Associations between blood arsenic and urinary arsenic species concentrations as an exposure characterization tool.

Blood arsenic has various toxicities including carcinogenicity, but urinary concentrations are often substituted to determine the exposure level. Since there is little information on the relation of urinary arsenic species to blood arsenic, the aim was to investigate relationships between blood total arsenic (T-As) and the urinary species adjusted by creatinine and specific gravity (SG). Blood and spot urine samples were collected from 109 Japanese subjects aged 18-66 years without occupational exposure. Positive correlations of blood T-As (median, 3.49 µg/L) with urinary creatinine-adjusted and SG-adjusted T-As and arsenobetaine were statistically significant and greater than those with the unadjusted ones. The magnitude of associations of blood T-As with creatinine-adjusted arsenic species was significantly larger than those with unadjusted or SG-adjusted ones. Most of the correlation coefficients among urinary arsenic species concentrations were significant in three adjustment methods, but there was not a significant correlation between monomethylarsonic acid and arsenobetaine after urinary creatinine and SG corrections. Given multiple regression analysis, plasma T-As concentrations showed significant relations to creatinine-adjusted T-As, dimethylarsinic acid, and arsenobetaine concentrations, but erythrocyte T-As did hardly reflect the variation of urinary arsenic species. In conclusion, creatinine-adjusted arsenic concentrations are suggested to be the most appropriate predictor of blood T-As; by contrast, use of the urinary unadjusted arsenic concentration may result in a misleading interpretation of inorganic arsenic toxicity because the associations between inorganic and organic arsenic species based on the unadjusted concentration were mutually close. Plasma T-As appeared to be the best indicator of low-level exposure in blood samples.

Associations between prenatal exposure to organochlorine pesticides and thyroid hormone levels in mothers and infants: The Hokkaido study on environment and children's health.

Organochlorine pesticides (OCPs) are environmental contaminants with potentially adverse effects on neurodevelopment. Previous findings on the association between prenatal exposure to OCPs and the maternal or infant thyroid hormone system are inconsistent. Moreover, the influence of exposure to multiple OCPs and other chemical compounds is not clearly understood. Our study therefore aimed to examine the association between OCP exposure and both maternal and infant thyroid hormone systems. We also explored multiple exposure effects of OCPs and the influence of each compound using weighted quantile sum (WQS) methods. The study population included 514 participants in the Hokkaido study, recruited from 2002 to 2005 at one hospital in Sapporo, Japan. To quantify 29 OCPs, maternal blood samples were analyzed using gas chromatography/mass spectrometry. Blood samples for measuring thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were obtained from mothers during the early gestational stage (mean 11.4 weeks), and from infants between 7 and 43 days of age. The data of 333 mother child pairs with OCP and thyroid hormone measurements were included in the final analyses. Multivariate regression models showed a negative association between maternal FT4 and levels of o,p'-dichlorodiphenyldichloroethylene (DDE), o,p'-dichlorodiphenyltrichloroethane (DDT), and dieldrin. The WQS analysis showed that o,p'-DDT (48.6%), cis-heptachlorepoxide (22.8%), dieldrin (15.4%) were the primary contributors to the significant multiple exposure effect of OCPs on maternal FT4. For infants, we found a positive association between FT4 and cis-nonachlor and mirex. The most contributory compounds in the multiple exposure effect were trans-nonachlor (27.1%) and cis-nonachlor (13.8%), while several compounds contributed to the WQS via small weights (0.4-9.1%). These results indicate that OCPs, even at very low levels, may influence maternal and child thyroid hormone levels, which could modulate child development.

Prenatal organochlorine pesticide exposure and the disruption of steroids and reproductive hormones in cord blood: The Hokkaido study.

