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PubMed1993

[A comparison of different endotracheal tubes. Tracheal cuff seal, peak centering and the incidence of postoperative sore throat].

UNLABELLED: The study objective was to evaluate cuff seal, tube tip position and incidence of postoperative sore throat in three different endotracheal tubes: the reusable Rüsch "red rubber" tube (low-volume, high-pressure cuff) and the disposable Rüsch "Super Safety Clear" and Mallinckrodt "lo-pro" tubes (both high-volume, low-pressure cuffs). METHODS: In a prospective randomized trial, 150 consecutive patients scheduled for minor orthopaedic surgery under standardized general anaesthesia, including standardized cuff pressure control, were allocated to one of the three types of endotracheal tube. Leakage and intratracheal tube tip position were investigated by means of fiberoptic tracheoscopy via the endotracheal tube, preceded by pharyngeal instillation of indigocarmine. The semi-standardized interviews for the recording of postoperative sore throat were performed once a day under double-blind conditions from the day of operation to postoperative day 3. Statistical independence testing was based on the chi 2-test, significance was assumed at P < 0.05. MAIN RESULTS: A past-cuff leakage of the pharyngeally instilled dye was found in three patients with "red rubber" tubes. In all of these cases the tracheal cross section deviated markedly from circular. The tips of the "Super Safety Clear" tubes tended to be better centred (P = 0.099). Bad tip position, however, had little influence on postoperative throat complaints (P = 0.394). The differences in incidence of postoperative throat complaints between the "red rubber" (48.9%), "Super Safety Clear" (35.6%) and "lo-pro" tubes (34.1%) did not reach the 5% level (P = 0.288). Such complaints, however, were significantly more frequent in females and in obese patients who exceeded their Broca weights by more than 25%. By contrast, postoperative throat complaints did not vary statistically significantly by age group, tracheal cross-sectional shape, use of atropine or duration of intubation. CONCLUSION: Despite the economic (usable up to 100 times) and ecological (less PVC waste) advantages of the rubber tube, the disposable tubes with high-volume, low-pressure cuffs tended to be superior regarding cuff seal, tube tip position and incidence of postoperative throat complaints. Nevertheless, the continued use of "red rubber" type reusable tubes may be justified in cases where the tube has to stay in place for only a short time.

Adult↗

PubMed1992

Clinical experience and physiologic results with an implantable intratracheal oxygen catheter.

Ten patients with chronic lung disease received an implanted ITOC. Seven patients continue to use their catheters after a mean period of 14.75 months. Four catheters were removed, 2 at 1 month, 1 after 10 months and 1 after 13 months. One patient requested a second catheter. Three patients experienced mucus plug formation; this was transient in two patients, but led to removal of the catheter in the third. To determine the degree of oxygen-saving afforded by the ITOC, SaO2 was measured at rest and during exercise for eight of the ten subjects using a double-blind technique. The calculated oxygen savings were around 40 percent both at rest and during exercise. The ITOCs were well received by the majority of our patients and were shown to produce a useful saving of oxygen which is of benefit to patients using portable systems and those who require high oxygen flow rates.

Adult↗

PubMed2007

Horizontal diffusion elutriation: a new size-separation technique for preparation of rodent-respirable fibers for animal testing.

Short-and long-term animal experiments are used to examine the toxicology and biopersistence of various types of fibers. In order to ensure an adequate exposure dose for testing, modern experimental protocols specify that the exposure aerosol (in an inhalation test) or the fibers (in an intratracheal instillation [IT] test) must contain at least a minimum concentration of long (> 20 mum) rodent-respirable fibers. As produced and handled, most fibers contain a distribution of diameters and lengths, only some of which are both long and rodent-respirable. Therefore, it is necessary to size-separate the fibers to enrich the proportion of long, rodent-respirable fibers in the material to be tested. This article presents a new and relatively simple method for size separation that avoids some of the difficulties associated with other methods. The method, termed horizontal diffusion elutriation (HDE), is illustrated by size-separating refractory ceramic fiber (RCF) and four polycrystalline alumina (PCA) fibers.

Aluminum Oxide↗

PubMedDate not supplied

Subchronic pulmonary inflammation and fibrosis induced by silica in rats are attenuated by amiodarone.

