Workers regularly using vibrating hand tools may develop a disorder referred to as hand-arm vibration syndrome (HAVS). HAVS is characterized by cold-induced vasospasms in the hands and fingers that result in blanching of the skin, loss of sensory function, pain, and reductions in manual dexterity. Exposure to vibration induces some of these symptoms. However, the soft tissues of the hands and fingers of workers are compressed as a result of the force generated when a worker grips a tool. The compression of these soft tissues might also contribute to the development of HAVS. The goal of this study was to use an established rat tail model to determine the mechanisms by which compression of the tail tissues affects (1) the ventral tail artery (VTA) and ventral tail nerves (VTN), (2) nerves and sensory receptors in the skin, (3) dorsal root ganglia (DRG), and (4) spinal cord. Tissue compression resulted in the following changes (1) circulating pituitary and steroid hormone concentrations, (2) expression of factors that modulate vascular function in the skin and tail artery, and (3) factors associated with nerve damage, DRG, and spinal cord. Some of these observed effects differed from those previously noted with vibration exposure. Based upon these findings, the effects of applied force and vibration are different. Studies examining the combination of these factors might provide data that may potentially be used to improve risk assessment and support revision of standards.

Over-exposure of the hand-arm system to intense vibration and force over time may cause degeneration of the vascular, neurological, and musculoskeletal systems in the fingers. A novel animal model using rat tails has been developed to understand the health effects on human fingers exposed to vibration and force when operating powered hand tools or workpieces. The biodynamic responses, such as vibration stress, strain, and power absorption density, of the rat tails can be used to help evaluate the health effects related to vibration and force and to establish a dose-effect relationship. While the biodynamic responses of cadaver rat tails have been investigated, the objective of the current study was to determine whether the biodynamic responses of living rat tails are different from those of cadaver rat tails, and whether the biodynamic responses of both living and cadaver tails change with exposure duration. To make direct comparisons, the responses of both cadaver and living rat tails were examined on four different testing stations. The transfer function of each tail under a given contact force (2 N) was measured at each frequency in the one-third octave bands from 20 to 1000 Hz, and used to calculate the mechanical system parameters of the tails. The transfer functions were also measured at different exposure durations to determine the time dependency of the response. Differences were observed in the vibration biodynamic responses between living and cadaver tails, but the general trends were similar. The biodynamic responses of both cadaver and living rat tails varied with exposure duration. © 2024 by the authors.

Three-dimensional (3D) printing with polycarbonate (PC) plastic occurs in manufacturing settings, homes, and schools. Emissions generated during printing with PC stock and bisphenol-A (BPA), an endocrine disrupter in PC, may induce adverse health effects. Inhalation of 3D printer emissions, and changes in endocrine function may lead to cardiovascular dysfunction. The goal of this study was to determine whether there were any changes in markers of peripheral or cardiovascular dysfunction in animals exposed to PC-emissions. Male Sprague Dawley rats were exposed to PC-emissions generated by 3D printing for 1, 4, 8, 15 or 30 d. Exposure induced a reduction in the expression of the antioxidant catalase (Cat) and endothelial nitric oxide synthase (eNos). Endothelin and hypoxia-induced factor 1α transcripts increased after 30 d. Alterations in transcription were associated with elevations in immunostaining for estrogen and androgen receptors, nitrotyrosine, and vascular endothelial growth factor in cardiac arteries of PC-emission exposed animals. There was also a reduction eNOS immunostaining in cardiac arteries from rats exposed to PC-emissions. Histological analyses of heart sections revealed that exposure to PC-emissions resulted in vasoconstriction of cardiac arteries and thickening of the vascular smooth muscle wall, suggesting there was a prolonged vasoconstriction. These findings are consistent with studies showing that inhalation 3D-printer emissions affect cardiovascular function. Although BPA levels in animals were relatively low, exposure-induced changes in immunostaining for estrogen and androgen receptors in cardiac arteries suggest that changes in the action of steroid hormones may have contributed to the alterations in morphology and markers of cardiac function.

