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PubMed1975

Neurotoxicity of topically applied hexachlorophene in the young rat.

Young rats 6 to 22 days of age are extremely susceptible to the neurotoxic effects of hexachlorophene given as a daily bath of undiluted antiseptic detergent containing 3% hexachlorophene (pHiso-Hex). At this age, most rats are clinically and histologically damaged by as few as two daily baths. Younger rats are relatively resistant, probably because they have less myelin to be affected; older rats cannot be poisoned by this route, probably because the more mature liver excretes the drug more effectively. Age-dose-response curves in rats are similar to those in humans. This experimental model is potentially useful in defining other characteristics of this drug.

Administration, Topical↗
PubMed1975

Clinical and microbiologic surveillance of neonatal staphylococcal disease. Relationship to hexachlorophene whole-body bathing.

Neonatal staphylococcal disease occurred in the nurseries of a university hospital three weeks after discontinuation of routine, daily, whole-body bathing of newborns with hexachlorophene. Of 16 infants who had clinical manifestations within a two-week period, 11 cases were confirmed bacteriologically. Shortly after onset of the outbreak, daily clinical and microbiologic surveillance and control measures on all infants and personnel were inaugurated. Clinical surveillance after the outbreak did not yield any new case. Average incidence of cultures positive for coagulase-positive Staphylococcus aureus was highest (13% per week) during the first three weeks of microbiologic surveillance (when hexachlorophene was not used). This is lower than that reported in most previous studies. These findings indicate the importance of scrupulous hand washing before and after handling each infant and of enforcement of other basic nursery techniques.

Baths↗
PubMed1975

Staphylococcal bacteremia and hexachlorophene bathing. Epidemic in a newborn nursery.

An outbreak of staphylococcal bacteremia in healthy, full-term neonates occurred in the newborn nursery at a large county hospital not employing prophylactic hexachlorophene bathing. Seven infants had staphylococcal bacteremia and one had omphalitis. Two of the three isolates obtained for phage typing were type 86, and the other was 3c/71. Staphylococcal colonization rate in the nursery was 64% when the outbreak was recognized; 86% of these isolates were type 86. No predominant phage type was isolated from nursery personnel. The outbreak followed a six-month preliminary study that showed a rise in staphylococcal colonization rate from 2.2% with hexachlorophene bathing to 67% with a nonhexachlorophene-containing preparation. In a community survey of infants born during the two months prior to the epidemic, seven of eight babies with lesions were infected with Staphylococcus aureus type 86.

Axilla↗
PubMed1975

Colorimetric analysis of hexachlorophene in topical formulations.

The commonly used 4-aminoantipyrine dye formation procedure for hexachlorophene analysis in topical formulations was modified to overcome interference due to other components. Bar soaps and nonemulsion formulations are analyzed directly, employing a chloroform back-extraction stage of the dye prior to quantitation. Hexachlorophene in emulsions and liquid soaps is determined using a TLC separation prior to dye formation.

Ammonia↗
PubMed1983

Hexachlorophene-induced degeneration of adrenergic nerves: application of quantitative image analysis to Falck-Hillarp fluorescence histochemistry.

Possible toxic effects of hexachlorophene (HCP) on sympathetic adrenergic nerves were studied using Falck-Hillarp fluorescence histochemistry on whole-mounts of albino rat irides. HCP dissolved in 5 microliters DMSO, or DMSO alone, was injected into the anterior chamber of the eye. HCP caused a dose-dependent degeneration of adrenergic nerves, first observable after 7 micrograms and profound after 21 micrograms. One and 3 days after 35 micrograms of HCP there was an almost total loss of adrenergic nerves. Regeneration from remaining non-terminal axons led to an almost complete reformation of the adrenergic nerve plexus after 18 days. The results demonstrate a new aspect of hexachlorophene neurotoxicity, degeneration of peripheral adrenergic nerve terminals and suggest that neurotoxic actions on thin unmyelinated fiber systems should be looked for also in the central nervous system (CNS).

Animals↗
PubMed1978

Percutaneous absorption of hexachlorophene in rats, guinea pigs and pigs.

