Toxicokinetic and mass balance of morpholine in rats.

Morpholine (MOR) has a broad spectrum of use and represents high risk of human exposure. Ingested MOR can undergo endogenous N-nitrosation in the presence of nitrosating agents forming N-nitrosomorpholine (NMOR), classified as possible human carcinogen by the International Agency for Research on Cancer.In this study, we evaluated the MOR toxicokinetics in six groups of male Sprague-Dawley rats orally exposed to 14C-radiolabelled MOR and NaNO2. The major urinary metabolite of MOR, N-nitrosohydroxyethylglycine (NHEG), was measured through HPLC as an index of endogenous N-nitrosation. Mass balance and toxicokinetic profile of MOR were determined by measuring radioactivity in blood/plasma and excreta.MOR reached maximum blood concentration 30 minutes after administration. Elimination rate was rapid (70% in 8h). Most of the radioactivity was excreted in the urine (80.9 ± 0.5%) and unchanged 14C-MOR was the main compound excreted in the urine (84% of the dose recovered). 5.8% of MOR is not absorbed and/or was not recovered.Endogenous nitrosation of MOR was demonstrated by the detection of NHEG. The maximum conversion rate found was 13.3 ± 1.2% and seems to be impacted by the MOR/NaNO2 ratio.These results help refining our knowledge of the endogenous production of NMOR, a possible human carcinogen.

Probabilistic Analysis of a French Legionellosis Outbreak Shows Potential Role of Wastewater Basin.

Based on the data from a French outbreak of legionellosis, a probabilistic approach was developed to analyze and assess the potential role of several suspected sources of contamination. Potential dates of exposure of all cases were determined using back-calculation, using two probability distribution functions to model incubation period. A probabilistic analysis and risk assessment were then used to determine the most probable sources of contamination for each wave of the outbreak. The risk assessment was based on parameters representing emission and dispersion of Legionella: level and duration of emission; aerosol dispersion capacity; and probability of potential exposure for each patient. Four types of facilities containing the Legionella epidemic strain were analyzed: cooling towers, aerated wastewater basins, high pressure water cleaners, and car wash stations. The results highlighted the potential role of an aerated wastewater basin in the outbreak in addition to cooling towers. The role of high-pressure water cleaners and car wash stations appeared to be non-significant. This study also reveals the lack of knowledge on facility parameters that can be useful for microbial risk assessments. This type of probabilistic analysis can be used to quantitatively assess the risk for various facilities in order to manage a legionellosis outbreak.

Repeated nitrogen dioxide exposures and eosinophilic airway inflammation in asthmatics: a randomized crossover study.

BACKGROUND: Nitrogen dioxide (NO2), a ubiquitous atmospheric pollutant, may enhance the asthmatic response to allergens through eosinophilic activation in the airways. However, the effect of NO2 on inflammation without allergen exposure is poorly studied. OBJECTIVES: We investigated whether repeated peaks of NO2, at various realistic concentrations, induce changes in airway inflammation in asthmatics. METHODS: Nineteen nonsmokers with asthma were exposed at rest in a double-blind, crossover study, in randomized order, to 200 ppb NO2, 600 ppb NO2, or clean air once for 30 min on day 1 and twice for 30 min on day 2. The three series of exposures were separated by 2 weeks. The inflammatory response in sputum was measured 6 hr (day 1), 32 hr (day 2), and 48 hr (day 3) after the first exposure, and compared with baseline values measured twice 10-30 days before the first exposure. RESULTS: Compared with baseline measurements, the percentage of eosinophils in sputum increased by 57% after exposure to 600 ppb NO2 (p = 0.003) but did not change significantly after exposure to 200 ppb. The slope of the association between the percentage of eosinophils and NO2 exposure level was significant (p = 0.04). Eosinophil cationic protein in sputum was highly correlated with eosinophil count and increased significantly after exposure to 600 ppb NO2 (p = 0.001). Lung function, which was assessed daily, was not affected by NO2 exposure. CONCLUSIONS: We observed that repeated peak exposures of NO2 performed without allergen exposure were associated with airway eosinophilic inflammation in asthmatics in a dose-related manner.

Outcome of occupational electrical injuries among French electric company workers: a retrospective report of 311 cases, 1996-2005.

