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PubMed2005

Nine cases of accidental exposure to dimethyl sulphate--a potential chemical weapon.

Dimethyl sulphate (DMS) is an innocuous appearing, widely used, and highly toxic chemical. It is used both as a methylating agent in industrial chemical synthesis and in medical laboratories for chemical cleavage of DNA. It is readily absorbed through the skin, mucous membranes, and gastrointestinal tract. Delayed toxicity allows potentially fatal exposures to occur prior to development of any warning symptoms. Toxicity is manifested initially by mucosal inflammation of eyes, nose, oropharynx, and airways. This can progress to severe airway oedema and necrosis, and non-cardiogenic pulmonary oedema. Other systemic effects include convulsions, delirium, coma, and renal, hepatic, and cardiac failure. All these features make DMS a potential chemical weapon. We report nine cases of varying degrees of inhalational exposure to DMS, occurring as a result of a single chemical spillage incident in the United Kingdom. Industrial poisoning is surprisingly rare and there are few previous reports in the literature outside China.

Accidents, Occupational↗
PubMed1998

Urinary excretion of platinum from platinum industry workers.

OBJECTIVES: Assessment of level of exposure to platinum and platinum concentration in urine from platinum industry workers to evaluate internal exposures and excretion kinetics. METHODS: Platinum concentrations in urine samples from 34 workers were measured by adsorptive voltammetry after UV-photolysis. Morning and evening samples were taken two to six times during six months. Individual exposures were assessed by personal air sampling. Also, two male volunteers were exposed to platinum dust for four hours at a typical platinum refinery workplace. RESULTS: Urinary platinum excretion after a shift in platinum industry workers was found to be up to 6270 ng/g creatinine--that is, 1000 times above the median value of unexposed people. Urinary excretion reached the maximum nearly 10 hours after inhalative exposure to dust containing platinum. Elimination corresponded to a first half life of about 50 (95% confidence interval (95% CI) 36 to 66) hours, but there were indications that a part of the incorporated platinum is stored longer. The amount of urinary platinum excretion showed a close correlation with the exposure level monitored by personal air sampling. CONCLUSIONS: A newly developed analytical method enabled the detection of even natural background concentrations of platinum. Thus, increased urinary platinum concentrations could be detected early, which is important to avoid damaging health of exposed workers.

Adult↗
PubMed1998

Supercomputer description of human lung morphology for imaging analysis.

A supercomputer code that describes the three-dimensional branching structure of the human lung has been developed. The algorithm was written for the Cray C94. In our simulations, the human lung was divided into a matrix containing discrete volumes (voxels) so as to be compatible with analyses of SPECT images. The matrix has 3840 voxels. The matrix can be segmented into transverse, sagittal and coronal layers analogous to human subject examinations. The compositions of individual voxels were identified by the type and respective number of airways present. The code provides a mapping of the spatial positions of the almost 17 million airways in human lungs and unambiguously assigns each airway to a voxel. Thus, the clinician and research scientist in the medical arena have a powerful new tool to be used in imaging analyses. The code was designed to be integrated into diverse applications, including the interpretation of SPECT images, the design of inhalation exposure experiments and the targeted delivery of inhaled pharmacologic drugs.

Computer Simulation↗
PubMed2006

Chronic vanadium poisoning in calves and its treatment with calcium disodium ethylenediaminetetraacetate.

Sixteen Friesland heifer calves aged between 96 and 157 days were removed from a dairy farm that had been polluted with vanadium and randomly allocated into two equal groups (n = 8). The objective of the trial was to determine whether calcium disodium ethylenediaminetetraacetate (CaNa(2)EDTA) could be used as a treatment for cattle running in environments high in background vanadium. The treatment group received 80 mg CaNa(2)EDTA per kg body weight intraperitonealy (i.p.) twice a week over a 10-week period. The control group received normal saline i.p. over the same period. During the trial calves were exposed to a daily intake of vanadium in the form of contaminated tef hay derived from the farm of origin. In addition, the total mixed ration was spiked with a further 20 mg V(2)O(5)/kg feed to compensate for possible on-farm inhalation exposure. A stochastic model was used to estimate daily intake of vanadium as a distribution function. The model estimated that the daily intake of vanadium varied between an absolute minimum of 33 mg/day to an absolute maximum of 124 mg/day. The average intake of vanadium was 71.8 mg per day per calf. Various chemical pathology parameters were measured throughout the trial as well as urine excretion rates of vanadium and lymphocyte stimulation counts. All calves were slaughtered and necropsied in cohorts of 4-6 animals at monthly intervals after completion of the trial and withdrawal of vanadium from the ration. Tissue concentrations of vanadium were determined and necropsy findings were noted. The study found that CaNa(2)EDTA appears to enhance the excretion of vanadium in calves, but could not prove that the treatment had a protective effect against vanadium exposure. Calves were able to tolerate the prolonged treatment with CaNa(2)EDTA without side-effects.

