Narcotic effects of acute exposure to trichlorofluoromethane (Freon 11).

Injurious effects of acute ethanol exposure during late gestation on developing white matter in fetal sheep

Aflatoxin B1 (AFB1) has mutagenesis, carcinogenesis and teratogenesis effects and mainly found in food crops and their processed foods. AFB1 exposure can cause acute or chronic liver poisoning, but there were few studies on the persistent effects of acute AFB1 exposure on the liver. In this study, rat liver injury models were established 2 and 7 days after single exposure to high and low doses of AFB1. The persistent effects of AFB1 single acute exposure (ASAE) on rat liver were analyzed from the phenotypic and genetic levels. The results showed that compared with the control group, liver function indexes, MDA content in liver and the number of apoptotic hepatocytes in model groups increased to the highest on the 2nd day after ASAE (p < 0.001). However, the changes of liver coefficient were most significant on the 7th day after ASAE (p < 0.01). The results of liver pathology showed that the liver injury was not alleviated and the activities of antioxidant enzymes GSH-Px and SOD were the lowest on the 7th day (p < 0.001). RNA-Seq results indicated that there were 236, 33, 679, and 78 significantly differentially expressed genes (DEGs) in the model groups (LA-2d, LA-7d, HA-2d, HA-7d) compared with the control group. Among them, the Gtse1 gene related to the proliferation, differentiation and metastasis of liver cancer cells, the Lama5 and Fabp4 gene related to the inflammatory response were significantly DEGs in the four model groups, and the differential expression of the immune system-related Bcl6 gene increased with the prolonged observation time after ASAE. In conclusion, ASAE can cause persistent liver damage in rats. The persistently affected genes Lama5, Gtse1, Fabp4, and Bcl6 possess the potential to be therapeutic targets for liver disease induced by AFB1.

Purpose A question echoed by the National Biodefense Science Board (NBSB) in 2010, remains a reasonable question in 2023; ‘Where are the Countermeasures?’. A critical path for development of medical countermeasures (MCM) against acute, radiation-induced organ-specific injury within the acute radiation syndrome (ARS) and the delayed effects of acute radiation exposure (DEARE) requires the recognition of problems and solutions inherent in the path to FDA approval under the Animal Rule. Keep Rule number one in mind, It’s not easy. Considerations The current topic herein is focused on defining the nonhuman primate model(s) for efficient MCM development relative to consideration of prompt and delayed exposure in the context of the nuclear scenario. The rhesus macaque is a predictive model for human exposure of partial-body irradiation with marginal bone marrow sparing that allows definition of the multiple organ injury in the acute radiation syndrome (ARS) and the delayed effects of acute radiation exposure (DEARE). The continued definition of natural history is required to delineate an associative or causal interaction within the concurrent multi-organ injury characteristic of the ARS and DEARE. A more efficient development of organ specific MCM for both pre-exposure and post-exposure prophylaxis to include acute radiation-induced combined injury requires closing critical gaps in knowledge and urgent support to rectify the national shortage of nonhuman primates. The rhesus macaque is a validated, predictive model of the human response to prompt and delayed radiation exposure, medical management and MCM treatment. A rational approach to further development of the cynomolgus macaque as a comparable model is urgently required for continued development of MCM for FDA approval. Conclusion It is imperative to examine the key variables relative to animal model development and validation, The pharmacokinetics, pharmacodynamics and exposure profiles, of candidate MCM relative to route, administration schedule and optimal efficacy define the fully effective dose. The conduct of adequate and well-controlled pivotal efficacy studies as well as safety and toxicity studies support approval under the FDA Animal Rule and label definition for human use.

This article deals with health risks resulting from exposure to zinc and its inorganic compounds in industry. The main source of zinc exposure are fumes generated during thermal and chemical processes, mainly zinc oxide fume formed by immediate oxidation of metallic zinc vapor formed during high-temperature processes, as well as dust generated during the mechanical processing of zinc-containing materials. It is recognized that zinc ions are responsible for health effects of exposure to dust/fumes of the majority of zinc compounds, and the final effect of exposure depends on the degree of dispersion of dusts/fumes suspended in the air. Since the effects of exposure depends on the particle size, occupational exposure limits have began to be established separately for respirable and inhalable fractions. A critical effect of acute exposure to respirable fraction is a "fume fever" which in chronic exposure occurs as an effect associated with recurrent symptoms of acute poisoning. Impaired lung function and asthma symptoms are considered to be the main effects of exposure to inhalable fraction. Due to the limited number of the available data it is not possible to assess carcinogenicity, reproductive toxicity and teratogenicity of zinc and its compounds. The aim of the study was to analyze the major health hazards resulting from occupational exposure to zinc and its inorganic compounds in the context of their physico-chemical properties, a wide range of applications and occupational exposure data. Med Pr 2017;68(6):779-794.

