Person:

Hauser, Russ

Particulate air pollution has been associated with adverse respiratory health effects. This study assessed the utility of expired nitric oxide to detect acute airway responses to metal-containing fine particulates. Using a repeated-measures study design, we investigated the association between the fractional concentration of expired nitric oxide (F(E)NO) and exposure to particulate matter with an aerodynamic mass median diameter of less than or equal to 2.5 micro m (PM({2.5})) in boilermakers exposed to residual oil fly ash and metal fumes. Subjects were monitored for 5 days during boiler repair overhauls in 1999 (n = 20) or 2000 (n = 14). The Wilcoxon median baseline F(E)NO was 10.6 ppb [95% confidence interval (CI): 9.1, 12.7] in 1999 and 7.4 ppb (95% CI: 6.7, 8.0) in 2000. The Wilcoxon median PM({2.5}) 8-hr time-weighted average was 0.56 mg/m(3) (95% CI: 0.37, 0.93) in 1999 and 0.86 mg/m(3) (95% CI: 0.65, 1.07) in 2000. F(_E)NO levels during the work week were significantly lower than baseline F(E)NO in 1999 (p < 0.001). A significant inverse exposure-response relationship between log-transformed F(E)NO and the previous workday's PM({2.5}) concentration was found in 1999, after adjusting for smoking status, age, and sampling year. With each 1 mg/m(^3) incremental increase in PM({2.5}) exposure, log F(E)NO decreased by 0.24 (95% CI: -0.38, -0.10) in 1999. The lack of an exposure-response relationship between PM({2.5}) exposure and F(_E)NO in 2000 could be attributable to exposure misclassification resulting from the use of respirators. In conclusion, occupational exposure to metal-containing fine particulates was associated with significant decreases in F(_E)NO in a survey of workers with limited respirator usage.

Background: Phthalates are used extensively in many personal-care and consumer products, resulting in widespread nonoccupational human exposure through multiple routes and media. A limited number of animal studies suggest that exposure to phthalates may be associated with altered thyroid function, but human data are lacking. Methods: Concurrent samples of urine and blood were collected from 408 men. We measured urinary concentrations of mono(2-ethylhexyl) phthalate (MEHP), the hydrolytic metabolite of di(2-ethylhexyl) phthalate (DEHP), and other phthalate monoester metabolites, along with serum levels of free thyroxine (T(_4)), total triiodothyronine (T(_3)), and thyroid-stimulating hormone (TSH). Oxidative metabolites of DEHP were measured in urine from only 208 of the men. Results: We found an inverse association between MEHP urinary concentrations and free T(_4) and T(_3) serum levels, although the relationships did not appear to be linear when MEHP concentrations were categorized by quintiles. There was evidence of a plateau at the fourth quintile, which was associated with a 0.11 ng/dL decrease in free T(_4) [95% confidence interval (CI), –0.18 to –0.03] and a 0.05 ng/mL decrease in T(_3) (95% CI, –0.10 to 0.01) compared with the first (lowest) MEHP quintile. The inverse relationship between MEHP and free T(_4) remained when we adjusted for oxidative metabolite concentrations; this simultaneously demonstrated a suggestive positive association with free T(_4). Conclusions: Urinary MEHP concentrations may be associated with altered free T(_4) and/or total T(_3) levels in adult men, but additional study is needed to confirm the observed findings. Future studies must also consider oxidative DEHP metabolites relative to MEHP as a potential marker of metabolic susceptibility to DEHP exposure.

Background: Although sources and routes of exposure to dioxins and polychlorinated biphenyls (PCBs) have been studied, information regarding exposure among children is limited. Breast-feeding and diet are two important contributors to early life exposure. To further understand other significant contributors to childhood exposure, we studied a cohort of children from a city with high environmental dioxin levels. Objectives: We investigated predictors of serum concentrations of polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzofurans (PCDFs)/co-planar PCBs (C-PCBs), toxic equivalents (TEQs), and PCBs among 8- to 9-year-old boys in Chapaevsk, Russia. Methods: We used general linear regression models to explore associations of log10-transformed serum concentrations of PCDDs/PCDFs/C-PCBs, TEQs, and PCBs at study entry with anthropometric, demographic, geographic, and dietary factors in 482 boys in Chapaevsk, Russia. Results: The median (25th, 75th percentile) concentration for total 2005 TEQs was 21.1 pg/g lipid (14.4, 33.2). Boys who were older, consumed local foods, were breast-fed longer, and whose mothers were employed at the Khimprom chemical plant (where chlorinated chemicals were produced) or gardened locally had significantly higher serum dioxins and PCBs, whereas boys with higher body mass index or more educated parents had significantly lower serum dioxins and PCBs. Boys who lived less than 2 km from Khimprom had higher total TEQs (picograms per gram lipid) [adjusted mean = 30.6; 95% confidence interval (CI), 26.8–35.0] than boys who lived greater than 5 km away (adjusted mean = 18.8; 95% CI, 17.2–20.6). Conclusions: Our findings suggest that there are specific local sources of dioxin and PCB exposure among children in Chapaevsk including maternal gardening, consumption of locally grown food, and residential proximity to the Khimprom plant.

