Grantee Research Project Results
1998 Progress Report: Mechanism of Salinity-Induced Toxicity of Aldicarb in Euryhaline Fish
EPA Grant Number: R826109Title: 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 Period Covered by this Report: December 29, 1997 through December 28, 1998
Project Amount: $263,149
RFA: Exploratory Research - Environmental Biology (1997) RFA Text | Recipients Lists
Research Category: Biology/Life Sciences , Aquatic Ecosystems
Objective:
Certain agrichemicals are more toxic to euryhaline fish at high salinity. Mechanisms explaining this relationship are not known. Expression of a family of enzymes found in euryhaline fish, the flavin-containing monooxygenases (FMOs), which are known to bioactivate aldicarb, also are directly related to salinity. The project was designed to test the hypothesis that one or more forms of FMO, which are upregulated during high salinity, are responsible for the bioactivation and subsequent enhanced toxicity of the thioether pesticide, aldicarb, in euryhaline fish. In Year 1, portions of each specific aim were carried out: (1) the effects of salinity on aldicarb uptake and the interactions of aldicarb and its metabolites with acetylcholinesterase were examined in the euryhaline fish, the Japanese Medaka (Oryzias latipes); (2) the effect of salinity on in vitro aldicarb metabolism in medaka was examined and demonstrated a significant role of FMO in aldicarb activation; and (3) the effect of salinity on FMO expression and activity in medaka also was examined.Progress Summary:
Specific Aim 1. Examination of the effect of salinity on aldicarb and its receptor cholinesterase, as well as uptake and elimination in medaka. Results concerning acute toxicity showed aldicarb sulfoxide did not cause mortality in any treatment group up to 1 ppm.96h LC50 of Aldicarb to Japanese Medaka at 1.5 ppths Salinity
Age Group | Aldicarb 96h LC50 (ppm) |
Larvae (12?14 d post hatch) | 0.25 |
Juveniles (4 weeks old) | 0.60 |
Adult Males (12 weeks old) | 0.56 |
Adult Females (12 weeks old) | 0.67 |
Results concerning cholinesterase inhibition showed no sexual differences in cholinesterase or inhibition by aldicarb and its metabolites. Aldicarb led to a dose-dependent decrease in cholineserase at 1.5 ppt salinity. Aldicarb sulfoxide is 48 times more potent than aldicarb. Salinity enhances inhibition of cholinesterase by aldicarb, but not aldicarb sulfoxide. Salinity does not effect overall cholinesterase activities. Each of the samples above have been cataloged for subsequent cholinesterase measurements.
Results showed that uptake of aldicarb, measured at 1.5, 12, and 25 ppt salinity, was unchanged. Measurements of elimination rates have not yet been performed.
Specific Aim 2. Examination of the effect of salinity on the in vitro and in vivo biotransformation of aldicarb in medaka. Results concerning in vitro biotransformation showed there were no sexual differences in aldicarb biotransformation in medaka. The predominant metabolite of liver and gill microsomes is aldicarb sulfoxide with a lesser amount of aldicarb nitrile. Formation of the sulfoxide is directly related to salinity in the liver and gill of medaka. One or more forms of cytochrome P450 account for approximately 25 percent of aldicarb sulfoxide formation.
Specific Aim 3. Characterization of the effect of salinity on FMO expression in medaka. Results of the effects of salinity on expression of FMO activity and FMO-like protein exhibited no significant differences in FMO activity between males and females. Preliminary studies concerning the effects of osmoregulatory modulating compounds on FMO activity and FMO-like proteins in medaka indicate estradiol downregulates branchial FMO activity and may protect against aldicarb toxicity in medaka. The effects of osmoregulatory modulating compounds on toxicity also were investigated.
Conclusions. The direct relationship between aldicarb sulfoxide formation, FMO activity, and salinity is consistent with our proposed mechanism: salinity upregulates FMO in euryhaline fish leading to enhanced aldicarb sulfoxide formation, which is a more potent cholinesterase inhibitor that enhances toxicity. Although preliminary studies indicated potential hormonal regulation, there do not appear to be gender-related differences in expression of enzyme or effect. The ramifications of these results suggest that hazard assessments for ecological risk assessments should include an euryhaline species, and toxicity studies should be conducted in a range of salinities.
Future Activities:
Continuation of Specific Aims as detailed in the original proposal with the addition of antibody manufacture for Specific Aim 3, which is currently under way.Journal Articles on this Report : 2 Displayed | Download in RIS Format
Other project views: | All 11 publications | 3 publications in selected types | All 3 journal articles |
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Type | Citation | ||
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El-Alfy A, Schlenk D. Potential mechanisms of the enhancement of aldicarb toxicity to Japanese medaka, Oryzias latipes, at high salinity. Toxicology and Applied Pharmacology 1998;152(1):175-183. |
R826109 (1998) |
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Schlenk D, El-Afy A. Expression of branchial flavin-containing monooxygenase is directly correlated with salinity-induced aldicarb toxicity in the euryhaline fish (Oryzias latipes). Marine Environmental Research, Volume 46, Issues 1-5, 12 July 1998, Pages 103-106. |
R826109 (1998) |
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Supplemental Keywords:
flavin-containing monooxygenases, salinity, aldicarb, euryhaline., 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 ecosystemsProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.