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At least 1,747 records · Page 97Linked to original sources
PubMed1992

The acute toxicity evaluation of a low-temperature hydraulic fluid.

A low-temperature version of MIL-H-83282 (LT 83282) is a candidate hydraulic fluid to be used as a replacement for the current low-temperature fluid used on Strategic Air Command aircraft. A single neat dose of 0.1 mL LT 83282 into New Zealand White (NZW) rabbit eyes resulted in slight conjunctival irritation for up to 24 hr after treatment in two of nine rabbits. Rinsing the eyes after treatment appeared beneficial. A single treatment of 0.5 mL neat LT 83282 to rabbit skin produced no irritation. A total of 40% of the guinea pigs receiving repeated dermal application of the fluid demonstrated a positive sensitization response. A single oral dose of 5 g LT 83282/kg body weight given to five male and five female Fischer 344 (F-344) rats and a single dermal application of 2 g LT 83282/kg body weight applied to five male and five female NZW rabbits resulted in no deaths. Inhalation exposures to aerosol concentrations of LT 83282 resulted in an LC50 of 2.13 and 1.50 mg/L for male and female F-344 rats, respectively. No clinical signs of acute delayed neurotoxicity were observed in hens twice dosed at limit levels (5 g/kg) and observed for 21 days.

Administration, Inhalation↗
PubMed1995

Burns and smoke inhalation.

Smoke inhalation injury affects nearly one third of all major burn victims. Significant inhalation exposures must be suspected in persons who were entrapped in a closed space or who became unconscious during a fire. Each individual fire generates a characteristic smoke depending on the type of materials burnt, temperatures reached during pyrolysis, and the availability of oxygen to sustain combustion. In addition to variable amounts of thermal loads, firesmoke may contain mixtures of carbon monoxide, hydrogen cyanide, nitrogen oxides, and other highly irritating gases. Each constituent of firesmoke may potentially create pulmonary and systemic toxicities and must be considered in every victim of smoke inhalation.

Burns↗
PubMedDate not supplied

The effects of inhaled toluene, halothane, 1,1,1-trichloroethane, and ethanol on fixed-interval responding in mice.

Adult male mice were trained to lever press under a fixed-interval (FI) 60-sec schedule for milk presentation during 15-min sessions. Concentration-effect curves were then determined at the termination of 30-min inhalation exposures to various volatile agents--halothane, toluene, 1,1,1-trichloroethane (1,1,1-TCE), and ethanol. The mice were also tested after ethanol administered orally. Each compound produced both response rate increases and decreases, initially or during the recovery phase. Recovery from the response rate decreasing effects generally occurred during the 15-min sessions. The highest concentration of toluene and the high dose of oral ethanol produced the longest duration of effects. Response rates in the first 3 min of the session were used to evaluate peak effects following inhalation. Linear regression analyses of these data indicated the potency order to be toluene greater than halothane greater than 1,1,1-TCE greater than ethanol. Patterning of responding characteristics of FI performance was affected after high concentrations of all but ethanol vapor. This study provided evidence that the effects of two industrial solvents, toluene and 1,1,1-TCE, were qualitatively similar to those of two volatile CNS depressants, halothane and ethanol, as well as to those reported for other centrally-acting drugs.

Conditioning, Operant↗
PubMed1977

Potential exposure from smoking parathion-contaminated cigarettes.

Pesticide workers usually contaminate their cigarettes with less than 100 microgram per cigarette by handling them, but in some instances such contamination has been found to be over 200 microgram. To obtain values for potential exposure resulting from smoking contaminated filter tip and nonfilter cigarettes, from 10 to 200 microgram of parathion was applied to the cigarette surface area found to be most often contaminated by hands. This was followed in two separate experiments by simulated smoking using a special apparatus to determine (1) passage of toxic material through cigarettes in mainstream smoke, (2) amount found in sidestream smoke, (3) amount trapped in the filter or equivalent butt end, and (4) amount recovered in ashes. The amount of parathion passing through cigarettes as a potential for inhalation exposure ranged up to 28% of dosing levels. No paraoxon or S-ethyl parathion was detected. Although there was an indication that slightly more pesticide was recovered from filters than from equivalent butt ends, the amount recovered in mainstream smoke of filter type cigarettes was not significantly lower than for nonfilter cigarettes. Location of contamination on a cigarette had minimal effect on the amount found in mainstream smoke.

