Hepatic Transcriptomic Patterns in the Neonatal Rat After Pentabromodiphenyl Ether Exposure.

Human exposure to pentabromodiphenyl ether (PBDE) mixture (DE-71) and its PBDE-47 congener can occur both in utero and during lactation. Here, we tested the hypothesis that PBDE-induced neonatal hepatic transcriptomic alterations in Wistar Han rat pups can inform on potential toxicity and carcinogenicity after longer term PBDE exposures. Wistar Han rat dams were exposed to either DE-71 or PBDE-47 daily from gestation day (GD 6) through postnatal day 4 (PND 4). Total plasma thyroxine (T4) was decreased in PND 4 pups. In liver, transcripts for CYPs and conjugation enzymes, Nrf2, and ABC transporters were upregulated. In general, the hepatic transcriptomic alterations after exposure to DE-71 or PBDE-47 were similar and provided early indicators of oxidative stress and metabolic alterations, key characteristics of toxicity processes. The transcriptional benchmark dose lower confidence limits of the most sensitive biological processes were lower for PBDE-47 than for the PBDE mixture. Neonatal rat liver transcriptomic data provide early indicators on molecular pathway alterations that may lead to toxicity and/or carcinogenicity if the exposures continue for longer durations. These early toxicogenomic indicators may be used to help prioritize chemicals for a more complete toxicity and cancer risk evaluation.

Exposure to DDT from indoor residual spraying and biomarkers of inflammation among reproductive-aged women from South Africa.

BACKGROUND: Evidence from animal studies suggests that DDT and DDE can adversely affect immuno-competence while human data are less conclusive. We aimed to assess the association of plasma concentrations of DDT and DDE with biomarkers of inflammation among reproductive-aged women residing in homes sprayed with DDT through Indoor Residual Spraying (IRS). METHODS: This study included 416 women from the Study of Women and Babies, South Africa (2010-2011). DDT, DDE, and biomarkers of inflammation (immunoglobulins A, G and M, interleukins 1ß, 6, and 8, tumor necrosis factor-α, C-reactive protein, serum amyloid-A, intercellular adhesion molecule-1, vascular cell adhesion molecule-1) were quantified in plasma. Linear regression was used to assess associations of DDT and DDE with each natural log-transformed biomarker. Models were adjusted for age, body mass index, parity, income, and season; beta estimates were expressed as percent differences. RESULTS: Compared to women with the lowest plasma concentrations of DDT and DDE, those with the highest concentrations of both compounds had higher levels IL-1ß, IL6, and TNF- α. While associations were statistically significant for both DDT and DDE, the magnitude of the associations was slightly stronger for DDT. Compared to women in the lowest quintile of DDT, women in the highest quintile were estimated to have 53.0% (95%CI: 21.7%, 84.4%), 28.1% (95%CI: 6.4%, 49.8%), and 26.6% (95%CI: 12.0%, 41.1%) higher levels of IL-1ß, IL6, and TNF- α, respectively. CONCLUSIONS: Our results suggest that increased plasma concentrations of DDT and DDE resulting from exposure to IRS may increase concentrations of pro-inflammatory biomarkers among reproductive-aged women in South Africa.

A Black Cohosh Extract Causes Hematologic and Biochemical Changes Consistent with a Functional Cobalamin Deficiency in Female B6C3F1/N Mice.

Black cohosh rhizome, available as a dietary supplement, is most commonly marketed as a remedy for dysmenorrhea and menopausal symptoms. A previous subchronic toxicity study of black cohosh dried ethanolic extract (BCE) in female mice revealed a dose-dependent ineffective erythropoiesis with a macrocytosis consistent with the condition known as megaloblastic anemia. The purpose of this study was to investigate potential mechanisms by which BCE induces these particular hematological changes. B6C3F1/N female mice (32/group) were exposed by gavage to vehicle or 1,000 mg/kg BCE for 92 days. Blood samples were analyzed for hematology, renal and hepatic clinical chemistry, serum folate and cobalamin, red blood cell (RBC) folate, and plasma homocysteine and methylmalonic acid (MMA). Folate levels were measured in liver and kidney. Hematological changes included decreased RBC count; increased mean corpuscular volume; and decreased reticulocyte, white blood cell, neutrophil, and lymphocyte counts. Blood smear evaluation revealed increased Howell-Jolly bodies and occasional basophilic stippling in treated animals. Plasma homocysteine and MMA concentrations were increased in treated animals. Under the conditions of our study, BCE administration caused hematological and clinical chemistry changes consistent with a functional cobalamin, and possibly folate, deficiency. Further studies are needed to elucidate the mechanism by which BCE causes increases in homocysteine and MMA.

