Aggregate Exposure Research Articles

P19-78 Simulating chronic exposure to DEHP with an open-source PBK model: first steps towards aggregate exposure with PK-Sim

P19-78 Simulating chronic exposure to DEHP with an open-source PBK model: first steps towards aggregate exposure with PK-Sim

International exposure and the transmission of financial shocks: Evidence from China

This study explores the impact of adverse financial shocks on Chinese firms through the bank lending channel and the firm borrowing channel. Using new data linking Chinese firms to their bank(s) and three measures of exposure to international markets, we find that banks with greater exposure to the international markets cut lending more during the financial and sovereign debt crises or when there is a negative shock to OECD GDP growth. Furthermore, state-owned bank loans are more pro-cyclical than private bank loans, and would have been even more pro-cyclical if state-owned banks had not assumed any responsibility for stimulus policies. With regard to the firm borrowing channel, we find that firms with higher weighted aggregate exposure to the international markets through banks have lower net debt, cash, employment, and capital investment during crises or when there is a negative shock to OECD GDP growth. Our results have significant implications for how global financial shocks are transmitted in a regulated financial market such as China.

Toxicological evidence integration to confirm the biological plausibility of the association between humidifier disinfectant exposure and respiratory diseases using the AEP-AOP framework.

Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease. We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into 3 lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway-adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases. The integration of each AEP-AOP component for PHMG and CMIT/MIT led to the development of an AEP-AOP model, wherein disinfectants released from humidifiers in aerosol or gaseous form reached target sites, causing respiratory damage through molecular initiating events and key events. The model demonstrated high reliability and relevance to the pathogenesis of respiratory diseases. The AEP-AOP model developed in this study provides strong evidence that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.

Environmental determinants of health: Measuring multiple physical environmental exposures at the United States census tract level

Physical environment plays a key role in determining human health risks. Exposure to toxins, weather extremes, degraded air and water quality, high levels of noise and limited accessibility to green areas can negatively affect health. Furthermore, adverse environmental exposures are often correlated with each other and with socioeconomic status, thereby compounding disadvantages in marginalized populations. Moreover, despite their importance in determining human health risks, the role of multiple environmental exposures is not well studied, and only a few resources contain aggregate environmental exposure data and only for selected areas of the contiguous US. To fill these gaps, we took a cumulative approach to measuring the environment by generating a composite Multi-Exposure Environmental Index (MEEI) as a US Census Tract-level summary of key environmental factors with known health effects. This measure quantifies multiple environmental exposures in the same area that can result in additive and synergistic effects on health outcomes. This information is crucial to better understand and possibly leverage environmental determinants of health for informed policy-making and intervention.

Roadmap for action for advancing aggregate exposure to chemicals in the EU

Roadmap for action for advancing aggregate exposure to chemicals in the EU

Assessing dietary bisphenol A exposure among Koreans: comprehensive database construction and analysis using the Korea National Health and Nutrition Examination Survey

Bisphenol A (BPA) exposure primarily occurs through dietary intake. This study aimed to estimate the extent of dietary BPA exposure among Koreans. A thorough literature search was conducted to establish a BPA content database encompassing common foods consumed in Korea, including various food raw materials and processed food products. Dietary exposure levels were estimated by integrating the constructed BPA database with comprehensive nationwide 24 h-dietary recall datasets. The finding revealed that dietary BPA exposure was low for most Koreans, with a mean of 14.5 ng/kg bw/day, but was higher for preschool-age children (over 23 ng). Canned foods accounted for 9–36% of the total dietary exposure of the highest dietary exposure groups; while across all age groups, a considerable amount was derived from canned tuna, contribution of canned fruits and canned coffee (milk-containing) was high for preschool-age children and adults, respectively. Notably, for adults, a substantial proportion also stemmed from beer packaged in cans. While diet contributed over 80% of aggregate exposure for most age groups, preschool-age children experienced 60% exposure through diet due to additional exposure from indoor dust. Even at the high exposure scenario, aggregate BPA exposure levels remained lower than the current tolerable daily intake (TDI) set by the Korean agency (20 μg/kg bw/day). Nevertheless, most Koreans were exposed to BPA levels surpassing the strictest TDI (0.2 ng/kg bw/day) set by the European Food Safety Authority.

