Undernutrition combined with dietary mineral oil hastens depuration of stored dioxin and polychlorinated biphenyls in ewes. 1. Kinetics in blood, adipose tissue and faeces.

Food safety crises involving persistent organic pollutants [POPs, e.g. dioxins, polychlorinated biphenyls (PCBs), organochlorine pesticides] lead to systematic slaughter of livestock to prevent their entry into the food chain. Therefore, there is a need to develop strategies to depurate livestock moderately contaminated with POPs in order to reduce such economic and social damages. This study aimed to test a POPs depuration strategy based on undernutrition (37% of energy requirements) combined with mineral oil (10% in total dry matter intake) in nine non-lactating ewes contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and PCBs 126 and 153. In order to better understand the underlying mechanisms of the depuration process, POPs kinetics and body lipids dynamics were followed concomitantly over 57-day of depuration in POPs storage (adipose tissue, AT), central distribution (blood) and excretion (faeces) compartments. Faecal POPs concentrations in underfed and mineral oil supplemented ewes increased by 2.0 to 2.6-fold, but not proportionally to lipids concentration which increased by 6-fold, compared to the control ewes. Nonetheless, after 57 days of depuration in undernutrition and mineral oil supplementation, AT POPs concentrations were 1.5 to 1.6-fold higher while serum concentrations remained unchanged compared to the control ewes. This was concomitant with a decrease by 2.7-fold of the AT estimated lipids weight along the depuration period. This reduction of the volume of the storage compartment combined with the increase of POPs faecal excretion in underfed and mineral oil supplemented ewes led to a reduction by 1.5-fold of the PCB 126 AT burden, while no changes were observed for TCDD and PCB 153 burdens (vs. no change for PCB 126 and increases for TCDD and PCB 153 AT burdens in control ewes). The original approach of this study combining the fine description at once of POPs kinetic and of body lipids dynamic improved our understanding of POPs fate in the ruminant.

Prenatal exposure to legacy contaminants and visual acuity in Canadian infants: a maternal-infant research on environmental chemicals study (MIREC-ID).

BACKGROUND: Prenatal exposure to environmental contaminants can have deleterious effects on child development. While psychomotor, cognitive and behavioural outcomes have been investigated in relation to chronic exposure, the associations with visual functions remains unclear. The present study's aim was to assess the associations of prenatal exposure to legacy persistent organic pollutants and heavy metals with visual acuity in Canadian infants. The potential protective effects of selenium against mercury toxicity were also examined. METHODS: Participants (mean corrected age = 6.6 months) were part of the Maternal-Infant Research on Environmental Chemicals (MIREC) study. Concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), lead and mercury were measured in maternal blood during pregnancy, as well as in the cord blood. The Teller acuity card test (TAC) (n = 429) and the visual evoked potentials in a sub-group (n = 63) were used to estimate behavioural and electrophysiological visual acuity, respectively. Multivariable linear regression models were used to investigate the relationship between exposure to each contaminant and visual acuity measures, while controlling for potential confounders. Breastmilk selenium, which was available for about half of the TAC and VEP samples, was also taken into account in the mercury models as exploratory analyses. RESULTS: We observed no significant associations between exposure to any contaminants and TAC. Analyses revealed a negative trend (p values < 0.1) between cord blood lead and mercury and electrophysiological visual acuity, whereas PCB and PBDE showed no association. When adding breastmilk selenium concentration to the mercury models, this association became statistically significant for cord concentrations (ß = - 3.41, 95% CI = - 5.96,-0.86), but also for blood levels at 1st and 3rd trimesters of pregnancy (ß = - 3.29, 95% CI = - 5.69,-0.88). However, further regression models suggested that this change in estimates might not be due to adjustment for selenium, but instead to a change in the study sample. CONCLUSIONS: Our results suggest that subtle, but detectable alterations of infant electrophysiological visual acuity can be identified in a population prenatally exposed to low mercury concentrations. Compared to behavioural visual acuity testing, electrophysiological assessment may more sensitive in detecting visual neurotoxicity in relation with prenatal exposure to mercury.