Anti-Müllerian hormone and lifestyle, reproductive, and environmental factors among women in rural South Africa.

BACKGROUND: Few data exist regarding anti-Müllerian hormone, a marker of ovarian reserve, in relation to environmental factors with potential ovarian toxicity. METHODS: This analysis included 420 women from Limpopo, South Africa studied in 2010-2011. Women were administered comprehensive questionnaires, and plasma concentrations of anti-Müllerian hormone and dichlorodiphenyltrichloroethane were determined. We used separate multivariable models to examine the associations between natural log-transformed anti-Müllerian hormone concentration (ng/ml) and each of the lifestyle, reproductive, and environmental factors of interest, adjusted for age, body mass index, education, and parity. RESULTS: The median age of women was 24 years (interquartile range [IQR] = 22 to 26); the median anti-Müllerian hormone concentration was 3.1 ng/ml (IQR = 2.0 to 6.0). Women who reported indoor residual spraying in homes with painted walls (indicative of exposure to pyrethroids) had 25% lower (95% confidence interval [CI] = -39%, -8%) anti-Müllerian hormone concentrations compared with women who reported no spraying. Little evidence of decreased anti-Müllerian hormone concentrations was observed among women with the highest dichlorodiphenyltrichloroethane levels. Compared with women who used an electric stove, no association was observed among women who cooked indoors over open wood fires. The findings also suggested lower anti-Müllerian hormone concentrations among women who drank coffee (-19% [95% CI = -31%, -5%]) or alcohol (-21% [95% CI = -36%, -3%]). CONCLUSIONS: These are among the first data regarding anti-Müllerian hormone concentrations relative to pesticides and indoor air pollution. Our results are suggestive of decreased ovarian reserve associated with exposure to pyrethroid pesticides, which is consistent with laboratory animal data.

Perfluoroalkyl substances during pregnancy and validated preeclampsia among nulliparous women in the Norwegian Mother and Child Cohort Study.

Perfluoroalkyl substances (PFAS) are persistent and ubiquitous environmental contaminants, and human exposure to these substances may be related to preeclampsia, a common pregnancy complication. Previous studies have found serum concentrations of PFAS to be positively associated with pregnancy-induced hypertension and preeclampsia in a population with high levels of exposure to perfluorooctanoate. Whether this association exists among pregnant women with background levels of PFAS exposure is unknown. Using data from the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health, we carried out a study of nulliparous pregnant women enrolled in 2003-2007 (466 cases, 510 noncases) to estimate associations between PFAS concentrations and an independently validated diagnosis of preeclampsia. We measured levels of 9 PFAS in maternal plasma extracted midpregnancy; statistical analyses were restricted to 7 PFAS that were quantifiable in more than 50% of samples. In proportional hazards models adjusted for maternal age, prepregnancy body mass index (weight (kg)/height (m)(2)), educational level, and smoking status, we observed no strongly positive associations between PFAS levels and preeclampsia. We found an inverse association between preeclampsia and the highest quartile of perfluoroundecanoic acid concentration relative to the lowest quartile (hazard ratio = 0.55, 95% confidence interval: 0.38, 0.81). Overall, our findings do not support an increased risk of preeclampsia among nulliparous Norwegian women with background levels of PFAS exposure.

Perfluorinated compounds in relation to birth weight in the Norwegian Mother and Child Cohort Study.

