Grantee Research Project Results
1998 Progress Report: Developmental Effects of Fish-Borne Toxicants in the Rat
EPA Grant Number: R825812Title: Developmental Effects of Fish-Borne Toxicants in the Rat
Investigators: Seegal, Richard F. , Schantz, Susan L.
Institution: The State University of New York , University of Illinois Urbana-Champaign
EPA Project Officer: Aja, Hayley
Project Period: December 15, 1997 through December 15, 2000
Project Period Covered by this Report: December 15, 1997 through December 15, 1998
Project Amount: $470,560
RFA: Issues in Human Health Risk Assessment (1997) RFA Text | Recipients Lists
Research Category: Human Health
Objective:
Epidemiological studies suggest an association between consumption of contaminated Great Lakes fish by pregnant women and behavioral deficits in their children. Polychlorinated biphenyls (PCBs) are correlated with these dysfunctions suggesting that PCBs may either be the relevant toxicant or serve as a marker for the relevant toxicant(s). The objectives of this project are to determine if the neurobehavioral effects attributed to PCBs are due either to other neuroactive contaminants or to additive or synergistic interactions between PCBs and other contaminants. The project will determine the class(es) of contaminants in Lake Ontario (LO) salmon which induce neurobehavioral and neurochemical alterations in rats following perinatal exposure to lyophilized LO salmon and solvent-extracted contaminants from LO salmon. The contaminant concentrations of these diets, as well as the resulting brain levels of the contaminants, will be characterized. Experiments will include three dose levels at all exposure conditions, providing data useful in the design of new risk assessment methods. These data will provide more accurate information concerning the risk due to fish consumption and the importance of incorporating data on the identity and levels of the contaminants and their possible interactive effects on neurological endpoints.Progress Summary:
Procurement and Preparation of Fish for Exposure Studies. We have obtained sufficient quantities of fish for all of the proposed studies. We purchased 100 kg of control salmon (Pacific Ocean, PO) and obtained 300 kg of contaminated salmon (Lake Ontario, LO) from the Salmon River Hatchery (NYS ENCON). The fillets were skinned, ground, mixed and frozen at -80oC for subsequent experiments.Sufficient fish for the four cohorts of the first experiment has been lyophilized (30 kg PO and 60 kg LO). Half of each type of lyophilized salmon was soxhlet-extracted in 75 g aliquots in 1000-ml extractors for 16 h using residue-analysis grade methylene chloride. These extractions resulted in the generation of 1,409 g of PO oil and 562 g of LO oil. The balance of each type of lyophilized salmon will be used for directly exposing the dams to lyophilized fish diets.
In order to separate the contaminants from the oil we will use semi-permeable membrane dialysis because this technique minimizes the destruction of contaminants that might otherwise occur if we had used sulfuric acid to destroy the lipids.
Preliminary contaminant characterization of the PO and LO salmon has been completed and includes PCBs, pesticides, dioxins, dibenzofurans, inorganic metals, and methylmercury. We are now confirming contaminant concentrations in the nine exposure groups (diets) prepared for the first experiment (control chow; 20% lyophilized PO salmon; extracted PO oil equivalent to 20% lyophilized salmon; 7, 14 and 20% lyophilized LO salmon; and extracted LO oil equivalent to 7, 14 and 20% lyophilized salmon). In addition, brain tissue collected at 21 days of age from exposed animals will be analyzed for contaminant residues and changes in neurotransmitter function.
Developmental Exposure Experiment 1. Exposure of the first cohort of 27 litters has been completed. Dams were exposed from gestational day six through weaning (21 days of age) to one of the above nine diets. Litter characteristics were recorded on day 2 (culling). Date of eye opening, vaginal opening (in females) and preputial separation (in males) were recorded as developmental landmarks. One male and one female pup from each litter has been shipped to Dr. Schantz at the University of Illinois at Urbana/Champaign for behavioral testing.
Behavioral Test Procedures at the University of Illinois. A postdoctoral research associate with a Ph.D. in Psychology and extensive experience in operant behavior and computer programming was hired (John Widholm). An automated operant behavior testing lab was set up with new equipment purchased from Med Associates, Inc. including 12 operant testing chambers, a computer interface and two Gateway 233 Pentium PCs. Five behavioral tests, including three learning tests (spatial and visual discrimination-reversal learning and delayed spatial alternation) and two operant schedules (fixed interval (FI) and differential reinforcement of high rates (DRH)), were programmed using the Med Sked programming language. As detailed in the original proposal, these tests were selected to assess behavioral functions that appear to be compromised in children exposed to contaminants from Great Lakes fish. The programming was carried out by the post doc in close consultation with the Dr. Schantz and the two consultants (Drs. Barbara Strupp and Chris Newland). The test battery was debugged and has been piloted on a set of animals exposed during gestation and lactation to either PCBs or TCDD, providing important background data. Testing of animals from the first cohort of exposure experiment 1 will begin when they are approximately 75 days of age and will continue until they are approximately 220 days of age.
Future Activities:
Completion of the first exposure experiment (4 cohorts) will take approximately one and one-half years. Upon completion we will have (i) characterized the behavioral effects of the complex mixture of chemicals found in GL fish and (ii) determined whether methylmercury, which is present in the lyophilized fish but absent from the extracted fish oil, is important in mediating the behavioral effects of the complex mixture of contaminants found in the fish.Journal Articles on this Report : 1 Displayed | Download in RIS Format
| Other project views: | All 8 publications | 5 publications in selected types | All 5 journal articles |
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Seegal RF, Pappas BA, Park GAS. Neurochemical effects of consumption of Great Lakes salmon by rats. Regulatory Toxicology and Pharmacology 1998;27(1):S68-S75. |
R825812 (1998) R825812 (1999) |
Exit Exit |
Supplemental Keywords:
Complex mixtures, contaminated Great Lakes fish, solvent extraction and fractionation, polychlorinated biphenyls, pesticides, heavy metals, human cognitive dysfunctions, neurobehavioral and neurochemical alterations, mechanisms of toxicity., RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Toxics, Geographic Area, Waste, Toxicology, Ecology, Environmental Chemistry, Chemistry, pesticides, Risk Assessments, chemical mixtures, Susceptibility/Sensitive Population/Genetic Susceptibility, Physical Processes, Children's Health, genetic susceptability, Biology, Great Lakes, pesticide exposure, fish borne toxicant, health effects, dioxin, sensitive populations, adolescents, mothers, Great Lakes salmon consumption, health risks, prenatal exposure, developmental toxicity, lead, polychlorinated biphenyl, animal model, developmental effects, perinatal exposure, exposure, Human Health Risk Assessment, children, environmental mutagens, polychlorinated dibenzofuran, neuropsychological, human exposure, behavioral deficits, furans, growth and development, environmental toxicant, perinatanl exposure, pregnant women, biological markers, arsenic exposure, pregnancy, dietary exposure, developmental disorders, arsenic, dioxin exposure, fish-borne toxicants, biomarker, Lake Ontario, heavy metals, synergistic interactionsProgress and Final Reports:
Original AbstractThe 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.