Long-Term Health Effects of PCBs and Related Compounds: A Comparative Analysis of Patients Suffering from Yusho and the General Population.

Yusho, which refers to a mass poisoning caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans, was first reported in October 1968 in Japan. Yusho patients suffer from various symptoms; however, after 40 years, some emerging symptoms have been attributed to aging. The prevalence of symptoms and diseases among Yusho patients and the general population was compared in this study. The data obtained from the survey among Yusho patients (1131 patients) by the Ministry of Health, Labour, and Welfare of Japan in 2008 were compared with the data from a survey conducted among the general population. When selecting the comparison group, the age and residential area (prefecture) were taken into account to match the baseline characteristics of Yusho patients. A logistic regression analysis was performed to identify the association between Yusho and the prevalence of symptoms and was adjusted for various potential confounding factors (age, sex, body mass index, cigarette smoking, frequency of drinking, and walking time). Skin pigmentation and acneiform eruption were found to be characteristic symptoms of Yusho and were more prevalent in these patients. Other symptoms and diseases associated with Yusho included orthostatic hypotension, hypohidrosis, dysgeusia, Basedow's disease, hoarseness, cardiac insufficiency, tachycardia, eczema, and hair loss. Symptoms related to aging, such as general fatigue, arthralgia, and numbness in the extremities, were significantly higher in Yusho patients after adjusting for age and lifestyle. This study demonstrated that, 40 years after the outbreak of Yusho, the prevalence of various symptoms and diseases in Yusho patients, including age-related diseases, was higher than that in the general population.

Change in decay rates of dioxin-like compounds in Yusho patients.

BACKGROUND: Once ingested, dioxins and dioxin-like compounds are excreted extremely slowly. Excretion can be evaluated by its half-life. Half-lives estimated from observed concentrations are affected by excretion and ongoing exposure. We investigated the change in apparent half-life using a theoretical model based on exposure to dioxin and dioxin-like compounds. METHODS: We carried out longitudinal measurements of the blood concentration of dioxins and dioxin-like compounds in a Yusho cohort during 2002 to 2010. We estimated the change in decay rates of 2,3,4,7,8-PeCDF and octachlorodibenzodioxin (OCDD) using a second-order equation. RESULTS: We found that the decay rate of OCDD increased, whereas the decay rate of 2,3,4,7,8-PeCDF of patients with a relatively high concentration of 2,3,4,7,8-PeCDF decreased. OCDD results were in accordance with decreasing levels of dioxin and dioxin-like compounds in the environment. The decay rate of OCDD in the body was affected by the decay rate of OCDD in the environment by ingestion because it was near the steady-state. In contrast, the decay rate of 2,3,4,7,8-PeCDF in the body was affected less by ingestion from the environment because it was far higher than in the steady-state. CONCLUSION: We demonstrated that the level of 2,3,4,7,8-PeCDF in the environment is decreasing. The excretion half-life is longer than the environmental half-life, thus the excretion half-life in a Yusho patient is increased.

Unexpectedly long half-lives of blood 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) levels in Yusho patients.

BACKGROUND: Dioxins and dioxin-like compounds have half-lives typically between 7.2 years and 15 years. Our previous study of patients poisoned by extremely high concentrations of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) in the 'Yusho incident' in 1968 found that in some the half-life of blood 2,3,4,7,8-PeCDF tended towards infinity. This suggests that there are two groups of Yusho patients, those with 2,3,4,7,8-PeCDF half-lives around 10 years, and those with half-lives near infinity. We sought to establish the proportions of each in a cohort of 395 Yusho patients, and whether the proportions were changing over time. METHODS: We undertook longitudinal measurement of the blood concentration of 2,3,4,7,8-PeCDF in our cohort between 2002 and 2010. We estimated the change in concentration for each patient using linear regression for measured 2,3,4,7,8-PeCDF concentration, then compared the distribution of changes in concentrations with our previous study. RESULTS: In patients in whom the blood concentration of 2,3,4,7,8-PeCDF exceeded 50 pg/g lipid, the proportion 8.0% of patients exhibiting half-lives less than 13.3 years fell compared with our previous study (28.2%), while the proportion with near infinity half-lives increased. CONCLUSION: The prolongation of the half-lives was likely a consequence of age-related factors.