OBJECTIVE: Inhalation of diesel exhaust (DE) has been shown to be an occupational hazard in the transportation, mining, and gas and oil industries. DE also contributes to air pollution, and therefore, is a health hazard to the general public. Because of its effects on human health, changes have been made to diesel engines to reduce both the amounts of particulate matter and volatile fumes they generate. The goal of the current study was to examine the effects of inhalation of diesel exhaust. MATERIALS AND METHODS: The study presented here specifically examines the effects of exposure to 0.2 and 1.0 mg/m(3) DE or filtered air (6h/d for 4 d) on measures of peripheral and cardio-vascular function, and biomarkers of heart and kidney dysfunction in male rats. A Tier 2 engine used in oil and gas fracking operations was used to generate the diesel exhaust. RESULTS: Exposure to 0.2 mg/m(3) DE resulted in an increase in blood pressure 1d following the last exposure, and increases in dobutamine-induced cardiac output and stroke volume 1 and 27d after exposure. Changes in peripheral vascular responses to norepinephrine and acetylcholine were minimal as were changes in transcript expression in the heart and kidney. Exposure to 1.0 mg/m(3) DE did not result in major changes in blood pressure, measures of cardiac function, peripheral vascular function or transcript expression. DISCUSSION AND CONCLUSIONS: Based on the results of this study, we suggest that exposure to DE generated by a Tier 2 compliant diesel engine generates acute effects on biomarkers indicative of cardiovascular dysfunction. Recovery occurs quickly with most measures of vascular/cardiovascular function returning to baseline levels by 7d following exposure.

OBJECTIVE: This study described the effects of applied force (grip) on vascular and sensorineural function in an animal model of hand-arm vibration syndrome (HAVS). METHODS: Rat tails were exposed to 0, 2 or 4 newtons (N) of applied force 4 hr/day for 10 days. Blood flow and sensitivity to transcutaneous electrical stimulation and pressure were measured. RESULTS: Applied force increased blood flow but reduced measures of arterial plasticity. Animals exposed to force tended to be more sensitive to 250 Hz electrical stimulation and pressure applied to the tail. CONCLUSIONS: Effects of applied force on blood flow and sensation are different than those of vibration. Studies examining co-exposures to force and vibration will provide data that can be used to determine how these factors affect risk of workers developing vascular and sensorineural dysfunction (i.e., HAVS).

Three-dimensional (3D) printing of manufactured goods has increased in the last 10 years. The increased use of this technology has resulted in questions regarding the influence of inhaling emissions generated during printing. The goal of this study was to determine if inhalation of particulate and/or toxic chemicals generated during printing with polycarbonate (PC) plastic affected the neuroendocrine system. Male rats were exposed to 3D-printer emissions (592 µg particulate/m(3) air) or filtered air for 4 h/day (d), 4 days/week and total exposures lengths were 1, 4, 8, 15 or 30 days. The effects of these exposures on hormone concentrations, and markers of function and/or injury in the olfactory bulb, hypothalamus and testes were measured after 1, 8 and 30 days exposure. Thirty days of exposure to 3D printer emissions resulted in reductions in thyroid stimulating hormone, follicle stimulating hormone and prolactin. These changes were accompanied by (1) elevation in markers of cell injury; (2) reductions in active mitochondria in the olfactory bulb, diminished gonadotropin releasing hormone cells and fibers as well as less tyrosine hydroxylase immunolabeled fibers in the arcuate nucleus; and (3) decrease in spermatogonium. Polycarbonate plastics may contain bisphenol A, and the effects of exposure to these 3D printer-generated emissions on neuroendocrine function are similar to those noted following exposure to bisphenol A.

It has been hypothesized that the biodynamic responses of the human finger tissues to vibration are among the major stimuli that cause vibration health effects. Furthermore, the finger contact pressure can alter these effects. It is difficult to test these hypotheses using human subjects or existing animal models. The objective of this study was to develop a new rat-tail vibration model to investigate the combined effects of vibration and contact pressure and to identify their relationships with the biodynamic responses. Physically, the new exposure system was developed by adding a loading device to an existing rat-tail model. An analytical model of the rat-tail exposure system was proposed and used to formulate the methods for quantifying the biodynamic responses. A series of tests with six tails dissected from rat cadavers were conducted to test and evaluate the new model. The experimental and modeling results demonstrate that the new model behaves as predicted. Unlike the previous model, the vibration strain and stress of the rat tail does not depend primarily on the vibration response of the tail itself but on that of the loading device. This makes it possible to quantify and control the biodynamic responses conveniently and reliably by measuring the loading device response. This study also identified the basic characteristics of the tail biodynamic responses in the exposure system, which can be used to help design the experiments for studying vibration biological effects.