A previous study demonstrated that the acute phase of silica-induced lung injury in rats can be attenuated by concomitant administration of amiodarone, a cationic amphiphilic drug that inhibits phospholipase activity in the lungs. The purpose of the present study was to determine whether continued amiodarone administration could inhibit subchronic silica-induced lung injury and fibrosis. Male Fischer-344 rats were administered amiodarone (150 mg/kg, p.o., 5 days/week) for 14 days and were then instilled with silica (100 mg/kg) intratracheally. Amiodarone treatment then continued for 60 days. Injury was evaluated by parameters in bronchoalveolar lavage fluid and fibrosis was assessed by lung hydroxyproline content and trichrome staining of collagen. Within the bronchoalveolar lavage fluid, amiodarone treatment resulted in significant decreases in silica-induced elevations in albumin levels, lactate dehydrogenase activity, beta-glucuronidase activity, and neutrophil influx. Amiodarone treatment resulted in significant reductions in silica-induced increases in lung weight and hydroxyproline levels; the diminution of fibrosis due to amiodarone treatment was confirmed histologically. These results indicate that subchronic pulmonary inflammation and fibrosis induced by silica in the rat can be attenuated by the concomitant administration of amiodarone.

Albumins↗

PubMed2000

Role of p38 mitogen-activated protein kinase in a murine model of pulmonary inflammation.

Early inflammatory events include cytokine release, activation, and rapid accumulation of neutrophils, with subsequent recruitment of mononuclear cells. The p38 mitogen-activated protein kinase (MAPK) intracellular signaling pathway plays a central role in regulating a wide range of inflammatory responses in many different cells. A murine model of mild LPS-induced lung inflammation was developed to investigate the role of the p38 MAPK pathway in the initiation of pulmonary inflammation. A novel p38 MAPK inhibitor, M39, was used to determine the functional consequences of p38 MAPK activation. In vitro exposure to M39 inhibited p38 MAPK activity in LPS-stimulated murine and human neutrophils and macrophages, blocked TNF-alpha and macrophage inflammatory protein-2 (MIP-2) release, and eliminated migration of murine neutrophils toward the chemokines MIP-2 and KC. In contrast, alveolar macrophages required a 1000-fold greater concentration of M39 to block release of TNF-alpha and MIP-2. Systemic inhibition of p38 MAPK resulted in significant decreases in the release of TNF-alpha and neutrophil accumulation in the airspaces following intratracheal administration of LPS. Recovery of MIP-2 and KC from the airspaces was not affected by inhibition of p38 MAPK, and accumulation of mononuclear cells was not significantly reduced. When KC was instilled as a proinflammatory stimulus, neutrophil accumulation was significantly decreased by p38 MAPK inhibition independent of TNF-alpha or LPS. Together, these results demonstrate a much greater dependence on the p38 MAPK cascade in the neutrophil when compared with other leukocytes, and suggest a means of selectively studying and potentially modulating early inflammation in the lung.

Aminopyridines↗

PubMed1983

Allergic contact dermatitis induced by intratracheal administration of hapten.

It is known that the skin is the natural route for induction of allergic contact dermatitis (ACD). Because the lung is another potential portal of entry for sensitizing chemicals, studies were performed to evaluate immune responses to haptens deposited in the lung. As a result, a new method for inducing ACD was developed. Intratracheal (IT) inoculation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) led to maximal ear swelling 24 hr after challenge on the ear with 2,4,6-trinitrochlorobenzene (TNCB) in carrier. This response was specific for immunizing hapten. Furthermore, it was equally possible to induce ACD by intratracheal inoculation of trinitrophenyl- (TNP) modified bronchoalveolar cells (BAC) or haptenated spleen cells. Adoptive transfer studies demonstrated that the hypersensitivity that resulted from IT inoculation of TNBS or TNP BAC could be transferred with cells. With a monoclonal anti-hamster Ia reagent, it was demonstrated that, like Langerhans cells, 80 to 90% of cells in the bronchial lavage fluid expressed Ia determinants on their membrane. These cells were morphologically indistinguishable from macrophages. Because an individual is capable of being sensitized when hapten is introduced by the pulmonary or epicutaneous routes, the possibility is raised that the alveolar macrophages in the lung possess a similar capability for antigen presentation of hapten in the induction of ACD as does the Langerhans cell.

Animals↗

PubMed2002

Early inflammatory response to asbestos exposure in rat and hamster lungs: role of inducible nitric oxide synthase.