Animals↗
PubMed2002

Brain manganese concentrations in rats following manganese tetroxide inhalation are unaffected by dietary manganese intake.

Manganese-deficient individuals have decreased manganese elimination. This observation has prompted suggestions that relative manganese deficiency may increase the risk for manganese neurotoxicity following inhalation exposure. The objective of this study was to determine whether dietary manganese intake influences the pharmacokinetics of inhaled manganese tetroxide (Mn3O4). Postnatal day (PND) 10 rats were placed on either a low (2 ppm), sufficient (10 ppm), or high-normal (100 ppm) manganese diet for 2 months. Beginning on PND 77 +/- 2, male littermates were exposed 6 h per day for 14 consecutive days to 0, 0.042, or 0.42 mg Mn3O4/m3. End-of-exposure tissue manganese concentrations and whole-body 54Mn elimination rates were determined. Tissue manganese concentrations were dependent on the dietary intake of manganese, thus confirming that altered hepatic manganese disposition or metabolism occurred. Male rats given 100 ppm manganese diet developed increased manganese concentrations in the femur, liver, and bile and had elevated whole-body 54Mn clearance rates when compared to animals given 2 ppm manganese diet. Male rats exposed to 0.42 mg Mn3O4/m3 had increased manganese concentrations in the olfactory bulb, lung, liver, and bile when compared to air-exposed male rats. A significant interaction between the concentration of inhaled Mn3O4 and dietary manganese level was observed only with the end-of-exposure liver manganese concentration. Our results indicate that animals maintained on either a manganese-deficient or high manganese diet do not appear to be at increased risk for elevated brain manganese concentrations following inhalation exposure to high levels of Mn3O4.

Administration, Inhalation↗
PubMedDate not supplied

Effect of chronic inhalation of sulfuric acid mist upon mucociliary clearance from the lungs of donkeys.

The effect of chronic inhalation exposures to sulfuric acid mist upon mucociliary clearance from the lungs was studied, using the donkey as an analogue for man. Four animals were exposed 1 hr/day, 5 days/week, for 6 months. The mean mass concentration of acid mist was 102 microgram/m3 for two animals, and 106 microgram/m3 for the other two. The mass median aerodynamic diameter was approximately 0.5 micrometer. Clearance was monitored by serial, external in vivo measurements of the retention of an insoluble, radioactively tagged ferric oxide aerosol which was inhaled following exposure to the acid mist. Bronchial clearance became erratic within the first week of exposure; rates were significantly different, usually slower than control on many test days, although the degree of response varied among the four animals. Two animals exhibited a sustained impairment of clearance towards the end of the 6-month exposure period and continued to have erratic clearance during a 3-month follow-up period. No changes in the regional deposition of the ferric oxide occurred during the course of the study in any of the animals. It is proposed that alterations in bronchial mucociliary clearance may be an early, if not the first, physiologic effect resulting from the inhalation of sulfuric acid mist, and this may be a factor in the pathogenesis of chronic bronchitis in populations exposed to the sulfur oxide-particulate-complex in the ambient air, which often includes sulfuric acid.

Aerosols↗
PubMed2002

Assessment of long-term effects of exposure to toluene based on the analysis of selected behavioral responses with particular reference to the ability to trigger behavioral hypersensitivity in rats.

Toluene is a major component of numerous commercial organic solvent formulations. It is often listed among the chemicals capable of producing the organic solvent syndrome and a neurobehavioral hypersensitivity condition. The hypersensitivity condition (continued long-term intensification of some behavioral reactions in response to pharmacological or environmental stressors) is usually associated with the increased tonus of the functional dopaminergic system. The aim of our current research was to determine whether, under conditions of inhalation exposure, toluene can produce long-term behavioral changes or modify the intensity of the behavioral response to apomorphine, a dopaminergic receptor agonist. In our experiment, male rats were exposed to 25, 100 and 250 ppm toluene for 4 weeks (5 days/week, 6h/day). The following behaviors were tested: finding water in a radial maze; open field motor activity, acquiring the conditional response of passive avoidance; sensitivity to a thermal pain stimulus (hot plate test) and changes in this sensitivity caused by stress; and acquiring the conditional response of two-directional active avoidance. The behavioral response to apomorphine, i.e. the increased spontaneous locomotor activity, was assessed on day 10 after the termination of the exposure in the rotary drum test. In the behavioral experiment, significant differences between groups were recorded only for the hot plate test; in the 100 and 250 ppm rats, electric-shock-related anxiety response was stronger than in the control group. In the experiment using pharmacological provocation, the behavioral response to apomorphine in the rats exposed to 100 ppm or 250 ppm toluene was significantly lower. Our results indicate that low concentrations of toluene may produce long-term behavioral changes in rats. However, these changes seem to be linked with reduced rather than increased functional tonus of the dopaminergic system.

