Talc fits the framework of poorly soluble low-toxicity particles - implications for hazard classification.

Although nitrosamines are known as potent carcinogenic contaminants with multisystem toxicity, the metabolic mechanisms driving esophageal carcinogenesis under multi-nitrosamine co-exposure remain poorly understood. This molecular epidemiological study sought to identify dynamic metabolic signatures mediating nitrosamine-associated esophageal squamous cell carcinoma (ESCC) risk. We quantified urinary levels of nine nitrosamines in participants across esophageal lesion stages (RE/BCH, DYS, ESCC) and employed UPLC-MS/MS metabolomics to investigate exposure-response relationships and mediation effects of key metabolites. Distinct stage-specific nitrosamine profiles were observed. Sphingolipid metabolism emerged as a critical pathway in ESCC pathogenesis: DH-SPH, DH-S1P, and S1P were positively associated with increased risk, while SPH and the SPH/S1P ratio demonstrated protective effects. Mediation analysis revealed metabolite-specific pathways, with DH-S1P acting as a shared mediator in NDphA-, NMEA-, and NPIP-induced ESCC pathways, and S1P mediating NMEA-associated progression from RE/BCH to ESCC. Sensitivity analyses indicated differential robustness across pathways. E-value assessment revealed that NDphA-related pathways exhibited high resistance to unmeasured confounding (E-value > 2). Critical ρ analysis indicated that DH-S1P-mediated pathways in ESCC exhibited high credibility (ρ thresholds ≈ 0.3), and SPH/S1P-mediated pathways yielded conservative effect estimates. ROC analysis with bootstrapping validation suggested the potential discriminative ability of sphingolipid metabolites: S1P showed promise in distinguishing across the disease spectrum, and a combined panel demonstrated improved performance for ESCC prediction and nitrosamine exposure discrimination in this study population. Collectively, these findings underscore sphingolipid dysregulation as a key associative mediator linking nitrosamine exposure to ESCC progression, and support their potential as candidate biomarkers for early screening and exposure monitoring in high-risk populations. However, due to the cross-sectional design and absence of external validation, these findings await confirmation in prospective and functional studies.

Isonicotinic acid (INA) is a widely used chemical and agricultural intermediate, which contaminates agricultural products, causes lysine isonicotinylation of histones, and increases the risk of cancer in humans. The microbial degradation of INA has been continuously investigated for 60 years, but its molecular mechanism remains unclear. In this study, a newly isolated strain, Alicycliphilus denitrificans DP3, was found to degrade 2.5 mM INA to undetectable levels within 48 h. A novel ina gene cluster located on the plasmid encodes two consecutive three-component molybdenum-dependent hydroxylases: InaA1A2A3 catalyzes the first hydroxylation of INA to 2-hydroxyisonicotinate (2HINA), while InaB1B2B3 catalyzes the second hydroxylation to 2,6-dihydroxyisonicotinate (26HINA). H218O isotope labeling confirmed that the incorporated oxygen atoms are derived from water. RT-qPCR demonstrated that seven ina genes were strongly induced by INA. Comparative genomics showed that homologous ina clusters are globally distributed, and these findings provide the first genetic framework for microbial INA degradation.

Health effects of PFASs on five major human cancers: A network toxicology perspective on molecular pathogenesis.

Obesity, type 2 diabetes and cancers of the digestive system.

Smoking is considered a global pandemic with more than 1.3 billion people being active smokers. Increasing evidence suggests that nicotine exposure can lead to changes in the gut microbiome, increases in permeability, and impaired mucosal immune responses in the gastrointestinal tract. However, the literature on behavioral aspects of nicotine-microbiome interaction, such as dependence and withdrawal, is limited. In this study, we used homologous fecal material transplants (FMT) to modify the gut microbiome and its impact on the intensity of nicotine withdrawal in mice. We used osmotic minipumps as an application of chronic nicotine for 15days and orally gavaged FMT 2x a day to the mice. We assessed the nicotine withdrawal by measuring the number of somatic signs and anxiety-like behaviors at 24h and 1week after the mini pump removal. Fecal samples were also collected points to identify the gut microbiome changes. Fecal transplants reduced the number of somatic signs and anxiety-like behaviors in nicotine-treated mice up to a week after the removal of minipumps. The shotgun metagenomic results of the fecal samples from 24h after minipumps removal time point show altered gut microbiome with a significant shift in the species composition between the nicotine treated and its homologous FMT treatment. Our results indicate that under our experimental conditions fecal transplant can reduce the severity of nicotine withdrawal. This suggests that interactions along the gut-brain axis are important for the development of nicotine dependence and might help lower the risk of cancer and other serious health problems in humans.