Certain organochlorine pesticides (OCPs) are designated as persistent organic pollutants and are regulated in many countries. The effects of OCPs on pediatric endocrinology are a concern; however, only limited data exist from human studies on maternal OCP exposure and its effects on infants' hormone levels. This study was conducted as part of the Hokkaido Study Sapporo Cohort, a prospective birth cohort study in Japan. Participants included 514 women who enrolled at 23-35weeks of gestation between 2002 and 2005; maternal blood samples were collected in late pregnancy, and 29 OCPs were measured. Reproductive and steroid hormone levels in cord blood were also determined. Characteristics of mothers and their infants were obtained from self-administered questionnaires and medical records. Ultimately, 232 samples with both OCP and hormone data were analyzed. Fifteen of 29 investigated OCPs were detected in over 80% of the samples, with p,p'-dichlorodiphenyldichloroethylene showing the highest concentration (median value: 619pg/g-wet). The association between OCPs and sex hormone levels varied by sex. Linear regression models after sex stratification showed that chlordanes, cis-hexachlorobenzene, heptachlor epoxide, Mirex, and toxaphenes in maternal blood were inversely associated with testosterone, cortisol, cortisone, sex hormone-binding globin, prolactin, and androstenedione-dehydroepiandrosterone (DHEA) and testosterone-androstenediones ratios among boys. Furthermore, these OCPs were positively correlated with DHEA, follicle stimulating hormone (FSH), and adrenal androgen-glucocorticoid and FSH-inhibin B ratios among boys. In categorical quartile models, testosterone and DHEA were inversely and positively associated with OCPs, respectively. Estradiol-testosterone and adrenal androgen-glucocorticoid ratios tended to increase with increasing OCP concentrations in the higher quartile, while the testosterone-androstenedione ratio tended to decrease. Sex hormone-binding globulin and prolactin showed an inverse association with OCPs. Among girls, the linear regression model showed that only p,p'-dichlorodiphenyltrichloroethane was inversely associated with the level of DHEA and the adrenal androgen-glucocorticoid ratio, but was positively associated with cortisone levels. However, no associations were observed using the quartile categorical model. These results suggest that prenatal exposure to OCPs disrupt reproductive hormones of fetuses in utero among boys, even at relatively low levels.

Association between prenatal exposure to organochlorine pesticides and the mental and psychomotor development of infants at ages 6 and 18 months: The Hokkaido Study on Environment and Children's Health.

Organochlorine pesticides (OCPs) are environmental contaminants that persist in the environment and bioaccumulate through the food chain in humans and animals. Although previous studies have shown an association between prenatal OCP exposure and subsequent neurodevelopment, the levels of OCPs included in these studies were inconsistent. A hospital-based prospective birth cohort study was conducted to examine the associations between prenatal exposure to relatively low levels of OCPs and neurodevelopment in infants at 6 (n=164) and 18 (n=115)months of age. Blood samples were analyzed using gas chromatography/mass spectrometry techniques to quantify 29 OCPs. The Bayley Scales of Infant Development 2nd edition (BSID-II) was used to assess the Mental and Psychomotor Developmental Index. After controlling for confounders, we found an inverse association between prenatal exposure to cis-heptachlor epoxide and the Mental Developmental Index at 18 months of age. Furthermore, infants born to mothers with prenatal concentrations of cis-heptachlor epoxide in the highest quartile had Mental Developmental Index scores -9.8 (95% confidence interval: -16.4, -3.1) lower than that recorded for infants born to mothers with concentrations of cis-heptachlor epoxide in the first quartile (p for trend <0.01). These results support the hypothesis that prenatal exposure to OCPs, especially cis-heptachlor epoxide, may have an adverse effect on the neurodevelopment of infants at specific ages, even at low levels.

A methodological consideration for blood lead concentrations obtained from the earlobe in Japanese adults occupationally unexposed to lead.