[Comparison of the prevalence of symptoms and medical histories between Yusho patients and healthy controls].

Yusho disease was first reported in October 1968 in western Japan. Although a previous survey revealed that Yusho patients have suffered from various symptoms for 40 years after the outbreak of Yusho, some symptoms could be caused by aging. Therefore, we compared the prevalence of symptoms and medical histories (symptoms or patient-reported diseases) between Yusho patients and healthy controls to demonstrate the effects of Yusho on health conditions. We conducted a survey of healthy controls who had already registered to a survey company and created a dataset of symptoms and medical histories. We then merged the healthy control data with the Yusho survey data obtained from The Ministry of Health, Labour, and Welfare of Japan. Statistical analyses were performed using a chi-square analysis for the incidence of symptoms. Symptoms included in the major diagnostic criteria for Yusho, such as pigmentation and acneform eruption, were expectedly higher in the Yusho patients than in the healthy individuals. Symptoms that could be caused by aging, such as general fatigue, arthralgia, and numbness in the extremities, were also significantly higher in the Yusho patients after adjustment for age, indicating the possibility that Yusho may cause various systemic symptoms and diseases.

[Relationships between Half-Lives of Dioxins and SNPs in AhR among Yusho Patients].

Half-lives of blood levels of 2,3,4,7,8-Pentachlorodibenzofuran (PeCDF) are varied in Yusho patients. The objective was to evaluate a relationship between half-lives of PeCDF levels and types of SNP rs10249788 of aryl hydrocarbon receptor (AHR) gene in 93 Yusho patients. Based on physical symptoms, age, sex, body mass index and other factors, we set up suitable calculation formulas to fit the actual PeCDF levels thorough rates of change in PeCDF. We found that patients with C/T SNP had longer half lives than patients with C/C and T/T SNPs. Patients with T/T SNP are known to express higher amount of AHR mRNAs. However, detailed analysis could not be carried out in T/T group due to a limited number of patients (n = 11). Further research is warranted to determine the cause of the longer half-lives in C/T patients.

Developing a national food defense guideline based on a vulnerability assessment of intentional food contamination in Japanese food factories using the CARVER+Shock vulnerability assessment tool.

The awareness of food terrorism has increased following the September 11, 2001 terrorist attacks in New York City, United States, and many measures and policies dealing with this issue have been established worldwide. Suspected deliberate food-poisoning crimes have occurred in Japan, although they are not regarded as acts of food terrorism. One area of concern is that the small- to medium-sized companies that dominate Japan's food industry are extremely vulnerable to deliberate food poisoning. We conducted a literature research on food defense measures undertaken by the World Health Organization and in the United States and Europe. Using the Carver+Shock vulnerability assessment tool, eight food factories and related facilities in Japan were evaluated and we found the level of awareness of food defense to be low and the measures inappropriate. On the basis of this evaluation, we developed a set of guidelines that Japanese food companies can use to help develop their food defense strategies and to serve as a reference in considering specific measures.

Tentative food defense guidelines for food producers and processors in Japan.

OBJECTIVES: With increasing global interest in intentional food contamination, expert meetings have been held by the G8, while the U.S. government has proposed policies for preventing food terrorism and intentional contamination. However, Japan has no food defense policy, and some food companies are concerned about an impending terrorism and contamination crisis. METHODS: We developed a Food Defense Checklist for Food Producers and Processors and published the details on the website. We also developed tentative Food Defense Guidelines for Food Producers and Processors on the basis of the checklist. In this study, we tested the usability of the guidelines through a hearing survey regarding food plants. We also compared the checklist with the implementation manual for the approval system of Comprehensive Sanitation Management and Production Process (the Japanese equivalent of the HACCP). RESULTS: We organized the comments gleaned from the hearing survey and provided a detailed explanation of the guidelines. As the HACCP has been adopted by Japanese food companies, we included both precautionary measures and the HACCP perspective in the explanation regarding the rapid dissemination of information. CONCLUSION: The guidelines are useful for Japanese food companies, and it is important to disseminate knowledge on this topic and implement food defense measures.

