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
Mk. Walker et al., 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, Fundamental and applied toxicology, 30(2), 1996, pp. 178-186
Use of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity equivalents
concentration (TEC) assumes that polychlorinated dibenzo-p-dioxins (P
CDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) act additively and
via a common mechanism to cause toxicity. To test these assumptions, 1
1 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 tr
out early life stage mortality. Signs of toxicity following exposure o
f newly fertilized eggs to the mixture or to TCDD were indistinguishab
le; sac fry mortality associated with blue-sac disease, and slopes of
the dose-response curves for percentage sac fry mortality versus egg T
EC or versus egg TCDD were parallel. However, the mixture dose-respons
e curves were significantly shifted to the right of the TCDD dose-resp
onse curves by 1.3- to 1.8-fold as illustrated by LD(50) values. Follo
wing exposure to the mixture or TCDD, LD(50) for lake trout early life
stage mortality were 97 (89-110) pg TE/g egg and 74 (70-80) pg TCDD/g
(LD(50), 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 duri
ng trout early development, but may not act strictly additively when c
ombined in a mixture of TCDD- and non-TCDD-like congeners at ratios fo
und in Great Lakes fish. The deviation from additivity, however, is le
ss than current safety factors of 10-fold commonly applied in ecologic
al risk assessments, providing support for the continued use of a TE a
dditivity model for assessing risk posed by complex mixtures of PCDDs,
PCDFs, and PCBs to fish. (C) 1996 society of Toxicology