Perfluorooctane sulfonate and perfluorooctanoic acid are perfluorinated compounds (PFCs) widely distributed in the environment. Previous studies of PFCs and birth weight are equivocal. The authors examined this association in the Norwegian Mother and Child Cohort Study (MoBa), using data from 901 women enrolled from 2003 to 2004 and selected for a prior case-based study of PFCs and subfecundity. Maternal plasma samples were obtained around 17 weeks of gestation. Outcomes included birth weight z scores, preterm birth, small for gestational age, and large for gestational age. The adjusted birth weight z scores were slightly lower among infants born to mothers in the highest quartiles of PFCs compared with infants born to mothers in the lowest quartiles: for perfluorooctane sulfonate, ß = -0.18 (95% confidence interval: -0.41, 0.05) and, for perfluorooctanoic acid, ß = -0.21 (95% confidence interval: -0.45, 0.04). No clear evidence of an association with small for gestational age or large for gestational age was observed. Perfluorooctane sulfonate and perfluorooctanoic acid were each associated with decreased adjusted odds of preterm birth, although the cell counts were small. Whether some of the associations suggested by these findings may be due to a noncausal pharmacokinetic mechanism remains unclear.

Perfluorinated compounds and subfecundity in pregnant women.

BACKGROUND: Perfluorinated compounds are ubiquitous pollutants; epidemiologic data suggest they may be associated with adverse health outcomes, including subfecundity. We examined subfecundity in relation to 2 perfluorinated compounds-perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). METHODS: This case-control analysis included 910 women enrolled in the Norwegian Mother and Child Cohort Study in 2003 and 2004. Around gestational week 17, women reported their time to pregnancy and provided blood samples. Cases consisted of 416 women with a time to pregnancy greater than 12 months, considered subfecund. Plasma concentrations of perfluorinated compounds were analyzed using liquid chromatography-mass spectrometry. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for each pollutant quartile using logistic regression. Estimates were further stratified by parity. RESULTS: The median plasma concentration of PFOS was 13.0 ng/mL (interquartile range [IQR] = 10.3-16.6 ng/mL) and of PFOA was 2.2 ng/mL (IQR = 1.7-3.0 ng/mL). The relative odds of subfecundity among parous women was 2.1 (95% CI = 1.2-3.8) for the highest PFOS quartile and 2.1 (1.0-4.0) for the highest PFOA quartile. Among nulliparous women, the respective relative odds were 0.7 (0.4-1.3) and 0.5 (0.2-1.2). CONCLUSION: Previous studies suggest that the body burden of perfluorinated compounds decreases during pregnancy and lactation through transfer to the fetus and to breast milk. Afterward, the body burden may increase again. Among parous women, increased body burden may be due to a long interpregnancy interval rather than the cause of a long time to pregnancy. Therefore, data from nulliparous women may be more informative regarding toxic effects of perfluorinated compounds. Our results among nulliparous women did not support an association with subfecundity.

Uterine leiomyomata in relation to insulin-like growth factor-I, insulin, and diabetes.

BACKGROUND: Insulin-like growth factor-I (IGF-I) and insulin stimulate cell proliferation in uterine leiomyoma (fibroid) tissue. We hypothesized that circulating levels of these proteins would be associated with increased prevalence and size of uterine fibroids. METHODS: Participants were 35-49-year-old, randomly selected members of an urban health plan who were enrolled in the study in 1996-1999. Premenopausal participants were screened for fibroids with ultrasound. Fasting blood samples were collected. Associations between fibroids and diabetes, plasma IGF-I, IGF binding protein 3 (BP3), and insulin were evaluated for blacks (n = 585) and whites (n = 403) by using multiple logistic regression. RESULTS: IGF-I showed no association with fibroids in blacks, but in whites the adjusted odds ratios (aORs) for both mid and upper tertiles compared with the lowest tertile were 0.6 (95% confidence intervals [CI] = 0.3-1.0 and 0.4-1.1, respectively). Insulin and diabetes both tended to be inversely associated with fibroids in blacks. The insulin association was with large fibroids; aOR for the upper insulin tertile relative to the lowest was 0.4 (0.2-0.9). The aOR for diabetes was 0.5 (0.2-1.0). Associations of insulin and diabetes with fibroids were weak for whites. Binding protein 3 showed no association with fibroids. CONCLUSIONS: Contrary to our hypothesis, high circulating IGF-I and insulin were not related to increased fibroid prevalence. Instead, there was suggestion of the opposite. The inverse association with diabetes, although based on small numbers, is consistent with previously reported findings. Future studies might investigate vascular dysfunction as a mediator between hyperinsulinemia or diabetes and possible reduced risk of fibroids.

