The relationship between dioxin congeners in the breast milk of Vietnamese women and sister chromatid exchange.

The aim of this study was to clarify the relationship between dioxin concentrations in breast milk and the sister chromatid exchange (SCE) frequency in women from herbicide-sprayed and non sprayed areas. Blood samples were taken from 21 women with high TCDD (tetrachlorodibenzo-p-dioxin) levels from sprayed areas, 23 women with moderate TCDD levels from sprayed areas, and 19 women from non sprayed areas to determine their SCE frequency. The SCE frequencies for the high and moderate TCDD groups from the sprayed area and for the non sprayed area group were 2.40, 2.19, and 1.48 per cell, respectively. Multiple regression analysis showed that the standardized ß values for 1,2,3,6,7,8-hexaCDD (ß = 0.60), 1,2,3,4,6,7,8-heptaCDD (ß = 0.64), and octaCDD (ß = 0.65) were higher than those for TCDD (ß = 0.34) and 1,2,3,7,8-pentaCDD (ß = 0.42). The adjusted R² value for polyCDDs (R² = 0.38) was higher than that for polyCDD toxic equivalents (TEQ (toxic equivalents); R² = 0.23). This study therefore shows that levels of hexa-, hepta-, and octaCDD, which were previously regarded as being less toxic than TCDD, are closely related to SCE frequency and that the level of dioxin (pg/g lipid) is potentially more useful as an indicator than TEQ value for explaining SCE frequency.

Dioxin concentrations in breast milk of Vietnamese nursing mothers: a survey four decades after the herbicide spraying.

In an operation by United States Armed Forces during 1961 to 1971, large quantities of herbicides were sprayed in South Vietnam. These herbicides contained 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD), the most toxic congener of dioxins. Several decades after the herbicide spraying ceased, dioxin concentrations in the environment and human remained elevated in the sprayed areas. Breast milk samples from 520 nursing mothers residing in areas including the hot spots as well as the sprayed and unsprayed areas were collected to quantify the levels of dioxins. The total toxic equivalents of 2,3,7,8-substitued PCDDs/PCDFs in breast milk of mothers living in the hot spots, and the sprayed and unsprayed areas were 14.10 pg/g lipid, 10.89 pg/g lipid, and 4.09 pg/g lipid for primiparae and 11.48 pg/g lipid, 7.56 pg/g lipid, and 2.84 pg/g lipid for multiparae, respectively, with significant differences in the values among the three areas. In the hot spots, dioxin levels were highly correlated with the residency of mothers after adjustment for their age and parity.

Residual congener pattern of dioxins in human breast milk in southern Vietnam.

This study evaluated residual congener patterns of dioxin/furan (=PCDD/DF) related to tactical herbicides aerially sprayed over the regions of southern Vietnam through Operation Ranch Hand. The study focused on Cam Chinh (CC) commune, Quang Tri province (an area sprayed with tactical herbicides), and the Cam Phuc (CP) commune, Ha Tinh province (a non-sprayed area). Breast milk samples for analysis were collected in September 2002 and July 2003 from lactating primiparous and multiparous mothers born after the war (<31 years old). We found the levels of each congener in the CC commune were higher than in the CP commune, and determined specificity in the PCDD/DF congener pattern in CC commune samples by cluster analysis. The congener pattern is characterized by higher (the hexa-, the hepta-, and the octa-) chlorinated PCDD/DFs; this appears to be the same profile as that presented by pentachlorophenol (PCP), rather than 2,4,5-trichlorophenoxy acid (2,4,5-T) contaminated with 2,3,7,8-TCDD. A GC/MS study in the 1970s detected the chlorophenols 2,4-di and 2,4,6-trichlorophenol in some Agent Orange samples, which contained, like PCP, a wide variety of PCDD/DF congeners. In this context, it may be expected that certain tactical herbicides contaminated with various chlorophenol impurities, have a unique congener pattern when compared with pure 2,4,5-T formulations.

Association between dioxin concentrations in breast milk and food group intake in Vietnam.

