Adverse respiratory effects in rats following inhalation exposure to ammonia: respiratory dynamics and histopathology

Acute respiratory dynamics and histopathology of the lungs and trachea following inhaled exposure to ammonia were investigated. Respiratory dynamic parameters were collected from male Sprague–Dawley rats (300–350?g) during (20?min) and 24?h (10?min) after inhalation exposure for 20?min to 9000, 20,000, and 23,000?ppm of ammonia in a head-only exposure system. Body weight loss, analysis of blood cells, and lungs and trachea histopathology were assessed 1, 3, and 24?h following inhalation exposure to 20,000?ppm of ammonia. Prominent decreases in minute volume (MV) and tidal volume (TV) were observed during and 24?h post-exposure in all ammonia-exposed animals. Inspiratory time (IT) and expiratory time (ET) followed similar patterns and decreased significantly during the exposure and then increased at 24?h post-exposure in all ammonia-exposed animals in comparison to air-exposed controls. Peak inspiratory (PIF) and expiratory flow (PEF) significantly decreased during the exposure to all ammonia doses, while at 24?h post-exposure they remained significantly decreased following exposure to 20,000 and 23,000?ppm. Exposure to 20,000?ppm of ammonia resulted in body weight loss at 1 and 3?h post-exposure; weight loss was significant at 24?h compared to controls. Exposure to 20,000?ppm of ammonia for 20?min resulted in increases in the total blood cell counts of white blood cells, neutrophils, and platelets at 1, 3, and 24?h post-exposure. Histopathologic evaluation of the lungs and trachea tissue of animals exposed to 20,000?ppm of ammonia at 1, 3, and 24?h post-exposure revealed various morphological changes, including alveolar, bronchial, and tracheal edema, epithelial necrosis, and exudate consisting of fibrin, hemorrhage, and inflammatory cells. The various alterations in respiratory dynamics and damage to the respiratory system observed in this study further emphasize ammonia-induced respiratory toxicity and the relevance of efficacious medical countermeasure strategies.     

Evaluation of subchronic inhalation toxicity of methylcyclopentane in rats

The aim of this study was to verify subchronic inhalation toxicity of methylcyclopentane (CAS No. 96-37-7) in Sprague-Dawley rats. Four groups of 10 rats of each gender were exposed to methylcyclopentane vapor by whole-body inhalation at concentrations of 0, 290, 1300, or 5870 ppm for 6 h per day, 5 days/week over a 13-week period. During the study period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross pathology, organ weights, and histopathology were examined. Exposure-related clinical signs (salivation and rubbing) were observed in both genders of the 5870 ppm group. There was an increase in liver weight for both genders but the kidney weight was only higher in females than controls. However, no toxicologically significant changes were observed in body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings, or histopathology in any of the treatment groups. Under the present experimental conditions, the target organs were determined to be kidney and liver in rats. The no-observed-adverse-effect concentration was considered to be 1300 ppm/6 h/day in rats.     

Acute inhalation toxicity of cerium oxide nanoparticles in rats

The aim of the present study was to assess the acute toxic potential of cerium oxide nanoparticles (CeO₂ NPs) in rats when exposed through the head and nose inhalation route. The rats were exposed to CeO₂ NPs and the resultant effects if any, to cause cytotoxicity, oxidative stress and inflammation in the lungs were evaluated on a 24 h, 48 h and 14 day post exposure period. Our results showed a significant decrease in the cell viability, with the increase of lactate dehydogenase, total protein and alkaline phosphatase levels in the bronchoalveolar lavage fluid (BALF) of the exposed rats. Total leukocyte count and the percentage of neutrophils in BALF were elevated within 24 h of post exposure. The concentrations of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) were significantly increased in the BALF and in the blood throughout the observation period. The level of malondialdehyde was elevated with the decreased levels of intracellular reduced glutathione (GSH) in the lung after exposure. The alveolar macrophages (AMs) and neutrophils overloaded with phagocytosed CeO₂ NPs were observed along with non-phagocytosed free CeO₂ NPs that were deposited over the epithelial surfaces of the bronchi, bronchiole and alveolar regions of lungs within 24 h of post exposure and were consistent throughout the observation period. A well distributed, multifocal pulmonary microgranulomas due to impairment of clearance mechanism leading to biopersistence of CeO₂ NPs for an extended period of time were observed at the end of the 14 day post exposure period. These results suggest that acute exposure of CeO₂ NPs through inhalation route may induce cytotoxicity via oxidative stress and may lead to a chronic inflammatory response.     