Silicone wristbands reveal ubiquitous human exposure to ortho-phthalates and non-ortho-phthalate plasticizers in Southern California

In the United States and abroad, ortho-phthalates and non-ortho-phthalate plasticizers continue to be used within a diverse array of consumer products. Prior California-specific biomonitoring programs for ortho-phthalates have focused on rural, agricultural communities and, to our knowledge, these programs have not measured the potential for exposure to non-ortho-phthalate plasticizers. Therefore, the potential for human exposure to ortho-phthalates and non-ortho-phthalate plasticizers have not been adequately addressed in regions of California that have higher population density. Since there are numerous sources of ortho-phthalates and non-ortho-phthalate plasticizers in population-dense, urban regions, the objective of this study was to leverage silicone wristbands to quantify aggregate ortho-phthalate and non-ortho-phthalate plasticizer exposure over a 5-day period across two different cohorts (2019 and 2020) of undergraduate students at the University of California, Riverside (UCR) that commute from all over Southern California. Based on 5 d of aggregate exposure across two different cohorts, total ortho-phthalate plus non-ortho-phthalate plasticizer concentrations ranged, on average, from ∼100,000–1,000,000 ng/g. Based on the distribution of individual ortho-phthalate and non-ortho-phthalate plasticizer concentrations, the concentrations of di-isononyl phthalate (DiNP, a high molecular weight ortho-phthalate), di (2-ethylhexyl) phthalate (DEHP, a high molecular weight ortho-phthalate), and di-2-ethylhexyl terephthalate (DEHT, a non-ortho-phthalate plasticizer) detected within wristbands were higher than the remaining seven ortho-phthalates and non-ortho-phthalate plasticizers measured, accounting for approximately 94–97% of the total mass depending on the cohort. Overall, our findings raise concerns about chronic DiNP, DEHP, and DEHT exposure in urban, population-dense regions throughout California.

Occurrence, distribution characteristics and exposure assessment of perchlorate in the environment in China

Recognizing the extent of perchlorate pollution in the environment is critical to preventing and mitigating potential perchlorate harm to human health. The presence and distribution of perchlorate in Chinese environmental matrixes (water, atmosphere, and soil) were systematically investigated and comprehensively analyzed, and cumulative perchlorate exposure at the regional level was assessed using a combined aggregate exposure pathway method. The results showed that perchlorate is ubiquitous in the environment of China with significant regional differences. The total perchlorate exposure levels in each region of China ranked as South China > Southwest China > East China > North China > Northeast China > Northwest China. Although the average exposure dose of 0.588 (95 %CI: 0.142 −1.914) μg/kg bw/day being lower than the reference dose of 0.70 μg/kg bw/day, it was observed that the intake of perchlorate in some regions exceed this reference dose. Oral ingestion was the primary route of perchlorate exposure (89.97–96.57 % of the total intake), followed by dermal contact (3.21–9.16 %) and respiratory inhalation. Food and drinking water were the main sources of total perchlorate intake, contributing 52.54 % and 31.12 % respectively, with the latter contributing significantly more in southern China than in northern China. In addition, perchlorate exposure from dust sources was also noteworthy, as its contribution was as high as 23.18 % in some regions. These findings will improve understanding of the perchlorate risk and serve as a critical reference for policymakers in crafting improved environmental management and risk mitigation strategies in China and other nations.

