Skin sensitization in silico protocol

Candice Johnson; Ernst Ahlberg; Lennart T. Anger; Lisa Beilke; Romualdo Benigni; Joel Bercu; Sol Bobst; David Bower; Alessandro Brigo; Sarah Campbell; Mark T.D. Cronin; Ian Crooks; Kevin P. Cross; Tatyana Doktorova; Thomas Exner; David Faulkner; Ian M. Fearon; Markus Fehr; Shayne C. Gad; Véronique Gervais; Amanda Giddings; Susanne Glowienke; Barry Hardy; Catrin Hasselgren; Jedd Hillegass; Robert Jolly; Eckart Krupp; Liat Lomnitski; Jason Magby; Jordi Mestres; Lawrence Milchak; Scott Miller; Wolfgang Muster; Louise Neilson; Rahul Parakhia; Alexis Parenty; Patricia Parris; Alexandre Paulino; Ana Theresa Paulino; David W. Roberts; Harald Schlecker; Reinhard Stidl; Diana Suarez-Rodrigez; David T. Szabo; Raymond R. Tice; Daniel Urbisch; Anna Vuorinen; Brian Wall; Thibaud Weiler; Angela T. White; Jessica Whritenour; Joerg Wichard; David Woolley; Craig Zwickl; Glenn J. Myatt

doi:10.1016/j.yrtph.2020.104688

Skin sensitization in silico protocol

Candice Johnson, Ernst Ahlberg, Lennart T. Anger, Lisa Beilke, Romualdo Benigni, Joel Bercu, Sol Bobst, David Bower, Alessandro Brigo, Sarah Campbell, Mark T.D. Cronin, Ian Crooks, Kevin P. Cross, Tatyana Doktorova, Thomas Exner, David Faulkner, Ian M. Fearon, Markus Fehr, Shayne C. Gad, Véronique GervaisAmanda Giddings, Susanne Glowienke, Barry Hardy, Catrin Hasselgren, Jedd Hillegass, Robert Jolly, Eckart Krupp, Liat Lomnitski, Jason Magby, Jordi Mestres, Lawrence Milchak, Scott Miller, Wolfgang Muster, Louise Neilson, Rahul Parakhia, Alexis Parenty, Patricia Parris, Alexandre Paulino, Ana Theresa Paulino, David W. Roberts, Harald Schlecker, Reinhard Stidl, Diana Suarez-Rodrigez, David T. Szabo, Raymond R. Tice, Daniel Urbisch, Anna Vuorinen, Brian Wall, Thibaud Weiler, Angela T. White, Jessica Whritenour, Joerg Wichard, David Woolley, Craig Zwickl, Glenn J. Myatt

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

Abstract

The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducting a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship between skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework. Based on the relevance of the mechanisms and effects as well as the strengths and limitations of the experimental systems used to identify them, rules and principles are defined for deriving skin sensitization in silico assessments. Further, the assignments of reliability and confidence scores that reflect the overall strength of the assessment are discussed. This skin sensitization protocol supports the implementation and acceptance of in silico approaches for the prediction of skin sensitization.

Original language	English
Article number	104688
Journal	Regulatory Toxicology and Pharmacology
Volume	116
DOIs	https://doi.org/10.1016/j.yrtph.2020.104688
State	Published - Oct 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020 The Author(s)

Funding

Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number R43ES026909. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number R44ES026909. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number R43ES026909 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number R44ES026909 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funders	Funder number
National Institutes of Health.Research
National Institutes of Health
National Institute of Environmental Health Sciences	R43ES026909

Keywords

(Q)SAR
Computational toxicology
Computational toxicology protocols
Defined approach
Expert alerts
Expert review
Extractables and leachables
In silico
In silico toxicology
Integrated approaches to testing and assessment (IATA)
Skin sensitization

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Johnson, C., Ahlberg, E., Anger, L. T., Beilke, L., Benigni, R., Bercu, J., Bobst, S., Bower, D., Brigo, A., Campbell, S., Cronin, M. T. D., Crooks, I., Cross, K. P., Doktorova, T., Exner, T., Faulkner, D., Fearon, I. M., Fehr, M., Gad, S. C., ... Myatt, G. J. (2020). Skin sensitization in silico protocol. Regulatory Toxicology and Pharmacology, 116, Article 104688. https://doi.org/10.1016/j.yrtph.2020.104688

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title = "Skin sensitization in silico protocol",

abstract = "The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducting a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship between skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework. Based on the relevance of the mechanisms and effects as well as the strengths and limitations of the experimental systems used to identify them, rules and principles are defined for deriving skin sensitization in silico assessments. Further, the assignments of reliability and confidence scores that reflect the overall strength of the assessment are discussed. This skin sensitization protocol supports the implementation and acceptance of in silico approaches for the prediction of skin sensitization.",

keywords = "(Q)SAR, Computational toxicology, Computational toxicology protocols, Defined approach, Expert alerts, Expert review, Extractables and leachables, In silico, In silico toxicology, Integrated approaches to testing and assessment (IATA), Skin sensitization",

author = "Candice Johnson and Ernst Ahlberg and Anger, {Lennart T.} and Lisa Beilke and Romualdo Benigni and Joel Bercu and Sol Bobst and David Bower and Alessandro Brigo and Sarah Campbell and Cronin, {Mark T.D.} and Ian Crooks and Cross, {Kevin P.} and Tatyana Doktorova and Thomas Exner and David Faulkner and Fearon, {Ian M.} and Markus Fehr and Gad, {Shayne C.} and V{\'e}ronique Gervais and Amanda Giddings and Susanne Glowienke and Barry Hardy and Catrin Hasselgren and Jedd Hillegass and Robert Jolly and Eckart Krupp and Liat Lomnitski and Jason Magby and Jordi Mestres and Lawrence Milchak and Scott Miller and Wolfgang Muster and Louise Neilson and Rahul Parakhia and Alexis Parenty and Patricia Parris and Alexandre Paulino and Paulino, {Ana Theresa} and Roberts, {David W.} and Harald Schlecker and Reinhard Stidl and Diana Suarez-Rodrigez and Szabo, {David T.} and Tice, {Raymond R.} and Daniel Urbisch and Anna Vuorinen and Brian Wall and Thibaud Weiler and White, {Angela T.} and Jessica Whritenour and Joerg Wichard and David Woolley and Craig Zwickl and Myatt, {Glenn J.}",