[Relationships between concentrations of dioxin isomers and symptoms, and among concentrations and half-lives of dioxin isomers, in patients with Yusho disease].

The relationships among dioxin isomers are not well understood. This study aimed to clarify the relationships among isomers using two methods. First, the relationships between isomers and symptoms were analyzed by analysis of variance. Second, concentrations and half-lives were determined for each isomer in each patient, and correlation coefficients for the concentrations and half-lives among isomers were calculated. Two isomers very similar to 2, 3, 4, 7, 8-pentachlorodibenzofuran (2, 3, 4, 7, 8-PeCDF) were correlated with symptoms of Yusho disease. The correlation coefficients among three isomers similar to 2, 3, 4, 7, 8-PeCDF were very high at 0.98, indicating that there may be a mechanism which maintains constant ratios among these isomers.

Consumer Willingness to Pay for Food Defense and Food Hygiene in Japan: Cross-Sectional Study.

BACKGROUND: In Japan, incidents of falsified expiration dates on popular cookie brands and health hazards associated with frozen Chinese dumplings have raised food safety awareness. To prevent the intentional contamination of food by foreign substances, large food manufacturing companies have adopted the concept of food defense. OBJECTIVE: The aim of this study was to assess people's willingness to pay for food protection measures. In addition, the impact of participants' personalities and considerations regarding their purchase choices on how much they were willing to pay when shopping for food and other products were measured. METHODS: A questionnaire on willingness to pay for food hygiene and food defense was administered via a web survey and 1414 responses were included in the analysis. Univariate logistic regression analyses were performed with individuals willing and unwilling to pay additional costs as the objective variable and other questionnaire items as explanatory variables. A principal component analysis was performed on 12 questions regarding how much additional money people were willing to pay, and the principal component scores and other questions were examined for implications and other information. RESULTS: Approximately one-third of the respondents stated that they were unwilling to pay additional costs and reported a willingness to consume delivery food even if it contained items that were not part of the original order. The first principal component reflected the extent to which people were willing to pay additional money, and if so, how much. This tendency existed even if the individual foods and amounts varied. The third principal component reflected the amount of extra money that people were willing to pay, which was determined by the amount people had to pay toward food safety measures. Those who answered "zero" were more likely to believe that consumers should not have to pay to ensure food safety. The second principal component reflected an axis separating food defense and food hygiene. Some items not directly related to food were correlated with this axis. CONCLUSIONS: In Japan, the concept of food hygiene is well-established and is generally taken for granted. In contrast, the concept of food defense is relatively new and has not yet fully penetrated the Japanese market. Our research shows that people who think that clothing brands provided added value to clothing products may have similar feelings about food defense. In addition, food hygiene efforts to prevent outbreaks of food poisoning are common in Japan and have been established as the basis of food safety. While food defense efforts are spreading, mainly in companies, it is presumed that they are valuable for the general public as supplementary measures to routine (or basic) food hygiene.

Consumer Awareness of Food Defense Measures at Food Delivery Service Providers and Food Manufacturers: Web-Based Consumer Survey Study.

