Mechanism of Salinity-Induced Toxicity of Aldicarb in Euryhaline Fish

EPA Grant Number: R826109
Title: Mechanism of Salinity-Induced Toxicity of Aldicarb in Euryhaline Fish
Investigators: Schlenk, Daniel
Institution: University of California - Riverside
EPA Project Officer: Hahn, Intaek
Project Period: December 29, 1997 through December 28, 2000
Project Amount: $263,149
RFA: Exploratory Research - Environmental Biology (1997) RFA Text |  Recipients Lists
Research Category: Biology/Life Sciences , Ecosystems

Description:

Certain agrichemicals are more toxic to euryhaline fish at high salinity. The mechanism for this relationship is not known. However, we have recently shown that the expression of a family of enzymes found in euryhaline fish, the flavin-containing monooxygenases (FMOs), which are known to bioactivate thioether pesticides, are also directly related to salinity. Thus the hypothesis of this proposal is that one or more FMOs which are upregulated during high salinity are responsible for the bioactivation and subsequent enhanced toxicity of the thioether pesticide, aldicarb, in euryhaline fish. To test this hypothesis, the following specific aims will be carried out:

Approach:

1) To determine the contribution of other toxicokinetic factors toward salinity-induced toxicity, the effects of salinity on aldicarb uptake, elimination, and the interactions with its specific receptor will be examined in the euryhaline fish, the Japanese Medaka (Oryzias latipes).
2) Examine the effect of salinity on aldicarb metabolism in medaka. In vivo metabolism studies will be performed with each fish as well as in vitro incubations with gill and liver microsomes to determine the metabolite profile of aldicarb. Various inhibitors of other Phase I biotransformation pathways will also be used to establish the relationship between FMO and aldicarb biotransformation.
3) Examine the effect of salinity on FMO expression and activity in medaka. Preliminary studies have shown the presence of a FMO-like protein and FMO activity in the gill of medaka that correlates with salinity. Gill microsomal FMO activity will be characterized in each fish and the effects of various osmoregulation modulators on FMO expression and activity will also be explored.

Expected Results:

Documenting how hydrological parameters (i.e. salinity) influence and regulate biological function such as osmoregulation will provide a better understanding of "basic" mechanisms of adaptation and selection for euryhaline organisms. In addition, understanding how salinity affects FMO expression will provide a mechanistic basis for the enhanced toxicity of thioether pesticides to euryhaline fish exposed at high salinity either in estuarine or hypersaline freshwater environments. Results from this research will also provide insight for risk assessors who must evaluate the effects of water quality parameters on the toxicity of environmental contaminants in such dynamic ecosystems. Lastly, through characterization of the affinity and rate constants for maximum enzymatic velocity, critical parameters for physiologically-based toxicokinetic (PBTK) models will be obtained and used to accurately assess exposure and target organ concentrations of the toxicant under varied environmental conditions. Thus, better assessments of exposure and risk will be the ultimate benefits of the proposed research.

Publications and Presentations:

Publications have been submitted on this project: View all 11 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 3 journal articles for this project

Supplemental Keywords:

Aldicarb, Salinity, Flavin-containing monooxygenases, biotransformation, mechanism., RFA, Scientific Discipline, Toxics, Ecosystem Protection/Environmental Exposure & Risk, Toxicology, Ecosystem/Assessment/Indicators, Ecosystem Protection, exploratory research environmental biology, pesticides, Ecological Effects - Environmental Exposure & Risk, Biochemistry, Ecology and Ecosystems, Ecological Risk Assessment, Ecological Indicators, ecological exposure, flavin containing monooxygenases (FMOs), hydrological, Japanese medaka, Euryhaline fish, salinity, Aldicarb, physiologically-based toxicokinetic models (PBTK), agrochemcial, aquatic ecosystems

Progress and Final Reports:

  • 1998 Progress Report
  • 1999 Progress Report
  • Final