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Dive into the research topics where Cameron MacKay is active.

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Featured researches published by Cameron MacKay.


Toxicological Sciences | 2017

How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology

Clemens Wittwehr; Hristo Aladjov; Gerald T. Ankley; Hugh J. Byrne; Joop de Knecht; Elmar Heinzle; Günter Klambauer; Brigitte Landesmann; Mirjam Luijten; Cameron MacKay; Gavin Maxwell; M. E. (Bette) Meek; Alicia Paini; Edward J. Perkins; Tomasz Sobanski; Daniel L. Villeneuve; Katrina M. Waters; Maurice Whelan

Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework provides a systematic approach for organizing knowledge that may support such inference. Likewise, computational models of biological systems at various scales provide another means and platform to integrate current biological understanding to facilitate inference and extrapolation. We argue that the systematic organization of knowledge into AOP frameworks can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. This concept was explored as part of a workshop on AOP-Informed Predictive Modeling Approaches for Regulatory Toxicology held September 24–25, 2015. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development is described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment.


Toxicological Sciences | 2011

Determining Epidermal Disposition Kinetics for Use in an Integrated Nonanimal Approach to Skin Sensitization Risk Assessment

Michael Davies; Ruth Pendlington; Leanne Page; Clive S. Roper; David J. Sanders; Clare Bourner; Camilla Pease; Cameron MacKay

Development of risk assessment methods for skin sensitization in the absence of toxicological data generated in animals represents a major scientific and technical challenge. The first step in human skin sensitization induction is the transport of sensitizer from the applied dose on the skin surface to the epidermis, where innate immune activation occurs. Building on the previous development of a time course in vitro human skin permeation assay, new kinetic data for 10 sensitizers and 2 nonsensitizers are reported. Multicompartmental modeling has been applied to analyze the data and determine candidate dose parameters for use in integrated risk assessment methods: the area under the curve (AUC) and maximum concentration (C(max)) in the epidermis. A model with two skin compartments, representing the stratum corneum and viable skin (epidermis and dermis), was chosen following a formal model selection process. Estimates of the uncertainty, as well as average values of the epidermal disposition kinetics parameters, were made by fitting to the time course skin permeation data from individual skin donors. A potential reduced time course method is proposed based on two time points at 4 and 24 h, which gives results close to those from the full time course for the current data sets. The time course data presented in this work have been provided as a resource for development of predictive in silico skin permeation models.


Cutaneous and Ocular Toxicology | 2008

DEVELOPMENT OF A MODIFIED IN VITRO SKIN ABSORPTION METHOD TO STUDY THE EPIDERMAL/DERMAL DISPOSITION OF A CONTACT ALLERGEN IN HUMAN SKIN

Ruth Pendlington; Helen J. Minter; Leanne Stupart; Cameron MacKay; Clive S. Roper; David J. Sanders; Camilla Pease

In vitro skin absorption methods exist in Organisation for Economic Co-operation and Development (OECD) guideline form (No. 428) and are used to estimate the degree of systemic penetration of chemicals through skin. More detailed kinetics of permeation through skin compartments are not described well by existing methods. This study was designed to assess the practical feasibility of generating compartmental (stratum corneum/epidermal/dermal) disposition and kinetic data of topically applied chemicals. For chemically induced effects initiated in the skin (e.g., skin allergy), the delivery of tissue concentrations of chemical will impact the incidence and severity of biological effect. Explicit data on the kinetics of chemical disposition in skin have not traditionally been needed for skin allergy risk assessment: current in vivo assays embody delivery implicitly. Under the 7th Amendment to the European Cosmetics Directive, in vivo assays (such as the local lymph node assay for skin sensitization) will not be permitted to assess cosmetic ingredients. New in vitro and in silico alternative approaches and ways of predicting risk of adverse effects in humans need to be developed, and new methods such as that described here provide a way of estimating delivered concentrations and the effect of formulation changes on that delivery. As we continue to deconstruct the contributing factors of skin allergy in humans, it will be useful to have methods available that can measure skin tissue compartment exposure levels delivered from different exposure use scenarios. Here we provide such a method. The method could also be used to generate useful data for developing in silico kinetic models of compartmental skin delivery and for refining data for skin delivery in relation to the evaluation of systemic toxicity.


ALTEX-Alternatives to Animal Experimentation | 2013

From pathways to people: applying the adverse outcome pathway (AOP) for skin sensitization to risk assessment.

Cameron MacKay; Michael Davies; Vicki Summerfield; Gavin Maxwell


Toxicology in Vitro | 2014

Applying the skin sensitisation adverse outcome pathway (AOP) to quantitative risk assessment.

Gavin Maxwell; Cameron MacKay; Richard Cubberley; Michael L. Davies; Nichola Gellatly; Stephen E. Glavin; Todd Gouin; Sandrine Jacquoilleot; Craig Moore; Ruth Pendlington; Ouarda Saib; David Sheffield; Richard B. Stark; Vicki Summerfield


Atla-alternatives To Laboratory Animals | 2008

Application of a systems biology approach to skin allergy risk assessment.

Gavin Maxwell; Cameron MacKay


Atla-alternatives To Laboratory Animals | 2008

Assuring Consumer Safety Without Animal Testing: A Feasibility Case Study for Skin Sensitisation

Gavin Maxwell; Maja Aleksic; Aynur O. Aptula; Paul L. Carmichael; Julia H. Fentem; Nicola Gilmour; Cameron MacKay; Camilla Pease; Ruth Pendlington; Fiona Reynolds; Daniel Scott; Guy Warner; Carl Westmoreland


ALTEX-Alternatives to Animal Experimentation | 2010

Assuring safety without animal testing: Unilever's ongoing research programme to deliver novel ways to assure consumer safety.

Carl Westmoreland; Paul L. Carmichael; Dent M; Fentem J; Cameron MacKay; Gavin Maxwell; Pease C; Reynolds F


Atla-alternatives To Laboratory Animals | 2009

Non-animal approaches for consumer safety risk assessments: Unilever's scientific research programme.

Paul L. Carmichael; Michael Davies; Matt Dent; Julia H. Fentem; Samantha Fletcher; Nicola Gilmour; Cameron MacKay; Gavin Maxwell; Leona Merolla; Camilla Pease; Fiona Reynolds; Carl Westmoreland


Toxicology Letters | 2018

Evaluation of an integrated strategy for skin allergy risk assessment using six ingredients and two cosmetic product types

E. Vandenbossche; M. Baltazar; J. Butcher; R. Cubberley; N. Gilmour; Cameron MacKay; Ruth Pendlington; J. Reynolds; Gavin Maxwell

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Gavin Maxwell

University of Bedfordshire

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Ruth Pendlington

University of Bedfordshire

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Camilla Pease

University of Bedfordshire

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Carl Westmoreland

University of Bedfordshire

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Michael Davies

University of Bedfordshire

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Vicki Summerfield

University of Bedfordshire

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Clive S. Roper

Charles River Laboratories

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Craig Moore

University of Bedfordshire

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David Sheffield

University of Bedfordshire

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