96.4% by ball milling with nano-metallic Ca/PO₄. In Japan, the major concern on ¹³⁷Cs deposition and soil contamination due to the emission from the Fukushima Daiichi nuclear power plant showed up after a massive quake on March 11, 2011. The accident rated 7, the highest possible on the international nuclear event scale, released 160 petabecquerels (PBq) of iodine ¹³¹I and 15 PBq of ¹³⁷Cs according to the Japanese Nuclear and Industrial Safety Agency. Both ¹³⁷Cs and ¹³¹I radioactive nuclides are increasing cancer risk. Nonetheless, ¹³⁷Cs, with a half-life of about 30 years compared with 8 days for ¹³¹I, is a major threat for agriculture and stock farming and, in turn, human life for decades. Therefore, in Japan, the ¹³⁷Cs fixation and immobilization in contaminated soil is the most important problem, which should be solved by suitable technologies. Ball milling treatment is a promising treatment for the remediation of cesium-contaminated soil in dry conditions. Here, we studied the effect, factors and mechanisms of soil Cs immobilization by ball milling with the addition of nano-metallic Ca/CaO/NaH₂PO₄, termed “nano-metallic Ca/PO₄.” We used scanning electron microscopy combined with electron dispersive spectroscopy (SEM/EDS) and X-ray diffraction. Results show that immobilization efficiency increases from 56.4% in the absence of treatment to 89.9, 91.5, and 97.7 when the soil is ball-milled for 30, 60 and 120 min, respectively. The addition of nano-metallic Ca/PO₄ increased the immobilization efficiency to about 96.4% and decreased the ball milling time. SEM/EDS analysis allows us to observe that the amount of Cs decreased on soil particle surface. Use of nano-metallic Ca/PO₄ over a short milling time also decreases Cs leaching. Therefore, ball milling with nano-metallic Ca/PO₄ treatment may be potentially applicable for the remediation of radioactive Cs-contaminated soil in dry conditions.     

Evaluation of surface runoff and road dust as sources of nitrogen using nitrate isotopic composition

Stable nitrogen and oxygen isotope ratios of nitrate (δ¹⁵N-NO₃ and δ¹⁸O-NO₃) have recently been used to identify nitrogen sources in water environments. However, there have been no investigations designed to determine nitrate isotopes in non-point sources in urban areas for evaluating the impact of surface deposits on nitrogen in surface runoff. In this study, we collected rainwater, surface runoff and surface deposits (road dust, roof dust and soil) to evaluate the nitrogen sources in surface runoff using nitrate isotopes. There were no large differences in δ¹⁵N-NO₃ among rainwater (−0.3‰ to 1.5‰), surface runoff (−2.7‰ to 0.4‰), leachates from road dust (−5.8‰ to 6.2‰) and soil (−11.5‰ to 0.6‰). In contrast, the δ¹⁸O-NO₃ in surface runoff (28.5-47.9‰) was lower than that in rainwater (62.7-78.6‰), and higher than that in leachates from road dust (6.1-27.6‰) and soil (−1.1‰ to 6.6‰). δ¹⁸O-NO₃ is a useful indicator for evaluating the NO₃-N sources in surface runoff. Using this indicator, NO₃-N from road dust was estimated to account for more than half of the NO₃-N in surface runoff. This is consistent with a result based on a comparison of their loads per unit surface between rainwater and surface runoff, which also showed that most of the nitrogen in surface runoff was derived from surface deposits.     

Total immobilization of soil heavy metals with nano-Fe/Ca/CaO dispersion mixtures

This report shows that soil heavy metals can be totally immobilized by grinding with nano-Fe/Ca/CaO. Remediation of soils contaminated by heavy metals is a critical issue in Japan. Indeed, contaminated soils are notoriously difficult to remediate using available technologies. Major setbacks in typical immobilization techniques for heavy metals are wet conditions, forming secondary effluents and further treatment for effluents. Solidification with nano-Fe/Ca/CaO dispersion mixture is a promising treatment for the total immobilization of soil heavy metals As, Cd, Cr, Pb, and separation in dry conditions. Here, we studied the heavy metal immobilization by simple grinding with the addition of three mixtures: nano-Fe/CaO, nano-Fe/Ca/CaO, and nano-Fe/Ca/CaO/PO₄. Samples were analyzed by inductively coupled plasma optical emission spectrometry (ICP-OES) and scanning electron microscopy combined with electron dispersive spectroscopy (SEM–EDS). Results show that the addition of nano-Fe/Ca/CaO immobilized 95–99 % of heavy metals, versus 65–80 % by simple grinding. After treatment, 36–45 wt% of magnetic and 64–55 wt% of nonmagnetic fractions of soil were separated. Their condensed heavy metal concentration was 85–95 % and 10–20 %, respectively. Nano-Fe/Ca/CaO treatment reduced the concentration of leachates heavy metals to values lower than the Japan soil elution standard regulatory threshold of 0.01 mg/l for As, Cd, and Pb; and 0.05 mg/l for Cr. This technology can therefore immobilize totally soil heavy metals and reduce heavy metal by separation.     