BACKGROUND: Various stages of the food chain, from production to processing to distribution, can impact food safety. The concept of "food defense" has emerged as a countermeasure against intentional contamination of food with foreign substances. Although knowledge of food hygiene is common among consumers, there are currently no reports of consumer surveys on food defense. OBJECTIVE: This study aims to investigate consumer awareness of food defense and food safety. We analyzed the results focusing on how consumers behave when they find abnormalities in food to further our knowledge on promoting food defense measures. METHODS: Participants completed a web-based questionnaire that included items related to awareness of food safety and food defense, as well as actions to be taken in cases of food abnormalities, such as contamination by foreign substances, the presence of a bad smell in purchased food, and the inclusion of extra items not selected by the individual. The participants were asked to indicate their preference among the 5 suggested actions in each case using a 6-point Likert scale. Data analysis involved aggregating responses into binary values. Stepwise linear regression analysis was conducted to examine the relationship between selected actions and questionnaire items, such as sex, age, and personality. RESULTS: A total of 1442 respondents completed the survey, and the majority of participants placed importance on food safety when making food purchases. The recognition of each term was as follows: 95.2% (n=1373) for "food security and safety," 95.6% (n=1379) for "food hygiene," and 17.1% (n=247) for "food defense." The percentages of those who answered that they would "eat without worrying" in the case of "contamination by foreign substances," "bad smell," or "including unpurchased product" in the frozen food they purchased were 9.1% (n=131), 4.8% (n=69), and 30.7% (n=443), respectively. The results showed that contacting the manufacturer was the most common action when faced with contaminated food or food with a bad smell. Interestingly, a significant percentage of respondents indicated they would upload the issue on social networking sites. Logistic regression analysis revealed that male participants and the younger generation were more likely to choose the option of eating contaminated food without worrying. Additionally, the tendency to upload the issue on social networking sites was higher among respondents who were sociable and brand-conscious. CONCLUSIONS: The findings of this study indicate that if food intentionally contaminated with a foreign substance is sold and delivered to consumers, it is possible consumers may eat it and experience health problems. Therefore, it is crucial for not only food manufacturers but also food delivery service providers to consider food defense measures such as protecting food from intentional contamination. Additionally, promoting consumer education and awareness regarding food defense can contribute to enhancing food safety throughout the food chain.

[Relationship between half-lives of blood dioxins and possible metabolic mechanism].

Blood levels of dioxins in Yusho patients have been measured for 10 years. The purposes of this study were to determine the half-lives of dioxins on the basis of the data obtained from Yusho patients and to compare the half-lives of the compounds. Linear regression analysis was performed using the binary logarithmic value of each dioxin level as the dependent variable and the year of measurement as the independent variable. The linear coefficient obtained from this linear regression analysis was the reciprocal number of the half-life. The relationship between the blood dioxin levels estimated in 2004 and the reciprocal number of half-life was evaluated. Of the studied dioxins, the concentrations of some compounds were strongly correlated with that of 2,3,4,7,8-PeCDF. For 2 such compounds, the correlation coefficient of the reciprocal numbers of half-life were greater than the correlation coefficient of the logarithmic values of the estimated concentrations. Of these 2 compounds, the concentration of 3,3,4,4,5,5-HxCB was at least 50 times less than that of the 2,3,4,7, 8-PeCDF in rice oil: however, their current concentrations are equivalent. Patients with high levels of 2,3,4,7,8-PeCDF also showed high levels of 3,3,4,4,5,5-HxCB. Yusho patients may have a disease-specific mechanism to supply 3,3,4,4,5,5-HxCB.

Risk of Seasonal Influenza by Occupation in a Railway Company in a Metropolitan Area of Japan during Three Influenza Seasons.

Station staff may be at high risk for influenza due to high frequency contact with other people. We examined the risk of influenza by occupational group in a railway company. A retrospective observational study was conducted among employees at a branch office of a railway company in eastern Japan, located in a metropolitan area, for 2012/13, 2013/14, and 2014/15 influenza seasons. The study population included employees who had received influenza vaccination for the season in question and the previous season. Outcome was defined as self-reported influenza illness during the respective season, identified through the vaccine screening questionnaire in the following season. Study participants included employees whose outcome information could be obtained. Standardized morbidity ratios (SMRs) by occupational group (station staff, engineers, train crew) for each season were calculated. For 2012/13, 2013/14, and 2014/15 seasons, attack rates were 4.7% (19/403), 5.2% (21/407), and 7.8% (31/397), respectively. Among the participants, SMRs of station staff were lower in the 2012/13 (SMR = 57; 95% confidence intervals [CI] = 18-133) and 2014/15 (SMR = 75; 95%CI = 36-138) seasons and similar to other groups in the 2013/14 season. Enhanced countermeasures, regardless of occupational group, may be effective in preventing the spread of influenza infection.