Measurement of various respiratory dynamics parameters following acute inhalational exposure to soman vapor in conscious rats

Abstract

Respiratory dynamics were investigated in head-out plethysmography chambers following inhalational exposure to soman in untreated, non-anesthetized rats. A multipass saturator cell was used to generate 520, 560 and 600?mg?×?min/m³ of soman vapor in a customized inhalational exposure system. Various respiratory dynamic parameters were collected from male Sprague-Dawley rats (300--350?g) during (20?min) and 24?h (10?min) after inhalational exposure. Signs of CWNA-induced cholinergic crisis were observed in all soman-exposed animals. Percentage body weight loss and lung edema were observed in all soman-exposed animals, with significant increases in both at 24?h following exposure to 600?mg?×?min/m³. Exposure to soman resulted in increases in respiratory frequency (RF) in animals exposed to 560 and 600?mg?×?min/m³ with significant increases following exposure to 560?mg?×?min/m³ at 24?h. No significant alterations in inspiratory time (IT) or expiratory time (ET) were observed in soman-exposed animals 24?h post-exposure. Prominent increases in tidal volume (TV) and minute volume (MV) were observed at 24?h post-exposure in animals exposed to 600?mg?×?min/m³. Peak inspiratory (PIF) and expiratory flow (PEF) followed similar patterns and increased 24?h post-exposure to 600?mg?×?min/m³ of soman. Results demonstrate that inhalational exposure to 600?mg?×?min/m³ soman produces notable alterations in various respiratory dynamic parameters at 24?h. The following multitude of physiological changes in respiratory dynamics highlights the need to develop countermeasures that protect against respiratory toxicity and lung injury.     

Acute inhalation toxicity of eugenol in rats

The acute toxicity of inhaled eugenol was assessed by exposure of three groups of five male and five female rats to a submicron aerosol of eugenol for 4 h followed by a 14-day observation period. A fourth group, also of five male and five female rats and exposed to air only under similar conditions, served as a control group for comparison. The three concentrations of eugenol to which the different groups were exposed were 2.58, 1.37 and 0.77 mg/l. The mass median aerodynamic diameters and geometric standard deviations of the aerosols were, respectively, 0.82 m (g 2.26), 0.88 m (g 2.05) and 0.9 m (g 1.87). Clinical signs observed during exposure consisted principally of moderately increased salivation and restlessness (indicative of irritation) and abnormal breathing patterns. The signs were graded, being less marked in animals exposed to the lower concentrations of eugenol. All three groups, exposed to high, medium and low levels of eugenol, lost weight overnight following exposure. Associated with the weight loss were marked reductions in food and water intake. The responses appeared to be largely independent of the concentration of eugenol inhaled, although there was some evidence of a graded effect on water intake. There was rapid recovery, with food and water consumption data comparable with control values throughout most of the remainder of the 14-day observation period. Also, by the end of the observation period, group mean body weights were comparable. Upon sacrifice and macroscopic examination of the animals, abnormalities were detected in the lungs only of a few animals: 3/10 control, 2/10 eugenol 2.58 mg/l, and 2/10 eugenol 0.77 mg/l. These consisted of dark red/red (raised) areas up to 4×4 mm. Such abnormalities are not uncommon in the lungs of laboratory maintained rats and their presence with equal incidence in control animals suggests that they are unlikely to be related to inhalation of eugenol. Lung weight to body weight ratio values for all groups were similar, providing no evidence of any persistent effect of eugenol on the lungs of the rats. Similarly, histopathological examination of the lung failed to reveal any treatment-related changes. A few incidental lesions present were considered spontaneous in origin and therefore of no toxicological importance.     

