Publications
597 results found
Autrup H, Barile FA, Berry SC, et al., 2020, Human exposure to synthetic endocrine disrupting chemicals (S-EDCs) is generally negligible as compared to natural compounds with higher or comparable endocrine activity: how to evaluate the risk of the S-EDCs?, ARCHIVES OF TOXICOLOGY, Vol: 94, Pages: 2549-2557, ISSN: 0340-5761
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- Citations: 8
Autrup H, Barile FA, Colin Berry S, et al., 2020, Human exposure to synthetic endocrine disrupting chemicals (S-EDCs) is generally negligible as compared to natural compounds with higher or comparable endocrine activity. How to evaluate the risk of the S-EDCs?, Computational Toxicology, Vol: 14, ISSN: 2468-1113
Theoretically, both synthetic endocrine disrupting chemicals (S-EDCs) and natural (exogenous and endogenous) endocrine disrupting chemicals (N-EDCs) can interact with endocrine receptors and disturb hormonal balance. However, compared to endogenous hormones, S-EDCs are only weak partial agonists with receptor affinities several orders of magnitude lower than S-EDCs. Thus, to elicit observable effects, S-EDCs require considerably higher concentrations to attain sufficient receptor occupancy or to displace natural hormones and other endogenous ligands. Significant exposures to exogenous N-EDCs may result from ingestion of foods such as soy-based diets, green tea and sweet mustard. While their potencies are lower as compared to natural endogenous hormones, they usually are considerably more potent than S-EDCs. Effects of exogenous N-EDCs on the endocrine system were observed at high dietary intakes. A causal relation between their mechanism of action and these effects is established and biologically plausible. In contrast, the assumption that the much lower human exposures to S-EDCs may induce observable endocrine effects is not plausible. Hence, it is not surprising that epidemiological studies searching for an association between S-EDC exposure and health effects have failed. Regarding testing for potential endocrine effects, a scientifically justified screen should use in vitro tests to compare potencies of S-EDCs with those of reference N-EDCs. When the potency of the S-EDC is similar or smaller than that of the N-EDC, further testing in laboratory animals and regulatory consequences are not warranted.
Punt A, Firman J, Boobis A, et al., 2020, Potential of ToxCast Data in the Safety Assessment of Food Chemicals, TOXICOLOGICAL SCIENCES, Vol: 174, Pages: 326-340, ISSN: 1096-6080
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- Citations: 11
Parish ST, Aschner M, Casey W, et al., 2020, An evaluation framework for new approach methodologies (NAMs) for human health safety assessment, REGULATORY TOXICOLOGY AND PHARMACOLOGY, Vol: 112, ISSN: 0273-2300
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- Citations: 82
Vinken M, Kramer N, Allen TEH, et al., 2020, The use of adverse outcome pathways in the safety evaluation of food additives, ARCHIVES OF TOXICOLOGY, Vol: 94, Pages: 959-966, ISSN: 0340-5761
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- Citations: 9
Felter SP, Boobis AR, Botham PA, et al., 2020, Hazard identification, classification, and risk assessment of carcinogens: too much or too little? - Report of an ECETOC workshop, CRITICAL REVIEWS IN TOXICOLOGY, Vol: 50, Pages: 72-95, ISSN: 1040-8444
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- Citations: 10
Punt A, Boobis A, Cronin MT, et al., 2019, High throughput screening in the risk and benefit assessment of food ingredients, 55th Congress of the European-Societies-of-Toxicology (EUROTOX) - Toxicology - Science Providing Solutions, Publisher: ELSEVIER IRELAND LTD, Pages: S30-S30, ISSN: 0378-4274
Desprez B, Birk B, Blaauboer B, et al., 2019, A mode-of-action ontology model for safety evaluation of chemicals: Outcome of a series of workshops on repeated dose toxicity, TOXICOLOGY IN VITRO, Vol: 59, Pages: 44-50, ISSN: 0887-2333
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- Citations: 15
Kramer NI, Hoffmans Y, Wu S, et al., 2019, Characterizing the coverage of critical effects relevant in the safety evaluation of food additives by AOPs, ARCHIVES OF TOXICOLOGY, Vol: 93, Pages: 2115-2125, ISSN: 0340-5761
There is considerable interest in adverse outcome pathways (AOPs) as a means of organizing biological and toxicological information to assist in data interpretation and method development. While several chemical sectors have shown considerable progress in applying this approach, this has not been the case in the food sector. In the present study, safety evaluation reports of food additives listed in Annex II of Regulation (EC) No 1333/2008 of the European Union were screened to qualitatively and quantitatively characterize toxicity induced in laboratory animals. The resulting database was used to identify the critical adverse effects used for risk assessment and to investigate whether food additives share common AOPs. Analysis of the database revealed that often such scrutiny of AOPs was not possible or necessary. For 69% of the food additives, the report did not document any adverse effects in studies based on which the safety evaluation was performed. For the remaining 31% of the 326 investigated food additives, critical adverse effects and related points of departure for establishing health-based guidance values could be identified. These mainly involved effects on the liver, kidney, cardiovascular system, lymphatic system, central nervous system and reproductive system. AOPs are available for many of these apical endpoints, albeit to different degrees of maturity. For other adverse outcomes pertinent to food additives, including gastrointestinal irritation and corrosion, AOPs are lacking. Efforts should focus on developing AOPs for these particular endpoints.
