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2002 Progress Report: Neurobehavioral Effects of PCBs and Methylmercury in Rats

EPA Grant Number: R829390C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R829390
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: CECEHDPR - University of Illinois FRIENDS Children’s Environmental Health Center
Center Director: Schantz, Susan L.
Title: Neurobehavioral Effects of PCBs and Methylmercury in Rats
Investigators: Schantz, Susan L. , Widholm, John J.
Current Investigators: Schantz, Susan L.
Institution: University of Illinois at Urbana
EPA Project Officer: Saint, Chris
Project Period: October 17, 2001 through October 16, 2002
Project Period Covered by this Report: October 17, 2001 through October 16, 2002
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2001)
Research Category: Children's Health , Health Effects

Description:

Objective:

The FRIENDS Children's Environmental Health Center is a university/community partnership, which was established to investigate the health effects of combined exposure to polychlorinated biphenyls (PCBs) and methylmercury (MeHg) in Hmong and Laotian refugees consuming contaminated fish from the Fox River in northeastern Wisconsin. PCBs and MeHg are neurotoxic compounds that tend to occur together in the environment, especially in fish and seafood. Recent research suggests that the two compounds may have additive or synergistic effects on nervous system function. The goals of the FRIENDS Center are to study the impact of PCB and MeHg exposure on women's reproductive health and child development-focusing on neuropsychological development, to develop effective educational strategies to reduce exposure to these contaminants in reproductive age women and children, and to conduct laboratory studies aimed at understanding the mechanisms through which these contaminants induce neurological deficits in children. Partners in the research include the Hmong Association of Green Bay and the Fort Howard/Jefferson Neighborhood Family Resource Center of Green Bay, as well as researchers from the University of Illinois at Urbana-Champaign, Texas A & M University, Michigan State University, the University of Illinois at Chicago, SUNY Buffalo and the New York State Department of Health.

This particular project is being conducted at the University of Illinois at Urbana-Champaign. The primary objectives are to characterize the cognitive, motor and sensory effects of perinatal exposure to PCBs alone, MeHg alone or PCBs and MeHg in combination in the laboratory rat, to investigate the role of changes in specific neurotransmitter systems in mediating specific behavioral effects, to investigate the role of altered thyroid hormones in mediating specific behavioral effects and to use the results from these animal experiments to guide the selection of behavioral tests for use in children exposed to PCBs and MeHg through maternal consumption of contaminated fish.

Progress Summary:

Preliminary experiments investigating the effects of combined exposure to the commercial PCB mixture Aroclor 1254 and MeHg are nearing completion. Female rats were exposed to Aroclor 1254 (6 mg/kg/day), MeHg (0.5 ppm in the drinking water) or a combination of Aroclor 1254 and MeHg beginning 4 weeks prior to breeding and continuing until postnatal day 16. Male and female offspring were evaluated for long-term effects of this exposure on cognitive, motor and sensory function. Combined exposure to PCBs and MeHg caused a pronounced deficit in the animals' ability to traverse a rotating rod, a test of balance and coordination that relies heavily on the cerebellum (Roegge et al., 2002). When given individually neither compound had a significant effect on rotating rod performance. However, PCBs appeared to have a larger impact than MeHg. It has been known for some time that MeHg targets the cerebellum and impairs performance on cerebellar motor tasks, but this is the first in vivo study to suggest that PCBs may also target the cerebellum and impair balance and coordination. The results also suggest that the two compounds may be having an additive effect on motor function. Morphological studies of the cerebellum are currently underway to determine if there are underlying changes in cerebellar structure that could account for the functional changes.

Studies of cognitive function have yielded somewhat different results. Although both Aroclor 1254 and MeHg exposure caused deficits in spatial learning on a delayed non-match to sample task, combined exposure to Aroclor 1254 and MeHg did not result in a larger deficit than was seen with exposure to the individual compounds (Widholm et al., 2002). Detailed trial-by-trial analyse of error patterns are being conducted to help us understand the underlying deficits that resulted in the learning impairment on the delayed non-match to sample task. In addition, data from other learning tasks including a timing task are currently under analysis. Tests of auditory function in these animals are currently underway and the results should be available soon. Papers reporting the motor and cognitive results will be submitted for publication during the coming year.

The findings from these initial studies using Aroclor 1254 will be very helpful in designing neurobehavioral studies using the Fox River fish PCB mixture. A goal of the Center is to conduct laboratory animal studies using a PCB mixture that closely models the PCB mixture being consumed by the study population in Green Bay, WI. A mixture containing 35% Aroclor 1242, 35% Aroclor 1248, 15% Aroclor 1254 and 15% Aroclor 1260 was selected after studying the PCB congener profiles in white bass and walleye from the Fox River. The mixture has undergone confirmational analysis by GC/ECD to verify its similarity to the congener profile in Fox River fish and neurobehavioral studies using the mixture will be conducted during the coming year.

Future Activities:

During the next year tests of the effects of combined exposure to PCBs (Aroclor 1254) and MeHg on auditory function will completed and manuscripts describing the cognitive, motor and auditory findings from the Aroclor 1254/MeHg studies will be submitted for publication. In addition, new behavioral studies will be initiated using our new experimental PCB mixture that closely models the PCB mixture found in the fish being consumed by our study population in Green Bay, WI.


Journal Articles on this Report: 2 Displayed | Download in RIS Format

Other subproject views: All 15 publications 6 publications in selected types All 6 journal articles
Other center views: All 40 publications 24 publications in selected types All 23 journal articles

Type Citation Sub Project Document Sources
Journal Article Roegge CS, Wang VC, Powers BE, Klintsova A, Villareal S, Greenough WT, Schantz SL. Motor functions in rats exposed to PCBs and methylmercury during early development. Neurotoxicology and Teratology 2002;24(3):424-425. R829390C001 (2002)
R829390C001 (2003)
 not available
Journal Article Widholm, J., Villareal, S., Seegal, R., and Schantz, S. (2002). Impaired spatial alternation following developmental exposure to PCBs and methylmercury in rats. The Toxicologist, 66(1S): LB128. R829390C001 (2002)
 not available
Supplemental Keywords:

PCBs, MeHg, cognitive, auditory, motor, rats, thyroid hormones, neurotransmitters. , ENVIRONMENTAL MANAGEMENT, Scientific Discipline, Health, RFA, PHYSICAL ASPECTS, Susceptibility/Sensitive Population/Genetic Susceptibility, Molecular Biology/Genetics, Risk Assessment, Risk Assessments, genetic susceptability, Health Risk Assessment, Physical Processes, Epidemiology, Children's Health, Environmental Chemistry, biomarkers, developmental neurotoxicology, environmental hazard exposures, neurodevelopmental toxicity, methylmercury, developmental effects, neurotransmitters, assessment of exposure, childhood cancer, PCBs, toxics, sensitive populations, neurotoxic, biological markers, children, residential populations, exposure, PCB, children's vulnerablity, neurobehavioral effects, human exposure, Human Health Risk Assessment

Progress and Final Reports:
Original Abstract
2003 Progress Report
2004 Progress Report
2005 Progress Report


Main Center Abstract and Reports:
R829390    CECEHDPR - University of Illinois FRIENDS Children’s Environmental Health Center

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R829390C001 Neurobehavioral Effects of PCBs and Methylmercury in Rats
R829390C002 Perinatal PCB Exposure and Neuropsychological/Auditory Function
R829390C003 FRIENDS Analytical Toxicology Core Facility
R829390C004 Developmental Effects of PCBs and Methylmercury

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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