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.

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.

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

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

[The difference between male and female dioxin concentrations in the blood of Yusho patients].

In 1968, the contamination of cooking oil by heat-degraded polychlorinated biphenyls (PCBs) caused a case of mass poisoning, the so-called Yusho incident. The cause of Yusho disease is thought to be ingested toxic substances, including not only PCBs but polychlorinated dibenzofuran (PCDFs) in Kanemi rice oil. Extensive studies have been performed since 1995 by the Yusho study group involving follow-up surveys of human blood concentrations of the casual compounds in Yusho patients as well as clinical trials of the acceleration of the excretion of these compounds in Yusho patients. We have previously measured dioxin concentrations in the blood of 649 Yusho patients in annual medical examinations from 2001 to 2009. We determined that the concentrations of 2,3,4,7,8-PeCDF 1,2,3,4,7,8-HxCDF 1,2,3,6,7,8-HxCDF, and 3,3',4,4',5,5'-HxCB (#169) in the blood of Yusho patients were more than twice as high levels to as those of normal controls. In this study, we compared the concentrations of 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF, 1,2,3,6,7,8-HxCDF, and 3,3',4,4',5,5'-HxCB (#169) in the blood of male Yusho patients with those of female Yusho patients. As a result, it was found that the mean concentrations of 2,3,4,7,8-PeCDF 1,2,3,4, 7,8-HxCDF 1,2,3,6,7,8-HxCDF, and 3,3',4,4',5,5'-HxCB (#169) in female Yusho patients were 2.9, 3.7, 2.4, and 1.3 times higher, respectively, than those of male Yusho patients.

[Analysis of residual nature of dioxins in blood of Yusho patients and controls in relation to the Yusho oil and food as respective exposure routes].

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.

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

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

[Follow-up survey of dioxins in the blood of Yusho patients (in 2001)].

Follow-up survey of the blood concentration of polychlorinated dibezo-p-dioxin (PCDDs), polychlorinated dibenzofuran (PCDFs), Non-ortho-coplaner PCBs (Non-Co-PCB), and Mono-ortho-coplaner PCBs (Mo-Co-PCB) in Yusho patients is very important for their health control. We determined the blood concentration of these dioxin-like isomers in 78 blood samples collected in 2001 using by a high-resolution gas chromatograph/high-resolution mass spectrometer (HRGC/HRMS) equipped with a solvent-cut large volume injection system (SCLV). The accelerated solvent extraction (ASE) method was employed for the treatment of blood samples. The method employed here can allow a reduced amount of blood collecting from Yusho patients compared with the conventional method. In typical Yusho patients (Group A of PCB pattern), the mean TEQ concentrations of PCDDs, PCDFs, Non-Co-PCBs, and Mono-Co-PCBs in blood collected in 2001 were 36, 260, 9.3, and 64 pg-TEQ/g lipid, respectively. As well, the toxic contribution of PCDDs, PCDFs, Non-Co-PCBs, and Mono-Co-PCBs in typical Yusho patients (Group A of PCB pattern) were 10, 70, 3, and 17% of the total TEQ value, respectively. The toxic contribution rate of PCDFs TEQ was still at high levels in relation to total TEQ in typical Yusho patients as mention above. The Yusho patients showing B pattern also had the same A pattern contribution rate. In the patients of group C, however, the mean blood levels of dioxin TEQ in 2001 was two times those of the normal controls determined in 2000 in Fukuoka prefecture. As well, the contribution rates were similar to those of normal subjects, although some patients in this group showed a high toxic contribution rate of PCDFs TEQ in relation to total TEQ. Thirty-three years had passed since the Yusho accident, and the total blood concentrations of PCDFs in the blood of Yusho patients were still higher than those of normal subjects. Among the different groups of PCB patterns, the concentration of 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF and 1,2,3,6,7,8-HxCDF showed significant differences. These findings indicate that these isomers are not metabolized in the human body since traces of them continued to be detected in these patients since they had been contaminated by the rice oil in the original incident.

Levels of certain metals, organochlorine pesticides and dioxins in cord blood, maternal blood, human milk and some commonly used nutrients in the surroundings of the Aral Sea (Karakalpakstan, Republic of Uzbekistan).