An Evaluation of Neurotoxicity Following Fluoride Exposure from Gestational Through Adult Ages in Long-Evans Hooded Rats.

At elevated levels, fluoride (F-) exposure has been associated with adverse human health effects. In rodents, F- exposure has been reported to induce deficits in motor performance and learning and memory. In this study, we examined Long-Evans hooded male rats maintained on a standard diet (20.5 ppm F-) or a low F- diet (3.24 ppm F-) with drinking water exposure to 0, 10, or 20 ppm F- from gestational day 6 through adulthood. At postnatal day 25, brain F- levels were 0.048 or 0.081 µg/g and femur 235 or 379.8 µg/g for 10 and 20 ppm F-, respectively. Levels increase with age and in adults, levels for plasma were 0.036 or 0.025 µg/ml; for the brain 0.266 or 0.850 µg/g; and for the femur, 681.2 or 993.4 µg/g. At these exposure levels, we observed no exposure-related differences in motor, sensory, or learning and memory performance on running wheel, open-field activity, light/dark place preference, elevated plus maze, pre-pulse startle inhibition, passive avoidance, hot-plate latency, Morris water maze acquisition, probe test, reversal learning, and Y-maze. Serum triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) levels were not altered as a function of 10 or 20 ppm F- in the drinking water. No exposure-related pathology was observed in the heart, liver, kidney, testes, seminal vesicles, or epididymides. Mild inflammation in the prostate gland was observed at 20 ppm F-. No evidence of neuronal death or glial activation was observed in the hippocampus at 20 ppm F-.

Heat map visualization of high-density clinical chemistry data.

Clinical chemistry data are routinely generated as part of preclinical animal toxicity studies and human clinical studies. With large-scale studies involving hundreds or even thousands of samples in multiple treatment groups, it is currently difficult to interpret the resulting complex, high-density clinical chemistry data. Accordingly, we conducted this study to investigate methods for easy visualization of complex, high-density data. Clinical chemistry data were obtained from male rats each treated with one of eight different acute hepatotoxicants from a large-scale toxicogenomics study. The raw data underwent a Z-score transformation comparing each individual animal's clinical chemistry values to that of reference controls from all eight studies and then were visualized in a single graphic using a heat map. The utility of using a heat map to visualize high-density clinical chemistry data was explored by clustering changes in clinical chemistry values for >400 animals. A clear distinction was observed in animals displaying hepatotoxicity from those that did not. Additionally, while animals experiencing hepatotoxicity showed many similarities in the observed clinical chemistry alterations, distinct differences were noted in the heat map profile for the different compounds. Using a heat map to visualize complex, high-density clinical chemistry data in a single graphic facilitates the identification of previously unrecognized trends. This method is simple to implement and maintains the biological integrity of the data. The value of this clinical chemistry data transformation and visualization will manifest itself through integration with other high-density data, such as genomics data, to study physiology at the systems level.

Preconceptional fasting of fathers alters serum glucose in offspring of mice.

OBJECTIVE: Maternal nutrition has long-term effects on offspring characteristics. Similar effects mediated through fathers have not been tested. METHODS: Outbred Swiss male mice were fasted one or six times 1 to 4 wk before mating. Offspring were killed at age intervals of 4 to 10 wk and their sera were analyzed for glucose, corticosterone, and insulin-like growth factor-1. Statistical linear mixed effects models were used to determine treatment (paternal diet restriction versus control) differences and possible effects of covariates, including sex, litter membership, and litter size. RESULTS: Paternal food deprivation resulted in a consistent decrease in average serum glucose in male and female offspring. Significant changes in corticosterone and insulin-like growth factor-1 were found for some groups. The results indicated a male-mediated transgenerational effect on metabolism- and growth-related parameters, in particular glucose. CONCLUSIONS: Effects of paternal nutritional experiences on offspring metabolism, if confirmed, would be novel and could have far-reaching implications in the context of transgenerational effects on chronic diseases.

Insulin-like growth factor I, IGF-binding protein 3, and lung cancer risk in a prospective study of men in China.