Findings from epidemiological studies suggest that occupational exposure to whole-body vibration (WBV) may increase the risk of miscarriage and contribute to a reduction in fertility rates in both men and women. However, workers exposed to WBV may also be exposed to other risk factors that contribute to reproductive dysfunction. The goal of this experiment was to examine the effects of WBV on reproductive physiology in a rat model. Male and female rats were exposed to WBV at the resonant frequency of the torso (31.5 Hz, 0.3 g amplitude) for 4 hr/day for 10 days. WBV exposure resulted in a significant reduction in number of developing follicles, and decrease in circulating estradiol concentrations, ovarian luteinizing hormone receptor protein levels, and marked changes in transcript levels for several factors involved in follicular development, cell cycle, and steroidogenesis. In males, WBV resulted in a significant reduction in spermatids and circulating prolactin levels, elevation in number of males having higher circulating testosterone concentrations, and marked alterations in levels of transcripts associated with oxidative stress, inflammation, and factors involved in regulating the cell cycle. Based upon these findings data indicate that occupational exposure to WBV contributes to adverse alterations in reproductive physiology in both genders that may lead to reduction in fertility.

Workers in the oil and gas extraction industry are at risk of inhaling volatile organic compounds. Epidemiological studies suggest oil vapor inhalation may affect cardiovascular health. Thus, in this hazard identification study we investigated the effects of inhalation of crude oil vapor (COV) on cardiovascular function. Male rats were exposed to air or COV (300ppm) for 6h (acute), or 6h/day 4 d/wk. 4 wk. (sub-chronic). The effects of COV inhalation were assessed 1, 28, and 90 d post-exposure. Acute exposure to COV resulted in a reduction in mean arterial and diastolic blood pressures 1 and 28 d after exposure, changes in nitrate-nitrite and H(2)O(2) levels, and in the expression of transcripts and proteins that regulate inflammation, vascular remodeling, and the synthesis of NO in the heart and kidneys. The sub-chronic exposure resulted in a reduced sensitivity to (1)-adrenoreceptor-mediated vasoconstriction in vitro 28 d post-exposure, and a reduction in oxidative stress in the heart. Sub-chronic COV exposure led to alterations in the expression of NO synthases and anti-oxidant enzymes, which regulate inflammation and oxidative stress in the heart and kidneys. There seems to be a balance between changes in the expression of transcripts associated with the generation of reactive oxygen species (ROS) and antioxidant enzymes. The ability of antioxidant enzymes to reduce or inhibit the effects of ROS may allow the cardiovascular system to adapt to acute COV exposures. However, sub-chronic exposures may result in longer-lasting negative health consequences on the cardiovascular system.

An investigation into the potential toxicological effects of fracking sand dust (FSD), collected from unconventional gas drilling sites, has been undertaken, along with characterization of their chemical and biophysical properties. Using intratracheal instillation of nine FSDs in rats and a whole body 4-d inhalation model for one of the FSDs, i.e., FSD 8, and related in vivo and in vitro experiments, the effects of nine FSDs on the respiratory, cardiovascular and immune systems, brain and blood were reported in the preceding eight tandem papers. Here, a summary is given of the key observations made in the organ systems reported in the individual studies. The major finding that inhaled FSD 8 elicits responses in extra-pulmonary organ systems is unexpected, as is the observation that the pulmonary effects of inhaled FSD 8 are attenuated relative to forms of crystalline silica more frequently used in animal studies, i.e., MIN-U-SIL®. An attempt is made to understand the basis for the extra-pulmonary toxicity and comparatively attenuated pulmonary toxicity of FSD 8.

Hydraulic fracturing is used to access oil and natural gas reserves. This process involves the high-pressure injection of fluid to fracture shale. Fracking fluid contains approximately 95% water, chemicals and 4.5% fracking sand. Workers may be exposed to fracking sand dust (FSD) during the manipulation of the sand, and negative health consequences could occur if FSD is inhaled. In the absence of any information about its potential toxicity, a comprehensive rat animal model study (see Fedan, J.S., Toxicol Appl Pharmacol. 000, 000-000, 2020) was designed to investigate the bioactivities of several FSDs in comparison to MIN-U-SIL® 5, a respirable α-quartz reference dust used in previous animal models of silicosis, in several organ systems. The goal of this study was to assess the effects of inhalation of one FSD, i.e., FSD 8, on factors and tissues that affect cardiovascular function. Male rats were exposed to 10 or 30 mg/m(3) FSD (6 h/d for 4 d) by whole body inhalation, with measurements made 1, 7 or 27 d post-exposure. One day following exposure to 10 mg/m(3) FSD the sensitivity to phenylephrine-induced vasoconstriction in tail arteries in vitro was increased. FSD exposure at both doses resulted in decreases in heart rate (HR), HR variability, and blood pressure in vivo. FSD induced changes in hydrogen peroxide concentrations and transcript levels for pro-inflammatory factors in heart tissues. In kidney, expression of proteins indicative of injury and remodeling was reduced after FSD exposure. When analyzed using regression analysis, changes in proteins involved in repair and remodeling were correlated. Thus, it appears that inhalation of FSD does have some prolonged effects on cardiovascular, and, possibly, renal function. The findings also provide information regarding potential mechanisms that may lead to these changes, and biomarkers that could be examined to monitor physiological changes that could be indicative of impending cardiovascular dysfunction.

