Toxicology and regulatory sciences bibliography and resources
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Acute toxicity testing
Adoption of the Fixed Concentration Procedure (FCP) for acute inhalation studies
Sewell F et al, (2018). An evaluation of the fixed concentration procedure for assessment of acute inhalation toxicity. Regulatory Toxicology and Pharmacology 94: 22-32. doi: 10.1016/j.yrtph.2018.01.001
OECD (2017). Test no. 433: Acute Inhalation Toxicity: Fixed Concentration Procedure. OECD Publishing, Paris. doi: 10.1787/9789264284166-en
Sewell F et al, (2015). A global initiative to refine acute inhalation studies through the use of ‘evident toxicity’ as an endpoint: towards adoption of the fixed concentration procedure. Regulatory Toxicology and Pharmacology 73(3): 770-9. doi: 10.1016/j.yrtph.2015.10.018
Price C et al, (2011). A statistical evaluation of the effects of gender differences in assessment of acute inhalation toxicity. Human and Experimental Toxicology 30(3): 217-238. doi: 10.1177/0960327110370982
Stallard N et al, (2011). A new sighting study for the fixed concentration procedure to allow for gender differences. Human and Experimental Toxicology 30(3): 239-249. doi: 10.1177/0960327110370983
Applying the 3Rs in fish acute toxicity studies
Katsiadaki I et al, (2021). Dying for change: A roadmap to refine the fish acute toxicity test after 40 years of applying a lethal endpoint. Ecotoxicology and Environmental Safety 223:112585. doi: 10.1016/j.ecoenv.2021.112585
Burden N et al, (2020). Key opportunities to replace, reduce and refine regulatory fish acute toxicity tests. Environmental Toxicology and Chemistry doi: 10.1002/etc.4824
Burden N et al, (2016). The utility of QSARs in predicting acute fish toxicity of pesticide metabolites: A retrospective validation approach. Regulatory Toxicology and Pharmacology 80:241-6. doi: 10.1016/j.yrtph.2016.05.032
Creton S et al, (2014). Application of the threshold approach for acute fish toxicity testing to plant protection products: a proposed framework. Chemosphere 96: 195-200. doi: 10.1016/j.chemosphere.2013.10.015
Redundancy in the acute toxicity testing of chemicals
Moore NP et al, (2013). Can acute dermal systemic toxicity tests be replaced with oral tests? A comparison of route-specific systemic toxicity and hazard classifications under the Globally Harmonized System of Classification and Labelling of Chemicals (GHS). Regulatory Toxicology and Pharmacology 66(1): 30-7. doi: 10.1016/j.yrtph.2013.02.005
Creton S et al, (2010). Acute toxicity testing of chemicals – Opportunities to avoid redundant testing and use alternative approaches. Critical Reviews in Toxicology 40: 50-83. doi: 10.3109/10408440903401511
Seidle T et al, (2010). Cross-sector review of drivers and available 3Rs approaches for acute systemic toxicity testing. Toxicological Sciences 116(2): 382-396. doi: 10.1093/toxsci/kfq143
Single dose acute toxicity studies for new medicines
Chapman K et al, (2010). The value of acute toxicity studies to support the clinical management of overdose and poisoning: a cross-discipline consensus. Regulatory Toxicology and Pharmacology 58(3): 354-359. doi: 10.1016/j.yrtph.2010.07.003
Robinson S and Chapman K (2009). Are acute toxicity studies required to support overdose for new medicines? Regulatory Toxicology and Pharmacology 55(1): 110. doi: 10.1016/j.yrtph.2009.06.012
Robinson S et al, (2008). A European pharmaceutical company initiative challenging the regulatory requirement for acute toxicity studies in pharmaceutical drug development. Regulatory Toxicology and Pharmacology 50(3): 345-352. doi: 10.1016/j.yrtph.2007.11.009
Chapman K and Robinson S (2007). Workshop Report: Challenging the regulatory requirement for acute toxicity studies in the development of new medicines. NC3Rs, London.
