Toxicology and Industrial Health

Latimer, James; McDowall, Kiera

doi: 10.1177/07482337261419191pmid: 41555637

Ktari, Naourez; Boukholda, Khadija; Ben Slama-Ben Salem, Rabeb; Bkhairia, Intidhar; Ben Salah, Riadh

doi: 10.1177/07482337261420596pmid: 41669791

Human exposure to triazole fungicides such as flutriafol (FFL) is raising concerns regarding their potential toxic effects. FFL has been reported to induce oxidative stress and systemic toxicity, yet its subacute effects remain incompletely characterized. This study investigated the subacute oral toxicity of FFL in adult male mice, with a particular focus on behavioral, biochemical, hematological, and histological alterations. Behavioral assessment and median lethal dose (LD50) determination were performed initially. Mice were then administered FFL by oral gavage at doses of 25, 50, 75, or 100 mg/kg body weight for 15 consecutive days. Hematological indices and biochemical parameters reflecting hepatic, renal, cardiac, and lipid metabolic function were evaluated. Oxidative stress markers, including catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and thiobarbituric acid–reactive substances (TBARS), were measured in multiple organs, including the liver, intestine, brain, kidney, testis, lungs, pancreas, and heart. Histological examinations were conducted to assess tissue-level alterations. FFL exposure resulted in dose-dependent behavioral changes, hematological disturbances, and significant alterations in serum biochemical parameters. Antioxidant enzyme activities were reduced, while lipid peroxidation was increased across several organs, indicating enhanced oxidative stress. These findings were supported by histopathological changes consistent with organ injury. In conclusion, subacute oral exposure to FFL induced behavioral and multisystem toxicity in mice, largely mediated by oxidative stress mechanisms. These results highlight potential health risks associated with repeated FFL exposure and underscore the need for further toxicological evaluation.

Ye, Lu; Ma, Weichao; Ming, Yuhan; Zhou, Fengjuan; Liu, Juan

doi: 10.1177/07482337261418749pmid: 41630576

This study endeavored to elucidate the association between exposure to individual and combined volatile organic compounds (VOCs) and the occurrence of periodontitis in adults. Data were derived from the 2009–2012 National Health and Nutrition Examination Survey (NHANES). Weighted logistic regression and restricted cubic spline (RCS) analyses were employed to assess the relationship between blood VOC concentrations and periodontitis. Significant positive associations were observed for benzene, furan, 2,5-dimethylfuran, ethylbenzene, m-/p-xylene, and o-xylene, with adjusted odds ratios (ORs) ranging from 1.44 to 2.31. RCS analyses demonstrated linear associations for benzene, furan, 2,5-dimethylfuran, m-/p-xylene, and 1,4-dichlorobenzene, whereas ethylbenzene and o-xylene exhibited nonlinear associations. In addition, weighted quantile sum regression revealed that cumulative VOC exposure was positively associated with periodontitis, with 2,5-dimethylfuran, ethylbenzene, benzene, and furan identified as the most influential contributors. Collectively, these findings suggested that VOC exposure possibly plays a substantive role in the pathogenesis and progression of periodontitis, underscoring the need for strategies aimed at reducing environmental VOC exposure as part of comprehensive preventive and therapeutic public health measures.

Jones, Kylie; Kemp, Megan J; Barlow, Christy A

doi: 10.1177/07482337261419181pmid: 41572664

Methylparaben and propylparaben are widely used as preservatives in consumer products, including cosmetics, personal care items, and pharmaceuticals. Concerns have been raised regarding their potential for systemic absorption and estrogenic activity, which may contribute to endocrine disruption. This review evaluates current evidence on dermal absorption, metabolism, and systemic distribution of methylparaben and propylparaben, emphasizing factors influencing their bioavailability. Additionally, the estrogenic potential of these compounds in experimental studies is examined, assessing receptor binding affinity and biological effects. Overall, while parabens exhibit weak estrogenic activity compared to endogenous hormones, repeated exposure and cumulative effects warrant further investigation. The toxicokinetic data combined with estrogenic activity assessments provide critical insight into the risk of endocrine disruption associated with paraben exposure. This assessment provides an understanding of methylparaben and propylparaben safety, supporting informed regulatory decisions and consumer awareness.

Utembe, Wells; Andraos, Charlene

doi: 10.1177/07482337261422823pmid: 41653473

The Globally Harmonized System (GHS) is a crucial framework for chemical hazard communication, especially in protecting workers from skin sensitizers. A critical assessment of the principles, issues, and challenges around classification of skin sensitization in GHS is warranted. Classification of dermal sensitizers relies on a weight of evidence (WoE) approach that incorporates human, animal, and non-test data. However, current testing methods have limitations in sensitivity, specificity, and predictive accuracy. Current test methods take into account the issue of potency and thresholds for sensitization. However, the focus on induction thresholds rather than induction and elicitation thresholds may create a gap in protecting already sensitized individuals since elicitation thresholds are in some cases lower than induction thresholds. While the sensitization process may take weeks or years, current test methods are largely acute in nature, potentially incapable of identifying all (chronic) sensitizers. Moreover, current methods used for classification of skin sensitizers only take into account the dermal route, whereas some chemicals may cause dermal sensitization through other routes, which presents a significant limitation, especially when considering non-animal testing methods. Finally, lack of UV irradiation in current methods may inadvertently miss potential photosensitizers, which may result in misclassification. Continuous refinement of testing methods and integrating novel approaches are essential to improve GHS classifications for skin sensitizers.