Modeling of aggregated exposure to chemical substances of biological origin for various types of water use in case of priority cyanotoxins

Modeling of aggregated exposure to chemical substances of biological origin for various types of water use in case of priority cyanotoxins

In vitro to in vivo extrapolation to derive a metabolism factor for estimating the aggregate exposure to salicylic acid after dermal exposure of its esters

As part of the safety assessment of salicylate esters in cosmetics, we developed a metabolism factor based on in vitro to in vivo extrapolation (IVIVE) to provide a better estimation of the aggregate internal exposure to the common metabolite, salicylic acid. Optimal incubation conditions using human liver S9 were identified before measuring salicylic acid formation from 31 substances. Four control substances, not defined as salicylic esters but which could be mistaken as such due to their nomenclature, did not form salicylic acid. For the remaining substances, higher in vitro intrinsic clearance (CLint, in vitro) values generally correlated with lower LogP values. A “High-Throughput Pharmacokinetic” (HTPK) model was used to extrapolate CLint, in vitro values to human in vivo clearance and half-lives. The latter were used to calculate the percentage of substance metabolised to salicylic acid in 24 h in vivo following human exposure to the ester, i.e. the “metabolism factor”. The IVIVE model correctly reproduced the observed elimination rate of 3 substances using in silico or in vitro input parameters. For other substances, in silico only-based predictions generally resulted in lower metabolism factors than when in vitro values for plasma binding and liver S9 CLint, in vitro were used. Therefore, in vitro data input provides the more conservative metabolism factors compared to those derived using on in silico input. In conclusion, these results indicate that not all substances contribute equally (or at all) to the systemic exposure to salicylic acid. Therefore, we propose a realistic metabolism correction factor by which the potential contribution of salicylate esters to the aggregate consumer exposure to salicylic acid from cosmetic use can be estimated.

A systematic toxicologic study of polycyclic aromatic hydrocarbons on aquatic organisms via food-web bioaccumulation

Pollution-induced declines in fishery resources restrict the sustainable development of fishery. As a kind of typical environmental pollutant, the mechanism of polycyclic aromatic hydrocarbons (PAHs) facilitating fishery resources declines needs to be fully illustrated. To determine how PAHs have led to declines in fishery resources, a systematic toxicologic analysis of the effects of PAHs on aquatic organisms via food-web bioaccumulation was performed in the Pearl River and its estuary. Overall, PAH bioaccumulation in aquatic organisms was correlated with the trophic levels along food-web, exhibiting as significant positive correlations were observed between PAHs concentration and the trophic levels of fishes in the Pearl River Estuary. Additionally, waterborne PAHs exerted significant direct effects on dietary organisms (P < 0.05), and diet-borne PAHs subsequently exhibited significant direct effects on fish (P < 0.05). However, an apparent block effect was found in dietary organisms (e.g., zooplankton) where 33.49 % of the total system throughput (TST) was retained at trophic level II, exhibiting as the highest PAHs concentration, bioaccumulation factor (BAF), and biomagnification factor (BMF) of ∑15PAHs in zooplankton were at least eight-fold greater than those in fishes in both the Pearl River and its estuary, thereby waterborne PAHs exerted either direct or indirect effects on fishes that ultimately led to food-web simplification. Regardless of the block effect of dietary organisms, a general toxic effect of PAHs on aquatic organisms was observed, e.g., Phe and BaP exerted lethal effects on phytoplankton Chlorella pyrenoidosa and zooplankton Daphnia magna, and decreased reproduction in fishes Danio rerio and Megalobrama hoffmanni via activating the NOD-like receptors (NLRs) signaling pathway. Consequently, an assembled aggregate exposure pathway for PAHs revealed that increases in waterborne PAHs led to bioaccumulation of PAHs in aquatic organisms along food-web, and this in turn decreased the reproductive ability of fishes, thus causing decline in fishery resources.

