Children's Vulnerability to Environmental Immunotoxicant ExposureEPA Grant Number: R830758
Title: Children's Vulnerability to Environmental Immunotoxicant Exposure
Investigators: Grandjean, Philippe
Current Investigators: Grandjean, Philippe , Weihe, Pal
Institution: Harvard T.H. Chan School of Public Health
EPA Project Officer: Hahn, Intaek
Project Period: May 5, 2003 through May 4, 2006 (Extended to May 4, 2007)
Project Amount: $750,000
RFA: Children's Vulnerability to Toxic Substances in the Environment (2002) RFA Text | Recipients Lists
Research Category: Children's Health , Health Effects , Human Health , Health
This project aims at determining the immunotoxic risk in children exposed prenatally and postnatally to polychlorinated biphenyls. Experimental animal studies with Aroclor 1254 used by EPA for calculating a Reference Dose (RfD) for PCB suggest that immunotoxicity may be critical, but current exposures, especially those from breast-feeding, greatly exceed the RfD.
A birth cohort of 547 Faroese children was established in 1998-2000. Because of PCB-contaminated seafood, some mothers have PCB concentrations that exceed U.S. averages by up to 100-fold. In a small-scale pilot study, we showed PCB-related decreases in antibody responses against primary protein antigens from the 12-month vaccination. The proposed study will focus on antibody responses of the full cohort to the scheduled vaccinations at age 5 years. The response variables depend on both T-cell and B-cell functions and are feasible for a field study, clinically highly relevant and also ethically acceptable. Immune deficits will be related to measures of prenatal and postnatal PCB exposure and to in vitro activation of the arylhydrocarbon receptor measured in maternal pregnancy serum by a novel approach. This new technique will include a newly discovered promoter sequence to assess different aspects of AhR activation. The high statistical power will allow advanced statistical analyses.
Because the birth cohort has already been established, and exposure assessment is already under way, the proposed study of antibody responses to the 5-year vaccinations will be possible within the 3-year grant period. The vaccine response is a clinically valid and highly relevant indicator of immune function, which is also feasible for population studies in the field. Exposure-related deficits in antibody responses are already known to occur in this population. With about 500 children examined, benchmark dose calculations will be possible, the relative impact of prenatal and lactational exposures may be assessed, as will the validity of individual chemical exposure biomarkers and the AhR activation by serum as assessed by the traditional and a novel method.