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Dioxins have been suggested to induce inflammation in the intestine and brain and to induce neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), partly due to deficits in parvalbumin-positive neurons in the brain that are sensitive to inflammatory stress. Previously, we reported ADHD traits with increased aggressiveness in children with prenatal exposure to dioxins in Vietnam, whereas dried bonito broth (DBB) has been reported to suppress inflammation and inhibit aggressive behavior in animal and human studies. In the present study, we investigated the association between dioxin exposure and the prevalence of children with highly aggressive behaviors (Study 1), as well as the effects of DBB on the prevalence of children with highly aggressive behaviors (Study 2)., Methods: In Study 1, we investigated the effects of dioxin exposure on the prevalence of children with high aggression scores, which were assessed using the Children's Scale of Hostility and Aggression: Reactive/Proactive (C-SHARP) in dioxin-contaminated areas. The data were analyzed using a logistic regression model after adjusting for confounding factors. In Study 2, we performed nutritional intervention by administering DBB for 60 days to ameliorate the aggressiveness of children with high scores on the C-SHARP aggression scale. The effects of DBB were assessed by comparing the prevalence of children with high C-SHARP scores between the pre- and post-intervention examinations., Results: In Study 1, only the prevalence of children with high covert aggression was significantly increased with an increase in dioxin exposure. In Study 2, in the full ingestion (>80% of goal ingestion volume) group, the prevalence of children with high covert aggression associated with dioxin exposure was significantly lower in the post-ingestion examination compared with in the pre-ingestion examination. However, in other ingestion (<20% and 20-79%) groups and a reference (no intervention) group, no difference in the prevalence of children with high covert aggression was found between the examinations before and after the same experimental period., Conclusions: The findings suggest that DBB ingestion may ameliorate children's aggressive behavior, which is associated with perinatal dioxin exposure.

Poisoning by high concentrations of dioxin and its related compounds manifests variable toxic symptoms such as general malaise, chloracne, hyperpigmentation, sputum and cough, paresthesia or numbness of the extremities, hypertriglyceridemia, perinatal abnormalities, and elevated risks of cancer-related mortality. Such health hazards are observed in patients with Yusho (oil disease in Japanese) who had consumed rice bran oil highly contaminated with 2,3,4,7,8-pentachlorodibenzofuran, polychlorinated biphenyls, and polychlorinated quaterphenyls in 1968. The blood concentrations of these congeners in patients with Yusho remain extremely elevated 50 years after onset. Dioxins exert their toxicity via aryl hydrocarbon receptor (AHR) through the generation of reactive oxygen species (ROS). In this review article, we discuss the pathogenic implication of AHR in dioxin-induced health hazards. We also mention the potential therapeutic use of herbal drugs targeting AHR and ROS in patients with Yusho.

Dermatology is frequently viewed by physician and surgical colleagues as a specialty with few emergencies. Although the majority of dermatology practice is in the office setting, cutaneous emergencies do occur through referrals from primary care and as ward consults. Even though cutaneous signs of poisoning would be an uncommon emergency consultation, it is important for dermatologists to be aware of the clinical presentations so as to be able instigate appropriate time critical treatments., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Assessing potential alterations of metabolic pathways using large-scale approaches today plays a central role in clinical research. Because several thousands of mass features can be measured for each sample with separation techniques hyphenated to mass spectrometry (MS) detection, adapted strategies should be implemented to detect altered pathways and help to elucidate the mechanisms of pathologies. These procedures include peak detection, sample alignment, normalization, statistical analysis, and metabolite annotation. Interestingly, considerable advances have been made over the last years in terms of analytics, bioinformatics, and chemometrics to help massive and complex metabolomic data to be more adequately handled with automated processing and data analysis workflows. Recent developments and remaining challenges related to MS signal processing, metabolite annotation, and biomarker discovery based on statistical models are illustrated in this chapter considering their application to clinical research.

A probabilistic risk assessment was conducted to characterize risks to a representative piscivorous mammal (mink, Mustela vison) and a representative carnivorous mammal (short-tailed shrew, Blarina brevicauda) exposed to PCBs, dioxins, and furans in the Housatonic River area downstream of the General Electric (GE) facility in Pittsfield, Massachusetts. Contaminant exposure was estimated using a probabilistic total daily intake model and parameterized using life history information of each species and concentrations of PCBs, dioxins, and furans in prey collected in the Housatonic River study area. The effects assessment preferentially relied on dose-response curves but defaulted to benchmarks or other estimates of effect when there were insufficient toxicity data. The risk characterization used a weight of evidence approach. Up to 3 lines of evidence were used to estimate risks to the selected mammal species: 1) probabilistic exposure and effects modeling, 2) field surveys, and 3) species-specific feeding or field studies. The weight of evidence assessment indicated a high risk for mink and an intermediate risk for short-tailed shrew., (© 2015 SETAC.)

