Li Li

Novel organophosphate esters (OPEs), formed through chemical transformation of commercial antioxidants, are emerging contaminants with widespread environmental occurrence and potential health effects. Despite their widespread detection, the atmospheric reactivity, persistence, and transformation of novel OPEs remain unknown. Here, the heterogeneous OH oxidation of two surface-bound novel OPEs [tris(2,4-ditert-butylphenyl) phosphate (TDtBPP) and triisodecyl phosphate (TiDeP)] was explored by investigating the reaction kinetics and chemical mechanisms. The measured heterogeneous rate constants for TDtBPP and TiDeP were (2.81 ± 0.12) × 10–12 and (1.99 ± 0.16) × 10–12 cm3 molecules–1 s–1, respectively, equivalent to atmospheric lifetimes of up to 6.3 and 9.0 days. These lifetimes are significantly longer than previously predicted values (<1 day), suggesting that they are much more persistent in air than predicted. Based on UPLC-HRMS measurements, 22 transformation products from the heterogeneous reactions were identified for the first time. Analysis of atmospheric particle samples from two megacities in China identified four TDtBPP transformation products, demonstrating that the oxidation chemistry can occur under genuine environmental conditions. In-silico hazard screening further indicated that many transformation products may be more bioaccumulative and more toxic than the parent novel OPEs. The results not only provide new insights into the atmospheric persistence of novel OPEs but also underscore the significance of considering atmospheric transformation in the risk assessment of these emerging contaminants.

Indoor smoking of psychoactive substances exposes not only users through “firsthand smoke” (FHS) but also bystanders through pathways of “secondhand smoke” (SHS; exhaled or side-stream smoke) and “thirdhand smoke” (THS; residual contamination that persists indoors) via different routes of inhalation, mouthing-mediated ingestion, and dermal absorption. Here, we explore how chemical properties, smoking behaviors, and features of exposed individuals together shape exposure pathways and routes, using a mechanistic indoor chemical fate and exposure model with scenarios varying by retention rate (the fraction of smoke-generated chemicals absorbed by the smoker) and smoking frequency. We estimate adult and child exposure to seven representative compounds spanning orders-of-magnitude differences in volatility and hydrophobicity. We find that dominant exposure pathways and routes are strongly chemical-specific and scenario-dependent. FHS is consistently the dominant exposure pathway for substance users, whereas among nonsmoking exposed individuals, the relative importance of SHS and THS is determined jointly by chemical partitioning properties and the relative durations of active-smoking and postsmoking periods. Exposure to volatile chemicals (e.g., nicotine) is dominated by inhalation, exposure to compounds with intermediate hydrophobicity by dermal absorption, while highly hydrophobic, lowly volatile compounds (e.g., Δ9-tetrahydrocannabinol) receive meaningful contributions from all three routes. These findings highlight that broad generalizations about exposure dominance can misrepresent risks, particularly for nonusers and children.

Background: Scientific and regulatory efforts have been taken in the past 60 years to tackle chemical pollution. Evaluating the benefits and efficacy of chemical regulations is essential for convincing society of the necessity of such efforts. This study quantifies chemical pollution and exposure in a hypothetical world without chemical regulation, and assesses whether it would have led to a transgression of the safe operating space for humanity.Methods: Using polychlorinated biphenyls (PCBs) as indicator chemicals, we reconstruct their production and use in the absence of control measures. Based on estimations with a mechanistic modelling framework comprising the models CiP-CAFE, BETR-Global, and PROTEX, we contrast “historically observed” global emissions, environmental burdens, human exposures, and health hazards with those in a “world avoided” scenario.Findings: Without control measures, we estimate 6-fold higher cumulative global PCB emissions from 1930 to 2025, and a 7-fold higher global environmental PCB burden by 2025. The relative difference is particularly large in oceanic, less industrialized, and polar regions. A 34-fold higher human exposure suggests that at least 40% of the human population would have experienced average exposure exceeding a health-based threshold by 2025.Interpretation: The counterfactual analysis indicates that national and global regulatory measures targeting chemical pollution have prevented the transgression of a planetary boundary for novel entities. Simulations of the global risks posed by toxic chemicals under different regulatory scenarios can inform the delineation of the safe operating space.

