\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[english]{babel}



\usepackage{float}








\begin{document}

\title{Interpretation of In Vitro Concentration-Response Data for Risk
Assessment and Regulatory Decision-making: Report from 2022 IWGT
Quantitative Analysis Expert Working Group Meeting}



\author[1]{Marc Beal}%
\author[2]{Guangchao Chen}%
\author[3]{Kerry Dearfield}%
\author[4]{Min Gi}%
\author[5]{Bhaskar Gollapudi}%
\author[6]{Robert Heflich}%
\author[7]{Katsuyoshi Horibata}%
\author[1]{Alexandra Long}%
\author[8]{David Lovell}%
\author[9]{Barbara Parsons}%
\author[10]{Stefan Pfuhler}%
\author[11]{John Wills}%
\author[12]{Andreas Zeller}%
\author[13]{George Johnson}%
\author[1]{Paul White}%
\affil[1]{Health Canada}%
\affil[2]{Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), the Netherlands}%
\affil[3]{Retired}%
\affil[4]{Department of Environmental Risk Assessment, Graduate School of Medicine, Osaka Metropolitan University}%
\affil[5]{Toxicology Consultant}%
\affil[6]{NCTR}%
\affil[7]{National Institute of Health Sciences}%
\affil[8]{University of London}%
\affil[9]{US FDA/National Center for Toxicological Research}%
\affil[10]{Procter \& Gamble, Cosmital SA}%
\affil[11]{GSK}%
\affil[12]{F. Hoffmann-La Roche Ltd.}%
\affil[13]{Swansea University}%


\vspace{-1em}



  
  \date{May 19, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Quantitative risk assessments of chemicals are routinely performed in
rodents; however, there is growing recognition that non-animal
approaches can be human-relevant alternatives. There is an urgent need
to build confidence in non-animal alternatives given the international
support to reduce the use of animals in toxicity testing where possible.
In order for scientists and risk assessors to prepare for this paradigm
shift in toxicity assessment, standardization and consensus on in vitro
testing strategies and data interpretation will need to be established.
To address this issue, an Expert Working Group (EWG) of the 8th
International Workshop on Genotoxicity Testing (IWGT) evaluated the
utility of quantitative in vitro genotoxicity concentration-response
data for risk assessment. The EWG first evaluated available in vitro
methodologies and then examined the variability and maximal response of
in vitro tests to estimate biologically relevant values for the critical
effect sizes considered adverse or unacceptable. Next, the EWG reviewed
the approaches and computational models employed to provide
human-relevant dose context to in vitro data. Lastly, the EWG evaluated
risk assessment applications for which in vitro data are ready for use
and applications where further work is required. The EWG concluded that
in vitro genotoxicity concentration-response data can be interpreted in
a risk assessment context. However, prior to routine use in regulatory
settings, further research will be required to address the remaining
uncertainties and limitations.%
\end{abstract}%



\sloppy


\textbf{Hosted file}

\verb`2023-06-04-Beal_IWGT_in_vitro_subgroup_manuscript.docx`  available at \url{https://authorea.com/users/527120/articles/647761-interpretation-of-in-vitro-concentration-response-data-for-risk-assessment-and-regulatory-decision-making-report-from-2022-iwgt-quantitative-analysis-expert-working-group-meeting}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/20230503-esCES-schematic-4/20230503-esCES-schematic-4}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

