Journal of Toxicology and Environmental Health-Part B-Critical Reviews最新文献

Particulate matter with an aerodynamic diameter of less than 2.5 µm (PM_2.5) is one of the criteria air pollutants that (1) serve as an essential carrier of airborne toxicants arising from combustion-related events including emissions from industries, automobiles, and wildfires and (2) play an important role in transient to long-lasting cognitive dysfunction as well as several other neurological disorders. A systematic review was conducted to address differences in study design and various biochemical and molecular markers employed to elucidate neurological disorders in PM_2.5 -exposed humans and animal models. Out of 340,068 scientific publications screened from 7 databases, 312 studies were identified that targeted the relationship between exposure to PM_2.5 and cognitive dysfunction. Equivocal evidence was identified from pre-clinical (animal model) and human studies that PM_2.5 exposure contributes to dementia, Parkinson disease, multiple sclerosis, stroke, depression, autism spectrum disorder, attention deficit hyperactivity disorder, and neurodevelopment. In addition, there was substantial evidence from human studies that PM_2.5 also was associated with Alzheimer's disease, anxiety, neuropathy, and brain tumors. The role of exposome in characterizing neurobehavioral anomalies and opportunities available to leverage the neuroexposome initiative for conducting longitudinal studies is discussed. Our review also provided some areas that warrant consideration, one of which is unraveling the role of microbiome, and the other role of climate change in PM_2.5 exposure-induced neurological disorders.

Developmental neurotoxicity (DNT) is a well-established hazard attributed to methylmercury (MeHg) exposure. This evidence is based primarily upon includes studies that measured biomarkers of MeHg exposure in samples of maternal hair and blood, and cord blood. The aim of this review was to investigate which of these prenatal biomarkers is most appropriate for quantifying the DNT effects attributed to MeHg. A comprehensive literature search covered MeHg dose-response literature published 1998-2022. Studies were evaluated for risk of bias and study sensitivity using IRIS approach. Quantitative results of investigations were extracted and statistically compared. Seven studies were identified that measured both maternal hair and cord blood Hg levels. In these investigations, several DNT umbrella tests and their sub-tests results were modeled. Cord blood MeHg was more sensitive, producing larger estimates of MeHg potency, in most of the comparisons (91%) with maternal hair MeHg estimates for the same sub-tests in the same study. When comparing results from cord blood Hg to maternal hair Hg there was a 75% increase in sensitivity (range: 4-583%). In the two domains where results for maternal hair Hg were more sensitive, the rise was only 18% (Range: 7-29%). There were limited data (two studies) that compared maternal blood and maternal hair biomarkers (maternal blood Hg was more sensitive (mean 320% and range 43-855%) and cord blood biomarkers (maternal blood Hg was more sensitive by approximately 30%). Maternal hair Hg remains an appropriate biomarker for exposure monitoring in many populations, but these data suggest that cord blood Hg is more appropriate for dose-response modeling of MeHg DNT effects.

Nanoplastics (NPs), defined as plastic particles with dimensions less than 100 nm, have emerged as a persistent environmental contaminant with potential risk to both environment and human health. Nanoplastics might translocate across biological barriers and accumulate in vital organs, leading to inflammatory responses, oxidative stress, and genotoxicity, already reported in several organisms. Disruptions to cellular functions, hormonal balance, and immune responses were also linked to NPs exposure in in vitro assays. Further, NPs have been found to adsorb other pollutants, such as persistent organic pollutants (POPs), and leach additives potentially amplifying their advere impacts, increasing the threat to organisms greater than NPs alone. However, NPs toxic effects remain largely unexplored, requiring further research to elucidate potential risks to human health, especially their accumulation, degradation, migration, interactions with the biological systems and long-term consequences of chronic exposure to these compounds. This review provides an overview of the current state-of-art regarding NPs interactions with environmental pollutants and with biological mechanisms and toxicity within cells.

