Use of toxicokinetics to support chemical evaluation: Informing high dose selection and study interpretation
Abstract
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 TK information in new and draft OECD test guidelines. To help promote increased consideration of the important role TK can play in chemical risk assessment, we have gathered practical examples from the peer-reviewed literature, as well as in-house industry data, that highlight opportunities for the use of TK in the selection of dose levels. Use of TK can help to ensure studies are designed to be of most relevance to assessing potential risk in humans, and avoid the use of excessively high doses that could result in unnecessary suffering in experimental animals. Greater emphasis on the potential contribution of TK in guiding study design and interpretation should be incorporated in regulatory data requirements and associated guidance.
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Differences in physiology, anatomy, and behavior between test species and humans can lead to positive or negative findings that may not accurately reflect human responses.
“Differences in physiology (toxicokinetics, toxicodynamics, nutritional requirements, and other biochemical characteristics), anatomical structure, and behavior can lead to positive or negative findings that may not accurately reflect human responses”
From The use of whole food animal studies in the safety assessment of genetically modified crops: Limitations and recommendations (2013) · cites this paper as Creton et al., 2012
Animal toxicology studies intended for human risk assessment have inherent limitations and challenges due to the use of a surrogate species and relatively small numbers of animals in each study group.
“It is recognized that animal toxicology studies intended for human risk assessment have inherent limitations and challenges due to the use of a surrogate species and relatively small numbers of animals in each study group.”
From The use of whole food animal studies in the safety assessment of genetically modified crops: Limitations and recommendations (2013) · cites this paper as Creton et al., 2012
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“…characteristics), anatomical structure, and behavior can lead to positive or negative findings that may not accurately reflect human responses; however, toxicology study design seeks to overcome these limitations by utilizing compensatory design elements (Creton et al., 2012; Gad, 2007).”
Background
- Authors
- Creton, S., Saghir, S. A., Bartels, M. J., Billington, R., Bus, J. S., Davies, W., Dent, M. P., Hawksworth, G. M., Parry, S., & Travis, K. Z.
- Affiliations
- National Centre for the Replacement Refinement and Reduction of Animals in Research (GB)
- Dow Chemical (United States) (US)
- Dow Agrosciences (United Kingdom) (GB)
- Unilever (United Kingdom) (GB)
- University of Aberdeen (GB)
- GlaxoSmithKline (United Kingdom) (GB)
- Syngenta (United Kingdom) (GB)
- Corresponding author
- Creton, Stuart
- Venue
- Regulatory Toxicology and Pharmacology
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 62
- Issue
- 2
- Pages
- 241-247
- ISSN
- 0273-2300 (ISSN-L)
- OpenAlex
- W1991029540
- Cited by
- 47
- References
- 22
- Citations by year
- 2024: 4 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 6 · 2018: 1 · 2017: 5 · 2016: 3 · 2015: 8 · 2014: 2 · 2013: 6 · 2012: 3
- FWCI
- 4.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Regulatory Toxicology and Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Life Sciences › Agricultural and Biological Sciences › Food Science › Agricultural safety and regulations
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- toxicokinetics, dose selection, chemical risk assessment, research design, study interpretation, animal welfare, regulatory data requirements, OECD test guidelines, agrochemicals, consumer goods
- MeSH terms
- Animals, Dose-Response Relationship, Drug, Female, Humans, Male, Pharmacokinetics, Research Design, Guidelines as Topic, Risk Assessment, Rats
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