Some Observations on the Toxic Properties of 3:5-Dinitro-Ortho-Cresol

Parker, V. H.; Barnes, J. M.; Denz, F. A.

doi:10.1136/oem.8.4.226

Cited by 17 publications

(13 citation statements)

References 13 publications

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“…Rapid onset of rigor mortis was also observed in these fish, occasionally commencing just prior to death. This rapid onset of rigor mortis has also been reported in mammals [51,52] and is thought to be caused by the increased body temperatures associated with the hypermetabolic state brought on by uncouplers. Other investigators have observed increased oxygen consumption in fish exposed to PCP [53, 541.…”

Section: Discussionsupporting

confidence: 54%

Use of Respiratory-Cardiovascular Responses of Rainbow Trout (Salmo Gairdneri) in Identifying Acute Toxicity Syndromes in Fish: Part 1. Pentachlorophenol, 2,4-Dinitrophenol, Tricaine Methanesulfonate and 1-Octanol

McKim¹,

Schmieder²,

Carlson³

et al. 1987

Environ Toxicol Chem

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An in vivo fish model was adapted to monitor respiratory-cardiovascular responses of spinally transected rainbow trout exposed to acutely toxic aqueous concentrations of two uncouplers of oxidative phosphorylation, pentachlorophenol (PCP) and 2,4-dinitrophenol (DNP), and two narcotics, tricaine methanesulfonate (MS-222) and 1-octanol. The most evident toxic response to the uncouplers was a rapid 150 to 200% increase in ventilation volume ( VG) and oxygen consumption (V02) over the entire survival period. This caused an initial increase in total arterial oxygen ( Ta02) content of the blood, which then fell slowly as the tissues used more and more oxygen to generate ATP. Arterial blood pressure (BP,) and other blood measurements did not change appreciably in response to PCP, yet DNP caused increases in hematocrit (Hct) and hemoglobin (Hb) and slight decreases in total arterial carbon dioxide ( Taco2) and arterial pH (pH,). In contrast to the uncouplers, the response of the respiratory-cardiovascular system of trout to toxic levels of narcotics was a dramatic slowing of all respiratory-cardiovascular functions. While V, and VOz decreased 40 to 50% from predose levels, oxygen utilization (U) increased 20 to 30%. Ventilation rate (VR) declined initially and then increased slowly until death occurred, but remained within the control range. As respiration declined T,Oz significantly decreased, as did pH,. In response to hypoxia, Hct increased substantially, and Hb increased slightly only in the 1-octanol exposure. A rapid 40 to 50% drop in heart rate (reflex bradycardia) was also observed. The final phase of toxicity caused by both uncouplers and narcotics appeared to eventually produce acute tissue hypoxia, with a generalized loss of respiratory-cardiovascular coordination, and finally respiratory paralysis. Individual principal component analyses of the cardiovascular-respiratory responses of fish exposed to the first two principal components explained 68 to 76% of the variation in the 18 parameters analyzed. A two-dimensional diagram of the first two principal components illustrated this multivariate response and the increased variability in the responses of exposed fish as compared with control fish. The general sets of responses described for these two fish acute toxicity syndromes have provided the initial information necessary to group similar responses caused by other chemicals into a fish uncoupler syndrome, a fish narcosis syndrome or some new syndrome.

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Section: Discussionsupporting

confidence: 54%

Use of Respiratory-Cardiovascular Responses of Rainbow Trout (Salmo Gairdneri) in Identifying Acute Toxicity Syndromes in Fish: Part 1. Pentachlorophenol, 2,4-Dinitrophenol, Tricaine Methanesulfonate and 1-Octanol

McKim¹,

Schmieder²,

Carlson³

et al. 1987

Environ Toxicol Chem

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“…The effect of 2-amino-1,1,3-tricyanopropene on mitochondria was described by Eberts (1961), and this was followed by descriptions of experiments with compounds of related structure, the carbonyl cyanide phenylhydrazones (Heytler & Pritchard, 1962) some of which were more efficient uncouplers of oxidative phosphorylation than 2,4-dinitrophenol itself. The possibility of other non-phenolic uncouplers was suggested in a personal communication from Dr E. F. Edson of Fison Pest Control Ltd., who had noticed that a derivative of benzotriazole induced early and intense rigor at death strikingly similar to that induced by 3,5-dinitro-o-cresol (Parker, Barnes & Denz, 1951). In addition to these compounds new phenolic compounds have been described as uncouplers of oxidative phosphorylation of plant tissues, e.g.…”

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confidence: 96%

Uncouplers of rat-liver mitochondrial oxidative phosphorylation

Parker¹

1965

Biochemical Journal

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1. The ability of a series of compounds to uncouple oxidative phosphorylation of rat-liver mitochondria has been investigated. 2. The compounds were: 2-amino-1,1,3-tricyanopropene; carbonyl cyanide phenylhydrazone and its m-chloro and p-trifluoromethoxy derivatives; 4,5,6,7-tetrachloro-, 5-chloro-4-nitro-, 5-nitro-and 4,5,6,7-tetrachloro-1-methyl-benzotriazole; 4-hydroxy-3,5-di-iodo-, 3,5-di-bromo-4-hydroxy- and 3,5-dichloro-4-hydroxy-benzonitrile; and pentafluorophenol. 3. In a medium the components and physical condition of which were, as far as possible, kept constant, each compound was tested for ability to stimulate adenosine triphosphatase, to stimulate respiration in the presence of pyruvate as substrate, to inhibit phosphate uptake and to prevent swelling by trimethyltin. 4. Each compound was also examined with respect to its ability to produce rapid rigor mortis in mice. 5. The biological properties were compared with the dissociation constant and the hexane-water partition coefficient for each compound. 6. With the exception of 4,5,6,7-tetrachloro-1-methylbenzotriazole, all the compounds behaved qualitatively as 2,4-dinitrophenol. 7. Within each class of compound there is a relation between biological activity and the physical attributes measured. 8. The most efficient uncouplers were the most acidic and the most hydrophobic.

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“…The appearance of rapid, or even of premature, rigor mortis is also found in dinitrophenol poisoning (Hall, Field, Sahyun, Cutting, and Tainter, 1933;Parker, 1954;Parker, Barnes, and Denz, 1951) and it has been suggested there may be a common mechanism underlying this rapid rigor mortis and contracture of the isolated diaphragm (Barnes et al, 1955). Further evidence for the association between these two effects is provided by the present work since four of the chlorophenols shown to cause contracture of the isolated diaphragm also caused rapid rigor mortis (Tables I and II).…”

Section: Chlorination Of Phenol Produces a Series Ofmentioning

confidence: 99%

The Biological Action of Chlorophenols

Farquharson¹,

Gage²,

Northover

1958

British Journal of Pharmacology and Chemotherapy

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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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Some Observations on the Toxic Properties of 3:5-Dinitro-Ortho-Cresol

Cited by 17 publications

References 13 publications

Use of Respiratory-Cardiovascular Responses of Rainbow Trout (Salmo Gairdneri) in Identifying Acute Toxicity Syndromes in Fish: Part 1. Pentachlorophenol, 2,4-Dinitrophenol, Tricaine Methanesulfonate and 1-Octanol

Use of Respiratory-Cardiovascular Responses of Rainbow Trout (Salmo Gairdneri) in Identifying Acute Toxicity Syndromes in Fish: Part 1. Pentachlorophenol, 2,4-Dinitrophenol, Tricaine Methanesulfonate and 1-Octanol

Uncouplers of rat-liver mitochondrial oxidative phosphorylation

The Biological Action of Chlorophenols

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