ABSTRACTSeveral cancer potency estimates have been proposed by regulatory agencies to characterize the dose response of cobalt and/or cobalt compounds. The objective of this research is to investigate whether these proposed cancer potency estimates for certain cobalt substances align with the available epidemiology literature. After review of the epidemiological literature, we identified a study appropriate for our analysis. We established whether our identified study was adequately powered to detect an elevated lung cancer risk. The power analysis assumed a Poisson distribution and used a one‐sided significance level of 0.05. Lung tumors in animals served as the basis for cancer potency estimates for several regulatory bodies. The study population from our identified study was used to calculate predicted excess lung cancer deaths using potency values reported by four regulatory organizations, which were then compared to observed lung cancer deaths. Monte Carlo methods were used to estimate sample size and cobalt exposure distribution of the highest exposure group. We determined that the our identified study has ≥ 98% statistical power to detect a 1.5‐fold or greater increase in lung cancer due to cobalt exposure in all but the lowest exposure group and all four exposure groups had 100% statistical power to detect a 2.0‐fold or greater increase in lung cancer due to cobalt exposure. Cobalt exposure at the estimated median of the highest exposure group resulted in hypothetical standardized mortality ratios (SMR) estimated from the regulatory potency values ranging from 3.54 to 8.61 compared to an observed SMR of 1.15 (95% CI: 0.92–1.43) in our identified study. On the basis of this analysis, the cancer potency estimates proposed by the included regulatory organizations are likely overestimations of excess lifetime human cancer risk after cobalt inhalation exposure.

Exposure to radiofrequency electromagnetic fields (RF-EMF; frequencies 100kHz to 300GHz) is ubiquitous. As the use of RF-EMF has grown steadily since the 1950s due to advances in telecommunications and other technologies, concerns about potential health effects have persisted. The World Health Organization (WHO) identified key areas of concern, with cancer being most frequently rated as critical. To synthesize evidence on the association between RF-EMF exposure and neoplastic diseases, we will carry out two separate umbrella reviews to account for different RF-EMF exposure conditions: one will focus on near-field exposure and the other on far-field exposure. Both umbrella reviews will include RF-EMF exposure in living and occupational settings. Systematic reviews and meta-analyses of human observational studies on RF-EMF and cancer were searched in MEDLINE, Web of Science Core Collection, EMF-Portal, and Epistemonikos databases. Eligibility criteria will follow the PECOS (Population, Exposure, Comparator, Outcome, Study type) scheme. Eligibility and quality of the identified articles will be evaluated by two reviewers independently. The tools AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews) and ROBIS (Risk of Bias in Systematic Reviews) will be used to systematically assess methodological quality and risk of bias. Data will be extracted and summarized in a qualitative synthesis using standardized forms and presented in text and tables. These umbrella reviews aim to offer a comprehensive overview of the topic by including systematic reviews and meta-analyses that studied cancer-related health effects of near-field and far-field RF-EMF exposure. In addition, a risk of bias rating will be performed to assess the quality of existing systematic reviews and meta-analyses in the field. PROSPERO CRD42024529007.

Widely used phthalates, especially di-(2-ethylhexyl) phthalate (DEHP), increase breast cancer risk in experimental animals and humans, but long-term follow-up evidence of its human breast carcinogenicity remains inconclusive. This nested case-control study included 119 invasive breast cancer cases and 245 matched controls from a longitudinal cohort of 11,923 women recruited in 1991-1992 and followed to 2010 in Taiwan. Urine samples at baseline and follow-up visit were tested for 11 metabolites of seven phthalates using LC-ESI-MS/MS. DEHP metabolism susceptibility was evaluated by the percentage of mono-2-ethylhexyl phthalate (MEHP%) in the sum of five DEHP metabolites (∑DEHP). Odds ratios (ORs) with 95% CI from conditional logistic regression were used to examine risk predictors. DEHP was the only phthalate significantly associated with breast cancer risk. Risk increased significantly with elevated urinary levels of ∑DEHP (> 0.381 μmol/g creatinine, OR = 1.71, 95% CI = 1.02 to 2.43), MEHP (> 0.022 μmol/g creatinine, OR = 1.87, 95% CI = 1.07 to 3.25), and MEHP% (> 6.7%, OR = 1.65, 95% CI = 0.96 to 2.82). Elevated ∑DEHP and MEHP% combined with early menarche (≤ 14 years) was associated with further increased risk (OR = 7.52, 95% CI = 2.68 to 21.05). The intraclass correlation coefficient between paired baseline and follow-up samples of 152 women was 0.06 for ∑DEHP and 0.31 for MEHP%. High DEHP exposure, high MEHP%, and early menarche were associated with increased breast cancer risk. MEHP% was a better biomarker for DEHP metabolism.

