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Comparison of the effects of two lipophilic acids, hexachlorophene and decanoate, on Bacillus subtilis.

The minimal growth-inhibitory amount of either hexachlorophene (HCP) or decanoate stopped growth, respiration, adenosine 5'-triphosphate synthesis, and amino acid transport of Bacillus subtilis in a culture containing amino acids and citrate as carbon sources. The electron transport system was not affected by this dose. Addition of 27.8 mM glucose or 10 mM malate to an inhibited culture did not reverse the binding of HCP or decanoate to the cells, but it allowed resumption of growth, respiration, and adenosine 5'-triphosphate synthesis, as the glucose or malate then supplied the needed carbon. The addition of glucose or malate did not reverse amino acid transport inhibition caused by decanoate, but it did reverse that due to HCP. However, if the dose of HCP was raised in the presence of glucose or malate, only growth and amino acid transport were affected; this indicates that both HCP and decanoate act at their minimal growth inhibitory doses by inhibiting substrate transport. As active transport of amino acids and ketoacids depends on the proton gradient and the membrane potential of the cells, we conclude that the primary effect of these lipophilic acids is the destruction of the proton-motive force.

Adenosine Triphosphate↗

Antimicrobial actions of hexachlorophene: inhibition of respiration in Bacillus megaterium.

Hexachlorophene (HCP) inhibits both endogenous and exogenous respiration (oxygen uptake) in Bacillus megaterium, without sparing by any of several substrates. The inhibition is maximal when the cells are treated with 8 mug of HCP per mg of cells (dry weight), which corresponds to the minimal lethal dose. Levels as low as 2 mug/mg are inhibitory but not lethal. HCP also inhibits the respiration of isolated B. megaterium membranes and can act on several components of the electron transport chain in the membranes and on soluble enzymes. Although both forms of nicotinamide adenine dinucleotide, reduced form dehydrogenase and malic dehydrogenase are inhibited by HCP, they are less susceptible than is oxygen uptake. The site of maximal sensitivity is nearer the terminal electron acceptor, but the exact location depends on the cytochrome composition of the membranes. If cytochromes b(1), a, and a(3) are present, but not o, HCP inhibits electron transport on the substrate side of cytochrome b(1); if cytochromes b(1), a(3), and o are present, but not a, the inhibition occurs on the oxygen side of cytochrome b(1). Exogenous menadione, an analogue of menaquinone, reverses the inhibition in both circumstances. The primary lethal action of HCP thus appears to be respiratory inhibition at a site within the membrane-bound part of the electron transport chain.

Bacillus megaterium↗

Hexachlorophene in the newborn nursery. A risk-benefit analysis and review.

A critical review of the available data on the risks and benefits of hexachlorophene suggests that there is ample evidence fror the toxic potential; whereas there is no substantial evidence of its benefit in life-threatening staph 80/81 epidemics, and effective less toxic alternatives are available. In view of its limited usefulness and definite toxicity, the routine use of hexachlorphene is unjustified;

Animals↗

A comparison of spongiosis induced in the brain by hexachlorophene, cuprizone and triethyl tin in the Sprague-Dawley rat.

The effect of hexachlorophene (HCP; 2,2'-methylenebis(3,4,6-trichlorophenol), cuprizone (CPZ; bicyclohexone oxaldihydrazone) and triethyl tin (TET; triethyl tin sulphate) in producing vacuoles in the brain of the Sprague-Dawley rat has been quantified by image analysis of the extent of the spongy change in the white matter. The state of the astrocytes was assessed by immunocytochemical staining for glial fibrillary acidic protein (GFAP). HCP and TET caused a dose-related spongiosis, but cuprizone had no significant effect on the brain. With chronic HCP treatment, the spongiosis was accompanied by astrocyte hypertrophy and proliferation, and the extent of the gliotic reaction was related to the dose of HCP. The results demonstrate that HCP can produce and maintain astrocyte proliferation in the rat brain. Such an agent was required for use in an investigation of a putative tumour promoter in the rat.

Animals↗

Effect of urinary alkalinisation and acidification on the tissue distribution of hexachlorophene in rats.

1. Urinary alkalinisation may be helpful in treating acute poisoning with uncouplers of oxidative phosphorylation containing a phenolic hydroxyl (pKa 4-6) or other acidic moiety. 2. We studied the effects of urine alkalinisation and acidification on the tissue distribution of hexachlorophene (HCP, pKa 5.7) in male Sprague Dawley rats (10 rats/group). 3. Ammonium chloride (10 mL kg-1, 2% m/v) or sodium bicarbonate (10 mL kg-1, 2% m/v) were administered by gavage on three occasions over 24 h, prior to a single gavage dose of HCP (180 mg kg-1). Controls received aqueous sodium chloride (10 mL kg-1, 0.9% m/v) followed by either HCP (180 mg kg-1) or vehicle alone. 4. Urine pH, body mass and body temperature were monitored during the study and, at the conclusion of the experiment (12 h post-HCP dose), organ mass (liver, kidney, brain), and plasma, urine and tissue HCP concentrations were measured. 5. No clinical features of toxicity were observed in any group. However, sodium bicarbonate significantly reduced median HCP in liver--median plasma and kidney HCP concentrations were also reduced but not significantly. Conversely, ammonium chloride significantly increased median HCP concentrations in liver and kidney--median plasma HCP was also increased but not significantly. 6. The results provide some support for the hypothesis that blood pH influences the tissue distribution of uncouplers of oxidative phosphorylation containing an acidic moiety. Urinary alkalinisation may be useful in treating acute poisoning with these compounds.