Association of blood polychlorinated biphenyls and cholesterol levels among Canadian Inuit.

BACKGROUND: It has generally been thought that Inuit populations have low risk of cardiovascular disease due to high consumption of omega-3 fatty acids found in traditional marine-based diets. However, results of recent surveys showed that Inuit populations are experiencing increasing rates of cardiovascular disease and related risk factors. OBJECTIVE: The purpose of this study was to investigate if blood polychlorinated biphenyls (PCBs) are associated with high cholesterol and related parameters in Canadian Inuit, known risk factors for cardiovascular disease. METHODS: The Adult Inuit Health Survey (IHS, 2007-2008) included 2595 Inuit participants from three regions of the Canadian Arctic, of which 2191 could be classified as with or without high cholesterol. The high cholesterol outcome was defined by LDL-C > 3.36mmol/L or taking medication(s) that reduce cholesterol, and was examined in adjusted logistic regression models with individual blood levels of PCB congeners, sum of dioxin-like PCBs (∑DL-PCBs), or sum of non-dioxin-like PCBs (∑NDL-PCBs). Statistically significant covariates for high cholesterol were ranked in importance according to the proportion of the model log likelihood explained. Continuous clinical parameters of total cholesterol, triglycerides, LDL-C, and HDL-C were examined in multiple linear regression models with ∑DL-PCBs or ∑NDL-PCBs. RESULTS: A total of 719 participants had high cholesterol (32.8%). PCBs were associated with increased risk of high cholesterol, and higher levels of serum triglycerides, total cholesterol, and LDL-C. No association was observed between PCBs and serum HDL-C. With respect to other statistically significant covariates for high cholesterol, the log likelihood ranking of PCBs generally fell between body mass index (BMI) and age. CONCLUSION: Further work is needed to corroborate the associations observed with PCBs and lipids in Canadian Inuit and to examine if they are causal in the direction anticipated.

Yusho and its latest findings-A review in studies conducted by the Yusho Group.

The Yusho incident is an unprecedented mass food poisoning that occurred in Japan in 1968. It was caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds, such as polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). The victims of Yusho have suffered from characteristic skin manifestations associated with systemic, ophthalmological, and mucosal symptoms for a long period of time. The Study Group of Yusho (the Yusho Group) has been conducting annual medical check-ups on Yusho victims for more than 45years. Since 2002, when concentrations of dioxins in the blood of Yusho patients started to be measured, the pharmacokinetics of dioxins, relationship between blood levels of dioxins and symptoms/signs in patients directly exposed to dioxins, and the adverse effects on the next generation have become dramatically clear. Herein we review recent findings of studies conducted by the Yusho Group to evaluate chronic dioxin-induced toxicity to the next generation as well as Yusho patients in comparison with a similar food mass poisoning, the Yucheng incident. Additionally, we summarized basic studies carried out by the Yusho Group to re-evaluate the mechanisms of dioxin toxicities in experimental models and various functions of the aryl hydrocarbon receptor (AhR), known as the dioxin receptor, pathway.

A cleanroom sleeping environment's impact on markers of oxidative stress, immune dysregulation, and behavior in children with autism spectrum disorders.

