Journal of Toxicology and Environmental Health-Part A-Current Issues最新文献

Immune responses occur through orchestration of various immune components. Considering immune system complexity, immunotoxicity was evaluated primarily in vivo in rodents. Worldwide restrictions in animal use for toxicity research has driven development of in vitro methods for screening chemicals postulated to be potentially immunotoxic. One in vitro assay of immunotoxicity (IMMUNOTOX-T) uses human monocytic leukemia cell line THP-1. Since cytokine profiling might predict immunotoxicities, the aim of this study was to determine levels of 27 cytokines derived from THP-1 cells in response to chemical treatment. Seven immunosuppressives and 14 non-immunotoxicants in vivo were used as references to distinguish between immunosuppression and aberrant immunostimulation. Immunotoxicity of 41 in vivo immunomodulatory chemicals, at 0.01×, 0.1×, or 0.5× of 75% cell viability concentrations, was tested under blinded conditions by measuring relative cytokine production level (RCPL, %) versus control. The mean cytokine production value for immunosuppressants (MCPVS) of each cytokine was calculated by averaging mean RCPLs of three test concentrations of seven immunosuppressants. The acceptable cytokine production range (ACPR) for 14 non-immunotoxicants was defined as the highest mean RCPL of these 14 non-immunotoxicants for each cytokine. A target test substance was considered immunotoxic if mean RCPL of three test concentrations of the substance for at least one cytokine was below MCPVS or above the highest ACPR. Of 41 substances tested, 40, all except toluene, exhibited immunotoxic properties, with 9 and 6 substances downregulating and upregulating immune activity, respectively. This assay may contribute to the identification of immunotoxicological properties attributed to exposure to chemical substances.

Under the United States Environmental Protection Agency's (U.S. EPA) CERCLA program, soils suspected of lead (Pb) contamination are evaluated to assess the impact of soil Pb exposure on blood Pb levels. The decision to remediate relies, in part, on whether the measured soil exposure point concentration (EPC) excee ds an action level. The U.S. EPA established data quality objectives (DQOs) to support data collection used to estimate the EPC and assess confidence in remediation decisions. To support DQO processes at sites where site-specific soil Pb relative bioavailability (RBA) is assessed, a statistical simulation model was developed that estimates false compliance/exceedance decision error probabilities based upon uncertainty in the RBA-adjusted EPC, employing model inputs defining (1) the sampling protocol being evaluated, (2) variability in total and bioavailable soil Pb across the assessed area, and (3) analytical measurement uncertainty. A framework for utilizing the simulation model is presented using a hypothetical site informed by concentration and soil Pb bioavailability distributions from an actual Pb-contaminated site. Pre-sampling, false compliance/exceedance decision error probabilities were predicted for various sampling protocols. A DQO-compliant sampling protocol was then selected, and accuracy and precision in the measured EPC were assessed relative to a specified risk-based action level.

The chemical characterization of the species Eugenia florida identified compounds with diverse beneficial pharmacological potential, making it a target for extensive research. The aim of this study was to investigate the phytotoxic and cytogenotoxic effects attributed to exposure to E. florida, leaf extracts obtained from different positions in the canopy (inside and periphery) and through aqueous and hydroethanolic extraction methods. Bioassays were conducted using Lactuca sativa L. measuring parameters such as germination percentage on days 4 and 7, germination speed index, shoot length, root elongation, percentage of abnormal seedlings, and cytogenetic parameters (mitotic index and frequency of chromosomal abnormalities). The results demonstrated that different leaf extracts of E. florida displayed no variation in phytochemical composition, with the presence of flavonoids, phenols, tannins, catechin, saponins, and terpenes. However, the collection position and extraction method have a significant impact on the allelopathic potential of the different extracts. Peripheral leaves, when subjected to hydroethanolic extraction, demonstrated greater efficiency, showing phytotoxic effects on root elongation and morphological abnormalities. Furthermore, a mitodepressive effect greater than 50% was observed, without the detection of genotoxic damage. Thus, this study provides the first evidence that E. florida extracts possess allelopathic potential, especially in the post-emergence phase in bioassays with L. sativa, inducing morphological and cytotoxic alterations. These results highlight the feasibility of using these extracts and pave the way for future research, contributing to the development of more ecological alternatives in agriculture.