Graphenes isolated from crystalline graphite are used in several industries. Employees working in the production of graphenes may be at risk of developing respiratory problems attributed to inhalation or contact with particulate matter (PM). However, graphene nanoparticles might also enter the circulation and accumulate in other organs. The aim of this study was to examine how different forms of graphene affect peripheral vascular functions, generation of reactive oxygen species (ROS) and changes in gene expression that may be indicative of cardiovascular and/or renal dysfunction. In the first investigation, different doses of graphene nanoplatelets were administered to mice via oropharyngeal aspiration. These effects were compared to those of dispersion medium (DM) and carbon black (CB). Gene expression alterations were observed in the heart for CB and graphene; however, only CB produced changes in peripheral vascular function. In the second study, oxidized forms of graphene were administered. Both oxidized forms increased the sensitivity of peripheral blood vessels to adrenoreceptor-mediated vasoconstriction and induced changes in ROS levels in the heart. Based upon the results of these investigations, exposure to graphene nanoparticles produced physiological and alterations in ROS and gene expression that may lead to cardiovascular dysfunction. Evidence indicates that the effects of these particles may be dependent upon dose and graphene form to which an individual may be exposed to.

OBJECTIVES: Laser Doppler blood flow measurements have been used for diagnosis or detection of peripheral vascular dysfunction. This study used a rat tail model of vibration-induced vascular injury to determine how laser Doppler measurements were affected by acute and repeated exposures to vibration, and to identify changes in the Doppler signal that were associated with the exposure. METHODS: Blood flow was measured immediately after a single exposure to vibration, or before vibration exposure on days 1, 5, 10, 15, and 20 of a 20 days exposure. RESULTS: After a single exposure to vibration, average tail blood flow was reduced. With 20 days of exposure, there was a reduction in the amplitude of the arterial pulse on days 10 to 20 in vibrated rats and days 15 to 20 in control rats. CONCLUSIONS: More detailed statistical analyses of laser Doppler data may be needed to identify early changes in peripheral circulation after exposure to vibration.

Prolonged occupational exposure to hand-held vibrating tools leads to pain and reductions in tactile sensitivity, grip strength and manual dexterity. The goal of the current study was to use a rat-tail vibration model to determine how vibration frequency influences factors related to nerve injury and dysfunction. Rats were exposed to restraint, or restraint plus tail vibration at 62.5 Hz or 250 Hz. Nerve function was assessed using the current perception threshold (CPT) test. Exposure to vibration at 62.5 and 250 Hz, resulted in a reduction in the CPT at 2000 and 250 Hz electrical stimulation (i.e. increased Abeta and Adelta, nerve fiber sensitivity). Vibration exposure at 250 Hz also resulted in an increased sensitivity of C-fibers to electrical stimulation and thermal nociception. These changes in nerve fiber sensitivity were associated with increased expression of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha in ventral tail nerves, and increases in circulating concentrations of IL-1 beta in rats exposed to 250 Hz vibration. There was an increase in glutathione, but no changes in other measures of oxidative activity in the peripheral nerve. However, measures of oxidative stress were increased in the dorsal root ganglia (DRG). These changes in pro-inflammatory factors and markers of oxidative stress in the peripheral nerve and DRG were associated with inflammation, and reductions in myelin basic protein and post-synaptic density protein (PSD)-95 gene expression, suggesting that vibration induced changes in sensory function may be the result of changes at the exposed nerve, the DRG and/or the spinal cord.

OBJECTIVE: Epidemiology suggests that occupational exposure to hand-transmitted (segmental) vibration has local and systemic effects. This study used an animal model of segmental vibration to characterize the systemic effects of vibration. METHODS: Male Sprague Dawley rats were exposed to tail vibration for 10 days. Genes indicative of inflammation, oxidative stress, and cell cycle, along were measured in the heart, kidney, prostate and liver. RESULTS: Vibration increased oxidative stress and pro-inflammatory gene expression, and decreased anti-oxidant enzymes in heart tissue. In the prostate and liver, vibration resulted in changes in the expression of pro-inflammatory factors and genes involved in cell cycle regulation. CONCLUSIONS: These changes are consistent with epidemiological studies suggesting that segmental vibration has systemic effects. These effects may be mediated by changes in autonomic nervous system function, and/or inflammation and oxidative stress.