Blood and urine are historically the most frequent matrices used for measuring chemical levels in human biomonitoring studies. As biomonitoring programs are refreshed, consideration of specific priority substances and specific population targets provide opportunities for inclusion of alternative non- or minimally invasive matrices. This review describes methods used in health risk assessment to characterize exposure and risk based upon biomarkers from noninvasive matrices other than urine or blood, including human milk, hair, fingernails, toenails, exhaled breath, deciduous teeth, sweat, semen, meconium, and feces. Illustrative examples of these methods relevant to chemical management are provided. This review suggests that, although these alternative noninvasive biomarkers are not frequently used in human health risk assessment at present, these biomarkers may prove useful in (1) characterizing exposure and health risk in vulnerable populations, (2) cumulative risk assessments, and (3) community-based risk assessments, depending upon the substance of concern. To incorporate alternative noninvasive biomarkers into human health risk assessments with confidence, more research is needed to improve our knowledge of the relationships between external dose, internal dose, and biologic consequent effects in matrices other than blood and urine.

Terrestrial and aquatic ecosystems face various chemicals that might induce acute and/or long-term harm. To assess these impacts, ecotoxicological bioassays are essential. However, bioassays using animals, particularly mammals, are costly, time-consuming, and raise ethical concerns. In this context, terrestrial plants emerge as a viable alternative to conventional assays. Thus, the aim of this review was to address the history and evolution of plant bioassays, highlighting the main regulations, guidelines, and protocols governing the use of terrestrial plants in ecotoxicological tests. Initially, plant bioassays were employed to assess the cytogenotoxic effects of chemicals, gaining prominence with the GENE-TOX program in the 80s. Subsequently, plants were used in allelopathy bioassays and in studies aimed to examine the ecotoxicity of pesticides in soil. Currently, ecotoxicological bioassays with plants are regulated by specific standards, such as ASTM E1963-22, EPA 600/3-88/029, EPS 1/RM/45, ISO 11269-1, ISO 11269-2, ISO 17126, ISO 18763, ISO 29200, ISO 22030, OECD-208, OECD-227, OCSPP 850.4100, OCSPP 850.4230, OCSPP 850.4800 and OPPTS 850.4200. The existing protocols standardize bioassays in greenhouse and lab environments, and the duration of the tests varies from hours to months. The main ecotoxicological parameters to be analyzed after exposure include germination percentage, survival rate, root length, aerial part length, fresh mass of exposed plants, and phytotoxicity symptoms. In addition, the absorption rate of substances and genotoxic and mutagenic effects might also be assessed. Therefore, data in this review demonstrate that terrestrial plants represent an important tool in the analysis of environmental risks associated with chemicals and might serve as crucial allies in modern ecotoxicology.

Regulatory dose-response assessments traditionally rely on in vivo data and default assumptions. New Approach Methods (NAMs) present considerable opportunities to both augment traditional dose-response assessments and accelerate the evaluation of new/data-poor chemicals. This review aimed to determine the potential utilization of NAMs through a unified conceptual framework that compartmentalizes derivation of toxicity values into five sequential Key Dose-response Modules (KDMs): (1) point-of-departure (POD) determination, (2) test system-to-human (e.g. inter-species) toxicokinetics and (3) toxicodynamics, (4) human population (intra-species) variability in toxicodynamics, and (5) toxicokinetics. After using several "traditional" dose-response assessments to illustrate this framework, a review is presented where existing NAMs, including in silico, in vitro, and in vivo approaches, might be applied across KDMs. Further, the false dichotomy between "traditional" and NAMs-derived data sources is broken down by organizing dose-response assessments into a matrix where each KDM has Tiers of increasing precision and confidence: Tier 0: Default/generic values, Tier 1: Computational predictions, Tier 2: Surrogate measurements, and Tier 3: Direct measurements. These findings demonstrated that although many publications promote the use of NAMs in KDMs (1) for POD determination and (5) for human population toxicokinetics, the proposed matrix of KDMs and Tiers reveals additional immediate opportunities for NAMs to be integrated across other KDMs. Further, critical needs were identified for developing NAMs to improve in vitro dosimetry and quantify test system and human population toxicodynamics. Overall, broadening the integration of NAMs across the steps of dose-response assessment promises to yield higher throughput, less animal-dependent, and more science-based toxicity values for protecting human health.