Multicenter field trial on possible health effects of toluene. II. Cross-sectional evaluation of acute low-level exposure

The effects of radiofrequency electromagnetic fields exposure on human self-reported symptoms: A systematic review of human experimental studies

The objectives of the Health Division of the Plutonium Project were essentially (a) to study the fundamental and comparative biological action of external radiations and internally administered radioactive materials, (b) to apply the findings for the protection of individuals who worked in the Project, and (c) to use the findings generally for the protection of the public which was potentially in danger of exposure to these physical hazards. The hematologic studies2 conducted on the Plutonium Project were divided into four main categories, namely, the effects of acute3 whole-body exposure to externally administered penetrating radiation, the effects of chronic4 whole-body exposure to externally administered penetrating radiations, acute toxicity of parenterally and enterally administered radioactive compounds, and chronic toxicity of parenterally and enterally administered radioactive isotopes. In order to correlate properly studies on the peripheral blood effects with those occurring in the hemopoietic tissue, the animals in the same or parallel experiments were sacrificed at intervals for histologic study. All experiments included an adequate number of controls, and the frequency of sampling depended upon the chronic nature of the experiment. Comparative Effects of Acute Whole-Body Exposure to X-Rays and Fast Neutrons In considering the irradiation of the whole body with penetrating radiations of external origin, those of significance in so far as direct effects on the blood and bloodforming tissue are concerned are x-rays, gamma rays, fast neutrons, and slow neutrons. The beta and alpha rays that originate from radioactive substances can largely be neglected, because penetration in tissue is only a few millimeters in the former and a fraction of a millimeter in the latter. The studies on animals by Raper and Barnes (1), Raper, Zirkle, and Barnes (2), Raper, Henshaw, and Snider (3), and others, have demonstrated that, although beta rays may penetrate the skin, the hematologic effects, if any occur, are minimal and are secondary to other more serious pathological changes. No experiments similar to those of Raper and Zirkle have been performed using alpha rays. Since alpha rays have such shallow penetrability (e.g., those emitted by plutonium or radium will penetrate only about 40μ into the skin), no direct effects and only minimal indirect effects on hemopoietic tissue appear likely. Studies on the effects of acute exposure of animals to a slow neutron flux have been carried out by Zirkle (4a). This slow neutron source, however, was contaminated with fast neutrons, and the effect on the hemopoietic system, as reported by Raper, Henshaw, and Snider (3), is therefore difficult to interpret.

2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most widely used herbicides in the world, but its mutagenic and carcinogenic potential is still controversial. We simulated environmental exposure to 2,4-D, with the objective of evaluating the genotoxic effect of acute and chronic exposure to 2,4-D in rodents. We also evaluated the performance of machine learning algorithms in detecting differences in exposure groups through recognition performed from genotoxic characteristics. In the acute phase, 88 Swiss mice were used, distributed in five groups and exposed to nebulizations at different time intervals (24, 48, 72 and 192 hr). In the chronic phase, 88 Wistar rats were used, distributed in two groups (inhaled and oral) and exposed for six months. Femoral bone marrow cells were collected for a micronucleus test and comet assay. Data were evaluated by pattern recognition algorithms. In acute exposure, medium and high concentrations induced DNA damage in the comet assay, but these concentrations did not increase micronucleated cells. In the chronic exposure, there was an increase in micronuclei and DNA damage in the comet assay in all exposed groups regardless of the exposure route. The data showed a robust pattern of distinction between exposed and nonexposed groups to 2,4-D. Our data showed that both acute inhalation exposure and chronic oral and inhalation exposure to 2,4-D can cause genotoxic effects regardless of concentration. Machine learning showed a clear distinction between the control groups and those exposed to 2,4-D, and the effects of exposure are not concentration-dependent.

A series of acute inhalation exposures was performed with airborne hydrogen fluoride (HF) to establish the concentration response for nonlethal effects in the rat. Exposures were either 2 or 10 min long; concentrations ranged from 135 to 8621 ppm. Three additional exposures (20 to 48 ppm) were performed for 60 min. A mouth-breathing (MB) model with a tracheal cannula was used in most of the exposures to maximize delivery of the HF to the lower respiratory tract. Endpoints on the day after exposure included hematology, serum chemistry, bronchoalveolar lavage, pulmonary function, organ weights, and histopathology. Nasal resistance was measured in nose-breathing (NB) groups. Effects of exposure were generally limited to the respiratory tract and included alveolitis, bronchial lesions, altered parameters of pulmonary function and bronchoalveolar lavage, and mucosal necrosis, inflammation, and fibrinopurulent exudate in airways. Observed changes were concentration related and appeared more pronounced in major airways near the point of entry (trachea in MB animals and nose in NB animals). One group of MB animals exposed for 10 min to 1454 ppm was evaluated at 3 and 14 wk after exposure; the acute effects had resolved by those times. The effects of 2-min exposures were consistently more severe than those from 10-min exposures to the same product of concentration x time. Exposures of MB animals for 60 min to 20 or 48 ppm HF did not result in observable adverse effects, although quasistatic pressure-volume curves were shifted upward slightly after 48 ppm. These data provide an integrated picture of the concentration-related effects of short nonlethal exposures to HF.