Development of a model for nerve agent inhalation in conscious rats

Abstract

This study characterizes the development of a head-out inhalation exposure system for assessing respiratory toxicity of vaporized chemical agents in untreated, non-anesthetized rats. The organophosphate diisopropyl fluorophosphate (DFP) induces classical cholinergic toxicity following inhalation exposure and was utilized to validate the effectiveness of this newly designed inhalation exposure system. A saturator cell apparatus was used to generate DFP vapor at 9750, 10?950, 12?200, 14?625 and 19?500?mg?×?min/m³ which was carried by filtered nitrogen into a glass mixing tube, where it combined with ambient air before being introduced to the custom-made glass exposure chamber. Male Sprague-Dawley rats (250–300?g) were restrained in individual head-out plethysmography chambers, which acquired respiratory parameters before, during and after agent exposure. All animals were acclimated to the exposure system prior to exposure to reduce novel environment-induced stress. The LCt₅₀, as determined by probit analysis, was 12?014?mg?×?min/m³. Weight loss in exposed animals was dose-dependent and ranged from 8 to 28% of their body weight 24?h after exposure. Increased salivation, lacrimation, urination, defecation (SLUD) and mild muscular fasciculation were observed in all DFP-exposed animals during and immediately following exposure. In all exposed animals, DFP vapor produced significant inhibition of acetylcholinesterase (AChE) activity in cardiac blood, bronchoalveolar lavage fluid (BALF), whole brain and lung tissue as well as alterations in tidal volume and minute volume. These studies have provided valuable information leading to the initiation of studies evaluating inhalational toxicity and treatments following exposure to the more lethal and potent chemical warfare nerve agents.     

Acute effects of styrene inhalation on the neuroendocrinological system of rats and the different effects in male and female rats

There have been several epidemiological and experimental studies about styrene from the neuroendocrinological viewpoint. Some reported that styrene exposure affected the neuroendocrinological system and enhanced prolactin (PRL) secretion, but others have denied those effects. It was assumed that styrene exposure caused depletion of dopamine (DA), which is a PRL inhibitor, and that, in consequence, the PRL level increased. However, not only DA but also many other factors control PRL secretion. Therefore, the mechanism of hypersecretion of PRL has not yet been clearly elucidated. In addition, effects of styrene on the female reproductive system have been reported, but the susceptibility needs to be further studied. Therefore, to investigate what causes hypersecretion of PRL and how different the susceptibility is in males and females, we studied acute effects of styrene exposure on the neuroendocrinological system in male and female rats. Immediately after exposure to 150 ppm styrene vapor for 10 days (8 h/day), male and female rats were killed, and blood and brain samples were collected. The styrene concentration in blood, hormones such as PRL, growth hormone (GH) and thyroid-stimulating hormone (TSH) in plasma and neurotransmitters in various brain regions were measured. The styrene concentration in the blood of female rats was higher than that in male rats, and the PRL level was significantly increased in female exposed rats compared with controls. No significant change was observed in male rats. We did not observe any significant changes in DA, 5-hydroxytryptamine (5-HT) or their metabolites. Because neurotransmitters were not affected in either male or female rats, the mechanism enhancing PRL secretion remains unclear. These results suggest that styrene exposure may cause hypersecretion of PRL and that the sensitivity to styrene exposure of the female may be higher than that of the male.     

雾化吸入布地奈德预防急性上感诱发婴幼儿喘息的临床研究

目的：探讨雾化吸入布地奈德预防急性上呼吸道感染（AU砌）诱发婴幼儿喘息的临床效果。方法：将既往有毛细支气管炎病史的AURI患儿126例随机分成两组,对照组63例采用常规治疗,治疗组63例在常规治疗的基础上加用布地奈德雾化治疗．统计两组出现喘息性征象和诱发喘息性疾病的病例数。结果：治疗组出现喘息性征象和诱发喘息性疾病的病例敬均明显少于对照组（P〈0．01）。结论：雾化吸入布地奈德预防AURI诱发婴幼儿喘息疗效确切,方法简便,副作用小,值得临床推广。     

布地奈德混悬液雾化吸入治疗急性喉炎的疗效观察

目的:观察布地奈德混悬液雾化吸入治疗小儿急性感染性喉炎的疗效.方法:将90例喉炎患儿随机分为三组,三组均采用综合治疗.观察组加用布地奈德混悬液雾化吸入,对照组采用地塞米松雾化或静脉给药,对治疗后症状、体征持续时间进行比较.结果:观察组在犬吠样咳嗽、声嘶、喉梗阻症状的缓解作用在早期与对照组差异有统计学意义(P＜0.01),雾化吸入地塞米松疗效差.结论:布地奈德混悬液雾化吸入治疗小儿急性喉炎起效快,疗效好,方法简单,不良反应少.     

