TY - JOUR

T1 - Methods

T2 - Using R in regulatory toxicology

AU - Kluxen, Felix M.

AU - Jensen, Signe M.

PY - 2022

Y1 - 2022

N2 - Statistical analyses are an essential part of regulatory toxicological evaluations. While projects would be ideally monitored by both toxicologists and statisticians, this is often not possible in practice. Hence, toxicologists should be trained in some common statistical approaches but also need a tool for statistical evaluations. Due to transpar-ency needed in regulatory processes and standard tests that can be evaluated with template approaches, the freely available open-source statistical software R may be suitable. R is a well-established software in the statistical community. The principal input method is via software code, which is both benefit and weakness of the tool. It is increasingly used by regulating authorities globally and can be easily extended by software packages, e.g., for new statistical functions and features. This manuscript outlines how R can be used in regulatory toxicology, allowing toxicologists to perform all regulatory required data evaluations in a single software solution. Practical applications are shown in case studies on simulated and experimental data. The examples cover a) Dunnett testing of treatment groups against a common control and in relation to a biological relevance threshold, assessing the test's assump-tions and plotting the results; b) dose-response analysis and benchmark dose derivation for chronic kidney inflam-mation as a function of Pyridine; and c) graphical/exploratory data analysis of previously published developmental neurotoxicity data for Chlorpyrifos.

AB - Statistical analyses are an essential part of regulatory toxicological evaluations. While projects would be ideally monitored by both toxicologists and statisticians, this is often not possible in practice. Hence, toxicologists should be trained in some common statistical approaches but also need a tool for statistical evaluations. Due to transpar-ency needed in regulatory processes and standard tests that can be evaluated with template approaches, the freely available open-source statistical software R may be suitable. R is a well-established software in the statistical community. The principal input method is via software code, which is both benefit and weakness of the tool. It is increasingly used by regulating authorities globally and can be easily extended by software packages, e.g., for new statistical functions and features. This manuscript outlines how R can be used in regulatory toxicology, allowing toxicologists to perform all regulatory required data evaluations in a single software solution. Practical applications are shown in case studies on simulated and experimental data. The examples cover a) Dunnett testing of treatment groups against a common control and in relation to a biological relevance threshold, assessing the test's assump-tions and plotting the results; b) dose-response analysis and benchmark dose derivation for chronic kidney inflam-mation as a function of Pyridine; and c) graphical/exploratory data analysis of previously published developmental neurotoxicity data for Chlorpyrifos.

KW - Regulatory toxicology

KW - statistics

KW - continued education

KW - software tutorial

KW - R

U2 - 10.17179/excli2022-5097

DO - 10.17179/excli2022-5097

M3 - Journal article

C2 - 36320807

VL - 21

SP - 1130

EP - 1150

JO - EXCLI Journal

JF - EXCLI Journal

SN - 1611-2156

ER -