Chromatography, Gas↗
PubMed2006

Potential uses of petrochemical products can result in significant benzene exposures: MSDSs must list benzene as an ingredient.

According to 29 CFR1910.1200 (Hazard Communication Standard [HCS]), a material safety data sheet (MSDS) must list a carcinogen as an ingredient if its concentration in a product is 0.1% or more by weight. However, according to the HCS, when the concentration of a carcinogen in a product is less than 0.1% (by weight) it may not be necessary to list it as an ingredient on the MSDS. The standard stipulates that if potential uses of the product can result in exposures to the carcinogen that exceed the Occupational Safety and Health Administration (OSHA) permissible exposure limit or the ACGIH threshold limit value (TLV), then it must be listed. This article focuses on the failure of MSDSs to report benzene as a listed ingredient in products that incorporate petroleum-derived ingredients such as toluene and hexane. In the United States, approximately 238,000 people are occupationally exposed to benzene each year. Only rarely is benzene listed as an ingredient on MSDSs even though it often comprises more than 0.1% of petroleum solvents and, when its concentrations in petroleum-derived products are much less than 0.1%, inhalation exposures to benzene can be much higher that its OSHA PEL of one part per million (ppm) by volume (v/v) andACGIH TLV of/one-half ppm (v/v). As a consequence of benzene's omission from MSDSs as a listed ingredient, employers are frequently unaware of their requirement to implement 29 CFR 1910.1028 (Benzene Standard) and of the need to address employee exposures to benzene in the workplace. This article demonstrates that benzene should be listed as an ingredient on MSDSs, even at concentrations in benzene-containing products that are between one and two orders of magnitude below OSHA's 0.1% threshold. An exposure assessment methodology is presented that is applicable to employees whose conditions of exposure are similar to those in the published study. These workers make up a similar exposure group. The information and methodology presented here are germane to preparation of accurate MSDSs for benzene-containing products, employers who must comply with 29 CFR 1910.1028, and retrospectively estimating exposures to benzene.

Air Pollutants, Occupational↗
PubMed2001

Assessing elemental mercury vapor exposure from cultural and religious practices.

Use of elemental mercury in certain cultural and religious practices can cause high exposures to mercury vapor. Uses include sprinkling mercury on the floor of a home or car, burning it in a candle, and mixing it with perfume. Some uses can produce indoor air mercury concentrations one or two orders of magnitude above occupational exposure limits. Exposures resulting from other uses, such as infrequent use of a small bead of mercury, could be well below currently recognized risk levels. Metallic mercury is available at almost all of the 15 botanicas visited in New York, New Jersey, and Pennsylvania, but botanica personnel often deny having mercury for sale when approached by outsiders to these religious and cultural traditions. Actions by public health authorities have driven the mercury trade underground in some locations. Interviews indicate that mercury users are aware that mercury is hazardous, but are not aware of the inhalation exposure risk. We argue against a crackdown by health authorities because it could drive the practices further underground, because high-risk practices may be rare, and because uninformed government intervention could have unfortunate political and civic side effects for some Caribbean and Latin American immigrant groups. We recommend an outreach and education program involving religious and community leaders, botanica personnel, and other mercury users.

Adult↗
PubMed1992

Diethylbenzene inhalation-induced electrophysiological deficits in peripheral nerves and changes in brainstem auditory evoked potentials in rats.

Motor and sensory conduction velocities (MCV and SCV), amplitude of the sensory action potential (ASAP) of the tail nerve and parameters of brainstem auditory evoked potentials (BAEP) were studied in male Sprague-Dawley rats after prolonged inhalation exposure to a commercial isomer mixture of diethylbenzene (DEB mixture) containing 6% 1,2-DEB. The MCV, SCV and ASAP were studied in one control group (10 rats) and three groups of 12 rats exposed to 500, 700 or 900 ppm DEB mixture for 6 h daily, 5 days per week, for 18 weeks. Rats used for recording BAEP (one control group and two other groups of 15 rats) were exposed to 600 and 800 ppm DEB mixture. The exposure time was the same. Rats exposed to DEB mixture exhibited a time- and concentration-dependent decrease in MCV, SCV and ASAP and a time- and concentration-dependent increase of both the peak latencies of all BAEP components and the interpeak (I-V) differences.

