1461 / 2024-09-27 14:56:38

Arsenic Transformation and Detoxification in Marine Fish: Application of a Physiologically Based Pharmacokinetic Model

arsenic,arsenobetaine,biotransformation,fish,PBPK

Session 57 - Contaminants across the marine continuum: behavior, fate and ecological risk assessment

In marine fish, the primary form of arsenic (As) is the non-toxic arsenobetaine (AsB), however, the biokinetics of the transformation from the ingested arsenate (As(V)) to AsB is not understood. This study utilized a physiologically based pharmacokinetic (PBPK) model to analyzes the As species in the Acanthopagrus latus during a 7-day dietary exposure to As(V) and a subsequent 15-day depuration period, simulating the quantification of As transport and transformation processes among organs. Throughout the experimental process, As(V), dimethylarsinic acid (DMA), and AsB were detected as the predominant. As(V) and AsB were gradually increased in various tissues during the exposure and then rapidly decreased during the depuration, and DMA only existed in the intestine and liver. The net absorption rate of As(V) during exposure was 0.45 ug/g/d, and the transformation rate to AsB was 0.36 ug/g/d.  At the end of the exposure, AsB accounted for 94.0% of the total As in the whole fish. These results indicated that As(V) was efficiently and quickly transformed into AsB in marine fish. At the end of the depuration, 36% of the transformed AsB remained stored in the body (mostly in the muscle and carcass) and the residual As(V) was below the detection limit, suggesting that the synthesis of AsB contributes to the majority of the total As accumulation. Methylation of As(V) occurs primarily in the intestine (14 μg d-1), and the conversion of DMA to AsB occurs predominantly in the liver (18.5 μg d-1). The results indicate that the metabolism of inorganic arsenic in marine fish involves initial methylation to DMA in the intestine, followed by transfer to the liver for further synthesis of AsB. Intestine and liver may collaborate in the biological transformation of arsenic. In summary, marine fish possess an efficient mechanism for As transformation, which reduce the internal exposure to the toxic inorganic As and thus attenuate the toxic effects.