A comparative study of the percutaneous absorption of hexachlorophene (HCP) was undertaken in rats, guinea pigs and pigs. [14C]Hexachlorophene ([14C]HCP) was applied evenly over the shaved back of the animals at a dose of 40 microgram/cm2 skin surface. Urine and feces were collected at 24-h intervals for 5 days from animals kept in metabolism cages. Different methods were used for quantitating the percutaneous absorption of HCP. This study showed that skin permeability to HCP decreased in the following order: rat, guinea pig and pig. The permeability characteristics of the pig skin to topically applied HCP were comparable to the published human data. We suggest that pig may be a suitable animal model for studying the percutaneous absorption of antimicrobial drugs.

Animals↗
PubMed1980

Quantitative aspects of spermatogenesis in rats and dogs after repeated hexachlorophene treatment.

Hexachlorophene was administered orally, at subneurotoxic doses, to rats (5 mg/kg/day) and dogs (3 mg/kg/day) for 9 weeks: some of the rats and dogs were observed for a further 13 weeks. The serum concentrations of pituitary gonadotrophin and testosterone were unaffected in either species. No changes were induced in the testicular dimensions or semen characteristics of dogs and no macroscopic post mortem abnormalities, organ weight differences or lesions detectable by conventional light microscopy were found in their testes, pituitaries or secondary sex organs. A transient reduction in the number of germ cells counted in cross-sections of seminiferous tubules was seen in rats after 4 weeks treatment. After 9 weeks treatment, reduced spermatogonial counts were recorded in canine seminiferous tubules; in other respects spermatogenesis was proceeding normally. No delayed effects were apparent in eith species. It is concluded that repeated administration of hexachlorophene at subneurotoxic levels did not induce significant impairment of spermatogenesis in rats or dogs.

Animals↗
PubMed1975

Hexachlorophene in mice. Effects after long-term percutaneous applications.

The toxicity and carcinogenicity of life-time applications of hexachlorophene on the skin of Swiss mice were studied. Twice weekly applications of 0.02 ml of a 50% or 25% solution produced necrosis and ulceration of the skin as well as neurological symptoms and a mortality of up to 22% within two weeks. At autopsy, edema and cystic lesions were seen in the white matter of the central nervous system. The neurological symptoms were reversible, though a proportion of the cystic lesions persisted. Only one skin tumor was seen and the number of tumors of other organs, lymphomas, lung adenomas, liver hemangiomas, and other tumors, was not higher than in the controls. It is concluded from this study that percutaneous application of hexachlorophene has toxic local and systemic effects in mice, but no carcinogenic effects.

Animals↗
PubMed1970

Survival of gram-negative bacteria on plastic compounded with hexachlorophene.

Gram-negative bacteria representing nine genera were screened for their ability to survive surface exposure to polyethylene sheet plastic containing chemically compounded hexachlorophene (0.25%). Subcultures were made at hourly intervals over a 6-hr period of time. An exceedingly large drop in viable cells beginning at the 1-hr exposure was noted for each genus except one tested on the hexachlorophene-plastic, whereas most nonadditive controls grew bacterial colonies too numerous to count.

Culture Media↗
PubMed1987

Neurotoxicosis associated with the use of hexachlorophene in a cat.

Two weeks after daily topical application of hexachlorophene, a 4-week-old female kitten developed cardiovascular collapse, corneal ulcers, trembling, lethargy, and weakness. The kitten was euthanatized. At necropsy, the tissues appeared macroscopically normal; however, microscopic examination of tissue specimens indicated status spongiosis, astrocytosis, and microgliosis of the cerebral and cerebellar white matter and corticospinal tracts. Neuronal cell bodies forming the affected white matter were intact, indicating that demyelination may have been the cause of the lesions. The neurologic lesions were considered compatible with those of hexachlorophene-induced toxicosis.

Animals↗
PubMed1987

[Carcinogenic activity of hexachlorophene].

Albino noninbred rats were exposed to hexachlorophene (chronic inhalation of 0.1 CL50 for 12 months). The tumors detected occurred mostly in the lungs. Increased incidence of lung tumors as well as their histomorphologic pattern (not typical of spontaneous neoplasms of these animals) suggested carcinogenicity of hexachlorophene under the said conditions.

Animals↗
PubMed1976

Hexachlorophene metabolism in rats: the hepatic route.

The terminal elimination rate of radioactivity from the bile of bile-duct cannulated rats, that had received hexachlorophene-14C via the hepatic portal vein, had an apparent first-order half-life of about 10 hr. Tissue distribution studies in these rats indicated that 35-47% of the carbon-14 of the dose was eliminated through the bile within 24 hr. Significant amounts of radioactivity were also found in the liver and carcass at that time; the brain was the only tissue that did not consistently have much higher concentrations of carbon-14 than the blood. The rate limiting step in the disposition of hexachlorophene may be excretion into the bile. A bile-feeding technique demonstrated enterohepatic circulation.