BACKGROUND: Insulin-like growth factor I (IGF-I) stimulates cell proliferation and inhibits apoptosis in the lung and other tissues by interacting with the IGF-I receptor. The major binding protein for IGF-I, insulin-like growth factor-binding protein 3 (IGFBP-3), modulates the effects of IGF-I but also inhibits cell growth and induces apoptosis independent of IGF-I and its receptor. In a prospective study of men in Shanghai, China, we examined the association between serum levels of IGF-I and IGFBP-3 and the subsequent risk of lung cancer. METHODS: From 1986 to 1989, serum was collected from 18,244 men aged 45-64 years living in Shanghai without a history of cancer. We analyzed IGF-I and IGFBP-3 levels in serum from 230 case patients who developed incident lung cancer during follow-up and from 740 control subjects. RESULTS: Among 230 case patients and 659 matched control subjects, increased IGF-I levels were not associated with increased risk of lung cancer. However, for subjects in the highest quartile relative to the lowest quartile of IGFBP-3, the odds ratio (OR) for lung cancer, adjusted for smoking and IGF-I, was 0.50 (95% confidence interval [CI] = 0.25 to 1.02). When the analysis was restricted to ever smokers (184 case patients and 344 matched control subjects), the OR for lung cancer in men in the highest quartile of IGFBP-3 relative to those in the lowest quartile, adjusted for smoking and IGF-I, was 0.41 (95% CI = 0.18 to 0.92). CONCLUSIONS: In this prospective study of Chinese men, higher serum levels of IGF-I did not increase the risk of lung cancer. However, subjects with higher serum levels of IGFBP-3 were at reduced risk of lung cancer. This finding is consistent with experimental data that indicate that IGFBP-3 can inhibit cellular proliferation and induce apoptosis independent of IGF-I and the IGF-I receptor.

Correction: Maternal Glomerular Filtration Rate in Pregnancy and Fetal Size.

[This corrects the article DOI: 10.1371/journal.pone.0101897.].

Recreational Exercise Before and During Pregnancy in Relation to Plasma C-Reactive Protein Concentrations in Pregnant Women.

BACKGROUND: Pregnant women who are physically active have a lower risk of preeclampsia and gestational diabetes than women who are less active. One possible mechanism is a reduction in low-grade inflammation, as measured by plasma concentrations of C-reactive protein (CRP). The association between exercise and CRP in pregnant women, however, has not been adequately investigated. METHODS: A total of 537 pregnant women, enrolled around the 17th week of gestation in the Norwegian Mother and Child Cohort Study in 2003 to 2004, were studied. Self-reported recreational exercise was recalled for both 3 months before pregnancy and early pregnancy. The total energy expenditure from recreational exercise (total recreational exercise, metabolic equivalent of task [MET]-hr/week) was estimated, and low-, moderate- and vigorous-intensity exercise was defined. Plasma CRP concentrations were measured during pregnancy. RESULTS: In adjusted linear regression models, mean CRP concentration was 1.0% lower [95% CI = -1.9% to 0.2%] with each 1 MET-hr/week of total recreational exercise before pregnancy. In addition, vigorous-intensity exercise before pregnancy was more strongly related to a reduction in CRP levels than low- or moderate-intensity exercise. However, we observed no association between recreational exercise during pregnancy and plasma CRP levels. CONCLUSIONS: Recreational exercise before pregnancy, especially vigorous exercise, may reduce the risk of maternal inflammation during pregnancy.

Susceptibility to postnatal growth retardation induced by 5-AZA-2'-deoxycytidine in utero: gender specificity and correlation with reduced insulin-like growth factor 1.

The DNA demethylating agent 5-AZA-2'-deoxyxytidine (5-AZA-CdR) alters gene expression in mice exposed during developmental stages and causes malformations and growth suppression. The aim of this study was to determine if 5-AZA-CdR-induced growth retardation is associated with alterations in energy metabolism or in serum IGF-1 levels. Mice were exposed in utero to 5-AZA-CdR at gestation day 10. At postnatal day 21, exposed pups were weaned and body weights recorded. At 3 months of age, reproductive capacity was studied. At 5 months old, after body weight was recorded mice were killed and serum was collected to determine serum glucose, corticosterone, and IGF-1 levels. The body weights of both treated males and females were reduced at weaning compared with controls, but by 5 months of age, only the male body weight was affected. Reproductive capacity of males and females was reduced with males being more affected. Levels of corticosterone and glucose were not altered. Serum IGF-1 levels were lower in males exposed in utero to 5-AZA-CdR when compared to controls, but not in females, and correlated significantly with body weights. Our data suggest that the decreased levels of IGF-1 associated with the treatment could be the cause of the observed growth retardation in the in utero-exposed mice. A gender dimorphic effect, where males are more affected, is evident.