BACKGROUND: An emerging paradigm suggests children with autism display a unique pattern of environmental, genetic, and epigenetic triggers that make them susceptible to developing dysfunctional heavy metal and chemical detoxification systems. These abnormalities could be caused by alterations in the methylation, sulfation, and metalloprotein pathways. This study sought to evaluate the physiological and behavioral effects of children with autism sleeping in an International Organization for Standardization Class 5 cleanroom. METHODS: Ten children with autism, ages 3-12, slept in a cleanroom for two weeks to evaluate changes in toxin levels, oxidative stress, immune dysregulation, and behavior. Before and after the children slept in the cleanroom, samples of blood and hair and rating scale scores were obtained to assess these changes. RESULTS: Five children significantly lowered their concentration of oxidized glutathione, a biomarker of oxidative stress. The younger cohort, age 5 and under, showed significantly greater mean decreases in two markers of immune dysregulation, CD3% and CD4%, than the older cohort. Changes in serum magnesium, influencing neuronal regulation, correlated negatively while changes in serum iron, affecting oxygenation of tissues, correlated positively with age. Changes in serum benzene and PCB 28 concentrations showed significant negative correlations with age. The younger children demonstrated significant improvements on behavioral rating scales compared to the older children. In a younger pair of identical twins, one twin showed significantly greater improvements in 4 out of 5 markers of oxidative stress, which corresponded with better overall behavioral rating scale scores than the other twin. CONCLUSIONS: Younger children who slept in the cleanroom altered elemental levels, decreased immune dysregulation, and improved behavioral rating scales, suggesting that their detoxification metabolism was briefly enhanced. The older children displayed a worsening in behavioral rating scale performance, which may have been caused by the mobilization of toxins from their tissues. The interpretation of this exploratory study is limited by lack of a control group and small sample size. The changes in physiology and behavior noted suggest that performance of larger, prospective controlled studies of exposure to nighttime or 24 hour cleanroom conditions for longer time periods may be useful for understanding detoxification in children with autism. TRIAL REGISTRATION: Clinical Trial Registration Number NCT02195401 (Obtained July 18, 2014).

The Northern Norway Mother-and-Child Contaminant Cohort (MISA) Study: PCA analyses of environmental contaminants in maternal sera and dietary intake in early pregnancy.

BACKGROUND: Although predictors of contaminants in serum or whole blood are usually examined by chemical groups (e.g., POPs, toxic and/or essential elements; dietary sources), principal component analysis (PCA) permits consideration of both individual substances and combined variables. OBJECTIVES: Our study had two primary objectives: (i) Characterize the sources and predictors of a suite of eight PCBs, four organochlorine (OC) pesticides, five essential and five toxic elements in serum and/or whole blood of pregnant women recruited as part of the Mother-and-Child Contaminant Cohort Study conducted in Northern Norway (The MISA study); and (ii) determine the influence of personal and social characteristics on both dietary and contaminant factors. METHODS: Recruitment and sampling started in May 2007 and continued for the next 31 months until December 2009. Blood/serum samples were collected during the 2nd trimester (mean: 18.2 weeks, range 9.0-36.0). A validated questionnaire was administered to obtain personal information. The samples were analysed by established laboratories employing verified methods and reference standards. PCA involved Varimax rotation, and significant predictors (p≤0.05) in linear regression models were included in the multivariable linear regression analysis. RESULTS: When considering all the contaminants, three prominent PCA axes stood out with prominent loadings of: all POPs; arsenic, selenium and mercury; and cadmium and lead. Respectively, in the multivariate models the following were predictors: maternal age, parity and consumption of freshwater fish and land-based wild animals; marine fish; cigarette smoking, dietary PCA axes reflecting consumption of grains and cereals, and food items involving hunting. PCA of only the POPs separated them into two axes that, in terms of recently published findings, could be understood to reflect longitudinal trends and their relative contributions to summed POPs. CONCLUSIONS: The linear combinations of variables generated by PCA identified prominent dietary sources of OC groups and of prominent toxic elements and highlighted the importance of maternal characteristics.

Influence of the rehabilitation of injured loggerhead turtles (Caretta caretta) on their blood levels of environmental organic pollutants and elements.

We monitored the levels of 57 organic pollutants and 11 elements in the blood of 61 live stranded loggerhead sea turtles at the beginning and end of the rehabilitation period with the goal of evaluating whether recuperation of normal physiological conditions has an influence on the circulating levels of these pollutants from the blood. According to our results, several pollutants (OCPs, PCBs and toxic elements) are mobilized from storage tissues to the blood in sick turtles, and this is more evident in the subgroup of cachectic animals. We observed a significant decrease in the concentrations of some contaminants at the end of the rehabilitation period, probably due to redistribution processes. In contrast, an increase in the levels of the essential elements selenium and zinc was observed after a period of correct feeding and supplementation during hospitalization.

Reduction of the body burden of PCBs and DDE by dietary intervention in a randomized trial.