Animals in environmental safety testing
Applying the one concentration approach in fish bioaccumulation studies
Burden N et al, (2017). Reducing the number of fish in regulatory bioconcentration testing: Identifying and overcoming the barriers to using the 1-concentration approach. Integrated Environmental Assessment and Management 13(1): 212-4. doi: 10.1002/ieam.1851
Creton S et al, (2013). Reducing the number of fish in bioconcentration studies for plant protection products by reducing the number of test concentrations. Chemosphere 90(3): 1300-4. doi: 10.1016/j.chemosphere.2012.09.029
Applying the 3Rs in non-mammalian endocrine disruptor testing
Ortego L et al, (2021). The Extended Amphibian Metamorphosis Assay (EAMA): A thyroid-specific and less animal-intensive alternative to the Larval Amphibian Growth and Development Assay (LAGDA, OECD TG 241). Environmental Toxicology and Chemistry 40(8):2135-2144. doi: 10.1002/etc.5078
Burden N et al, (2021). Investigating endocrine disrupting properties of chemicals in fish and amphibians: opportunities to apply the 3Rs. Integrated Environmental Assessment and Management doi: 10.1002/ieam.4497
Wheeler JR et al, (2021). Hormone data collection in support of endocrine disruption (ED) assessment for aquatic vertebrates: Pragmatic and animal welfare considerations. Environ International 146:106287. doi: 10.1016/j.envint.2020.106287
Lagadic L et al, (2019). Recommendations for reducing the use of fish and amphibians in endocrine-disruption testing of biocides and plant protection products in Europe. Integrated Environmental Assessment and Management 15: 659-662. doi: 10.1002/ieam.4156
Assessing the need for chronic fish studies on formulated pesticides
Creton S et al, (2010). Challenging the requirement for chronic fish toxicity studies on formulated plant protection products. Toxicology Letters 199(2): 111-4. doi: 10.1016/j.toxlet.2010.08.019
Reducing repetition of regulatory vertebrate ecotoxicology studies
Burden N et al, (2017). Reducing repetition of regulatory vertebrate ecotoxicology studies. Integrated Environmental Assessment and Management 13(5) 955-7. doi: 10.1002/ieam.1934
Reviews / Other / Miscellaneous
Burden N et al, (2016). Advancing the 3Rs in regulatory ecotoxicology: A pragmatic cross-sector approach. Integrated Environmental Assessment and Management 12(3): 417-421. doi: 10.1002/ieam.1703
Lillicrap A et al, (2016). Alternative approaches to vertebrate ecotoxicity tests in the 21st century: A review of developments over the last 2 decades and current status. Environmental Toxicology and Chemistry 35(11): 2637-2646. doi: 10.1002/etc.3603
Hutchinson TH et al, (2015). Promoting the 3Rs to enhance the OECD fish toxicity testing framework. Regulatory Toxicology and Pharmacology 76: 231-3. doi: 10.1016/j.yrtph.2016.02.006
Burden N and Hutchinson TH (2015). Benefits of the ARRIVE Guidelines for improving scientific reporting in ecotoxicology – An academic perspective. Environmental Toxicology and Chemistry 34(11): 2446-8. doi: 10.1002/etc.3111
Exposure and dose selection
Applying exposure science to increase the utility of non-animal data in efficacy and safety testing
Sewell F et al, (2017). The current status of exposure-driven approaches for chemical safety assessment: A cross-sector perspective. Toxicology 389: 109-117. doi: 10.1016/j.tox.2017.07.018
NC3Rs/Unilever (2017). Workshop report: Applying exposure science to increase the utility of non-animal data in efficacy and safety testing. NC3Rs/Unilever, London.
Rowbotham AL and Gibson RM (2011). Exposure-driven risk assessment: Applying exposure-based waiving of toxicity tests under REACH. Food and Chemical Toxicology 49(8): 1661-1673. doi: 10.1016/j.fct.2011.03.050
Pharmacokinetics in candidate selection
Beaumont K et al, (2011). Towards an integrated human clearance prediction strategy that minimizes animal use. Journal of Pharmaceutical Sciences 100:1167–1783. doi: 10.1002/jps.22635
Lave T et al, (2009). Human clearance prediction: shifting the paradigm. Expert Opinion on Drug Metabolism & Toxicology 5(9): 1039-1048. doi: 10.1517/17425250903099649
Refining MTD studies
ECETOC Guidance on Dose Selection (2020). Technical report 138, Brussels, March 2021. ISSN-2079-1526-138.