Doe JE, Boobis AR, Dellarco V, et al., 2019, Chemical carcinogenicity revisited 2: Current knowledge of carcinogenesis shows that categorization as a carcinogen or non-carcinogen is not scientifically credible, REGULATORY TOXICOLOGY AND PHARMACOLOGY, Vol: 103, Pages: 124-129, ISSN: 0273-2300
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- Citations: 34
Wolf DC, Cohen SM, Boobis AR, et al., 2019, Chemical carcinogenicity revisited 1: A unified theory of carcinogenicity based on contemporary knowledge, REGULATORY TOXICOLOGY AND PHARMACOLOGY, Vol: 103, Pages: 86-92, ISSN: 0273-2300
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- Citations: 47
Cohen SM, Boobis AR, Dellarco VL, et al., 2019, Chemical carcinogenicity revisited 3: Risk assessment of carcinogenic potential based on the current state of knowledge of carcinogenesis in humans, REGULATORY TOXICOLOGY AND PHARMACOLOGY, Vol: 103, Pages: 100-105, ISSN: 0273-2300
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- Citations: 47
Pires SM, Boue G, Boobis A, et al., 2019, Risk Benefit Assessment of foods: Key findings from an international workshop, FOOD RESEARCH INTERNATIONAL, Vol: 116, Pages: 859-869, ISSN: 0963-9969
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- Citations: 22
Arcella D, Boobis A, Cressey P, et al., 2019, Harmonized methodology to assess chronic dietary exposure to residues from compounds used as pesticide and veterinary drug, CRITICAL REVIEWS IN TOXICOLOGY, Vol: 49, Pages: 1-10, ISSN: 1040-8444
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- Citations: 11
Schilter B, Burnett K, Eskes C, et al., 2019, Value and limitation of <i>in vitro</i> bioassays to support the application of the threshold of toxicological concern to prioritise unidentified chemicals in food contact materials, FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT, Vol: 36, Pages: 1903-1936, ISSN: 1944-0049
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- Citations: 18
Rotter S, Beronius A, Boobis AR, et al., 2018, Overview on legislation and scientific approaches for risk assessment of combined exposure to multiple chemicals: the potential EuroMix contribution, CRITICAL REVIEWS IN TOXICOLOGY, Vol: 48, Pages: 796-814, ISSN: 1040-8444
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- Citations: 66
Boobis AR, 2018, A framework for a fit-for-purpose evaluation of non-animal methods, 54th Congress of the European-Societies-of-Toxicology (EUROTOX) - Toxicology Out of the Box, Publisher: ELSEVIER IRELAND LTD, Pages: S17-S17, ISSN: 0378-4274
Aschner M, Autrup H, Berry CL, et al., 2018, Obfuscating transparency?, REGULATORY TOXICOLOGY AND PHARMACOLOGY, Vol: 97, Pages: A1-A3, ISSN: 0273-2300
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- Citations: 2
Boobis A, Safe SH, Farland W, 2018, Editorial overview: Risk assessment in toxicology, Current Opinion in Toxicology, Vol: 9, Pages: iii-v
Baker N, Boobis A, Burgoon L, et al., 2018, Building a developmental toxicity ontology, BIRTH DEFECTS RESEARCH, Vol: 110, Pages: 502-518, ISSN: 2472-1727
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- Citations: 20
Athersuch TJ, Antoine DJ, Boobis AR, et al., 2018, Paracetamol metabolism, hepatotoxicity, biomarkers and therapeutic interventions: a perspective, Toxicology Research, Vol: 7, Pages: 347-357, ISSN: 2045-452X
