Advances in neurotoxicology, Год журнала: 2023, Номер unknown, С. 325 - 366
Опубликована: Янв. 1, 2023
Язык: Английский
Environmental Science & Technology, Год журнала: 2024, Номер 58(2), С. 1064 - 1075
Опубликована: Янв. 1, 2024
Perfluoro-2-methoxyacetic acid (PFMOAA) is a short-chain perfluoroalkyl ether carboxylic that has been detected at high concentrations (∼10 μg/L) in drinking water eastern North Carolina, USA, and human serum breastmilk China. Despite documented exposure there are almost no toxicity data available to inform risk assessment of PFMOAA. Here we exposed pregnant Sprague–Dawley rats range PFMOAA doses (10–450 mg/kg/d) via oral gavage from gestation day (GD) 8 postnatal (PND) 2 compared results those previously reported for perfluorooctanoic (PFOA) hexafluoropropylene oxide–dimer (HFPO–DA or GenX). Newborn pups displayed reduced birthweight (≥30 mg/kg), depleted liver glycogen (all doses), hypoglycemia (≥125 numerous significantly altered genes the associated with fatty glucose metabolism similar gene changes produced by HFPO–DA. Pup survival was ≥125 mg/kg, necropsy on PND2 both maternal neonatal animals increased weights, aspartate aminotransferase (AST), thyroid hormones all (≥10 mg/kg). Pups also highly elevated cholesterol doses. dose F1 were PFOA but considerably higher than We calculated 10% effect levels (ED10 EC10) relative potency factors (RPF; = index chemical) among three compounds based concentration (μM). Reduced pup glycogen, weights hormone (maternal pup) most sensitive end points modeled. ∼3–7-fold less potent RPFs, slightly more weights. developmental toxicant rat producing constellation adverse effects
Язык: Английский
Процитировано
7
Archives of Toxicology, Год журнала: 2023, Номер 98(2), С. 507 - 524
Опубликована: Дек. 20, 2023
Abstract Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants with various adverse health effects in humans including disruption of lipid metabolism. Aim the present study was to elucidate molecular mechanisms PFAS-mediated on metabolism human cells. Here, we examined impact a number PFAS (PFOS, PFOA, PFNA, PFDA, PFHxA, PFBA, PFHxS, PFBS, HFPO-DA, PMPP) some exposure-relevant mixtures being composed PFOS, PFNA PFHxS HepaRG cells, an vitro model for hepatocytes. At near cytotoxic concentrations, selected induced triglyceride accumulation cells consistently affected expression marker genes steatosis, as well PPARα target related cholesterol metabolism, pointing common disrupting cellular homeostasis. activation by transactivation assay HEK293T synergistic were observed at sum concentrations higher than 25 µM, whereas additivity lower µM. Of note, any effect assays occurred that least four five magnitudes above real-life internal exposure levels general population.
Язык: Английский
Процитировано
16
The Science of The Total Environment, Год журнала: 2024, Номер 953, С. 175978 - 175978
Опубликована: Сен. 1, 2024
Язык: Английский
Процитировано
6
The Science of The Total Environment, Год журнала: 2024, Номер 953, С. 175958 - 175958
Опубликована: Сен. 2, 2024
Язык: Английский
Процитировано
6
Environmental Science & Technology, Год журнала: 2023, Номер 57(51), С. 21627 - 21636
Опубликована: Дек. 13, 2023
Per- and polyfluoroalkyl substances (PFAS) are ubiquitous persistent chemicals associated with multiple adverse health outcomes; however, the biological pathways affected by these unknown. To address this knowledge gap, we used data from 264 mother–infant dyads in Health Outcomes Measures of Environment (HOME) Study employed quantile-based g-computation to estimate covariate-adjusted associations between a prenatal (∼16 weeks' gestation) serum PFAS mixture [perfluorooctanesulfonic acid (PFOS), perfluorooctanoic (PFOA), perfluorohexanesulfonic (PFHxS), perfluorononanoic (PFNA)] 14,402 features measured cord serum. The was four features: PFOS, PFHxS, putatively identified metabolite (3-monoiodo-l-thyronine 4-O-sulfate), an unidentified feature (590.0020 m/z 441.4 s retention time; false discovery rate <0.20). Using pathway enrichment analysis coupled g-computation, 49 metabolic pathways, most notably amino acid, carbohydrate, lipid cofactor vitamin metabolism, as well glycan biosynthesis metabolism (P(Gamma) <0.05). Future studies should assess if mediate exposure infant or child outcomes, such birthweight vaccine response.