Human toxicokinetics vary widely across individuals due to differences in physiological and biochemical factors. Yet, since such interindividual variability is difficult to quantify, most chemical risk assessment models rely on an “average” individual, potentially under-protecting those with disproportionately high susceptibility. Here, using the case of nicotine and its metabolites, we performed personalized mechanistic toxicokinetic simulations on the PROTEX model for 1,801 Americans to characterize interindividual variability in biotransformation and renal clearance capacities. We quantified interindividual variability by calculating fold deviations in each individual’s biotransformation and renal clearance rates, denoted as semiempirical, effective scaling factors α and β, from expected values based on demographic (age, sex) and anthropometric (body weight, height, body fat percentage) features. Results showed an approximately 40-fold range (5th–95th percentile; same after) in α and a 10-fold range in β. When individuals are exposed to the same absorbed chemical dose, interindividual variability in toxicokinetics can result in 15- to 18-fold differences in serum concentrations, of which ∼5-fold can be attributed to physiological variability linked to differences in demographics and anthropometry, while an additional 3- to 3.5-fold can be attributed to variability in α and β. A key implication of this work is to improve personalized reverse dosimetry modeling in the “new approach methodologies” framework. Using the derived α and β values, we estimated average daily absorbed doses of nicotine and compared them with self-reported smoking status. The highest doses were observed among individuals reporting both active and passive smoking, while evidence of underreporting was also detected among some individuals who reported no exposure.

Reliable quantification of children's ingestion of dust and soil is essential for accurate exposure and risk assessment. Yet, most existing estimation strategies, typically relying on a single tracer element or evaluating multiple tracers independently, suffer from measurement uncertainties, the burdensome collection of excreta volumes, incomplete accounting of exposure and elimination pathways, reliance on population-average assumptions, and the inability to distinguish dust ingestion from soil ingestion. To address these limitations, we develop a novel "multitracer" reconciliation approach that estimates individual-level ingestion rates of dust and soil particles by jointly using concurrent measurements of multiple elements in dust, soil, urine, and fecal samples and mathematically identifying the physiologically plausible solution that best satisfies all tracer-specific mass-balance equations simultaneously. This approach supports deriving personalized dust and soil ingestion rates that maintain physiological plausibility while minimizing inconsistencies across tracers. Applied to 112 U.S. children representing diverse demographic backgrounds, our approach produced estimates of dust, soil, and "combined" dust and soil ingestion rates (medians: 38, 10, and 75 mg/day, respectively; the sum of dust and soil medians differs from the "combined" median because individual children had varying relative contributions from dust and soil). These estimates agree with reference values provided in the U.S. EPA's Exposure Factors Handbook. Ingestion patterns varied with age, season, race/ethnicity, and body-mass-index category. This multitracer reconciliation framework provides a data-driven foundation for reducing uncertainty in exposure factors and refining child-specific risk characterization.

Consensus values from multiple QSAR models improved prediction of missing pesticides properties for more accurate risk assessment while PROTEX highlights the influential role of reactivity parameters.

Quaternary ammonium compounds (QACs) have been used as antimicrobial additives in textiles, but information on their levels in textiles and ecological impacts from laundry wastewater is scarce. Here, 119 textile products from Chinese online vendors were analyzed for traditional and emerging QACs using target and suspect screening approaches with high-resolution mass spectrometry. The total concentrations of 18 traditional QACs ranged from 7.34 to 145,000 ng/g, and 16 emerging QACs were identified with total concentrations at 5.45 to 349,000 ng/g. Under laboratory-controlled conditions, over 76% of the selected textiles exhibited QAC migration rates exceeding 50% after washing. In simulated laundry experiments, hand-washing released a ΣQAC concentration of 42.1 ng/mL, and machine-washing released 22.4 ng/mL, with differences attributed to the water volume used by different methods. Both laundry wastewater and QACs solution at equivalent concentrations caused dose-dependent immobilization of Daphnia magna. Combining bioassay-based risk characterization factors with environmental dilution factors across 150 countries, 7% of regions showed high risk after WWTP-treatment, increasing to 41% for direct discharge with sewage. The high migration rates suggest that QAC-treated textiles not only fail to maintain long-term antimicrobial efficacy but also contribute to continuous low-level environmental exposures, raising concerns about their essential use in nondisposable textile materials.