Background: Phthalates can alter steroidogenesis and peroxisome proliferator–activated receptor gamma (PPARγ)–mediated transcription in rodent tissues. The placenta offers a rich source of biomarkers to study these relationships in humans. Objective: We evaluated whether gestational phthalate exposures in humans were associated with altered human placental steroidogenesis and trophoblast differentiation as measured by markers of mRNA transcription. Methods: We measured seven target genes in placentas collected from 54 Dominican and African-American women at delivery in New York City using quantitative real-time polymerase chain reaction (qPCR), normalized to 18S rRNA. qPCR results for the target genes were log-transformed, converted to Z-scores, and grouped into two functional pathways: steroidogenesis (aromatase, cholesterol side chain cleavage enzyme, 17β-hydroxysteroid dehydrogenase type 1, and cytochrome P450 1B1) and trophoblast differentiation (PPARγ, aryl hydrocarbon receptor, and human chorionic gonadotropin). Repeated measures models were used to evaluate the association of phthalate metabolites measured in third-trimester urine samples with each group of target genes, accounting for correlation among the genes within a pathway. Results: Higher urinary concentrations of five phthalate metabolites were associated with lower expression of the target genes reflecting trophoblast differentiation. Results were less consistent for genes in the steroidogenesis pathway and suggested a nonlinear dose–response pattern for some phthalate metabolites. Conclusions: We observed a significant association between prenatal exposure to phthalates and placental gene expression within two pathways. Further studies are warranted to understand the significance of this association with respect to fetal development and placental function.

Background: Epidemiologic studies suggest a temporal trend of earlier onset and longer duration of puberty, raising concerns regarding the potential impact of environmental factors on pubertal development. Lead exposure has been associated with delayed pubertal onset in girls; however, epidemiologic data in boys are limited. Methods: We used multivariable logistic regression models to explore the cross-sectional association of blood lead levels with growth and pubertal onset based on physician-assessed testicular volume (TV) and pubertal staging in 489 boys 8–9 years of age from Chapaevsk, Russia. We used multivariable linear regression models to assess associations of blood lead levels with somatic growth at the study entry visit. Results: The median (25th–75th percentile) blood lead level was 3 μg/dL (2–5 μg/dL). Height, weight, body mass index, birth weight, and gestational age were predictive of the onset of puberty as assessed either by TV (greater than 3 mL), genitalia stage (G2), or both. Blood lead level was inversely associated with height (p less than 0.001) and weight (p = 0.06) after adjustment for birth weight, gestational age, and age at examination. In multivariable adjusted analyses, boys with blood lead levels ≥ 5 μg/dL had 43% reduced odds of having entered G2 compared with those with lower levels (odds ratio = 0.57; 95% confidence interval, 0.34–0.95, p = 0.03). Conclusions: Relatively low environmental blood lead levels were associated with decreased growth and differences in pubertal onset in periadolescent Russian boys. Future analyses of this prospective cohort will address pubertal onset and progression in relation to lead and other environmental chemicals.

Previously, we reported evidence of inverse associations between exposure to some polychlorinated biphenyls (PCBs) and some phthalate monoesters in relation to semen parameters, specifically sperm motility. Because humans are exposed to both phthalates and PCBs and because experimental studies suggest that PCBs may interact with glucuronidative enzymes that are responsible for phthalate metabolism, we explored the potential interaction between phthalates and PCBs in relation to human semen quality. We studied 303 men who were partners in subfertile couples seeking infertility diagnosis from the andrology laboratory at Massachusetts General Hospital. Semen parameters were dichotomized based on World Health Organization reference values, and phthalate and PCB levels were dichotomized at their respective medians. After adjusting for age and abstinence time, for below reference sperm motility there was a greater than additive interaction between monobenzyl phthalate and PCB-153 [relative excess risk due to interaction (RERI) = 1.40; 95% confidence interval (CI), 0.41–3.22], sum of PCBs (RERI = 1.24; 95% CI, 0.15–2.94), and cytochrome P450 (CYP450)-inducing PCBs (RERI = 1.30; 95% CI, 0.21–3.06). For below-reference sperm motility, there was also a greater than additive interaction between monobutyl phthalate (MBP) and PCB-153 (RERI = 1.42; 95% CI, 0.09–3.76) and CYP450-inducing PCBs (RERI = 1.87; 95% CI, 0.56–4.52) and a suggestive interaction between MBP and sum of PCBs (RERI = 1.35; 95% CI, −0.11 to 3.48). In conclusion, because there are important risk assessment and public health implications of interactions between these two ubiquitous classes of compounds, further studies need to be conducted to confirm these results and identify potential mechanisms of interactions.

