Polychlorinated biphenyls: correlation between in vivo and in vitro quantitative structure-activity relationships (QSARs)

Journal Article · Tue Jan 01 00:00:00 EST 1985 · J. Toxicol. Environ. Health; (United States)

DOI:https://doi.org/10.1080/15287398509530748· OSTI ID:5799827

Leece, B; Denomme, M A; Towner, R; Li, S M.A.; Safe, S

The in vivo quantitative structure-activity relationships (QSARs) for several polychlorinated biphenyls (PCBs) were determined in the immature male Wistar rat. The ED25 and ED50 values for hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction as well as for body weight loss and for thymic atrophy were determined for nine PCB congeners and 4'-bromo-2,3,4,5-tetrachlorobiphenyl. The most active compounds were the coplanar PCB congeners, 3,3',4,4',5-penta- and 3,3',4,4',5,5'-hexachlorobiphenyl; for example, their ED50 values for body weight loss were 3.25 and 15.1 ..mu..mol/kg, respectively. The in vivo toxicity of the coplanar PCB, 3,3',4,4'-tetrachlorobiphenyl, was significantly lower (ED50 for body weight loss = 730 ..mu..mol/kg) than the values observed for the more highly chlorinated homologs, and this was consistent with the more rapid metabolism of the lower chlorinated congener. The dose-response biologic and toxic effects of several mono-ortho-chloro-substituted analogs of the coplanar PCBs, including 2,3,4,4',5-, 2,3,3',4,4'-, 2',3,4,4',5- and 2,3',4,4',5-penta-, 2,3,3',4,4',5- and 2,3,3',4,4',5-hexachlorobiphenyl were also determined, and members of this group of compounds were all less toxic than 3,3',4,4',5-penta and 3,3',4,4',5,5'-hexachlorobiphenyl. There was a good rank order correlation between the in vivo QSAR data and the in vitro QSAR data and the in vitro QSARs for PCBs that were developed from their relative receptor binding affinities and potencies as inducers of AHH and EROD in rat hepatoma H-4-II E cells in culture.

• Research Organization: Univ. of Guelph, Ontario
• OSTI ID: 5799827
• Journal Information: J. Toxicol. Environ. Health; (United States), Vol. 16:3-4
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CHLORINATED AROMATIC HYDROCARBONS
STRUCTURE-ACTIVITY RELATIONSHIPS
TOXICITY
CORRELATIONS
HYDROXYLASES
IN VITRO
IN VIVO
LIVER CELLS
METABOLISM
OXIDOREDUCTASES
RATS
RECEPTORS
WEIGHT
ANIMAL CELLS
ANIMALS
AROMATICS
ENZYMES
HALOGENATED AROMATIC HYDROCARBONS
MAMMALS
MEMBRANE PROTEINS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
PROTEINS
RODENTS
SOMATIC CELLS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
560301 - Chemicals Metabolism & Toxicology- Cells- (-1987)