Glyphosate is an herbicide found worldwide in glyphosate-based formulations (GBFs). Although glyphosate appears to have a low toxicity profile for humans and mammals, conflicting reports exist regarding the risk for cancer in humans. US-EPA and European regulatory agencies have described glyphosate as unlikely to pose a carcinogenic hazard to humans. However, the International Agency for Research on Cancer (IARC) classified glyphosate as "probably carcinogenic to humans (Group 2A)," citing "mechanistic data provide strong evidence for genotoxicity and oxidative stress." Given these discrepancies, the Division of Translational Toxicology at NIEHS designed an experimental strategy to expand mechanistic evidence and address critical gaps within existing literature (e.g. mechanistic evaluations of glyphosate alongside GBFs, inclusion of context-defining positive controls). Cell morphology, viability, H2O2, and γH2AX formation were assayed in human keratinocytes (HaCaT), previously cited by IARC, and human hepatocytes (HepaRG) to derive benchmark concentrations and fold-change response metrics. Our findings revealed glyphosate alone was weakly and inconsistently bioactive for oxidative stress and DNA damage when compared with positive controls. In contrast, most of the 13 GBFs evaluated were more clearly bioactive with no apparent correlation to varied glyphosate concentrations. Hierarchical clustering of biological responses revealed some bioactive GBFs to cluster near well-characterized positive controls for oxidative stress, whereas 4 GBFs clustered more similarly to negative controls and glyphosate. Collectively, this study provides a robust dataset with context-defining results that advance our understanding of the hazard potential of GBFs while revealing that glyphosate is likely not a primary driver of oxidative stress from GBF exposures.

Maternal Phthalate Exposure Alters Prostate Proteome in Rat Offspring: Linking Omics Insights to Prostate Cancer Risk in Humans.

Associations between plasma ANGPTL4 levels and the risk of 24 cancers: a prospective cohort study.

Females with HIV (FWH) are recommended to receive cervical cancer screening annually, with the interval extended to every 3 years after three sequential normal results. Lifelong screening is highly recommended due to their increased risk of human papillomavirus infection and cervical cancer. We assessed the trends in cervical cancer screening rates and cervical cancer/precancer prevalence among older FWH and females without HIV (FWOH) using 2007-2019 US Medicare data. We found that age-adjusted cervical cancer screening rates decreased similarly in both FWH and FWOH (average annual percentage change: -4.4 [95% CI: -5.2, -3.6] vs. -5.7 [95% CI: -6.8, -4.7], p = 0.11). However, the age-adjusted cervical cancer/precancer prevalence showed increasing rates among FWH (5.4, [2.9, 7.9]) while stable in FWOH (-0.6 [-1.4, 0.1]). These findings underscore the need for strict adherence to clinical practice guidelines for cervical cancer screening in older FWH.

In this study, the natural radioactivity and its ecological implications in Jabi Lake were assessed, focusing on radiological risks to humans and aquatic biodiversity. Ambient radiation dose rates were measured in situ using a GMC-800 survey meter, while water and sediment samples were analyzed for radionuclide content. Radon concentrations in water were determined using a Tri-Card LSA 1000 liquid scintillation counter, and sediment samples were analyzed with NaI(Tl) gamma spectrometry at the Centre for Energy Research and Training, Ahmadu Bello University, Zaria, Nigeria. The mean ambient dose rate was found to be , which is below the global average of . However, the excess lifetime cancer risk (ELCR) averaged is greater than ICRP's recommended limit by a factor of two, and it is attributed to a cumulative exposure over time. Radon in water ranged from with a mean , exceeding the USEPA limit of but below the WHO/UNSCEAR guideline of 100 Bq/L Sediment analysis revealed mean activity concentrations of were 8.62 ±2.63, 5.98± 1.11, and 202.6± 16.42 Bq/kg respectively, all lower than the global averages.ERICA code assessment showed dose rates to aquatic organisms below the ecological dose rate screening criterion of 40 nGy/h. The findings indicate low ecological risk but highlight elevated human cancer risk, which suggest minimization of lifetime exposure, waste disposal control, wider scope assessment and monitoring around Jabi Lake, and stakeholder engagement to ensure optimized protection of biodiversity.