Recent studies have suggested that inducible nitric oxide synthase (iNOS) plays a role in the development of asbestos-related pulmonary disorders. The pulmonary reactions of rats and hamsters upon exposure to asbestos fibers are well known to be disparate. In addition, in vitro experiments have indicated that mononuclear phagocytes from hamsters, in contrast to those from rats, lack the iNOS pathway. Therefore, the purpose of this study was to investigate whether rats and hamsters differ in lung iNOS expression in vivo upon exposure to asbestos fibers and whether differences in iNOS induction are associated with differences in the acute pulmonary inflammatory reaction. Body weight, alveolar-arterial oxygen difference, differential cell count in bronchoalveolar lavage fluid, total protein leakage, lung myeloperoxidase activity and lipidperoxidation, wet/dry ratio, iNOS mRNA and protein expression, and nitrotyrosine staining of lung tissue were determined 1 and 7 days after intratracheal instillation of asbestos fibers in CD rats and Syrian golden hamsters. Exposure of rats to asbestos fibers resulted in enhanced pulmonary iNOS expression and nitrotyrosine staining together with an acute inflammation that was characterized by an influx of neutrophils, enhanced myeloperoxidase activity and lipid peroxidation, damage of the alveolar-capillary membrane, edema formation, and impairment of gas exchange. In comparison, instillation of asbestos fibers in hamsters resulted in a significantly milder inflammatory reaction of the lung with no induction of iNOS in pulmonary cells. The data obtained provide important information to understand the underlying mechanisms of species differences in the pulmonary response upon exposure to asbestos fibers.

Animals↗

PubMed2006

Intratracheal and subcutaneous liposomal VIP normalizes arterial pressure in spontaneously hypertensive hamsters.

We determined whether a single intratracheal and subcutaneous administration of biocompatible and biodegradable vasoactive intestinal peptide self-associated with sterically stabilized liposomes (VIP-SSL) normalizes mean arterial pressure (MAP) in spontaneously hypertensive hamsters (SHH). We found that VIP-SSL (0.1 nmol) administered by either routes normalizes MAP (p < 0.05). Maximal effect was observed within 10-20 min and lasted for 6 h. VIP-SSL had no significant effects on heart rate. VIP alone (0.1 nmol) and empty SSL had no significant effects on MAP. VIP-SSL (0.1 nmol) had no significant effects on MAP and heart rate in age/genetically-matched control hamsters. Given these data, we suggest that pulmonary and subcutaneous delivery of VIP-SSL should be further developed as peptide nanomedicine for essential hypertension.

Animals↗

PubMed1995

Investigation on the biodurability of chemically different stone wool fibres.

The biodurability is one of the essential factors for a carcinogenic potential of mineral fibres. The in vivo solubility of commercial fibre products can be influenced by modifications of the chemical composition. Two types of experimental stone wool samples with new chemical composition were compared to a commercial stone wool sample. Sized fractions of these samples with median lengths of 7.1, 9.3 and 6.7 microns, respectively, and median diameters of 0.76, 1.02 and 0.63 microns, respectively, were intratracheally instilled into female Wistar rats with a single dose of 2 mg in 0.3 ml. 5 animals per group were sacrificed after 2 days, 1, 3, 6, 12 and 18 months. After low-temperature ashing of the lungs about 1,000 fibres per group and sacrifice date were analysed in SEM for length and diameter. The number of fibres in the total lung was calculated. An analysis of fibre number of different length and diameter fractions was used to estimate whether dissolution, breakage or mechanical clearance is responsible for the elimination of fibres from the lung. Results indicate that the breakage of fibres with length above 20 microns and the dissolution of fibres was faster in the experimental stone wool samples compared to the commercial sample.

Animals↗

PubMed2001

[Intratracheal lymphotropic ozone therapy in erosive-ulcerous tracheitis].

Under observation there were 452 patients with chronic stenosis of hollow organs of the neck having cannulas during the period from 3 months to several years. During the tracheobronchoscopic examination it was found that 35 patients had trachea ulcers, 46 patients had erosive tracheobronchitis. The ulcers were localized on the anterior wall of the thoracic part of the trachea. Their diameter was from 1 to 2.5 cm. The ulcers were accompanied by diffuse bilateral bronchitis of the II-III degree of the inflammation intensity. 2-3 ml of ozonated sodium chloride solution with the concentration of ozone in it 5 mg/l were introduced into the ulcer edges, i.e. lymphotropically, into the submucous membrane. The same solution (40-60 ml) was used for daily sanitation of the tracheobronchial tree. Complete epithelization of the ulcers and cleansing of the bronchial tree took 3-4 curative bronchoscopies.

