This paper describes DARAN (Defined Approach for Risk Assessment of New Nitrosamines), an new defined approach that uses lines of reasoning based on structure-activity relationship (SAR) patterns and ...Read-Across (RAx) to set transparent and acceptable limits for new N-nitrosamines for which no toxicological data exist. We selected the compound 1-methyl-4-nitrosopiperazine (MeNP) as a target to calculate a new acceptable limit on the basis of a more transparent and scientifically reasoned RAx. We used publicly available databases and datasets to retrieve experimental in vitro mutagenicity and in vivo carcinogenicity data for N-nitrosopiperazine compounds and to form the chemical category for an RAx. We carried out SAR analyses to try to understand patterns and to obtain interpretable inferences of variation in carcinogenic potency among the N-nitrosopiperazines compounds and their differences with the potent nitrosamines NDMA (N-nitrosodimethylamine) and NDEA (N-nitrosodiethylamine). To estimate an acceptable limit for the target MeNP, we used the scientifically based hypotheses and the evidence lines of about the influence of structural attributes for a robust RAx. On the basis of the criteria proposed in the Assessment Report EMA/369136/20202 and by using the SAR hypotheses obtained by the analysis, we obtained a robust RAx, scientifically supported assumptions, which resulted in TD50 values predicted from the closest structurally related compounds and a worst-case approach.
•A well-defined approach for setting limits for new N-nitrosamines in drugs is proposed.•Structure-activity relationship and Read-across analyses can provide more transparent and interpretable limits.•A practical example of a new acceptable limit calculation is shown for a new nitrosamine without toxicological data.•Based on the predicted carcinogenic potency of the new nitrosamine, regulatory insights for review of limits are provided.
Abstract Zoonotic spillover is a phenomenon characterized by the transfer of pathogens between different animal species. Most human emerging infectious diseases originate from non-human animals, and ...human-related environmental disturbances are the driving forces of the emergence of new human pathogens. Synthesizing the sequence of basic events involved in the emergence of new human pathogens is important for guiding the understanding, identification, and description of key aspects of human activities that can be changed to prevent new outbreaks, epidemics, and pandemics. This review synthesizes the connections between environmental disturbances and increased risk of spillover events based on the One Health perspective. Anthropogenic disturbances in the environment (e.g., deforestation, habitat fragmentation, biodiversity loss, wildlife exploitation) lead to changes in ecological niches, reduction of the dilution effect, increased contact between humans and other animals, changes in the incidence and load of pathogens in animal populations, and alterations in the abiotic factors of landscapes. These phenomena can increase the risk of spillover events and, potentially, facilitate new infectious disease outbreaks. Using Brazil as a study model, this review brings a discussion concerning anthropogenic activities in the Amazon region and their potential impacts on spillover risk and spread of emerging diseases in this region.
Background
Considering socioeconomic status (SES) in the diagnosis of obstructive sleep apnea (OSA) will enhance our understanding of socioeconomic disparities in clinical practice of sleep medicine. ...This systematic review analyzes the relations between SES and OSA measures.
Methodology
Eleven articles were identified through the Pubmed database. The National Institute of Health’s Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to rate the quality of these studies.
Results
This systematic review revealed that associations between socioeconomic status and OSA measures are similar for both adults, children, and adolescents. Our findings showed that: (1) A lower SES is associated with an increased risk of OSA, both in adults and children/adolescents as well as for men and women. (2) Several studies assessed sleep outcomes with a single question, an approach that is unable to capture the multi-dimensionality and day-to-day variability of sleep in general or OSA in particular, (3) Low SES has detrimental effects on sleep health. (4) Sleep questionnaires are more commonly used than objective measure to assess OSA.
Conclusions
Interaction between SES and OSA must be better understood to improve current clinical guidelines. Living conditions influence the trajectory of OSA with unknown speed and for an, undetermined period, pointing to the need for more studies on this topic. Future work should identify the effect of SES on the development and progression of OSA, determine the effect of behavioral intervention and local public health programs to reduce social inequalities associated with OSA.
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