There is increasing need to understand the toxicity of complex environmental mixtures. The organic phase of a leachate (OPL) from the Love Canal chemical dump site is a
complex mixture that contains over 100 organic compounds, including 0.74 ppm
2,3,7,8-tetrachlorodibenzo-p-dioxin (
TCDD). Mice congenic at the Ah locus were used to evaluate several toxic effects of the OPL, including immune function and hepatic enzyme induction. OPL toxicity was compared with that of pure
TCDD in both C57BL/6J Ahb/b and congenic C57BL/6 Ahd/d (B6.D2) mice. Mice were given single oral doses of up to 2 g OPL/kg or 100 micrograms
TCDD/kg, immunized, and evaluated after 7 days. The
TCDD equivalent of the OPL was determined to be 3.9 and 5.0 ppm in C57BL/6J and B6.D2 mice, respectively. This is six times the
TCDD content. The Ah phenotype-dependent response ratio was calculated by dividing the dose required to cause an effect in the B6.D2 strain by the dose causing the same effect in the C57BL/6J strain. Ratios based on both ED50s and the lowest observed adverse effect levels were used to determine whether each adverse effect was Ah phenotype-dependent, the extent to which
TCDD contributed to the effect, whether there were interactive effects between the AhR
ligands and nonligands and if they were additive, antagonistic, or synergistic, and whether the response was predictable based on the known chemical composition of the mixture. It was concluded that the non-
TCDD component potentiated
TCDD immune suppression, and possibly thymic
atrophy, through AhR mechanisms. In contrast, this analysis indicated that the non-
TCDD component of the OPL antagonized the ability of the
TCDD component to induce hepatic AHH activity whereas OPL
hepatomegaly was caused primarily by the non-
TCDD component of the OPL. This study demonstrates that the toxicity of mixtures containing
TCDD may not be accurately predicted based on the
TCDD content alone and that this approach could be useful in the toxicologic assessment and management of environmental contamination.