Animals↗

PubMed1990

Pharmacokinetics and distribution of recombinant secretory leukocyte proteinase inhibitor in rats.

Secretory leukocyte proteinase inhibitor (SLPI) is a potent elastase, trypsin, and chymotrypsin inhibitor occurring in all mucous secretions. Its inhibitory potency and profile suggested that it may become a therapeutic adjuvant in diseases where proteinases play a pathogenetic role. In the course of developing recombinant SLPI for therapeutic purposes, we studied its pharmacokinetics after intravenous, intraperitoneal, and intratracheal application to rats. In plasma, SLPI was determined with an ELISA or by following a radiotracer [( 35S]SLPI). In bronchoalveolar lavage fluid (BALF), SLPI was determined additionally by a functional assay (elastase inhibitory capacity). Intravenously applied SLPI (2 mg/kg) was rapidly cleared, with half-times of distribution of 6 min and half-times of elimination of 50 min. Very little (less than 5%) appeared in the urine even after 24 h. Approximately 80% of intraperitoneally injected SLPI (12 mg/kg) was absorbed and generated maximal plasma concentration of 6 to 10 micrograms/ml 30 to 120 min after administration. When given intratracheally (8.6 mg/kg), SLPI disappeared from the lungs, with a half-time of 4 to 5 h. This value was the same whether the remaining SLPI in BALF was determined radiometrically, by ELISA or by the functional assay, indicating minimal metabolism in the lung. As in the case of intraperitoneal application, SLPI was absorbed systemically, resulting in a maximal plasma level of about 2 micrograms/ml 1 to 2 h after application. In contrast to the measurements in BALF, the ELISA and radiotracer measurements in plasma correlated only for the first 2 h after application and diverged progressively after that, suggesting breakdown of the molecule once it reaches the plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1976

The fate of intratracheally installed benzo(a)pyrene in the isolated perfused rat lung of both control and 20-methylcholanthrene pretreated rats.

The fate of intratracheally installed 3H-benzo(a)pyrene in the isolated perfused rat lung of both control and 20-methylcholanthrene pretreated rats and in perfusion fluid was studied. The covalent binding of benzo(a)pyrene metabolites in the lung tissue itself was greatly enhanced by 20-methylcholanthrene pretreatment of rats. Similarly, the appearance of unchanged 3H-benzo(a)pyrene in the perfusion fluid of 20-methylcholanthrene-lung was decreased as compared to control lung perfusion. This was accompanied with the increase of water-soluble metabolites of benzo(a)-pyrene in the perfusion fluid of 20-methylcholanthrene-lung. When analyzing the metabolite profile of benzo(a)-pyrene in the lungs, especially the phenols (7-fold) and 9,10-diols (5-fold) were found to be increased.

Animals↗

PubMed1998

Pharmacokinetics, protein binding and metabolic profile of 3H-icometasone enbutate following intravenous, oral and intratracheal administrations to Sprague-Dawley rats.

Absorption, distribution and excretion of 3H-icometasone enbutate (9 alpha-chloro-11 beta,17 alpha,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione, 17-butyrate, 21-acetate, CAS 103466-73-5 CL09) were studied in male and female Sprague-Dawley rats after a single dose administration by intravenous (1 mg/kg), oral and intratracheal (2 mg/kg) routes. The metabolic profile after the different routes and protein binding were also determined. Independent of the route, the radioactivity was mainly excreted in faeces. Less than 10% of the dose were excreted in urine. The majority of the administered doses was recovered within 24 h postdose, and the total recovery of the doses administered was obtained. After oral and intravenous administration to bile-duct cannulated rats, most of the radioactivity was excreted in the bile (80% of the administered dose) and some radioactivity was found in the faeces. It can thus be concluded that some intestinal secretion occurred. After oral administration, mean maximum blood concentrations were obtained about 0.75 h postdose. For the intratracheal route, the radioactive dose administered was too low to determine precise blood pharmacokinetic parameters. However, the distribution study results allowed us to conclude that the drug was absorbed first from the lungs and then from the gastrointestinal tract. Immediately after the intravenous injection, the liver, the kidneys, the small intestine and its contents and the carcass presented the highest levels of radioactivity. 168 h postdose, low radioactivity was still measurable in these organs. In other tissues, the radioactivity decreased reaching the limit of quantification 72 h postdose. After oral administration, the maximum concentrations were observed 1 h after administration in the liver, the small intestine and its contents. Then the radioactivity decreased in most of the tissues but a slight increase at 72 and/or 120 h postdose was noted in large intestine contents, carcass, lungs, eyes. After intratracheal administration, the maximum radioactivity was observed in lungs and trachea. A few minutes later the radioactivity reached the gastrointestinal tract. The protein binding study showed a saturable binding in rat and human plasma without notable differences between the two species. The binding on human serum albumin was shown to be non saturable with a total binding capacity of 7.48 +/- 1.83 mumol/l, suggesting that other proteins were involved in CL09 binding. This binding was demonstrated to be reversible. CL09 was extensively metabolized since no unchanged CL09 was recovered in bile or urine and at least nine metabolites have been detected. The profiles seemed to be different according to the route of administration.