Action Potentials↗
PubMed1993

Deposition patterns of aerosolized drugs within human lungs: effects of ventilatory parameters.

A mathematical model for inhaled aerosolized drugs is validated by comparisons of predicted particle deposition values with experimental data from adult subject inhalation exposure tests. The model is subsequently used to study the effects of ventilatory parameters on particle deposition patterns within the human lung. By altering breathing profiles, deposition values can be affected regarding quantity delivered and spatial location. Increased tidal volumes and breath-holding times increase deposition in the pulmonary region, while increased inspiratory flow rates increase deposition in the tracheobronchial region. Based upon fluid dynamics considerations (Reynolds numbers), an original method of partitioning the lung is also presented. The model has implications with regard to aerosol therapy, indicating that the efficacies of inhaled pharmacological drugs in the prophylaxis and treatment of airway diseases can be improved by regulating breathing profiles to deposit particles selectively at prescribed sites within the lung.

Adult↗
PubMed1997

Pharmacokinetics and disposition of methyl t-butyl ether in Fischer-344 rats.

Methyl t-butyl ether (MTBE) is a commonly used octane booster in gasoline. This study examines the pharmacokinetics and disposition of MTBE in Fischer-344 rats after i.v., oral, dermal and inhalation routes of administration. Groups of male and female rats were given single i.v. (40 mg kg-1), oral (40 and 400 mg kg-1) and dermal (40 and 400 mg kg-1 in occluded chambers) doses of [14C]MTBE. For inhalation studies, rats were exposed nose-only for 6 h to low (400 ppm), high (8000 ppm) and repeated daily 6-h low (400 ppm x 15 days) chamber concentrations of [14C]MTBE. Blood, expired air, and excreta (urine and feces) were collected at selected times up to 7 days post-dose and quantified for 14C content. Plasma concentrations of MTBE and t-butyl alcohol (TBA) were quantified and mean values used for pharmacokinetic analysis. The mean total recoveries of 14C ranged from 91 to 105%. Methyl t-butyl ether was rapidly and completely absorbed after oral and inhalation exposures; dermal absorption was low. After all routes, MTBE was rapidly eliminated from blood (ti = 0.5 h) by exhalation and metabolism to TBA. At the high doses, metabolism was saturated and the proportion of renal 14C excretion decreased relative to the pulmonary route. At 48 h post-exposure, virtually all of the 14C was eliminated. The major metabolites recovered in urine were 2-methyl-1,2-propanediol and alpha-hydroxyisobutyric acid. There were no significant gender or route-dependent differences in the pharmacokinetics and disposition of MTBE.

Absorption↗
PubMed1994

Physiologically based pharmacokinetics and cancer risk assessment.

Physiologically based pharmacokinetic (PBPK) modeling involves mathematically describing the complex interplay of the critical physicochemical and biological determinants involved in the disposition of chemicals. In this approach, the body is divided into a number of biologically relevant tissue compartments, arranged in an anatomically accurate manner, and defined with appropriate physiological characteristics. The extrapolation of pharmacokinetic behavior of chemicals from high dose to low dose for various exposure routes and species is possible with this approach because these models are developed by integrating quantitative information on the critical determinants of chemical disposition under a biological modeling framework. The principal application of PBPK models is in the prediction of tissue dosimetry of toxic moiety (e.g., parent chemical, reactive metabolite, macromolecular adduct) of a chemical. Such an application has been demonstrated with dichloromethane, a liver and lung carcinogen in the B6C3F1 mouse. The PBPK model-based risk assessment approach estimated a cancer risk to people of 3.7 x 10(-8) for a lifetime inhalation exposure of 1 micrograms/m3, which is lower by more than two orders of magnitude than that calculated by the U.S. Environmental Protection Agency using the linearized multistage model (for low-dose extrapolation) and body surface correction factor (for interspecies scaling). The capability of predicting the target tissue exposure to toxic moiety in people with PBPK models should help reduce the uncertainty associated with the extrapolation procedures adopted in conventional dose-response assessment.