Serum polychlorinated biphenyls (PCBs) in Anniston, AL, residents have been associated with hypertension and diabetes. There have been no systematic interventions to reduce PCB body burdens in Anniston or other populations. Our objective was to determine the efficacy of 15 g/day of dietary olestra to reduce PCBs in Anniston residents. Blood PCBs and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene were measured at baseline and 4-month intervals in a double-blind, placebo-controlled, 1-year trial. Participants with elevated serum PCBs were randomized into two groups of 14 and received potato crisps made with olestra or vegetable oil (VO). Elimination rates during the study period were compared with 5-year prestudy rates. Eleven participants in the olestra group and 12 in the VO group completed the study. Except for one participant in the VO group, reasons for dropout were unrelated to treatments. The elimination rate of 37 non-coplanar PCB congeners during the 1-year trial was faster during olestra consumption compared to the pretrial period (-0.0829 ± 0.0357 and -0.00864 ± 0.0116 year(-1), respectively; P=.04), but not during VO consumption (-0.0413 ± 0.0408 and -0.0283 ± 0.0096 year(-1), respectively; P=.27). The concentration of PCBs in two olestra group participants decreased by 27% and 25% during the trial. There was no significant time by group interaction in change from baseline. However, group main effects for total PCBs and PCB 153 were of borderline significance. This pilot study has demonstrated that olestra can safely reduce body burdens of PCBs and supports a larger intervention trial that may also determine whether reduction in PCBs will reduce the risk of hypertension and diabetes.

Associations between plasma persistent organic pollutant levels and blood pressure in Inuit adults from Nunavik.

BACKGROUND: Recent evidence suggests that exposure to persistent organic pollutants (POPs) increases the risk of hypertension in environmentally exposed populations. High POP levels have been detected in Arctic populations and the exposure is related to high consumption of fish and marine mammals, which represent the traditional diet of these populations. OBJECTIVE: We examined the associations between polychlorinated biphenyls (PCBs), organochlorine (OC) pesticides and hypertension among Inuit from Nunavik (Quebec, Canada). METHODS: A complete set of data was obtained for 315 Inuit≥18years who participated in the "Santé Québec" health survey that was conducted in the 14 villages of Nunavik in 1992. Fourteen polychlorinated biphenyls (PCBs) and 8 OC pesticides or their metabolites were measured in plasma samples using gas chromatography with electron capture detection. Blood pressure (BP) was measured using a standardized protocol and information regarding anti-hypertensive medication was obtained through questionnaires. The associations between log-transformed POPs and hypertension (systolic BP≥140mmHg, diastolic BP≥90mmHg or anti-hypertensive medication) were analyzed using multiple logistic regressions. RESULTS: Total PCBs as well as the sum of non-dioxin-like PCBs were significantly associated with higher risk of hypertension. Furthermore, the risk of hypertension increased with higher plasma concentrations of congeners 101, 105, 138 and 187. Models adjusted for BP risk factors became significant after including n-3 polyunsaturated fatty acids (PUFAs) and further adjustment for lead and mercury did not change the results. Regarding OC pesticides, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) was associated with increased risk of hypertension while inverse associations were observed with p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), ß-hexachlorocyclohexane (HCH) and oxychlordane. CONCLUSIONS: Some PCB congeners were associated with higher risk of hypertension in this highly exposed population. Most associations became significant after including n-3 PUFAs in the models. However, the analyses of OC pesticides revealed divergent results, which need to be confirmed in further cohort and experimental studies.

Pigmentation of the oral mucosa by PCB poisoning in Yusho patients.