Personal environmental exposure to plasticizers and organophosphate flame retardants using silicone wristbands and urine: Patterns, comparisons, and correlations

Plasticizers (PLs) and organophosphate flame retardants (OPFRs) are ubiquitous in the environment due to their widespread use and potential for leaching from consumer products. Environmental exposure is a critical aspect of the human exposome, revealing complex interactions between environmental contaminants and potential health effects. Silicone wristbands (SWBs) have emerged as a novel and non-invasive sampling device for assessing personal external exposure. In this study, SWBs were used as a proxy to estimate personal dermal adsorption (EDdermal) to PLs and OPFRs in Belgian participants for one week; four morning urine samples were also collected and analyzed for estimated daily intake (EDI). The results of the SWBs samples showed that all the participants were exposed to these chemicals, and the exposure was found to be highest for the legacy and alternative plasticizers (LP and AP), followed by the legacy and emerging OPFRs (LOPFR and EOPFR). In urine samples, the highest levels were observed for metabolites of diethyl phthalate (DEP), di-isobutyl phthalate (DiBP) and di-n-butyl phthalate (DnBP) among LPs and di(2-ethylhexyl) terephthalate (DEHT) for APs. Outliers among the participants indicated that there were other sources of exposure that were not identified. Results showed a significant correlation between EDdermal and EDI for DiBP, tris (2-butoxyethyl) phosphate (TBOEP) and triphenyl phosphate (TPhP). These correlations indicated their suitability for predicting exposure via SWB monitoring for total chemical exposure. The results of this pilot study advance our understanding of SWB sampling and its relevance for predicting aggregate environmental chemical exposures, while highlighting the potential of SWBs as low-cost, non-invasive personal samplers for future research. This innovative approach has the potential to advance the assessment of environmental exposures and their impact on public health.

Association between neighborhood poverty and ovarian reserve: the ovarian aging study.

This study aimed to examine the association between neighborhood poverty and ovarian reserve. Among 1,019 healthy premenopausal women in the Ovarian Aging Study, aggregate exposure to neighborhood poverty was examined in relation to biomarkers of ovarian reserve, antimüllerian hormone (AMH) and antral follicle count (AFC). Specifically, the interaction of age-x-neighborhood poverty was assessed cross-sectionally to determine whether AMH and AFC declines across women may be greater in women exposed to more neighborhood poverty. Neighborhood poverty was assessed by geocoding and linking women's residential addresses in adulthood to US Census data. Independent of covariates, a significant interaction term showed the association between age and AMH varied by degree of exposure to neighborhood poverty in adulthood ( b = -0.001, P < 0.05). AMH declines increased progressively across women exposed to low, medium, and high levels of neighborhood poverty. In addition, main effects showed that higher neighborhood poverty was related to higher AMH in the younger women only ( b = 0.022, P < 0.01). Results related to AFC were all nonsignificant ( P > 0.05). Across women, greater aggregate exposure to neighborhood poverty in adulthood was related to lower ovarian reserve, indexed by AMH. In addition, there was a positive association between neighborhood poverty and AMH in younger women that attenuated in the older women. Together, results suggest that neighborhood disadvantage may have detrimental impacts that manifest as initially higher AMH, resulting in greater ovarian follicle loss over time. However, it remains unclear whether these results examining differences across women may replicate when AMH declines by neighborhood poverty are examined longitudinally.

Cardiovascular and Kidney Risks in Individuals With Type 2 Diabetes: Contemporary Understanding With Greater Emphasis on Excess Adiposity.