Animals↗
PubMed2006

Pyrethroid illnesses in California, 1996-2002.

This survey summarizes California's recent experience with illnesses related to pyrethroid exposures and augments the data available on pyrethroid inhalation exposure and residue dissipation. We reviewed California Department of Pesticide Regulation (DPR) Pesticide Illness Surveillance Program (PISP) data and DPR Pesticide Use Reporting (PUR) data for 13 pyrethroids used during 1996-2002 and identified 317 illnesses associated with exposure. PUR found a total of 4,629,852 pound (2,100,068 kg) of the 13 active ingredients were applied during the 7 yr. Type II pyrethroids accounted for 1,979,352 (897,820 kg) and 42.7% of the total pounds applied and 220 (69.6%) of the reported illnesses. Cyfluthrin was associated with 122 cases (55% of illnesses related to type II pyrethroids and 38.4% of all pyrethroid illnesses). Agricultural uses accounted for 118 (37.3%) of the reported illness cases, with 116 cases associated with employment. For the 199 cases (62.8%) associated with nonagricultural use, 132 (66.3%) were occupationally related. Overall, approximately equal numbers of illnesses resulted from individual exposures (167 cases) and group exposures (150 cases). The symptom arrays associated with the pyrethroid illnesses included irritant effects or pares- thesias of the eye, skin, or respiratory tract in 269 cases (84.9%). Type II pyrethroids were more frequently associated with isolated irritant symptoms (107 cases) than the type I pyrethroids (26 of 97 cases). Systemic symptoms were reported in 184 illnesses (58% of cases). Isolated systemic effects occurred in 48 cases (15.1%), but systemic effects were also present in 136 (50.6%) of the 269 cases with irritant symptoms. Residue exposures accounted for 158 illnesses (49.8%). Single or multiple violations of pesticide use regulations contributed to exposures in 90 of the 317 illnesses (28.4%); 76 were related to nonagricultural pyrethroid use. We also report results of DPR Worker Health and Safety Branch (WH&S) investigations of three large group illness episodes related to exposure to type II pyrethroids cyfluthrin and lambda-cyhalothrin that involved primarily respiratory irritation symptoms. An inhalation monitoring study found cyfluthrin air levels that approached experimentally established irritant thresholds for airborne cyfluthrin, from which a mean estimated absorbed dosage of 1.311 microg/kg/d was calculated. Although additional data are needed to establish threshold levels for both irritant and systemic symptoms for cyfluthrin and other pyrethroids, these observations suggest that field residues can cause irritant respiratory symptoms. DPR conducted a residue dissipation study in seven orange groves and estimated cyfluthrin residue half-lives. The dissipation rates fell into two distinct decay patterns, with more rapid decay in groves 1-4 (overall average half-life = 4.9 d) and a considerably longer decay in groves 5-7. The half-life for groves exhibiting the slower residue dissipation was not constant. The first two half-lives for groves 5-7 can be approximated; they are 11 and 32d, respectively. The third investigation involved an illness episode in which 11 raisin harvesters developed acute respiratory irritation symptoms when they were exposed to residues of lambda-cyhalothrin, propargite, and sulfur. Gas chromatography analyses of eight dislodgeable foliar residue (DFR) samples verified mean residues of lambda-cyhalothrin (0.43 +/- 0.10 microg/cm2), propargite (0.35 +/- 0.11 microg/cm2), and sulfur (0.31 +/- 0.28 microg/cm2) on the grape leaves. Subsequent investigation confirmed that the lambda-cyhalothrin product, which was not registered for use on grapes, was mistakenly mixed and applied 45 d earlier at 35 times the highest legal rate for any crop. The effects of exposure to average lambda-cyhalothrin DFR levels of 0.43 microg/cm2 have not been previously documented.

