Combined Actions and Interactions of Chemicals in Mixtures

once more exposed and the kinetics of the compounds followed in blood. There
seemed to be a systematic decrease (although not statistically significant) in blood
concentrations indicative of greater metabolism due to enzyme induction.
Chaturvedi et al. (1991) studied the effects of mixtures of parathion, toxaphene
and/or 2,4-D on the hepatic mixed-function oxygenase in ICR male mice. They
found that a seven days toxaphene pre-treatment enhanced the hepatic
biotransformation of parathion and paraoxon both in the presence and in absence of
NADP. However, in the absence of NADP the enhancement was minor. The
authors suggest that toxaphene induced the metabolic pathways of parathion and
paraoxon involving the mixed-function oxygenase and that paraoxonase is not
involved in the toxaphene-induced decreases of the two compounds. Toxaphene is
enhancing the NADP-dependent metabolism of parathion and paraoxon and
thereby decreasing their toxicity. Carboxyl esterase is involved in decreasing the
toxicity of parathion and paraoxon by acting as a pool of non-critical enzymes,
which compete for the binding of paraoxon thereby preventing an inhibition of
cholinesterase. The increase in the level of Carboxyl esterase and cholinesterase
has the potential to enhance further the ability of toxaphene to limit the toxicity of
parathion. The authors therefore anticipated the toxicity of a mixture of parathion
and toxaphene to be lower than that of parathion. Thus the results of the study
could indicate an antagonistic effect of toxaphene on parathion and on paraoxon.
Chaturvedi (1993) also examined the effect of mixtures of ten pesticides (alachlor,
aldrin, atrazine, 2,4-D, DDT, dieldrin, endosulfan, lindane, parathion and
toxaphene) administered by oral intubations or by drinking water on the
xenobiotic-metabolising enzymes in male mice. He concluded, ”The pesticide
mixtures have the capability to induce the xenobiotic-metabolizing enzymes which
possibly would not have been observed with individual pesticides at the doses and
experimental conditions used in the study.” However, it is not possible to
categorise the type of combined action because Chaturvedi (1993) only examined
the combined effects of the ten compounds in the mixture and did not consider the
effect of the individual pesticides.
6.1.4 Interference with excretion
For excretion processes the same reasoning may be used as for absorption. Cases of
interaction are only to be expected when active processes are involved. Increased
excretion of a chemical following administration of an osmotic diuretic or
alteration of the pH of the urine is well known examples of dispositional
interaction.
72