Matthew Philip Dent

Matthew Philip Dent
Unilever · Research & Development

Doctor of Philosophy

About

46
Publications
6,288
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632
Citations

Publications

Publications (46)
Article
Full-text available
An important question in toxicological risk assessment is whether non-animal New Approach Methodologies (NAMs) can be used to make safety decisions that are protective of human health, without being overly conservative. In this work we propose a core NAM toolbox and workflow for conducting systemic safety assessments for adult consumers. We also pr...
Article
Full-text available
Parabens are esters of para-hydroxybenzoic acid that have been used as preservatives in many types of products for decades including agrochemicals, pharmaceuticals, food and cosmetics. This illustrative case study with propylparaben (PP) demonstrates a 10-step read-across (RAX) framework in practice. It aims at establishing a proof-of-concept for t...
Article
Full-text available
New Approach Methodologies (NAMs) promise to offer a unique opportunity to enable human-relevant safety decisions to be made without the need for animal testing in the context of exposure-driven Next Generation Risk Assessment (NGRA). Protecting human health against the potential effects a chemical may have on embryo-foetal development and/or aspec...
Article
Full-text available
Ethical and legal considerations have led to increased use of non-animal methods to evaluate the safety of chemicals for human use. We describe the development and qualification of a physiologically-based kinetics (PBK) model for the cosmetic UV filter ingredient, homosalate, to support its safety without the need of generating further animal data....
Article
This paper presents a 10-step read-across (RAX) framework for use in cases where a threshold of toxicological concern (TTC) approach to cosmetics safety assessment is not possible. RAX builds on established approaches that have existed for more than two decades using chemical properties and in silico toxicology predictions, by further substantiatin...
Article
Full-text available
Next generation risk assessment (NGRA) is an exposure-led, hypothesis-driven approach that has the potential to support animal-free safety decision-making. However, significant effort is needed to develop and test the in vitro and in silico (computational) approaches that underpin NGRA to enable confident application in a regulatory context. A work...
Article
Full-text available
The AR-CALUX® in vitro method is a reporter gene-based transactivation method where endocrine active chemicals with androgenic or anti-androgenic potential can be detected. Its primary purpose is for screening chemicals for further prioritisation and providing mechanistic (endocrine mode of action) information, as defined by the OECD Conceptual Fra...
Article
Next Generation Risk Assessment (NGRA) can use the so-called Dietary Comparator Ratio (DCR) to evaluate the safety of a defined exposure to a compound of interest. The DCR compares the Exposure Activity Ratio (EAR) for the compound of interest, to the EAR of an established safe level of human exposure to a comparator compound with the same putative...
Article
Full-text available
Many substances for which consumer safety risk assessments need to be conducted are not associated with specific toxicity modes of action, but rather exhibit non-specific toxicity leading to cell stress. In this work, a cellular stress panel is described, consisting of 36 biomarkers representing mitochondrial toxicity, cell stress and cell health,...
Article
Full-text available
Next Generation Risk Assessment (NGRA) is defined as an exposure-led, hypothesis-driven risk assessment approach that integrates New Approach Methodologies (NAMs) to assure safety without the use of animal testing. These principles were applied to a hypothetical safety assessment of 0.1% coumarin in face cream and body lotion. For the purpose of ev...
Article
https://doi.org/10.1016/j.tox.2020.152421 Although the need for non-animal alternatives has been well recognised for the human health hazard assessment of chemicals in general, it has become especially pressing for cosmetic ingredients due to the full implementation of testing and marketing bans on animal testing under the European Cosmetic Regulat...
Article
Although the need for non-animal alternatives has been well recognised for the human health hazard assessment of chemicals in general, it has become especially pressing for cosmetic ingredients due to the full implementation of testing and marketing bans on animal testing under the European Cosmetic Regulation. This means that for the safety assess...
Article
There is a growing recognition that application of mechanistic approaches to understand cross-species shared molecular targets and pathway conservation in the context of hazard characterization, provide significant opportunities in risk assessment (RA) for both human health and environmental safety. Specifically, it has been recognized that a more...
Article
There is a growing recognition that application of mechanistic approaches to understand cross-species shared molecular targets and pathway conservation in the context of hazard characterization, provide significant opportunities in risk assessment (RA) for both human health and environmental safety. Specifically, it has been recognized that a more...
Article
Full-text available
The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a Partners' Forum on repeated dose toxicity (RDT) testing to identify synergies between industrial sectors and stakeholders along with opportunities to progress these in existing research frameworks. Although RTD testing is not performed across all industrial sect...
