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PubMed1993

Biomonitoring of nickel and chromium in human pulmonary tissue.

Nickel (Ni) and chromium (Cr) and some of its compounds may be able to induce cancer in the lungs as well as in the nose and paranasal sinuses after occupational exposure. Latency periods amount to 20 years and more. Therefore objective exposure data are not available in the most cases and expert evaluation of the causal connection is often difficult. Recent investigations have shown, that Ni and Cr can cumulate in human lung tissue after occupational exposure. For the evaluation of "normal" Ni- and Cr-values a total of 495 human lung tissue samples of 30 occupationally non-exposed persons were analysed by AAS including ZEEMAN-compensation after wet oxidative digestion. Additional samples of 10 deceased persons who have been occupationally exposed to nickel in previous times by nickel-refining and welding, especially flame spraying have been investigated. The median Ni- and Cr- concentrations in the lungs of the non-exposed persons ranged between 20-40 resp. 133-277 ng/g (wet weight). In nickel refinery workers Ni- concentrations were found which exceeded the normal range about 1,000. In welders, especially flame sprayers, also values more than 100 times higher could be analysed for Ni and Cr. Partially these concentrations were found years after the end of the inhalative exposure.

Chromium↗
PubMed2004

Comparative study on Tp53 gene mutations in lung tumors from rats exposed to 239Pu, 237Np and 222Rn.

The tumor suppressor gene Tp53 was analyzed by polymerase chain reaction-amplification of genomic DNA extracted from paraffin-embedded tissue sections of rat lung tumors to compare mutations that occurred after inhalation exposures to plutonium dioxide, neptunium dioxide, or radon and radon progenies. Exons 5 to 8 of the gene were amplified in 16 plutonium-, 23 neptunium- and 15 radon-induced lung tumors, and their polymerase chain reaction products were examined for mutations by single strand conformational polymorphism analysis and direct sequencing method. Two point mutations were detected in the plutonium-induced tumors, i.e., a guanine to adenine transition at codon 219 of exon 6 and a cytosine to thymine transition at codon 266 of exon 8. Although only one point mutation was found at codon 175 of exon 5 (cytosine to thymine transition) from neptunium-induced tumors, no mutations were detectable from radon-induced tumors. These results indicate that the abnormalities of the Tp53 gene might not be so critical for the pulmonary carcinogenesis after the inhalation of different alpha emitters, even though the presence and frequencies of the Tp53 gene mutations were different.

Administration, Inhalation↗
PubMed1986

Macrophage depletion of mouse lung following inhalation of 239PuO2.

Changes in the free-cell population of the lungs of two strains of mice (SAS/4 and CBA/H) were studied up to 4 months after inhalation exposure to a sized fraction of 239PuO2 particles (1.5 micron AMAD) to give initial alveolar depositions (IADs) ranging from 17 to 810 Bq. A sample of the free-cell population of the lung was recovered by bronchoalveolar lavage, and a radiometric method was used to estimate the total number of pulmonary alveolar macrophages (PAM) in the lung. The response of the lung to 239PuO2 was characterized by an initial, dose-dependent depression in the total number of PAM following an IAD as low as 50 Bq. At IADs greater than 150 Bq, the initial depression continued for longer, merging into a chronic phase in which the PAM were larger and were accompanied by a minor infiltration of leukocytes. These findings were confirmed by histology, which also revealed focal accumulations of Type II pneumocytes. The results indicate that inhaled alpha-emitting particles are effective at producing a depletion in the alveolar macrophage population at relatively low IADs and that chronic effects on the cells can be produced by higher concentrations.

Aerosols↗
PubMedDate not supplied

Desflurane, enflurane, isoflurane and ether produce ethanol-like discriminative stimulus effects in mice.

