Physiologically-Based Toxicokinetic and Toxicodynamic model in rainbow trout for investigating the interaction between melamine and cyanuric acid

The R codes with the DOI: 10.5281/zenodo.2609136 presented here constitute a generic physiologically-based model for mixtures with a toxicodynamic interaction designed to model the interaction between melamine (MEL) and cyanuric acid (CYA) in the kidney or in urine in rainbow trout (Oncorhynchus mykiss). The implementation of the models using case studies is described in Tebby et al. (2019).

The R codes are provided for:

• R code for PBTK/TD modelling of a mixture of MEL and CYA with formation of crystals either in kidney or in urine (2 model files),
• R code for determination of partition coefficient using Quantitative Structure Activity Relationship (QSAR) models,
• Increase in body weight as a function of time,
• Parameterisation of the model for male Rainbow trout (Onchorhynchus mykiss) (2 files for calling either the urine or kidney PBTK/TD model file.

Compared to the initial PBTK model described in (Grech et al., 2018; DOI: 10.5281/zenodo.1414332), effect of temperature on renal excretion rate and oral absorption rates was added to the TK part of the model. The toxicodynamic interaction is modelled as a two-step process:

• formation of MEL-CYA complex in kidney from neutral forms of MEL and CYA,
• formation of MEL-CYA crystals by precipitation of the complex.

The full data collection and implementation of the models using case studies are described in Tebby et al. (2019) (https://doi.org/10.1016/j.taap.2019.03.021)

The tools are implemented in R. The model was developed using R software (version 3.3.3).