The study aims to assess the accumulation of ten heavy metals (As, Cd, Cr, Co, Cu, Fe, Mn, Ni, Pb, and Zn) in soils of the desert city of Rajasthan. Heavy metals analysis in industrial soils was assessed by following standard methods for two consecutive years. Principal component analysis (PCA), correlation matrix, spatial distribution, contamination factor (CF), degree of contamination (CD), pollution load index (PLI) and potential ecological risk index (PERI) in soil and plants were assessed to find out the metal contamination level. Furthermore, this study also conducted human health risk assessment for adults and children by using the health risk assessment model recommended by the United States Environmental Protection Agency (USEPA). The highest concentration of heavy metals such as As (7.74 mg/kg), Cu (18.22 mg/kg), Fe (2981 mg/kg), Ni (25.11 mg/kg), and Zn (106.12) in Rani Bazar, Co (5.54 mg/kg) and Pb (13.86 mg/kg) in Bichhwal and Cr (14.32 mg/kg) and Mn (71.8 mg/kg) in Khara in 2019. Whereas, Cd (4.50 mg/kg) was maximum in Karni industrial soil in 2020. Whereas, the high metal content in plants was observed mainly in 2020 such as As (30.9 mg/kg) and Zn (376.7 mg/kg) in Abutilon indicum, Cd (29.93 mg/kg) in Calotropis procera, Cr (341.6 mg/kg), Cu (400.61 mg/kg) and Ni (301.99 mg/kg) in Aerva pseudotomentosa, Fe (14496 mg/kg) and Mn (1319.89 mg/kg) in Cicer arietinum, Pb (976.7 mg/kg) in Coriandrum sativum. Though only Citrullus colocynthis contain high concentration of Co (11.96 mg/kg) in 2019. Plant species show hyperaccumulation towards As, Cd, Cr, Cu, Co, Fe, Mn, Ni, Pb, and Zn with more than 1 values of bioconcentration factor and translocation factor specifying their effectiveness in uptake and transfer of more than one element from soil to shoot. The non-carcinogenic heath risk assessment shows that HQ values for heavy metals such as As, Cd, Cr, Cu, Fe, Ni, Mn, Pb in plants were above the recommended guideline level. In carcinogenic risk assessment, CRI in adult group of Rani Bazar industrial soil in 2019 were found at high cancer risk. Moreover, selected plants also show cancer risk for As, Cd, Cr, Ni and Pb metals. Therefore, consumption of plants may produce cancer risk in humans too. Henceforth, monitoring and management of heavy metals is advocated to avert the metal health hazards to humans. The study can be utilized as baseline for further human health risk assessment of heavy metals.

Association of SMAD4 gene polymorphisms with human papillomavirus infection and risk of cervical cancer: a case-control study.

Coastal areas adjacent to urban and industrial regions are vulnerable to pollution from polycyclic aromatic hydrocarbons (PAHs), posing potential risks to both ecosystems and human health. This study quantified 16 priority PAHs in seawater and blue mussels (Mytilus edulis) from four beaches along Portugal's northwest coast over two years for seawater samples and four years for mussel samples. PAHs were measured in the dissolved aqueous phase (DAP), suspended particulate matter (SPM), and mussels using gas chromatography-mass spectrometry (GC-MS). Mean concentrations were 13.3ng/L (DAP), 134.0μg/kg dw (SPM) and 136.9μg/kg ww (mussels). Source identification indicated both pyrogenic (wildfires) and petrogenic (maritime activity) inputs. Toxicity assessment revealed low carcinogenic potential in DAP (TEQ≈0.7ng/L) and moderate risk in SPM (TEQ≈6μg/kg dw). Risk coefficients classified DAP as low risk and SPM as moderate risk. In mussels, although the hazard index values were below 1, the estimated lifetime cancer risk (≈ 2.5E-05) exceeded the EU safety threshold of 1.0E-06, indicating a potential carcinogenic risk from human consumption. These findings emphasize the necessity for continuous monitoring and more robust regulatory measures to manage PAH contamination in coastal environments, thereby mitigating associated ecological and public health risks.