Agriculture↗
PubMed2003

Clinical and laboratory investigation of allergy to genetically modified foods.

Technology has improved the food supply since the first cultivation of crops. Genetic engineering facilitates the transfer of genes among organisms. Generally, only minute amounts of a specific protein need to be expressed to obtain the desired trait. Food allergy affects only individuals with an abnormal immunologic response to food--6% of children and 1.5-2% of adults in the United States. Not all diseases caused by food allergy are mediated by IgE. A number of expert committees have advised the U.S. government and international organizations on risk assessment for allergenicity of food proteins. These committees have created decision trees largely based on assessment of IgE-mediated food allergenicity. Difficulties include the limited availability of allergen-specific IgE antisera from allergic persons as validated source material, the utility of specific IgE assays, limited characterization of food proteins, cross-reactivity between food and other allergens, and modifications of food proteins by processing. StarLink was a corn variety modified to produce a (Italic)Bacillus thuringiensis(/Italic) (Bt) endotoxin, Cry9C. The Centers for Disease Control and Prevention investigated 51 reports of possible adverse reactions to corn that occurred after the announcement that StarLink, allowed for animal feed, was found in the human food supply. Allergic reactions were not confirmed, but tools for postmarket assessment were limited. Workers in agricultural and food preparation facilities have potential inhalation exposure to plant dusts and flours. In 1999, researchers found that migrant health workers can become sensitized to certain Bt spore extracts after exposure to Bt spraying.

Animal Feed↗
PubMed1983

Deposition of Crocidolite asbestos and glass microfibers inhaled by the Beagle dog.

The respiratory tract deposition of neutron activated Crocidolite asbestos and glass microfibers was determined in two groups of four Beagle dogs. The dogs were given 60-minute, nose-only inhalation exposures to an aerosol of either asbestos or glass fibers. The radioactivity in tissues and excreta four days after exposure was used to determine the fraction of inhaled fibers deposited in the upper respiratory tract and the deep lung. The activity median aerodynamic diameter (AMAD), count median diameter (CMD) and count median length (CML) were determined from fibers sampled during exposure. Crocidolite asbestos fibers (obtained from the Union Internationale Contre le Cancer) had an AMAD of 1.8 microns, a CMD of 0.25 micron and a CML less than 5 microns. The fraction of inhaled mass deposited in deep lung was 13-19 percent, while total deposition in the respiratory tract was 54-72 percent. Glass microfibers had an AMAD of 2.5 microns, a CMD of 0.15 microns and a CML of 5.4 microns. Five to 17 percent of the mass of glass fiber was deposited in the deep lung; total respiratory tract deposition was 45-64 percent. The deposition patterns were similar for these small asbestos and glass fibers inhaled by dogs and in good agreement with previous predictions made for man.

Aerosols↗
PubMed2006

Effect of fly ash inhalation on biochemical and histomorphological changes in rat liver.

The effect of fly ash inhalation (4h daily, 5 days a week) for 28 days on the deposition of metal ions and histopathological changes in the liver and serum clinical enzymes has been studied. The results showed an increase in the concentration of metals such as cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), and lead (Pb) in the tissues of exposed rats. The level of metals varied from metal to metal and from organ to organ. Level of serum enzymes such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, and alkaline phosphatase were increased in fly ash exposed rats using whole body inhalation exposure as compared to sham controls. Histopathological studies of rat liver exposed to fly ash revealed infiltration of mononuclear cells in and around the portal triads, which seems to be laden with fly ash particles. Hepatocytes showed necrotic changes such as pyknotic nuclei, karyorrhexis, and karyolytic. These changes were more towards the centrolobular areas than the midzonal and periportal areas. These findings demonstrate that the toxic metals of inhaled fly ash in rats may get translocated into extrapulmonary organs, become deposited and hence may manifest their toxic effects on different tissues.

Alanine Transaminase↗
PubMed2003

Long term lung retention studies of 125Sb aerosols in humans.

This paper describes the retention of 125Sb oxide aerosols in human lungs based on the data obtained from a group of seven accidental inhalation exposure cases. Long-term follow-up studies for periods of time ranging from 1 to 3 d post intake to 199 to 2,422 d post intake have indicated the biological lung clearance half-time of this material ranging from about 600 to 1,100 d for non-smokers and 1,700 to 3,700 d for smokers. The retention in the lungs after 180 d in all the seven cases is found to be much more than 51% of the estimated initial alveolar deposit, which is consistent with the present ICRP criteria of assignment to the lung absorption Type S. There is little previously reported human data on this radionuclide compound. In these studies reliable information on actual time of intake, the likely type of material, and the amount of retained body/lung activity in initial days after the incident was also available, which adds to the importance of these data. The results of these studies provide a basis for firm classification and suggest that oxides of antimony need to be removed from absorption Type M (earlier class W) where these are presently listed by ICRP and be placed in absorption Type S (earlier class Y). The range of measured retained lung activities after the initial rapid clearance phase (7 d post exposure) was about 3 to 14 kBq, which was sufficient for long-term follow up studies using the whole body counters.

