Assessment of Cytotoxic and Genotoxic Responses to an Ipfencarbazone-Based Herbicide in Human Peripheral Lymphocytes İn Vitro
Current Issues in Molecular Biology, vol.48, no.6, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 48 Issue: 6
- Publication Date: 2026
- Doi Number: 10.3390/cimb48060565
- Journal Name: Current Issues in Molecular Biology
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, Directory of Open Access Journals
- Keywords: comet assay, cytotoxicity-associated genotoxic-like effects, genotoxicity in vitro, human lymphocytes, ipfencarbazone, ipfencarbazone-based herbicide (IPF-BH), micronucleus assay, mitotic index
- Çanakkale Onsekiz Mart University Affiliated: Yes
Abstract
This study evaluates the cytotoxic and genotoxic-like potential of an ipfencarbazone-based herbicide formulation (IPF-BH; commercial product Hokuto, containing 250 g/L of the triazolinone herbicide ipfencarbazone) in human peripheral lymphocytes in vitro across a concentration range of 62.5–1000 µg/mL. Cytotoxicity was monitored via the mitotic index (MI), while cytogenetic damage was assessed using the cytokinesis-block micronucleus (MN) assay and the alkaline comet assays. Comparisons were performed using one-way ANOVA, followed by Dunnett’s post hoc test, against the negative control. Results indicated a concentration-dependent cytotoxic effect, with a marked reduction in MI observed at all tested concentrations (p < 0.001). MN frequency was significantly elevated at concentrations ≥125 µg/mL, whereas the 62.5 µg/mL concentration did not induce significant micronuclei formation. The comet assay revealed increased DNA damage parameters (tail length, tail intensity (%), and tail moment) across the tested concentration range, albeit with a non-monotonic profile for tail length and tail intensity. These findings suggest that IPF-BH exposure is associated with marked cytotoxicity and a genotoxic response in this in vitro model at concentrations within the OECD 487-acceptable cytotoxicity window, together with cytotoxicity-associated genotoxic-like effects at strongly cytotoxic concentrations in human peripheral lymphocytes under in vitro conditions. Because IPF-BH is a commercial formulation, and no direct mechanistic endpoints (e.g., reactive oxygen species, mitochondrial transmembrane potential, lipid peroxidation, glutathione) were measured, and because the present design was performed without exogenous metabolic activation (no S9 supplementation), the observed effects cannot be unambiguously attributed to ipfencarbazone alone or to a defined mechanism of action; extrapolation to in vivo genotoxicity requires complementary +S9 and rodent in vivo follow-up studies.