OBJECTIVES: Toxins, such as PCBs, dramatically affect patients even decades after exposure. Although 40 years have passed since the accidental poisoning with polychlorinated biphenyl (PCB) in Western Japan in 1968, high concentrations of PCBs are still detected in the serum of the "Yusho" (oil disease) patients. In this study, an epidemiological examination was carried out to reveal the prevalence of the oral pigmentation and blood concentrations of PCBs and polychlorinated quaterphenyl (PCQ) in Yusho victims. DESIGN: We performed a group examination of patients (Yusho victims) from 2004 to 2006, including 72 Yusho victims and 15 control subjects. The oral examination was performed by two oral and maxillofacial surgeons. The serum concentrations of PCB and PCQ were determined using gas chromatography; blood samples from Yusho victims were analyzed for PCB and PCQ by saponification in 1M NaOH ethanol solution, extraction with n-hexane column chromatography on silica gel, and then gas chromatography with electron capture detection. RESULTS: The mean Yusho victim's serum PCB and PCQ concentrations were 3.3ppb and 0.9ppb, respectively. In controls, these were 0.7ppb and 0ppb, respectively. Oral pigmentation was observed in 24 out of 72 Yusho patients. In controls, oral pigmentation was observed in one out of 15 persons. Oral pigmentation was most frequently observed in the buccal mucosa, followed by gingival mucosa. The blood concentration of PCB in Yusho patients with oral pigmentations was significantly higher than that in Yusho patients without oral pigmentation. CONCLUSION: These results indicated that PCB-related compounds may be responsible for the higher prevalence of oral pigmentation in Yusho victims, even though a long time has passed since the Yusho poisoning accident.

Exposure to persistent organic pollutants and risk of hypertension among Inuit from Greenland.

BACKGROUND: Exposure to persistent organic pollutants (POPs) is of concern in Arctic populations since these contaminants accumulate in fish and marine mammals, which is an important part of the traditional diet of these populations. Epidemiological and experimental studies have reported significant associations between POPs and increased blood pressure (BP) in populations with different degrees of exposure. OBJECTIVE: We aimed to assess the risk of hypertension related to increasing levels of polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides. METHODS: Fifteen PCBs and 11 OC pesticides or their metabolites were determined in plasma of 1614 Inuit adults ≥ 18 years living in 9 towns and 13 villages in Greenland. BP was measured using a standardized protocol. The risk of hypertension was estimated through logistic regression using POPs as continuous variables (log-transformed). Hypertension was defined as systolic BP ≥ 140 mm Hg, diastolic BP ≥ 90 mm Hg and/or antihypertensive treatment. RESULTS: Overall, the odd ratios (ORs) of hypertension were not statistically significant for dioxin-like PCBs, non-dioxin-like PCBs and OC pesticides after adjusting for confounders. Once the analyses were stratified by age category (18-39 and ≥ 40 years), increased risk of hypertension was observed for total dioxin-like PCBs among the youngest [OR: 1.34 (95% CI: 1.03-1.74)] while a borderline protective effect was observed for total non-dioxin-like PCBs [OR: 0.81 (95% CI: 0.66-0.99)] among the oldest. Higher risk of hypertension was also associated with increasing p,p'-dichlorodiphenyltrichloroethane (DDT) concentrations among the youngest [OR: 1.42 (95% CI: 1.08-1.85)]. CONCLUSION: Overall, no significant associations were observed between PCBs, OC pesticides and blood pressure in this highly exposed population although the associations differed by age category.

Measurement method for hydroxylated polychlorinated biphenyls in the blood of Yusho patients by liquid chromatography-electrospray tandem mass spectrometry.

Hydroxylated polychlorinated biphenyls (OH-PCBs) are formed as major metabolites of PCBs by cytochrome P450 enzyme-mediated oxidation. It has been reported that their total concentration in serum samples of Yusho patients ranged from 390 to 1300 pg/g. We developed a measurement method for OH-PCBs in blood samples by LC/MS/MS. This method is effective at determining the concentrations of PCDDs, PCDFs, Co-PCBs and OH-PCBs from the same sample without special treatment of the sample. The concentration of OH-PCBs in the blood of Yusho patients was examined using this method. The major OH-PCB metabolites were 4-OH-CB187 (54-906 pg/g-wet), 4-OH-CB146 + 3-OH-CB153 (32-527 pg/g-wet), 4-OH-CB109 (ND-229 pg/g-wet) and 4'-OH-CB172 (ND-143 pg/g-wet). The total OH-PCBs ranged from 95 to 1740 pg/g-wet.

[Impaired mitogen-induced lymphocyte transformation in patients with Yusho].

