Browsing by Author "Bevan, Ruth"

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    Biomonitoring for workplace exposure to copper and its compounds is currently not interpretable
    (Elsevier, 2024-03-26) Bevan, Ruth; Levy, Len
    This paper sets out to explore the requirements needed to recommend a useable and reliable biomonitoring system for occupational exposure to copper and its inorganic compounds. Whilst workplace environmental monitoring of copper is used to measure ambient air concentrations for comparison against occupational exposure limits, biological monitoring could provide complementary information about the internal dose of workers, taking into account intra-individual variability and exposure from all routes. For biomonitoring to be of reliable use for copper, a biomarker and the analytical ability to measure it with sufficient sensitivity must be identified and this is discussed in a range of matrices. In addition, there needs to be a clear understanding of the dose-response relationship of the biomarker with any health-effect (clinical or sub-clinical) or, between the level of external exposure (by any route) and the level of the copper biomarker in the biological matrix being sampled, together with a knowledge of the half-life in the body to determine accurate sampling times. For many biologically non-essential metals the requirements for reliable biomarkers can be met, however, for ‘essential’ metals such as copper that are under homeostatic control, the relationship between exposure (short- or long-term) and the level of any copper biomarker in the blood or urine is complex, which may limit the use and interpretation of measured levels. There are a number of types of biomarker guidance values currently in use which are discussed in this paper, but no values have yet been determined for copper (or its inorganic compounds) due to the complexity of its essential nature; the US The American Conference of Governmental Industrial Hygienists (ACGIH) has however indicated that it is considering the development of a biological exposure index for copper and its compounds. In light of this, we present a review of the reliability of current copper biomarkers and their potential use in the occupational context to evaluate whether there is value in carrying out human biomonitoring for copper exposure. Based on the available evidence we have concluded that the reliable use of biomonitoring of occupational exposure to copper and its application in risk assessment is not possible at the present time.
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    Clarifying the absence of evidence regarding human health risks to microplastic particles in drinking-water: High quality robust data wanted
    (Elsevier, 2020-10-07) Gouin, Todd; Cunliffe, David; De France, J.; Fawell, John; Jarvis, Peter; Koelmans, A. A. (Bart); Marsden, Peter; Testai, Emanuela E.; Asami, Mari; Bevan, Ruth; Carrier, R.; Cotruvo, Joseph; Eckhardt, Alexander; Ong, ‪Choon Nam
    In a recently published article, Leslie and Depledge (2020) raise concerns regarding statements on the risk that microplastic particles represent to human health and which have been attributed to reports published by both the Science Academies’ Group, Science Advice for Policy (SAPEA) (part of the European Commission’s Science Advice Mechanism) and the World Health Organization (WHO) (SAPEA. Science Advice for Policy by European Academies, 2019, WHO, 2019). Leslie and Depledge (2020), for instance, suggest that WHO (2019) conclude that there is ‘no evidence to indicate a human health concern.’ This statement, taken out of context from the WHO report (WHO, 2019), is then used to imply that the WHO conclude there is ‘no risk’ related to the exposure of microplastic particles (Leslie and Depledge, 2020). While, Leslie and Depledge (2020) highlight the importance of debate and systematic assessment of claims related to the assessment of risk, observations that we agree are important to highlight, there are a number of points raised in the article that require clarification.