Repetitive exposure to hand-transmitted vibration is associated with development of peripheral vascular and sensorineural dysfunctions. These disorders and symptoms associated with it are referred to as hand-arm vibration syndrome (HAVS). Although the symptoms of the disorder have been well characterized, the etiology and contribution of various exposure factors to development of the dysfunctions are not well understood. Previous studies performed using a rat-tail model of vibration demonstrated that vascular and peripheral nervous system adverse effects of vibration are frequency-dependent, with vibration frequencies at or near the resonant frequency producing the most severe injury. However, in these investigations, the amplitude of the exposed tissue was greater than amplitude typically noted in human fingers. To determine how contact with vibrating source and amplitude of the biodynamic response of the tissue affects the risk of injury occurring, this study compared the influence of frequency using different levels of restraint to assess how maintaining contact of the tail with vibrating source affects the transmission of vibration. Data demonstrated that for the most part, increasing the contact of the tail with the platform by restraining it with additional straps resulted in an enhancement in transmission of vibration signal and elevation in factors associated with vascular and peripheral nerve injury. In addition, there were also frequency-dependent effects, with exposure at 250 Hz generating greater effects than vibration at 62.5 Hz. These observations are consistent with studies in humans demonstrating that greater contact and exposure to frequencies near the resonant frequency pose the highest risk for generating peripheral vascular and sensorineural dysfunction.

RATIONALE: There is limited evidence of the effect of exposure to heat on COPD morbidity and the interactive effect between indoor heat and air pollution has not been established. OBJECTIVES: To determine the effect of indoor and outdoor heat exposure on COPD morbidity and to determine whether air pollution concentrations modify the effect of temperature. METHODS: Sixty-nine participants with COPD were enrolled in a longitudinal cohort study and data from the 601 participant days that occurred during the warm weather season were included in the analysis. Participants completed home environmental monitoring with measurement of temperature, relative humidity, and indoor air pollutants and simultaneous daily assessment of respiratory health with questionnaires and portable spirometry. MEASUREMENTS AND MAIN RESULTS: Participants had moderate to severe COPD and spent the majority of their time indoors. Increases in maximum indoor temperature were associated with worsening of daily Breathlessness, Cough, and Sputum Scores (BCSS) and increases in rescue inhaler use. The effect was detected on the same day and lags of 1 and 2 days. The detrimental effect of temperature on these outcomes increased with higher concentrations of indoor fine particulate matter and nitrogen dioxide (p<0.05 for interaction terms). On days that participants went outdoors, increases in maximum daily outdoor temperature were associated with increases in BCSS scores after adjusting for outdoor pollution concentrations. CONCLUSIONS: For patients with COPD that spend the majority of their time indoors, indoor heat exposure during warmer months represents a modifiable environmental exposure that may contribute to respiratory morbidity. In the context of climate change, adaptive strategies that include optimization of indoor environmental conditions are needed to protect this high risk group from adverse health effects of heat.

OBJECTIVE: The aim of this study was to use an established model of vibration-induced injury to assess frequency-dependent changes in transcript expression in skin, artery, and nerve tissues. METHODS: Transcript expression in tissues from control and vibration-exposed rats (4 h/day for 10 days at 62.5, 125, or 250 Hz; 49 m/s, rms) was measured. Transcripts affected by vibration were used in bioinformatics analyses to identify molecular- and disease-related pathways associated with exposure to vibration. RESULTS: Analyses revealed that cancer-related pathways showed frequency-dependent changes in activation or inhibition. Most notably, the breast-related cancer-1 pathway was affected. Other pathways associated with breast cancer type 1 susceptibility protein related signaling, or associated with cancer and cell cycle/cell survivability were also affected. CONCLUSION: Occupational exposure to vibration may result in DNA damage and alterations in cell signaling pathways that have significant effects on cellular division.