Adult↗
PubMed1994

Benzene toxicokinetics in humans: exposure of bone marrow to metabolites.

A three compartment physiologically based toxicokinetic model was fitted to human data on benzene disposition. Two separate groups of model parameter derivations were obtained, depending on which data sets were being fitted. The model was then used to simulate five environmental or occupational exposures. Predicted values of the total bone marrow exposure to benzene and cumulative quantity of metabolites produced by the bone marrow were generated for each scenario. The relation between cumulative quantity of metabolites produced by the bone marrow and continuous benzene exposure was also investigated in detail for simulated inhalation exposure concentrations ranging from 0.0039 ppm to 150 ppm. At the level of environmental exposures, no dose rate effect was found for either model. The occupational exposures led to only slight dose rate effects. A 32 ppm exposure for 15 minutes predicted consistently higher values than a 1 ppm exposure for eight hours for the total exposure of bone marrow to benzene and the cumulative quantity of metabolites produced by the bone marrow. The general relation between the cumulative quantity of metabolites produced by the bone marrow and the inhalation concentration of benzene is not linear. An inflection point exists in some cases leading to a slightly S shaped curve. At environmental levels (0.0039-10 ppm) the curve bends upward, and it saturates at high experimental exposures (greater than 100 ppm).

Air↗
PubMed2004

Approaches to carcinogenic risk assessment for polycyclic aromatic hydrocarbons: a UK perspective.

This paper reviews the approaches to carcinogenic risk assessment of polycyclic aromatic hydrocarbons (PAHs) in air pollution with emphasis on high potency PAHs such as dibenzo[a,l]pyrene (DB[a,l]P). The potency of DB[a,l]P may be 100-fold greater than benzo[a]pyrene (B[a]P); thus the B[a]P surrogate approach currently used to monitor for compliance with UK air pollution standards may not be appropriate. It is suggested that an approach based on potency equivalency factors (PEFs) could be developed to include highly potent PAHs provided an appropriate reference data set for relevant PAHs using a route acceptable for inhalation risk assessment is selected. Available data suggest that intratracheal administration of low doses of PAHs to rats is likely to simulate the kinetics of inhalation exposure to PAHs in a feasible manner. The use of a measure of total DNA adducts as an endpoint, which correlates well with lung tumourigenicity, would provide surrogate data for setting PEFs without the need for long-term bioassays in rodents. Further, dose-response studies using intratracheal administration of a range of PAHs singly and in combination to assess additivity are required to develop a PEF system for inhalation PEFs derived from DNA adduct measurements.

Air Pollutants↗
PubMedDate not supplied

Correlation of urinary 1-hydroxypyrene and 2-naphthol with total suspended particulates in ambient air in municipal middle-school students in Korea.

The authors investigated Korean municipal middle school students to ascertain whether urinary 1-hydroxypyrene (1-OHP) and 2-naphthol-markers for polycyclic aromatic hydrocarbon (PAH) exposure-reflect PAHs in ambient air. The authors used the beta-ray absorption method, which is an index of ambient-air PAH exposure, to collect total suspended particulate (TSP) data. The authors measured urinary 1-OHP and 2-naphthol concentrations in 137 nonsmoking students in 4 municipal middle schools within 1 km of ambient air monitoring stations. The median concentrations of urinary 1-OHP and 2-naphthol in the study were 0.09 nmole/mol creatinine and 2.19 micromol/mol creatinine, respectively, and the geometric means were 0.10 nmole/mol creatinine and 2.47 micromol/mol creatinine, respectively. Urinary 1-OHP concentration did not correlate significantly with any TSP index. There were significant correlations between urinary 2-naphthol level and the daily mean TSP level calculated for 2 days before survey, for 1 day before survey, and for the day of survey. These data suggest that urinary 2-naphthol may be a good marker for inhalation exposure to PAHs in ambient air.

Adolescent↗
PubMed2006

Utility of the mouse dermal promotion assay in comparing the tumorigenic potential of cigarette mainstream smoke.