Background: Limited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children’s growth.: Objective: We evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels. Methods: A cohort of 499 boys enrolled in the Russian Children’s Study between 2003 and 2005 at 8–9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and height velocity were examined by multivariate mixed-effects regression models for repeated measures, controlling for potential confounders. Results: Among the 350 boys with OCP measurements, median serum hexachlorobenzene (HCB), (\beta)-hexachlorocyclohexane ((\beta)HCH), and (p,p^´)-dichlorodiphenyldichloroethylene ((p,p^´)-DDE) concentrations were 159 ng/g lipid, 168 ng/g lipid, and 287 ng/g lipid, respectively. Age-adjusted BMI and height (z)-scores generally fell within the normal range per World Health Organization standards at entry and during follow-up. However, in adjusted models, boys with higher serum HCB, ((\beta)HCH), and ((p,p^´)-DDE had significantly lower mean [95% confidence interval (CI)] BMI (z)-scores, by –0.84 (–1.23, –0.46), –1.32 (–1.70, –0.95), and –1.37 (–1.75, –0.98), respectively, for the highest versus lowest quintile. In addition, the highest quintile of ((p,p^´)-DDE was associated with a significantly lower mean (95% CI) height (z)-score, by –0.69 (–1.00, –0.39) than that of the lowest quintile. Conclusions: Serum OCP concentrations measured at 8–9 years of age were associated with reduced growth, particularly reduced BMI, during the peripubertal period, which may affect attainment of optimal adult body mass and height.

Background: Human exposure to polychlorinated biphenyls (PCBs) remains widespread. PCBs have been associated with adverse reproductive health outcomes including reduced fecundability and increased risk of pregnancy loss, although the human data remain largely inconclusive.

Objective: Our goal was to explore the relationship between serum PCB concentrations and early pregnancy loss among a large cohort of women undergoing in vitro fertilization (IVF) between 1994 and 2003.

Methods: Concentrations of 57 PCB congeners were measured in serum samples collected during 827 IVF/intracytoplasmic sperm injection cycles from 765 women. Joint statistical models that accommodate multiple outcomes and multiple cycles per woman were used to assess the relationship between serum PCB quartiles and implantation failure, chemical pregnancies (human chorionic gonadotropin level > 5.0 mIU/mL) that did not result in clinical pregnancy, or spontaneous abortion, while also adjusting for confounders.

Results: PCB-153 was the congener present in the highest concentration (median, 46.2 ng/g lipid). Increasing quartiles of PCB-153 and the sum of all measured PCB congeners (ΣPCBs) were associated with significantly elevated dose-dependent odds of failed implantation. Adjusted odds ratios (95% confidence interval) for highest versus lowest quartile were 2.0 (1.2–3.4) for PCB-153 and 1.7 (1.0–2.9) for ΣPCBs. There were suggestive trends for increased odds of implantation failure for PCB-118 and cytochrome P450–inducing congeners (p-values for trend = 0.06). No statistically significant associations between PCBs and chemical pregnancy or spontaneous abortion were found.

Conclusions: Serum PCB concentrations at levels similar to the U.S. general population were associated with failed implantation among women undergoing IVF. These findings may help explain previous reports of reduced fecundability among women exposed to PCBs.

Background: A reduction in the use of polybrominated diphenyl ethers (PBDEs) because of human health concerns may result in an increased use of and human exposure to organophosphate flame retardants (OPFRs). Human exposure and health studies of OPFRs are lacking. Objectives: We sought to define the degree of temporal variability in urinary OPFR metabolites in order to inform epidemiologic study design, and to explore a potential primary source of exposure by examining the relationship between OPFRs in house dust and their metabolites in urine. Methods: Nine repeated urine samples were collected from 7 men over the course of 3 months and analyzed for bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and diphenyl phosphate (DPP), metabolites of the OPFRs tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP), respectively. Intraclass correlation coefficients (ICCs) were calculated to characterize temporal reliability. Paired house dust and urine samples were collected from 45 men. Results: BDCPP was detected in 91% of urine samples, and DPP in 96%. Urinary BDCPP showed moderate-to-strong temporal reliability (ICC range, 0.55–0.72). ICCs for DPP were lower, but moderately reliable (range, 0.35–0.51). There was a weak [Spearman r (rS) = 0.31] but significant (p = 0.03) correlation between urinary BDCPP and TDCPP concentrations in house dust that strengthened when nondetects (rS = 0.47) were excluded. There was no correlation between uncorrected DPP and TPP measured in house dust (rS < 0.1). Conclusions: Household dust may be an important source of exposure to TDCPP but not TPP. Urinary concentrations of BDCPP and DPP were moderately to highly reliable within individuals over 3 months.

Among 2245 women, those who experienced a chemical pregnancy that failed to progress to a clinically recognized pregnancy or a spontaneous abortion on their first IVF cycle were more likely to discontinue IVF treatment than those whose first cycle ended prior to embryo transfer or who did not have a positive pregnancy test following transfer. However, among women who did continue to a second IVF cycle, those who had at least a chemical pregnancy on the first cycle were more likely to have a live birth on the second attempt than those women who had failed prior to conception in the first cycle (34% success rate compared to 21%, respectively).