Vapour dosing

Therefore, in order to meter small quantities of materials in vacuo, the use of glass phials or calibrated break-seals, described in Sections 3.1.2 and 3.1.3. respectively, is recommended. Even smaller quantities of moderately volatile materials can be dosed by means of calibrated vapour-dosing bulbs (see Section 3.1.5). 

LED, lowest effective dose HID. highest ineffective dose in-vitro tests, pg/nilNG, not given Cells were exposed to allyl chloride vapour dose = ug/nil, in air. 

Para and meta-Xylene adsorption has been performed in a mlorobalance connected to a vacuum manifold (ultimate vacuum 10 mbar). Before the adsorption measurement each sample has been treated in situ at 573K up to constant weight. The temperature has been then lowered to 303K, the xylene Isomer vapour dosed on the sample and the weight Increase due to the adsorption recorded. 

Toxicity rating Commonly used term LDso Single oral dose for rats (g/kg) 4hr Vapour exposure causing 2 to 4 deaths in 6-rat group (ppm) LDso Skin for rabbits (g/kg) Probable lethal dose for humans... 

Toxic effects of expositions are calculated for a variety of exposures and effect combinations, assuming a probabilistic dose-effect relationship. Lethal and incapacitating responses (e.g. respiratory effects, topical skin effects or incapacitating eye effects) of varying degrees of severity are addressed. The model also distinguishes between effects resulting from vapour exposure and from exposures to liquid droplets. These primary effect probabilities are subsequently combined to afford overall casualty probabilities for lethality, severe incapacitation and incapacitation due to topical eye effects. 

Methyl fluoroacetate, a mobile liquid, has an extremely faint odour. Animals did not usually exhibit any symptoms while being exposed to lethal concentrations of this vapour, and no obvious effects were noted until some 30-60 min. (depending upon the concentration) after exposure. Violent convulsions then took place and death usually followed within a few hours. For rabbits and guinea-pigs the lethal concentration (l.c. 50) for a 10 min. exposure was of the order of 0-1 mg./l. Mice were rather more resistant. Intravenous injection produced symptoms similar to those displayed after exposure to the vapour. Even with large doses a delayed action was observed. The l.d. 50 for rabbits (intravenously) was found to be about 0-25 mg./kg. 

Fig. 3.11. Schematic drawing of assembly for dosing water into phials by volume of vapour. A reservoir containing distilled, deaerated water, B dosing bulb of known volume, P breakable phials, C container holding MejSiCl, D thermostat bath.

Desflurane is a fluorinated methyl ethyl ether identical to isoflurane except for the substitution of a chlorine by a fluorine atom (Figure 3.2). It is the least soluble of all the volatile anaesthetics with a similar blood/gas solubility to nitrous oxide (0.42). It is non-flammable under all clinical conditions. The vapour pressure of desflurane approaches 1 atm at 23°C making controlled administration impossible with a conventional vaporiser. A desflurane vaporiser is an electronically controlled pressurised device that delivers an accurately metered dose of vaporised desflurane into a stream of fresh gases passing through it. The MAC of desflurane (6.5% in adults) is the highest of any modern fluorinated agent but in common with these the value decreases in the elderly and in other circumstances (see below). 

Rat. In a study previously reported in an abstract, four groups of 86 male and 86 female Sprague-Dawley rats, five weeks of age, were administered -butyl acrylate (purity, > 99.5% main impurities, butyl propionate and isobutyl acrylate) by whole-body inhalation at concentrations of 0, 15, 45 and 135 ppm (0, 86, 258 and 773 mg/m ) in air for 6 h per day on five days a week for 24 months. Interim kills were performed after 12 months (10 males and 10 females), 18 months (15 males and 15 females) and 24 months (10 males and 10 females). After a further six months, the study was terminated. No dose-related trend in mortality was observed. After 24 months of exposure, the mean cmnulative mortality w as approximately 20%. During the six-month post-exposure period, the cumulative mortality increased to approximately 45%. Exposure to -butyl acrylate vapour did not lead to an increased frequency of any tumour type in any organ that could be related to the test substance (Reininghaus et al., 1991). 

Young et al. (1977) exposed four volunteers to 50 ppm [180 mg/m ] 1,4-dioxane vapour for 6 h. It was rapidly taken up, with plasma levels reaching a plateau after 3 h. The major metabolite, P-hydroxyethoxyacetic acid (HEAA), was detected during the exposure period. At the end of the exposure, plasma levels of 1,4-dioxane fell with a half-life of 59 min. HEAA plasma levels reached their peak 1 h after the end of the exposure and fell thereafter with a half-life of 48 min. The absorption rate of 1,4-dioxane under these conditions was 76.1 mg/h and the total dose was 5.4 mg/kg. The dominant route of elimination was oxidation to HEAA, which is rapidly cleared in the urine 47% of the dose was excreted as HEAA during exposure and excretion was complete within 8 h of the end. The excretion half-life of HEAA was 2.7 h and its renal clearance was 121 mL/min, which indicates clearance by glomerular filtration, as creatinine clearance in these subjects was 124 mL/min. Renal clearance of 1,4-dioxane was 0.34 mL/min, compared with its metabolic clearance of 75 mL/min. 

In a 12-week, subacute toxicity test in rats given intraperitoneal injections of epichlorohydrin, treatment led to a dose-related decrease in haemoglobin values an increase in segmented neutrophils was seen with doses of 56 mg/kg bw and a reduction in the proportion of lymphocytes occurred at doses of 22 and 56 mg/kg bw (Lawrence et al., 1972). An increased leukocyte count was observed in animals exposed chronically to vapours of epichlorohydrin in air at concentrations of 2 mg/m (Fomin, 1966). The maximum tolerated dose in a 13-week subacute study in rats following oral administration of epichlorohydrin was 45 mg/kg bw per day (Oser et al., 1975). 

Phenol poisoning can occur in humans after skin absorption, inhalation of vapours or ingestion. Acute local effects are severe tissue irritation and necrosis. At high doses, the most prominent systemic effect is central nervous system depression (lARC, 1989). 

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