In the present studies, drug discrimination procedures were used to compare the discriminative stimulus effects of ethanol (ETOH) and several volatile anesthetics. Male albino mice were trained to discriminate between IP injections of ETOH (1.25 g/kg) and saline in a two-lever operant task in which responding was under the control of a fixed-ratio 20 (FR20) schedule of food presentation. Stimulus generalization was examined after 20-min inhalation exposures to desflurane (4,000-32,000 ppm), enflurane (3,000-12,000 ppm), isoflurane (1,000-8,000 ppm) and ether (4,000-32,000 ppm). Concentration-related increases in ETOH-lever responding were observed for all four volatile anesthetics. For enflurane and ether, maximal levels of > 85% ETOH-lever responding were obtained at one or more concentrations. For desflurane and isoflurane, the maximal mean percentages of ETOH-lever responding were somewhat lower, but 6 out of 7 mice showed full substitution with desflurane and 5 out of 7 for isoflurane. The shared discriminative properties of these compounds with ETOH suggest that these anesthetics may share some of ETOH's pharmacological properties. These results are similar to previous research results showing ETOH-like discriminative stimulus effects in mice with other anesthetics and abused volatile inhalants (i.e. halothane, toluene and 1.1,1-trichloroethane) and may reflect the CNS-depressant drug-like effects of inhaled anesthetics and abused solvents.

Anesthetics, Inhalation↗
PubMed1987

Glutathione peroxidase and glutathione transferase activity in rat lung and liver following cadmium inhalation.

A 2-h inhalation exposure to 4.6 mg Cd/m3 decreased pulmonary total glutathione peroxidase (GSH Px) activity and non-selenium peroxidase (GSH non-Se-Px) activity but had no effect on GSH selenium peroxidase (Se-Px) activity. Seventy-two hours after exposure there was an increase in total GSH Px and GSH Se-Px activity and a decrease in GSH non-Se-Px activity. Exposure to 0.44 mg Cd/m3 for 2 h caused no effect on GSH Se-Px at either 0 or 72 h post exposure, but total GSH Px and GSH non-Se-Px activities were decreased up to 72 h post exposure. Exposure to 4.6 mg Cd/m3 caused an increase in hepatic GSH Se-Px activity 72 h post exposure, but no other significant changes were observed in the liver. Changes in GSH non-Se-Px activity did not relate to changes in GSH transferase (Tr) activity. The data suggest that alterations in GSH Px activity by Cd2+ may be due to changes in GSH non-Se-Px activity and that changes in pulmonary GSH Tr and GSH non-Se-Px activities may not be as closely linked as in the liver.

Administration, Inhalation↗
PubMed2006

Uncertainty of the thyroid dose conversion factor for inhalation intakes of 131I and its parametric uncertainty.

Inhalation exposures of 131I may occur in the physical form of a gas as well as a particulate. The physical characteristics pertaining to these different types of releases influence the intake and subsequent dose to an exposed individual. The thyroid dose received is influenced by the route through which 131I enters the body and its subsequent clearance, absorption and movement throughout the body. The radioactive iodine taken up in the gas-exchange tissues is cleared to other tissues or absorbed into the bloodstream of the individual and transferred to other organs. Iodine in the circulatory system is then taken up by the thyroid gland with resulting dose to that tissue. The magnitude of and uncertainty in the thyroid dose is important to the assessment of individuals exposed to airborne releases of radioiodine. Age- and gender-specific modelling parameters have resulted in significant differences between gas uptake, particulate deposition and inhalation dose conversion factors for each age and gender group. Inhalation dose conversion factors and their inherent uncertainty are markedly affected by the type of iodine intake. These differences are expected due to the modelling of particulate deposition versus uptake of gas in the respiratory tract. Inhalation dose estimates via iodine gases are very similar and separate classifications may not be necessarily based on this assessment.

Administration, Inhalation↗
PubMedDate not supplied

Respiratory hypersensitivity to trimellitic anhydride in Brown Norway rats: a comparison of endpoints.

