Early pregnancy exposure to metal mixture and birth outcomes - A prospective study in Project Viva.

BACKGROUND: Prenatal exposure to metals has been individually associated with birth outcomes. However, little is known about the effect of metal mixture, particularly at low exposure levels. OBJECTIVES: To estimate individual and joint effects of metal mixture components on birth outcomes. METHODS: We used data from 1,391 mother-infant pairs in Project Viva (1999-2002). We measured 11 metals in maternal 1st trimester erythrocyte; abstracted birth weight from medical records; calculated gestational age from last menstrual period or ultrasound; and obtained birth length (n = 729) and head circumference (n = 791) from research measurements. We estimated individual and joint effects of metals using multivariable linear and Bayesian kernel machine regressions. RESULTS: In both single metal and metal mixture analyses, exposure to higher concentrations of arsenic was associated with lower birth weight in males, zinc with higher head circumference in females, and manganese with higher birth length in sex-combined analysis. We also observed sex-specific metal interactions with birth outcomes. Arsenic and manganese showed a synergistic association with birth weight in males, in whom an interquartile range (IQR) increase in arsenic was associated with 25.3 g (95% CI: -79.9, 29.3), 47.9 g (95% CI: -98.0, 2.1), and 72.2 g (95% CI: -129.8, -14.7) lower birth weight when manganese concentrations were at 25th, 50th, and 75th percentiles, respectively. Lead and zinc showed an antagonistic association with head circumference in males, where an IQR increase in lead was associated with 0.18 cm (95% CI: -0.35, -0.02), 0.10 cm (95% CI: -0.25, 0.04), 0.03 cm (95% CI: -0.2, 0.14) smaller head circumference when zinc concentrations were at 25th, 50th, and 75th percentiles, respectively. Exposure to higher concentrations of arsenic was also associated with lower gestational age in males when concentrations of manganese and lead were higher. DISCUSSION: Maternal erythrocyte concentrations of arsenic, manganese, lead, and zinc were individually and interactively associated with birth outcomes. The associations varied by infant sex and exposure level of other mixture components.

Altered lipid homeostasis in a PCB-resistant Atlantic killifish (Fundulus heteroclitus) population from New Bedford Harbor, MA, U.S.A.

Sentinel species such as the Atlantic killifish (Fundulus heteroclitus) living in urban waterways can be used as toxicological models to understand impacts of environmental metabolism disrupting compound (MDC) exposure on both wildlife and humans. Exposure to MDCs is associated with increased risk of metabolic syndrome, including impaired lipid and glucose homeostasis, adipogenesis, appetite control, and basal metabolism. MDCs are ubiquitous in the environment, including in aquatic environments. New Bedford Harbor (NBH), Massachusetts is polluted with polychlorinated biphenyls (PCBs), and, as we show for the first time, tin (Sn). PCBs and organotins are ligands for two receptor systems known to regulate lipid homeostasis, the aryl hydrocarbon receptor (AHR) and the peroxisome proliferator-activated receptors (PPARs), respectively. In the current study, we compared lipid homeostasis in laboratory-reared killifish from NBH (F2) and a reference location (Scorton Creek, Massachusetts; F1 and F2) to evaluate how adaptation to local conditions may influence responses to MDCs. Adult killifish from each population were exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB126, dioxin-like), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153, non-dioxin-like), or tributyltin (TBT, a PPARγ ligand) by a single intraperitoneal injection and analyzed after 3 days. AHR activation was assessed by measuring cyp1a mRNA expression. Lipid homeostasis was evaluated phenotypically by measuring liver triglycerides and organosomatic indices, and at the molecular level by measuring the mRNA expression of pparg and ppara and a target gene for each receptor. Acute MDC exposure did not affect phenotypic outcomes. However, overall NBH killifish had higher liver triglycerides and adiposomatic indices than SC killifish. Both season and population were significant predictors of the lipid phenotype. Acute MDC exposure altered hepatic gene expression only in male killifish from SC. PCB126 exposure induced cyp1a and pparg, whereas PCB153 exposure induced ppara. TBT exposure did not induce ppar-dependent pathways. Comparison of lipid homeostasis in two killifish populations extends our understanding of how MDCs act on fish and provides a basis to infer adaptive benefits of these differences in the wild.

Measurement of pesticides and other toxicants in amniotic fluid as a potential biomarker of prenatal exposure: a validation study.

Prenatal pesticide exposures may adversely affect children's health. However, exposure and health research is hampered by the lack of reliable fetal exposure data. No studies have been published that report measurements of commonly used nonpersistent pesticides in human amniotic fluid, although recent studies of pesticides in urine from pregnant women and in meconium indicate that fetuses are exposed to these chemicals. Amniotic fluid collected during amniocentesis is the only medium available to characterize direct fetal exposures early in pregnancy (approximately 18 weeks of gestation). As a first step in validating this exposure biomarker, we collected 100 amniotic fluid samples slated for disposal and evaluated analytical methods to measure organophosphate and carbamate pesticides and metabolites, synthetic pyrethroid metabolites, herbicides, and chlorinated phenolic compounds. The following six phenols were detected (detection frequency): 1- and 2-naphthol (70%), 2,5-dichlorophenol (55%), carbofuranphenol (5%), ortho-phenylphenol (30%), and pentachlorophenol (15%), with geometric mean concentrations of 0.72, 0.39, 0.12, 0.13, and 0.23 microg/L, respectively, for positive values. The organophosphate metabolites diethylphosphate and dimethylphosphate were detected in two (10%) samples, and dimethylthiophosphate was detected in one (5%) sample, with geometric mean concentrations of 0.31, 0.32, and 0.43 microg/L, respectively, for positive values. These levels are low compared with levels reported in urine, blood, and meconium in other studies, but indicate direct exposures to the young fetus, possibly during critical periods of development. Results of this pilot study suggest that amniotic fluid offers a unique opportunity to investigate fetal exposures and health risks.