The overexpression of ATP-binding cassette (ABC) transporters contributes to the failure of chemotherapies and symbolizes a great challenge in oncology, associated with the adaptation of tumor cells to anticancer drugs such that these transporters become less effective, a mechanism known as multidrug resistance (MDR). The aim of this review is to present the most widely used methodologies for induction and comprehension of in vitro models for detection of multidrug-resistant (MDR) modulators or inhibitors, including biochemical and morphological techniques for chemosensitivity studies. The overexpression of MDR proteins, predominantly, the subfamily glycoprotein-1 (P-gp or ABCB1) multidrug resistance, multidrug resistance-associated protein 1 (MRP1 or ABCCC1), multidrug resistance-associated protein 2 (MRP2 or ABCC2) and cancer resistance protein (ABCG2), in chemotherapy-exposed cancer lines have been established/investigated by several techniques. Amongst these techniques, the most used are (i) colorimetric/fluorescent indirect bioassays, (ii) rhodamine and efflux analysis, (iii) release of 3,30-diethyloxacarbocyanine iodide by fluorescence microscopy and flow cytometry to measure P-gp function and other ABC transporters, (iv) exclusion of calcein-acetoxymethylester, (v) ATPase assays to distinguish types of interaction with ABC transporters, (vi) morphology to detail phenotypic characteristics in transformed cells, (vii) molecular testing of resistance-related proteins (RT-qPCR) and (viii) 2D and 3D models, (ix) organoids, and (x) microfluidic technology. Then, in vitro models for detecting chemotherapy MDR cells to assess innovative therapies to modulate or inhibit tumor cell growth and overcome clinical resistance. It is noteworthy that different therapies including anti-miRNAs, antibody-drug conjugates (to natural products), and epigenetic modifications were also considered as promising alternatives, since currently no anti-MDR therapies are able to improve patient quality of life. Therefore, there is also urgency for new clinical markers of resistance to more reliably reflect in vivo effectiveness of novel antitumor drugs.

From a biological point of view, Diversity, Equity, and Inclusion (DEI) are important at multiple levels, which include our genetics, microbiomes, diets, and all organ system interactions. Considering only DEI's sociological aspects is equivalent to the error of "throwing out the baby with the bath water." Variances in microbial diversity within our microbiomes might affect our health through systemic interactions affecting metabolites, maintaining immune homeostasis, and wound healing of cellular damage from an infection, physical stress, or psychological trauma. An imbalance of our immune cell subsets, both innate and adaptive, and the microbes in any of our microbiomes might lead to more cellular damage from excessive inflammation and oxidative stress and less immune regulation. The immune dysregulation may occur due to the loss of endometrial barriers enabling the spread of microbes, environmental pollutants, and allergens. Heat waves, sleep deprivation, and increased prevalence of pollutants such as polychlorinated biphenyls, which weaken endothelial barriers, may be responsible for the enhanced prevalence of physical and psychological stresses. Leakage of our useful gut microbiota into the periphery might initiate inflammatory responses, and an altered gut microbiome might affect the gut-brain axis that influences physical and mental health.

Morphine has been widely used to treat physical non-cancer pain as well as cancer-related pain. However, a growing body of evidence has emerged indicating that morphine in addition to alleviating pain initiates and suppresses immune functions in different types of cancer. At present the actions of morphine on tumor growth are contradictory with both inhibition and stimulation reported. Thus, the effects of morphine use needs to be identified with respect to the immune system in consideration of the therapeutic course to follow. It is known that cancer cells express various types of opioid receptors and morphine interaction with these receptors needs to be elucidated in cancer treatment. The expression and distribution of different opioid receptors for morphine binding may provide a basis for varying effects attributed to morphine actions on cancer cell promotion and suppression. Evidence indicates that knowledge regarding distribution of opioid receptors may be considered as a therapeutic tool to determine the use of morphine as a painkiller to treat cancer-related pain.