Article
The development and normal function of prostate tissue depends on signalling interactions between stromal and epithelial compartments. Development of a prostate microtissue composed of these two components can help identify substance exposures that could cause adverse effects in humans as part of a non-animal risk assessment. In this study, prostat...
Article
Full-text available
This study investigated the use of androgen receptor (AR) reporter gene assay data in a non-animal exposure-led risk assessment in which in vitro anti-androgenic activity and exposure data were put into context using a naturally occurring comparator substance with a history of dietary consumption. First, several dietary components were screened to...
Article
Full-text available
Consumer safety is a prerequisite for any cosmetic product. Worldwide, there is an ever-increasing desire to bring safe products to market without animal testing, which requires a new approach to consumer safety. ‘Next Generation Risk Assessment’ (NGRA), defined as an exposure-led, hypothesis driven risk assessment approach that integrates in silic...
Article
When performing safety assessment of chemicals, the evaluation of their systemic toxicity based only on non-animal approaches is a challenging objective. The Safety Evaluation Ultimately Replacing Animal Test programme (SEURAT-1) addressed this question from 2011 to 2015 and showed that further research and development of adequate tools in toxicoki...
Technical Report
Full-text available
In response to the ‘Outline of draft Guidance Document for the implementation of the hazard-based criteria to identify endocrine disruptors’, published by ECHA and EFSA in December 2016 with support from the JRC, the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) has developed science-based guidance showing how the ECHA and...
Technical Report
IN A NUTSHELL Various European chemical regulations do not allow the marketing or use of substances known to have endocrine disrupting properties – chemicals that induce adverse effects in humans and/or wildlife as a result of interaction with the endocrine system. Adverse outcome pathways (AOPs) have the potential to be important tools for the ass...
Article
Toxicology testing is undergoing a transformation from a system based on high-dose studies in animals to one founded primarily on in vitro methods that evaluate changes in normal cellular signalling pathways using human-relevant cells or tissues. This is a challenge for anti-androgenic effects in humans, since some parts of the hypothalamus-pituita...
Article
Risk assessment methodologies in toxicology have remained largely unchanged for decades. The default approach uses high dose animal studies, together with human exposure estimates, and conservative assessment (uncertainty) factors or linear extrapolations to determine whether a specific chemical exposure is ‘safe’ or ‘unsafe’. Although some increme...
Article
Toxicokinetic (TK) information can substantially enhance the value of the data generated from toxicity testing, and is an integral part of pharmaceutical safety assessment. It is less widely used in the chemical, agrochemical and consumer products industries, but recognition of its value is growing, as reflected by increased reference to the use of...
Article
Assuring consumer safety without the generation of new animal data is currently a considerable challenge. However, through the application of new technologies and the further development of risk-based approaches for safety assessment, we remain confident it is ultimately achievable. For many complex, multi-organ consumer safety endpoints, the devel...
Article
Full-text available
Non-animal based approaches to risk assessment are now routinely used for assuring consumer safety for some endpoints (such as skin irritation) following considerable investment in developing and applying new methods over the past 20 years. Unilever's research programme into non-animal approaches for safety assessment is currently focused on the ap...
Article
While toxicokinetics has become an integral part of pharmaceutical safety assessment over the last two decades, its use in the chemical industry is relatively new. However, it is recognised as a potentially important tool in human health risk assessment and recent initiatives have advocated greater application of toxicokinetics as part of an improv...
Article
The upcoming European chemicals legislation REACH (Registration, Evaluation, and Authorisation of Chemicals) will require the risk assessment of many thousands of chemicals. It is therefore necessary to develop intelligent testing strategies to ensure that chemicals of concern are identified whilst minimising the testing of chemicals using animals....
Article
In recent years there has been an increasing body of literature describing the antihypertensive effects of peptides produced from milk protein. The tripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), isolated from hydrolysed casein have been shown to lower blood pressure by inhibiting angiotensin I-converting enzyme (ACE)...

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Project (1)
Project
The purpose of the OpenTox Association is to promote the community-based exchange and use of open knowledge, methods, tools, data, reference resources, and standards including open software, ontology and application programming interfaces in the scientific activities of predictive toxicology, safety assessment and risk management, including the “3Rs” goal of the Reduction, Refinement and Replacement of Animal Testing.