Workshop on Perinatal Exposure to Dioxin-Like Compounds. VI. Role of Biomarkers

Abstract

Studies of perinatal exposures to dioxin-like compounds (DLCs), coplanar polycyclic halogenated aromatics whose prototype is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), have employed a variety of outcome measures to investigate effects on the reproductive/developmental, endocrine, immune, and neurobehavioral systems. The effects include infertility, growth retardation, fetal loss, changed sexual differentiation, reduced cognitive/motor function, dermatologic and other ectodermal effects, and decreased immune response. Significant biomarkers have included sperm count; CD4/CD8 ratio; and levels of testosterone, T4, and dopamine. Using specific dioxin or PCB congeners, these and other markers were used to investigate the mechanisms of the observed effects. The DLCs, which include some PCB congeners, are characterized by high-affinity binding to the Ah receptor; most biological effects are thought to be mediated by the ligand-Ah receptor complex. Other PCB congeners have low affinity for the Ah receptor, and operate by non-Ah receptor mechanisms. The biologic activity of a PCB mixture is the sum of the agonist and antagonist activities of the different constituents in the mixture. Animal studies with specific PCB congeners can help to clarify these activities. With similar approaches, biologic markers of effect can be developed and applied in epidemiologic studies to monitor for, and predict, adverse effects in humans. -Environ Health Perspect 103(Suppl 2): 161-167 (1995)

Learning behavior in rat offspring after in utero and lactational exposure to either TCDD or PCB126

“…This TEF scheme was developed on the basis of the following four basic criteria. The compound must (1) show a structural relationship to the PCDDs and PCDFs, (2) bind to the aryl hydrocarbon receptor (AhR) receptor, (3) elicit AhR-receptor-mediated biochemical and toxic responses and (4) be persistent and accumulate in the food chain. The TEF scheme is a pragmatic concept and has been utilized for risk assessment and management purposes, but the REP dataset used to derive the TEF values has some innate limitations.…”

“…Among the more than 400 congeners belonging to this group, 29 are classified as dioxins and related compounds because they have been shown to exert several toxic responses similar to those of 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD), the prototype of these compounds [1]. Among the PCB congeners, both non-and mono-ortho PCB congeners have toxicological characteristics similar to those of TCDD via the aryl hydrocarbon receptor-mediated mechanism; these are often called dioxin-like PCBs [2]. For practical risk assessment purposes, the toxic equivalents (TEQ) is used to evaluate the total dioxin toxicity of various congeners to which humans are exposed through food and environmental media.…”