In high-income countries, rates of atherosclerotic complications in type 2 diabetes have declined markedly over time due to better management of traditional risk factors including lipids, blood pressure, and glycemia levels. Population-wide reductions in smoking have also helped lower atherosclerotic complications and so reduce premature mortality in type 2 diabetes. However, as excess adiposity is a stronger driver for heart failure (HF), and obesity levels have remained largely unchanged, HF risks have not declined as much and may even be rising in the increasing number of people developing type 2 diabetes at younger ages. Excess weight is also an underrecognized risk factor for chronic kidney disease (CKD). Based on evidence from a range of sources, we explain how excess adiposity must be influencing most risks well before diabetes develops, particularly in younger-onset diabetes, which is linked to greater excess adiposity. We also review potential mechanisms linking excess adiposity to HF and CKD and speculate on how some of the responsible pathways-e.g., hemodynamic, cellular overnutrition, and inflammatory-could be favorably influenced by intentional weight loss (via lifestyle or drugs). On the basis of available evidence, we suggest that the cardiorenal outcome benefits seen with sodium-glucose cotransporter 2 inhibitors may partially derive from their interference of some of these same pathways. We also note that many other complications common in diabetes (e.g., hepatic, joint disease, perhaps mental health) are also variably linked to excess adiposity, the aggregated exposure to which has now increased in type 2 diabetes. All such observations suggest a greater need to tackle excess adiposity earlier in type 2 diabetes.

A Machine Learning Approach to Predict Relative Residual Strengths of Recycled Aggregate Concrete after Exposure to High Temperatures

In recent years, there has been a heightened focus among researchers and policymakers on assessing the environmental impact and sustainability of human activities. In this context, the reutilization of construction materials, particularly recycled aggregate concrete, has emerged as an environmentally friendly choice in construction projects, gaining significant traction. This study addresses the critical need to investigate the mechanical properties of recycled aggregate concrete under diverse extreme scenarios. Conducting an extensive literature review, key findings were synthesized on the relative residual strength of recycled aggregate concrete following exposure to high temperatures. Leveraging these insights, innovative hybrid machine learning models were developed, offering practical equations and model trees for predicting the relative residual compressive strength, flexural strength, elasticity modulus, and splitting tensile strength of recycled aggregate concrete post high temperature exposure. Uncertainty analysis was performed on each model to assess the reliability, while sensitivity analysis was performed to find out the significance of each input variable for each predictive model. This paper presents interpretable models achieving high levels of performance, with R2 values of 0.91, 0.94, 0.9, and 0.96 for predicting the relative residual compressive strength, flexural strength, modulus of elasticity, and splitting tensile strength of RCA concrete exposed to high temperatures, respectively. The unique contribution of the paper lies in the provision of easily applicable equations and model trees, enhancing accessibility for practitioners seeking to estimate mechanical properties of recycled aggregate concrete. Notably, our hybrid machine learning models stand out for their user-friendly nature compared with conventional ML algorithms, without compromising on accuracy. This paper not only advances our understanding of sustainable construction practices but also equips industry professionals with efficient tools for practical implementation.

Experimental assessment of appropriate time for aggregate exposure at the surface of cement concrete pavement

ABSTRACT Exposed aggregate concrete (EAC) pavement is a commonly employed technology in Europe for the construction of highways. The technical challenges associated with pavement construction include achieving both a comfortable ride and the desired skid resistance, while ensuring the long-term concrete durability. Maintaining uniformity of concrete mix, precise dosing of retarding agents, optimal selection of brushing time, and ensuring adequate curing conditions are identified as critical factors for achieving the designed ride performance. This study is focused on determining the appropriate time for the brushing operation, conducted to expose aggregate grains at the surface of the pavement. Laboratory tests were performed on concrete mixes designed to replicate job mixes for the upper layer of a two-layer concrete pavement. Measurements of the mass of evaporated water from the cement paste, isothermal calorimetry tests, and modified Vicat tests were employed to predict the appropriate brushing time. The texture depth was determined using a laser profiler as a function of brushing time. Compressive strength, the rate of chloride ion migration, and scaling resistance were determined through tests conducted on specimens cut from exposed aggregate slabs. Results revealed the suitability of the developed test method for determining the appropriate time for brushing EAC pavements.