This study determined the phytotoxic and cytogenetic effects of two glyphosate-based herbicides (GBHs): XEQUE MATE HT IHARA® (restricted agricultural use - GBHn) and CITROMAX MAX 20 (used for gardening, sold for the general public - GBHg). Phytotoxicity bioassays were conducted using four non-target species (Lactuca sativa, Raphanus sativus, Pennisetum glaucum, and Hordeum vulgare) and one target species (Bidens pilosa). Both GBHs significantly reduced germination rate (G%), germination speed index (GSI), fresh mass (FM), and seedling growth (SG) in a dose-dependent manner. SG was the most sensitive endpoint with decreases over 99% at 480 mg/L for both GBHs. Bidens pilosa exhibited the highest sensitivity index (SI = 0.93 for GBHn, 0.8 for GBHg), confirming target specificity. Overall SI were similar (OSI = 0.75 for GBHn; 0.72 for GBHg), indicating comparable toxicity. Cytogenetic assays using Allium cepa demonstrated significant reductions in mitotic index (MI) at higher concentrations (> 40% decrease at higher doses), with limited chromosomal alterations but notable increases in micronuclei (MN) (up to 6 per 1,000 cells) for both GBHs. GBHn induced more MN formation than GBHg, suggesting greater genotoxicity. Despite similar phytotoxic profiles, GBHn's higher genotoxicity warrants concern. These results indicate the environmental risks posed by treatments with both formulations and emphasize the need for rigorous regulatory scrutiny for glyphosate-based herbicides.

The aim of this study was to investigate the anti-inflammatory properties of the ethyl acetate extract (EA) of Cordyceps neovolkiana DL0004, a native fungal species recently isolated in Vietnam and its purified compound, nicotinic acid (NCA), using in vitro assays. Data showed that both EA and NCA significantly inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages without inducing cytotoxicity. Further, western blot analysis demonstrated that both agents suppressed the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit p50 and p65 in a concentration-dependent manner, with NCA exhibiting greater potency at lower concentrations. In addition, EA and NCA effectively protected cellular DNA and proteins against hydrogen peroxide (H₂O₂)-induced oxidative damage, confirming their antioxidant potential. These findings suggest that C. neovolkiana and its constituents, particularly NCA, possess promising anti-inflammatory activities as evidenced by suppression of NO production, NF-κB activation, and oxidative stress.

Missions for federal facilities, such as the Department of Defense (DOD) and the Department of Energy (DOE), include protecting human health and the environment. The public is interested in whether ecological resources are protected on such lands, especially following remediation of legacy wastes remaining from World War II, Cold War, and industrial activities. Many DOE sites are remediated for future uses depending upon potential for exposure to residual contamination. This study: (1) examined the % ecological resources remaining on Rocky Flats following completion of cleanup, (2) compared the ecological resources (i.e. plant cover) of Rocky Flats (RF) with the surrounding 10-km and 30-km bands of land, and (3) measured % natural vegetation on RF with comparable % on three other large DOE facilities that are still undergoing remediation. Rocky Flats contains significantly more grassland than the surrounding region, with less development, and is mostly a National Wildlife Refuge open to the public. Agriculture and grazing do not occur on RF. The three sites undergoing remediation have significantly more natural habitat (climax vegetation) than their surrounding buffer areas. The aim of this study was to examine the implications of ecological protection of climax vegetation upon these sites and the importance of consistently examining regional ecologies.

Cadmium (Cd) is a highly toxic heavy metal commonly introduced into agricultural soils through phosphate fertilizers. Cadmium accumulation poses serious risks to human health, crop productivity, and environmental sustainability. Although the toxic effects of Cd on plant development are well documented, effective and sustainable strategies to mitigate its impact on seed germination and early plant growth remain limited. Nanomaterials such as graphene oxide (GO) demonstrated potential in alleviating abiotic stress, but application in Cd-contaminated agricultural systems requires further investigation. Therefore, the aim of this study was to examine the potential of GO as a possible mitigator of adverse Cd-initiated effects on seed germination and initial growth of rice (Oryza sativa L.) seedlings. Rice seeds were treated with varying concentrations of GO (0 to 500 mg/L), Cd chloride (0 to 0.4 mM), and combination of GO + Cd chloride simultaneously. The experiment was conducted on a germitest paper, where the rolls were kept for 7 days in a germination chamber (25 ± 2 °C and 12 hr light). The germination and seedling growth were subsequently assessed. Cadmium exposure inhibited seed germination and early seedling development, particularly at concentrations from 0.1 mM. Graphene oxide, on the other hand, proved to be a suitable alternative to mitigate Cd-induced stress, showing a significant enhanced germination at concentrations of up to 250 mg/L. Graphene oxide demonstrated potential as a protective agent against Cd-induced toxicity in rice seeds, suggesting its promising application in improving crop resilience in metal-contaminated environments.