Chapman K et al, (2013). A global pharmaceutical company initiative: An evidence-based approach to define the upper limit of body weight loss in short term toxicity studies. Regulatory Toxicology and Pharmacology 67(1): 27-38. doi: 10.1016/j.yrtph.2013.04.003
Robinson S et al, (2009). Guidance on dose level selection for regulatory general toxicology studies for pharmaceuticals. NC3Rs/LASA, London.
Toxicokinetics in the chemicals industry
Tan YM et al, (2021). Opportunities and challenges related to saturation of toxicokinetic processes: implications for risk assessment. Regulatory Toxicology and Pharmacology 127: 105070. doi: 10.1016/j.yrtph.2021.105070
Sewell F et al, (2020). Use of the kinetically-derived maximum dose: Opportunities for delivering 3Rs benefits. Regulatory Toxicology and Pharmacology. 116:104734. doi: 10.1016/j.yrtph.2020.104734
Creton S et al, (2012). Use of toxicokinetics to support chemical evaluation: Informing high dose selection and study interpretation. Regulatory Toxicology and Pharmacology 62(2): 241-7. doi: 10.1016/j.yrtph.2011.12.005
Creton S et al, (2009). Application of toxicokinetics to improve chemical risk assessment: Implications for the use of animals. Regulatory Toxicology and Pharmacology 55: 291-9. doi: 10.1016/j.yrtph.2009.08.001
Burden N et al, (2015). Pioneering better science through the 3Rs: An introduction to the National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs). Journal of the American Association for Laboratory Animal Science 54(2): 198-208.
Holmes AM et al, (2010). Working in partnership to advance the 3Rs in toxicity testing. Toxicology 267(1-3): 14-9. doi: 10.1016/j.tox.2009.11.006
New approach methodologies (NAMs) in toxicology
Application of non-animal approaches for decision making in chemical safety assessment
Sewell F et al, (2021). Rethinking Agrochemical Safety Assessment: A Perspective. Regulatory Toxicology and Pharmacology 127:105068. doi: 10.1016/j.yrtph.2021.105068
LaLone C et al, (2021). International consortium to advance cross species extrapolation of the effects of chemicals in regulatory toxicology. Environmental Toxicology and Chemistry. 126: e105029. doi: 10.1002/etc.5214
Prior H et al, (2019). Reflections on the progress towards non-animal methods for acute toxicity testing of chemicals. Regulatory Toxicology and Pharmacology 102 30-3. doi: 10.1016/j.yrtph.2018.12.008
Hoffmann S et al, (2018). Non-animal methods to predict skin sensitization (I): the Cosmetics Europe database. Critical Reviews in Toxicology 48: 344-358. doi: 10.1080/10408444.2018.1429385
Kleinstreuer NC et al, (2018). Non-animal methods to predict skin sensitization (II): an assessment of defined approaches. Critical Reviews in Toxicology 48: 359-374. doi: 10.1080/10408444.2018.1429386
van Vliet E et al, (2018). State-of-the-art and new options to assess T cell activation by skin sensitizers: Cosmetics Europe Workshop. ALTEX 35: 179-192. doi: 10.14573/altex.1709011
Sewell F et al, (2017). Steps towards the international regulatory acceptance of non-animal methodology in safety assessment. Regulatory Toxicology and Pharmacology 89: 50-6. doi: 10.1016/j.yrtph.2017.07.001
Burden N et al, (2015). Testing chemical safety: What is needed to ensure the widespread application of non-animal approaches? PLoS Biology 13(5): e1002156. doi: 10.1371/journal.pbio.1002156
Burden N et al, (2015). Aligning the 3Rs with new paradigms in the safety assessment of chemicals. Toxicology 330: 62-6. doi: 10.1016/j.tox.2015.01.014
Adler S et al, (2011). Alternative (non-animal) methods for cosmetics testing: current status and future prospects – 2010. Archives of Toxicology 85(5): 367-485. doi: 10.1007/s00204-011-0693-2
In vitro approaches for carcinogenicity testing
