Principal Investigator/Program Director (Last, First, Middle): Stewart, Paul W.
Abstract
Owing to a legacy of industrial pollution throughout the 20th Century, children in the
Great Lakes region in the United States are exposed to mixtures of environmental
contaminants; some of the most significant contaminants are polychlorinated biphenyls
(PCBS) and methylmercury (MeHg). It is important to underscore that these exposures
occur in children who are already exposed to background levels of well-understood
contaminants, such as lead (Pb). Each of these contaminants is potentially neurotoxic,
and, in fact, all have been implicated in neurobehavioral deficits in children. Families in
the Great Lakes region are particularly at risk for exposure. Multiple exposure pathways
include dietary intake of Great Lakes sport fish, the legacy of industrial, agricultural and
landfill waste and downwind pollution from energy production facilities. The fact that our
study population has likely experienced these exposure routes allows us to examine the
impact of both individual and combined exposure to these contaminants through the
middle teenage years. This goal is informed recent data by which show that prenatal
PCB exposure predicts impulsive behavior and impaired inhibitory control from ages 4 ¿
years through 13 years of age.
The Oswego Project has repeatedly demonstrated that PCB exposure is related to an
impaired ability to inhibit behavior, or impaired response inhibition. During the last
granting period, the data on this phenomenon has advanced to the point where the
Project can confirm that this deficit is characterized by an inability to inhibit prepotent
response tendencies, rather than just excessive motor activity, perseveration, or an
attentional deficit. While these findings have advanced the field in important ways, it is
the data that relate to the putative effects of PCBs, in combination with MeHg, and even
Pb, that is most compelling and hold the most promise for the current proposal. As the
behavioral significance of PCB exposure continues to be clarified and linked to inhibition
and response control, effects of both MeHg and Pb have begun to emerge on these
endpoints. The goal of the current proposal is to use the knowledge we have obtained to
test new and important hypotheses regarding the mixture of these toxics on behavior. In
doing so, we may reveal that both the effects of individual contaminants and the
cumulative impact of combined exposures may result in clinically significant
impairments. Within the scope of these parameters, we believe that the design and
methodology of the proposed project is ideally suited to examine the important putative
effects of PCB, MeHg and Pb on response inhibition.
PHS 98/50 Rv. 09/4, Reissued 4/2006) Pg Continuation Format Page Relevance
There is reasonable evidence from research studies that indicate that prenatal exposure
to PCBs produces impairments in cognitive development in children. The Oswego
Project represents one of the few major, longitudinal studies in the United States
designed to assess the effects of exposure to low levels of PCBs on child development.
The stable nature of the cohort, the 14 years of experience the Principal Investigators
have with these cohorts, the well-established testing protocols, and the extensive
database of exposure, outcome and potentially confounding/ mediating variables permit
rigorous assessment of the impact of prenatal PCB exposure in the early teen years.