Integrated approaches for immunotoxicity risk assessment: challenges and future directions DOI Creative Commons

Vaisali Chandrasekar,

Anu Jayanthi Panicker,

Avishek Dey

et al.

Deleted Journal, Journal Year: 2024, Volume and Issue: 1(1)

Published: Oct. 29, 2024

The integration of immunotoxicity data into chemical risk assessment paradigms is essential for comprehensively evaluating the potential health hazards posed by exposures. This review provides a comprehensive overview methodologies, challenges, and future directions integrating frameworks. It discusses fundamental principles immunotoxicology its relevance to assessment, highlighting critical roles immune system in defense against harmful agents. Next, we explore traditional frameworks, including exposure hazard identification, dose–response characterization, need incorporating endpoints enhance characterization estimation. Subsequently, delve modelling immunotoxicity, elucidating principles, methods, case studies illustrating relationships extrapolation from animal humans. Furthermore, discuss focusing on identification immunotoxic hazards, evaluation endpoints, utilization immunological biomarkers assessment. We then examine cumulative strategies, presenting conceptual framework assessing risks multiple exposures methods different chemicals. Lastly, emerging trends high-throughput screening assays, omics technologies, computational modelling, alternative testing along with regulatory implications research needs. valuable insights researchers, regulators, stakeholders involved public protection, facilitating development evidence-based strategies safeguarding human associated

Language: Английский

Sub-acute exposure of male guppies (Poecilia reticulata) to environmentally relevant concentrations of PFOA and GenX induces significant changes in the testis transcriptome and reproductive traits DOI Creative Commons
Clelia Gasparini, Silvia Iori, Edoardo Pietropoli

et al.

Environment International, Journal Year: 2024, Volume and Issue: 187, P. 108703 - 108703

Published: April 26, 2024

Poly- and perfluoroalkyl substances (PFAS) are frequently detected in the environment linked to adverse reproductive health outcomes humans. Although legacy PFAS have been phased out due their toxicity, alternative increasingly used despite fact that information on toxic effects traits is particularly scarce. Here, we exposed male guppies (Poecilia reticulata) for a short period (21 days) an environmentally realistic concentration (1 ppb) of PFOA, PFAS, its replacement compound, GenX, assess impact gene expression. Exposure did not impair survival but instead caused sublethal effects. Overall, exposure changes sexual behaviour had detrimental sperm motility. Sublethal variations were also seen at transcriptional level, with modulation genes involved immune regulation, spermatogenesis, oxidative stress. We observed bioaccumulation which was higher PFOA than GenX. Our results offer comprehensive comparison these two shed light toxicity newly emerging PFAS. It therefore evident even low concentrations exposure, can subtle yet significant behaviour, fertility, immunity. These findings underscore potential ramifications pollution under natural conditions fish populations.

Language: Английский

Citations

13
Advancements in detection techniques for per- and polyfluoroalkyl substances: A comprehensive review DOI

Yahan Cui,

Shenghui Wang, Dandan Han

et al.

TrAC Trends in Analytical Chemistry, Journal Year: 2024, Volume and Issue: 176, P. 117754 - 117754

Published: May 8, 2024

Language: Английский

Citations

13
Toward the development of a molecular toolkit for the microbial remediation of per-and polyfluoroalkyl substances DOI Creative Commons
Miao Hu, Colin Scott

Applied and Environmental Microbiology, Journal Year: 2024, Volume and Issue: 90(4)

Published: March 17, 2024

ABSTRACT Per- and polyfluoroalkyl substances (PFAS) are highly fluorinated synthetic organic compounds that have been used extensively in various industries owing to their unique properties. The PFAS family encompasses diverse classes, with only a fraction being commercially relevant. These found the environment, including water sources, soil, wildlife, leading human exposure fueling concerns about potential health impacts. Although degradation is challenging, biodegradation offers promising, eco-friendly solution. Biodegradation has effective for variety of contaminants but yet be successful due paucity identified microbial species capable transforming these compounds. Recent studies investigated biotransformation fluoride release; however, number specific microorganisms enzymes demonstrable activity remains limited. This review discusses could metabolism, haloacid dehalogenases, reductive cytochromes P450, alkane butane monooxygenases, peroxidases, laccases, desulfonases, mechanisms resistance intracellular fluoride. Finally, we emphasize enzyme engineering advance strategies provide insights future research this field.