After over 60 years of therapeutic use in the UK, paracetamol (acetaminophen, N-acetyl-p-aminophenol, APAP) remains the subject of considerable research into both its mode of action and toxicity. The pharmacological properties of APAP are the focus of some activity, with the role of the metabolite N-arachidonoylaminophenol (AM404) still a topic of debate. However, that the hepatotoxicity of APAP results from the production of the reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI/NABQI) that can deplete glutathione, react with cellular macromolecules, and initiate cell death, is now beyond dispute. The disruption of cellular pathways that results from the production of NAPQI provides a source of potential biomarkers of the severity of the damage. Research in this area has provided new diagnostic markers such as the microRNA miR-122 as well as mechanistic biomarkers associated with apoptosis, mitochondrial dysfunction, inflammation and tissue regeneration. Additionally, biomarkers of, and systems biology models for, glutathione depletion have been developed. Furthermore, there have been significant advances in determining the role of both the innate immune system and genetic factors that might predispose individuals to APAP-mediated toxicity. This perspective highlights some of the progress in current APAP-related research.
Felter SP, Foreman JE, Boobis A, et al., 2018, Human relevance of rodent liver tumors: Key insights from a Toxicology Forum workshop on nongenotoxic modes of action, REGULATORY TOXICOLOGY AND PHARMACOLOGY, Vol: 92, Pages: 1-7, ISSN: 0273-2300
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- Citations: 40
Haber LT, Dourson ML, Allen BC, et al., 2018, Benchmark dose (BMD) modeling: current practice, issues, and challenges, CRITICAL REVIEWS IN TOXICOLOGY, Vol: 48, Pages: 387-415, ISSN: 1040-8444
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- Citations: 108
Boobis A, Parish S, Wolf D, 2017, Towards establishing a consistent set of criteria to assess the use of non-animal methods in regulatory decision making, 53rd Congress of the European-Societies-of-Toxicology (EUROTOX), Publisher: ELSEVIER IRELAND LTD, Pages: S16-S16, ISSN: 0378-4274
Boobis A, Embry M, Pastoor T, 2017, The HESI Risk 21 project: An innovative tool in risk assessment, 53rd Congress of the European-Societies-of-Toxicology (EUROTOX), Publisher: ELSEVIER IRELAND LTD, Pages: S56-S56, ISSN: 0378-4274
Boobis AR, 2017, Thresholds of Toxicological Concern for cosmetics-related substances: New database, thresholds, and enrichment of chemical space., Food and Chemical Toxicology, Vol: 109, Pages: 170-193, ISSN: 0278-6915
A new dataset of cosmetics-related chemicals for the Threshold of Toxicological Concern (TTC) approach has been compiled, comprising 552 chemicals with 219, 40, and 293 chemicals in Cramer Classes I, II, and III, respectively. Data were integrated and curated to create a database of No-/Lowest-Observed-Adverse-Effect Level (NOAEL/LOAEL) values, from which the final COSMOS TTC dataset was developed. Criteria for study inclusion and NOAEL decisions were defined, and rigorous quality control was performed for study details and assignment of Cramer classes. From the final COSMOS TTC dataset, human exposure thresholds of 42 and 7.9 μg/kg-bw/day were derived for Cramer Classes I and III, respectively. The size of Cramer Class II was insufficient for derivation of a TTC value. The COSMOS TTC dataset was then federated with the dataset of Munro and colleagues, previously published in 1996, after updating the latter using the quality control processes for this project. This federated dataset expands the chemical space and provides more robust thresholds. The 966 substances in the federated database comprise 245, 49 and 672 chemicals in Cramer Classes I, II and III, respectively. The corresponding TTC values of 46, 6.2 and 2.3 μg/kg-bw/day are broadly similar to those of the original Munro dataset.
