INDEX inhalation

Announce. Index 12, 9—12 (1981). [A 121-page review of health effects Hterature primarily related to inhalation exposure.]... 

Workers in the metals treatment industry are exposed to fumes, dusts, and mists containing metals and metal compounds, as well as to various chemicals from sources such as grinding wheels and lubricants. Exposure can be by inhalation, ingestion, or skin contact. Historically, metal toxicology was concerned with overt effects such as abdominal coHc from lead toxicity. Because of the occupational health and safety standards of the 1990s such effects are rare. Subtie, chronic, or long-term effects of metals treatment exposure are under study. An index to safety precautions for various metal treatment processes is available (6). As additional information is gained, standards are adjusted. 

Improvements in asthma treatment include the development of more effective, safer formulations of known dmgs. The aerosol adrninistration of P2-agonists or corticosteroids results in a decrease in side effects. Also, the use of reUable sustained release formulations has revolutionized the use of oral xanthines which have a very narrow therapeutic index (see Controlled release technology). For many individuals, asthma symptoms tend to worsen at night and the inhaled bronchodilatots do not usually last through an entire night s sleep (26,27). 

So fares toxicity risk through Inhalation is concerned, which is the most common under normal working conditions, a quantitative index of toxicity is suggested on p.140. 

As is needed for all potential risks for chemical substances, an index of toxicity enables quantification of risk. Nevertheless, it only applies to risk by inhalation, which is yet the most common as well as insidious risk under normal working conditions with chemical substances. However, this approach should be treated with caution because of the difficulties inherent in toxicological risks. At this stage of the analysis it is essential to work in collaboration with the company doctor, whose total agreement is necessary. 

Theophylline is also considered an alternative to inhaled corticosteroids for the treatment of mild persistent asthma however, limited efficacy compared to inhaled corticosteroids, a narrow therapeutic index with life-threatening toxicity, and multiple clinically important drug interactions have severely limited its use. Theophylline causes bronchodilation through inhibition of phosphodiesterase and antagonism of adenosine and appears to have anti-inflammatory and immunomodulatory properties as well.36... 

Theophylline is a non-specific phosphodiesterase inhibitor that increases intracellular cAMP within airway smooth muscle resulting in bronchodilation. It has a modest bronchodila-tor effect in patients with COPD, and its use is limited due to a narrow therapeutic index, multiple drug interactions, and adverse effects. Theophylline should be reserved for patients who cannot use inhaled medications or who remain symptomatic despite appropriate use of inhaled bronchodilators. 

Radford, E. P., and E. A. Martell, Polonium-210 lead-210 ratios as an index of residence times of insoluble particles from cigarette smoke in bronchial epithelium, in Inhaled Particles IV, Part 2 (W. H. Walton, ed.) pp. 567-580, Pergamon Press, Oxford (1977). 

Administration by inhalation has been explored by Brilli [124], mentioned previously for his work with NONOates. Here he uses one of these same NONOates, DMAEP/NO (see Fig. 8.11), in aerosol form. When administered in an aerosolized state, DMAEP/NO again shows selective pulmonary vasodilation in a porcine model. This is achieved without affecting the systemic vascular resistance index (SVRI) or the cardiac index (Cl). Work from the same year by Adrie et al. [125] compared aerosolized DEA/NO with aerosolized SNP and inhaled NO, in sheep. As the NONOate has a short half-life (2.1 min), it was predicted that this would be a selective pulmonary vasodilator. However, compared with inhaled NO this was not observed, though SNP... 

Experimental design The authors investigated the ability of chloroform vapors to produce toxicity and regenerative cell proliferation in female B6C3Fj mice and male Fischer 344 rats. Groups of 5 animals were exposed to 0, 1,3, 10, 30, 100, or 300 ppm chloroform via inhalation for 6 hours a day for 7 consecutive days. Actual exposure concentrations measured for mice were 0, 1.2, 3.0, 10.0, 29.5, 101, and 288 ppm and for rats were 0, 1.5, 3.1, 10.4, 29.3, 100, and 271 ppm. Necropsies were performed on day 8. Animals were administered bromodeoxyuridine (BrdU) via implanted osmotic pump for the last 3.5 days. Cell proliferation was quantitated as the percentage of cells in S-phase (labeling index = LI) measured by the immunohistochemical detection of BrdU-labeled nuclei. 

