Immunotoxicity of Both Nondegraded and Biodegraded Polychlorinated Biphenyls (PCBs)EPA Grant Number: R826687
Title: Immunotoxicity of Both Nondegraded and Biodegraded Polychlorinated Biphenyls (PCBs)
Investigators: London, Lucille
Current Investigators: London, Lucille , Morris, Pamela , Quensen, John , Smithwick, Laura Ashley
Institution: Medical University of South Carolina
EPA Project Officer: Hahn, Intaek
Project Period: September 15, 1998 through September 14, 2001
Project Amount: $379,176
RFA: Exploratory Research - Human Health (1998) RFA Text | Recipients Lists
Research Category: Health Effects , Human Health , Health
The long term goal of our laboratory is to understand the biological process by which complex mixtures of contaminants can be degraded in the environment and to apply that knowledge to better understand potential human health effects associated with exposure. We will focus on the biodegradation of complex mixtures of polychlorinated biphenyls (PCBs) and their subsequent immunotoxicological effects on parameters of immune lymphocyte function. The potential for existing and newly emerging bioremediation technologies to treat complex waste sites is based upon their ability to remove these chemicals from contaminated environments. However, there has been little attempt to correlate disappearance of contaminated material with a discernible decrease in the health hazards associated with biotreated materials.
PCBs are wide spread environmental contaminants and available evidence suggests that the immune system is a target for PCBs toxicity (1-5). Thus, the persistence of PCBs in the environment and their bioaccumulation in living organisms raises concerns regarding their immunotoxic potential and subsequent effects on health. In preliminary studies, we have shown that complex mixtures of PCBs (Aroclors) which have been used industrially and are known environmental contaminants have immunotoxic effects on lymphocytes in an in vitro assay system. We hypothesize that the immunotoxicity of biodegraded PCBs will be lower than the immunotoxicity of the commercial mixtures since the biodegradation process results in the dechlorination of the PCB mixture and an association of increased immunotoxicity in vivo and in our in vitro proliferation assay correlates with more heavily chlorinated PCB aroclors.
In this proposal, we will examine the immunotoxicity of PCBs and their biodegraded products using two well defined immunologic parameters as indicators of immunotoxicity. First, we will assess both non-degraded and biodegraded PCBs on their ability to modulate the murine B cell proliferative response to the mitogen, lipopolysaccaride (LPS). Second, we will investigate the ability of these same chemical mixtures to modulate in vivo the generation of an anti-sheep red blood cell (sRBC) response in mice. We have chosen several mixtures of PCBs based on their prevalence in the environment and concerns over their general toxicological impact. Further, these mixtures are targets of novel bioremediation technologies that are currently being implemented in situ. We have chosen to examine the aerobic degradation of two commercial PCB mixtures, Aroclor 1242 and 1254 by two microorganisms, Pseudomonas sp. LB400 and Alcaligenes eutrophus H850. In addition, we will couple the anaerobic reductive dechlorination of Aroclor 1260, a heavily halogenated PCB mixture, with subsequent aerobic degradation of this mixture.
Three potential outcomes are possible from these studies: (i) the biodegraded product is less toxic than the parent compound; (ii) the biodegraded compound is more toxic than the parent compound; or (iii) the biodegraded compound is as toxic as the parent compound. The data sets will consist of dose-response curves for non-degraded Aroclor mixtures and biodegraded Aroclor mixtures. The trends associated with each non-degraded PCB Aroclor mixture and biodegraded PCB aroclor mixture will be compared and evaluated for three potential outcomes as listed above. For each data set, a gas chromatographic profile of the classes of compounds present in the biodegraded and nondegraded samples will be generated. If the biodegradation process results in the dechlorination of the PCB aroclor mixture, we predict a decrease of immunotoxicty since an association of increased immunotoxicity in vivo and in our in vitro proliferation assay correlates with more heavily chlorinated PCB aroclors. In this case, it would be predicted that cells exposed to these samples might exhibit normal growth rates and proliferative potential . In these cases the loss of chlorination will be analyzed in the biodegraded samples by chromatography. Second, a trend of increased or similar immunotoxicity as compared to the parent Aroclor following biodegradation may occur. The biodegradation of the Aroclor may produce co-metabolitic intermediates of PCB degradation, including chlorinated benzoates, which are more toxic than the parent compound. If this is the case, these compounds can be separated from the declorinated PCB sample and both fractions can be analyzed individually for immunotoxicity. In either case, the contribution to immunotoxicity of the dechlorination of PCB aroclors as well as the production of co-metabolites will be evaluated in this manner.
We predict that the results obtained in vivo will parallel the results ob