Dioxins are persistent environmental pollutants that cause multiple adverse health effects in humans, mainly through binding to the ligand-activated transcription factor, aryl hydrocarbon receptor (AhR). Genetic variation in AhR may modulate the susceptibility to dioxins. In this study, we aimed to evaluate the effects of the single nucleotide polymorphism (SNP) -130 C/T in the AhR promoter on dioxin-inducible gene transcription, and to investigate interleukin-24 (IL-24) and interleukin-1β (IL-1β) as proxies for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure. Using primary human chorionic stromal cells, we found that cells with the TT genotype showed higher AhR mRNA and protein levels than did those of the CC genotype. Microarray was carried out to analyze the gene expression profiles of cells (CC and TT genotype) after exposing the cells to TCDD. Several genes associated with human disorders were more highly up-regulated in cells of the TT genotype. Higher up-regulation of IL-24 and IL-1β mRNA in cells with the TT genotype was observed. Furthermore, blood samples from 64 Yusho patients who were accidentally exposed to high concentrations of dioxins were analyzed for the genotype, dioxins concentrations and serum levels of IL-24 and IL-1β. We observed higher serum IL-24 levels and lower serum IL-1β levels in Yusho patients with the TT genotype than in those with the CC genotype. AhR SNP -130 C/T affects serum IL-24 and IL-1β levels, independently of serum dioxins concentrations in Yusho patients. Our observations demonstrate that SNP -130 C/T modulates AhR expression and expression levels of IL-24 and IL-1β, and suggest an association of AhR SNP -130 C/T with the susceptibility to dioxins., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The world of communication has changed significantly in the last decade as a result of the evolution of social media. Food crisis managers and communicators should be cognizant of the messages presented to the public by all media channels during a crisis. Using the 2008 Irish dioxin contamination incident as an example, a quantitative content analysis was carried out to investigate the relationship between social and traditional media. Messages published in printed newspapers (n = 141), blogs and forums (n = 107), and Twitter (n = 68) were analysed to investigate sourcing practice, story topic and use of tone. Results revealed that traditional media relied on diverse offline sources in reporting a wide range of topics. In comparison, social media responded faster and diminished faster, using offline and online media news messages as the primary sources in reporting very limited topics. No significant difference was found in the presence of negative tone across media., (© The Author(s) 2013.)

Objectives: to verify if a carpenter using wood scraps, treated or not, to operate the heating system may involve an exposure to dioxins in a given target of workers., Design: the research was structured on literature sources analysis, study on field of the most relevant exposure, occurs through sampling. The results were recorded and plotted, and compared with the data available in literature., Setting and Participants: the study has involved maintenance workers of the heating system by means of wood refuse incineration. These workers were informed of the methods and aims of the sample., Main Outcome Measures: the results confirm a potential exposure to ash containing dioxins, presumably also in other similar situations, in this case not even evaluated by the employer., Results: the average exposure to the light ash during the maintenance operations of the plant dust abatement in emissive phase is about 5 mg/m(3), with a consequent exposure to dioxins inferred, at about 20 pg., Conclusion: operators are exposed to dioxins: this implies that in some operations it is crucial to review the risk assessment and consequently the measures on prevention and health protection to activate.

Results of recent studies showed that 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are equipotent in domestic chicken (Gallus gallus domesticus) while PeCDF is more potent than TCDD in ring-necked pheasant (Phasianus colchicus) and Japanese quail (Coturnix japonica). To elucidate the mechanism(s) underlying these differences in relative potency of PeCDF among avian species, we tested the hypothesis that this is due to species-specific differential binding affinity of PeCDF to the aryl hydrocarbon receptor 1 (AHR1). Here, we modified a cell-based binding assay that allowed us to measure the binding affinity of dioxin-like compounds (DLCs) to avian AHR1 expressed in COS-7 (fibroblast-like cells). The results of the binding assay show that PeCDF and TCDD bind with equal affinity to chicken AHR1, but PeCDF binds with greater affinity than TCDD to pheasant (3-fold) and Japanese quail (5-fold) AHR1. The current report introduces a COS-7 whole-cell binding assay and provides a mechanistic explanation for differential relative potencies of PeCDF among species of birds., (Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.)

Background: Dioxin-like chemicals are known to exert their effect by binding to aryl hydrocarbon receptor (AhR), forming complexes with aryl hydrocarbon nuclear translocator (ARNT), and binding to dioxin responsive elements (DREs) in promoter region to regulate the transcription of specific genes. In a previous study of the Yucheng cohort of humans who were exposed to high toxic levels of dioxin-like chemicals (PCDFs and PCBs), we reported marked induction of cytochrome P450 1A2 (CYP1A2) activity and this induction was an excellent biomarker of the exposure and adverse human health effects seen in the Yucheng cohort., Objectives: The goal of this study was to determine the relationship between inducibility of CYP1A2 and genetic polymorphisms of AhR, ARNT, and AhRR in human., Methods: The Yucheng victims who completed blood sample collecting in 1994-1995 for serum concentrations of PCB, PCDF, and PCDD congeners, and also completed the caffeine breath tests for CYP1A2 activity were identified. From the collected blood samples, six single nucleotide polymorphisms were selected for genotyping, including AhR (rs2066853), AhRR (rs2292596), ARNT (rs7517566), ARNT (rs3820541), ARNT (rs3768016), and ARNT (rs2228099)., Results: AhRR (rs2292596) polymorphism was significantly related to CYP1A2 inducibility (p=0.01). A linear trend test was observed between people with AhRR (rs2292596) GG, GC, and CC genotype (p=0.0014)., Conclusion: Overall, AhRR (rs2292596) genotypes predict the inducibility of CYP1A2 in people highly exposed to toxic dioxin-like chemicals. Future studies and analysis will determine to what degree these polymorphisms can predict a human's susceptibility to dioxin-related adverse human health effects., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Persistent organic pollutants (POPs) are a group of chemical substances that have the common properties of resistance to biodegradation, wide-range transportation, high lipophilicity, bioaccumulation in fat, and biomagnification in the food chain. POPs are persistent in the environment worldwide and have potential adverse impacts on human health and the environment. Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) are well known chemicals that are considered as POPs. The association between high-level exposure to dioxins and type 2 diabetes among U.S. Air Force veterans who had been exposed to Agent Orange contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during the Vietnam War was reported in the late 1990s. This association has been supported by similar epidemiologic studies, whose subjects were exposed to high doses of dioxins in their places of work involving phenoxyacid herbicide production and spraying, and in the industrial accident in Seveso, Italy. Recently, low-level exposure to dioxins and PCBs has been reported to be linked to type 2 diabetes. Cross-sectional studies in the U.S. general population and Japanese general population showed that body burden levels of some dioxins and PCBs were strongly associated with the prevalence of type 2 diabetes. Very recently, following these cross-sectional studies, several prospective studies have suggested that low-level exposure to some PCBs predicted the future risk of type 2 diabetes in the general population. Environmental exposure to some dioxins and PCBs, which mainly accumulate in adipose tissue, may play a role in the development of type 2 diabetes.