A rat bioassay has been developed to provide an objective approach for the identification and classification of respiratory allergy using trimellitic anhydride (TMA), which is a known respiratory tract irritant and asthmagen. Particular emphasis was placed on the study of route-of-induction-dependent effects and their progression upon inhalation challenge with TMA (approximately 23 mg m(-3) for a duration of 30 min), which included analysis of specific and non-specific airway hyperreactivity and pulmonary inflammation initiated and sustained by immunological processes. Refinement of the bioassay focused on procedures to probe changes occurring upon challenge with TMA or methacholine aerosols using physiological, biochemical and immunological procedures. Following challenge with TMA, the rats sensitized to TMA showed marked changes in peak inspiratory and expiratory air flows and respiratory minute volume. In these animals, a sustained pulmonary inflammation occurred, characterized by specific endpoints determined in bronchoalveolar lavage (lactate dehydrogenase, protein, nitrite, eosinophil peroxidase, myeloperoxidase). When compared with the naive controls, lung weights were increased significantly, as were the weights of lung-associated lymph nodes following inhalation induction and auricular lymph nodes following topical induction. The extent of changes observed was equal or more pronounced in animals sensitized epicutaneously (day 0:150 microl vehicle/50% TMA on each flank, day 7; booster administration to the skin of the dorsum of both ears using half the concentration and volume used on day 0) when compared with rats sensitized by 5 x 3 h day(-1) inhalation exposures (low dose: 25 mg TMA m(-3), high dose: 120 mg TMA m(-3)). In summary, the findings support the conclusion that the Brown Norway rat model is suitable for identifying TMA as an agent that causes both an immediate-type change of breathing patterns and a delayed-type sustained pulmonary inflammatory response. However, it remains unresolved whether the marked effects observed in the topically sensitized rats are more related to a route-of-induction or dose-dependent phenomenon.

Administration, Cutaneous↗
PubMed2003

Tissue dosimetry expansion and cross-validation of rat and mouse physiologically based pharmacokinetic models for trichloroethylene.

Trichloroethylene (TCE), a volatile liquid used as a degreasing agent, is a common environmental pollutant. In 2001, the EPA published a draft risk assessment for TCE that incorporates dosimetry predictions of physiologically based pharmacokinetic (PBPK) models. The current modeling effort represents an expansion and extensive tissue dosimetry validation of rodent PBPK models for TCE. The pharmacokinetics of TCE in male Sprague-Dawley (S-D) rats were characterized (1) during and after inhalation exposure to 50 or 500 ppm TCE, (2) following administration of 8 mg/kg TCE PO, and (3) following intra-arterial injection of 8 mg/kg TCE. Blood and tissues (including liver, kidney, fat, skeletal muscle, heart, spleen, gastrointestinal tract, and brain) were collected at selected time-points from 5 min up to 24 h post initial exposure. The fat compartment was modified to be diffusion-limited to predict the observed slow release of TCE from the fat. The addition of a deep liver compartment was necessary to accurately predict the slower hepatic clearance of TCE for all three exposure routes. Simulations of liver concentrations following gavage of male B6C3F1 mice with 300-2000 mg/kg TCE were also improved with the addition of a deep liver compartment. Liver predictions were calibrated and validated using a cross-validation technique novel to PBPK modeling. Splitting of compartments did not significantly affect predictions of TCE concentrations in the liver, fat, or venous blood. This model expansion and validation increases both the utility and our confidence in the current use of rodent TCE PBPK models in human health risk assessment.

Adipose Tissue↗
PubMed1994

The pharmacokinetics of inhaled 1,1,1-trichloroethane following high milk intake in mice.