UNLABELLED: Since the 1960s a massive decline in the volume of the Aral Sea has occurred as a result of the diversion of the supplying rivers to cotton irrigation schemes. The contaminated sediment of the former seabed has been disseminated over the surrounding area by strong winds. This deterioration of the ecosystem has created a hazardous situation for the health of approximately 3.5 million people. This pilot study was undertaken to assist Karakalpak health workers in investigating the degree of exposure to metals, persistent organochlorine pesticides (OCPs) and dioxins during the most vulnerable prenatal and postnatal period and to provide guidelines for future research. All subjects came from areas located within 200 km of the southern border of the Aral Sea. Blood was obtained from 18 pregnant women and 28 newborns (cord blood) to determine the levels of metals, lead, cadmium, zinc and selenium and the OCPs alpha-, beta- and gamma-hexachlorocyclohexane (HCH; lindane is the product name of gamma-hexachlorocyclohexane), hexachlorobenzene (HCB), and isomers and metabolites of dichlorodiphenyltrichloroethane (DDT), i.e. op-DDT, pp-DDT, pp-DDE and pp-TDE. Levels of metals were also determined in blood from 28 non-pregnant women. In addition, levels of 17 dioxins were determined in 41 human milk samples and 1batch of formula. Information about possible dietary sources of the fat-soluble OCPs and dioxins was obtained from a pooled sample of butter and from seven cottonseed oil samples. A mass-selective detector coupled to a gas chromatograph equipped with a large volume injector was used to analyse the selected OCPs, whereas the dioxins were determined by gas chromatography with high-resolution mass spectrometry. The levels of metals in cord and maternal blood were consistent with concentrations observed in European countries. Only three women (7%) had lead levels greater than 100 ppb. The most notable pollutants in maternal and cord blood were the OCPs, notably HCB, beta-HCH, pp-DDE and the most toxic dioxin, 2,3,7,8-TCDD, when calculated as TEQs. A similar pattern was observed in human milk: beta-HCH and pp-DDE levels of more than 1,000 ng g(-1) fat were found in 68 and 43% of the subjects, respectively. Levels of 2,3,7,8-TCDD were six times higher than those observed in Western Europe. Traces of pp-DDE were detected in the batch of formula milk. Contaminated animal fat, but not cottonseed oil, is the most likely dietary source of OCPs and dioxins. CONCLUSION: Further epidemiological research is needed to elucidate the health implications of these pollutants on perinatal and maternal health, including lactation. More importantly, an investigation should be initiated to identify the emission sources of persistent organic pollutants in Karakalpakstan and adjacent regions.

[Follow-up survey of dioxins in the blood of Yusho patients (in 1998-1999)].

Follow-up survey of the blood concentration of PCDDs, PCDFs and non-ortho-chlorine substituted PCBs in Yusho patients is very important for their health control. We determined the blood concentration of these dioxin isomers in 119 blood samples collected in 1998 and 1999 using by a high-resolution gas chromatograph/high-resolution mass spectrometry (HRGC/HRMS). Thirty years had passed since the Yusho occurrence, and the total blood concentrations of PCDFs in the blood of Yusho patients were still as high as ever, except the patients with the PCB pattern C. Among the different groups of PCB patterns, the concentration of 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF and 1,2,3,6,7,8-HxCDF showed significant differences, excluding the group BC because of the small number of cases. The findings indicate that these isomers are not decomposed in human body since they had highly contaminated the causal rice oil at the onset. In typical Yusho patients (Group A of PCB pattern), the mean TEQ concentrations of PCDDs, PCDFs and non-ortho-chlorine substituted PCBs in the blood collected in 1998 were 21, 206, and 14 pg-TEQ/g lipid, respectively, and in 1999, 30, 308 and 14 pg-TEQ/g lipid, respectively. The toxic contribution rate of PCDFs TEQ was still at high levels for total TEQ in both years. The patients of the group C, however, the mean blood levels of the dioxins TEQ in 1998 and 1999 did not differ from those of the normal controls determined in 1996 although some patients in this group showed a high toxic contribution rate of PCDFs TEQ for total TEQ. We will try the PCB isomer specific analysis of the Yusho patients blood, and will investigate the difference from normal controls blood.