Objectives: Little information is available on conditional survival among Yusho patients, who were accidentally exposed to PCBs and other dioxin-related compounds. In this study, we estimated relative survival among Yusho patients to quantify time trends in excess mortality compared to the general population., Methods: A total of 1664 Yusho patients (860 males, and 804 females) were analyzed as Yusho cohort subjects. Relative survival ratio (RSR) was calculated as a measure of patient survival., Results: Overall, 1-, 5-, 10-, and 15-year RSRs were 1.00 (95% confidence interval (CI): 0.99, 1.00), 1.00 (95% CI: 0.99, 1.01), 0.99 (95% CI: 0.98, 1.00), and 0.99 (95% CI: 0.98, 1.01), respectively. We did not observe meaningful increases or decreases in RSRs in either sex, which remained the same in all age groups for 1-, 5-, 10-, and 15-year RSRs., Conclusions: This study provides quantitative evidence that Yusho patients have no significant difference in relative survival compared with the general Japanese population. Our results suggest that PCBs and dioxin exposure confers no excess mortality. This information may be important for both the clinical management of and patient coping with Yusho disease., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We determined dioxin-like polychlorinated biphenyls (PCBs) and PCBs in 6 preserved umbilical cords of fetal Yusho patients and in 11 preserved umbilical cords of Yusho suspected persons who were born to mothers with Yusho from 1970 to 2002, which were Yusho group. As a control, we also analyzed dioxin-like PCBs and PCBs in 15 preserved umbilical cords of babies who were born to healthy mothers, which was healthy group, in the same period of time. As a result, concentrations of three dioxin-like PCBs, that is, #156, #157 and #189 which were 6 to 20 times higher in fetal Yusho patients than in healthy babies were still 4 to 6 times greater in Yusho group than in healthy group about 20 years after the outbreak of Yusho, but could not recognize this characteristic anymore about 30 years after the outbreak. Decreasing rate in concentrations of dioxin-like PCBs and PCBs seemed to higher in Yusho group than in healthy group during this period of time. Therefore, we considered due to heavy exposure to PCDFs some drug metabolizing enzymes such as aryl hydrocarbon hydroxylase were induced and excretion of the related agents to fetal Yusho were enhanced from the bodies of Yusho group. In order to clarify this hypothesis, further more detail studies are needed.

Breast cancer affects Iranian women one decade younger than their counterparts in other countries and the underlying risk factors have remained controversial. The aryl hydrocarbon receptor (AhR) mediates endocrine disruptive activities of polyaromatic hydrocarbons (PAHs) and dioxins, which may compromise ovarian functions of women in polluted environments. This study focused on tissue expression levels of AhR and associations with exposure to chemicals with estrogen-like activities (xenoestrogens) and other reproductive factors in premenopausal breast cancer patients. Fifty cases who underwent surgery from June 2009 to June 2010 were matched with 100 controls by age and hospital records. AhR overexpression was detected in 87% of epithelial cells of young breast cancer patients. Living near factories generating PAHs and dioxins was considered as a major risk factor in premenopausal breast cancer (p=0.001, OR=4.8). History of idiopathic infertility was identified as a second significant risk factor (p=0.002, OR=3.50), which could be affected by endogenous estrogen levels. Long term (>5 yrs) consumption of oral contraceptive pills was identified as the third most important risk factor (p=0.006, OR=2.27). Adiposity and abnormal weight gain after 18 years were considered as two major background factors, which may contribute to the levels of endogenous estrogens. Direct and indirect exposure to cigarette smoke (p=0.005, OR=1.43) was considered as a weak risk factor without association with AhR levels. It seems that AhR overexpression is affected by exposure to xenoestrogens and by adiposity. Early occurrence of breast cancer in Iran may be a result of interactions between hormonal and environmental factors.

An epidemiologic examination was carried out to reveal the prevalence of the periodontal diseases and oral pigmentation in patients with Yusho in 2008. The results obtained were as follows. 1) Yusho patients complained of tooth pain and periodontal diseases such as gingival swelling, gingival bleeding, but not of oral pigmentation. 2) 116 patients out of 148 patients with Yusho, who were measured periodontal pocket depth according to Ramfjord' methods, had at least one tooth with periodontal pocket deeper than 3 mm. Similarly, 399 teeth out of a total 710 examined teeth showed a periodontal pocket with more than 3 mm in depth. However, it was determined that 74 teeth had a periodontal pocket deeper than 4 mm. 3) Oral pigmentation was observed in 91 patients out of 155 patients with Yusho. In this study, gingival pigmentation was most predominant among oral pigmentation. The prevalence of oral pigmentation in male patients seemed to be somewhat higher than that in female patients. In addition, the prevalence of oral pigmentation tended to be higher in younger patients than in elder patients. Pigmentation of the buccal mucosa, lip or palate, however, was observed only in patients beyond the age of fifty. These results indicated that PCB-related compounds may be responsible for the higher prevalence of both periodontal diseases and oral pigmentation.