Effect of Acute Propanil Exposure on the Immune Response of C57BI/6 Mice. BARNETT, J. B., AND GANDY, J. (1989). Fundam. Appl. Toxicol. 12, 757–764. Propanil is a herbicide that is used extensively in rice farming to kill weeds without damaging the rice plant The immunotoxic effects of acute exposure to propanil were determined in adult C57B1/6 female mice exposed intraperitoneally to propanil at doses of 0, 10, 25, 50, 100,200, or 400 mg/kg body wt. One week following exposure, the immune competency of the animals was assessed. Contact hypersensitivity response (CHR), blastogenic response to T- and B-cell-specific mitogens, and mixed lymphocyte reaction (MLR) were significantly depressed only in propanil-treated animals at 400 mg/kg. However, the number of splenic antibody-producing cells was also significantly depressed in a dose-dependent manner at the lower doses of 50, 100, and 200 mg/kg. In addition, a significant reduction in the thymus weight and an increase in absolute and relative spleen weight were also measured in animals treated with 200 and 400 mg/kg. The increase in spleen weight also showed a concomitant rise in spleen cellularity. These data indicate that propanil has a dose-dependent immunotoxic effect on the adult mouse that affects primarily the humoral response

Organophosphates: the relationship between chronic and acute exposure effects.

There is growing evidence that the anticonvulsant topiramate is efficacious in reducing alcohol consumption. Further, an intronic single nucleotide polymorphism (rs2832407, C A) in the GRIK1 gene, which encodes the GluK1 subunit of the excitatory kainate receptor, predicted topiramate's effectiveness in reducing heavy drinking in a clinical trial. The molecular correlates of GRIK1 genotype that may relate to topiramate's ability to reduce drinking remain unknown. We differentiated induced pluripotent stem cells (iPSCs) characterized by GRIK1 rs2832407 genotype from 8 A/A and 8 C/C donors into forebrain-lineage neural cultures. Our differentiation protocol yielded mixed neural cultures enriched for glutamatergic neurons. Basal mRNA expression of the GRIK1 locus was examined via quantitative polymerase chain reaction (qPCR). The effects of acute topiramate exposure on excitatory spontaneous synaptic activity were examined via whole-cell patch-clamp electrophysiology. Results were compared and contrasted between iPSC donor genotypes. Although characterization of the GRIK1 locus revealed no effect of rs2832407 genotype on GRIK1 isoform mRNA expression, a significant difference was observed on GRIK1 antisense-2 expression, which was greater in C/C neural cultures. Differential effects of acute exposure to 5μM topiramate were observed on spontaneous synaptic activity in A/A versus C/C neurons, with a smaller reduction in excitatory event frequency observed in C/C donor neurons. This work highlights the use of iPSC technologies to study pharmacogenetic treatment effects in psychiatric disorders and furthers our understanding of the molecular effects of topiramate exposure in human neural cells.

Effects of acute exposure to hypoxia on sleep structure in healthy adults: A systematic review

Effects of acute exposure to moderate altitude on blood pressure and sleep breathing patterns

The present study explored the potential role of brain catecholaminergic and serotoninergic systems as neuronal targets for the toxicological effects of acute ammonia exposure (0.28 mg l(-1) of un-ionized ammonia for 12 and 24 h) in juvenile sole (Solea senegalensis). In addition, plasma cortisol levels were measured. The results showed significant increases in their concentrations that were similar after 12 and 24 h of exposure. These data indicate that acute exposure (12 and 24 h) to ammonia initiates a typical stress response in the Senegalese sole, with stimulation of the hypothalamus-pituitary-interrenal axis. The concentrations of dopamine (DA), serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (NA), and their metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxy-3-indoleacetic acid (5HIAA), were measured in the hypothalamus, telencephalon and optic tectum. The main changes induced by acute exposure to ammonia were decreases in the concentrations of 5-HT and DA, which were significant in most of the brain regions studied. The ratios of 5-HIAA/5-HT and DOPAC/DA increased in all regions and at all times studied, although in the case of the DOPAC/DA ratio, the increases were only significant in the hypothalamus (24 h exposure) and in the optic tectum (12 and 24 h exposure). These changes indicated that exposure to ammonia elicited time-dependent increases in serotoninergic and dopaminergic activity in the hypothalamus, telencephalon and optic tectum.