Enhanced heavy metal immobilization in soil by grinding with addition of nanometallic Ca/CaO dispersion mixture

This study investigated the use of a nanometallic Ca and CaO dispersion mixture for the immobilization of heavy metals (As, Cd, Cr and Pb) in contaminated soil. Simple grinding achieved 85-90% heavy metal immobilization, but it can be enhanced further to 98-100% by addition of a nanometallic Ca/CaO dispersion mixture produced by grinding. Observations using SEM-EDS elemental maps and semi-quantitative analysis showed that the amounts of As, Cd, Cr, and Pb measurable on the soil particle surface decrease after nanometallic Ca/CaO treatment. The leachable heavy metal concentrations were reduced after nanometallic Ca/CaO treatment to concentrations lower than the Japan soil elution standard regulatory threshold: <0.01 mg L⁻¹ for As, Cd, and Pb; and 0.05 mg L⁻¹ for Cr. Effects of soil moisture and pH on heavy metal immobilization were not strongly influenced. The most probable mechanisms for the enhancement of heavy metal immobilization capacity with nanometallic Ca/CaO treatment might be due to adsorption and entrapment of heavy metals into newly formed aggregates, thereby prompting aggregation of soil particles and enclosure/binding with Ca/CaO-associated immobile salts. Results suggest that the nanometallic Ca/CaO mixture is suitable for use in immobilization of heavy-metal-contaminated soil under normal moisture conditions.     

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.

Methods

Blood samples, obtained from 101 Yusho women (190 births) who gave birth after exposure, were analyzed for congeners of seven PCDDs, ten PCDFs, and four non-ortho PCBs.

Results

Total PCDD TEQ (adjusted beta = − 161.9 g; 95% CI, −265.3 to − 58.6), total PCDF TEQ (adjusted beta = − 105.9 g; 95% CI, −179.5 to − 32.2), and total non-ortho PCBs (adjusted beta = − 178.4 g; 95% CI, −318.3 to − 38.5) levels were inversely associated with birth weight. Significant inverse associations with birth weight were also found for total PCDD TEQ, total PCDF TEQ, and total non-ortho PCB TEQ levels among male, but not female, infants. Significant inverse associations with birth weight were also found for nine congeners among all infants; the adjusted beta coefficients were largest for 1,2,3,6,7,8-HxCDD and smallest for 2,3,4,7,8-PeCDF.

Conclusion

In the setting of exposure to high levels of dioxins, maternal blood levels of PCDDs, PCDFs and PCBs are associated with lower birth weight in Yusho patients. The association exhibited gender-specific differences, as male infants are more susceptible than females to growth restriction induced by in utero dioxin exposures.     

Mechanochemical degradation of chlorinated contaminants in fly ash with a calcium-based degradation reagent

This report presents our results in a low-temperature mechanochemical hydrodechlorination process applied to fly ash coming from a municipal waste incinerator in order to efficiently remove all traces of PCDDs, PCDFs and PCBs. We found that the most suitable degradation agent is a mixture of metallic calcium and calcium oxide. A sample of fly ash presenting a TEQ of 5200 pg g⁻¹ was completely detoxified (no traces of PCDDs, PCDFs and PCBs detected) after ball-milling at 400 rpm over night.     

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. From 2002 to 2008, blood samples were collected from 26 pairs of Yusho mothers and their children (19 mothers, 26 children). Specific congeners of seven polychlorinated dibenzo-p-dioxins (PCDDs), ten PCDFs, and four non-ortho PCBs were analyzed. The children had significantly lower TEQ concentrations of PCDDs, PCDFs, and coplanar PCBs compared to their mothers. The mother-child difference in blood concentrations varied with the congeners; the largest for 2,3,4,7,8-pentaCDF and the smallest for 1,2,3,4,6,7,8-heptaCDD. The level for 2,3,4,7,8-pentaCDF, which characterizes Yusho oil disease, was approximately 17-30 times higher in the mothers than in the general population, whereas there were no significant differences between children in the formula-fed group and the general population. In contrast, the mean level for 2,3,4,7,8-pentaCDF in the breast-fed group was approximately 1.5 times, (range 0.5-6.5 times) higher than that in the general population. Over 30 years after the Yusho incident, the mean blood dioxin levels in the offspring were only a fraction of the levels in their mothers. This is more consistent with exposure via breast milk than via transplacental transfer in the Yusho incident.     

Compound-specific isotopic and congener-specific analyses of polychlorinated biphenyl in the heat medium and rice oil of the Yusho incident

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.