To elucidate the exposure levels of polychlorinated biphenyls (PCBs) for Yusho patients, we conducted a congener-specific analysis of polychlorinated biphenyls (PCBs) in blood collected from 242, 237, 300, and 96 Yusho patients during medical check-ups performed from 2004 to 2007, respectively, and in samples from 74, 113, 125, and 148 Yusho-suspected persons during those same years, respectively, and compared the individual congener concentrations of PCBs among the groups of Yusho patients, Yusho-suspected persons, and normal controls with the concentrations previously reported. Among the 209 PCB congeners, 8 congeners of mono-ortho PCBs and 56 congeners of non-dioxin-like PCBs were identified in the blood of Yusho patients and Yusho-suspected persons. Among the PCB congeners measured in the present study, hexaCB-153, hexaCB-138, heptaCB-180, and heptaCB-182/heptaCB-187 showed high ratios to total concentrations of 64 PCB congeners detected in the blood of Yusho patients and Yusho-suspected persons from 2004 to 2007, and the profiles of the major congeners were the same as those obtained in normal controls. With respect to the minor congeners of PCBs, several differences were observed among the three groups. The sums of the concentrations of 64 PCB congeners in the blood of Yusho patients from 2004 to 2007 were 645, 760, 667, and 510 ng g(-1) lipid for each year, respectively, and the concentrations were 1.5, 1.8, 1.5, and 1.2 times higher than those of normal controls for each year, respectively. Those of the Yusho-suspected persons were approximately 0.8, 1.1, 0.9, and 1.0 times higher than those of normal controls for each year, respectively. The ratios of heptachlorinated biphenyls (heptaCBs) to the total concentrations of 64 PCB congeners in the blood of Yusho patients and Yusho-suspected persons from 2004 to 2007 tended to be slightly higher than those in the normal controls. From the results comparing the concentrations of 64 PCB congeners in the blood between Yusho patients and normal controls, the concentrations of hexaCB-156, hexaCB-157, heptaCB-181, and heptaCB-189 for Yusho patients were 3.4, 3.8, 3.9, and 3.8 times, respectively, 3.9, 4.1, 3.9, and 4.4 times, respectively, 3.6, 3.9, 5.0, and 4.1 times, respectively, and 2.3, 2.5, 2.7, and 2.9 times higher than those of the normal controls for each year from 2004 to 2007, respectively. These results indicated that Yusho patients still have higher concentrations of hexaCB-156, hexaCB-157, heptaCB-181, and heptaCB-189 in their blood than do unaffected people, even though over 35 years have passed since the outbreak of Yusho. These four congeners can therefore be considered to be the most important congeners for evaluating the PCBs exposure of Yusho patients.

Dioxins are known as endocrine disrupters and widespread environmental contaminants. They are bioaccumulated in the human body. In this study, we determined concentrations of dioxins (PCDD, PCDF, Non-ortho PCB and Mono-ortho PCB) in eighteen umbilical cords provided by twelve mothers of Yusho patients and twelve umbilical cords provided by ten mothers of normal controls. The average concentrations of PCDD, PCDF, Non-ortho PCB, Mono-ortho PCB and total dioxins (PCDD/ F + Dioxin-like PCB) in the umbilical cords of Yusho patients and normal controls were 0.55, 4.55, 0.08, 0.08 and 5.26 pg-TEQ/g, respectively, and 0.50, 0.11, 0.03, 0.02 and 0.66 pg-TEQ/g, respectively. Total dioxins and PCDF concentrations in the umbilical cords of Yusho patient were about 8 and 40 times higher than those in the umbilical cords of normal controls, respectively. The average concentration of 2,3,4,7,8-PeCDF in the umbilical cords of Yusho patients was 10 pg/g. We couldn't detect 2,3,4,7, 8-PeCDF in the umbilical cords of normal controls. We suspected the 2,3,4,7,8-PeCDF concentrations in the mothers' blood were related to the 2,3,4,7,8-PeCDF concentrations in umbilical cords.

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.

Yusho is recognized as a poisoning by a mixture of polychlorinated biphenyls (PCBs), dioxins and related compounds. We have continued a follow-up of skin symptoms in patients not only for supporting patients' health but also for understanding the possible prolonged effects of exposure to PCBs and dioxins in humans. We evaluated the severity grades and the skin severity scores of the symptoms who visited the annual examinations of Fukuoka prefecture from 2005 to 2007. Forty years have passed since the Yusho incident, and about 70% of the patients currently present no skin symptoms. In contrast, in about 30% of the patients, characteristic skin symptoms of Yusho, such as pigmentation of skin, black comedones and acneform eruptions, could still be observed. We analyzed statistical correlations between blood levels of PCBs or dioxin and skin severity grades.

PCB and dioxin-like PCB (DL-PCB) in 28 umbilical cords preserved from the time when 3 Yusho victims and 11 healthy subjects gave birth were examined in order to investigate the pollution evaluation with both the compounds in Yusho victims on the basis of the analytical value. As a result, in a period of 1968 to the 70s immediately after Yusho incident, the total concentration of the 12 DL-PCB isomers in both the Yusho victims s and healthy subjects was very high. After that, the total DL-PCB concentration decreased temporally. However, there was not observed a significant difference in the concentration and composition of both contaminants between the two groups.

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.

Polychlorinated biphenyls (PCB) causes the release of superoxide during the metabolic process. Therefore, Yusho victims are thought to be exposed to oxidative stress caused by PCB, because high concentrations of PCB are still detected in the serum of Yusho victims. Furthermore, oxidative stress contributes to the generation of autoantibodies because of oxidative modification. In order to estimate the autoantibody in Yusho victims, we mesured serum levels of anti-SS-A antibody (Ab) and anti-SS-B Ab both in certified Yusho victims and age-matched controls. The mean values of anti-SS-A Ab were 4.0 +/- 17.1 (Index) in certified Yusho victims and 0.7 +/- 0.5 (Index) in controls. And the mean values of anti-SS-B Ab were 7.4 +/- 4.6 (Index) in certified Yusho victims and 5.6 +/- 1.7 (Index) in controls. Although the occurrence rates of anti-SS-A Ab and anti-SS-B Ab were high in Yusho victims, there were no significant difference between Yusho victims and controls.

