ArticleMutagenesis2013
Seven benzimidazole pesticides combined at sub-threshold levels induce micronuclei in vitro.
Article in Mutagenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 59 citations in OpenAlex.
- Article
- A Review of Approaches to the Metallic and Non-Metallic Synthesis of Benzimidazole (BnZ) and Their Derivatives for Biological Efficacy.Molecules (Basel, Switzerland) · 2023Review
- Synthesis and characterization of different complexes derived from Schiff base and evaluation as a potential anticancer, antimicrobial, and insecticide agent.Saudi journal of biological sciences · 2023Article
- Article
- Multiresistance to Nonazole Fungicides in Aspergillus fumigatus TRAntimicrobial agents and chemotherapy · 2021Article
- Guidance on aneugenicity assessment.EFSA journal. European Food Safety Authority · 2021Article
- Environmentally relevant exposures of male mice to carbendazim and thiram cause persistent genotoxicity in male mice.Environmental science and pollution research international · 2020Article
- Assessment of developmental neurotoxicity induced by chemical mixtures using an adverse outcome pathway concept.Environmental health : a global access science source · 2020Article
- Genotoxicity of mixture of imidacloprid, imazalil and tebuconazole.Toxicology reports · 2020Article
- Recent advances in the use of benzimidazoles as corrosion inhibitors.BMC chemistry · 2019Review
- Antifungal Agents in Agriculture: Friends and Foes of Public Health.Biomolecules · 2019Review
- A Novel Strategy to Predict Carcinogenicity of Antiparasitics Based on a Combination of DNA Lesions and Bacterial Mutagenicity Tests.Frontiers in public health · 2017Review
- Genotoxicity of flubendazole and its metabolites in vitro and the impact of a new formulation on in vivo aneugenicity.Mutagenesis · 2016Article
- Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.Carcinogenesis · 2015Review
- Causes of genome instability: the effect of low dose chemical exposures in modern society.Carcinogenesis · 2015Review
- Genotoxic mixtures and dissimilar action: concepts for prediction and assessment.Archives of toxicology · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Benzimidazoles act by disrupting microtubule polymerisation and are capable of inducing the formation of micronuclei. Considering the similarities in their mechanisms of action (inhibition of microtubule assembly by binding to the colchicine-binding site on tubulin monomers), combination effects according to the principles of concentration addition might occur. If so, it is to be expected that several benzimidazoles contribute to micronucleus formation even when each single one is present at or below threshold levels. This would have profound implications for risk assessment, but the idea has never been tested rigorously. To fill this gap, we analysed micronucleus frequencies for seven benzimidazoles, including the fungicide benomyl, its metabolite carbendazim, the anthelmintics albendazole, albendazole oxide, flubendazole, mebendazole and oxibendazole. Thiabendazole was also tested but was inactive. We used the cytochalasin-blocked micronucleus assay with CHO-K1 cells according to OECD guidelines, and employed an automated micronucleus scoring system based on image analysis to establish quantitative concentration-response relationships for the seven active benzimidazoles. Based on this information, we predicted additive combination effects for a mixture of the seven benzimidazoles by using the concepts of concentration addition and independent action. The observed effects of the mixture agreed very well with those predicted by concentration addition. Independent action underestimated the observed combined effects by a large margin. With a mixture that combined all benzimidazoles at their estimated threshold concentrations for micronucleus induction, micronucleus frequencies of ~15.5% were observed, correctly anticipated by concentration addition. On the basis of independent action, this mixture was expected to produce no effects. Our data provide convincing evidence that concentration addition is applicable to combinations of benzimidazoles that form micronuclei by disrupting microtubule polymerisation. They present a rationale for grouping these chemicals together for the purpose of cumulative risk assessment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.