BACKGROUND: Neuropsychological effects of considerably low levels of lead exposure are observed in children, and a reliable and possibly painless technique that can detect such levels is required for the assessment of such exposure. We examined whether the blood lead (BPb) concentrations obtained from the earlobe were as valid and useful as those from the median cubital vein. METHODS: Paired blood samples were collected from the earlobe and cubital vein of 112 Japanese participants occupationally unexposed to lead, and the BPb levels were determined using ICP-MS. RESULTS: The limit of detection of BPb for the ICP-MS method was 0.015 µg/dL, and there was no participant with a BPb level below this limit. The median values of BPb concentrations were 0.91 (range, 0.41-2.48) µg/dL for earlobe blood using a 175-µL capillary tube and 0.85 (0.35-2.39) µg/dL for venous blood using a 5-mL vacuum tube. There was a significant correlation between the earlobe BPb levels and cubital vein BPb levels (Spearman rank correlation r S = 0.941), though the earlobe BPb levels were significantly higher than the cubital vein BPb levels. Most of the participants regarded earlobe puncture as a painless method. CONCLUSIONS: These data suggest that earlobe BPb levels can be used to assess lead exposure in children. Blood collection using a capillary tube should be done carefully and promptly because slow withdrawal may lead to measurement bias.

Blood persistent organochlorine pesticides in pregnant women in relation to physical and environmental variables in The Hokkaido Study on Environment and Children's Health.

The aim of this study was to document the exposure levels of pregnant women in Hokkaido to persistent organochlorine (POC) pesticides and the relationship between the body burdens of these pesticides and the study population's characteristics, such as age, pre-pregnancy body weight and calendar year in which blood was collected. From 2002 to 2005, whole blood samples were obtained from 186 pregnant women (aged 17 to 47 years) from the population of 514 women registered with the Sapporo Toho hospital cohort of the Hokkaido Study. Blood samples were analyzed by GC/NCIMS and GC/HRMS to quantify 29 POC pesticides. The subjects' demographic details were obtained from medical records and self-administered questionnaires. The Jonckheere-Terpstra test was used to determine relevant trends in the chemical concentrations of these pesticides and their relationship to the subjects' demographic details. Twenty-one of the 29 targeted compounds (including pesticides that have never been used in Japan, such as Mirex, Parlar-26 and Parlar-50) were detected in whole blood samples, and their log-transformed concentrations were found to significantly correlate with each other. The concentrations of p,p'-DDD, o,p'-DDE, p,p'-DDE, Parlar-26 and Parlar-50 declined from 2002 to 2005 (p<0.05). The pesticide concentrations appeared to have stronger associations with past conception than with parity, with most pesticide concentrations declining in a manner that appeared inversely related to past conceptions (p<0.05). Maternal age was positively associated with the following pesticide concentrations: p,p'-DDE, chlordanes group, cis-heptachlorepoxide, ß-HCH and mirex. Maternal pre-pregnancy body weight was positively associated with the concentrations of dieldrin, HCB, ß-HCH, Parlar-26 and Parlar-50, and appeared to be more strongly related to the body burdens of POC pesticides when compared with BMI associations. Further studies are required to evaluate the effects of POC pesticides on human health with regard to reproductive outcomes and child development.

[Concentrations of persistent organochlorine pesticides in whole blood of pregnant women in Hokkaido study on environment and children's health].

OBJECTIVES: This study was performed to evaluate the levels of exposure to persistent organochlorine pesticides in pregnant women in Hokkaido. METHODS: Whole-blood samples were obtained from 70 pregnant women aged 17 to 39 years in Hokkaido and analyzed to quantify 29 organochlorine pesticides by gas chromatography/negative ion chemical ionization mass spectrometry and gas chromatography/high-resolution mass spectrometry. RESULTS: Among 29 target compounds, 20 were detected in the whole-blood samples. Mirex, Parlar-26, and Parlar-50, which have never been used in Japan, were identified in all samples, as well as 11 compounds that have been used in Japan. Log-transformed concentrations of compounds with detection rates above 60% linearly correlated with each other (p<0.01). p,p'-DDE exhibited the highest concentration, with a geometric mean of 730 pg/g wet weight. From the results of the Jonckheere-Terpstra trend test, body weight or age was positively associated with the concentrations of several compounds. CONCLUSIONS: We detected 22 organochlorine pesticides including pesticides with no history of use in Japan in the whole-blood samples from pregnant women in Hokkaido. Through long-distance transport mechanisms, these pollutants may distribute widely, and further surveillance of human blood, in addition to foods and the environment, should be conducted.