OBJECTIVES: To clarify the association between dioxin concentrations in breast milk and food group intake in herbicide-sprayed and nonsprayed areas in Vietnam. METHODS: This survey was conducted in August 2007 in sprayed and nonsprayed areas, respectively. The interviews were performed using a questionnaire to obtain information on personal characteristics and usual dietary intake. Eighty mothers of sprayed area and 42 mothers of nonsprayed area participated in the study. Breast milk was analyzed for concentration of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). RESULTS: Multiple regression analysis showed that location (sprayed or nonsprayed area) has the highest association with the toxic equivalents (TEQ)-PCDDs, TEQ-PCDFs, and TEQ-Total rather than other factors. In the sprayed area, the adjusted R (2) values of regression were approximately 0.1. On the other hand, the adjusted R (2) values in the nonsprayed areas were higher than those in the sprayed area, i.e., between 0.2 and 0.3, and showed that there were significant associations with body mass index (BMI) in all models. CONCLUSIONS: Dioxin exposure was less affected by usual dietary intake in the sprayed area than in the nonsprayed area in Vietnam. It was clear that past exposure rather than present dietary intake may affect present dioxin concentrations in breast milk in the sprayed area in Vietnam. This study suggests that present dioxin concentrations in breast milk were maintained by continuous past exposure even after 30-40 years had passed.

A GIS study of dioxin contamination in a Vietnamese region sprayed with herbicide.

OBJECTIVES: The American-Vietnam War ended over 35 years ago, but dioxins still remain in human tissue and Vietnam's environment. The main objective of this study was to assess the correlation between dioxin concentration in soil, sediment and breast milk in one of the areas sprayed with herbicide, namely Cam Chinh commune, Quang Tri province, using a geographic information system (GIS). METHODS: The concentration of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in soil, sediment and breast milk samples was determined and the data analyzed using the geostatistical log-normal Kriging algorithm. RESULTS: The mean dioxin levels in soil and breast milk in the sprayed area were significantly higher than those in the non-sprayed area. The distribution pattern of PCDDs and PCDFs in soil was different, and there were no significant correlations between the estimated dioxin levels in soil obtained by the Kriging method and those in breast milk. CONCLUSIONS: The possibility remains that another exposure route, such as exposure to herbicides used during the Vietnam War, might affect dioxin levels in breast milk, although more soil data are needed to make more reliable geographical estimations.

Effects of maternal dioxin exposure on newborn size at birth among Japanese mother-infant pairs.

OBJECTIVE: Maternal exposure to dioxins [polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (DFs)] during pregnancy is known to affect infant growth and neurodevelopment in humans and animals. The aim of this study was to investigate the relationship between newborn size and the concentration of dioxin isomers in breast milk and to subsequently evaluate the potential toxicity of each dioxin isomer among mothers living in sea coast areas who are at a high risk of contamination due to a high consumption of fish. METHODS: A total of 75 milk samples were obtained within 1 month of delivery from Japanese mothers living in the coastal areas of the Japan Sea. The relationships between the levels of seven dioxins and ten furan isomers in maternal breast milk, measured by high-resolution-gas chromatography/mass spectrometry, and the birth size of newborns, which is related to fetal growth, were investigated after adjustment for confounding factors. RESULTS: The concentrations of 1,2,3,6,7,8-HxCDD (hexachlorodibenzo-p-dioxin), 2,3,4,7,8-PeCDF (pentachlorodibenzofuran), 2,3,4,6,7,8-HxCDF, and three dioxin toxic equivalent (TEQ) levels (PCDDs-TEQ, PCDFs-TEQ, and total-TEQ) in maternal breast milk were inversely correlated to newborn length even after adjustment for gestational weeks, infant sex, and maternal age and height. These isomers were abundant among the 17 isomers tested and reflected the TEQ levels. Only 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), the most toxic isomer, was negatively correlated with newborn head circumference, even after adjustment for gestational weeks, infant birth weight, and other confounding factors. CONCLUSIONS: Based on our results, fetal growth may be influenced by maternal total exposure to dioxins, but only exposure to 2,3,7,8-TCDD would appear to possibly affect fetal head size during pregnancy.