Endostatin inhibits migration and invasion of head and neck squamous cell carcinoma cells.

Head and neck cancers are significant due to their high morbidity and associated complications. We report, for the first time, that endostatin directly affects epithelial lineage human cells derived from tumors of patients with head and neck squamous cell carcinoma (HNSCC). This study investigated endostatin's effects on several HNSCC cellular functions that are essential for tumor progression. We determined that exposure of HNSCC cells to endostatin activated the transcription-activating factors, NF-xB and AP-1 in a cell-line-dependent fashion. Endostatin also down-regulated the gene expression of several pro-migratory molecules. Migration and invasion assays showed that endostatin significantly inhibited these functions that are essential for tumor progression. Fluorescent labeling studies showed endostatin co-localized to tropomysin-binding HNSCC the microfilaments, suggesting endostatin's suppression of HNSCC cell migration and invasion may reflect perturbation of the microfilament function. Our data imply that endostatin's clinical efficacy extends beyond angiostatic properties to encompass a direct anti-tumorigenic effect against HNSCC cells.

Maternal glomerular filtration rate in pregnancy and fetal size.

BACKGROUND: The relationship of maternal glomerular filtration rate (GFR) in pregnancy to fetal size needs to be better characterized as it impacts an ongoing debate about confounding effect of maternal GFR in investigations of important environmental contaminants. We aimed to characterize the size of the association between maternal GFR and infant birth weight. MATERIALS AND METHODS: A sub-cohort of 953 selected women (470 women with and 483 women without preeclampsia) in the Norwegian Mother and Child Cohort (MoBa), recruited during 2003-2007 were analyzed. GFR in the second trimester was estimated based on plasma creatinine. Birth weight was ascertained from the Medical Birth Registry of Norway. Multivariate linear regression was used to evaluate the association between maternal GFR in second trimester (estimated by the Cockroft-Gault [GFR-CG] and the modification of diet in renal disease [GFR-MDRD] formulas) and infant birth weight. Partial correlation coefficients were also calculated. RESULTS: Maternal GFR-CG (ß: 0.73 g/ml/min, p = 0.04) and GFR-MDRD (ß: 0.83 g/ml/min, p = 0.04) were associated with infant birth weight in models adjusted for maternal weight in kilograms, preeclampsia, and gestational age at delivery (days). Partial correlation coefficients for the association between infant birth weight and GFR were 0.07 for both formulas. Although the birth weight-GFR association was stronger among the women with preeclampsia, the difference from women without preeclampsia was not statistically significant. CONCLUSION: These data support an association between GFR during pregnancy and infant birth weight, and indicate that GFR may confound selected epidemiologic associations.

Predictors of plasma DDT and DDE concentrations among women exposed to indoor residual spraying for malaria control in the South African Study of Women and Babies (SOWB).