Kinkead ER, Haun CC, Schneider MG, et al Chronic inhalation exposure of experimental animals to methylcyclohexane. Govt Reports Announcements Index (GRA I), Issue 21, 1985... 

Neuroimaging techniques assessing cerebral blood flow (CBF] and cerebral metabolic rate provide powerful windows onto the effects of ECT. Nobler et al. [1994] assessed cortical CBE using the planar xenon-133 inhalation technique in 54 patients. The patients were studied just before and 50 minutes after the sixth ECT treatment. At this acute time point, unilateral ECT led to postictal reductions of CBF in the stimulated hemisphere, whereas bilateral ECT led to symmetric anterior frontal CBE reductions. Regardless of electrode placement and stimulus intensity, patients who went on to respond to a course of ECT manifested anterior frontal CBE reductions in this acute postictal period, whereas nonresponders failed to show CBF reductions. Such frontal CBF reductions may reflect functional neural inhibition and may index anticonvulsant properties of ECT. A predictive discriminant function analysis revealed that the CBF changes were sufficiently robust to correctly classify both responders (68% accuracy] and nonresponders (85% accuracy]. More powerful measures of CBF and/or cerebral metabolic rate, as can be obtained with positron-emission tomography, may provide even more sensitive markers of optimal ECT administration. 

The determination of mandelic acid in urine is recommended as a biological exposure test for ethylbenzene. The Biological Exposure Index (BEI) Committee of the American Conference of Governmental Industrial Hygienists recommends a mandelic acid concentration in urine of 1.5 g/g creatinine [about 10 mmol/L] as a BEI for ethylbenzene exposure. BEIs represent the levels of the determinants that are most likely to be observed in biological samples collected from healthy workers exposed by inhalation to air concentrations at the level of the TLV. Urine specimens must be collected during... 

For inhalational induction of anaesthesia in children, 6% sevoflurane in 50% nitrous oxide and oxygen is probably optimal. However, some anaesthetists consider it to be inferior to halothane for the management of the irritable or constricted airway and for anaesthesia for bronchoscopy. Sevoflurane is preferred for dental procedures as there is a lower risk of cardiac arrhythmias than with halothane, especially in children. In children with congenital heart disease, whereas the cardiac index is reduced by halothane it is preserved with sevoflurane. In adults, 8% sevoflurane is well tolerated and, provides rapid induction of anaesthesia without adversely affecting haemodynamic stability. 

FDA. Guidance for industry metered dose inhaler (MDI) and dry powder inhaler (DPI) drug products. Draft guidance 1998 www.fda.gov/cder/guidance/index.htm. 

Extensive destruction of the olfactory epithelium was observed in male Fischer 344 rats exposed to 200 ppm [780 mg/m ] methyl bromide for 6 h per day for five days. By day 3, despite continued exposure, there was replacement of the olfactory epithelium by a squamous-cell layer, followed by progressive reorganization toward the normal architecture, and by week 10,75-80% of the epithelium appeared histologically normal. Olfactory epithelial-cell replication was maximal on day 3 of exposure, with a labelling index of 14.7% compared with 0.7% in the controls (Hurtt et al., 1988). Degeneration and subsequent regeneration were also observed in an inhalation experiment w ith Fischer 344 rats exposed to 175 ppm [680 mg/m ] 6 h twice, separated by a 28-day interval (Bolon et al., 1991). 