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.

Dioxins may have impact on the human immunological system, which would increase the risk to develop allergic diseases, such as atopic dermatitis. In order to determine the lifetime prevalence of atopic dermatitis in Yusho patients, a questionnaire-based survey was conducted in 2007. Six hundred and thirty-eight out of 731 certified yusho patients answered the questionnaires, and the prevalence of atopic dermatitis in Yusho patients was 8.8%. We also measured serum IgE in 83 certified and 98 non-certified Yusho patients who attended an annual medical check-up in 2007. Mean serum levels of IgE in certified Yusho patients were 386.2 +/- 1128.0 IU/ml, whereas those in non-certified Yusho patients were 272.1 +/- 603.6 IU/ml. There was no significant difference in serum levels of IgE between certified and non-certified Yusho patients. In addition, no significant correlation was observed between serum levels of IgE and blood levels of dioxins in certified Yusho patients.

We measured bone mineral density of the distal end of radius with dual energy X-ray absorptiometry, serum cross-linked N-telopeptides of type I collagen, serum bone-specific alkaline phosphatase, serum Ca, serum P, blood PCB level, blood PCQ level and blood PCDF level in Yusho. As a result, the osteoporosis group (< 70% of the young adult mean [YAM] bone mineral density [BMD]) was observed in 7.1% of the studied male subjects. And, the moderate group (> or = 70% and < 80% of YAM BMD), 16.1%, the normal (> or = 80% of YAM BMD) group was 76.8%. Also, 42.3% of all female tested subjects observed in osteoporosis group. The moderate group, 19.2%, the normal group was 38.5%. There was no difference in PCB blood level, PCQ, PCDF for men and women in osteoporosis group, moderate group, and in the normal group. Serum cross-linked N-telopeptides of type I collagen increased in the male osteoporosis group, but serum bone-specific alkaline phosphatase did not change. This study was inconclusive since the results did not determine the influence that PCB, PCQ, PCDF gave to bone density and bone metabolism.

To investigate chronic immune effects of polychlorinated biphenyl (PCB) and polychlorinated dibenzofuran (PCDF), lymphocyte subpopulations in peripheral blood were studied in 156 patients with Yusho in 2008. Significant relationships between the concentrations of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) in the blood and the absolute densities of the total lymphocyte population, or of the T-cell subpopulation reactive with CD4 were observed, while there was no correlation between the blood PCB levels and the densities of total lymphocyte population, or CD4, CD8 or CD20 positive cells in peripheral blood. Mean absolute densities of total lymphocyte population and T-cell subpopulation expressing CD4 were significantly increased in the Yusho patients with high 2,3,4,7, 8-PeCDF levels compared with those in the patients with low 2,3,4,7,8-PeCDF levels. We conclude that the increase of CD4 positive cells in patients with Yusho may be associated with blood 2,3,4,7,8-PeCDF levels.

Forty years have passed since the outbreak of Kanemi rice oil poisoning, namely, Yusho in the western Japan. However, even now the patients with Yusho have been still suffering from several objective and subjective symptoms. In order to improve or, if possible, to cure such symptoms, the most important therapeutic treatment is considered to actively excrete the causative agents, that is, polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzo-p-dioxins (PCDDs) from the bodies of the patients and to reduce their body burdens. In rats, chlorophyll and dietary fiber have been shown to promote the fecal excretion of PCDFs and PCDDs and to reduce their levels in rats. In this study, we have examined whether such kinds of effect are also observed by fermented brown rice with Aspergillus oryzae (FBRA) containing 5% spirulina, which is so-called spirulina HI*GENKI, the health food and relatively rich with chlorophyll and dietary fiber, in eighteen patients with Yusho. They were divided into two groups, namely group A, ten patients (3 males and 7 females) with the mean age of 67.7 years old and group B, eight patients (4 males and 4 females) with the mean age of 64.1 years old. Respective mean concentrations of the three PCDF congeners, that is, 2,3,4,7,8-PenCDF, 1, 2,3,4,7,8-HxCDF and 1,2,3,6,7,8-HxCDF in the blood on lipid weight basis just before initiating this study were as follows; group A: 413, 152 and 45.7 pg/g lipid, and group B: 151, 42.7 and 17.3 pg/g lipid. Contamination levels of these PCDF congeners in group A were 2.6 to 3.6 times higher than those in group B. In respective mean concentrations of PCDFs, PCDDs and PCDFs/DDs in both groups were as follows; group A: 228, 30.9 and 258 pg-TEQ/g lipid, and group B: 82.4, 19.7 and 102 pg-TEQ/g lipid. Contamination levels of PCDFs and PCDDs were around 2 times higher in group A than in group B. Group A took around 7.0 g of spirulina HI*GENKI after each meal and tree times a day for the first one year and for the second one year, they did not take spirulina HI*GENKI any more. Group B took spirulina HI*GENKI with the same manner as the group A only for the second one year. The concentrations of PCDFs and PCDDs in the blood of groups A and B were also measured at the end of the first and second year, respectively. Assuming the body fat is also contaminated with PCDFs and PCDDs at their concentrations on lipid weight basis in the blood and the content of body fat is 20% of 60 kg body weight, we computed the average amounts in the net excretion of PCDFs and PCDFs/DDs from the body of the patients due to the intake of spirulina HI*GENKI in groups A and B. As a result, in group A, 85.0 and 99.6 ng-TEQ/patient, respectively were excreted from the body of the patients. In group B, only 38.1 nd 40.0 ng-TEQ/patient were excreted. Accordingly, promotive excretion of PCDFs and PCDDs from the patients with Yusho seemed much effective in group A, of which their concentrations in the blood were much higher than those of group B.

