ASSESSMENT OF METABOLIC ACTIVATION IN TROUT

Abstract

' Considerable progress has been made in recent years in assessing the risk of individual chemicals, as well as mixtures of chemicals, to aquatic organisms. Numerous chemicals have been studied for their toxicity to fish and invertebrates. One database that has'been widely used to assess individual chemicals for their acute toxicity toward aquatic life was developed jointly between the Environmental Research Laboratory-Duluth and· the University of Wisconsin Superior (University of Wisconsin-Superior, 984, 1985, 1986, 1988, 1990). This database has been used to develop quantitative structure-activity relationship (QSAR) models·for the prediction of acute toxicity of untested chemicals to the fathead minnow (Pimephales promelas) based upon chemical structure and toxic mode

ofaction.. -

Toxicity prediction models that have been developed from this database are for chemicals with the following modes of action: baseline narcosis or narcosis I (Veith et al., 1983a,b), polar narcosis or narcosis II (Veith et al., 1984-85; Veith and Broderius, 1987); and uncoupling of oxidative phosphorylation (Call et al., 1989). These models have been based upon chemical hydrophobicity, either exclusively or to a high degree. Recently, prediction models that incorporate a stereoelectronic parameter, in addition to a measure of hydrophobicity, have been developed for certain chemicals, such as unsaturated acetylenic and allelic alcohols that can be metabolically activated via alcohol dehydrogenase (Mekenyan et al, 1993), and for chemicals which act as soft electrophiles, such as substituted benzenes, phenols and anilines (Mekenyan and Veith, 1993a,b; Veith and Mekenyan, 1993). Additional models for other toxic modes of action may be forthcoming. Other known modes of action, based upon fish toxicity syndromes, include respiratory membrane irritation, acetylcholinestuase inhibition, and modes exhibiting syndromes typical of poisoning by cyclodiene insecticides, pyrethroid insecticides and strychnine (Bradbury et al., 1990).

Progress also has been made in testing the subchronic toxicity of chemicals· to fish (University of Wisconsin-Superior, 1992), and. in relating acute and subchronic. toxicities of chemicals. This allows for the assessment of hazard following longer term exposures. From this database, chronic or subchronic toxicity prediction models have been developed to date for chemicals having narcosis I and uncoupling modes of action (Call et al. 1985, 1989). .