Mckinney, JD; Singh, P; Levy, LA; Walker, MP
Structural requirements important to the toxicity of halogenated aromatic hydrocarbons were analyzed. Toxicity was differentiated by the molar median lethal dose (LD50) response in guinea-pigs. The compounds studied were 2,3,7,8-tetrachlorodibenzo-p-dioxin (1746016) (2,3,7,8-TCDD), 2,3,7-trichlorodibenzo-p-dioxin (33857282), 2,3,7,8-tetrachlorofluorenone (TCF), 2,3,7,8-tetrachlorodibenzofuran (51207319), 3,3',4,4',5,5'-hexachlorobiphenyl (32774166), 3,3',4,4'-tetrachlorobiphenyl (32598133), 2,3,6,7-tetrachloronaphthalene (34588404), and 2,3,6,7-tetrabromonaphthalene (69881921). All compounds except TCF were characterized and identified on the basis of their spectral properties and method of synthesis. Common structural features of the compounds were the possession of at least four halogens in the most lateral positions with no adjacent carbon. They were planar or assumed a coplanar relationship of aromatic rings, and they had at least one similar molecular distance between lateral halogens. The most toxic of the compounds was 2,3,7,8-TCDD with a single LD50 of about 2 micrograms per kilogram. A factor in the symmetry requirement for these compounds was high net polarizability. Molecular thickness was also a possible factor in determining activity in these compounds. Biological effects were alterations in certain enzymes and in macromolecular biosynthetic templates. Many of these compounds acted on functional macro structures that underlie cellular processes. These were manifested as cocarcinogenic, teratogenic, or immunosuppressive properties. The authors conclude that the common toxicopathology of the compound suggests a commonality for its molecular basis that may involve a specific biologic receptor. The symmetry and positions of halogens may impart a unique binding affinity to such a receptor.
