Carcinogenicity and genotoxicity of ethylene oxide : new aspects and recent advances

Long-term inhalation studies in rodents have presented unequivocal evidence of experimental carcinogenicity of ethylene oxide, based on the formation of malignant tumors at multiple sites. However, despite a considerable body of epidemiological data only limited evidence has been obtained of its carcinogenicity in humans. Ethylene oxide is not only an important exogenous toxicant, but it is also formed from ethylene as a biological precursor. Ethylene is a normal body constituent; its endogenous formation is evidenced by exhalation in rats and in humans. Consequently, ethylene oxide must also be regarded as a physiological compound. The most abundant DNA adduct of ethylene oxide is 7-(2-hydroxyethyl)guanine (HOEtG). Open questions are the nature and role of tissue-specific factors in ethylene oxide carcinogenesis and the physiological and quantitative role of DNA repair mechanisms. The detection of remarkable individual differences in the susceptibility of humans has promoted research into genetic factors that influence the metabolism of ethylene oxide. With this background it appears that current PBPK models for trans-species extrapolation of ethylene oxide toxicity need to be refined further. For a cancer risk assessment at low levels of DNA damage, exposure-related adducts must be discussed in relation to background DNA damage as well as to inter- and intraindividual variability. In rats, subacute ethylene oxide exposures on the order of 1 ppm (1.83 mg/m3) cause DNA adduct levels (HOEtG) of the same magnitude as produced by endogenous ethylene oxide. Based on very recent studies the endogenous background levels of HOEtG in DNA of humans are comparable to those that are produced in rodents by repetitive exogenous ethylene oxide exposures of about 10 ppm (18.3 mg/m3). Experimentally, ethylene oxide has revealed only weak mutagenic effects in vivo, which are confined to higher doses. It has been concluded that long-term human occupational exposure to low airborne concentrations to ethylene oxide, at or below current occupational exposure limits of 1 ppm (1.83 mg/m3), would not produce unacceptable increased genotoxic risks. However, critical questions remain that need further discussions relating to the coherence of animal and human data of experimental data in vitro vs. in vivo and to species-specific dynamics of DNA lesions.

Application of higher-order spectra for automated grading of diabetic maculopathy

Diabetic macular edema (DME) is one of the most common causes of visual loss among diabetes mellitus patients. Early detection and successive treatment may improve the visual acuity. DME is mainly graded into non-clinically significant macular edema (NCSME) and clinically significant macular edema according to the location of hard exudates in the macula region. DME can be identified by manual examination of fundus images. It is laborious and resource intensive. Hence, in this work, automated grading of DME is proposed using higher-order spectra (HOS) of Radon transform projections of the fundus images. We have used third-order cumulants and bispectrum magnitude, in this work, as features, and compared their performance. They can capture subtle changes in the fundus image. Spectral regression discriminant analysis (SRDA) reduces feature dimension, and minimum redundancy maximum relevance method is used to rank the significant SRDA components. Ranked features are fed to various supervised classifiers, viz. Naive Bayes, AdaBoost and support vector machine, to discriminate No DME, NCSME and clinically significant macular edema classes. The performance of our system is evaluated using the publicly available MESSIDOR dataset (300 images) and also verified with a local dataset (300 images). Our results show that HOS cumulants and bispectrum magnitude obtained an average accuracy of 95.56 and 94.39 % for MESSIDOR dataset and 95.93 and 93.33 % for local dataset, respectively.

Indoor Air Quality in Naturally Ventilated Italian Classrooms

Characterization of indoor air quality in school classrooms is crucial to children’s health and performance. The present study was undertaken to characterize the indoor air quality in six naturally ventilated classrooms of three schools in Cassino (Italy). Indoor particle number, mass, black carbon, CO2 and radon concentrations, as well as outdoor particle number were measured within school hours during the winter and spring season. The study found the concentrations of indoor particle number were influenced by the concentrations in the outdoors; highest BC values were detected in classrooms during peak traffic time. The effect of different seasons’ airing mode on the indoor air quality was also detected. The ratio between indoor and outdoor particles was of 0.85 ± 0.10 in winter, under airing conditions of short opening window periods, and 1.00 ± 0.15 in spring when the windows were opened for longer periods. This was associated to a higher degree of penetration of outdoor particles due to longer period of window opening. Lower CO2 levels were found in classrooms in spring (908 ppm) than in winter (2206 ppm). Additionally, a greater reduction in radon concentrations was found in spring. In addition, high PM10 levels were found in classrooms during break time due to re-suspension of coarse particles. Keywords: classroom; Ni/Nout ratio; airing by opening windows; particle number