Mode of action analysis for induction of mouse lung tumors by permethrin: Involvement of CYP2F2 enzyme and human relevancy.

Human papillomavirus is the most common viral sexually transmitted infection worldwide and affects individuals of all ages and both sexes. It is also the most preventable cause of cervical cancer. The World Health Organization’s Cervical Cancer Elimination Strategy (2030 targets) aims for 90% of girls to receive the Human papillomavirus vaccine by age 15, 70% of women to be screened by ages 35–45, and 90% of cervical-cancer cases to be appropriately treated. To determine cervical-cancer–related risk factors and knowledge levels, and to assess Human papillomavirus -related knowledge and attitudes toward vaccination. The survey also examined general adult vaccination behaviors—including measles, influenza, coronavirus, respiratory syncytial virus, and shingles vaccines—among adults. A cross-sectional study was conducted among 1,174 randomly selected adults from Egypt, Syria, Jordan, and Yemen between March and May 2025, using a validated Arabic self-administered questionnaire. Most participants were female (635, 54.2%), university-educated or higher (699, 59.6%), and living in urban areas (796, 67.9%). Regarding risk factors, 489 (41.7%) were smokers, 94 (8.0%) reported genital laser hair removal, 84 (7.2%) had oral or other herpes lesions, and 81 (6.9%) had a family history of reproductive-system cancer. Overall, 626 (53.4%) had poor Human papillomavirus knowledge and 779 (66.5%) had poor cervical-cancer knowledge. Only 60 (9.5%) had ever undergone cervical-cancer screening, and 23 (2.0%) had received at least one Human papillomavirus -vaccine dose. Reported adverse events included allergic reactions (13, 6.8%) and dizziness or fainting (13, 56.5%). Approximately 578 (49.3%) were unaware of the Human papillomavirus vaccine, while 976 (83.3%) had not received—and did not intend to receive—the vaccine, citing lack of information, perceived low risk, adherence to preventive measures, or vaccine unavailability. Most participants demonstrated poor overall knowledge of Human papillomavirus and cervical cancer. Several demographic determinants significantly influenced knowledge and attitudes toward vaccination. Comprehensive health-education initiatives are urgently needed to enhance awareness and progress toward the World Health Organization 2030 elimination targets.

Women Living with HIV (WLHIV) are at increased risk of persistent high-risk Human Papillomavirus (HR-HPV) infections and cervical cancer. However, data on HPV genotype distribution and cervical cytologic abnormalities remain limited in North Africa, particularly among women receiving effective antiretroviral therapy (ART). To assess the frequency of cytologic abnormalities in WLHIV in Sétif, Algeria, identify HR-HPV genotypes, and evaluate associated immunovirological factors. A cross-sectional study was conducted from January to December 2024 at the HIV/STI/AIDS Reference Center in Sétif. WLHIV aged ≥ 18 years who provided informed consent were included. Each participant underwent a gynecological examination, cervical cytology (Pap smear), HR-HPV genotyping by molecular biology, and immunovirological assessment (CD4 T-cell count, HIV viral load). Colposcopy and biopsy were performed when indicated. Among 115 enrolled participants, 100 smears were interpretable. Cytologic abnormalities : Atypical Squamous Cells of Undetermined Significance (ASC-US), Low-Grade/High-Grade Squamous Intraepithelial Lesions LSIL, HSIL) were found in 28% of WLHIV. HR-HPV infection was detected in 32% of participants, mainly genotypes HPV52, HPV16, and HPV18. A significant association was observed between HR-HPV positivity and high-grade lesions (HSIL) (p = 0.018; OR = 9.57, 95% CI: 1.02-89.48). WLHIV in Algeria show a high prevalence of HPV-related cytologic abnormalities, even with adequate immune status and viral suppression. These findings emphasize the importance of regular cervical screening and support current global recommendations for comprehensive prevention strategies, including HPV testing and vaccination.