Effects of alcohol before,during and after acute paraquat poisoning in rats

Abstract

This study aimed to explore the effects of alcohol on paraquat dichloride (PQ) poisoning. Compared to PQ administration alone, alcohol gavage intervention before PQ administration could delay the peak time of plasma C_max. Myeloperoxidase (MPO) levels were correlated with the level of hydroxyl radical inhibiting ability. The alcohol gavage intervention led to aggravated acute lung injury by improving the inflammatory reaction and reactive oxygen generation. There was a positive correlation between oxidative stress and inflammatory reaction after acute PQ administration. Alcohol intake in combination with PQ poisoning can increase MPO levels, reduce OH^? and aggravate lung tissue damage.     

Bioaccumulation and locomotor effects of manganese sulfate in Sprague-Dawley rats following subchronic (90 days) inhalation exposure

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic compound that was introduced as an anti-knock additive to replace lead in unleaded fuel. The combustion of MMT results in the emission of fine Mn particulates mainly in the form of manganese sulfate and manganese phosphate. The objective of this study is to determine the effects of subchronic exposure to Mn sulfate in different tissues, on locomotor activity, on neuropathology, and on blood serum biochemical parameters. A control group and three groups of 30 male Sprague-Dawley rats were exposed 6-h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3,000 microg/m(3) Mn sulfate. Locomotor activity was measured during 36 h using an Auto-Track System. Blood and the following tissues were collected and analyzed for manganese content by neutron activation analysis: olfactory bulb, globus pallidus, caudate/putamen, cerebellum, frontal cortex, liver, lung, testis, and kidney. Neuronal cell counts were obtained for the caudate/putamen and the globus pallidus and clinical biochemistry was assessed. Manganese concentrations were increased in blood, kidney, lung, and testis and in all brain regions in the 3,000 microg/m(3) exposure group. Significant differences were also noted in the 300 microg/m(3) exposure group. Neuronal cell counts for the globus pallidus were significantly different between the two highest exposed groups and the controls. Locomotor activity for all exposure concentrations and resting time for the middle and highest concentrations for the two night resting periods were significantly increased. Total ambulatory count was decreased significantly for all exposure concentrations. Biochemical profiles also presented significant differences. No body weight loss was observed between all groups. These results suggest that neurotoxicity could occur at low exposure levels of Mn sulfate, one of the main combustion products of MMT.     

Vapor inhalation exposure to soman in conscious untreated rats: preliminary assessment of neurotoxicity

Neurological toxicity and brain injury following vapor inhalation exposure to the chemical warfare nerve agent (CWNA) soman (GD) were examined in untreated non-anesthetized rats. In this study, male Sprague-Dawley rats (300–350?g) were exposed to 600?mg?×?min/m³ of soman or vehicle in a customized head-out inhalation system for 7?min. Convulsant animals were observed for clinical signs and various regions of the brain (dorsolateral thalamus, basolateral amygdala, piriform cortex, and lateral cortex) were collected for pathological observations 24?h post-exposure. Signs of CWNA-induced cholinergic crises including salivation, lacrimation, increased urination and defecation, and tremors were observed in all soman-exposed animals. Soman-exposed animals at 24?h post-exposure lost 11% of their body weight in comparison to 2% in vehicle-exposed animals. Whole blood acetylcholinesterase (AChE) activity was significantly inhibited in all soman-exposed groups in comparison to controls. Brain injury was confirmed by the neurological assessment of hematoxylin-eosin (H&E) staining and microscopy in the piriform cortex, dorsolateral thalamus, basolateral amygdala, and lateral cortex. Severe damage including prominent lesions, edematous, congested, and/or hemorrhagic tissues was observed in the piriform cortex, dorsolateral thalamus, and lateral cortex in soman-exposed animals 24?h post-exposure, while only minimal damage was observed in the basolateral amygdala. These results indicate that inhalation exposure to soman vapor causes neurological toxicity and brain injury in untreated unanesthetized rats. This study demonstrates the ability of the described soman vapor inhalation exposure model to cause neurological damage 24?h post-exposure in rats.     

