This study systematically evaluated the toxicological safety of superoxide dismutase (SOD) as a novel food ingredient. Acute oral toxicity testing revealed no toxicity or mortality in mice of both sexes following a single gavage dose of 10 g/kg BW, classifying SOD as a practically nontoxic substance. In the 90-day subchronic toxicity study, Wistar rats orally administered doses of 8.33, 25, or 75 mg/kg BW/day exhibited the following: Female rats in the high-dose group showed significantly increased body weight during Weeks 11–13, transient fluctuations in food efficiency occurred in the low-dose group, and high-dose males displayed reduced neutrophil percentage (NEUT%) at termination, whereas all observed alterations in hematological, clinical chemistry, and urinalysis parameters lacked dose dependency and were largely disappeared during the recovery period. Histopathological examination revealed no substance-specific lesions. Teratogenicity testing demonstrated a significant increase in fetal resorption rates in the 8.33 and 25 mg/kg BW groups (p < 0.01), whereas this effect showed no dose–response association and no structural malformations were observed. Three genotoxicity assays (mammalian erythrocyte micronucleus, chromosome aberration in vitro, and Ames tests) yielded negative results. Collectively, these findings demonstrate a favorable safety profile for SOD at the tested doses, with no evidence of genotoxicity either in vivo or in vitro.
Background Air pollution is a major risk factor for perinatal health. PM2.5 can cross the placenta and induce oxidative stress and inflammation, promoting fetal growth restriction and low birth weight (LBW). Sub‐Saharan Africa has the highest PM2.5 exposures in the world, but data on perinatal outcomes there are limited. In the DRC, urbanization and unregulated quarries degrade air quality. The Binza Ozone Health Zone in Kinshasa is home to the Carrigrès quarry within densely populated neighborhoods. No study in the DRC has evaluated the link between PM2.5 exposure and LBW. This study aimed to analyze the association between PM2.5 exposure, proximity to the quarry, and LBW. Methods Cross‐sectional study of 355 mothers who delivered between January and December 2021 in six healthcare facilities in Binza Ozone. Data were collected via interviews and reviews of antenatal care (ANC) and delivery registries. LBW was defined as a weight < 2500 g. PM2.5 was measured over 48–72 h per health area in September‐October 2022 using calibrated PurpleAir PA‐II‐SD sensors. The PurpleAir PA‐II‐SD sensor is a low‐cost optical particle counter that was calibrated against the Federal Reference Method (FRM) Beta Attenuation Monitor (BAM) in Kinshasa, as described by McFarlane et al. (2021); the calibration equation applied was as follows: PM2.5 (corrected) = 0.52 × PM2.5(raw)+3.2. Sites were classified as “highly polluted” > 75 μg/m 3 or “polluted” ≤ 75 μg/m 3 based on the median. Distance to the Carrigrès quarry was categorized as < 500 m and ≥ 500 m. Bivariate analysis was performed using the chi‐square test. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs), adjusted for age, parity, education level, maternal alcohol consumption, tobacco exposure (active and passive smoking), nutritional factors (dietary diversity score and mid‐upper arm circumference), and gestational complications. The significance threshold was set at p < 0.05. Results Median age was 26 years (IQR: 20–36). 67.3% had a secondary education level. LBW prevalence: 12.96%, n = 46/355, 95% CI [9.7–16.9]. This prevalence is significantly higher than 7.8% reported for Kinshasa Province in the MICS‐DRC 2017‐2018 survey, confirming the existence of a local aggravating factor. PM2.5 levels ranged from 54.6 to 102.5 μg/m 3 , exceeding both the WHO annual guideline of 5 μg/m 3 and the WHO 24‐h guideline of 15 μg/m 3 . In bivariate analysis, residing < 500 m from the quarry was associated with LBW: 33.3% versus 9.1%, p < 0.001, OR: 4.85 [2.42–9.72]. Gestational complications were also associated: 37.5% versus 10.5%, p < 0.001. PM2.5 > 75 μg/m 3 was not associated: 15.8% versus 11.5%, p = 0.312. In multivariable analysis, proximity < 500 m (aOR: 4.12 [1.98–8.57], p < 0.001) and gestational complications (aOR: 4.67 [2.11–10.34], p < 0.001) remained independently associated with LBW. PM2.5 > 75 μg/m 3 was no longer significantly associated: aOR: 1.18 [0.59–2.36], p = 0.642. Maternal alcohol consumption, tobacco exposure, and nutritional factors were not significantly associated with LBW in this sample ( p > 0.05 for all). Conclusion There is a high prevalence of LBW in Binza Ozone compared to the provincial reference of 7.8%, and an independent association with residing < 500 m from a quarry. Very high PM2.5 levels were not independently associated with LBW, suggesting the effect of a mixture of exposures: coarse particles, noise, and socio–economic factors. These results justify urgent interventions: air quality monitoring, buffer zones around quarries, and the integration of environmental risk assessment into prenatal care.