The quantitative characterization of multiple exposure routes to quaternary ammonium compounds (QACs) remains underexplored. In this study, paired samples of indoor dust, bulk air, hand wipes, silicone wristbands, and urine were collected from 109 adults residing in urban homes from South China in 2023. First, seven urinary biomarkers, including hydroxylated and carboxylated metabolites of C10-C14 benzylalkyldimethylammonium compounds (BACs), were identified using a combined in silico and in vitro workflow. Then, 23 QACs, including 6 C8-C18 BACs, 6 dialkyldimethylammonium compounds (C8-C18 DADMACs), 6 alkyltrimethylammonium compounds (C8-C18 ATMACs), and 5 emerging QACs, were ubiquitously detected in various environmental matrices, including dust (median ∑QAC concentrations of 39.6 μg/g), bulk air (130 pg/m³), hand wipes (1420 ng for two hands), and silicone wristbands (225 ng/g), respectively. A significantly positive correlation was observed between the logarithmically transformed masses of QACs detected in silicone wristbands and those from dust, bulk air, and hand wipes (r: 0.564, p < 0.01). Moreover, urinary hydroxylated and carboxylated C10- and C12-BACs were significantly correlated with corresponding parent compounds in wristbands (r: 0.481-0.607, p < 0.01). Finally, back calculation from urinary exposure biomarkers revealed that ingestion of surface residues was the dominant exposure route for C10-, C12-, and C14-BACs, accounting for 3.7%, 49.6%, and 18% of total exposure, respectively. The findings from this study propose suitable urinary exposure biomarkers and silicone wristbands as useful indicators for accurate internal and external exposure assessment, respectively, and highlight the importance of ingestion of surface residues as a major exposure route.

Different methods for estimating emission rates, mode of release and subsequent predicted environmental concentrations are illustrated and evaluated using monitoring data for some cyclic volatile methyl siloxanes (cVMS).

Humans are exposed to many chemicals from multiple sources through various pathways. Many semivolatile organic chemicals (SVOCs) are ubiquitous in indoor environments, but the extent of exposure and relative importance of different pathways (near-field or far-field) are uncertain. Here, 37 SVOCs with measured concentrations in indoor media are used in conjunction with a mass balance indoor fate, exposure, and toxicokinetic model to 1) estimate exposures from indoor environments, 2) incorporate measured dietary (far-field) exposures, 3) evaluate modeled biological concentrations in blood and urine against previously published human biomonitoring (HBM) estimates, 4) calculate the relative importance of different exposure pathways, and 5) demonstrate the value of using models and monitoring data to estimate aggregate exposure for human health assessment. All model calculated blood and urine concentrations are within 2 orders of magnitude of HBM values, and 73% are within 1 order of magnitude. The method explicitly considers uncertainty in measured indoor concentrations and mouthing-mediated ingestion (MMI). When median measured chemical concentrations in dust and MMI are used for modeling, far-field dietary intake is determined to be the dominant contributor to the overall exposure for almost all investigated SVOCs. However, when modeling with higher (third quartile reported) measured chemical concentrations in dust and ∼ 3x higher dust ingestion rates, near-field sources result in exposures for some SVOCs that are comparable to or exceed contributions from far-field exposure pathways. The model also addresses measurement data gaps and, combined with the monitoring data, provides a method to estimate chemical emission rates.