Boobis A, Cerniglia C, Chicoine A, et al., 2017, Characterizing chronic and acute health risks of residues of veterinary drugs in food: latest methodological developments by the joint FAO/WHO expert committee on food additives., Critical Reviews in Toxicology, Vol: 47, Pages: 885-899, ISSN: 1040-8444
The risk assessment of residues of veterinary drugs in food is a field that continues to evolve. The toxicological end-points to be considered are becoming more nuanced and in light of growing concern about the development of antimicrobial resistance, detailed analysis of the antimicrobial activity of the residues of veterinary drugs in food is increasingly incorporated in the assessment. In recent years, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has refined its approaches to provide a more comprehensive and fit-for-purpose risk assessment. This publication describes in detail the consideration of acute and chronic effects, the estimation of acute and chronic dietary exposure, current approaches for including microbiological endpoints in the risk assessment, and JECFA's considerations for the potential effects of food processing on residues from veterinary drugs. JECFA now applies these approaches in the development of health-based guidance values (i.e. safe exposure levels) for residues of veterinary drugs. JECFA, thus, comprehensively addresses acute and chronic risks by using corresponding estimates for acute and chronic exposure and suitable correction for the limited bioavailability of bound residues by the Gallo-Torres model. On a case-by-case basis, JECFA also considers degradation products that occur from normal food processing of food containing veterinary drug residues. These approaches will continue to be refined to ensure the most scientifically sound basis for the establishment of health-based guidance values for veterinary drug residues.
Bhat VS, Meek MEB, Valcke M, et al., 2017, Evolution of chemical-specific adjustment factors (CSAF) based on recent international experience; increasing utility and facilitating regulatory acceptance., Critical Reviews in Toxicology, Vol: 47, Pages: 729-749, ISSN: 1040-8444
The application of chemical-specific toxicokinetic or toxicodynamic data to address interspecies differences and human variability in the quantification of hazard has potential to reduce uncertainty and better characterize variability compared with the use of traditional default or categorically-based uncertainty factors. The present review summarizes the state-of-the-science since the introduction of the World Health Organization/International Programme on Chemical Safety (WHO/IPCS) guidance on chemical-specific adjustment factors (CSAF) in 2005 and the availability of recent applicable guidance including the WHO/IPCS guidance on physiologically-based pharmacokinetic (PBPK) modeling in 2010 as well as the U.S. EPA guidance on data-derived extrapolation factors in 2014. A summary of lessons learned from an analysis of more than 100 case studies from global regulators or published literature illustrates the utility and evolution of CSAF in regulatory decisions. Challenges in CSAF development related to the adequacy of, or confidence in, the supporting data, including verification or validation of PBPK models. The analysis also identified issues related to adequacy of CSAF documentation, such as inconsistent terminology and often limited and/or inconsistent reporting, of both supporting data and/or risk assessment context. Based on this analysis, recommendations for standardized terminology, documentation and relevant interdisciplinary research and engagement are included to facilitate the continuing evolution of CSAF development and guidance.
Boobis A, Brown P, Cronin MTD, et al., 2017, Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and an approach for their re-evaluation, CRITICAL REVIEWS IN TOXICOLOGY, Vol: 47, Pages: 705-727, ISSN: 1040-8444
Bus JS, 2017, “The dose makes the poison”: Key implications for mode of action (mechanistic) research in a 21st century toxicology paradigm, Current Opinion in Toxicology, Vol: 3, Pages: 87-91
The concept of “the dose makes the poison” is a core organizing tenet of toxicology, and associated investigations of mode of action (MoA) are a key means by which toxicity test data are translated to robust evidence-based human health risk assessments. As such, toxicology is responsible for providing the science and leadership assuring that dose considerations are fully integrated into design and interpretation of toxicity testing and MoA datasets. Such considerations are likely to impact MoA research in that many such investigations are not justified, if at all, when toxicity is noted only under conditions of excessively high-dose testing that is not quantitatively relevant to human risk, e.g., test dose(s) above onset of nonlinear ADME behavior; in vitro test concentrations not biologically attainable in vivo. Toxicology must also challenge continued use of the Linear-No-Threshold (LNT) hypothesis as a biologically-valid dose-response model for cancer risk assessment in that decades of modern biology has increasingly exposed its flawed fundamental assumption that biology has no compensatory homeostatic mechanisms protecting against low exposures. Thus, expanded attention to “dose” is essential in order for toxicology to fulfill its promise as a credible 21st century science protecting public health in an increasingly chemical technology-dependent world.
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