Project Summary:
History has shown repeatedly that man underestimates the effects of the chemicals that he produces. Now we hear about frogs with gross deformities in Minnesota, fish with cancers and sores in the Atlantic ocean, alligators with small penises in contaminated Florida lakes, and a decline in sperm counts in human males. And gradually we are becoming aware that new compounds, produced to replace the old troubling ones, are showing up in the environment. One group, the polyhalogenated diphenyl ethers (PBDEs and PCDEs), is found nearly everywhere and their concentrations in animal and human tissues are rapidly increasing. Structurally the polyhalogenated diphenyl ethers resemble the halogenated biphenyls, PCBs and PBBs. The few studies with PBDEs/PCDEs indicate that they may share many of the toxic mechanisms with PCBs. Since PBBs are more toxic than PCBs, PBDEs, the major contaminant in this group, may pose an even greater risk than the PCBs. An analysis of these compounds for toxicity is desperately needed for risk assessment and future regulation/legislation!
We propose to chemically synthesize selected congeners of PBDEs and, for SAR analysis, a few PCDEs. These congeners alone, in combination and one commercially available mixture (DE-71, Great Lake Chemicals), will be tested in three species of vertebrates: rats, fathead minnows (fish) and Xenopus laevis (frogs). The parameters that will be analyzed in rats are general effects on organs like liver, thymus, and blood cells. Biochemical parameters like activating (CYPs) and antioxidant (GSH-Px, catalase) enzymes, selenium, vitamin A and E levels, T4 and uterine weights will be determined as indicators of oxidative stress and/or endocrine and developmental change. Fish will be used as a very sensitive indicator of estrogenicity of these compounds, and the frog FETAX assay will be used to identify embryo toxic and teratogenic potential of the PBDEs/PCDEs. We fully expect that these compounds will give positive results in several, if not all, of these assays and that an SAR can be deduced. Together these assays should give a good impression about their toxicity, their potential as a future risk for the environment, and about chemical structural characteristics that are indicative for danger for animal and human health.
Supplementary Keywords: exposure, ecological effects, metabolism, vulnerability, sensitive populations, dose-response, carcinogen, public policy, decision making, biology, ecology, pathology, modeling, monitoring.