One of the factors that can result in musculoskeletal injuries, and time off work, is exposure to repetitive motion. The goal of this study was to determine if skeletal muscle injury induced by exposure to injurious stretch-shortening cycles (iSSCs), resulted in hyperalgesia in the hind limb and changes in calcitonin-gene related peptide (CGRP) immunolabeling in the dorsal root ganglia (DRG) in young and old male rats. METHODS: Young (3months) and old (30months) male Fisher 344xBN F1 rats were anesthetized with isoflurane and the left hind limbs were exposed to 15 sets of 10 SSCs. Control animals were exposed to a single bout of SSCs of equal intensity. Sensitivity to mechanical stimulation was assessed using von Frey filaments prior to beginning the experiment, and on days 2 and 9 following exposure to iSSCs. Rats were euthanized one, 3 or 10days after the exposure. The ipsilateral DRG were dissected from the L4-5 region of the spine, along with the left tibialis anterior (LTA) muscle. RESULTS: Rats exposed to iSSCs were more sensitive to mechanical stimulation than control rats 2days after the exposure, and showed a reduction in peak force 3days after exposure. Changes in sensitivity to pressure were not associated with increases in CGRP labeling in the DRG at 3days. However, 9days after exposure to iSSCs, old rats still displayed an increased sensitivity to mechanical stimulation, and this hyperalgesia was associated with an increase in CGRP immunolabeling in the DRG. Young rats exposed to iSSC did not display a change in CGRP immunolabeling and sensitivity to mechanical stimulation returned to control levels at 10days. CONCLUSIONS: These findings suggest that hyperalgesia seen shortly after exposure to iSSC is not influenced by CGRP levels. However, in cases where recovery from injury may be slower, as it is in older rats, CGRP may contribute to the maintenance of hyperalgesia.

Repeated exposure to hand-transmitted vibration through the use of powered hand tools may result in pain and progressive reductions in tactile sensitivity. The goal of the present study was to use an established animal model of vibration-induced injury to characterize changes in sensory nerve function and cellular mechanisms associated with these alterations. Sensory nerve function was assessed weekly using the current perception threshold test and tail-flick analgesia test in male Sprague-Dawley rats exposed to 28 d of tail vibration. After 28 d of exposure, Abeta fiber sensitivity was reduced. This reduction in sensitivity was partly attributed to structural disruption of myelin. In addition, the decrease in sensitivity was also associated with a reduction in myelin basic protein and 2',3'- cyclic nucleotide phosphodiasterase (CNPase) staining in tail nerves, and an increase in circulating calcitonin gene-related peptide (CGRP) concentrations. Changes in Abeta fiber sensitivity and CGRP concentrations may serve as early markers of vibration-induced injury in peripheral nerves. It is conceivable that these markers may be utilized to monitor sensorineural alterations in workers exposed to vibration to potentially prevent additional injury.

Exposure to hand-transmitted vibration in the work-place can result in the loss of sensation and pain in workers. These effects may be exacerbated by pre-existing conditions such as diabetes or the presence of primary Raynaud's phenomena. The goal of these studies was to use an established model of vibration-induced injury in Zucker rats. Lean Zucker rats have a normal metabolic profile, while obese Zucker rats display symptoms of metabolic disorder or Type II diabetes. This study examined the effects of vibration in obese and lean rats. Zucker rats were exposed to 4h of vibration for 10 consecutive days at a frequency of 125Hz and acceleration of 49m/sec2 for 10 consecutive days. Sensory function was checked using transcutaneous electrical stimulation on days 1, 5 and 9 of the exposure. Once the study was complete the ventral tail nerves, dorsal root ganglia and spinal cord were dissected, and levels of various transcripts involved in sensorineural dysfunction were measured. Sensorineural dysfunction was assessed using transcutaneous electrical stimulation. Obese Zucker rats displayed very few changes in sensorineural function. However they did display significant changes in transcript levels for factors involved in synapse formation, peripheral nerve remodeling, and inflammation. The changes in transcript levels suggested that obese Zucker rats had some level of sensory nerve injury prior to exposure, and that exposure to vibration activated pathways involved in injury and re-innervation.

Anti-vibration gloves have been used to block the transmission of vibration from powered hand tools to the user, and to protect users from the negative health consequences associated with exposure to vibration. However, there are conflicting reports as to the efficacy of gloves in protecting workers. The goal of this study was to use a characterized animal model of vibration-induced peripheral vascular and nerve injury to determine whether antivibration materials reduced or inhibited the effects of vibration on these physiological symptoms. Rats were exposed to 4 h of tail vibration at 125 Hz with an acceleration 49 m/s(2). The platform was either bare or covered with antivibrating glove material. Rats were tested for tactile sensitivity to applied pressure before and after vibration exposure. One day following the exposure, ventral tail arteries were assessed for sensitivity to vasodilating and vasoconstricting factors and nerves were examined histologically for early indicators of edema and inflammation. Ventral tail artery responses to an alpha2C-adrenoreceptor agonist were enhanced in arteries from vibration-exposed rats compared to controls, regardless of whether antivibration materials were used or not. Rats exposed to vibration were also less sensitive to pressure after exposure. These findings are consistent with experimental findings in humans suggesting that antivibration gloves may not provide protection against the adverse health consequences of vibration exposure in all conditions. Additional studies need to be done examining newer antivibration materials.

