RESUMEN
In mice, inhalation of formic, acetic, propionic and butyric acid caused a rapid decrease in the respiratory rate, which decreased to a stable level during the remaining part of the 30â¯min exposure period; this was due to sensory irritation. The concentration decreasing the respiratory rate (RD) by 50% (RD50) was 438, 308, 386 and 285â¯ppm, respectively, which allowed an adequate prediction of the Threshold Limit Values. In mice inhaling through a tracheal cannula, bypassing the trigeminal nerves, caused a slower decrease in respiratory rate due to pulmonary irritation. In the low concentration range, the pulmonary irritation response was less pronounced than the sensory irritation response. As the response in the normal (non-cannulated) mice was not influenced by pulmonary irritation, sensory irritation is the key effect, presumably due to the scrubbing effect of the upper airways, preventing access to the lungs. The activated receptors were in a non-lipophilic (hydrophilic) environment, from where the receptors may be activated by means of liberated protons. At the RD0, formic acid may, at least partly, activates ASIC, TRPV1 and TRPA1 receptors, whereas acetic, propionic and butyric acid may activate ASIC and TRPA1 receptors, based on the estimated pH in the mucus layer.
Asunto(s)
Ácido Acético/efectos adversos , Ácido Butírico/efectos adversos , Formiatos/efectos adversos , Irritantes/efectos adversos , Respiración/efectos de los fármacos , Canales Iónicos Sensibles al Ácido/metabolismo , Administración por Inhalación , Animales , Gases/efectos adversos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Ratones , Canal Catiónico TRPA1/metabolismo , Canales Catiónicos TRPV/metabolismoRESUMEN
Sensory irritation of eyes and upper airways is an important endpoint for setting occupational exposure limits (OELs) and indoor air guidelines. Sensory irritants cause a painful burning, stinging and itching sensation. Controlled chamber studies are the "golden standard" for evaluations. Well conducted workplace studies offer another possibility. For generalization, the number of participants and their age, smoking, gender, and prior exposure, experience and mood has to be considered. Exposure assessments have to be reliable and exposure duration sufficiently long to establish time-response relationships. A potential confounding by odour has to be assessed. For workplace exposures, mixed exposure and healthy worker effects have to be evaluated. The "Alarie test" is the only validated animal bioassay for prediction of sensory irritation in humans. The mouse bioassay uses the trigeminal reflex-induced decrease in the respiratory rate. The 50% decrease (RD50) has been correlated with OELs set for sensory irritants; predicted OELs for sensory irritants are 0.03xRD50. Evaluation of the bioassay comprises the number of mice and the strain, the reliability of the exposure concentrations and exposure-response relationships, and the similar mode-of-action in mice and humans. These approaches can be used for quality assurance of reported data to set air quality guidelines.
Asunto(s)
Contaminantes Ocupacionales del Aire/efectos adversos , Aire/normas , Ojo/efectos de los fármacos , Irritantes/toxicidad , Sistema Respiratorio/efectos de los fármacos , Valores Limites del Umbral , Contaminantes Ocupacionales del Aire/normas , Contaminación del Aire Interior/efectos adversos , Contaminación del Aire Interior/prevención & control , Animales , Bioensayo/métodos , Guías como Asunto , Humanos , Ratones , Odorantes , Reproducibilidad de los Resultados , Respiración/efectos de los fármacos , Factores de Tiempo , Pruebas de Toxicidad/métodos , Visión Ocular/efectos de los fármacosRESUMEN
INTRODUCTION: The total number of asthmatic patients in Denmark in the year 2000 was about 300,000 out of a total population of 5.3 million. The aim of this study was to evaluate cost-of-illness for all asthma patients in Denmark for the year 2000. MATERIAL AND METHODS: Direct and indirect costs were obtained from two Danish studies, Sørensen et al [1] and Søndergaard et al [2]. These studies allowed calculation of direct and indirect costs per year per patient. The costs were estimated in 2000-prices. Estimated cost of drugs was extrapolated to the population of asthmatics for which the actual cost was available from nation-wide statistics. The estimated costs of drugs were compared with the actual costs. As costs of asthma increase with the severity of the disease, a correction factor was obtained from the ratio between the actual costs of drugs and the estimated costs. This factor was used to normalise the subpopulations to reflect the entire group of asthma patients. RESULTS: The total costs of asthma were estimated at 1.9 billion DKK (745 DKK = 100 EURO, year 2000), the direct costs to medicine and treatment were estimated at 1.1 billion DKK and the indirect costs to sick-leave and early retirement pension were estimated at 0.8 billion DKK. Due to the differences in the estimates given by the sources, especially on the indirect costs, we obtained a range of the total cost from 1.4 billion DKK to 2.9 billion DKK in a sensitivity analysis. DISCUSSION: The estimated cost is consistent with data from other national and international sources, suggesting that our estimate be close to the real cost. Costs due to asthma may be expected to increase due to the increase in prevalence of asthma.