Reliability of toxicokinetic modelling for PFAS exposure assessment in contaminated water in northern Italy.

Introduction: Long-term contamination of tap water and groundwater by perfluoroalkyl and polyfluoroalkyl substances (PFASs) has been documented in the Veneto region of northern Italy. This study aimed to assess the exposure of individuals residing in the contaminated area and to test several toxicokinetic (TK) models of varying complexities to identify an efficient method for predicting perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) concentrations in human serum using observed data.The ultimate goal is to provide public health officials with guidance on selecting the appropriate TK model for specific contexts, a reliable and rapid tool to support human bio-monitoring (HBM) studies. Methods: Two simpler empirical TK models and a more complex multi-compartment physiologically based toxicokinetic (PBTK) model were compared with individual and aggregate data from an HBM study. In addition, the PBPK model was modified by adjusting input parameters and introducing new terms into the equations within the original model code. These modifications aimed to optimize the results compared to the original model, with some versions incorporating adjustments to account for the influence of menstruation in women. All models were evaluated to understand their strengths and weaknesses, providing guidance on the appropriate model to use according to specific scenarios. Results: The results obtained from the tested models were quite similar, with significant improvements observed only in the modified models. Simpler models also provided satisfactory results in scenarios involving low PFOS serum concentrations and recent exposure cessation. In many cases, predictions demonstrated high accuracy, particularly at the aggregate level and for women. Conclusions: These findings suggest that environmental protection agencies and health authorities may benefit from employing the tested models at the aggregate level as an initial step in HBM studies, rather than conducting more invasive and expensive screening campaigns.

Disparate exposure to physically demanding working conditions in France.

BACKGROUND: Our study was aimed at examining disparate exposure to physically demanding working conditions in France, a key objective being to identify the types of employees/jobs requiring high-priority preventive actions. METHODS: We analyzed the data from the 2017 French nationwide cross-sectional survey (SUMER) on occupational hazards to which French employees in various sectors were subjected. The prevalence of several types of physically demanding working conditions (lifting of heavy loads, awkward body postures, vibrations, noise, and extreme temperatures) was explored. Potential associations of individual and job characteristics with these factors of hardship at work were studied by multivariate logistic regression. RESULTS: In total, 48% of employees were exposed to at least one physically demanding working condition and 24.8% were exposed to multiple constraints. While managers and intellectual professionals were exposed relatively infrequently to physical constraints, blue-collar workers experienced the highest frequency of exposure. On the one hand, the role of company size depended on the factor of hardship at work considered; on the other hand, employees in large-scale companies were generally less exposed. As expected, employees in the construction industry were the most exposed to physical constraints; that said, our results also show that some activities in the services sector (e.g., personal care, administrative and support services) were quite significantly affected by a wide array of physically demanding working conditions. CONCLUSION: Notwithstanding the establishment in France of Plans de Santé au travail (preventive workplace health and safety plans), occupational risks were found to be high, and above all, they were unevenly distributed among the various socio-professional categories, and strongly contributed to social inequalities in health. Our results identify the types of publics to be designated as high-priority targets for preventive measures aimed at reducing the adverse impacts of physically demanding working conditions and the incidence of associated musculoskeletal disorders.

Genitourinary cancer in the elderly.

The subject of genitourinary cancer in the elderly becomes increasingly more important as our population of patients older than 50 years expands. Carcinoma of the kidney, bladder, and prostate all have an increasing incidence over the age of 50 and have a predilection for afflicting men more commonly than women. Etiologic factors, especially with bladder and kidney carcinomas, are well documented and in some cases preventable. Screening the urine for hematuria and careful digital rectal examinations may uncover a higher percentage of these malignancies in earlier, more curable stages. Recent advances in the treatment of all of these malignancies have improved survival and quality of life for these patients.

Antisera to a rabbit urinary tract antigen also react with human bladder and kidney tissue.

The mucin layer covering the bladder transitional cell mucosa appears to function as a primary defense mechanism against bacterial infection. We have previously prepared a glycoprotein fraction (GP1) from the urinary bladder mucosa of NZW rabbits and raised murine antisera against it. These antisera react with bladder, ureter and kidney tissue from rabbits, rats, guinea pigs, and hamsters. We now show that a similar substance occurs in human kidneys and bladder. In order to remove antibodies reactive with the Tamm-Horsfall protein (THP), the antisera were initially absorbed with an immunoadsorbent composed of purified human THP covalently bound to Sepharose CL-4B gel. Using an enzyme linked immunosorbent assay (ELISA) it could be shown that the absorbed antisera did not react with THP but retained a high titer in binding to GP1. Immunohistochemical procedures involving avidin-biotin-immunoperoxidase staining demonstrated that the absorbed anti-GP1 reacted well with six human urinary bladder biopsy specimens and two kidney autopsy specimens while normal murine sera showed little or no binding. Although this reactivity was not as strong as that found with homologous tissue (rabbit) these studies suggest that GP1, an antigen common to several animal species, is also related to a human urinary tract component.