Luijten M et al, (2020). A comprehensive view on mechanistic approaches for cancer risk assessment of non-genotoxic agrochemicals. Regulatory Toxicology and Pharmacology. 118: 104789. doi: 10.1016/j.yrtph.2020.104789
Creton S et al, (2012). Cell transformation assays for prediction of carcinogenic potential: state of the science and future research needs. Mutagenesis 27(1): 93-101. doi: 10.1093/mutage/ger053
Modelling and computational approaches
Gellatly N and Sewell F (2019). Regulatory acceptance of in silico approaches for the safety assessment of cosmetic-related substances. Computational Toxicology 11: 82-9. doi: 10.1016/j.comtox.2019.03.003
Hasselgren C et al, (2019). Genetic toxicology in silico protocol. Regulatory Toxicology and Pharmacology, 107: 104403. doi: 10.1016/j.yrtph.2019.104403
Myatt GJ et al, (2018). In silico toxicology protocols. Regulatory Toxicology and Pharmacology 96: 1-17. doi: 10.1016/j.yrtph.2018.04.014
Pathways based approaches
Rivetti C et al, (2020). Vision of a near future: Bridging the human health-environment divide. Toward an integrated strategy to understand mechanisms across species for chemical safety assessment. Toxicology In Vitro 62: 104692. doi: 10.1016/j.tiv.2019.104692
Sewell F et al, (2018). The future trajectory of adverse outcome pathways: a commentary. Archives of Toxicology 92(4): 1657-1661. doi: 10.1007/s00204-018-2183-2
Burden N et al, (2015). Adverse Outcome Pathways can drive non-animal approaches for safety assessment. Journal of Applied Toxicology 35(9): 971-975. doi: 10.1002/jat.3165
Reducing animal use in the safety assessment of nanomaterials
Burden N et al,(2021). Opportunities and Challenges for Integrating New In Vitro Methodologies in Hazard Testing and Risk Assessment. Small. (15):e2006298. doi: 10.1002/smll.202006298
Burden N et al, (2017). The 3Rs as a framework to support a 21st century approach for nanosafety assessment. Nano Today 12: 10-13. doi: 10.1016/j.nantod.2016.06.007
Burden N et al, (2017). Aligning nanotoxicology with the 3Rs: What is needed to realise the short, medium and long-term opportunities? Regulatory Toxicology and Pharmacology 91: 257-266. doi: 10.1016/j.yrtph.2017.10.021
Use of human or engineered tissues in safety assessment
Jackson SJ et al, (2018). The use of human tissue in safety assessment. Journal of Pharmacological and Toxicological Methods 93:29-34. doi: 10.1016/j.vascn.2018.05.003
Holmes A et al, (2017). Rising to the challenge: applying biofabrication approaches for better drug and chemical product development. Biofabrication 9: 033001. doi: 10.1088/1758-5090/aa7bbd
Holmes A et al, (2015). Assessing drug safety in human tissues — what are the barriers? Nature Reviews Drug Discovery 14: 585–7 (2015). doi: 10.1038/nrd4662
Westmoreland C and Holmes A (2009). Assuring consumer safety without animals: Applications for tissue engineering. Organogenesis 5: 67-72. doi: 10.4161/org.5.2.9128
Holmes A et al, (2009). Engineering tissue alternatives to animals: applying tissue engineering to basic research and safety testing. Regenerative Medicine 4: 572-92. doi.org/10.2217/rme.09.26
Abuse potential studies
O'Connor E et al, (2011). The predictive validity of the rat self-administration model for abuse liability. Neuroscience & Biobehavioral Reviews 35(3): 912-938. doi: 10.1016/j.neubiorev.2010.10.012
Assessing the predictive value of safety pharmacology studies
Jackson SJ et al, (2019). Neurofunctional test batteries in safety pharmacology – Current and emerging considerations for the drug development process. Journal of Pharmacological and Toxicological Methods 100: 106602 doi: 10.1016/j.vascn.2019.106602
Redfern WS et al, (2019). The functional observational battery and modified Irwin test as global neurobehavioral assessments in the rat: Pharmacological validation data and a comparison of methods. Journal of Pharmacological and Toxicological Methods 98: 106591 doi: 10.1016/j.vascn.2019.106591