Language: Английский

Citations

12
Associations of per- and polyfluoroalkyl substances (PFAS) and their mixture with risk of rheumatoid arthritis in the U.S. adult population DOI Creative Commons

Jian-Chao Qiao,

Zhenhua Li, Yubo Ma

et al.

Environmental Health, Journal Year: 2024, Volume and Issue: 23(1)

Published: April 13, 2024

Abstract Background Per- and polyfluoroalkyl substances (PFAS) are known environmental contaminants with immunosuppressive properties. Their connection to rheumatoid arthritis (RA), a condition influenced by the immune system, is not well studied. This research explores association between PFAS exposure RA prevalence. Methods utilized data from NHANES, encompassing sample of 10,496 adults 2003–2018 cycles, focusing on serum levels several PFAS. The presence was determined based self-reports. study used multivariable logistic regression assess relationship individual risk, adjusting for covariates calculate odds ratios (ORs). combined effects mixtures were evaluated using BKMR, WQS regression, quantile g-computation. Additionally, sex-specific associations explored through stratified analysis. Results Higher PFOA (OR = 0.88, 95% CI: 0.79, 0.98), PFHxS 0.91, 0.83, 1.00), PFNA 0.87, 0.77, PFDA 0.89, 0.81, 0.99) concentration related lower RA. Sex-specific analysis in single chemical models indicated significant inverse only evident females. BKMR did show an obvious pattern estimates across mixture. outcomes sex-stratified g-computation demonstrated that increase mixture associated decreased females (OR: 0.76, 0.62, 0.92). We identified interaction term WQS*sex 100 repeated hold out Notably, higher significantly reduced (mean OR 0.93, 0.98). Conclusions indicates potential various their observed relationships statistically but males. These findings contribute growing body evidence indicating may have effects.

Language: Английский

Citations

10
Uptake and distribution of perfluoroalkyl substances by grafted tomato plants cultivated in a contaminated site in northern Italy DOI Creative Commons
Ilaria Battisti, Anna Rita Trentin,

Emma Franzolin

et al.

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 915, P. 170032 - 170032

Published: Jan. 18, 2024

Poly- and perfluoroalkyl substances (PFAS) are highly persistent mobile pollutants raising alarming concerns due to their capability accumulate in living organisms exert toxic effects on human health. We studied the accumulation of different PFAS leaves fruits tomato plants grown a PFAS-polluted soil North-East Italy. Tomato were grafted with rootstocks characterized by vigor, irrigated groundwater. Leaves first sixth truss analyzed at full plant maturity. All varieties accumulated fruits, highest concentrations detected most vigorous rootstock reflecting concentration profile irrigation water. chain length from 4 8 C atoms carboxylic sulfonic functional groups leaves, whereas only C4, C5, C6 fruits. A general trend decreasing upon increasing height trusses was observed. Calculation target hazard quotient (THQ) showed values depending vigor. The index (HI) slightly higher than 1 for plants, indicating potential risks health associated consumption contaminated

Language: Английский

Citations

9
Investigating mouse hepatic lipidome dysregulation following exposure to emerging per- and polyfluoroalkyl substances (PFAS) DOI Creative Commons
Kaylie I. Kirkwood‐Donelson, Jessie R. Chappel, E. A. Tobin

et al.

Chemosphere, Journal Year: 2024, Volume and Issue: 354, P. 141654 - 141654

Published: March 8, 2024

Language: Английский

Citations

9
New approach methodologies to enhance human health risk assessment of immunotoxic properties of chemicals — a PARC (Partnership for the Assessment of Risk from Chemicals) project DOI Creative Commons

Igor Snapkow,

Nicola Smith, Emma Arnesdotter

et al.