Detailed aggregate exposure analysis shows that exposure to fragrance ingredients in consumer products is low: Many orders of magnitude below thresholds of concern

The Research Institute for Fragrance Materials (RIFM) and Creme Global Cremeglobal.com partnered to develop an aggregate exposure model for fragrance ingredients. The model provides a realistic estimate of the total exposure of fragrance ingredients to individuals across a population. The Threshold of Toxicological Concern (TTC) and Dermal Sensitization Threshold (DST) were used to demonstrate the magnitude of low exposure to fragrance materials. The total chronic systemic, inhalation, and dermal 95th percentile exposures on approximately 3000 fragrance ingredients in RIFM's inventory were compared to their respective TTC or DST. Additionally, representative fragrance ingredients were randomly selected and analyzed for exposure distribution by product type (i.e., cosmetic/personal care, household care, oral care, and air care) and route of exposure. It was found that 76 % of fragrance ingredients fall below their respective TTC limits when compared to 95th percentile systemic exposure, while 99 % are below inhalation TTC limits. The lowest 95th percentile aggregate exposure by product type was from household care products, then air care, and oral care products. The highest exposure was from personal care/cosmetic products. The volume of use for most fragrance ingredients (63 %) was <1 metric ton, estimating that environmental exposure to fragrance ingredients is likely low.

A systems toxicology approach for identification of disruptions in cholesterol homeostasis after aggregated exposure to mixtures of perfluorinated compounds in humans.

Per- and polyfluoroalkyl substances (PFAS) are used in various household and industrial products. In humans, positive associations were reported between PFAS, including perfluorsulfonic acid and perfluorooctanoic acid, and cholesterol, a cardiometabolic risk factor. Animal studies show the opposite. Human-centered approaches are needed to better understand the effects of PFAS mixtures on cholesterol. Here, a systems toxicology approach is described, using a gene-centered cholesterol biokinetic model. PFAS exposure-gene expression relations from published data were introduced into the model. An existing PFAS physiologically based kinetic model was augmented with lung and dermal compartments and integrated with the cholesterol model to enable exposure-effect modeling. The final model was populated with data reflecting lifetime mixture exposure from: tolerable weekly intake values; the environment; high occupational exposures (ski waxing, PFAS industry). Results indicate that low level exposures (tolerable weekly intake, environmental) did not change cholesterol. In contrast, occupational exposures clearly resulted in internal PFAS exposure and disruption of cholesterol homeostasis, largely in line with epidemiological observations. Despite model limitations (eg, dynamic range, directionality), changes in cholesterol homeostasis were predicted for ski waxers, hitherto unknown from epidemiological studies. Here, future studies involving lipid metabolism could improve risk assessment.

Study of acid-resistant behavior of hydroxylated hexagonal boron nitride/isobutyltriethoxysilane composite coatings on sulfoaluminate concrete surfaces

Concrete, as the most common building material, is susceptible to erosion in acidic environments, leading to issues such as surface cracking and aggregate exposure. This study employs iso-butyltrimethoxysilane (IBTS) as the coating matrix and incorporates h-BN as a filler material to prepare h-BN/IBTS hybrid latex for addressing the problem of acid corrosion in concrete. By characterizing the binding state between h-BN and IBTS, tracking changes in mortar specimen composition during the corrosion process, this study analyzes the acid corrosion protection mechanism provided by h-BN/IBTS hybrid latex on the surface of mortar specimens. The experimental results demonstrate that hydroxylation-modified h-BN can effectively disperse within IBTS, thus alleviating the agglomeration phenomenon caused by silane volatilization. This enhancement improves the film quality of silane and increases coating tightness. The h-BN/IBTS hybrid latex significantly reduces the corrosion rate of cement mortar specimens in a sulfuric acid environment. This reduction is attributed to the introduction of h-BN, which substantially prolongs the erosion pathway for H+ and SO42- in sulfuric acid, reduces the formation of gypsum within the concrete's internal structure, and effectively preserves the microscale pore structure within the concrete.

Estrogenic activity of plastic nanoparticle mixtures under in vitro settings

This study provides science-based evidence on endocrine disrupting effects of polyethylene, polystyrene and polypropylene nanoparticles and their mixtures indicating the importance of hazard assessment of aggregate exposure to nanoplastics.