The flowers of Lavandula sp. have been widely studied and attributed to their therapeutic and aromatic properties. However, no apparent study to date has examined the extraction of Lavandula dentata compounds from supercritical extraction with CO₂ solvent, a technique recognized for efficiency, selectivity, and ability to generate extracts without solvent residues. The aim of this study was to determine the cytotoxic potential of volatile compounds of L. dentata, extracted by supercritical technology and cytotoxic and antioxidant capacity examined using human cervical (SiHa) and hepatic tumor cells (Huh7.5). Supercritical fluid extraction was conducted under conditions of 180 bar, 40°C and carbon dioxide (CO₂) solvent flow rate of 1.06 × 10^-4 kg/sec. A yield of 1.68 ± 0.04% by mass was obtained. The major bioactive compounds detected by GC-MS were camphor and 1,8-cineol (oxygenated monoterpenes). The high presence of phenolic compounds was detected through the Folin-Ciocalteu test consequent potential of antioxidant capacity through DPPH inhibition. A high number of total carotenoids were identified, an unprecedented result for this species. The MTT cytotoxicity tests with SiHa and Huh7.5 cell lines were promising at concentrations of 200 to 1000 μg/ml at 24, 48 or 72 hr. Evidence indicates that supercritical extraction with CO₂ solvent was efficient in extraction of phenolic compounds and carotenoids as well as enhancing antioxidant capacity, which confer promising beneficial biological activities for human health.

The aim of this study was to examine whether intraperitoneal (ip) rutin administration is able to reduce or prevent Cryptococcus neoformans var. grubii-induced brain damage, as well as lower fungal burden in male Wistar rats. Inhibitory avoidance tasks revealed memory impairments in rats experimentally infected with C. neoformans var. grubii when compared to saline or uninfected rats. Rutin administration to infected rats prevented memory loss. Brain reactive oxygen species, thiobarbituric acid reactive substances, and nitric oxide levels were significantly higher in rats infected with C. neoformans var. grubii compared to saline or uninfected animals. Rutin administration to infected rats decreased (61%, 33%, and 58%, respectively) all these alterations. Brain catalase (CAT) activity and total antioxidant capacity (TAC) levels were significantly diminished in rats infected with C. neoformans var. grubii compared to saline or uninfected rats, while rutin administration to infected rats blocked reductions in brain TAC levels and partially restored brain CAT activity. Finally, administration of rutin decreased (49%) brain fungal burden compared to saline or uninfected rats. Summary data demonstrated that oxidative stress was involved in C. neoformans var. grubii-induced memory impairment. The novelty of the study is that rutin ameliorated C. neoformans var. grubii-initiated memory loss via stimulation of the antioxidant defense system protecting the brain against free radical-mediated effects and lipid peroxidation, as well as exerting antifungal action. Thus, rutin may be considered as a potential source for cryptococcosis treatment.

Cancer constitutes a major cause of death globally. Many current treatments are not very selective and often harm healthy cells. Inflammation is known to be associated with tumor growth, yet anti-inflammatory drugs alone are rarely used in a targeted manner. The aim of this study was to examine the synergic activity of two frequently used anti-inflammatory drugs, dexamethasone acetate (DA), and nimesulide (NIME) in nanoencapsulated form to diminish toxicity but enhance therapeutic effectiveness. The stability of the nanocapsules was established by applying light scattering, zeta potential, electron microscopy, and HPLC-DAD. The nanocapsules remained intact over time and exhibited a porosity and regular even shape, ideal for slow drug release. The encapsulated drugs initiated less harm to healthy HaCaT and L929 cells maintaining activity against cancer cells (HeLa, A375). Docking tests indicated that DA was bound effectively to the MMP-13/TIMP-2 complex, indicative of potential anti-inflammatory and anticancer effects. Molecular docking analysis noted that DA exhibited a stronger binding affinity to the target protein compared to NIME (binding energy: -8.7 kcal/mol, Ki: 0.423 µM vs. NIME: -6.8 kcal/mol, Ki: 10.4 µM), indicating a higher propensity for interaction. Further, DFT analysis demonstrated that NIME possessed a smaller HOMO - LUMO gap (0.132 eV), suggesting greater chemical reactivity, whereas DA exhibited a larger gap (2.806 eV), indicative of enhanced molecular stability. Computational results suggested that NIME was more reactive, while DA was more stable. Data suggest that nanocapsules may diminish side effects without reducing the benefits of these drugs against tumors.