title: Potency of a complex mixture of polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners compared to 2,3,7,8-tetrachlorodibenzo-p-dioxin in causing fish early life stage mortality.
abstract: Use of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity equivalents concentration (TEC) assumes that polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) act additively and via a common mechanism to cause toxicity. To test these assumptions, 11 TCDD-like congeners and three non-TCDD-like congeners were combined at ratios typically found in Lake Michigan lake trout. The potency of the mixture, expressed as TEC based on fish-specific toxic equivalency factors, was compared to TCDD for producing lake trout and rainbow trout early life stage mortality. Signs of toxicity following exposure of newly fertilized eggs to the mixture or to TCDD were indistinguishable; sac fry mortality associated with blue-sac disease, and slopes of the dose-response curves for percentage sac fry mortality versus egg TEC or versus egg TCDD were parallel. However, the mixture dose-response curves were significantly shifted to the right of the TCDD dose-response curves by 1.3- and 1.8-fold as illustrated by LD50 values. Following exposure to the mixture or TCDD, LD50S for lake trout early life stage mortality were 97 (89-110) pg TE/g egg and 74 (70-80) pg TCDD/g (LD50, 95% fiducial limits) and for rainbow trout were 362 (312-406) pg TE/g egg and 200 (148-237) pg TCDD/g egg. These data suggest that TCDD-like congeners act via a common mechanism to cause toxicity during trout early development, but may not act strictly additively when combined in a mixture of TCDD- and non-TCDD-like congeners at ratios found in Great Lakes fish. The deviation from additivity, however, is less than current safety factors of 10-fold commonly applied in ecological risk assessments, providing support for the continued use of a TE additivity model for assessing risk posed by complex mixtures of PCDDs, PCDFs, and PCBs to fish.
authors.affiliation: School of Pharmacy, University of Wisconsin, Madison 53706, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Walker
authors.forename: P M
authors.initials: PM
authors.lastname: Cook
authors.forename: B C
authors.initials: BC
authors.lastname: Butterworth
authors.forename: E W
authors.initials: EW
authors.lastname: Zabel
authors.forename: R E
authors.initials: RE
authors.lastname: Peterson
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D007928:Lethal Dose 50; D017686:Oncorhynchus mykiss; D010063:Ovum / Q000187:drug effects* / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000633:toxicity*; D013329:Structure-Activity Relationship; D014337:Trout; D014873:Water Pollutants / Q000633:toxicity*
chemical_list: D001572:Benzofurans; D004338:Drug Combinations; D000072317:Polychlorinated Dibenzodioxins; D014873:Water Pollutants; C023614:dibenzofuran; D011078:Polychlorinated Biphenyls