Spot welding is used in the automotive and aircraft industries, where high-speed, repetitive welding is needed to join thin sections of metal. Epoxy adhesives are applied as sealers to the metal seams. Pulmonary function abnormalities and airway irritation have been reported in spot welders, but no animal toxicology studies exist. Therefore, the goal of this study was to investigate vascular, immune and lung toxicity measures after exposure to these metal fumes in an animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m3 to either mild-steel spot welding aerosols with sparking (high metal, HM) or without sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL cell challenge were performed to assess lung toxicity. Lung resistance (RL) was evaluated before and after challenge with inhaled methacholine (MCh). Functional assessment of the vascular endothelium in isolated rat tail arteries and leukocyte differentiation in the spleen and lymph nodes via flow cytometry was also done. Immediately after exposure, baseline RL was significantly elevated in the LM spot welding aerosols, but returned to control level by 24 h postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and cytotoxicity were mild and transient. Lung epithelial permeability was significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM aerosol. HM aerosols also caused vascular endothelial dysfunction and increased CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages. Acute inhalation of mild-steel spot welding fumes at occupationally relevant concentrations may act as an irritant as evidenced by the increased RL and result in endothelial dysfunction, but otherwise had minor effects on the lung.

Work rotation schedules may be used to reduce the negative effects of vibration on vascular function. This study determined how long it takes vascular function to recover after a single exposure to vibration in rats (125 Hz, acceleration 5g). The responsiveness of rat-tail arteries to the vasoconstricting factor UK14304, an alpha2C-adrenoreceptor agonist, and the vasodilating factor acetylcholine (ACh) were measured ex vivo 1, 2, 7, or 9 d after exposure to a single bout of vibration. Vasoconstriction induced by UK14304 returned to control levels after 1 d of recovery. However, re-dilation induced by ACh did not return to baseline until after 9 d of recovery. Exposure to vibration exerted prolonged effects on peripheral vascular function, and altered vascular responses to a subsequent exposure. To optimize the positive results of work rotation schedules, it is suggested that studies assessing recovery of vascular function after exposure to a single bout of vibration be performed in humans.

Research regarding the risk of developing hand-arm vibration syndrome after exposure to impact vibration has produced conflicting results. This study used an established animal model of vibration-induced dysfunction to determine how exposure to impact vibration affects peripheral blood vessels and nerves. The tails of male rats were exposed to a single bout of impact vibration (15 min exposure, at a dominant frequency of 30 Hz and an unweighted acceleration of approximately 345 m/s(2)) generated by a riveting hammer. Responsiveness of the ventral tail artery to adrenoreceptor-mediated vasoconstriction and acetylcholine-mediated re-dilation was measured ex vivo. Ventral tail nerves and nerve endings in the skin were assessed using morphological and immunohistochemical techniques. Impact vibration did not alter vascular responsiveness to any factors or affect trunk nerves. However, 4 days following exposure there was an increase in protein-gene product (PGP) 9.5 staining around hair follicles. A single exposure to impact vibration, with the exposure characteristics described above, affects peripheral nerves but not blood vessels.

Exposure to wet aerosols generated during use of spray products containing silver (Ag) has not been evaluated. The goal was to assess the potential for cardiopulmonary toxicity following an acute inhalation of wet silver colloid. Rats were exposed by inhalation to a low concentration (100 mug/m(3) ) using an undiluted commercial antimicrobial product (20 mg/L total silver; approximately 33 nm mean aerodynamic diameter [MAD]) or to a higher concentration (1000 mug/m(3)) using a suspension (200 mg/L total silver; approximately 39 nm MAD) synthesized to possess a similar size distribution of Ag nanoparticles for 5 h. Estimated lung burdens from deposition models were 0, 1.4, or 14 mug Ag/rat after exposure to control aerosol, low, and high doses, respectively. At 1 and 7 d postexposure, the following parameters were monitored: pulmonary inflammation, lung cell toxicity, alveolar air/blood barrier damage, alveolar macrophage activity, blood cell differentials, responsiveness of tail artery to vasoconstrictor or vasodilatory agents, and heart rate and blood pressure in response to isoproterenol or norepinephrine, respectively. Changes in pulmonary or cardiovascular parameters were absent or nonsignificant at 1 or 7 d postexposure with the exceptions of increased blood monocytes 1 d after high-dose Ag exposure and decreased dilation of tail artery after stimulation, as well as elevated heart rate in response to isoproterenol 1 d after low-dose Ag exposure, possibly due to bioavailable ionic Ag in the commercial product. In summary, short-term inhalation of nano-Ag did not produce apparent marked acute toxicity in this animal model.