Administration, Oral↗

PubMed1997

In vivo and in vitro proinflammatory effects of particulate air pollution (PM10).

Epidemiologic studies have reported associations between fine particulate air pollution, especially particles less than 10 mm in diameter (PM10), and the development of exacerbations of asthma and chronic obstructive pulmonary disease. However, the mechanism is unknown. We tested our hypothesis that PM10 induces oxidant stress, causing inflammation and injury to airway epithelium. We assessed the effects of intratracheal instillation of PM10 in rat lungs. The influx of inflammatory cells was measured in bronchoalveolar lavage (BAL). Airspace epithelial permeability was assessed as total protein in bronchoalveolar lavage fluid (BALF) in vivo. The oxidant properties of PM10 were determined by their ability to cause changes in reduced glutathione (GSH) and oxidized glutathione (GSSG). We also compared the effects of PM10 with those of fine (CB) and ultrafine (ufCB) carbon black particles. Six hours after intratracheal instillation of PM10, we noted an influx of neutrophils (up to 15% of total BAL cells) in the alveolar space, increased epithelial permeability, an increase in total protein in BALF from 0.39 +/- 0.01 to 0.62 +/- 0.01 mg/ml (mean +/- SEM) and increased lactate dehydrogenase concentrations in BALF. An even greater inflammatory response was observed after intratracheal instillation of ufCB, but not after CB instillation. PM10 had oxidant activity in vivo, as shown by decreased GSH in BALF (from 0.36 +/- 0.05 to 0.25 +/- 0.01 nmol/ml) after instillation. BAL leukocytes from rats treated with PM10 produced greater amounts of nitric oxide, measured as nitrite (control 3.07 +/- 0.33, treated 4.45 +/- 0.23 mM/1 x 10(6) cells) and tumor necrosis factor alpha (control 21.0 +/- 3.1, treated 179.2 +/- 29.4 unit/1 x 10(6) cells) in culture than BAL leukocytes obtained from control animals. These studies provide evidence that PM10 has free radical activity and causes lung inflammation and epithelial injury. These data support our hypothesis concerning the mechanism for the adverse effects of particulate air pollution on patients with airway diseases.

Air Pollutants↗

PubMed1989

Multifactorial hamster respiratory carcinogenesis with interdependent effects of cannula-induced mucosal wounding, saline, ferric oxide, benzo[a]pyrene and N-methyl-N-nitrosourea.