Association analysis of food allergens.

Food allergy patients are known to present with allergic reactions to multiple allergens, but extrapolating these associations is difficult. Data mining, a procedure that analyzes characteristic combinations among large amounts of information, is often used to analyze and predict consumer purchasing behaviour. We applied this technique to the extrapolation of food allergen associations in allergy patients. We sent 1510 families our 'Questionnaire survey for the prevention of food allergies'. Responses noting 6549 allergens came from 878 families with 1383 patients, including 402 with anaphylaxis. Some results of the survey have already been published and here we presented the results of our association analysis of combinations of food allergens. Egg, milk, wheat, peanuts, and buckwheat are the most common food allergens. The most common simultaneous combinations of these allergens were 'egg-milk', 'egg-wheat', and 'milk-wheat'. The occurrence probability of a combination (i.e. one person suffering from a certain allergen also suffers from another) is called 'confidence'. Confidence was higher for 'chicken-egg', 'abalone-salmon eggs', and 'matsutake mushroom-milk'. As well, the combinations of 'crab-shrimp', 'squid-shrimp', and 'squid-crab' also indicated higher values in a statistical examination of the occurrence probabilities of these allergen combinations (Z-score). From the results of the association analysis, we speculated that some food allergens, such as abalone, orange, salmon, chicken, pork, matsutake mushroom, peach and apple did not independently induce food allergies. We also found that combinations, such as 'crab-shrimp', 'squid-shrimp', 'squid-crab', 'chicken-beef', and 'salmon-mackerel' had strong associations.

[Differential correlation of medical/laboratory examinations with blood levels of polychlorinated biphenyls, polychlorinated quarterphenyls and 2,3,4,7,8-pentachlorodibenzofuran in Yusho patients from 2001 to 2004].

BACKGROUND: Since 1968, when the Yusho poisoning incident occurred, annual physical, dermatological, dental, and ophthalmological and laboratory examinations, collectively called Yusho health checks, have been conducted for Yusho patients. The Yusho incident was a health hazard caused by intake of rice-bran oil contaminated with PCB and PeCDF; therefore, since 2001 the levels of dioxins such as PeCDF in the blood have been measured in applicants. Here, we investigated correlations among findings from various medical examinations and those between those findings and PeCDF, PCB, and PCQ. PATIENTS AND METHODS: Subjects were Yusho patients who underwent Yusho annual health checks and had their levels of PeCDF measured between 2001 and 2004. The results of 4 years of health checks of those who underwent the health checks for 2 years or longer were aggregated to extract representative inspection items by principal component analysis. We also investigated the presence or absence of correlations among these items and PeCDF, PCB, and PCQ levels in blood. RESULTS: Using 49 variables extracted by principal component analysis as objective variables, we determined that there were correlations between the following combinations: arthralgia, A/G ratio and PeCDF level, ophthalmological symptoms such as excessive eye discharge and PCB level, and total cholesterol, inferior gingival pigmentation and PCQ level.

[Estimated half-life of penta-chlorodibenzofuran (PeCDF) and simulation of PeCDF excretion].

The half-life of 2,3,4,7,8-penta-chlorodibenzofuran (PeCDF) in the Yusho patients has been reported to be approximately seven years. In the present study, we estimated the half-life of PeCDF using data from the medical check-ups of more than 300 Yusho patients. We performed linear regression analysis with a binary logarithm of PeCDF blood level in Yusho patients as the dependent variable, and the measurement year as the independent variable. Our results showed that there were many patients who had shown no reduction of their blood PeCDF level for several years. This result contradicts the previously reported half-life period. Therefore, we believe that a more complicated excretion model needs to be established to explain the discrepancy we found. We hypothesized that there might be two mechanisms of PeCDF assimilation in human digestive tract. In the present study, we also used our hypothesis to simulate PeCDF excretion in Yusho patients.

