The Biological Action of Chlorophenols

Abstract

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...

Bovine spermatozoa as anin vitro model for studies on the cytotoxicity of chemicals: effects of chlorophenols

“…2,4-DCP and 4-MCP tested up to concentrations of 250 #M and 1000 #m, respectively, did not induce a significant stimulation of respiration. The results of the respiration measurements reported here do well agree with data from studies using isolated rat liver mitochondria (Weinbach & Garbus, 1965) and rat brain homogenate (Farquharson et al, 1958), respectively.…”

“…The higher chlorinated phenols are known as potent uncouplers of oxidative phosphorylation (Weinbach & Garbus, 1965;Farquharson et al, 1958). From the above discussion it is evident that this mode of action is not responsible for the observed inhibition of sperm swimming activity.…”

Aliphatic and aromatic halocarbons as potential mutagens in drinking water

“…LD 50 in rats is 355mg/kgbw (Farquharson et al, 1958). The acute oral LD 50 in rats is approximately 3g/kgbw, when administered by gavage (McCollister et al, 1961).…”

“…LD 50 in rats amounts to 276mg/kgbw (Farquharson et al, 1958). The acute oral LD 50 in rats is 820mg/kgbw.…”

Experiments on the Mechanism of Action of Chlorocresol and Caffeine

“…caused a contraction of the frog rectus abdominis muscle, and Cori & Cori (1936) and Barnes, Duff & Threlfall (1955) showed that 2,4-dinitrophenol contracted frog skeletal muscle, and the latter also showed that this substance caused a contraction of the isolated diaphragm which was not abolished when the muscle was depolarized with potassium sulphate. Chlorinated phenols, containing from two to five chlorine atoms, cause a contraction of the isolated diaphragm of the rat (Farquharson, Gage & Northover, 1958). …”