Lack of effects of nose-only inhalation exposure on testicular toxicity in male rats.

Reductions in testicular mass, sperm motility, and mating frequency have been attributed to the stresses caused by confinement of Sprague-Dawley male rats in nose-only inhalation exposure tubes. Testicular changes, including an increase in testicular atrophy, have been detected at an increased incidence in male rats used in inhalation studies as compared with rats of the same age and strain used in oral toxicity studies. This study was designed to determine whether nose-only exposure of male rats caused testicular toxicity under conditions of cooling of the exposure room and appropriate acclimation to the exposure tubes. In order to acclimate the rats to the nose-only inhalation exposure apparatus, all male rats were placed in the exposure tubes for at least four successively increasing time intervals (15, 30, 45, and 60 min) on 4 separate days, with a rest period of approximately 48 h between the first and second acclimation. Twenty male rats were exposed nose-only to filtered air for approximately 2 h per day for 28 days before cohabitation and continuing throughout a 14-day cohabitation period. To reduce thermal stress, the exposure room temperature was maintained at 64 to 70 degrees F. Twenty control rats were housed in the same room as the exposed rats but were not placed in exposure tubes. End points monitored were body weight, testicular weight, sperm count, sperm motility, and histopathology of the testes, epididymides, prostate, and seminal vesicles. The control rats gained weight more rapidly than the exposed rats. All the rats in both groups mated successfully, and testicular weights, normalized to body weight, were similar for both groups. More importantly, there were no microscopic changes that could be considered an adverse effect on the reproductive tissues in the male rats placed in exposure tubes. Thus, nose-only exposure for up to 2 h per day for a total of 42 days did not cause adverse effects on the reproductive organs, fertility, or reproductive performance of male rats under the conditions of this study.     

布地奈德混悬液雾化吸入治疗小儿急性喉炎的疗效观察

目的研究布地奈德混悬液雾化吸入治疗小儿急性喉炎的疗效。方法选择67例急性喉炎患儿,随机分为治疗组与对照组。治疗组加用布地奈德混悬液雾化吸入,对照组采用地塞米松静脉给药,比较两组患儿的疗效。结果两组疗效比较,存在显著性差异（P〈0．005）。结论布地奈德混悬液雾化吸入治疗小儿急性喉炎起效快,疗效好,不良反应少。     

Acute and subacute inhalation toxicity of diborane in male ICR mice

 To clarify the toxicity of diborane, we conducted acute (15 ppm for 1, 2, 4 or 8 h) and subacute (5 ppm for 2 or 4 weeks) inhalation studies on ICR mice. The concentration resulting in a 50% kill after 4 h exposure was 31.5 ppm. Body weight gain was suppressed and the lung weight was increased in diborane-exposed mice in both acute and subacute studies. In the acute study, diffuse pan bronchiolitis-like lesions developed in the lung in various degrees depending on exposure time, which can be pathologically characterized as infiltration of inflammatory cells into the terminal bronchioles and surrounding alveoli, pulmonary congestion and bleeding and/or edema. In the subacute study, we observed lymphoid hyperplasia in the perivascular and peribronchial areas, and infiltration of macrophage and plasma cells into the alveoli. In the mice exposed for 4 weeks, the lesions were more severe than in those exposed for 2 weeks, consisting of hyperplasia and desquamation of Clara cells. In the nasal cavity, we saw mucous exudate and inflammatory cells, suggesting irritation caused by diborane. The histopathological findings, except for the respiratory organs, did not reveal any exposure-related changes. No significant changes were seen in hematological and serum biochemical examinations either. In conclusion, the target organ of diborane inhalation is the respiratory organs, particularly the lung. Further inhalation experiments are essential to investigate the safety exposure levels of diborane. Received: 31 May 1994 / Accepted: 3 November 1994     

Two-year inhalation study of carcinogenicity and chronic toxicity of 1,4-dioxane in male rats