Association of clinical findings in Yusho patients with serum concentrations of polychlorinated biphenyls, polychlorinated quarterphenyls and 2,3,4,7,8-pentachlorodibenzofuran more than 30 years after the poisoning event.

BACKGROUND: The Yusho poisoning incident, which was caused by rice bran oil contaminated with polychlorinated biphenyls (PCBs), polychlorinated quarterphenyls (PCQs) and polychlorinated dibenzofurans (PCDFs) generated by heat denaturation of PCB, occurred in 1968 in western Japan. Annual physical, dermatological, dental, ophthalmological and laboratory examinations were conducted for Yusho patients after the incident. From 2001, blood levels of individual PCDF congeners were also measured. The blood levels of 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PeCDF), PCBs and PCQs in Yusho patients were found to be significantly higher than those of the general population. We investigated the relationships between blood concentrations of 2,3,4,7,8-PeCDF, PCBs and PCQs in Yusho patients and the items measured in the annual medical examination. METHODS: Medical and laboratory examination data from 501 Yusho patients enrolled in the study from 2001 to 2004 were analyzed. The relationships between blood 2,3,4,7,8-PeCDF, PCB and PCQ concentrations and medical/laboratory examination data were investigated using principal components and logistic regression analyses. RESULTS: Serum Concentrations of 2,3,4,7,8-PeCDF, PCBs and PCQs in blood tended to correlate with either acneform eruptions, black comedones, cutaneous and mucosal pigmentation, and hypersecretion of meibomian glands as well as general fatigue, headaches, cough/sputum, abdominal pain, arthralgia, increased blood sugar, increased serum gamma-GTP and decreased total bilirubin. The majority of these signs and symptoms are included in the diagnostic criteria for Yusho. CONCLUSION: After Yusho patients had suffered chronic exposure to these chlorinated compounds for more than 35 years, the serum concentration of 2,3,4,7,8-PeCDF in blood was significantly related to arthralgia and decreased albumin/globulin (A/G) ratio; the serum concentration of PCBs was significantly related to ophthalmologic symptoms; and the serum concentration of PCQ to increased total cholesterol. These findings suggest that the co-contaminants may affect other functions than those originally associated with Yusho.

A technique for identifying three diagnostic findings using association analysis.

In diagnosing diseases in clinical practice, a combination of three clinical findings is often used to represent each disease. This is largely because it is often difficult or impractical to assess for all possible combinations of symptoms and abnormal exam findings that occur in any particular disease. For most diseases, diagnostic triads are based on empirical observations. In this study, we determined diagnostic triads for chronic diseases using data mining procedures. We also verified the combinations' validity as well as our procedure for determining them. We used symptoms and examination findings from 477 patients with chronic diseases, collected as part of a 35-year longitudinal study begun in 1968. For each patient there were 295 items from examinations in internal medicine, dermatology, ophthalmology, dentistry and blood tests. We judged each item to be either normal or abnormal, and restricted the analysis to the abnormal findings. To analyze such an exhaustive assortment, we used the data mining technique of association analysis. The analysis generated three clinical findings for each disease. Diseases were defined based on blood tests. Searching through all 295 items to find the three most useful clinical findings would be impractical on a commodity PC. However, by excluding normal items, we were able to sufficiently reduce the total number of combinations so as to make combinatorial analysis on a PC feasible. In addition to more accurate diagnoses, we believe our technique can identify those diagnostic data that are more cost effective in terms of time and other resources required for their collection.

[Average of the PCDFs value in blood in patients with Yusho in the 2001 to 2003 fiscal year and comparison between the clinical features and PCDFs].

