The use of biomarkers to measure the interactive effects of chemicals.

Biomarker assays that provide measures of the toxic effects of chemicals on key organisms are of particular interest in ecotoxicology and environmental risk assessment. Typically, such assays provide measures of the molecular mechanisms that underlie toxicity (e.g., inhibition of brain acetylcholinesterase activity by organophosphorus insecticides and retardation of the vitamin K cycle by anticoagulant rodenticides). They are particularly valuable for detecting and quantifying toxicity where organisms are exposed to mixtures of compounds and for identifying cases of potentiation. In birds, inhibition of brain acetylcholinesterase activity can provide an index of potentiation of organophosphorus and carbamate insecticides by other pesticides. Inhibition of serum butyrylcholinesterase also is very useful as a nondestructive assay but is not simply related to inhibition of brain acetylcholinesterase. Assays for DNA damage can indicate where there is an increase in the rate of activation of carcinogens and mutagens due to induction of the cytochrome P450 system. Assays for blood levels of retinol (vitamin A) and thyroxine can establish thyroxine antagonism by metabolites of 3,3,4,4-tetrachlorobiphenyl. Assays for changes in levels of clotting protein in serum can give an indication of the effect of mixtures of anticoagulant rodenticides on the vitamin K cycle. The interactive effects of mixtures of pesticides in the field are starting to be investigated by this approach (e.g., a recent study of the combined action of malathion and prochloraz in the red-legged partridge).