Research activities sought development of a method to adjust exposure limits for 694 substances for unusual work schedules. A consensus was established on the basic toxicological principle for adjustment; criteria for adjustment were selected by a panel of scientists coordinated by a committee of international experts and supported by toxicokinetic modeling; and a group of toxicologists attributed primary health effects and related adjustment category to each substance. A consensus among scientists and employers' and workers' representatives was established on the protocol of the application, in the field, of the adjusted exposure limits. The guiding toxicological principle for adjusting exposure standards to unusual work schedules is to guarantee an equivalent degree of protection for workers with unusual schedules as for workers with a conventional schedule of 8 hours per day, 5 days per week. The process of the adjustment is inspired from the Occupational Safety and Health Administration logic for attribution of primary health effects and adjustment categories ranging from no adjustment to daily or weekly adjustments. The adjusted exposure limits are calculated according to Haber's rule. Decisions on attribution of adjustment categories for the following toxicological effects were reached: respiratory sensitizers (asthma); skin sensitizers; tissue irritants versus tissue toxicants; methemoglobinenia-causing agents; cholinesterase inhibitors; and reproductive system toxicants and teratogens. A simple procedure is presented to facilitate the calculation, application, and interpretation of the adjusted exposure limits.

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Influence of aluminum treatments on pulmonary retention of quartz in sheep silicosis.

Previous experiments with the sheep model of silicosis have demonstrated a reduction of the pathological activity of quartz after treatments with aluminum lactate (Al-lac), such as Al-lac pretreatment of intratracheally injected quartz or Al-lac inhalation of quartz-exposed animals. Preliminary data also suggested a more effective alveolar clearance of quartz treated with Al-lac. The present study was undertaken to fully document the effect of Al-lac treatments on the pulmonary retention of quartz. Sheep (on average, 27 per group) received a single injection in the tracheal lobe of either 100 mg/100 mL of alpha-quartz, 100 mg/100 mL of alpha-quartz followed by Al-lac inhalations at 1-month intervals, or 100 mg/100 mL of alpha-quartz Al-lac pretreated in vitro. Samples of lung parenchyma were analyzed at 2, 6, and 10 months after the injection. The quartz concentration in each sample was measured using the X-ray diffraction method. The concentrations were expressed in micrograms of quartz per milligram of dry lung parenchyma. The geometric mean concentrations in each of the three groups at 2 months were statistically different (ANOVA of the log values; p = .016) as well as at 6 months (ANOVA of the log values; p = .001). Al-lac clearly reduced the pulmonary retention of quartz. Both modalities of Al delivery were equally effective in clearing quartz up to 2 months, which may explain the documented reduction in pathological activities after in both forms of therapy. However, quartz soaked in Al-Lac solution was more effective than inhalation of Al-lac after quartz exposure. The half-life of both native quartz and quartz Al-lactate inhaled was 5.05 and 4.99 months, respectively, while it was 3.1 months for Al-treated quartz. Al-lac inhalations after the second month of exposure do not significantly affect the rate of clearance of deposited quartz.

Animals↗

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[A specific domain (the omega 1 site) of the GABA(A) receptor may be implicated in the hypnotic effects of zolpidem].

Zolpidem (Stilnox) is a new hypnotic belonging to the imidazopyridine series. In animals, in contrast to the benzodiazepines which alter sleep architecture, zolpidem induces a physiological pattern of deep sleep. Zolpidem also differs from the benzodiazepines by its hypnoselective profile (its sedative effects are seen at doses much lower than those needed for anticonvulsant or myorelaxant effects). In this review, the authors analyze the hypothesis that the hypnoselective profile of zolpidem is linked to its interaction with a specific domain, the omega 1 site, of the GABAA receptor complex. This hypothesis is supported by: 1) the high selectivity of zolpidem for omega 1 as compared to omega 2 sites and its high intrinsic activity, 2) autoradiographic studies of the regional distribution of omega 1 and omega 2 sites in the human and non-human primate brains showing that omega 1 sites are located preferentially in sensorimotor cortical regions whereas omega 2 sites predominate in the limbic system and spinal cord. The selectivity of zolpidem for omega 1 sites could also account for the fact that in contrast to the benzodiazepines, this compound does not alter memory functions at hypnotic doses.

Animals↗

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[Cerebral protecting activity of 1-eburnamonine studied on 3 models of acute hypoxic agression. Comparison with vincamine].

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Animals↗

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Tentative explanatory variable of lung dust concentration in gold miners exposed to crystalline silica.

INTRODUCTION: The first objective of the study was to investigate the relationships between quantitative lung mineral dust burdens, dust exposure history, and pathological fibrosis grading in silicotic workers. The second objective was to evaluate the association between particle size parameters, concentration of retained silica particles and the severity of the silicosis. Sixty-seven paraffin-embedded lung tissue samples of silicotic patients were analyzed. The cases of silicosis included 39 non-lung cancer patients and 28 patients with lung cancer. All of the cases were gold miners in the Province of Ontario, Canada. MATERIAL AND METHODS: Particles, both angular and fibrous, were extracted from lung parenchyma by a bleach digestion method, mounted on copper microscopic grids by a carbon replica technique, and analyzed by transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS). Quartz concentration was also determined by X-ray diffraction (XRD) on a silver membrane filter after the extraction from the lung parenchyma. RESULTS: Total particles, silica, clay, and quartz also increase in concentration with increased age at death, although the trends are not statistically significant. Quartz concentration has a statistically significant correlation with the silicosis severity score (r = +0.45, p < 0.001), with the geometric mean concentration increasing from 2.24 micrograms/mg in the group having silicosis severity score less than 1 to 4.80 micrograms/mg in group with highest score. Quartz concentration is the only significant explanatory variable of the silicosis severity with a regression coefficient of +0.41 (p < 0.001). CONCLUSION: Among several dust exposure variables extracted from the work history of the miners, the calendar year of first exposure was the primary significant determinant of lung retained total particles, silica, and clay minerals, except for quartz. A statistically significant linear relationship between lung quartz concentration and silicosis severity in the gold miners was observed (p < 0.001). Among the several types of lung particles detected, quartz was the only significant determinant of the silicosis severity in the gold miners in this study and vice versa, although it explained only 20% of the variation in the severity. This study suggested no significant linear relationship between the duration of dust exposure and the lung burden of any particle types in the gold miners.

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