In the evaluation of lipophilic halocarbons for neurobehavioral toxicity in operant testing, animals often receive large amounts of milk as a behavioral reinforcer over time. If this increase of fat in the diet sufficiently impacted the lipid depots of the animal, the pharmacokinetics of lipophilic test compounds might be significantly affected and thus obscure the accompanying neurobehavioral effects. The effects of milk intake, comparable to what was consumed as behavioral reinforcer during operant behavioral sessions, on the pharmacokinetics of inhaled 1,1,1-trichloroethane (TRI) were therefore examined in the blood and nine organ tissues of mice. Male CD-1 mice were food restricted so that their body weights would be reduced to and maintained at 80% of their original, and received a single gavage dose of 1.0 ml evaporated milk daily for three weeks. A control group with similar food restrictions was dosed with the same volume of water. Inhalation exposures to 3500 ppm TRI for 100 minutes were conducted at the end of the treatment period. Blood and nine organ tissues were sampled at a series of time points, and their TRI contents were analyzed by headspace gas chromatography. The uptake of TRI was rapid, with near steady state approached in blood and most tissues after 40-60 minutes of exposure. All of the tissues except fat had similar TRI time-concentration profiles, while TRI concentrations in fat tissue were about 20-30 times higher than in other tissues. There was no statistically significant difference in the tissue concentrations between the milk-dosed group and water-dosed group at all of the time points for all tissues measured. Therefore, it appears unlikely that this level of milk intake as a reinforcer in behavioral studies will affect the results of operant testing evaluations by altering the pharmacokinetics of lipophilic halocarbons such as TRI.

Administration, Inhalation↗
PubMed1999

Subchronic inhalation study of 1-hexene in Fischer 344 rats.

The objective of this study was to evaluate the toxicity of 1-hexene following repeated inhalation exposures in male and female Fischer 344 rats. Groups of 40 male and 40 female rats were exposed for 6 hours per day, 5 days per week, over a 13-week period. Treatment groups consisted of air-exposed control (0 ppm) and three test groups of 300, 1000, and 3000 ppm 1-hexene. During the treatment period, the rats were observed daily for clinical signs of toxicity; body weights and neuromuscular coordination [females only] were measured at 7-day intervals. After 7 weeks of exposure and at the end of the treatment period, the rats were subject to macroscopic and microscopic pathology, clinical chemistry, hematology, urinalysis, and sperm counts. No mortalities were observed during the course of the study. No clinical signs of toxicity attributable to 1-hexene exposure were observed. Female rats exposed to 3000 ppm had significantly lower body weights compared to control rats from exposure day 5 persisting throughout the treatment period. Male rats exposed to 3000 ppm had slightly but not statistically significant lower body weights in comparison to controls. Male rats exhibited slightly increased absolute and relative testicular weights, and female rats had slightly decreased absolute [but not relative] liver and kidney weights, at 3000 ppm. There were no gross or microscopic morphological findings attributed to treatment. Exposure to 1-hexene did not affect neuromuscular coordination in females as determined using the Rotarod, nor sperm counts in male rats. Several statistically significant effects in hematology, clinical chemistry, and urinalysis evaluations were observed, but were either of small magnitude or did not correlate with histopathological findings, and thus did not appear to be of biological significance. In summary, the no-adverse-effect-level for this study was determined to be 1000 ppm, based on decreased weight gain in female rats, and on slight organ weight changes in both sexes at 3000 ppm.

Administration, Inhalation↗
PubMed1989

Infectious papillomavirus in the vapor of warts treated with carbon dioxide laser or electrocoagulation: detection and protection.

Papillomavirus DNA has been reported recently in the vapor (smoke plume) derived from warts treated with carbon dioxide laser; this raises concerns for operator safety. We therefore have studied a group of human and bovine warts to define further the potential risk of wart therapy and to test whether a surgical mask could reduce exposure. Half of each wart was treated with carbon dioxide laser and the other half with electrocoagulation. The vapor produced by each form of therapy was collected with a dry filter vacuum apparatus and analyzed for the presence of papillomavirus. Vapor from human plantar warts was analyzed for the presence of human papillomavirus DNA, because there is no infectivity assay for human papillomavirus. Of plantar warts treated, five of eight laser-derived vapors and four of seven electrocoagulation-derived vapors were positive for human papillomavirus DNA. Greater amounts of papillomavirus DNA were usually recovered in the laser vapor than in the electrocoagulation vapor from the same wart. Bioassay readily detected infectious bovine papillomavirus in the vapor from bovine warts treated with either modality; more virus was present in laser-derived material. A surgical mask was found capable of removing virtually all laser- or electrocoagulation-derived virus, strongly suggesting that such masks can protect operators from potential inhalation exposure to papillomavirus.

