Guidance Notes for Analysis and Evaluation of Chronic Toxicity and Carcinogenicity Studies

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doi:10.1787/9789264078499-en

Cited by 8 publications

(1 citation statement)

References 60 publications

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“…The association in rats of caloric consumption, the spontaneous formation of tumours and life span is well established. Although the zero-dose group may be expected to control for the influence of diet, dietary constituents may still profoundly affect the outcome of an experiment (OECD, 2002).…”

mentioning

confidence: 99%

Guidance Document 116 on the Conduct and Design of Chronic Toxicity and Carcinogenicity Studies, Supporting Test Guidelines 451, 452 and 453

2014

OECD Series on Testing and Assessment

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Biomarker: A characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.Carcinogenicity: Substances are defined as carcinogenic if they induce tumours (benign or malignant), increase its incidence or shorten the time of tumour, when inhaled, ingested, dermally applied or injected. CES: Critical Effect SizeChronic Toxicity: Toxicity (adverse effect) after an exposure period of 12 months or longer due to a test article that has been ingested inhaled, dermally applied or injected.

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confidence: 99%

Guidance Document 116 on the Conduct and Design of Chronic Toxicity and Carcinogenicity Studies, Supporting Test Guidelines 451, 452 and 453

2014

OECD Series on Testing and Assessment

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Biomarkers for Environmental Exposure

Gallagher¹,

Hubal²,

Edwards³

2010

Biomarkers

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Recommendations on dose level selection for repeat dose toxicity studies

Sewell

Green²,

Andrus

et al. 2022

Arch Toxicol

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Prior to registering and marketing any new pharmaceutical, (agro)chemical or food ingredient product manufacturers must, by law, generate data to ensure human safety. Safety testing requirements vary depending on sector, but generally repeat-dose testing in animals form the basis for human health risk assessments. Dose level selection is an important consideration when designing such studies, to ensure that exposure levels that lead to relevant hazards are identified. Advice on dose level selection is provided in test guidelines and allied guidance documents, but it is not well harmonised, particularly for selection of the highest dose tested. This paper further builds on concepts developed in a technical report by the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) which recommends pragmatic approaches to dose selection considering regulatory requirements, animal welfare and state of the art scientific approaches. Industry sectors have differing degrees of freedom to operate regarding dose level selection, depending on the purpose of the studies and the regulatory requirements/legislation, and this is reflected in the overall recommended approaches. An understanding of systemic exposure should be utilised where possible (e.g., through toxicokinetic approaches) and used together with apical endpoints from existing toxicity studies to guide more appropriate dose level selection. The highest dose should be limited to a reasonable level, causing minimal but evident toxicity to the test animals without significantly compromising their well-being. As the science of predictive human exposure further develops and matures, this will provide exciting and novel opportunities for more human-relevant approaches to dose level selection.

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Guidance Notes for Analysis and Evaluation of Chronic Toxicity and Carcinogenicity Studies

Cited by 8 publications

References 60 publications

Guidance Document 116 on the Conduct and Design of Chronic Toxicity and Carcinogenicity Studies, Supporting Test Guidelines 451, 452 and 453

Guidance Document 116 on the Conduct and Design of Chronic Toxicity and Carcinogenicity Studies, Supporting Test Guidelines 451, 452 and 453

Biomarkers for Environmental Exposure

Recommendations on dose level selection for repeat dose toxicity studies

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