BACKGROUND: Few studies have examined predictors of DDT (dichlorodiphenyltrichloroethane) and DDE (dichlorodiphenyldichloroethylene) levels among residents in homes sprayed with DDT for malaria control with the aim of identifying exposure-reduction strategies. METHODS: The present analysis included 381 women enrolled in the Study of Women and Babies (SOWB) during 2010-2011, from eight South African villages in the Limpopo Province, South Africa. Indoor residual spraying (IRS) occurred in half of the villages. Questionnaires regarding various demographic and medical factors were administered and blood samples were obtained. We classified the women into three exposure groups by type of residence: unsprayed village (n = 175), IRS village in household with a low likelihood of DDT use (non-DDT IRS household, n = 106), IRS village in household with a high likelihood of DDT use (DDT IRS household, n = 100). We used multivariable models of natural log-transformed DDT plasma levels (in micrograms per liter) and DDE (in micrograms per liter) to identify predictors for each group. RESULTS: Median levels of DDT and DDE among women in unsprayed villages were 0.3 [interquartile range (IQR): 0.1-0.9] and 1.7 (IQR: 0.7-5.5), respectively. Median levels of DDT and DDE among women in DDT IRS households were 2.6 (IQR: 1.1-6.6) and 8.5 (IQR: 4.7-18.0), respectively. In unsprayed villages, women with water piped to the yard, rather than a public tap, had 73% lower DDT (95% CI: -83, -57%) and 61% lower DDE (95% CI: -74, -40%) levels. In DDT IRS households, women who reported taking more than six actions to prepare their home before IRS (e.g., covering water and food) had 40% lower DDT levels (95% CI: -63, -0.3%) than women who took fewer than four actions. CONCLUSION: The predictors of DDT and DDE plasma levels identified in the present study may inform interventions aimed at decreasing exposure. Among households where DDT is likely to be used for IRS, education regarding home preparations may provide an interventional target.

Perfluoroalkyl substances and lipid concentrations in plasma during pregnancy among women in the Norwegian Mother and Child Cohort Study.

BACKGROUND: Perfluoroalkyl substances (PFASs) are widespread and persistent environmental pollutants. Previous studies, primarily among non-pregnant individuals, suggest positive associations between PFAS levels and certain blood lipids. If there is a causal link between PFAS concentrations and elevated lipids during pregnancy, this may suggest a mechanism by which PFAS exposure leads to certain adverse pregnancy outcomes, including preeclampsia. METHODS: This cross-sectional analysis included 891 pregnant women enrolled in the Norwegian Mother and Child (MoBa) Cohort Study in 2003-2004. Non-fasting plasma samples were obtained at mid-pregnancy and analyzed for nineteen PFASs. Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured in plasma. Linear regression was used to quantify associations between each PFAS exposure and each lipid outcome. A multiple PFAS model was also fitted. RESULTS: Seven PFASs were quantifiable in >50% of samples. Perfluorooctane sulfonate (PFOS) concentration was associated with total cholesterol, which increased 4.2mg/dL per inter-quartile shift (95% CI=0.8, 7.7) in adjusted models. Five of the seven PFASs studied were positively associated with HDL cholesterol, and all seven had elevated HDL associated with the highest quartile of exposure. Perfluoroundecanoic acid showed the strongest association with HDL: HDL increased 3.7 mg/dL per inter-quartile shift (95% CI=2.5, 4.9). CONCLUSION: Plasma concentrations of PFASs were positively associated with HDL cholesterol, and PFOS was positively associated with total cholesterol in this sample of pregnant Norwegian women. While elevated HDL is not an adverse outcome per se, elevated total cholesterol associated with PFASs during pregnancy could be of concern if causal.

Artifactual changes in Sprague-Dawley rat hematologic parameters after storage of samples at 3 °C and 21 °C.

Circumstances can occur that prevent timely analysis of blood samples. The purpose of this study was to characterize artifactual changes in rat hematologic parameters after storage of samples at 3 and 21 °C and to document the effects of storage on peripheral blood smear findings. EDTA-treated blood samples were collected from 12 male Sprague-Dawley rats. Samples were analyzed on an impedance hematology analyzer within 5 min after collection and then at 6, 24, 48, and 72 h after storage at 3 °C or 21 °C. Corresponding blood smears were examined microscopically. RBC count and hemoglobin concentration had not changed after 72 h at either temperature. At 3 °C, the instrument-derived hematocrit and manually measured PCV remained unchanged for 72 h. Compared with 0-h values, platelet counts and MCV at 6 h and MPV at 24 h were higher at either temperature. In general, WBC count and neutrophil and lymphocyte percentages were unchanged for at least 48 h at either temperature. Prominent blood smear findings were smudge cells, pyknotic leukocytes, echinocytes, and spheroechinocytes. Although some observed changes were within analytic variability or clinically negligible, the best practice likely is to measure hematologic parameters within 6 h after collection. In the event of delayed analysis, specimens should be stored in the refrigerator, and care must be taken not to misinterpret artifactual changes as pathologic findings.