Air Microbiology↗
PubMed1991

A 90-day continuous vapor inhalation toxicity study of JP-8 jet fuel followed by 20 or 21 months of recovery in Fischer 344 rats and C57BL/6 mice.

The kerosene-type jet fuel, JP-8, consists of a complex mixture of aliphatic and aromatic hydrocarbons. Because of the utility of JP-8, studies have been conducted to identify the potential long-term consequence of occupational inhalation exposure. Fischer 344 rats and C57BL/6 mice of both sexes were exposed to JP-8 vapors at 0, 500, and 1,000 mg/m3 on a continuous basis for 90 days, then followed by recovery until approximately 24 months of age. Occurrence of necrotizing dermatitis associated with fighting resulted in an increase in mortality in mice (male greater than female) during the 2 week to 9 month post-exposure recovery period. The male rat kidney developed a reversible ultrastructural increase in size and propensity for crystalloid changes of phagolysosomal proteinic reabsorption droplets in the proximal convoluted tubular epithelium. A specific triad of persisting light microscopic renal lesions occurred but functional change was limited to a decrease in urine concentration compared to controls that persisted throughout the recovery period. The response is comparable to the chronic effect of lifetime exposure of the male rat to unleaded gasoline, d-limonene, and p-dichlorobenzene, except for the absence of tubular tumorigenesis. The active toxicologic response presumably must occur over a greater proportion of the male rat's life span for the tumor component of this male rat hydrocarbon nephropathy syndrome. The predictiveness for humans must be questioned, since the pathologic response to JP-8 involved only one tissue in one sex of one species, and since the male rat response appears to be linked to an inherent renal protein peculiarity.

Administration, Inhalation↗
PubMed2005

Polychlorinated biphenyl (PCB) exposure assessment by multivariate statistical analysis of serum congener profiles in an adult Native American population.

The major determinants of human polychlorinated biphenyl (PCB) body burden include the source and route of exposure and the toxicokinetic processes occurring after uptake. However, the relative importance of each factor for individual subjects cannot currently be determined. The present study characterizes levels and patterns of PCB congeners in a large cohort of adult Akwesasne Mohawks with historical PCB exposure. Total serum PCB ranged from 0.29 to 48.32 ng/g and was higher in adult men than in women (median of 3.81 vs. 2.94 ng/g). The mean serum congener profile for the full cohort was dominated by persistent penta- to hepta-chlorinated biphenyls; several labile congeners were also prominent. In order to provide additional information on individual body burden determinants, multivariate exploratory data analysis techniques were applied to the congener-specific serum PCB data. A self-training receptor model, polytopic vector analysis (PVA), was employed to determine the number, composition, and relative proportions of independent congener patterns that contributed to the overall serum PCB profile for each Mohawk subject. PVA identified five such patterns, each of which was characterized by a unique mix of congeners. One pattern observed in a limited number of Mohawks was similar to those reported for air sampled near contaminated sediment deposits at Akwesasne and for volatilized Aroclor 1248 and is hypothesized to reflect recent inhalation exposure in these subjects. A second pattern was consistent with unaltered Aroclor 1254. A third pattern, resembling Aroclor 1262 but without labile congeners, was correlated with age and is interpreted as representing a lifetime PCB accumulation profile. The final two patterns were dominated by subsets of major persistent congeners and are hypothesized to reflect intermediate bioaccumulation profiles and/or differences in individual toxicokinetics. The results confirm the utility of a multivariate exploratory analysis approach to congener-specific PCB data and provide additional insight into the exposure and individual factors that determine PCB body burden in this population.

Adolescent↗
PubMed1999

High frequency of codon 61 K-ras A-->T transversions in lung and Harderian gland neoplasms of B6C3F1 mice exposed to chloroprene (2-chloro-1,3-butadiene) for 2 years, and comparisons with the structurally related chemicals isoprene and 1,3-butadiene.