Mead AN et al, (2016). Assessing the predictive value of the rodent neurofunctional assessment for commonly reported adverse events in phase I clinical trials. Regulatory Toxicology and Pharmacology. 80: 348-357. doi: 10.1016/j.yrtph.2016.05.002
Social housing during rodent and non-rodent telemetry recordings
Prior H and Holbrook M (2021). Strategies to encourage the adoption of social housing during cardiovascular telemetry recordings in non-rodents. Journal of Pharmacological and Toxicological Methods 108: 106959. doi: 10.1016/j.vascn.2021.106959
Skinner M et al, (2019). Social-housing and use of double-decker cages in rat telemetry studies. Journal of Pharmacological and Toxicological Methods 96: 87-94. doi: 10.1016/j.vascn.2019.02.005
Prior H et al, (2016). Social housing of non-rodents during cardiovascular recordings in safety pharmacology and toxicology studies. Journal of Pharmacological and Toxicological Methods 81: 75-87. doi: 10.1016/j.vascn.2016.03.004
Reviews / Other
Guns PJ et al, (2020). INSPIRE: A European training network to foster research and training in cardiovascular safety pharmacology. Journal of Pharmacological and Toxicological Methods 105: 106889. doi: 10.1016/j.vascn.2020.106889
Saleem U et al, (2020). Blinded, Multicenter Evaluation of Drug-induced Changes in Contractility Using Human-induced Pluripotent Stem Cell-derived Cardiomyocytes. Toxicological Sciences 176: 103–123. doi: 10.1093/toxsci/kfaa058
Tse K et al, (2018). Pharmacological validation of individual animal locomotion, temperature and behavioural analysis in group-housed rats using a novel automated home cage analysis system: A comparison with the modified Irwin test. Journal of Pharmacological and Toxicological Methods 94: 1-13. https://doi.org/10.1016/j.vascn.2018.03.008
Grant C et al, (2017). Provision of food and water in rodent whole body plethysmography safety pharmacology respiratory studies - Impact on animal welfare and data quality. Journal of Pharmacological and Toxicological Methods. 88: 79-84. doi: 10.1016/j.vascn.2017.07.004
Redfern W et al, (2017). Automated recording of home cage activity and temperature of individual rats housed in social groups: The Rodent Big Brother. PLoS One 12(9): e0181068. doi: 10.1371/journal.pone.0181068
Study designs for pharmaceutical and chemical development
Maximising the success of bile duct cannulation (BDC) studies
Burden N et al, (2017). Maximizing the success of bile duct cannulation studies in rats: recommendations for best practice. Laboratory Animals 51(5): 457-464. doi: 10.1177/0023677217698001.
Coleman D et al, (2017). Capillary microsampling in nonclinical safety assessment: practical sampling and bioanalysis from a CRO perspective. Bioanalysis 9(10): 787-798. doi: 10.4155/bio-2017-0032
Chapman K et al, (2014). Overcoming the barriers to the uptake of nonclinical microsampling in regulatory safety studies. Drug Discovery Today 19(5): 528-532. doi: 10.1016/j.drudis.2014.01.002.
Chapman K et al, (2014). Reducing pre-clinical blood volumes for toxicokinetics: toxicologists, pathologists and bioanalysts unite. Bioanalysis 6(22): 2965-8. doi: 10.4155/bio.14.204.
Reducing animal use in monoclonal antibody (mAb) development
Sewell F et al, (2017). Challenges and opportunities for the future use of monoclonal antibody development: improving safety assessment and reducing animal use. mAbs 9(5): 742-755. doi: 10.1080/19420862.2017.1324376.
Chapman K et al, (2016). Waiving in vivo studies for monoclonal antibody biosimilar development: National and global challenges. mAbs 8(3): 427-435. doi: 10.1080/19420862.2016.1145331.
Chapman KL et al, (2012). The design of chronic toxicology studies of monoclonal antibodies: implications for the reduction in use of non-human primates. Regulatory Toxicology and Pharmacology 62(2): 347-354. doi: 10.1016/j.yrtph.2011.10.016.
