Asthma-like syndrome in school children after accidental exposure to xylene and methylene diphenyl diisocyanate.

BACKGROUND AND PURPOSE: We assessed the signs and symptoms, pulmonary function changes and residual chemical body burden of school children in the vicinity of an accidental exposure to volatile xylene and methylene diphenyl diisocyanate (MDI). METHODS: After the exposure episode, children with significant symptoms after MDI exposure (e.g., dizziness, nausea, sore throat, and breathing difficulties) were sent to nearby emergency medical units for evaluation and admission if necessary. Clinical work-up included pulmonary function tests and measurement of residual MDI in the body by high-performance liquid chromatography analysis of urine. RESULTS: 203 students appeared to develop symptoms associated with contaminant exposure, and 173 affected students were sent to nearby emergency units. In the subsequent surveillance, 22 of 203 affected students (10.8%) revealed a positive history of asthma, which was strongly correlated with the incidence of dyspnea arising from the incident. For children with no previous history of asthma, 60.8% (110 of 181) complained of dyspnea during the episode, and 16.2% required inhaled bronchodilator therapy at the emergency medical units for relief of wheezing symptoms. In a simulation, we found the raw material used for tract surfacing, primarily MDI dissolved in xylene, to be present at a concentration (870 ppm w/w) more than 8000-fold the level defined as safe for a working environment. CONCLUSIONS: We have detected a direct cause-effect relationship between the accidental spillage of MDI and the appearance of an acute asthma-like syndrome among previously unexposed school children.

Cryopreservation of human limbal stem cells ex vivo expanded on amniotic membrane.

PURPOSE: After cornea transplantation, the donor's limbal zone is currently discarded as medical waste. However, the limbal zone is rich in limbal stem cells and can be used in therapeutic applications of limbus loss. This study aimed to increase the availability of limbal stem cells and develop the optimal conditions of cryopreservation for ex vivo expanded limbal stem cells. METHODS: Pieces of the limbus were cultured on amniotic membrane (AM) to outgrow limbal stem cells as cell sheets for 3 weeks. Different formulas of cryoprotectants were tested to preserve the expanded cell sheets in liquid nitrogen. Before and after cryopreservation, expanded cell sheets were assessed for cellular characteristics by viability, histologic examination, and expression of ABCG2, vimentin, and keratin 3. RESULTS: Expanded cell sheets usually exhibited 3-6 stratified layers after 3-week culture on AM and expressed specific markers of ABCG2 and vimentin for limbal stem cells. The effects of cryopreservation with different cryoprotectants were analyzed by histopathology, stem cell markers, and cell viability. The results showed that the optimal formula of cryoprotectants for expanded limbal cell sheets was 60% Dulbecco modified Eagle medium, 30% fetal bovine serum, and 10% dimethyl sulfoxide. After 8-week cryopreservation in liquid nitrogen, the characteristics of limbal stem cells were maintained, and the average viability of thawed cells was 53.8% +/- 5.8%. CONCLUSIONS: These results showed that limbal stem cells expanded on AM could be cryopreserved and provide a promising source without delay, if banking, for patients with limbal stem cell deficiency in the future.

Urinary excretion of toluene diisocyanates in rats following dermal exposure.

Toluene diisocyanates (TDI) are commonly used in polyurethane (PU)-related products. TDIs have been documented as the leading cause of occupational asthma. Skin exposure to TDI in the workplace is common. However, no studies in the literature have investigated the exact biomarker concentration profile for skin TDI absorption through any in vivo animal studies. In this study a rat model was used to evaluate the TDI skin absorption to explore the dose-response pattern and to determine the kinetic characteristics of urinary toluene diamine (U-TDA) during skin exposure. TDIs were topically exposed on the dorsum of rat skin at 0.2%, 1% and 5%. Consecutive urine samples were collected for 6 days and U-TDA were analysed using GC/ECD. It was demonstrated in this rat study that absorption of 2,4- and 2,6-TDI through skin contact is possible. A clear dose-dependent skin absorption relationship for 2,4- and 2,6-TDI was demonstrated by the AUC, Cmax findings and accumulative amounts (r > or = 0.968). U-TDA concentration profiles in 6-day consecutive urine samples fit well in the first-order kinetics, although higher order kinetics could not be excluded for the high dose. The apparent half-lives for excretory urinary TDA were about 20 h consistent at various skin exposures. It is concluded that skin absorption of TDI was confirmed in a rat model and a clear dose-dependent skin absorption relationship for 2,4- and 2,6-TDI was demonstrated. Excretory U-TDA concentrations in 6-day consecutive urine samples via skin exposure reveal the first-order kinetics and the half-lives were about 20 h.

Microwave-assisted acid hydrolysis of toluene diamine conjugates in urine samples for biomarkers in toluene diisocyanate analysis.

Toluene diamines (TDAs) in urine have been used widely to determine the amount of toluene diisocyanate (TDI) absorbed by humans. Conventional hydrolysis to prepare a sample of urine takes approximately 16h. An attempt is made to apply microwave-assisted heating (MAH) to reduce the duration of analysis. Urine collected from rats exposed to a mixture of 2,4- and 2,6-TDI was diluted with non-exposed human urine 1/1250-, 1/500- and 1/250-fold. The urine samples were hydrolyzed by both conventional heating and MAH. The hydrolysis efficiency obtained using MAH significantly exceeded that obtained using conventional heating. Hydrolysis by MAH required only 20min, 48 times faster than with conventional heating. The use of the MAH method in hydrolysis was demonstrated to be reproducible, timesaving and efficient technique in measuring the concentration of urinary TDAs.

Toluene diisocyanate concentration investigation among TDI-related factories in Taiwan and their relations to the type of industry.

OBJECTIVES: To determine nationwide 2,4- and 2,6-toluene diisocyanates (TDI) concentrations among polyurethane (PU) resin, PU foam, and other TDI-related industries in Taiwan. The ratios of 2,4-/2,6-TDI and the noncarcinogenic risk among these three industries were also investigated. METHOD: Personal and fixed-area monitoring of TDI concentrations as well as questionnaires were performed for 26 factories in Taiwan. The modified OHSA 42 method was applied in sampling and analysis. Noncarcinogenic hazard index was estimated for these three industries based on the average concentration measurements. RESULTS: Significant differences of TDI concentrations were found among the three industry categories. For personal monitoring, PU foam was found to have the highest TDI levels [18.6 (+/-33.6) and 22.1 (+/-42.3) ppb for 2,4- and 2,6-TDI], Others average [8.3 (+/-18.9) and 10.2 (+/-17.2) ppb], and PU resin lowest [2.0 (+/-3.5) and 0.7 (+/-1.2) ppb]. The estimated average hazard indices were found to be 310-3310. CONCLUSION: A substantial percentage of airborne TDI concentrations among in Taiwan industries exceeded current TDI occupational exposure limit, and significant difference of TDI levels were found among the three industry categories. The control remedy for the tasks of charging and foaming should be enforced with the highest priority. A separate 2,6-TDI exposure standard is warranted.