Animals↗
PubMed1981

Multicellular in vivo sister-chromatid exchanges induced by urethane.

Following urethane inhalation exposure, clear dose--response relationships were apparent in all cell types examined in hepatectomized and intact mice. At concentrations of 0.1 mg/l and higher, induced SCE frequencies were linearly related to log urethane concentrations. No significant differences in SCE response between like cell types of hepatectomized and intact mice were apparent. In hepatectomized mice, there was no significant difference in the SCE response of regenerating liver and alveolar macrophage cells. However, bone-marrow response was significantly lower (p = 0.01). Likewise, in intact mice bone marrow response was significantly lower than in alveolar macrophages (p = 0.01). Inhalation and intravenous infusions of the same total dose of urethane (193 mg/kg) administered over a 4-h period produced comparable SCE responses in all cell types. However, a single intraperitoneal injection of 193 mg/kg just prior to BrdU infusion produced significantly higher SCE frequencies in bone marrow (alpha = 0.01), and alveolar macrophages (alpha = 0.05) of intact mice than did the equivalent inhalation dose. Intraperitoneal injections produced similar results in 2-month-old mice as in 4-month-old mice. However, regardless of the route of administration SCE frequencies in regenerating liver and/or alveolar macrophages were significantly higher than in bone marrow.

Aerosols↗
PubMed2001

Genotoxic effects of butadiene in mouse lung cells detected by an ex vivo micronucleus test.

Lung fibroblasts from BD-exposed mice have been analysed for the occurrence of micronuclei. Primary cultures set up 24h after the end of exposure were treated with cytochalasin B and micronuclei scored in binucleate cells. A three-fold statistically significant increase of micronucleated cells was detected after exposure to 500ppm, the lowest tested concentration. A linear dose effect relationship was observed between 500 and 1300ppm. Immunofluorescent staining of kinetochore proteins was applied to distinguish between acentric micronuclei produced by chromosome breaks and micronuclei containing a centromeric region, most likely induced by chromosome loss. A statistically significant increase of both types of MN in 1300ppm-exposed females and a significant increase in centromeric MN in 500ppm-exposed males were detected. These data demonstrate that an intermediate of BD metabolism with a potential for clastogenic and aneugenic effects is active in lung cells after inhalation exposure. These effects can play a role in the initiation and promotion of BD-induced lung tumours.

Animals↗
PubMed1988

Inhalation hazard test. Interlaboratory trial with OECD method 403.

Six industrial laboratories validated the Inhalation Hazard Test (OECD Method 403) using eight volatile chemicals. The test gave similar results in all laboratories, despite variation in inhalation exposure systems and strain of rat used. Detailed atmosphere analyses are not necessary, since nominal atmosphere concentrations were close to the analysed values. The method gives reproducible results directly applicable to hazard evaluation, and is quicker and cheaper and uses fewer animals than the conventional LC50 test.

Administration, Inhalation↗
PubMed2003

Site of inflammation influences site of hyperresponsiveness in experimental asthma.

BACKGROUND: Our recently developed murine asthma model is capable of inducing airway-specific chronic inflammatory changes and remodeling, features of human asthma commonly missing in conventional animal models. OBJECTIVES: To validate this model by site-specific physiological evaluation of hyperresponsiveness. METHODS: Non-sensitized and sensitized mice received either short-term uncontrolled or long-term controlled low-level exposures to aerosolized ovalbumin (OVA). Respiratory impedance (Zrs) was measured in response to increasing doses of methacholine (Mch). The constant-phase model was fitted to Zrs spectra to determine the specific site of hyperresponsiveness. RESULTS: Sensitized acutely exposed mice had significantly increased tissue damping (G), tissue elastance (H) and hysteresivity (eta) in response to Mch, but no significant increase in airway resistance (Raw), indicating tissue-specific hyperresponsiveness. In contrast, sensitized chronically exposed mice had significantly elevated Raw at all concentrations of Mch but no increases in G, H or eta indicating airway-specific hyperresponsiveness. CONCLUSIONS: Chronic inhalational exposure of sensitized mice to low-mass concentrations of OVA induces airway-specific hyperresponsiveness.

