2004 Progress Report: Neurobehavioral Effects of PCBs and Methylmercury in RatsEPA 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.
Institution: University of Illinois at Urbana
EPA Project Officer: Hahn, Intaek
Project Period: October 17, 2001 through October 16, 2002
Project Period Covered by this Report: October 17, 2003 through October 16, 2004
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2001) RFA Text | Recipients Lists
Research Category: Children's Health , Health Effects , Health
The objectives of this research project are to: (1) characterize the cognitive, motor, and sensory effects of perinatal exposure to polychlorinated biphenyls (PCBs) alone, methylmercury (MeHg) alone, or PCBs and MeHg in combination in the laboratory rat; (2) investigate the role of changes in specific neurotransmitter systems in mediating specific behavioral effects; (3) investigate the role of altered thyroid hormones in mediating specific behavioral effects; and (4) 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.
The data from initial behavioral studies assessing the combined effects of commercial polychlorinated biphenyls (PCBs) (i.e., Aroclor 1254 [A1254]) and methylmercury (MeHg) on cognitive and motor function were statistically analyzed and manuscripts were submitted for publication. Both PCBs and MeHg produced deficits in spatial learning and memory, but combined exposure to the two chemicals did not exacerbate the deficit seen with either chemical alone (Widholm, et al., 2004). The pattern of the deficit suggested impaired attentional or associational processes rather than impaired memory function. Therefore, we developed and pilot tested an attentional task that will help us to define further the nature of this cognitive deficit. The first PCB-exposed animals will be tested on this attentional task in summer of 2004. In contrast to the cognitive results, combined exposure to PCBs and MeHg did appear to have an additive effect on motor function. Neither chemical alone produced a significant deficit in motor function, but animals exposed to both PCBs and MeHg showed a clear deficit in balance and coordination as measured by their ability to cross a rotating rod (Roegge, et al., 2004). This research and our Center were highlighted in the National Institute of Environmental Health Sciences News section of the June 2004 issue of Environmental Health Perspectives.
Studies of auditory function in A1254- and MeHg- exposed rats were completed during the current grant year. Measurements of distortion product otoacoustic emissions (DPOAEs), which provide a direct measure of cochlear function, showed that PCB-related hearing deficits are present across a broader range of frequencies than indicated by previous studies using less sensitive assessment techniques. MeHg does not appear to affect cochlear function. Statistical analysis of the DPOAE results revealed significant effects of exposure for both DPOAE amplitude and threshold. Comparisons of the exposed groups to the control group indicated that exposure to PCBs alone or PCBs and MeHg reduced the signal-to-noise ratio across all frequencies tested, with significant reductions at 2, 3, 4, and 6 kHz. DPOAE thresholds were increased across all frequencies, with significant differences at 3, 4, 6, and 12 kHz. MeHg alone did not alter DPOAE amplitudes or thresholds, and exposure to MeHg did not exacerbate the effects of PCBs. These results confirm earlier reports of PCB-related hearing loss and implicate the cochlea as a primary site of damage.
Studies of auditory brainstem-evoked responses and behavioral measurements of auditory thresholds were completed recently, and the data are under analysis. Preliminary analyses indicate that peak latencies are not altered by PCB or MeHg exposure, but the amplitudes of both peak one and peak two are decreased in PCB-exposed rats (Figure 1). The clearest reductions were noted for peak one (lower graph on panel B), with significant reductions observed at 3, 6, and 12 kHz. The results of the auditory assessments were presented at two international conferences: Dioxin 2003, held in Boston, in August 2003, and the Third International PCB Workshop held in Champaign, Illinois, in June 2004. The results will be submitted for publication in the upcoming grant year.
Figure 1. (A) Peak Latency and (B) Peak Amplitude Following PCB or MeHg Exposure
Initial behavioral studies using the newly formulated Fox River PCB mix, which closely models the PCB exposure profile in our human cohort, began during the summer of 2003. Cognitive, motor and auditory assessments of these animals currently are underway and will be completed during the coming grant year. The initial findings will be presented at scientific conferences and manuscripts will be prepared for publication. Studies evaluating combined exposure to MeHg and the Fox River PCB mix will be initiated during the coming grant year. These data will be used to identify appropriate tests that should be included in the neurobehavioral assessment battery that will be used to test infants in the Hmong and Laotian birth cohort. A key finding is that PCB-related hearing loss appears to be present across a wider range of frequencies than previous studies using less sensitive techniques had suggested. Thus, it will be important to evaluate newborn auditory function across a range of frequencies. The first births are expected during the coming grant year.
Cognitive, motor and auditory assessments of animals will be completed during Year 4 of the project. We also will evaluate newborn auditory function across a range of frequencies.
Journal Articles on this Report : 2 Displayed | Download in RIS Format
|Other subproject views:||All 15 publications||5 publications in selected types||All 5 journal articles|
|Other center views:||All 38 publications||22 publications in selected types||All 21 journal articles|
||Roegge CS, Wang VC, Powers BE, Klintsova AY, Villareal S, Greenough WT, Schantz SL. Motor impairment in rats exposed to PCBs and methylmercury during early development. Toxicological Sciences 2004;77(2):315-324.||
||Widholm JJ, Villareal S, Seegal RF, Schantz SL. Spatial alternation deficits following developmental exposure to Aroclor 1254 and/or methylmercury in rats. Toxicological Sciences 2004;82(2):577-589.||
Supplemental Keywords:children’s health, disease and cumulative effects, ecological risk assessment, susceptibility, sensitive population, toxicology, Fox River, PCBs, exposure assessment, heavy metals, methylmercury, neurotoxicity, pesticides, fish consumption.,, RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, ENVIRONMENTAL MANAGEMENT, Environmental Chemistry, Health Risk Assessment, Epidemiology, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Physical Processes, Children's Health, genetic susceptability, Molecular Biology/Genetics, Risk Assessment, developmental neurotoxicology, neurotoxic, sensitive populations, childhood cancer, biomarkers, animal model, developmental effects, exposure, PCBs, Human Health Risk Assessment, children, assessment of exposure, children's vulnerablity, residential populations, methylmercury, PCB, neurodevelopmental toxicity, human exposure, neurobehavioral effects, biological markers, neurotransmitters, toxics
Progress and Final Reports:Original Abstract
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