Necropsy and histopathologic examination of three Great Cormorants (Phalacrocorax carbo) shot in Niigata, central Japan, revealed goitrous changes in the thyroids. Thyroids had a hypertrophic follicular epithelium, loss or deficiency of luminal colloid, occasional small follicles suggesting hyperplasia, and occasional collapsed follicles. Irregularly shaped follicles were frequent, and hyperemia, deposition of dark pigment, and sporadic lymphoid aggregates were also seen. Chemical analysis simultaneously conducted showed higher than normal levels of dioxins in the liver, muscle, and fat, i.e., polychlorinated dibenzo-dioxins, polychlorinated dibenzo-furans, and coplanar polychlorinated biphenyls. The present results, together with those of relevant previous studies, strongly suggest an association between these pollutants and thyroid lesions in the Great Cormorant.

Objective: The pathogenesis of sporadic pituitary tumors is unknown. Loss-of-function mutations of aryl hydrocarbon receptor-interacting protein (AIP) have been identified in patients with familial pituitary tumors. AIP is a chaperone protein with multifunction properties, including modulation of the transcriptional activity of the aryl hydrocarbon receptor, which mediates toxicological and carcinogenic dioxin effects., Design: We investigated the incidence of pituitary tumors in the Seveso population exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin following an industrial accident in 1976., Methods: Through the hospital discharge registration system of Lombardy Region, we identified incident cases of pituitary adenomas between 1976 and 1996 in the Seveso population, subdivided in zone A (n=804), B (n=5.941), and R (n=38.624) according to high, intermediate, and low exposure to dioxin respectively, and in the surrounding non-contaminated area, as reference (n=232 745)., Results: We identified 42 pituitary adenomas in the reference area, 1 prolactinoma in zone A (rate ratio (RR) 6.2; 95% CI 0.9-45.5, P=0.07), 2 nonfuctioning pituitary tumors (NFPAs) in zone B (RR 1.9; 95% CI 0.5-7.7, P=0.39), and 3 prolactinomas and 2 NFPAs in zone R (RR 0.7; 95% CI 0.3-1.8, P=0.48)., Conclusions: The study is unique with regard to the availability of epidemiological and clinical data in an area of relatively pure dioxin exposure. The study indicates no statistically significant increase of incident pituitary tumors in this area, although the tendency toward a higher risk (three cases in zones A and B) of pituitary tumors in subjects exposed to high-intermediate dioxin concentrations in comparison with nonexposed population suggests the need for extended follow-up.

Background: Dioxin emissions from municipal solid waste incinerators are one of the major sources of dioxins and therefore are an exposure source of public concern. There is growing epidemiologic evidence of an increased risk for non-Hodgkin's lymphoma (NHL) in the vicinity of some municipal solid waste incinerators with high dioxin emission levels. The purpose of this study was to examine this association on a larger population scale., Methods: The study area consisted of four French administrative departments, comprising a total of 2270 block groups. NHL cases that had been diagnosed during the period 1990-1999, and were aged 15 years and over, were considered. Each case was assigned a block group by residential address geocoding. Atmospheric Dispersion Model System software was used to estimate immissions in the surroundings of 13 incinerators which operated in the study area. Then, cumulative ground-level dioxin concentrations were calculated for each block group. Poisson multiple regression models, incorporating penalized regression splines to control for covariates and dealing with Poisson overdispersion, were used. Five confounding factors were considered: population density, urbanisation, socio-economic level, airborne traffic pollution, and industrial pollution., Results: A total of 3974 NHL incident cases was observed (2147 among males, and 1827 among females) during the 1990-1999 time period. A statistically significant relationship was found at the block group level between risk for NHL and dioxin exposure, with a relative risk (RR) of 1.120 (95% confidence interval [CI] 1.002 - 1.251) for persons living in highly exposed census blocks compared to those living in slightly exposed block groups. Population density appeared positively linked both to risk for NHL and dioxin exposure. Subgroup multivariate analyses per gender yielded a significant RR for females only (RR = 1.178, 95% CI 1.013 - 1.369)., Conclusion: This study, in line with previous results obtained in the vicinity of the incinerator located in Besançon (France), adds further evidence to the link between NHL incidence and exposure to dioxins emitted by municipal solid waste incinerators. However, the findings of this study cannot be extrapolated to current incinerators, which emit lower amounts of pollutants.

The Seveso accident in 1976 caused a large, populated area north of Milan, Italy, to be contaminated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In this study, the authors followed up the exposed population for chronic effects; this paper reports the results of the mortality follow-up extension for 1997-2001. The study cohort includes 278,108 subjects resident at the time of the accident or immigrating/born in the 10 years thereafter in three contaminated zones with decreasing TCDD soil levels (zone A, very high; zone B, high; zone R, low) and in a reference territory comprising surrounding, noncontaminated municipalities. Vital status and cause-of-death ascertainment were 99% complete. Adjusted rate ratios and 95% confidence intervals were calculated by using Poisson regression. Results confirmed previous findings of excesses of lymphatic and hematopoietic tissue neoplasms in zones A (six deaths; rate ratio = 2.23, 95% confidence interval: 1.00, 4.97) and B (28 deaths; rate ratio = 1.59, 95% confidence interval: 1.09, 2.33). These zones also showed increased mortality from circulatory diseases in the first years after the accident, from chronic obstructive pulmonary disease, and from diabetes mellitus among females. A toxic and carcinogenic risk to humans after high TCDD exposure is supported by the results of this study.