Carcinogenicity and chronic toxicity of 1,4-dioxane were examined by inhalation exposure of 50 male F344 rats to 1,4-dioxane vapor at 0 (clean air), 50, 250, or 1250 ppm (v/v) for 6 h/day, 5 days/wk, and 104 wk. Survival rates of 250 and 1250 ppm-exposed groups were decreased near the end of the 2-yr exposure period, due probably to the occurrence of malignant tumors. A statistically significant but marginal decrement of terminal body weight (<10%) was found in the 1250 ppm-exposed group, suggesting slight systemic toxicity. Significant changes in plasma levels of AST, ALT, ALP, and γ-GTP and relative weight of the liver occurred in the 1250 ppm-exposed group. Dose-dependent and statistically significant increases in incidences of nasal squamous cell carcinomas, hepatocellular adenomas, and peritoneal mesotheliomas were found primarily in the 1250 ppm-exposed group. The incidences of renal cell carcinomas, fibroadenomas in the mammary gland, and adenomas in the Zymbal gland were also increased dose-dependently. Preneoplastic lesions occurred in the nasal cavity and liver of the 1,4-dioxane-exposed groups. As nonneoplastic lesions, the significantly increased incidences of nuclear enlargement, atrophy, and respiratory metaplasia in the nasal cavity were noted at 50 ppm and above. A LOAEL (lowest observed adverse effect level) was determined at 50 ppm for the nasal endpoint of general chronic toxicity. This study provides clear evidence of carcinogenicity for 1,4-dioxane in male rats. A cytotoxic-proliferative and in vivo genotoxic mode of action is suggested to operate in 1,4-dioxane-induced carcinogenesis.     

Acute inhalation toxicity of high concentrations of silane in male ICR mice

In order to examine the toxicity of silane, male ICR mice were exposed to silane for 30 min (n=8), 1 or 4 h (n=12) at concentrations of 2500, 5000, 7500 (30-min experiment only) or 10000 ppm. In the 1- and 4-h experiments, 12 mice were divided into two sub-groups: four for 2-day observation and eight for 2-week observation. The mortality was six deaths out of eight mice exposed to 10000 ppm for 4 h. No deaths occurred in any of the other experiments. In the mice sacrificed 2 days after the exposure, acute renal tubular necrosis was observed at 10000 ppm (1-h exposure) or at 2500 ppm or more (4-h exposure). Reduction in body weight, increase in relative kidney weight and blood urea nitrogen (BUN) level, and splenic atrophy and inflammatory changes of the nasal mucosa were also seen in the 10000 ppm-4 h exposure group. In the mice sacrificed 2 weeks after the exposure, tubulo-interstitial nephritis (TIN) developed at 7500 ppm or more (30-min exposure) or at 5000 ppm or more (1- and 4-h exposure). BUN increased in a dose-dependent manner, and BUN in TIN positive mice was significantly higher than that in TIN negative mice (1- and 4-h exposure). No histopathological changes were observed in the glomeruli. These results indicate that the LC₅₀ of silane in mice is between 5000 and 10000 ppm for 4-h exposure and is greater than 10000 ppm for 1-h or 30-min exposure. The target site of silane toxicity is the renal tubule, and the no-observed-effect levels of silane for acute inhalation exposure in mice are 1000 ppm for 4-h exposure (from the previous report of our research group), 2500 ppm for 1-h exposure and 5000 ppm for 30-min exposure.     

Mercury vapor inhalation and poisoning of a family

Acute mercury vapor poisoning is a rare but fatal toxicological emergency. People are exposed to mercury in daily life by the way of foods, vaccines, antiseptics, ointments, amalgam or occupation. We present here, the clinical picture and management of four members of the same family who were exposed to elemental mercury. Three of the family members were seen in another hospital with malaise, fever, eritematous rash and pulmonary problems. Their questioning revealed the mercury exposure. Having a suspicion of heavy metal intoxication, blood and urine mercury levels were measured and mercury intoxication was diagnosed. On admission to our hospital, two patients already had chelation therapy. In three of them we found three distinct abnormalities: encephalopathy, nephrotic syndrome and polyneuropathy. The fourth family member had minor symptoms. This family is an example for the inhalation exposure resulting from inappropriate handling of liquid mercury. During the first days, flu like illness ensues. Then, severe pulmonary, neurological, renal, hepatic, hematological and dermatological dysfunctions develop. Blood and urine mercury levels should be tested on suspicion, but it must be kept in mind that blood level is unreliable in predicting the severity of mercury toxicity. The priority in the treatment should be removing the patient from the source of exposure. Then British anti-Lewisite, edetate calcium disodium, penicillamine, Sodium 2,3-dimercaptopropane-1-sulfhonate and 2,3-dimercaptosuccinic acid can be used for binding the mercury. We conclude that since mercury-containing devices are present in daily life, physicians must be able to recognize the clinical manifestations and treatment of mercury poisoning.     