Язык: Английский
Процитировано
10
Journal of Hazardous Materials, Год журнала: 2025, Номер unknown, С. 137751 - 137751
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
Critical Reviews in Toxicology, Год журнала: 2025, Номер unknown, С. 1 - 25
Опубликована: Апрель 9, 2025
The benchmark dose (BMD) approach employs dose-response modeling to determine the associated with a small change in response relative background response. Here, we introduce conceptual framework for continuous data that is based on key risk assessment principles and requirements. Based this framework, define class of models sharing same four biologically interpretable model parameters, while exhibiting five common properties are essential from perspective: such denoted as "canonical" models. first two canonical straightforward: property 1. should predict positive values only (as measurements endpoints typically positive) 2. outcomes not depend measurement unit. Canonical 3 reflects observation toxicological related different subgroups (e.g. species, sexes, exposure durations) (at least approximately) parallel log-dose scale, which at time an implicit assumption defining fundamental concepts, extrapolation factors, potency factors (RPFs), sensitivity (RSFs). Property 4 needed enable comparisons differing maximum A fifth our view choices regarding expression, assumed distribution within-group variation, (BMR) being used be internally consistent. discuss suitable fit curves combined datasets durations). Doing so provides tool check particular analyzed. We provide review empirical evidence indicating has general validity, highly fortunate, legitimizes use RPFs assessment. then evaluate what extent approaches current BMD guidance by European Food Safety Authority (EFSA) or U.S. Environmental Protection Agency (US-EPA) comply modeling, concluding partly case. latter can have unfavorable sometimes far-reaching consequences. For instance, some recommended non-canonical result BMDs when changing unit µg mg). As another example, recently developed EFSA implements covariate analysis way cannot possibly represented any disadvantage, preclude effective development prior distributions Bayesian approach. Finally, argue concomitant but important advantage using methodology will more transparent, assessors better able understand it, high societal impact easily defended. present paper may helpful toxicologists critically follow developments level.
Язык: Английский
Процитировано
0
Environmental Toxicology and Chemistry, Год журнала: 2023, Номер 43(1), С. 97 - 104
Опубликована: Сен. 27, 2023
Biomonitoring data have consistently demonstrated that fish, wildlife, and humans are exposed to multiple per- polyfluoroalkyl substances (PFAS) in drinking water foods. Despite ubiquitous exposure mixtures of PFAS, there is a lack vivo PFAS mixture research addresses whether these chemicals act cumulative, dose-additive (DA) manner or they behave independently. For this reason, critical need for studies designed evaluate the cumulative toxicity potential chemical interactions support assessment human ecological risks also define appropriate regulatory actions. Our primary objective was previously published Japanese quail chick mortality concentration-response perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), PFOS + PFOA use statistical modeling determine effects were accurately predicted by either DA response addition modeling. In addition, we wanted compare different models one model produced more accurate predictions than others. results hypothesis on shared endpoints from co-exposure approaches predictive estimates effects. Given limited number been executed with enough individual test mixtures, re-analysis an important contribution our understanding how act. The analysis will provide agencies as begin implement hazard assessments higher vertebrates. Environ Toxicol Chem 2024;43:97-104. © 2023 SETAC. This article has contributed U.S. Government employees their work public domain USA.
Язык: Английский
Процитировано
3
Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
0
Toxicological Sciences, Год журнала: 2024, Номер 202(1), С. 36 - 49
Опубликована: Авг. 13, 2024
Abstract Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals known for their environmental persistence resistance to biodegradation. This study investigated the impact of adolescent exposure a PFAS mixture on adult ovarian function. Female CD-1 mice were orally exposed vehicle control or (comprised perfluorooctanoic acid, perfluorooctanesulfonic undecafluoro-2-methyl-3-oxahexanoic perfluorobutanesulfonic acid) 15 d. After 42-d recovery period, reproductive hormones, fibrosis, gene protein expression analyzed using ELISA, Picrosirius red staining, qPCR, immunoblotting, respectively. Results revealed that did not affect body organ weight, although weight slightly decreased. PFAS-exposed exhibited disturbed estrous cycle, with less time spent in proestrus than mice. Follicle counting indicated reduction primordial primary follicles. Serum analysis no changes steroid follicle-stimulating hormone, anti-Müllerian but significant increase luteinizing hormone was observed PFAS-treated Ovaries collected from had increased mRNA transcripts steroidogenic enzymes fatty acid synthesis-related genes. also collagen content ovary. Additionally, serum tumor necrosis factor-α levels higher Finally, abundance Hippo pathway components upregulated ovaries Overall, these findings suggest can disrupt function adulthood.
Язык: Английский
Процитировано
0