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    Evaluation of in silico and in vitro screening methods for characterising endocrine disrupting chemical hazards
    (Cranfield University, 2014-11) Youngs, Louise Claire; Bevan, Ruth
    Anthropogenic activities have drastically altered chemical exposure, with traces of synthetic chemicals detected ubiquitously in the environment. Many of these chemicals are thought to perturb endocrine function, leading to declines in reproductive health and fertility, and increases in the incidence of cancer, metabolic disorders and diabetes. There are over 90 million unique chemicals registered under the Chemical Abstracts Service (CAS), of which only 308,000 were subject to inventory and/or regulation, in September 2013. However, as a specific aim of the EU REACH regulations, the UK is obliged to reduce the chemical safety initiatives reliance on in vivo apical endpoints, promoting the development and validation of alternative mechanistic methods. The human health cost of endocrine disrupting chemical (EDC) exposure in the EU, has been estimated at €31 billion per annum. In light of the EU incentives, this study aims to evaluate current in silico and in vitro tools for EDC screening and hazard characterisation; testing the hypothesis that in silico virtual screening accurately predicts in vitro mechanistic assays. Nuclear receptor binding interactions are the current focus of in silico and in vitro tools to predict EDC mechanisms. To the author’s knowledge, no single study has quantitatively assessed the relationship between in silico nuclear receptor binding and in vitro mechanistic assays, in a comprehensive manner. Tripos ® SYBYL software was used to develop 3D-molecular models of nuclear receptor binding domains. The ligand binding pockets of estrogen (ERα and ERβ), androgen (AR), progesterone (PR) and peroxisome proliferator activated (PPARγ) receptors were successfully modelled from X-ray crystal structures. A database of putative-EDC ligands (n= 378), were computationally ‘docked’ to the pseudo-molecular targets, as a virtual screen for nuclear receptor activity. Relative to in vitro assays, the in silico screen demonstrated a sensitivity of 94.5%. The SYBYL Surflex-Dock method surpassed the OECD Toolbox ER-Profiler, DfW and binary classification models, in correctly identifying endocrine active substances (EAS). Aiming to evaluate the current in vitro tools for endocrine MoA, standardised ERα transactivation (HeLa9903), stably transfected AR transactivation (HeLa4-11) assays in addition to novel transiently transfected reporter gene assays, predicted the mechanism and potency of test substances prioritised from the in silico results (n = 10 potential-EDCs and 10 hormone controls). In conclusion, in silico SYBYL molecular modelling and Surflex-Dock virtual screening sensitively predicted the binding of ERα/β, AR, PR and PPARγ potential EDCs, and was identified as a potentially useful regulatory tool, to support EAS hazard identification.
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    Setting evidence-based occupational exposure limits for manganese
    (Elsevier, 2016-08-09) Bevan, Ruth; Ashdown, Lini; McGough, Doreen; Huici-Montagud, Alicia; Levy, Leonard
    In 2004, a review by the Institute of Environment and Health (IEH) made recommendations on occupational exposure limits (OELs) for manganese and its inorganic compounds for inhalable and respirable fractions respectively. These OELs were based on a detailed comprehensive evaluation of all the scientific data available at that time. Since then, more published studies have become available and a number of occupational standard-setting committees (EU SCOEL, US ACGIH-TLV, and German MAK) have proposed OEL’s for manganese and its inorganic compounds that are somewhat lower that those proposed in the 2004 review. Based on current understanding, the key toxicological and human health issues that are likely to influence a health-based recommendation relate to: neurotoxicology; reproductive and developmental toxicology; and mutagenicity/carcinogenicity. Of these, it is generally considered that neurotoxicity presents the most sensitive endpoint. As such, many of the studies that have been reported since the IEH review have sought to use those neurofunctional tests that appear to be particularly sensitive at identifying the subtle neurological changes thought to associate with manganese toxicity. These recent studies have, however, continued to be limited to a significant extent by reliance on cross-sectional designs and also by use of unreliable exposure estimation methods. Consequently the strength of the potential association between manganese exposure and these subtle subclinical cognitive or neuromotor changes is still poorly characterised and the relevance of these minor differences in terms of either their clinical or quality of life consequences remains unknown. Based upon the overall evidence, it is concluded that the 8-h time weighted averages (TWA) for respirable (0.05 mg/m3 as Mn) and inhalable (0.2 mg/m3 as Mn) fractions as recommended by the SCOEL in 2011 are the most methodologically-sound, as they are based on the best available studies, most suited to the development of health-based OELs for both respirable and inhalable fractions. The dose-response characterisation informed by the examined studies used can be considered to establish a true human NOAEL for all the neurofunctional endpoints examined within the selected studies.