Chloroprene is the 2-chloro analog of 1,3-butadiene, a potent carcinogen in laboratory animals. Following 2 years of inhalation exposure to 12.8, 32 or 80 p.p.m. chloroprene, increased incidences of lung and Harderian gland (HG) neoplasms were observed in B6C3F1 mice at all exposure concentrations. The present study was designed to characterize genetic alterations in the K- and H-ras proto-oncogenes in chloroprene-induced lung and HG neoplasms. K-ras mutations were detected in 80% of chloroprene-induced lung neoplasms (37/46) compared with only 30% in spontaneous lung neoplasms (25/82). Both K- and H-ras codon 61 A-->T transversions were identified in 100% of HG neoplasms (27/27) compared with a frequency of 56% (15/27) in spontaneous HG neoplasms. The predominant mutation in chloroprene-induced lung and HG neoplasms was an A-->T transversion at K-ras codon 61. This mutation has not been detected in spontaneous lung tumors of B6C3F1 mice and was identified in only 7% of spontaneous HG neoplasms. In lung neoplasms, greater percentages (80 and 71%) of A-->T transversions were observed at the lower exposures (12.8 and 32 p.p.m.), respectively, compared with 18% at the high exposure. In HG neoplasms, the percentage of A-->T transversions was the same at all exposure concentrations. The chloroprene-induced ras mutation spectra was similar to that seen with isoprene, where the predominant base change was an A-->T transversion at K-ras codon 61. This differed from 1,3-butadiene, where K-ras codon 13 G-->C transitions and H-ras codon 61 A-->G transitions were the predominant mutations. The major finding of K-ras A-->T transversions in lung and Harderian gland neoplasms suggests that this mutation may be important for tumor induction by this class of carcinogens.

Adenoma↗
PubMed1985

Aerosol resuspension from fabric: implications for personal monitoring in the beryllium industry.

The fabric used for work clothing at an industrial site can significantly influence personal monitor (PM) exposure estimates because dust resuspension from clothing can increase the concentration at the sampler inlet. The magnitude of the effect depends on removal forces and on the interaction of the contaminant particles with work garments. Aerosol deposition and resuspension on cotton and Nomex aramid fabrics was evaluated at a beryllium refinery. Electrostatically charged cotton backdrops collected more beryllium than neutral controls, but electronegative Nomex backdrops did not. Moving fabrics collected more beryllium than did stationary controls. When contaminated fabrics were agitated, PMs mounted 2.5 cm in front of the fabric collected more beryllium than monitors above the fabric, positioned to simulate the nose or mouth. The difference between the air concentrations measured by these PMs increased with Be loading and tended to level off for highly contaminated fabric. Cotton resuspended a larger fraction of its contaminant load than Nomex. These results are consistent with current knowledge of the behavior of particles on fabric fibers. Aerosol resuspension from garments is an important consideration in assessing inhalation exposure to toxic dusts. A garment may attract and retain toxic particles. This contamination is then available for later resuspension.

Aerosols↗
PubMed1989

Exposure to mutagenic chemicals in foundry and urban environments.

The study was aimed at the estimation of occupational exposure to mutagenic substances in a piston-ring foundry. The following samples were examined: solid phase of aerosol from the foundry and from different places of urban environment together with the foundry workers' urine collected during the 8-hour shift. The mutagenic substances were extracted from the collected material with acetone or concentrated with XAD-2 resin. The mutagenic property was estimated with the Ames' test using S. typhimurium strain TA98 without and with S9 fraction. The highest mutagenic activity was found at the following work-posts: caster, moulder, steerer of an induction furnace, and smelter and in the office rooms and in the flat occupied by heavy smokers. The mutagenic activity of aerosol at some other productive workposts in the foundry was similar to the mutagenic activity of aerosol in the office and flat rooms occupied by nonsmokers or in the street in Lodz. The mutagenic activity of urine from foundry workers was not correlated with the level of the occupational inhalation exposure to the mutagenic substances, however, the mutagenic activity of urine from smoking workers was about 10-20 times higher than from nonsmokers.

