2024 SETAC Europe Poster: Evaluation of Positive Control Substrates for the OECD319 In Vitro Rainbow Trout Bioaccumulation Estimation Studies

2024 SETAC Europe Poster: Evaluation of Positive Control Substrates for the OECD319 In Vitro Rainbow Trout Bioaccumulation Estimation Studies

The OECD 319 guidelines for the determination of in vitro intrinsic clearance using cryopreserved rainbow trout hepatocytes (RT-HEP, OECD319A) and S9 sub-cellular fraction (RT-S9, OECD319B) were published in 2018. The studies are intended as a means of estimating the potential for bioaccumulation of chemicals in fish without the need for an in vivo fish bioconcentration factor (BCF) study (OECD305). They can be used in cases where it is not possible to run the BCF study, for example, ethical reasons such as cosmetic use, to reduce animal usage or it is not technically feasible. They may also be used to provide early screening information about bioconcentration potential or metabolism.

Since the release of the guidelines there have been discussions around the most applicable positive control substrates for the experiments. Positive controls are used to ensure the metabolic viability of the test system used (S9 or hepatocytes). A positive control usually should typically result in a minimum transformation of 20% with 10% remaining unchanged by the terminal time-point of the experiment. This can present a challenge in the case of particularly high or low turnover as the positive control could be entirely transformed or remain unchanged at the end of the experiment. To validate the OECD319 study at our facility we have tested several different substrates that have the potential to be used as a convenient positive control. These can be matched to the clearance of the chemical under investigation. 

This poster presentation will summarise the results from the testing of several different potential positive control substrates for both the RT-HEP and RT-S9 assays.

Rory Mumford and Daniel Evans will present this research at the SETAC Europe 34th Annual Meeting, 5-9 May 2024, in Seville, Spain. (Monday, 6 May, Location: 1.02.P-Mo022)

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2024 SETAC Europe Poster: Evaluation of Positive Control Substrates for the OECD319 In Vitro Rainbow Trout Bioaccumulation Estimation Studies

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