The International Agency for Research on Cancer (IARC) has classified a number of the chemical constituents reported in cigarette mainstream smoke (MS) as carcinogens. In the international literature, 81 IARC classified carcinogens have been reported historically in MS. Cigarette smoke is a complex aerosol of minute liquid droplets (termed the particulate phase) suspended within a mixture of gases (CO(2), CO, NO(x), etc.) and semi-volatile compounds. The gases and semi-volatiles are termed the vapor phase. Due to early difficulties in inducing carcinomas in laboratory animals following inhalation exposure to MS, the mouse dermal promotion assay became the standard method of comparing the tumorigenic potential of cigarette smoke condensates (the particulate phase of MS nearly devoid of MS gases and having a significant reduction of the semi-volatile components of the vapor phase). Of the 81 IARC carcinogens reported in MS, 48 are found exclusively in the particulate phase, 29 in the vapor phase only, and four IARC carcinogens in both phases. A general comparison of the quantity and potency of the individual carcinogenic constituents of the MS vapor and particulate phases illustrates that the potential carcinogenic contribution from the vapor phase might be significant. Therefore, the mouse dermal promotion assay may not be a sensitive comparator of the tumorigenic potential of different MSs displaying a diversity of vapor phase components. However, when used in a weight-of-the-evidence approach that includes smoke chemistry, in vitro studies using whole smoke and human exposure studies evaluating both vapor and particulate phase smoke constituents, the mouse dermal promotion assay remains an important risk assessment tool as the only test that reproducibly measures the tumorigenic potential of cigarette smoke condensate.

Animals↗
PubMed2000

Biotransformation and kinetics of excretion of ethyl tert-butyl ether in rats and humans.

Ethyl tert-butyl ether (ETBE) may be used in the future as an additive to gasoline to increase oxygen content and reduce tailpipe emissions of pollutants. Therefore, widespread human exposure may occur. To contribute to the characterization of potential adverse effects of ETBE, its biotransformation was compared in humans and rats after inhalation exposure. Human volunteers (3 males and 3 females) and rats (5 males and 5 females) were exposed to 4 (4.5+/-0.6) and 40 (40.6+/-3.0) ppm ETBE for 4 h in a dynamic exposure system. Urine samples from rats and humans were collected for 72 h at 6-h intervals, and blood samples were taken in regular intervals for 48 h. In urine, ETBE and the ETBE-metabolites tert-butanol (t-butanol), 2-methyl-1,2-propane diol, and 2-hydroxyisobutyrate were quantified; ETBE and t-butanol were determined in blood samples. After the end of the exposure period to inhalation of 40-ppm ETBE, blood concentrations of ETBE were found at 5.3+/-1.2 microM in rats and 12.1+/-4.0 microM in humans. The ETBE blood concentrations, after inhalation of 4-ppm ETBE, were 1.0+/-0.7 microM in rats and 1.3+/-0.7 microM in humans. ETBE was rapidly cleared from blood. After the end of the 40-ppm ETBE exposure period, the blood concentrations of t-butanol were 13.9+/-2.2 microM in humans and 21.7+/-4.9 microM in rats. After 4-ppm ETBE exposure, blood concentrations of t-butanol were 1.8+/-0.2 microM in humans and 5.7+/-0.8 microM in rats. t-Butanol was cleared from human blood with a half-life of 9.8+/-1.4 h in humans after 40-ppm ETBE exposure. In urine samples from controls and in samples collected from the volunteers and rats before the exposure, low concentrations of t-butanol, 2-methyl-1,2-propane diol, and 2-hydroxyisobutyrate were present. In the urine of both humans and rats exposed to ETBE, the concentrations of these compounds were significantly increased. 2-Hydroxy-isobutyrate was recovered in urine as the major excretory product formed from ETBE; t-butanol and 2-methyl-1,2-propane diol were minor metabolites. All metabolites of ETBE excreted with urine were rapidly eliminated in both species after the end of the ETBE exposure. Excretion half-lives for the different urinary metabolites of ETBE were between 10.2 and 28.3 h in humans and 2.6 and 4.7 h in rats. The obtained data indicate that ETBE biotransformation and excretion are similar for rats and humans, and that ETBE and its metabolites are rapidly excreted by both species. Between 41 and 53% of the ETBE retained after the end of the exposure was recovered as metabolites in the urine of both humans and rats.

Administration, Inhalation↗
PubMed1998

Short-term exposures of rats to airborne hydrogen fluoride.

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

Administration, Inhalation↗