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Toxicology and Industrial Health
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Development and Validation of in Vitro Induction Assays for Toxic Halogenated Aromatic Mixtures: A Review

Stephen Safe

Department of Veterinary Physiology and Pharmacology College of Veterinary Medicine Texas A&M University College Station, Texas

Grant Mason

Department of Veterinary Physiology and Pharmacology College of Veterinary Medicine Texas A&M University College Station, Texas

Thomas Sawyer

Department of Veterinary Physiology and Pharmacology College of Veterinary Medicine Texas A&M University College Station, Texas

Tim Zacharewski

Department of Veterinary Physiology and Pharmacology College of Veterinary Medicine Texas A&M University College Station, Texas

Mark Harris

Department of Veterinary Physiology and Pharmacology College of Veterinary Medicine Texas A&M University College Station, Texas

C. Yao

Department of Veterinary Physiology and Pharmacology College of Veterinary Medicine Texas A&M University College Station, Texas

Barbara Keys

Department of Veterinary Physiology and Pharmacology College of Veterinary Medicine Texas A&M University College Station, Texas

Kathy Farrell

Department of Veterinary Physiology and Pharmacology College of Veterinary Medicine Texas A&M University College Station, Texas

Michael Holcomb

Department of Veterinary Physiology and Pharmacology College of Veterinary Medicine Texas A&M University College Station, Texas

Deanne Davis

Department of Veterinary Physiology and Pharmacology College of Veterinary Medicine Texas A&M University College Station, Texas

Lorna Safe

Department of Veterinary Physiology and Pharmacology College of Veterinary Medicine Texas A&M University College Station, Texas

Jagoda Piskorska-Pliszczynska

Department of Veterinary Physiology and Pharmacology College of Veterinary Medicine Texas A&M University College Station, Texas

Brian Leece

Department of Chemistry and Biochemistry University of Guelph Guelph, Ontario, Canada

Mary Anne Denomme

Department of Chemistry and Biochemistry University of Guelph Guelph, Ontario, Canada

Otto Hutzinger

Chair of Ecological Chemistry and Geochemistry University of Bayreuth Bayreuth, Federal Republic of Germany

Heinz Thoma

Chair of Ecological Chemistry and Geochemistry University of Bayreuth Bayreuth, Federal Republic of Germany

Brock Chittim

Wellington Environmental Consultants Guelph, Ontario, Canada

Jocelyn Madge

Wellington Environmental Consultants Guelph, Ontario, Canada

Halogenated aromatic industrial compounds, typified by the polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) have been identified as residues in almost every component of the global ecosystem. Risk assessment of the complex mixtures of halogenated aromatics found in envi ronmental samples is complicated by analytical problems and the lack of toxicological information on individual compounds and mixtures. Research in our laboratory has focused on the develop ment and vadidation of the in vitro aryl hydrocarbon hydroxylase (AHH) induction assay in rat hepatoma H-4-II E cells in culture for quantitating individual toxic halogenated aryl hydrocarbons and their mixtures. For several PCB, PCDD, PCDF congeners, their mixed bromo/chloro analogs and reconstituted mixtures there was an excellent linear correlation between their -log ED50 values for AHH induction in rat hepatoma cells and their -log ED50 values for in vivo hepatic microsomal AHH induction, inhibi tion of body weight gain and thymic atrophy in the rat. It has also been shown for selected compounds that there was a good correla tion between their in vitro AHH induction potencies and their effects in guinea pigs (AHH induction, inhibition of body weight gain) and mice (immunotoxicity). This assay system has been uti lized to quantitate the "2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents "present in extracts from diverse sources including fly ash from a municipal incinerator and pyrolyzed brom inated flame retardants which contain a complex mixture of halo genated dibenzo-p-dioxins and dibenzofurans.

Key Words: 2. Key words: bioassays • halogenated aromatics • toxic equivalents.

Toxicology and Industrial Health, Vol. 5, No. 5, 757-775 (1989)
DOI: 10.1177/074823378900500513
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