Ammonium Chloride↗

Effect of hexachlorophene on the coagulation process in beagle dogs.

In a dermal toxicological study the effect of hexachlorophene on the blood coagulation process in dogs over a period of 12 weeks was investigated. The thrombelastographic results revealed a reduction in reaction time, coagulation time and an increase in maximal amplitude supplemented with subsequent increase in the number of platelets and the enhancement of ESR.

Animals↗

Experimental hexachlorophene intoxication in young swine.

Hexachlorophene (HCP) intoxication in swine was studied as a possible model of HCP poisoning in human beings. Swine were topically or orally given HCP each day, and observations were made on central nervous system function, hematologic measurements, serum chemical analyses, necropsy, microscopic examination of tissues, and concentrations of HCP residues in blood and tissue. Intoxication was observed in orally exposed swine, but the syndrome was not consistently produced in topically exposed swine. Signs and microscopic lesions were all related to dysfunction of the central nervous system, e.g., incoordination, paresis, and status spongiosus. Occurrence of signs and lesions, mortality rates, and concentrations of HCP residue were positively correlated with the dosage of HCP given.

Animals↗

[Hygienic evaluation of experimental samples of antimicrobial underwear containing hexachlorophene].

The hygienic examination of 12 samples of knitted underwear which contained hexachlorophene added during fiber formation allowed the selection of four types that can be used under poor sanitation conditions. Taking into consideration possible changes in the proportion of various micoorganisms during prolonged space flights, it is recommended to carry out a complex investigation in order to allow the use of the antimicrobial underwear by specific crewmembers during a certain period of time.

Ecological Systems, Closed↗

Dermal exposure of hexachlorophene to guinea pigs.

The skins of guinea pigs were exposed to 50 mg/kg hexachlorophene (HCP) for 7, 15 or 30 days. The activities of skin marker enzymes (beta-glucuronidase, histidase, tyrosinase) increased, but glutathione decreased. Lipid peroxidation and histamine contents increased during different time intervals. The histopathological changes showed damage to epidermis and dermis. Depending on the duration of exposure, HCP produces biochemical and histopathological damage to skin.

Animals↗

Effect of chronic exposure to hexachlorophene on rat brain cell specific marker enzymes.

The neurotoxicity associated with chronic exposure to hexachlorophene (HCP) was evaluated by measuring the activity of seven cell specific marker enzymes in brain and by comparing these measurements to morphological changes analyzed by light microscopy. Animals were divided into two groups, the experimental group received HCP at a daily dose of 20 mg/kg p.o. for 53 consecutive days whereas the control group received an equivalent amount of the vehicle only. HCP produced no change in the rate of gain in body weight nor did it produce a statistically significant change in brain weight. Furthermore, no overt abnormal neurological symptoms were observed at this level of exposure to HCP. The white matter throughout the brain was extensively vacuolated in the HCP-treated rats, imparting a spongiform structure which was absent in the white matter of the control animal brains. The data obtained reveal that chronic HCP treatment produce little change in any of the neuronal marker enzymes with the exception of a significant decrease in tyrosine hydroxylase activity in the striatum. Of the nonneuronal enzymes assayed, a significant increase in non-neuronal enolase, glutamine synthetase, and 2',3'-cyclic nucleotide phosphohydrolase was observed in the sciatic nerve, hippocampus and optic nerve, respectively.

Animals↗

Alternatives to hexachlorophene bathing of newborn infants.

In controlled trials newborn infants were bathed with Lactacyd, pHisoHex, Hibitane, Lanohex or tap water. Bacteriologic samples were taken from three sites (groin, axilla and cord) immediately after birth, following an initial bath with one of the test agents, and on day 3 or 5 after a water bath. Initial bathing with all agents, including water, reduced the concentration of bacteria on the skin to a similar extent. However, comparisons of bacterial flora at birth versus those on days 3 and 5 indicated differences in the actions of the various agents on pathogenic and nonpathogenic organisms. Lactacyd and Hibitane appeared to be suitable alternatives to hexachlorophene in the control of pathogenic bacteria on the skin of newborns. However, their absorption and toxicity in the newborn are unknown and, unless use of a skin disinfectant is warranted, routine bathing of newborns with tap water appears to be satisfactory.

Asepsis↗

A comparison of hexachlorophene and lactacyd on growth of skin flora in healthy term newborn infants.