OBJECTIVE: Occupational exposure to hand-transmitted vibration can result in damage to nerves and sensory loss. The goal of this study was to assess the frequency-dependent effects of repeated bouts of vibration on sensory nerve function and associated changes in nerves. METHODS: The tails of rats were exposed to vibration at 62.5, 125, or 250 Hz (constant acceleration of 49 m/s) for 10 days. The effects on sensory nerve function, nerve morphology, and transcript expression in ventral tail nerves were measured. RESULTS: Vibration at all frequencies had effects on nerve function and physiology. However, the effects tended to be more prominent with exposure at 250 Hz. CONCLUSION: Exposure to vibration has detrimental effects on sensory nerve function and physiology. However, many of these changes are more prominent at 250-Hz exposure than at lower frequencies.

Our laboratory has previously demonstrated that application of an antimicrobial spray product containing titanium dioxide (TiO(2)) generates an aerosol of titanium dioxide in the breathing zone of the applicator. The present report describes the design of an automated spray system and the characterization of the aerosol delivered to a whole body inhalation chamber. This system produced stable airborne levels of TiO(2) particles with a median count size diameter of 110 nm. Rats were exposed to 314 mg/m(3) min (low dose), 826 mg/m(3) min (medium dose), and 3638 mg/m(3) min (high dose) of TiO(2) under the following conditions: 2.62 mg/m(3) for 2 h, 1.72 mg/m(3) 4 h/day for 2 days, and 3.79 mg/m(3) 4 h/day for 4 days, respectively. Pulmonary (breathing rate, specific airway resistance, inflammation, and lung damage) and cardiovascular (the responsiveness of the tail artery to constrictor or dilatory agents) endpoints were monitored 24 h post-exposure. No significant pulmonary or cardiovascular changes were noted at low and middle dose levels. However, the high dose caused significant increases in breathing rate, pulmonary inflammation, and lung cell injury. Results suggest that occasional consumer use of this antimicrobial spray product should not be a hazard. However, extended exposure of workers routinely applying this product to surfaces should be avoided. During application, care should be taken to minimize exposure by working under well ventilated conditions and by employing respiratory protection as needed. It would be prudent to avoid exposure to children or those with pre-existing respiratory disease.

These studies characterized cardiovascular responses after an acute inhalation exposure to COREXIT EC9500A, the oil dispersant used in the Deepwater Horizon oil spill. Male Sprague-Dawley rats underwent a single 5-h inhalation exposure to COREXIT EC9500A (average exposure level 27.12 mg/m(3)) or air. On d 1 and 7 following the exposure, rats were implanted with indwelling catheters and changes in heart rate and blood pressure were assessed in response to increasing levels of adrenoreceptor agonists. A separate group of rats was euthanized at the same time points, ventral tail arteries were dissected, and vascular tone along with dose-dependent responses to vasoconstricting and dilating factors were assessed in vitro. Agonist-induced dose-dependent increases in heart rate and blood pressure were greater in COREXIT EC9500A-exposed than in air-exposed rats at 1 d but not 7 d after the exposure. COREXIT EC9500A exposure also induced a rise in basal tone and reduced responsiveness of tail arteries to acetylcholine-induced vasodilation at 1 d but not 7 d following the exposure. These findings demonstrate that an acute exposure to COREXIT EC9500A exerts transient effects on cardiovascular and peripheral vascular functions.

Vibration-induced white finger (VWF) is a disorder seen in workers exposed to hand-transmitted vibration, and is characterized by cold-induced vasospasms and ringer blanching. Because overweight people with metabolic syndrome are pre-disposed to developing peripheral vascular disorders, it has been suggested that they also may be at greater risk of developing VWF if exposed to occupational vibration. We used an animal model of metabolic syndrome, the obese Zucker rat, to determine if metabolic syndrome alters vascular responses to vibration. Tails of lean and obese Zucker rats were exposed to vibration (125 Hz, 49 m/s(2) r.m.s.) or control conditions for 4 h/d for 10 d. Ventral tail arteries were collected and assessed for changes in gene expression, levels of reactive oxygen species (ROS) and for responsiveness to vasomodulating factors. Vibration exposure generally reduced the sensitivity of arteries to acetylcholine (ACh)-induced vasodilation. This decrease in sensitivity was most apparent in obese rats. Vibration also induced reductions in vascular nitric oxide concentrations and increases in vascular concentrations of ROS in obese rats. These results indicate that vibration interferes with endothelial-mediated vasodilation, and that metabolic syndrome exacerbates these effects. These findings are consistent with idea that workers with metabolic syndrome have an increased risk of developing VWF.