We have investigated the effects of prenatal exposure to dioxin-like compounds (PCDDs, PCDFs and dioxin-like PCBs), PCBs and organochlorine pesticides (DDT, HCH, chlordane, HCB and their metabolites) on the incidence of congenital hypothyroidism and/or cretinism in Fukuoka, Japan from 2001 to 2004. Thirty-four positive neonates of the mass-screening for cretinism were classified into three groups by the pediatrician after the reevaluation of the serum TSH level, that is, negative in reevaluation group, hyper thyroid stimulating hormone (TSH) emia group and cretinism group. One-hundred and two negative neonates of the mass-screening were classified into the normal group. Concentrations of these organochlorine compounds in the breast milk of mothers, which were considered as the indicator of prenatal exposures to them, were gradually increased from the normal group to the cretinism group in the four groups and were around two times higher in the cretinism group than in the normal group. According to the case-control study adjusted for the parity and mother's age, odds ratios of PCBs, DDT and HCB were 10 (p=0.003), 10 (p=0.003) and 22 (p=0.004), respectively and in dioxin-like compounds, PCDFs showed the highest odds ratio, 9.8 (p=0.005). Based upon those findings, these compounds seemed play an important role in the incidence and/or causation of the cretinism.

In this study, we examined the dioxin levels and congener distributions in blood samples of Yusho patients and normal control subjects, especially in relation to the respective exposure routes. Remarkable differences were observed between the blood of Yusho patients and general population in terms of both congener distributions and concentration levels. Cumulative dioxin intake for Yusho patients was estimated using the mean Yusho oil consumption and congener-specific dioxin contamination data for Yusho oil; for control subjects, it was estimated from food consumption and dioxin congener contamination data. Estimated total intake of dioxins was 2.44 microg-TEQ for control subjects and 357 microg-TEQ for Yusho patients, respectively. The total intake of some congeners such as 2,3,4,7,8-PeCDF and 1,2,3,4,7,8-HxCDF for Yusho patients was more than 100 times higher than those of control subjects. The congener distribution of PCB and PCDD in the blood of control subjects was similar to those of the food. In the case of Yusho patients, however, the congener distribution did not resemble those of either the food or the causal Kanemi rice oil, nor did not match that of control subjects' blood. Selective metabolizing of congeners was suggested to have occurred in the Yusho patients. In a 2001 fiscal year survey, the concentration ratio of TEQ between Yusho and normal subjects was 4.5. However, the level of 2,3,4,7,8-PeCDF, thought to be the congener that had the closest relation to various symptoms of the Yusho patients, was ten times or more in Yusho patients than in controls. It is suggested that further examinations should be conducted in the future to follow up this survey monitoring the blood levels of toxic congeners in Yusho patients.

Fish meat content high nutritive value and essential polyunsaturated fatty acids, while low consumption of fish and fishery products in Poland. Fat meat of Baltic sea fish can also contain higher levels of dioxins and organochlorinated contaminants. Consumption of fish and fishery products in Poland ought to include different species from various catch areas.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and member of the bHLH/PAS (basic Helix-Loop-Helix/Per-Arnt-Sim) family of chemosensors and developmental regulators. It represents a multifunctional molecular switch regulating endo- and xenobiotic metabolism as well as cell proliferation and differentiation. Physiologic functions of the AhR are beginning to be understood, including functions in vascular development, and in detoxification of endo- and xenobiotics. The AhR is also recognized as the culprit for most toxic responses observed after exposure to dioxins and related compounds such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The non-metabolizable AhR agonist TCDD has to be distinguished from the myriad of metabolizable agonists present as dietary contaminants and plant constituents as well as endogenous toxins. The hypothesis is emerging that the diverse tissue-specific, TCDD-mediated toxicities are due to sustained and inappropriate AhR activation leading to deregulated physiologic functions. In support of this hypothesis recent observations in the context of some TCDD-mediated toxic responses are discussed, such as chloracne, cleft palate, thymus involution and in particular carcinogenesis. Major open questions are addressed, such as ligand-independent AhR activation by phosphorylation and the large differences in species-dependent susceptibility to toxic responses. Though important issues remain unresolved, the commentary is intended to stimulate efforts to understand dioxin-mediated toxic responses with emphasis on carcinogenesis in comparison with AhR-mediated physiologic functions.

Objective: Dioxins decrease prostate weight, reduce androgen responsiveness, and inhibit prostate morphogenesis in rats. We assessed the association of dioxins and benign prostatic hyperplasia (BPH) in participants in the National Health and Nutritional Examination Survey 1999-2000., Methods: Forty-two participants were classified as having BPH and 99 were classified as controls. Dioxin exposure was expressed as dioxin toxic equivalents (TEQ). Age, body mass index, waist circumference, race/ethnicity, smoking, physical activity, and education were assessed as potential confounders., Results: After age adjustment, men without BPH had 20.9% higher TEQs (95% confidence interval [CI] = 5.4-38.7%) as compared with men with BPH. On weighted, multivariate, logistic regression analyses, men with higher dioxin levels had lower odds of having BPH (odds ratio = 0.22, 95% CI = 0.08-0.62)., Conclusions: Dioxin exposure in the general population may be associated with decreased odds of BPH. Our study findings need to be confirmed.

