RESUMEN
OBJECTIVES: This study employed computational fluid dynamics (CFD), physiologically based toxicokinetics (PBTK), and statistical modeling to reconstruct exposure to methylene diphenyl-4,4'-diisocyanate (MDI) aerosol. By utilizing a validated CFD model, human respiratory deposition of MDI aerosol in different workload conditions was investigated, while a PBTK model was calibrated using experimental rat data. Biomonitoring data and Markov Chain Monte Carlo (MCMC) simulation were utilized for exposure assessment. RESULTS: Deposition fraction of MDI in the respiratory tract at the light, moderate, and heavy activity were 0.038, 0.079, and 0.153, respectively. Converged MCMC results as the posterior means and prior values were obtained for several PBTK model parameters. In our study, we calibrated a rat model to investigate the transport, absorption, and elimination of 4,4'-MDI via inhalation exposure. The calibration process successfully captured experimental data in the lungs, liver, blood, and kidneys, allowing for a reasonable representation of MDI distribution within the rat model. Our calibrated model also represents MDI dynamics in the bloodstream, facilitating the assessment of bioavailability. For human exposure, we validated the model for recent and long-term MDI exposure using data from relevant studies. CONCLUSION: Our computational models provide reasonable insights into MDI exposure, contributing to informed risk assessment and the development of effective exposure reduction strategies.
Asunto(s)
Hidrodinámica , Isocianatos , Humanos , Ratas , Animales , Isocianatos/toxicidad , Toxicocinética , AerosolesRESUMEN
BACKGROUND: Noise-induced hearing loss (NIHL) is one the major causes of acquired hearing loss in developed countries. Noise can change the pattern of gene expression, inducing sensorineural hearing impairment. There is no investigation on the effects of noise frequency on the expression of GJB2 and SLC26A4 genes involved in congenital hearing impairment in cochlear tissue. Here we investigated the impacts of white and purple noise on gene expression and pathologic changes of cochlear tissue. METHODS: In this study, 32 adult male Westar rats were randomly divided into experimental groups: WN, animals exposed to white noise with a frequency range of 100-20000 Hz; PN, animals exposed to purple noise with a frequency range of 4-20 kHz, and control group, without noise. The experimental groups were exposed to a 118-120 dB sound pressure level for 8 h per 3 days and 6 days. 1 h and 1 week after termination of noise exposure, cochlear tissue was prepared for pathology and gene expression analysis. RESULTS: Both white and purple noises caused permanent damage to the cortical, estrosilica systems of hair cells and ganglion of the hearing nerve. GJB2 and SLC26A4 were downregulated in both groups exposed with white and purple noise by increasing the time of noise exposure. However, differences are notably more significant in purple noise, which is more intensified. Also, 1 weak post noise exposure, the downregulation is remarkably higher than 1 h. CONCLUSIONS: Our findings suggest that downregulation of GJB2 and SLC26A4 genes are associated with pathological injury in response to noise exposure in cochlear tissue. It would be suggested the demand for assessment of RNA and protein expression of genes involved in noise-induced hearing loss and subsequently the practice of hearing protection programs.