Air Pollutants, Occupational↗
PubMed1998

Metabolic interaction between toluene, trichloroethylene and n-hexane in humans.

OBJECTIVES: This human experimental study describes the mutual metabolic interaction between toluene, trichloroethylene, and n-hexane. METHODS: Eight healthy male volunteers were exposed to combinations of toluene (1.5 or 4 mg/min), trichloroethylene (1.5 or 4 mg/min), and n-hexane (0.3 or 1.0 mg/min) for 60 min. End exhaled air concentrations were measured before and up to 240 min after the start of exposure. The urinary excretion of hippuric acid, o-cresol, trichloroethanol, trichloroacetic acid, and 2,5-hexanedione was measured before and up to 270 min after the start of the exposures. RESULTS: When the low dose rates were combined, the end exhaled concentrations were at or below the detection limit, while an increase in the dose rate of toluene increased the area under the end exhaled air concentration curve (AUC) of toluene, trichloroethylene, and n-hexane by factors of 44 (16-117) [geometric mean and 95% confidence interval], 12.8 (4.1-40.0), and 2.2 (1.2-4.1), respectively. Trichloroethylene, in turn, increased the AUC 5.0 (1.9-13.4), 25.8 (8.2-80.8) and 2.9 (1.6-5.4), respectively, whereas the corresponding values for n-hexane were 1.9 (0.7-5.1), 1.5 (0.5-4.6), and 3.2 (1.8-5.9). An 18 (range 2-34)% decrease in hippuric acid was the only interaction measured in the metabolite excretion. No correlation occurred between the individual measures of the end exhaled concentrations or the excretion of metabolites. CONCLUSIONS: The study shows that the threshold for the flow-limited metabolism of the 3 solvents in humans is exceeded at liver dose rates corresponding to inhalation exposure at occupational exposure limits. At these levels there are metabolic interactions between the 3 solvents.

Adult↗
PubMed1988

Disposition of inhaled 1-chloro-2-propanol in F344/N rats.

Propylene chlorohydrins, of which 1-chloro-2-propanol (1-CP) is a constituent, used as intermediates in the manufacture of propylene oxide and have been identified as potential air pollutants. The objective of these studies was to determine whether changes in the inhaled exposure concentration would affect the disposition of 1-CP in rats. In addition, experiments were conducted to identify the carbon atom of 1-CP that is metabolized to CO2. Rats were exposed nose-only to [14C]1-CP for 6 hr to 8.3 +/- 1.0 ppm (26.1 +/- 3.2 micrograms/liter air) or 77 +/- 4 ppm (245 +/- 13 micrograms/liter air) (mean +/- SE). There were two major routes of elimination of 14C, urinary and exhalation of CO2, which together accounted for about 80% of the total 14C in excreta and carcass. Half-times for elimination of 14C in urine as 14CO2 were between 3 and 7 hr with no effect of exposure concentration on the elimination half-times for either route. After the end of exposure, kidneys, livers, trachea, and nasal turbinates contained high concentrations of [14C]1-CP equivalents at both exposure concentrations (30-50 nmol 14C/g tissue for the 8 ppm exposure level and 200-350 nmol 14C/g tissue for the 80 ppm exposure level). Elimination of 14C from tissues was biphasic with about 50% of the material in a tissue being rapidly eliminated with a half-time of 1 to 3 hr and the remaining material slowly eliminated with a half-time of 40 to 80 hr. There was no effect of exposure concentration on elimination half-times in tissues. Major metabolites detected in urine and tissues (liver, kidney, and lung) were N-acetyl-S-(hydroxypropyl)cysteine and/or S-(2-hydroxypropyl)-cysteine. Little unmetabolized 1-CP (less than 1%) was detected in analyzed tissues or urine. We propose a metabolic scheme in which the major pathway for metabolism of 1-CP is to CO2 (which is exhaled) and to cysteine conjugates and mercapturic acids that are excreted in the urine. Both carbon-2 and carbon-3 are metabolized in part to CO2.

Administration, Inhalation↗

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