Elsevier

Aquatic Toxicology

Volume 61, Issues 3–4, 3 December 2002, Pages 225-232
Aquatic Toxicology

Gender differences in the effect of salinity on aldicarb uptake, elimination, and in vitro metabolism in Japanese medaka, Oryzias latipes

https://doi.org/10.1016/S0166-445X(02)00059-0Get rights and content

Abstract

Toxicity studies have shown that salinity enhances the toxicity of aldicarb to female Japanese medaka. Although previous studies indicated that biotransformation may be important in these effects, other dispositional factors may play a role in this scenario. Male and female medaka were separately acclimated to three salinity regimens: 1.5, 12, and 20 parts per thousand (‰) for 2 weeks. The fish were then aqueously exposed to 96 h LC20 of [14C]aldicarb for 24 h. [14C]aldicarb equivalents (aldicarb and its metabolites) were measured in whole-fish homogenates of half the fish. The other half of the population was transferred to clean water for 48 h. During this 48 h period, fish were removed and whole animal homogenates were measured radiometrically at 0, 2, 4, 8, 12, and 24 h time points. Salinity did not have an effect on the uptake of aldicarb in either male or female medaka. Elimination data showed that elimination of [14C]aldicarb equivalents was biphasic. Salinity did not have an effect on the elimination half life in either males or females. In vitro metabolism using gill and liver microsomes from fish acclimated to three salinity regimens showed that aldicarb sulfoxide production by male gill microsomes increased 6-fold by salinity compared to a 9-fold increase in female gills. In conclusion, the increased sensitivity of female medaka to salinity enhanced toxicity seems to be caused by a higher metabolic activation of aldicarb to the sulfoxide compared to the males. This study supports the hypothesis that the differential expression and regulation of FMOs is an important factor in determining the sensitivity of euryhaline fish to aldicarb, especially at high salinity regimens.

Introduction

The bioavailability of chemicals to aquatic organisms can be affected by various physicochemical factors of the water such as alkalinity, hardness, pH, temperature, and salinity. Several studies have shown that salinity potentiates the toxicity of various chemicals, including certain organophosphorus compounds, atrazine, and detergents (Brecken-Folse et al., 1994, Eisler, 1965, Halls et al., 1994, Katz, 1961). However, none of these studies examined whether such an effect is gender specific. In addition, the effect of salinity on the pharmacokinetic parameters governing the fate of pollutants in aquatic organisms has not been extensively studied.

Aldicarb is a carbamate insecticide that is rapidly and extensively metabolized in most animals and plants. Metabolism studies have shown that aldicarb is biotransformed into both oxidized and hydrolytic products (Risher et al., 1987). While aldicarb inhibits acetylcholinesterase, S-oxygenation to the sulfoxide metabolite enhances its toxicity (Pelekis and Krishnan, 1997, WHO, 1991). Further oxidation to the sulfone reduces or eliminates the anti-cholinesterase activity (Hastings et al., 1970). All of the hydrolytic metabolites lack any acute toxicity (Risher et al., 1987). Thus factors influencing the metabolic pathway of aldicarb can greatly alter the acute toxicity of this compound.

Both in vitro and in vivo studies have examined the biotransformation of aldicarb in aquatic organisms. Studies have focused on two species with different sensitivities to aldicarb toxicity: namely, rainbow trout and channel catfish, with the latter exhibiting more resistance to aldicarb toxicity (Perkins et al., 1999, Perkins and Schlenk, 2000, Schlenk and Buhler, 1991, Schlenk et al., 1992). Aldicarb resistance in channel catfish was primarily due to the delayed biotransformation of aldicarb to the sulfoxide metabolite compared to rainbow trout (Perkins and Schlenk, 2000). Toxicokinetic and dispositional studies indicated that species differences in biotransformation were due to the lack of the flavin monooxygenase (FMO) enzyme system in channel catfish.

In the southeastern USA, aldicarb is widely applied on crops that are grown adjacent to estuaries. Significant residues have been shown to occur in estuaries after acute runoff events (Colbert et al., 1999). We have shown earlier that salinity enhanced the toxicity of aldicarb to female Japanese medaka (El-Alfy and Schlenk, 1998). Such enhanced toxicity appears to be partially mediated by the increase in gill FMO activity, which bioactivated aldicarb to the more toxic sulfoxide metabolite. Earlier studies also showed that female medaka were more sensitive to salinity enhanced toxicity. Since other dispositional processes may also influence gender responses to altered salinity, the effect of salinity on the uptake, elimination, and in vitro metabolism of aldicarb in both male and female medaka was examined.

Section snippets

Chemicals

Radiolabeled (S-methyl 14C) aldicarb (23 mCi/mmol) was a gift from Rhone Poulenc Inc. (Research Triangle Park, NC). [14C]aldicarb was diluted to 1 μCi/μmol with unlabeled compound (99% purity, ChemService, West Chester, PA) and stored at −20 °C until use. Prior to use, aldicarb was purified using a Waters Sep-PakC18 solid phase extraction column and a methanol step gradient. Purity was determined by radio HPLC. HPLC grade solvents and Scinti-Safe™ scintillation cocktail were purchased from

Uptake study

Whole body analysis showed that both male and female medaka accumulated almost 100% of the aldicarb after 24 h of exposure. Salinity did not have an effect on the amount of radioactivity taken up by either male or female fish (Fig. 1).

Elimination study

Table 1 summarizes the pharmacokinetic parameters of [14C]aldicarb as determined in both male and female medaka as well as the effect of salinity on these parameters. Following an aqueous exposure of 0.25 mg/l [14C]aldicarb, the elimination of total [14C]aldicarb

Discussion

Aldicarb is a carbamate insecticide that exerts its toxicity in both target and non-target organisms by the inhibition of cholinesterase enzymes leading to accumulation of acetylcholine, sustained cholinergic stimulation, and eventual death (Coppage, 1977). Thus any factors that might influence the degree of inhibition of cholinesterases by aldicarb are likely to change its toxicity. Several mechanisms can alter the interactions of aldicarb with its target; including uptake, elimination,

Acknowledgements

This study was supported by the US Environmental Protection Agency Exploratory Grants Program (grant number R826109-01-0). The authors would like to thank Dr. Lisa Ortego and Rhone Poulenc for the provision of radiolabeled aldicarb and wish to acknowledge the Environmental Toxicology Research Program at the University of Mississippi for the partial support of Abir El-Alfy. Special thanks are also extended to Erica Marsh for her technical help in maintaining fish cultures.

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