The carcinogenic response induced in the respiratory tract of Syrian golden hamsters by repeated intratracheal instillations of benzo[a]pyrene (BP) adsorbed to ferric oxide (Fe2O3) particles suspended in saline, is shown to result from the interactions of these factors and cannula-induced tracheal wounding. Previous acute studies of intratracheal cannulation (ITC) versus intralaryngeal cannulation (ILC) showed that tracheal cell proliferation increased significantly in ITC-induced mucosal wounds. Only mild increases in intrapulmonary cell proliferation were produced by Fe2O3-saline given by ILC or ITC (Keenan et al., Cancer Res., 49: 1521-1527, 1989). The present chronic studies included the following variables: a single instillation by ILC of N-methyl-N-nitrosourea (MNU) at 5 weeks of age; 15 weekly treatments (beginning at 7 weeks of age) by ILC or ITC alone, or with instillations of saline, or Fe2O3-saline, or BP-Fe2O3-saline; and appropriate controls. Repeated ITC-induced tracheal wounds caused persistent tracheal epithelial hyperplasia, metaplasia and/or atrophy and submucosal fibroplasia during the observation period of 22 to 78 weeks of age (the time of terminal sacrifice). Tracheal cancers (in situ or invasive carcinomas) were seen only in those hamsters which had received repeated ITC and one or both carcinogens. The cancer latency was shortest and the incidence of tracheal (50%) and main-stem bronchial (21%) cancers highest in hamsters given MNU and repeated ITC with BP-Fe2O3-saline. Hamsters given carcinogens by ILC (which induced laryngeal but not tracheal wounds) developed proliferative lesions and cancers of the larynx but no tracheobronchial cancers. These data show the singular importance of repeated ITC-induced intratracheal wounding as an enhancing factor in this respiratory carcinogenesis model. The findings suggest that the mechanism of tumor enhancement involves not only changes in target epithelial cell proliferation, but also alterations in normal epithelial-mesenchymal interactions during tracheal regeneration from repeated chronic submucosal inflammation and mesenchymal repair. In the present experimental model, a single dose of MNU at 5 weeks of age, repeated instilled doses of BP, and tracheal mucosal wounding were each found to be important determinants of the carcinogenic response. Additional effects were observed for instilled Fe2O3 particles, and possibly saline. Interplay of all these factors, as well as of genetic, nutritional, and infectious factors, are considered in relation to risk assessment and prevention.

Animals↗

PubMed1990

Sequence of cardiorespiratory effects of soman altered by route of administration.

Dilute soman was administered to anesthetized guinea-pigs by slow infusion (30 micrograms/kg/10 min); intravenous (IV), subcutaneous (SC), intraperitoneal (IP), intratracheal (IT), and upper-airway (UAW) routes were used. Times to ventilatory failure were 8.8 +/- 1.3 min (IV), 10.5 +/- 1.2 min (I.T.), 17.3 +/- 2.8 min (IP), 34.8 +/- 5.1 min (UAW), and 36.0 +/- 4.4 min (SC) for the 5 routes of exposure. Atrioventricular (AV) block occurred before ventilatory failure with all routes of challenge except IT and IP; when it did occur, AV block typically began after one-half reduction in minute volume. The results reflect the effects of rate of absorption and noncritical-site binding of the organophosphorus compound when all routes are compared and suggest that the pathogenesis of intoxication in the anesthetized guinea-pig is different when soman is infused into regions heavily enervated by vagal afferents.

Administration, Intranasal↗

PubMed1975

A method for intratracheal instillation in the rat.

A method was developed to provide safe, rapid, and accurate intratracheal instillation of radionuclides into the rat lung. Rats were anesthetized with halothane and suspended vertically on an animal support stand with rubber bands attached to the incisor teeth, holding the mouth open. A speculum was inserted into the trachea and the radionuclide was injected from a syringe through tubing inserted through the tracheal speculum into the trachea. The amount of radionuclide retained in the lung varied by less than a factor of 2 within groups of rats observed 4 hr-20 da after employing this method of instillation. When a volume of 2 ml was instilled, the radionuclide distribution between the left and right lung was similar to that observed following incorporation by inhalation. Instillations of less than 2 ml showed unequal distribution of radionuclide between the right and left lung.

Anesthesia, Inhalation↗

PubMed1996

A physiologically based pharmacokinetic model for arsenic exposure. I. Development in hamsters and rabbits.

A physiologically based pharmacokinetic model for exposure to inorganic arsenic in hamsters and rabbits has been developed. The model in its present state simulates three routes of exposure to inorganic arsenic: oral intake, intravenous injection, and intratracheal instillation. It describes the tissue concentrations and the urinary and fecal excretions of the four arsenic metabolites: inorganic As(III) and As(V), methylarsonic acid, and dimethylarsinic acid. The model consists of five tissue compartments, chosen according to arsenic affinities: liver, kidneys, lungs, skin, and others. The model is based on physiological parameters, which were scaled according to body weight. When physiological parameters were not available, the data for the model were obtained by fitting (tissue affinity, absorption rate, and metabolic rate constants). The excretions of the arsenic metabolites in urine and feces are well simulated with the model for both species. Further validation of the arsenic metabolite concentrations in the tissues and in vitro measurements of the tissue affinity constants are discussed.

Administration, Oral↗