Isolated tissues are employed for a variety of biological studies, and it is usually found that considerable changes in their ion content have occurred following immersion in physiological saline. The present investigation was commenced in an endeavour to maintain mammalian muscle at body temperature with the same sodium content as that found in the normal animal.After attempts with other preparations rat diaphragm was selected, as this muscle is not too thick for oxygenation and it can be rapidly dissected and immersed in the medium. It was known from previous work that the potassium could be maintained at normal values (Creese, 1954), though in these experiments there was a large rise in sodium content. In the present study it was found possible to maintain the sodium of the muscle at its normal low value provided the dissection was rapid, the tissue was well oxygenated and the medium was fortified with serum or certain proteins. Some initialresults have been reported earlier (Creese, D'Silva & Northover, 1958). METHODSRats. Male albino rats of 110-130 g were used and were maintained on a rat cake diet. The range of weights for any one set of results did not exceed 8 g.Saline. The composition except where otherwise stated was (mM): Na+ 145, K+ 5-0, Ca2+ 1-3, Mg2+ 1*2, Cl-125, HCOO 25, S02-1-2, HPO2-plus H,PO; 1-2. The glucose content was 200 mg/100 ml.; the temperature was 380 C. Double-glass-distilled water was used for the solutions.G6la&wnare was cleaned with the use of a detergent, and boiled in distilled water before use. No chromic acid was used.Ditsection and immersion. It was necessary that the muscle should be dissected, attached to a holder and suspended in a small volume of medium in a time short enough to prevent deterioration. The rats were stunned and decapitated. The left hemidiaphragm was rapidly exposed, two cotton threads were inserted around the rib with a needle, and parallel cuts were made about 1 cm apart in the diaphragm in such a way that a minimum number of fibres was damaged. The holders were made of glass rod with a plastic cross-piece (Perspex), and a platinum hook was attached to the lower end of the glass rod (Fig. 1). A hole was made

The biological action of a series of chlorinated phenols has been investigated. With increasing chlorination there is an increase in toxicity in which the convulsant action of phenol is replaced by the signs characteristic of poisoning by dinitrophenol; the higher chlorinated phenols produce a contracture of the isolated rat phrenic nerve diaphragm and a stimulation of in vitro oxygen uptake of rat brain homogenate. These actions of the chlorinated phenols have been correlated with their dissociation constants; it is suggested that the higher chlorinated phenols interfere with oxidative phospborylation, and that this property may be attributed to the chlorophenate ion. The convulsant action of the lower chlorinated phenols is probably associated with the undissociated molecule.Chlorination of phenol produces a series of Employing eleven chlorophenols as well as nineteen compounds comprising mono-, di-, tri-, phenol itself, a systematic study has been made of and tetrachloro-isomers, and one pentachloro-the quantitative changes in toxicity occurring with form. All are crystalline solids at room tempera-progressive chlorination of phenol. Median lethal ture with the exception of orthochlorophenol doses have been taken as the basis for comparison which is a liquid. The lower compounds in the and have been determined under strictly controlled series are employed medically for their powerful conditions. An attempt has been made to correlate antiseptic properties which, in many cases, are these quantitative changes in toxicity with changes greater than those of phenol itself (von Oettingen, in the qualitative nature of the effects, and also 1949). Tetra-and penta-chlorophenols are impor-with the action on oxidative processes studied in tant wood preservatives, while the latter is also vitro. In turn, these changes have been considered used as a herbicide, fungicide, insecticide, and in conjunction with the dissociation constants of molluscicide. These uses of the higher chloro-the phenols. phenols have been reviewed by Truhaut, Vitte and The effect of the progressive chlorination of Boussemart (1952).phenol upon the isolated rat diaphragm has alsoOn account of the differences in test animals and been examined. injection techniques employed by authors, including the fact that only seven chlorophenols appear METHODS AND MATERIALS to have been studied, it is difficult to trace the way in which chlorination affects the toxicity of phenol carried out on male albino rats, weighing 125 to (Bechold and Ehrlich, 1906;Binet, 1896; Deich-175 g., which had been fasted for 24 hr. Experiments mann, 1943; Kehoe, Deichmann-Gruebler, and on rats which had received food prior to dosing Kitzmiller, 1939). The general effect of chlorina-showed a considerably lower toxicity. tion is to increase the toxicity while reducing Median lethal doses were determined by injecting the convulsant activity characteristic of phenol. the chlorophenols intraperitoneally in 10 ml. olivePentachlorophenol is non-convulsant and is oil/kg. body weight. Usin...

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