Acute pulmonary toxicity following inhalation exposure to aerosolized VX in anesthetized rats

ABSTRACT

This study evaluated acute toxicity and pulmonary injury in rats at 3, 6 and 24?h after an inhalation exposure to aerosolized O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX). Anesthetized male Sprague-Dawley rats (250–300?g) were incubated with a glass endotracheal tube and exposed to saline or VX (171, 343 and 514?mg×min/m³ or 0.2, 0.5 and 0.8?LCt₅₀, respectively) for 10?min. VX was delivered by a small animal ventilator at a volume of 2.5?ml?×?70 breaths/minute. All VX-exposed animals experienced a significant loss in percentage body weight at 3, 6, and 24?h post-exposure. In comparison to controls, animals exposed to 514?mg×min/m³ of VX had significant increases in bronchoalveolar lavage (BAL) protein concentrations at 6 and 24?h post-exposure. Blood acetylcholinesterase (AChE) activity was inhibited dose dependently at each of the times points for all VX-exposed groups. AChE activity in lung homogenates was significantly inhibited in all VX-exposed groups at each time point. All VX-exposed animals assessed at 20 min and 3, 6 and 24?h post-exposure showed increases in lung resistance, which was prominent at 20 min and 3?h post-exposure. Histopathologic evaluation of lung tissue of the 514?mg×min/m³ VX-exposed animals at 3, 6 and 24?h indicated morphological changes, including perivascular inflammation, alveolar exudate and histiocytosis, alveolar septal inflammation and edema, alveolar epithelial necrosis, and bronchiolar inflammatory infiltrates, in comparison to controls. These results suggest that aerosolization of the highly toxic, persistent chemical warfare nerve agent VX results in acute pulmonary toxicity and lung injury in rats.     

Bioaccumulation and locomotor effects of manganese phosphate/sulfate mixture in Sprague-Dawley rats following subchronic (90 days) inhalation exposure

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline in Canada. The primary combustion products of MMT are Mn phosphate, Mn sulfate, and a Mn phosphate/Mn sulfate mixture. Concerns have been raised that the combustion products of MMT containing Mn could be neurotoxic, even at low levels of exposure. The objective of this study is to investigate exposure-response relationships for bioaccumulation and locomotor effects following subchronic inhalation exposure to a mixture of manganese phosphates/sulfate mixture. A control group and three groups of 30 male Sprague-Dawley rats were exposed in inhalation chambers for a period of 13 weeks, 5 days per week, 6 h a day. Exposure concentrations were 3000, 300, and 30 microg/m(3). At the end of the exposure period, locomotor activity and resting time tests were conducted for 36 h using a computerized autotrack system. Rats were then euthanized by exsanguination and Mn concentrations in different tissues (liver, lung, testis, and kidney) and blood and brain (caudate putamen, globus pallidus, olfactory bulb, frontal cortex, and cerebellum) were determined by neutron activation analysis. Increased manganese concentrations were observed in blood, kidney, lung, testis, and in all brain sections in the highest exposure group. Mn in the lung and in the olfactory bulb were dose dependent. Our data indicate that the olfactory bulb accumulated more Mn than other brain regions following inhalation exposure. Locomotor activity was increased at 3000 microg/m(3), but no difference was observed in resting time among the exposed groups. At the end of the experiment, rats exposed to 300 and 3000 microg/m(3) exhibited significantly decreased body weight in comparison with the control group. Biochemical profiles also revealed some significant differences in certain parameters, specifically alkaline phospatase, urea, and chlorate.