2,3,7,8-Tetrachlorodibenzo-p-dioxin in maternal breast milk and newborn head circumference.

Dioxins are known to affect infant growth and neurodevelopment in both humans and animals. In this study, we examined the relationship between neonatal head circumference, which is related to fetal brain development, and the concentration of dioxins in breast milk as an indicator of maternal exposure. A total of 42 milk samples were obtained on the fifth to eighth postpartum day from mothers in Japan exposed to dioxins in the environment. The levels of seven dioxins and 10 furan isomers were measured in each milk sample using an HR-GC/MS system. The relationships between the concentration of each dioxin isomer and newborn size, including head circumference, were then investigated after adjustment for confounding factors. The concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic dioxin isomer, negatively correlated with newborn head circumference, even after adjustment for gestational age, infant sex, parity and other confounding factors. However, there were no significant relationships between the concentration of other dioxin and furan isomers in maternal breast milk and infant height, weight and chest circumference at birth. These facts suggested that fetal brain development might be influenced by maternal exposure to TCDD in the environment.

Effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on fetal brain growth and motor and behavioral development in offspring rats.

The effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during pregnancy on fetal brain growth and neurobehavioral development in early developmental stages were investigated using rat offspring. TCDD in corn-oil (0.1microg/kg) was orally administrated to the dams from the 9th to 19th gestational day. When TCDD effects on the fetal brain weight were analyzed on the 19th gestational day, weight ratio of the brain to the whole body, and that of the forebrain without the cerebral cortex to the whole brain were larger in the exposed group than those of the control group, suggesting premature fetal brain development. TCDD effects on motor functions were investigated using newborns in an inclined plane task. Motor development assessed by righting response on an inclination was delayed in the exposed offspring in the 8th-12th postnatal day, especially in male. Also, TCDD effects on active avoidance behavior in a shuttle box were investigated using the offspring after weaning. Latency in the active avoidance learning was longer, and locomotor activity was reduced in the exposed male offspring in the 41st-44th postnatal day. The results demonstrated that maternal TCDD exposure delayed fetal brain growth and neurodevelopment of the offspring in early stage, especially in male rats.

Urinary cadmium and mortality among inhabitants of a cadmium-polluted area in Japan.

The influence of cadmium (Cd) body burden on mortality remains controversial. Excess mortality and the dose-response relationship between mortality and urinary cadmium excretion were investigated in this study among environmentally exposed subjects. A 15-year follow-up study was carried out on 3119 inhabitants (1403 men and 1716 women) of the Cd-polluted Kakehashi River basin, whose urinary Cd concentration was examined in a 1981-1982 health impact survey. The mortality risk of high urinary Cd (> or = 10 microg/g Cr) subjects after adjustment for age using Cox's proportional hazard model was higher than that of moderate urinary Cd (< 10 microg/g Cr) subjects in both sexes. When the subjects were divided into five groups according to the amount of urinary Cd (<3, 3-5, 5-10, 10-20, > or = 20 microg/g Cr), the mortality risk was significantly increased among the subjects with urinary Cd > or = 3 microg/g Cr in proportion to the increases in the amount of urinary Cd concentration after adjustment for age, especially in women. Furthermore, special causes of death among high and moderate urinary Cd were investigated, and mortality risk ratio for heart failure, which is a cause of death often diagnosed in cases with a gradual deterioration culminating in death, was significantly increased in both sexes, compared with the moderate urinary Cd subjects. Also, in women the mortality risk for renal diseases in the high urinary Cd subjects was significantly higher than that in the moderate urinary Cd subjects. These results suggest that a causal association between Cd body burden and mortality exists among inhabitants environmentally exposed to Cd but that no special disease may be induced except renal diseases.

Effects of cadmium exposure during pregnancy on trace elements in fetal rat liver and kidney.