Sprague-Dawley rats and Swiss CD-I mice were exposed by inhalation to 0, 280, 1400 or 7000 ppm [800-19 530 mg/m ] isoprene for 6 h per day on seven days per week on gestational days 6-19 (rats) or 6-17 (mice) (lARC, 1994). There was no adverse effect on rat dams or other reproductive index at any dose level. The only fetal malformation observed in rats was reduced ossification of the vertebral centra, which occurred at 7000 ppm isoprene. In mice, there was reduced fetal body weight at all dose levels and decreased maternal weight gain in the 7000-ppm group. Also in the 7000-ppm group, there was an increased incidence of supernumerary ribs but no increase in fetal malformations. 

Rat LD50 is 560 mg/kg (rat) and the lowest lethal dose, LDlo is 800 mg/kg (mouse). By inhalation, the LC50 is 3 g/m3 for a 2 h period which is approximately 860 ppm (guinea pig) and the LC is 20,000 ppm/I h (rat). By skin application, the LD50 is 2830 mg/kg (rabbit). The DOT skin irritation index is 5.0 (strongly irritating). No ACGIH threshold limit values or OSHA permissible exposure limits have been established. No odor threshold is available. 

Kelly HW. Establishing a therapeutic index for the inhaled corticosteroids. Part I. Pharmacokinetic/pharmacodynamic comparison of the inhaled corticosteroids. J Allergy Clin Immunol 1998 102(4 Pt 2) S36-51. 

The Dow Fire and Explosion Index (FEI) (12) and the Dow Chemical Exposure Index (CEI) (14) are two commonly used tools that measure inherent safety characteristics. Gowland (25) reports on the use of the FEI and CEI in the development of safety improvements for a urethane plant. Tables 1 and 2 illustrate the application of the FEI and CEI in measuring inherent safety characteristics of process design options. These indices measure the inherent safety characteristics of processes in only two specific areas—fire and explosion hazards and acute chemical inhalation toxicity hazards. Other indices would be required to evaluate other types of hazards. 

Stochastic Risk Index for Hazardous Chemical Constituents. Calculation of the risk index for all hazardous chemicals in the waste that cause stochastic effects is performed in the same manner as in the previous examples for radioactive wastes. The calculated risk for each such substance, based on the assumed exposure scenario, is summed and then divided by the acceptable lifetime risk of 10 3 for classification as low-hazard waste (see Table 7.1). The risk for each chemical is calculated by multiplying the arithmetic mean of the concentration in the waste given in Table 7.5 by the intake rate from ingestion, inhalation, or dermal absorption per unit concentration discussed in Section 7.1.7.3 and 10 percent of the appropriate slope factor in Table 7.7 (see Section 7.1.7.1) adjusted for the exposure time. Since the slope factors assume chronic lifetime exposure, they must be reduced by a factor of 70 based on the assumption that the exposure scenario at the hazardous waste site occurs only once over an individual s lifetime. In addition, a simplifying assumption is made that whenever more than one slope factor is given for a hazardous substance in Table 7.7, the higher value was applied to the total intake rate by all routes of exposure of about 4 X 10 8 mg (kg d) 1 per ppm. This assumption should be conservative. 

As an alternative to the assumption of a one-time exposure for 1,000 h at the time of facility closure, permanent occupancy of a disposal site following loss of institutional control could be assumed (see Section 7.1.3.4). The assumption of chronic lifetime exposure would affect the analysis for hazardous chemicals that induce deterministic effects only if estimated intakes due to additional pathways, such as consumption of contaminated vegetables or other foodstuffs produced on the site, were significant. Based on the results for lead in Table 7.8, an intake rate from additional pathways of about 50 percent of the assumed intake rate by soil ingestion, inhalation, and dermal absorption would be sufficient to increase the deterministic risk index above unity. The importance of additional pathways was not investigated in this analysis, but they clearly would warrant consideration. The increase in exposure time during permanent occupancy does not otherwise affect the analysis for chemicals that induce deterministic effects, provided RfDs are appropriate for chronic exposure, because chronic RfDs incorporate an assumption that the levels of contaminants in body organs relative to the intake rate (dose) are at steady state. 

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