note = "Publisher Copyright: {\textcopyright} 2020 The Author(s)",

year = "2020",

month = oct,

doi = "10.1016/j.yrtph.2020.104688",

language = "אנגלית",

volume = "116",

journal = "Regulatory Toxicology and Pharmacology",

issn = "0273-2300",

publisher = "Academic Press Inc.",

}

Johnson, C, Ahlberg, E, Anger, LT, Beilke, L, Benigni, R, Bercu, J, Bobst, S, Bower, D, Brigo, A, Campbell, S, Cronin, MTD, Crooks, I, Cross, KP, Doktorova, T, Exner, T, Faulkner, D, Fearon, IM, Fehr, M, Gad, SC, Gervais, V, Giddings, A, Glowienke, S, Hardy, B, Hasselgren, C, Hillegass, J, Jolly, R, Krupp, E, Lomnitski, L, Magby, J, Mestres, J, Milchak, L, Miller, S, Muster, W, Neilson, L, Parakhia, R, Parenty, A, Parris, P, Paulino, A, Paulino, AT, Roberts, DW, Schlecker, H, Stidl, R, Suarez-Rodrigez, D, Szabo, DT, Tice, RR, Urbisch, D, Vuorinen, A, Wall, B, Weiler, T, White, AT, Whritenour, J, Wichard, J, Woolley, D, Zwickl, C & Myatt, GJ 2020, 'Skin sensitization in silico protocol', Regulatory Toxicology and Pharmacology, vol. 116, 104688. https://doi.org/10.1016/j.yrtph.2020.104688

TY - JOUR

T1 - Skin sensitization in silico protocol

AU - Johnson, Candice

AU - Ahlberg, Ernst

AU - Anger, Lennart T.

AU - Beilke, Lisa

AU - Benigni, Romualdo

AU - Bercu, Joel

AU - Bobst, Sol

AU - Bower, David

AU - Brigo, Alessandro

AU - Campbell, Sarah

AU - Cronin, Mark T.D.

AU - Crooks, Ian

AU - Cross, Kevin P.

AU - Doktorova, Tatyana

AU - Exner, Thomas

AU - Faulkner, David

AU - Fearon, Ian M.

AU - Fehr, Markus

AU - Gad, Shayne C.

AU - Gervais, Véronique

AU - Giddings, Amanda

AU - Glowienke, Susanne

AU - Hardy, Barry

AU - Hasselgren, Catrin

AU - Hillegass, Jedd

AU - Jolly, Robert

AU - Krupp, Eckart

AU - Lomnitski, Liat

AU - Magby, Jason

AU - Mestres, Jordi

AU - Milchak, Lawrence

AU - Miller, Scott

AU - Muster, Wolfgang

AU - Neilson, Louise

AU - Parakhia, Rahul

AU - Parenty, Alexis

AU - Parris, Patricia

AU - Paulino, Alexandre

AU - Paulino, Ana Theresa

AU - Roberts, David W.

AU - Schlecker, Harald

AU - Stidl, Reinhard

AU - Suarez-Rodrigez, Diana

AU - Szabo, David T.

AU - Tice, Raymond R.

AU - Urbisch, Daniel

AU - Vuorinen, Anna

AU - Wall, Brian

AU - Weiler, Thibaud

AU - White, Angela T.

AU - Whritenour, Jessica

AU - Wichard, Joerg

AU - Woolley, David

AU - Zwickl, Craig

AU - Myatt, Glenn J.

PY - 2020/10

Y1 - 2020/10

N2 - The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducting a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship between skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework. Based on the relevance of the mechanisms and effects as well as the strengths and limitations of the experimental systems used to identify them, rules and principles are defined for deriving skin sensitization in silico assessments. Further, the assignments of reliability and confidence scores that reflect the overall strength of the assessment are discussed. This skin sensitization protocol supports the implementation and acceptance of in silico approaches for the prediction of skin sensitization.

AB - The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducting a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship between skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework. Based on the relevance of the mechanisms and effects as well as the strengths and limitations of the experimental systems used to identify them, rules and principles are defined for deriving skin sensitization in silico assessments. Further, the assignments of reliability and confidence scores that reflect the overall strength of the assessment are discussed. This skin sensitization protocol supports the implementation and acceptance of in silico approaches for the prediction of skin sensitization.

KW - (Q)SAR

KW - Computational toxicology

KW - Computational toxicology protocols

KW - Defined approach

KW - Expert alerts

KW - Expert review

KW - Extractables and leachables

KW - In silico

KW - In silico toxicology

KW - Integrated approaches to testing and assessment (IATA)

KW - Skin sensitization

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U2 - 10.1016/j.yrtph.2020.104688

DO - 10.1016/j.yrtph.2020.104688

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C2 - 32621976

AN - SCOPUS:85087984333

SN - 0273-2300

VL - 116

JO - Regulatory Toxicology and Pharmacology

JF - Regulatory Toxicology and Pharmacology

M1 - 104688

ER -

Skin sensitization in silico protocol

Abstract

Bibliographical note

Funding

Keywords

Access to Document

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