This study reviewed records of all electrical incidents involving work-related injury to employees Electricité de France (EDF) from 1996 through 2005 and analysed data for 311 incidents. The results are compared with 1231 electrical incidents that occurred during 1970-1979 and 996 incidents during 1980-1989. A total of 311 electrical incidents were observed. The medical consequences of electrical incident remain severe and particularly, the current fatality rate (3.2%) is similar to that recorded in the 1980s (2.7%) and 1970s (3.3%). Among individuals with non-fatal incidents, any change has occurred in the prevalence of permanent functional sequelae (23.6% in the 1970s vs. 27.6% in the 1980s and 32.5% currently). An increase in the incidence of neuropsychiatric sequelae (5.4% in the 1980s vs. 13% currently) has been observed and they are now the second most common type of sequelae after those directly related to burns. Among the neurological sequelae, peripheral nervous system disorders are the most common, as observed in the 1980s. Since the definition of post-traumatic stress disorder (PTSD) has changed between the two periods, we can only report that the current prevalence of PTSD is 7.6%. This study emphasises the need for specific management of neurological and psychological impairments after electrical injuries, including especially early recognition and initiation of effective treatment.

Effect of formaldehyde on asthmatic response to inhaled allergen challenge.

BACKGROUND: Exposure to formaldehyde may lead to exacerbation of asthma. OBJECTIVES: Our aim in this study was to investigate whether exposure to a low level (500 microg/m(3)) of formaldehyde enhances inhaled allergen responses. METHODS: Twelve subjects with intermittent asthma and allergy to pollen were exposed, at rest, in a double-blind crossover study to either formaldehyde or purified air for 60 min. The order of exposure to formaldehyde and air-only was randomized, and exposures were separated by 2 weeks. We also performed an allergen inhalation challenge after each exposure. Airway responsiveness to methacholine and lower airway inflammation (induced sputum) were assessed 8 hr after allergen challenge. RESULTS: The median dose of allergen producing a 15% decrease in forced expiratory volume in 1 sec (PD(15)FEV(1)) was 0.80 IR (index of reactivity) after formaldehyde exposure compared with 0.25 IR after air-only exposure (p = 0.06). Formaldehyde exposure did not affect allergen-induced increase in responsiveness to methacholine (p = 0.42). We found no formaldehyde-associated effect on the airway inflammatory response, in particular the eosinophilic inflammatory response, induced by the allergen challenge 8 hr before. CONCLUSION: In this study, exposure to 500 microg/m(3) formaldehyde had no significant deleterious effect on airway allergen responsiveness of patients with intermittent asthma; we found a trend toward a protective effect.

An enzyme-linked immunosorbent assay (ELISA) for the identification of Naegleria fowleri in environmental water samples.

Naegleria fowleri, a free-living amoeba, is the causative agent of primary amoebic meningoencephalitis, a fatal human disease of the central nervous system often contracted after swimming in fresh water. Identifying sites contaminated by N. fowleri is important in order to prevent the disease. An Enzyme-Linked ImmunoSorbent Assay (ELISA) has been developed for the specific identification of N. fawleri in primary cultures of environmental water samples. Of 939 samples isolated from artificially heated river water and screened by ELISA, 283 were positive. These results were subsequently confirmed by isoelectric focusing, the established reference method. A sensitivity of 97.4% and a specificity of 97% were obtained. These results indicate that this ELISA method is reliable and can be considered as a powerful tool for the detection of N. fowleri in environmental water samples.

Development of a nested PCR assay to detect the pathogenic free-living amoeba Naegleria fowleri.

Naegleria fowleri is the causative agent of primary amoebic meningoencephalitis, a fatal disease of the central nervous system that is acquired while swimming or diving in freshwater. A cDNA clone designated Mp2C15 obtained from N. fowleri was used as a probe to distinguish N. fowleri from other free-living amoebae. The Mp2C15 probe hybridized to genomic DNA from pathogenic N. fowleri and antigenically related non-pathogenic N. lovaniensis. Mp2C15 was digested with the restriction enzyme XbaI, resulting in two fragments, Mp2C15.G and Mp2C15.P. Four species of Naegleria and four species of Acanthamoeba were examined for reactivity with Mp2C15.P. Mp2C15.P was specific for N. fowleri and was used in the development of a nested PCR assay which is capable of detecting as little as 5 pg of N. fowleri DNA or five intact N. fowleri amoebae. In summary, a rapid, sensitive, and specific assay for the detection of N. fowleri was developed.