Objectives: Animal experiments suggest that thyroid function alterations in newborns and infants may represent one of the most sensitive markers of toxicity from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dioxin can be transferred from the mother to the offspring either in utero or through lactation. It has been suggested that thyroid-hormone alterations produced by dioxin in utero or shortly after birth may underlie long-term effects, such as cognitive-ability and neurodevelopment impairment. In the present review article, we appraise available evidence on the effects of perinatal exposure to dioxin on fetal and infant thyroid function., Methods: We summarized the routes of perinatal dioxin exposure and research results on possible mechanisms of dioxin toxic effects on thyroid function. We performed a systematic review of epidemiology studies conducted on mother-child pairs exposed to background environmental levels to investigate dioxin effects on neonatal and infant thyroid function., Results: Toxicological and mechanistic data indicate that dioxin may impair thyroid function in exposed newborns and infants. Investigations on background-exposed children have not consistently demonstrated an association between perinatal TCDD exposure and thyroid function, although some of the studies suggest that sub-clinical hypothyroidism may be induced by perinatal dioxin exposure within 3 months from birth. Between studies inconsistencies may be related to lab method differences, mixed exposures, and small sample size of the populations evaluated., Conclusion: Epidemiology studies have as yet failed to demonstrate an association between perinatal TCDD exposure and thyroid function alterations in human subjects, although suggestive evidence from animal and in-vitro experimental data is available.

The presence of dioxins and dioxin-containing ecotoxicants (DCE) in human environment leads to multi-level homeostasis disbalance and, eventually, dioxin pathology (DP) develops. This was demonstrated for the adult population of South Vietnam (1), who had suffered from the use of military chlorphenoxiherbicides to which dioxins had been added. The subjects of this study were children who belonged to the second generation of the inhabitants of DCE-polluted South Vietnam areas. In this sample, the frequency of malformations depending on two factors, genes GSTMI, GSTT1, CYP1A1 genotypes, and DCE exposure, were estimated. The study demonstrates that an increased level of congenital morphogenetic variants per one child is associated with the presence of DCE in the environment, as well as the fact that this parameter is influenced by genotypes of xenobiotic detoxication genes.

Polychlorinated biphenyls (PCB) have been suspected as possible contributors to increasing non-Hodgkin's lymphoma incidence during the latter half of the 20th century based on their toxicologic properties and provocative epidemiologic reports. We investigated PCBs and other organochlorines and risk of non-Hodgkin's lymphoma in a population-based case-control study in the United States. Congeners of PCBs (including coplanar congeners), dioxins, furans and pesticides or pesticide metabolites were measured in plasma of 100 untreated cases and 100 control subjects. We used a multiple imputation procedure to fill in missing values of levels determined to be below the detection limits. Risks of non-Hodgkin's lymphoma associated with each analyte were estimated using conditional logistic regression for the continuous measure, exposure quartiles, trend across quartile categories, and exposures above the 95th percentile. Certain PCB congeners were associated with increased risk of non-Hodgkin's lymphoma, including coplanar PCBs 156, 180, and 194, with odds ratios for the highest versus lowest quartile ranging from 2.7 to 3.5, and significant trends. Each of the furan congeners was associated with risk of non-Hodgkin's lymphoma, as were total furans, with 3.5-fold increased risk for the highest versus lowest quartile and a significant trend across quartiles (P = 0.006). The toxic equivalency quotient (TEQ), a summed metric that weights congeners by their dioxin-like potency, was associated with non-Hodgkin's lymphoma, with 35% increased risk per 10 TEQ pg/g lipid (95% confidence interval, 1.02-1.79). Our results add to existing literature, which suggests that exposure to organochlorines contributes to non-Hodgkin's lymphoma risk; these risks were most apparent for certain PCBs and furans.

Commonly designed by the term "dioxins", polychlorinated aromatic hydrocarbons are environmental pollutants leading to several toxic effects during development and growth in embryo and child. The general consequences of dioxin exposure are particularly well-documented whereas only few data are mentioned by the experts concerning tooth development. However, studies performed in rodents have shown many disruptions during odontogenesis and enamel mineralisation. Moreover, recent epidemiological studies have demonstrated in human the incidence of dioxin exposure on enamel hypomineralisation and hypodontia. The aim of this review is to report recent data about consequences of dioxin exposure on tooth development, tooth being considered as a biological marker of potential dioxin poisoning.

The recent attempt to poison Ukrainian President, Viktor Yuschenko with dioxins, raised public concern regarding this toxic chemical. In industrial countries, there is a constitutive exposure of humans to dioxin compounds, which are formed as by-products in manufacturing processes of various chlorinated organic chemicals and in waste incinerators. Dioxins are extremely stable in the environment and have a low turnover rate in the body--sometimes they are detected years after the original exposure. Of the dioxins, the most notoriously famous is the TCDD (2,3,7,8 tetrachlorodibenzo-p-dioxin). Dioxins exhibit high acute toxicity in various animal species. Humans, however, are considered less susceptible and so far there were no reported deaths following acute dioxin poisoning. Nevertheless, numerous adverse health effects are attributed to dioxin exposure. The most prominent is the chloracne--an acute acneiform eruption, usually appearing on facial skin. There is a solid evidence base that some dioxins are carcinogens. Other long-term deleterious effects of dioxin include: immunosuppression, effects on reproduction, impairments in developmental, neurological and cognitive functions in infants, increased risk for diabetes and cardiovascular diseases and various hormonal alterations. The action of dioxins resembles that of hormones, since their toxicity is mostly receptor-mediated. Dioxins manifest their toxicity in extremely low concentrations. Although there are compounds that exhibit their biological activity at even lower dose range (e.g. nerve gases), this potency of dioxins is considered extraordinary, since there is an every-day exposure to dioxins through environmental vectors mostly via the food chain. Until now, there is no antidotal cure for dioxins, but only symptomatic treatment combined with techniques that accelerate its excretion rate from the body.