BACKGROUND: Kanemi Yusho is the name given to a 1968 food poisoning incident resulting from the ingestion of PCB contaminated rice bran oil that had been used as a heating medium. At the time, victims presented with mainly cutaneous manifestations and various other symptoms such as of the eyes and teeth, general fatigue, headaches, and paresthesia of the extremities. The characteristic symptoms then resolved with time. Yusho patients have been followed from immediately after the incident. Blood levels of dioxins such as PeCDF have been measured for those who wishing to since 2001. SUBJECTS AND METHODS: The presence or absence of relationships between blood PeCDF level and various examination items/symptoms was investigated in 359 subjects whose blood levels of PCB-related chemical compounds such as PeCDF were measured in the Yusho related examinations between 2001 and 2003. Characteristic symptoms were also compared with the results of examinations done 15 years previously. RESULTS AND DISCUSSION: The average blood 2,3,4,7,8-PeCDF level in designated Yusho patients was 177.50 pg/g lipids; showing a markedly higher value than that of the normal control group (15.2 pg/g lipids). As well, the blood PeCDF level was related to PCB level, hexachlorobiphenyl level, urinary sugar, erythrocyte sedimetation rate (ESR) (2-hour), thymol and Na. There were also relationships with cutaneous findings (acneiform eruption and comedones), mucosal findings (oral pigmentation), constipation, numbness in the extremities, body weight loss, and abnormal abdominal ultrasonography. Symptoms seen in the skin and eyes in 2001 and 2003 had decreased compared with those in seen 1988. However, PCB and blood PeCDF levels remained high. Patients are continuing to present with mucosal and subjective symptoms as chronic conditions.

[Relationship between blood dioxin levels and present/past clinical symptoms in Kanemi Yusho patients].

BACKGROUND: Kanemi Yusho was a food poisoning incident caused by rice bran oil that occurred in western Japan, particularly in northern Kyushu, in 1968. It is difficult to determine the symptoms in patients after many years since the occurrence. Techniques for measuring blood dioxins have advanced recently. More accurate data measurement has now become possible, and techniques for mass data analysis, such as data mining, have also advanced. It has also become possible to find unknown characteristics, even in an object group with elusive characteristics, by checking all the combinations in all the patients. AIM: There are already several reports on the incidence of symptoms in Yusho patients. These reports are limited to symptoms in a single period, and there has been no analysis taking into account the time that has elapsed. Here, we evaluated the relationship between recent and past symptoms and 2,3,4,7,8-penta-chlorodibenzofuran (PeCDF) levels in the same subject patient, in order to demonstrate the correlation between PeCDF levels and symptoms at a time point close to the incident. METHODS: Subjects were examined for symptoms of Yusho and had blood PeCDF levels measured, both recently and in the past. Combinations were extracted using association analysis of data mining technique for comparison, which had strong correlations between the presence or absence of symptoms in the medical examination, tests including blood test, dermatological examination, dental examination and ophthalmologic examination in recent years (2001-2004) and the blood PeCDF levels and those between the presence or absence of past (1986-1989) symptoms and recent blood PeCDF levels. RESULTS: Subjects with higher PeCDF levels were more likely to present with pigmentation, a symptom included in the diagnostic criteria for Yusho. Pigmentation was a commonly found symptom in the past. Past pigmentation was a common symptom in the present. DISCUSSION: PeCDF levels were measured recently and therefore should not be compared directly with past symptoms. However, among the symptoms included in the diagnostic criteria, past symptoms tended to have a stronger relationship with PeCDF levels than did recent symptoms. We suggest that the present PeCDF level is strongly related to the past symptoms since the present PeCDF level is correlated with the past PeCDF level due to constant emission rate. More specifically, if the past PeCDF level is strongly related to the past symptoms, it can indirectly be concluded that the present PeCDF level is also strongly related to the past symptoms. Thus, the present PeCDF level cannot be related to the past symptoms directly but can indirectly. CONCLUSIONS: Combining recent and past symptoms further demonstrated that clinical symptoms are strongly related to PeCDF toxicity. This may have resulted from the increase in symptoms with aging, however, it was demonstrated that the symptoms of each patient were relieved and become obscure.