The rapid deployment in early 2021 of modified mRNA (modRNA) as a vaccine platform for the COVID-19 pandemic sparked a wave of optimism for its potential as a preventive medicine. However, this compacted timeframe may not have fully addressed certain toxicological risks associated with this new technology, which would typically require more extensive preclinical testing. Five years postrollout, an accumulating body of postauthorisation evidence has highlighted safety signals that require closer scrutiny, such as those concerning biodistribution, off-target effects and persistent adverse events. Independent analyses of Phase III trial data and pharmacovigilance reports have raised questions regarding benefit–risk balance and potential long-term biological effects. This narrative review examines the evolution of the toxicological understanding of modified RNA as a vaccine technology from platform design through long-term observational data, identifying areas of uncertainty and vulnerability that may inform future development and regulatory evaluation. The review emphasises that fast-tracked decision-making under exceptional uncertainty requires explicit safeguards to prevent premature certainty and to support learning from emerging evidence over time.
Chronic exposure to lead (Pb) remains a critical global public health challenge, extending beyond its established neurotoxic effects to its emerging role in the pathogenesis of neurodegenerative disorders, particularly tauopathies. Accumulating evidence indicates that prolonged Pb exposure disrupts neuronal homeostasis through multiple interconnected mechanisms, including oxidative stress, mitochondrial dysfunction, neuroinflammation, epigenetic alterations, and dysregulation of tau phosphorylation. These molecular perturbations contribute to synaptic impairment, neuronal loss, and progressive cognitive decline. Current therapeutic strategies primarily rely on metal chelation and antioxidant interventions; however, their clinical efficacy is limited by poor blood–brain barrier penetration, nonselective metal removal, and systemic adverse effects. Recent advances in nanotechnology offer promising alternatives for targeted neuroprotection. Nanocarrier systems, including dendrimers, liposomes, polymeric nanoparticles, and micelles, enable enhanced brain delivery, controlled drug release, and reduced systemic toxicity. This review synthesizes current knowledge on the molecular mechanisms linking Pb exposure to tau-related neurodegeneration and critically evaluates existing therapeutic approaches. Furthermore, it highlights the potential of nano-based delivery systems to overcome the limitations of conventional therapies and outlines future directions for translational research in Pb-associated neurodegenerative disorders.
Objectives Vitex negundo and Zingiber officinale are predominantly used in day‐to‐day life as food or supplements. Both are being reported individually for therapeutic properties. A food supplement consisting of leaves and twigs of Vitex negundo and rhizome of Zingiber officinale , the first‐of‐a‐kind proprietary blend extract (MUVZ), was developed for joint health. Methods As part of the safety profile, a subchronic toxicity study was performed in Sprague Dawley rats under compliance with Good Laboratory Practice (GLP). The study aimed to determine the potential toxicity of MUVZ following oral (gavage) administration by following Organisation for Economic Co‐operation and Development (OECD) Guideline 408. MUVZ was administered for 90 days, with a recovery period of 28 days. MUVZ was administered at 0 (G1), 1000 (G2), 2000 (G3) and 3000 (G4) mg.kg −1 body weight ( n = 10/sex/group); vehicle control (G1R) and high‐dose recovery groups 3000 mg.kg −1 ·b.w (G4R) ( n = 5/sex/group). Results No MUVZ‐related effects were observed in mortality, morbidity, detailed clinical signs, body weight and feed consumption. Statistical significance was found in levels of clinical pathology parameters; however, there was no dose dependency, and further correlative histopathological findings were observed. At the end of the experimental trial, no test article–induced gross and microscopic pathological lesions were observed across the treatment groups. Conclusions Based on the findings, no toxicologically significant findings were derived at the highest dose of 3000 mg.kg −1 body weight.
