Medical Toxicology Commons^™

A Longitudinal Study Of Peripubertal Serum Organochlorine Concentrations And Semen Parameters In Young Men: The Russian Children's Study, Lidia Minguez-Alarcon, Oleg Sergeyev, Jane S. Burns, Paige L. Williams, Mary M. Lee, Susan A. Korrick, Luidmila Smigulina, Boris Revich, Russ Hauser

Mary M. Lee

BACKGROUND: Exposures to endocrine disrupting chemicals during critical phases of testicular development may be related to poorer semen parameters. However, few studies have assessed the association between childhood organochlorine (OC) exposure and adult semen parameters.

OBJECTIVE: We examined whether peripubertal serum OC concentrations are associated with semen parameters among young Russian men.

METHODS: From 2003 to 2005, 516 boys were enrolled at age 8-9 years and followed for up to ten years. Serum OCs were measured in the enrollment samples using high-resolution mass spectrometry. At age 18-19 years, 133 young men provided one or two semen samples (256 samples) collected …

A Modular One-Generation Reproduction Study As A Flexible Testing System For Regulatory Safety Assessment, Richard Vogel, Troy Seidle, Horst Spielmann

Troy Seidle, PhD

The European Union’s Registration, Evaluation and Authorisation of Chemicals (REACH) legislation mandates testing and evaluation of approximately 30,000 existing substances within a short period of time, beginning with the most widely used “high production volume” (HPV) chemicals. REACH testing requirements for the roughly 3000 HPV chemicals specify three separate tests for reproductive toxicity: two developmental toxicity studies on different animal species (OECD Test Guideline 414) and a two-generation reproduction toxicity study (OECD TG 416). These studies are highly costly in both economic and animal welfare terms. OECD TG 416 is a fertility study intended to evaluate reproductive performance of animals …

Genetic Modification Of The Association Between Peripubertal Dioxin Exposure And Pubertal Onset In A Cohort Of Russian Boys, Olivier Humblet, Susan A. Korrick, Paige L. Williams, Oleg Sergeyev, Claude Emond, Linda S. Birnbaum, Jane S. Burns, Larisa Altshul, Donald G. Patterson Jr., Wayman E. Turner, Mary M. Lee, Boris Revich, Russ Hauser

Mary M. Lee

BACKGROUND: Exposure to dioxins has been associated with delayed pubertal onset in both epidemiologic and animal studies. Whether genetic polymorphisms may modify this association is currently unknown. Identifying such genes could provide insight into mechanistic pathways. This is one of the first studies to assess genetic susceptibility to dioxins. OBJECTIVES: We evaluated whether common polymorphisms in genes affecting either molecular responses to dioxin exposure or pubertal onset influence the association between peripubertal serum dioxin concentration and male pubertal onset. METHODS: In this prospective cohort of Russian adolescent boys (n = 392), we assessed gene-environment interactions for 337 tagging single-nucleotide polymorphisms …

Early Chronic Low-Level Lead Exposure Produces Glomerular Hypertrophy In Young C57bl/6j Mice, Christina Sobin, John Basgen

Christina Sobin, Ph.D.

Early chronic lead exposure continues to pose serious health risks for children, particularly those living in lower socioeconomic environments. This study examined effects on developing glomeruli in young C57BL/6J mice exposed to low (30 ppm), higher (330 ppm) or no lead via dams’ drinking water from birth to sacrifice on post-natal day 28. Low-level lead exposed mice [BLL mean (SD); 3.19 (0.70) µg/dL] had an increase in glomerular volume but no change in podocyte number compared to control mice [0.03 (0.01) µg/dL]. Higher-level lead exposed mice [14.68 (2.74) µg/dL] had no change in either glomerular volume or podocyte number. The …

Microglial Disruption In Young Mice With Early Chronic Exposure To Lead, Christina Sobin, Mayra Flores Montoya, Natali Parisi, Tanner Schaub, Miguel Cervantes, Rodrigo Armijos

Christina Sobin, Ph.D.

The mechanisms by which early chronic lead (Pb) exposure alters brain development have not been identified. We examined neuroimmune system effects in C57BL/6J mice with Pb exposure, including levels that may be common among children in lower socioeconomic income environments. Pups were exposed via dams’ drinking water from birth to post-natal day 28 to low, high or no Pb conditions. We compared gene expression of neuroinflammatory markers (study 1); and microglial mean cell body volume and mean cell body number in dentate gyrus, and dentate gyrus volume (study 2). Blood Pb levels in exposed animals at sacrifice (post-natal day 28) …

Δ-Aminolevulinic Acid Dehydratase Single Nucleotide Polymorphism 2 And Peptide Transporter 2*2 Haplotype May Differentially Mediate Lead Exposure In Male Children, Christina Sobin, Natali Parisi, Tanner Schaub, Marisela Gutierrez, Alma Ortega

Christina Sobin, Ph.D.

Child low-level lead (Pb) exposure is an unresolved public health problem and an unaddressed child health disparity. Particularly in cases of low-level exposure, source removal can be impossible to accomplish, and the only practical strategy for reducing risk may be primary prevention. Genetic biomarkers of increased neurotoxic risk could help to identify small subgroups of children for early intervention. Previous studies have suggested that, by way of a distinct mechanism, d-aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and/or peptide transporter 2*2 haplotype (hPEPT2*2) increase Pb blood burden in children. Studies have not yet examined whether sex mediates the effects …

A Bland–Altman Comparison Of The Lead Care® System And Inductively Coupled Plasma Mass Spectrometry For Detecting Low-Level Lead In Child Whole Blood Samples, Christina Sobin, Tanner Schaub, Natali Parisi, Eva De La Riva

Christina Sobin, Ph.D.

Chronic childhood lead exposure, yielding blood lead levels consistently below 10 μg/dL, remains a major public health concern. Low neurotoxic effect thresholds have not yet been established. Progress requires accurate, efficient, and cost-effective methods for testing large numbers of children. The LeadCare® System (LCS) may provide one ready option. The comparability of this system to the “gold standard” method of inductively coupled plasma mass spectrometry (ICP-MS) for the purpose of detecting blood lead levels below 10 μg/dL has not yet been examined. Paired blood samples from 177 children ages 5.2–12.8 years were tested with LCS and ICP-MS. Triplicate repeat tests …