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      Exposure limits for indoor volatile substances concerning the general population: The role of population-based differences in sensory irritation of the eyes and airways for assessment factors

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          Abstract

          Assessment factors (AFs) are essential in the derivation of occupational exposure limits (OELs) and indoor air quality guidelines. The factors shall accommodate differences in sensitivity between subgroups, i.e., workers, healthy and sick people, and occupational exposure versus life-long exposure for the general population. Derivation of AFs itself is based on empirical knowledge from human and animal exposure studies with immanent uncertainty in the empirical evidence due to knowledge gaps and experimental reliability. Sensory irritation in the eyes and airways constitute about 30–40% of OELs and is an abundant symptom in non-industrial buildings characterizing the indoor air quality and general health. Intraspecies differences between subgroups of the general population should be quantified for the proposal of more ‘empirical’ based AFs. In this review, we focus on sensitivity differences in sensory irritation about gender, age, health status, and vulnerability in people, based solely on human exposure studies. Females are more sensitive to sensory irritation than males for few volatile substances. Older people appear less sensitive than younger ones. However, impaired defense mechanisms may increase vulnerability in the long term. Empirical evidence of sensory irritation in children is rare and limited to children down to the age of six years. Studies of the nervous system in children compared to adults suggest a higher sensitivity in children; however, some defense mechanisms are more efficient in children than in adults. Usually, exposure studies are performed with healthy subjects. Exposure studies with sick people are not representative due to the deselection of subjects with moderate or severe eye or airway diseases, which likely underestimates the sensitivity of the group of people with diseases. Psychological characterization like personality factors shows that concentrations of volatile substances far below their sensory irritation thresholds may influence the sensitivity, in part biased by odor perception. Thus, the protection of people with extreme personality traits is not feasible by an AF and other mitigation strategies are required. The available empirical evidence comprising age, lifestyle, and health supports an AF of not greater than up to 2 for sensory irritation. Further, general AFs are discouraged for derivation, rather substance-specific derivation of AFs is recommended based on the risk assessment of empirical data, deposition in the airways depending on the substance’s water solubility and compensating for knowledge and experimental gaps. Modeling of sensory irritation would be a better ‘empirical’ starting point for derivation of AFs for children, older, and sick people, as human exposure studies are not possible (due to ethical reasons) or not generalizable (due to self-selection). Dedicated AFs may be derived for environments where dry air, high room temperature, and visually demanding tasks aggravate the eyes or airways than for places in which the workload is balanced, while indoor playgrounds might need other AFs due to physical workload and affected groups of the general population.

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          Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment.

          Ecological risk assessors face increasing demands to assess more chemicals, with greater speed and accuracy, and to do so using fewer resources and experimental animals. New approaches in biological and computational sciences may be able to generate mechanistic information that could help in meeting these challenges. However, to use mechanistic data to support chemical assessments, there is a need for effective translation of this information into endpoints meaningful to ecological risk-effects on survival, development, and reproduction in individual organisms and, by extension, impacts on populations. Here we discuss a framework designed for this purpose, the adverse outcome pathway (AOP). An AOP is a conceptual construct that portrays existing knowledge concerning the linkage between a direct molecular initiating event and an adverse outcome at a biological level of organization relevant to risk assessment. The practical utility of AOPs for ecological risk assessment of chemicals is illustrated using five case examples. The examples demonstrate how the AOP concept can focus toxicity testing in terms of species and endpoint selection, enhance across-chemical extrapolation, and support prediction of mixture effects. The examples also show how AOPs facilitate use of molecular or biochemical endpoints (sometimes referred to as biomarkers) for forecasting chemical impacts on individuals and populations. In the concluding sections of the paper, we discuss how AOPs can help to guide research that supports chemical risk assessments and advocate for the incorporation of this approach into a broader systems biology framework.
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            In recent studies of the structure of affect, positive and negative affect have consistently emerged as two dominant and relatively independent dimensions. A number of mood scales have been created to measure these factors; however, many existing measures are inadequate, showing low reliability or poor convergent or discriminant validity. To fill the need for reliable and valid Positive Affect and Negative Affect scales that are also brief and easy to administer, we developed two 10-item mood scales that comprise the Positive and Negative Affect Schedule (PANAS). The scales are shown to be highly internally consistent, largely uncorrelated, and stable at appropriate levels over a 2-month time period. Normative data and factorial and external evidence of convergent and discriminant validity for the scales are also presented.
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              A Review of the Pathways of Human Exposure to Poly- and Perfluoroalkyl Substances (PFASs) and Present Understanding of Health Effects

              Here we review present understanding of sources and trends in human exposure to poly- and perfluoroalkyl substances (PFASs) and epidemiologic evidence for impacts on cancer, immune function, metabolic outcomes, and neurodevelopment. More than 4000 PFASs have been manufactured by humans and hundreds have been detected in environmental samples. Direct exposures due to use in products can be quickly phased out by shifts in chemical production but exposures driven by PFAS accumulation in the ocean and marine food chains and contamination of groundwater persist over long timescales. Serum concentrations of legacy PFASs in humans are declining globally but total exposures to newer PFASs and precursor compounds have not been well characterized. Human exposures to legacy PFASs from seafood and drinking water are stable or increasing in many regions, suggesting observed declines reflect phase-outs in legacy PFAS use in consumer products. Many regions globally are continuing to discover PFAS contaminated sites from aqueous film forming foam (AFFF) use, particularly next to airports and military bases. Exposures from food packaging and indoor environments are uncertain due to a rapidly changing chemical landscape where legacy PFASs have been replaced by diverse precursors and custom molecules that are difficult to detect. Multiple studies find significant associations between PFAS exposure and adverse immune outcomes in children. Dyslipidemia is the strongest metabolic outcome associated with PFAS exposure. Evidence for cancer is limited to manufacturing locations with extremely high exposures and insufficient data are available to characterize impacts of PFAS exposures on neurodevelopment. Preliminary evidence suggests significant health effects associated with exposures to emerging PFASs. Lessons learned from legacy PFASs indicate that limited data should not be used as a justification to delay risk mitigation actions for replacement PFASs.
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                Author and article information

                Contributors
                Kleinbeck@ifado.de
                Journal
                Arch Toxicol
                Arch Toxicol
                Archives of Toxicology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-5761
                1432-0738
                19 January 2024
                19 January 2024
                2024
                : 98
                : 3
                : 617-662
                Affiliations
                [1 ]Leibniz Research Centre for Working Environment and Human Factors, ( https://ror.org/05cj29x94) Dortmund, Germany
                [2 ]National Research Centre for the Working Environment, ( https://ror.org/03f61zm76) Copenhagen, Denmark
                Author information
                http://orcid.org/0000-0003-3705-6983
                https://orcid.org/0000-0003-1933-7351
                Article
                3642
                10.1007/s00204-023-03642-w
                10861400
                38243103
                b15e968f-bbda-4caa-aa3b-a464e23275ae
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 September 2023
                : 16 November 2023
                Funding
                Funded by: European Panel Foundation
                Categories
                Review Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2024

                Toxicology
                age,assessment factor,children,gender,sensitivity,sensory irritation
                Toxicology
                age, assessment factor, children, gender, sensitivity, sensory irritation

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