Female rats were exposed by intragastric administration with a cannula 1mg/kg/day or 10mg/kg/day CdCl2 for the 11 days from the 9th to 19th day of pregnancy, and the effects of Cd exposure on eight elements, Na, K, Ca, Mg, P, Fe, Zn, and Cu in fetal liver, kidney, brain, fetal membrane and placenta then examined. We found that: (1) although Cd was not detected in fetal kidney and brain, significant Cd accumulation was found in fetal liver, fetal membrane and placenta in the 10 mg/kg Cd group, (2) the Zn and Fe concentrations in fetal liver in the 10 mg/kg Cd group were significantly lower than those in the control group, but no difference was found in the placenta, (3) the Cu concentrations in the placenta, fetal membrane and liver in the 10 mg Cd groups were significantly lower than those in the control group, (4) Na/K ratio in the placenta and fetal kidney and the Ca concentration in the placenta in the 10 mg/kg Cd group were lower than those in the controls. These results suggest that Cd exposure inhibits Zn and Fe transportation from the placenta to fetus, as well as Cu, Ca, Na and K uptake and transportation across the placenta, possibly influencing fetal growth and metabolism.

Cadmium and nutritional intake in pregnant Japanese women.

A study to clarify the food composition and nutritional factors that contribute to the levels of blood and urinary cadmium (Cd) was conducted on 50 pregnant Japanese women with mean age of 29 years. The mean iron (Fe) intake of subjects was 9.2 mg, which is much lower than the recommended level of 20 mg for pregnant women. Cd in urine samples collected at 30-32 weeks of gestation were correlated (r = 0.354), but urinary Cd was related to age more than blood Cd. Urinary Cd and blood Cd levels were inversely related to total energy (rpartial = -0.325, and -0.334, respectively) and fat intake (rpartial = -0.419, and -0.379, respectively), even after adjustment for age. Blood Cd was also correlated to protein and iron intake (rpartial = -0.299, and -0.353, respectively). These results indicate that Cd exposure levels of pregnant women with low energy intake, especially less fat intake, were higher than those of women with more energy and fat intake. In particular, blood Cd may be affected by protein and iron intake in pregnant women with increased these nutrients demand.

Relationship between newborn size and mother's blood cadmium levels, Toyama, Japan.

The effect of blood cadmium (Cd), which reflects not only Cd body burden but also recent Cd exposure and communicates with fetal blood in the placenta, on newborn size at birth was investigated. Blood Cd of 55 mothers from Toyama, Japan, at 30-32 gestational weeks was measured using a flameless atomic absorption spectrophotometer. The relationship between blood Cd and newborn size was analyzed after adjustment for gestational age and maternal build. A significant inverse correlation was found between infant height and maternal blood Cd. After adjustment for gestational age and maternal weight at 30-32 gestational weeks, the significant inverse relationship between maternal blood Cd and infant height was shown using the multiple regression analysis. Newborn size might be influenced by maternal blood Cd levels to which infants may be exposed during gestation.

Cadmium exposure and trace elements in human breast milk.

The interrelations of the seven elements, calcium (Ca), magnesium (Mg), sodium (Na), potassium (K), phosphorus (P), copper (Cu), zinc (Zn), and cadmium (Cd) in human breast milk were examined in Japanese mothers to clarify the effects of Cd exposure on these important elements for infant growth. Breast milk and urine samples were obtained from 68 mothers, aged 19-38 years, at 5-8 days postpartum. The concentrations were determined by inductively-coupled plasma atomic emission spectrometry for Ca, Mg, Na, K, P, by flame atomic absorption spectrophotometry for Cu and Zn, and by flameless atomic absorption spectrophotometry for Cd. Geometrical mean Cd concentrations were 0.28 (geometrical standard deviation=1.82) microg/l in breast milk and 1.00 (1.93) microg/g creatinine in urine. Among the above elements only Cd concentration in breast milk was significantly correlated with urinary Cd concentration (r=0.451, P<0.001). Significant positive correlations were found between Cu and Ca (r=0.500, P<0.001), Cu and Mg (r=0.378, P<0.01), and Zn and Mg (r=0.355, P<0.01) in breast milk. Cd concentration in breast milk showed an inverse relationship with Ca concentration in breast milk (r=-0.248, P<0.05). These results indicate that the Cd concentration in breast milk closely reflects Cd body burden, with increased Cd in breast milk possibly affecting Ca secretion in breast milk.