Aerosols↗
PubMed1997

Dissolution of metal tritides in a simulated lung fluid.

Metal tritides including titanium tritide (Ti 3Hx) and erbium tritide (Er 3Hx) have been used as components of neutron generators. The current understanding of metal tritides and their radiation dosimetry for internal exposure is very limited, and the ICRP Publication 30 does not provide for tritium dosimetry in metal tritide form. However, a few papers in the literature suggest that the solubility of metal tritides could be low. The current radiation protection guidelines for metal tritide particles are based on the assumption that their biological behavior is similar to tritiated water, which could be easily absorbed into body fluid. Therefore, these particles could have relatively short biological half-lives (10 d). If the solubility is low, the biological half-life of metal tritide particles and the dosimetry of an inhalation exposure to these particles could be quite different from tritiated water. This paper describes experiments on the dissolution rate of titanium tritide particles in a simulated lung fluid. Titanium tritide particles with mean sizes of 103 microm (coarse) and 0.95 microm (fine) were used. The results showed that the coarse particles dissolved much more slowly than the fine particles. The long-term dissolution half times were 361 and 33 d for the coarse and fine particles, respectively. Dissolution data of the fine particles were consistent with the diffusion theory. The dissolution half times were longer than the 10-d biological half time for tritiated water in the body. This finding has significant implications for the current health protection guidelines, including annual limits of intakes and derived air concentrations.

Body Fluids↗
PubMed2004

Brain microdialysis study of the effects of hazardous chemicals on the central nervous system 2. Toluene exposure and cerebral acetylcholine.

The microdialysis technique was applied to detect the changes in the activity of acetylcholine (ACh) neurons in the rat brain. The effects of intraperitoneal (i.p.) injection of toluene on the amount of ACh release from the nerve terminals of the brain cholinergic neurons were investigated in freely moving rats. In the striatum, injection of toluene decreased the extracellular concentration of ACh in a dose dependent manner in the range 200 to 2,000 mg/kg. Similar effects of toluene on ACh release were observed in the hippocampus after i.p. administration. The increases in ACh content in brain homogenate after i.p. injection of toluene seemed to be caused by the decreased release of ACh from cholinergic nerve endings. Injection of toluene at doses higher than 200 mg/kg decreased ACh release and a similar decrease was suggested to occur in 8-h inhalation exposure to toluene at 1,000 ppm or higher concentrations.

Acetylcholine↗
PubMed1987

Evaluation of the subacute and subchronic toxicity of inhaled EDS hydrotreated naphtha in the rat.

Inhalation studies were conducted to assess the subacute and subchronic toxicity of EDS hydrotreated naphtha (HN). In the subacute toxicity study, male and female Sprague-Dawley rats were exposed to various concentrations of HN vapor (0.2, 1.0, and 5.0 g/m3) 6 hr/day for 5 consecutive days. Following 2 recovery days, the animals were exposed for 4 additional days and then sacrificed on the 12th study day. In the subchronic toxicity study, a similar protocol was utilized; however, the animals were exposed 5 days/week for 13 weeks. Following a 2-week recovery period, the animals were sacrificed. Parameters examined in both studies included survival, growth, clinical observations, urinalysis, blood chemistry at necropsy, and microscopic examination of selected tissues. There was some evidence of systemic effects associated with repeated inhalation exposure to HN, although these effects were mild and were primarily confined to the high-exposure groups. The major systemic effect appeared to be renal toxicity in male rats as evidenced by increased urinary excretion of renal epithelial cells, creatinine, glucose, and protein and decreased urine osmolality. However, the absence of consistent pathologic changes in the kidneys of these animals suggested that the lesions were either slight or reversible during the 2-week recovery period.

Administration, Inhalation↗
PubMed1995

Acute pulmonary toxicity linked to use of a leather protector.

Leather protectors are used extensively for waterproofing leather garments. Inhalation exposure to this type of product is usually considered a benign incident. We report two cases of acute pulmonary toxicity associated with the use of a new leather protector recently introduced to the Canadian market. Emergency physicians must be aware of the potential acute toxicity of new leather protectors.

Adolescent↗