To investigate chronic immune effects of polychlorinated biphenyl (PCB) and polychlorinated dibenzofuran (PCDF), in vitro lymphocyte transformation in response to phytohemagglutinin (PHA) and concanavalin A (Con A) was studied in 139 patients with Yusho and 61 controls. PHA-induced lymphocyte transformation was significantly lower in patients with Yusho than in controls. PHA-induced lymphocyte transformation was inversely correlated with the concentrations of PCB and 2,3,4,7, 8-pentachlorodibenzofuran (PeCDF) in the blood. Con A-induced lymphocyte transformation showed similar inverse correlations with the concentrations of PCB and 2,3,4,7, 8-PeCDF. We conclude that impairment of mitogen-induced lymphocyte transformation in patients with Yusho may be associated with PCB and 2,3,4,7,8-PeCDF in the blood.

[Blood PCB concentrations and their tendencies examined in Fukuoka 2007-2010 annual inspections for Yusho].

We performed PCB congener specific analysis using HRGC/HRMS and determined their concentrations and blood chromatogram classifications in 275 individual blood samples collected during annual Yusho examinations between 2007 and 2010. When both blood total PCB concentrations and blood chromatogram classifications were compared among eleven Yusho patients undergoing examinations between 2007 and 2010, the longitudinal concentrations and classifications in the respective individuals hardly changed over these years. In a subset of persons suspected of Yusho, it was found that the mean total blood concentrations of three index congeners, that is, 2, 3', 4, 4', 5-pentaCB (PCB118), 2, 2', 4, 4', 5, 5'-hexaCB (PCB153), 2, 3, 3', 4, 4', 5-hexaCB (PCB156) and mean blood total PCB concentrations gradually decreased between 2007 and 2010. Mean concentration of PCB118 in blood from persons suspected of Yusho was calculated as 0.035 ng/g in the 2010 examination, which was 36% lower than the mean value of 0.054 ng/g in the 2007 examination: the concentration of PCB118 showed the highest degree of decrease among the three index congeners. Among persons suspected of Yusho, occupational rates of persons with blood PCB concentrations below one ppb in the entire population increased from approx. 50% in 2007 to approx. 70% in 2010. The lowest concentration of PCB156 in blood of persons suspected of Yusho in 2010 was 0.43 pg/g, which was almost equivalent to the limit of the determination value on HRGC/HRMS, S/N = 10.

Prenatal exposure to methylmercury and PCBs affects distinct stages of information processing: an event-related potential study with Inuit children.

Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are seafood contaminants known for their adverse effects on neurodevelopment. This study examines the relation of developmental exposure to these contaminants to information processing assessed with event-related potentials (ERPs) in school-aged Inuit children from Nunavik (Arctic Québec). In a prospective longitudinal study on child development, exposure to contaminants was measured at birth and 11 years of age. An auditory oddball protocol was administered at 11 years to measure ERP components N1 and P3b. Multiple regression analyses were performed to examine the associations of levels of the contaminants to auditory oddball performance (mean reaction time, omission errors and false alarms) and ERP parameters (latency and amplitude) after control for potential confounding variables. A total of 118 children provided useable ERP data. Prenatal MeHg exposure was associated with slower reaction times and fewer false alarms during the oddball task. Analyses of the ERP parameters revealed that prenatal MeHg exposure was related to greater amplitude and delayed latency of the N1 wave in the target condition but not to the P3b component. MeHg effects on the N1 were stronger after control for seafood nutrients. Prenatal PCB exposure was not related to any endpoint for sample as a whole but was associated with a decrease in P3b amplitude in the subgroup of children who had been breast-fed for less than 3 months. Body burdens of MeHg and PCBs at 11 years were not related to any of the behavioural or ERP measures. These data suggest that prenatal MeHg exposure alters attentional mechanisms modulating early processing of sensory information. By contrast, prenatal PCB exposure appears to affect information processing at later stages, when the information is being consciously evaluated. These effects seem to be mitigated in children who are breast-fed for a more extended period.

PCB exposure in sea otters and harlequin ducks in relation to history of contamination by the Exxon Valdez oil spill.