Buckley LA et al, (2011). Considerations regarding nonhuman primate use in safety assessment of biopharmaceuticals. International Journal of Toxicology 30(5): 583-590. doi: 10.1177/1091581811415875.
Chapman KL et al, (2010). The future of non-human primate use in mAb development. Drug Discovery Today 15(5-6): 235-242. doi: 10.1016/j.drudis.2010.01.002.
Chapman K et al, (2009). Preclinical development of monoclonal antibodies: considerations for the use of non-human primates. mAbs 1(5): 505-516. doi: 10.4161/mabs.1.5.9676.
Chapman K et al, (2007). Preclinical safety testing of monoclonal antibodies: the significance of species relevance. Nature Reviews Drug Discovery 6(2): 120-6. doi: 10.1038/nrd2242.
NC3Rs/ABPI (2006). Workshop report: Opportunities for reducing the use of non-human primates in the development of monoclonal antibodies. NC3Rs/ABPI, London.
Reducing the use of recovery animals
Sewell F et al, (2014). Recommendations from a global cross-company data sharing initiative on the incorporation of recovery phase animals in safety assessment studies to support first-in-human clinical trials. Regulatory Toxicology and Pharmacology 70(1): 413-429. doi: 10.1016/j.yrtph.2014.07.018.
Review of the use of two species
Namdari R et al, (2021). Species selection for nonclinical safety assessment of drug candidates: Examples of current industry practice. Regulatory Toxicology and Pharmacology 126: 105029. doi: 10.1016/j.yrtph.2021.105029.
Prior H et al, (2020). Justification for species selection for pharmaceutical toxicity studies. Toxicology Research 9: 758-770. doi: 10.1093/toxres/tfaa081.
Prior H et al, (2020). Opportunities for use of one species for longer-term toxicology testing during drug development: A cross-industry evaluation. Regulatory Toxicology and Pharmacology 113: 104624. doi: 10.1016/j.yrtph.2020.104624.
Prior H et al, (2019). Integration of consortia recommendations for justification of animal use within current and future drug development paradigms. International Journal of Toxicology 38(4), 319–325. doi: 10.1177/1091581819852922.
Prior H et al, (2018). Reviewing the utility of two species in general toxicology related to drug development. International Journal of Toxicology 37(2): 121-4. doi: 10.1177/1091581818760564.
Reviews / Other
Prior H et al, (2021). Refining Procedures within Regulatory Toxicology Studies: Improving Animal Welfare and Data. Animals 11: 3057. doi: 10.3390/ani11113057.
Sewell F et al, (2021). Preclinical screening for antidepressant activity – shifting focus away from the Forced Swim Test to the use of translational biomarkers. Regulatory Toxicology and Pharmacology 125:105002. doi: 10.1016/j.yrtph.2021.105002.
Lilley E et al, (2021). Integrating 3Rs approaches in WHO guidelines for the batch release testing of biologicals. Biologicals 74: 24-27. doi: 10.1016/j.biologicals.2021.10.002
Clements JM et al, (2020). Predicting the Safety of Medicines in Pregnancy: a Workshop Report. Reproductive Toxicology, S0890-6238(20)30024-1. doi: 10.1016/j.reprotox.2020.02.011.
NC3Rs (2019). Workshop report: Applying the 3Rs in pharma: Improving delivery of innovative medicines to patients. NC3Rs, London.
Prior H et al, (2018). Overview of 3Rs opportunities in drug discovery and development using non-human primates. Drug Discovery Today: Disease Models 23, 11-16. doi: 10.1016/j.ddmod.2017.11.005.
Sewell F et al, (2016). Opportunities to apply the 3Rs in safety assessment programs. Institute for Laboratory Animal Research Journal 57(2): 234-245. doi: 10.1093/ilar/ilw024.
Chapman KL et al, (2013). Pharmaceutical toxicology: designing studies to reduce animal use, while maximizing human translation. Regulatory Toxicology and Pharmacology 66(1): 88-103. doi: 10.1016/j.yrtph.2013.03.001.
Sparrow SS et al, (2011). Opportunities to minimise animal use in pharmaceutical regulatory general toxicology: A cross company review. Regulatory Toxicology and Pharmacology 61(2): 222-9. doi: 10.1016/j.yrtph.2011.08.001.