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Food and Chemical Toxicology : An... Feb 2023Aspartame has been studied extensively and evaluated for its safety in foods and beverages yet concerns for its potential carcinogenicity have persisted, driven... (Review)
Review
Aspartame has been studied extensively and evaluated for its safety in foods and beverages yet concerns for its potential carcinogenicity have persisted, driven primarily by animal studies conducted at the Ramazzini Institute (RI). To address this controversy, an updated systematic review of available human, animal, and mechanistic data was conducted leveraging critical assessment tools to consider the quality and reliability of data. The evidence base includes 12 animal studies and >40 epidemiological studies reviewed by the World Health Organization which collectively demonstrate a lack of carcinogenic effect. Assessment of >1360 mechanistic endpoints, including many guideline-based genotoxicity studies, demonstrate a lack of activity associated with endpoints grouped to key characteristics of carcinogens. Other non-specific mechanistic data (e.g., mixed findings of oxidative stress across study models, tissues, and species) do not provide evidence of a biologically plausible carcinogenic pathway associated with aspartame. Taken together, available evidence supports that aspartame consumption is not carcinogenic in humans and that the inconsistent findings of the RI studies may be explained by flaws in study design and conduct (despite additional analyses to address study limitations), as acknowledged by authoritative bodies.
Topics: Animals; Humans; Aspartame; Carcinogenesis; Carcinogenicity Tests; Carcinogens; Reproducibility of Results; Sweetening Agents
PubMed: 36493943
DOI: 10.1016/j.fct.2022.113549 -
IARC Monographs on the Evaluation of... 2012
Topics: Animals; Carcinogenicity Tests; Drug-Related Side Effects and Adverse Reactions; Humans; Neoplasms
PubMed: 23189749
DOI: No ID Found -
Report on Carcinogens : Carcinogen... 2011
Topics: Animals; Carcinogenicity Tests; Carcinogens, Environmental; Environmental Exposure; Humans; Mice; Mirex; Molecular Structure; Occupational Exposure; Rats
PubMed: 21860486
DOI: No ID Found -
Regulatory Toxicology and Pharmacology... Dec 2021Agrochemical safety assessment has traditionally relied on the use of animals for toxicity testing, based on scientific understanding and test guidelines developed in... (Review)
Review
Agrochemical safety assessment has traditionally relied on the use of animals for toxicity testing, based on scientific understanding and test guidelines developed in the 1980s. However, since then, there have been significant advances in the toxicological sciences that have improved our understanding of mechanisms underpinning adverse human health effects. The time is ripe to 'rethink' approaches used for human safety assessments of agrochemicals to ensure they reflect current scientific understanding and increasingly embrace new opportunities to improve human relevance and predictivity, and to reduce the reliance on animals. Although the ultimate aim is to enable a paradigm shift and an overhaul of global regulatory data requirements, there is much that can be done now to ensure new opportunities and approaches are adopted and implemented within the current regulatory frameworks. This commentary reviews current initiatives and emerging opportunities to embrace new approaches to improve agrochemical safety assessment for humans, and considers various endpoints and initiatives (including acute toxicity, repeat dose toxicity studies, carcinogenicity, developmental and reproductive toxicity, exposure-driven approaches, inhalation toxicity, and data modelling). Realistic aspirations to improve safety assessment, incorporate new technologies and reduce reliance on animal testing without compromising protection goals are discussed.
Topics: Acute Disease; Agrochemicals; Animal Testing Alternatives; Carcinogenicity Tests; Dose-Response Relationship, Drug; Guidelines as Topic; Mutagenicity Tests; Research Design; Risk Assessment; Species Specificity; Time Factors
PubMed: 34678328
DOI: 10.1016/j.yrtph.2021.105068 -
IARC Monographs on the Evaluation of... 1999
Topics: Animals; Carcinogenicity Tests; Carcinogens; Humans; Hydrocarbons, Chlorinated; Neoplasms, Experimental
PubMed: 10476417
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1999
Topics: Animals; Carcinogenicity Tests; Carcinogens; Chlorofluorocarbons, Methane; Humans; Mutagenicity Tests; Mutagens; Neoplasms, Experimental
PubMed: 10476408
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1999
Topics: Animals; Carcinogenicity Tests; Carcinogens; Humans; Mutagenicity Tests; Mutagens; Neoplasms, Experimental; Phenyl Ethers
PubMed: 10476400
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1999
Topics: Animals; Carbazoles; Carcinogenicity Tests; Carcinogens; Humans; Neoplasms, Experimental
PubMed: 10476405
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1999
Topics: Carcinogenicity Tests; Carcinogens; Humans; Hydrazines; Mutagenicity Tests; Mutagens; Neoplasms, Experimental; Salmonella typhimurium
PubMed: 10476419
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1996
Review
Topics: Animals; Anticonvulsants; Carcinogenicity Tests; Carcinogens; Humans; Phenytoin
PubMed: 9097125
DOI: No ID Found