Exposure to contaminants other than petroleum hydrocarbons could confound interpretation of Exxon Valdez oil spill effects on biota at Prince William Sound, Alaska. Hence, we investigated polychlorinated biphenyls (PCBs) in blood of sea otters and harlequin ducks sampled during 1998. PCB concentrations characterized by lower chlorinated congeners were highest in sea otters from the unoiled area, whereas concentrations were similar among harlequin ducks from the oiled and unoiled area. Blood enzymes often elevated by xenobiotics were not related to PCB concentrations in sea otters. Only sea otters from the unoiled area had estimated risk from PCBs, and PCB composition or concentrations did not correspond to reported lower measures of population performance in sea otters or harlequin ducks from the oiled area. PCBs probably did not influence limited sea otter or harlequin duck recovery in the oiled area a decade after the spill.

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.

Increased levels of urinary nitrite and nitrotyrosine in Yusho victims 40 years after accidental poisoning with polychlorinated biphenyls in Nagasaki, Japan.

Forty years have passed since the accidental poisoning with polychlorinated biphenyls (PCB) in Japan in 1968, named Yusho. High concentrations of PCB are still detected in the serum of the Yusho victims. PCB produces superoxide (O(2) (-)) in the metabolic process and we reported high concentrations of serum nitrite, a stable metabolite reflecting nitric oxide (NO), in the Yusho victims. NO reacts with O(2) (-) and immediately produces peroxynitrite (ONOO(-)). ONOO(-) causes nitration of tyrosine residues and produces nitrotyrosine (NT). Therefore, we measured urinary concentrations of nitrite and NT in the victims and age-matched controls. The mean urinary concentrations of nitrite and NT were significantly higher than in the controls. There was a positive correlation between urinary nitrite and NT in the Yusho victims. Furthermore, there was a positive correlation between the ratio of urinary NT to nitrite and serum PCB concentrations in the Yusho victims. It was considered that the emergence of some ailments could be presumed to have been caused by high levels of urinary nitrite and NT in the Yusho victims.

Environmental contaminants and redox status of coenzyme Q10 and vitamin E in Inuit from Nunavik.

The Inuit are heavily exposed to potentially prooxidant contaminants such as methylmercury (MeHg) and polychlorinated biphenyls (PCB) through their traditional diet. This diet is also an abundant source of n-3 polyunsaturated fatty acids (n-3 PUFA), selenium, and antioxidants, which might reduce cardiovascular risk. Although Inuit from Nunavik have low concentrations of plasma oxidized low-density lipoprotein (OxLDL) and elevated glutathione-related antioxidant defenses, the variance in OxLDL was predicted by PCB and blood glutathione, leaving the issue of contaminant-associated oxidative stress unresolved. The objective of the study was to assess oxidative stress in these Inuit by measuring the plasma concentrations and redox states of alpha-tocopherol and coenzyme Q10 (CoQ10), 2 sensitive biomarkers of oxidative stress, in relation to exposure. Plasma lipophilic antioxidants were determined by high-performance liquid chromatography-coupled electrochemical detection; and their relations to PCB, MeHg, n-3 PUFA, selenium, and OxLDL were assessed by multivariate analyses. Ubiquinol-10, ubiquinone-10, and ubiquinone-10 to CoQ10(total) ratio were elevated as compared with white populations but showed no associations with PCB, MeHg, or n-3 PUFA. Ubiquinol-10 (beta = .23, P = .007) and CoQ10(total) (beta = .27, P = .009) were predicted by blood selenium; and alpha-tocopherol, by PCB (beta = 4.12, P = .0002), n-3 PUFA (beta = 9.16, P = .02), and OxLDL (beta = 3.04, P = .05). Unexpectedly, the alpha-tocopheryl quinone to alpha-tocopherol ratio, in the reference range, was negatively predicted by PCB (beta = -0.41, P = .02). Using sensitive biomarkers of redox alterations, we found no evidence for MeHg- or PCB-associated oxidative stress in these Inuit. However, despite robust blood antioxidant defenses, the unusually elevated ubiquinone-10 to CoQ10(total) ratio (0.21 +/- 0.11) suggests some form of oxidative stress of unknown origin.

[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.