Reports of toxicity from the routine bathing of newborn infants with hexachlorophene resulted in discontinuing its use in the newborn nurseries of the Ottawa Civic Hospital, only to be followed by an outbreak of skin infections. As a result, a controlled trial of bathing newborn babies with either Lactacyd or pHisoHex was begun. The efficacy of the soaps was evaluated by comparing the colonization of the nose and umbilical cords of 158 pHisoHex-washed babies and 156 Lactacyd-washed babies on the day of discharge from hospital. The gram-negative and gram-positive bacterial flora of nose and cord of infants washed with pHisoHex and Lactacyd were identical in frequency and distribution.

Antisepsis↗

Antimicrobial and toxicological studies on an antiseptic based on hexachlorophene and destructive distillate of castor oil.

Bactericidal, bacteriostatic, fungistatic and toxicological evaluaton of an emulsion containing 0.25% hexachlorophene (W/V), 9.5% terpineol (V/V), 1.5% oil of terpentine (V/V), 13% ethanol (V/V), 6% castor oil distillate 1201275 degrees C (V/V) and 6% sodium salt of the residue (W/V) in aqueous medium was performed. The bactericidal concentration for Salmonella typhi was found to be 1:400 which increased to 1:350 in the presence of 5% horse serum. The bacteriostatic concentration of the emulsion varied from organism to organism. A 4% solution of the emulsione was found to be most effective against Microsporum vanbreuseghemii showing an inhibition zone of 7.2 cm and was least effective on Aspergillus niger. 1 to 8% solution of the emulsion given orally or instilled into conjunctival sacs of albino mice indicated lethal and insignificant toxic manifestations respectively but a dose equivalent to 50 mg/Kg given subcutaneously was found to produce a subacute lethal effect in guinea pigs.

Animals↗

Extraction, gas-liquid chromatographic detection, and quantitation of hexachlorophene residues from plant tissues high in lipid content.

A method has been developed for the extraction, cleanup, derivatization, detection, and quantitation of hexachlorophene (HCP) residues from 2 types of plant storage tissue high in lipid content. Wet soybean or peanut tissue was homogenized and extracted with ethyl ether and chromatographed on silica gel to remove the neutral lipids. The cleaned up sample was methylated with diazomethane and the dimethoxyhexachlorophene was eluted from a second silical gel column and chromatographed on a 6' glass column packed with 3% OV-1 or 3% SE-30 on Gas-Chrom Q. The instrument detection limit for the 63Ni electron capture detector was less than 0.1 ng for dimethoxyhexachlorophene and about 1 ppb HCP residue in plant issue. Recovery of 10-420 ppb HCP added to tissue averaged 90.9 +/- 5.7%. Interfering substances were removed, column life was increased, peak sharpness was increased, and tailing of the parent compound was decreased by using appropriate column chromatography.

Arachis↗

Hexachlorophene-induced changes in erythrocyte membrane ATPase activity.

Hexachlorophene (HCP) has been found to dramatically affect erythrocyte membrane ATPase activity. The Na+,K+,Mg2+-ATPase of erythrocyte membranes was strongly inhibited by HCP. The Mg2+-ATPase was stimulated at lower concentrations of HCP, while at higher concentrations of HCP the activity decreased toward control levels. Inclusion of bovine serum albumin in the incubation medium protected each enzyme from the effect of HCP. A possible mechanism for the alteration of erythrocyte membrane ATPase activity by HCP is presented.

Adenosine Triphosphatases↗

Hexachlorophene storage in a burn patient associated with encephalopathy.

Hexachlorophene (HCP), a chlorinated phenolic hydrocarbon with bacteriostatic properties against Staphylococcus, is used in a number of topical products. Absorption through normal and damaged human skin has been appreciated and neurologic changes have been described in experimental animals, but instances of human toxicity have been reported infrequently. A 10-year-old boy who sustained a 25% burn did well initially but died in the second week of convalescence with hyperthermia, lower-extremity weakness, and cerebral edema. His treatment had included frequent applications of HCP. Analysis of post-mortem tissue revealed the presence of toxic levels of HCP in the blood (2.2 mug/gm) and brain (2.2 mug/gm), with storage in skin (25 mug/gm), liver (4.4 mug/gm), and fat (6.0 mug/gm). This case suggests that topical applications of HCP in man may result in an extensive absorption with fat storage and may cause fatal encephalopathy.

Brain Diseases↗

Extraction and gas-liquid chromatographic determination of hexachlorophene from several plant tissues.

Conditions are described for extraction, cleanup, derivatization, detection, and quantitation of hexachlorophene (HCP) residues from several types of plant material. Wet plant tissue was homogenized and extracted with ethyl ether, dried, and methylated with excess diazomethane. Samples were precleaned by column chromatography on silica gel with benzene-petroleum ether (1 + 1), and then 1-10 microliter concentrated sample was chromatographed on a 6' column of 3% SE-30 on 80-100 mesh Gas-Chrom Q. The detection limit for the electron capture detector was less than 0.1 ng dimethoxyhexachlorophene and 1 ppb HCP in plant tissue. Recoveries (%) of 11-610 ppb HCP added to tissue averaged 94.3 for tomatoes, 86.4 for green peppers, 92.6 for cucumbers, 93.3 for green beans, 93.7 for peanut hay, and 91.6 for peanut shells.

Arachis↗