Biotransformation Potential of Cationic Surfactants in Fish Assessed with Rainbow Trout Liver S9 Fractions

Abstract

Biotransformation may substantially reduce the extent to which organic environmental contaminants accumulate in fish. Presently, however, relatively little is known regarding the biotransformation of ionized chemicals, including cationic surfactants, in aquatic organisms. To address this deficiency, a rainbow trout liver S9 substrate depletion assay (RT‐S9) was used to measure in vitro intrinsic clearance rates (CLint; ml min–1 g liver–1) for 22 cationic surfactants that differ with respect to alkyl chain length and degree of methylation on the charged nitrogen atom. None of the quaternary N,N,N‐trimethylalkylammonium compounds exhibited significant clearance. Rapid clearance was observed for N,N‐dimethylalkylamines, and slower rates of clearance were measured for N‐methylalkylamine analogs. Clearance rates for primary alkylamines were generally close to or below detectable levels. For the N‐methylalkylamines and N,N‐dimethylalkylamines, the highest CLint values were measured for C10–C12 homologs; substantially lower clearance rates were observed for homologs containing shorter or longer carbon chains. Based on its cofactor dependency, biotransformation of C12–N,N‐dimethylamine appears to involve one or more cytochrome P450–dependent reaction pathways, and sulfonation. On a molar basis, N‐demethylation metabolites accounted for up to 25% of the N,N‐dimethylalkylamines removed during the 2‐h assay, and up to 55% of the removed N‐methylalkylamines. These N‐demethylation products possess greater metabolic stability in the RT‐S9 assay than the parent structures from which they derive and may contribute to the overall risk of ionizable alkylamines. The results of these studies provide a set of consistently determined CLint values that may be extrapolated to whole trout to inform in silico bioaccumulation assessments. Environ Toxicol Chem 2021;40:3123–3136. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Bioconcentration of Several Series of Cationic Surfactants in Rainbow Trout

“…Demethylation of T10 to form S10 was reported in an in vitro S9 assay, and it was proposed that this is an important elimination mechanism for tertiary amines in fish . There is in vitro evidence that demethylation of secondary alkylamines also occurs, which will be reported elsewhere . Our observations show that demethylation also occurs in vivo.…”

“…27 There is in vitro evidence that demethylation of secondary alkylamines also occurs, which will be reported elsewhere. 34 Our observations show that demethylation also occurs in vivo. Bioconcentration Factors (BCFs).…”

“…Furthermore, shorter chained secondary and tertiary alkylamines for which our results indicate limited biotransformation are readily transformed in the S9 assay. 27,34 More research is required to resolve this apparent contradiction.…”

Oxidative Stress and Histopathological Changes in Gills and Kidneys of Cyprinus carpio following Exposure to Benzethonium Chloride, a Cationic Surfactant

“…Cationic surfactants interact by ionic bonds with negatively charged humic acids and clay colloids and are accumulated in sediments. However, a dissolved fraction remains in water and can be uptaken by aquatic organisms [ 43 ]. Their microbicidal activity is exerted by the destabilization of cell membrane [ 44 ], especially at concentrations close to their critical micellar concentrations [ 45 ].…”

In Vivo Bioconcentration of 10 Anionic Surfactants in Rainbow Trout Explained by In Vitro Data on Partitioning and S9 Clearance

“…Properties and measured activity levels are presented in Table S7 . The test was conducted using the same method applied for a series of cationic surfactants in Droge et al 29 and is summarized together with the in vitro – in vivo extrapolation in Text S4 .…”