Frontiers in Toxicology, Journal Year: 2024, Volume and Issue: 6

Published: April 9, 2024

As a complex system governing and interconnecting numerous functions within the human body, immune is unsurprisingly susceptible to impact of toxic chemicals. Toxicants can influence through multitude mechanisms, resulting in immunosuppression, hypersensitivity, increased risk autoimmune diseases cancer development. At present, regulatory assessment immunotoxicity chemicals relies heavily on rodent models limited number Organisation for Economic Co-operation Development (OECD) test guidelines, which only capture fraction potential properties. Due this limitation, various authorities, including World Health Organization European Food Safety Authority have highlighted need development novel approaches without use animals testing In paper, we present concise overview ongoing efforts dedicated developing standardizing methodologies comprehensive characterization immunotoxic effects chemicals, are performed under EU-funded Partnership Assessment Risk from Chemicals (PARC).

Language: Английский

Citations

9
A Review of the Occurrence and Distribution of Per- and Polyfluoroalkyl Substances (PFAS) in Human Organs and Fetal Tissues DOI Creative Commons
José L. Domingo

Environmental Research, Journal Year: 2025, Volume and Issue: unknown, P. 121181 - 121181

Published: Feb. 1, 2025

Language: Английский

Citations

1
Associations of PFAS and OH-PCBs with risk of multiple sclerosis onset and disability worsening DOI Creative Commons
Aina Vaivade, Ida Erngren, Henrik Carlsson

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 27, 2025

Abstract Exposure to per- and polyfluorinated substances (PFAS) hydroxylated polychlorinated biphenyls (OH-PCBs) is associated with adverse human health effects, including immunosuppression. It unknown if these can affect the course of autoimmune diseases. This study was based on 907 individuals multiple sclerosis (MS) matched controls, where MS cases were followed longitudinally using Swedish register. We demonstrate sex- disease-specific differences in serum PFAS concentrations between controls. Moreover, two OH-PCBs (4-OH-CB187 3-OH-CB153) are an increased risk developing sclerosis, regardless sex immigration status. With a clinical follow-up time up 18 years, increase perfluorooctanoic acid (PFOA), perfluorooctane sulfonic (PFOS), perfluorodecanoic (PFDA) decreases confirmed disability worsening both sexes, as well perfluoroheptanesulfonic (PFHpS) perfluorononanoic (PFNA), only males MS. These results show previously associations MS, inverse exposure

Language: Английский

Citations

1
In vitro approaches to investigate the effect of chemicals on antibody production: the case study of PFASs DOI Creative Commons
Martina Iulini, Valeria Bettinsoli, Ambra Maddalon

et al.

Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

The increasing variety and quantity of new chemical substances have raised concerns about their potential immunotoxic effects, making it essential to assess impact on human health. One key concern is the reduction antibody production, as seen with per- poly-fluoroalkyl (PFASs), commonly known "forever chemicals." Both in vivo epidemiological data show that PFASs immunosuppressive leading reduced responses, particularly following vaccination. In animal studies, T cell-dependent (TD) response gold standard for assessing effects immune function. This study utilized two vitro approaches investigate chemicals production using peripheral blood mononuclear cells. Initial tests used unstimulated, negative (vehicle), positive (rapamycin) controls confirm robustness models. Subsequently, four long-chain (PFOA, PFOS, PFNA, PFHxS) were tested. Keyhole limpet hemocyanin (KLH) was mimic TD response, while a TLR9 agonist IL-2 activated B cells cell-independent (TI) immunoglobulin production. results demonstrated ability reproduce TI responses robust, reproducible outcomes across cohort 20 donors. data, consistent existing literature, showed significant anti-KLH IgM especially PFOA male Similar trends observed all suppressing total IgG These methods closely replicated conditions, offering alternative models immunotoxicity assessments.

Language: Английский

Citations

1