Animals↗
PubMed1976

Hexachlorophene emulsions and antiseptic skin care of newborn infants.

This paper reviews 81,756 live births and 858 infant deaths occurring during the years 1959 to 1969. Sixty-three instances of central nervous system vacuolation are reported. Prematurity is shown to be a necessary prerequisite for central nervous system vacuolation to occur during routine antiseptic skin care of newborn infants with 3% hexachlorophene emulsions. Hyperbilirubinaemia is a contributory factor in such premature infants. Long-term clinical follow-up studies show that, should central nervous system vacuolation occur in premature infants, there is no resultant detriment to their immediate clinical progress and physical and neurological development. Normal newborn infants weighing more than 2,000 g do not develop such central nervous system vacuolation during routine antiseptic skin care. The writers conclude that there is no rationale for regulations to restrict the use of 3% hexachlorophene emulsions in routine antiseptic skin care of normal newborn infants and that the benefits of such use far outweigh any possible risks from central nervous system vacuolation.

Autopsy↗
PubMed1999

In vitro kinetics of the rat brain succinate dehydrogenase inhibition by hexachlorophene.

Brain succinate dehydrogenase (SDH) activity was inhibited by in vitro hexachlorophene (HCP) with a half inhibitory concentration (IC50) of 0.65 x 10(-3) M. The HCP exerted noncompetitive inhibition at 0.5 mM ( IC50) on SDH activity. The brain SDH demands more energy of activation (deltaE) in the presence of HCP. The ionizable groups of SDH such as the sulfhydral group of cysteine and alpha-amino groups of cysteine were not altered qualitatively in the presence of HCP.

Animals↗
PubMed1981

Experimental hexachlorophene encephalopathy in mice and baboons: light and electron microscopic study.

An experimental study on acute Hexachlorophene (HCP) neurotoxicity is reported in mice and baboons: - by light microscopy, a severe spongiform lesion of the central nervous system is localized in the white matter without myelin breakdown or cellular reaction; - by electron microscopy, the myelin alteration is characterized by the presence of vacuolation of "splitting" in the intralamellar spaces of compact sheaths; myelinated axons are occasionally involved. The changes described are discussed according to various reports on HCP neurotoxicity in humans and experimental animals. The effects of this chemical agent on the central nervous system is related to the percentage of HCP in talcum powder or solution for topical use. The toxicity of very low dosage level is demonstrated in baboons. Therefore HCP use cannot be recommended for young infants.

Administration, Topical↗
PubMed1978

Studies on hexachlorophene-induced myelin lesions in the trigeminal root transitional region in developing and adult mice.

Hexachlorophene (HCP)-induced intramyelinic vacuolation was studied in the transitional region of the trigeminal root of suckling and adult mice. HCP produced an extensive vacuolation in the central compartment of the region in both suckling and adult mice, while in the peripheral compartment myelin lesions were only seen in mice less than 16 days of age. Gas chromatographic measurements showed that in suckling mice the blood concentration of HCP decreased with age, apparently reflecting a faster elimination of HCP from the blood. By substantially increasing the HCP dose, higher blood concentrations were obtained in adult than less the 16-day-old mice; in spite of this, PNS myelin changes occurred only in the latter. Thus, by observing the HCP effect on the transitional region, where CNS and PNS directly meet, it is concluded that CNS of both suckling and adult mice is more severely effected by HCP than PNS, and that the reaction of the PNS myelin is age-dependent during the period of myelinogenesis; it is particularly vulnerable to a cytotoxic edema inducing substance.

Age Factors↗
PubMed1977

The distribution of peroxidases in the sciatic nerves of normal and hexachlorophene intoxicated developing rats.

Horseradish peroxidase (mol. wt. 40 000) or microperoxidase (mol. wt. 1900) were injected over the sciatic nerve of normal or hexachlorophene (HCP) intoxicated developing rats (3,7,14 and 21 days). Light and electron microscopic studies of nerves after histochemical staining for peroxidase revealed: a) the perineurial barrier to the two peroxidases was established in 21 day normal and HCP intoxicated rats; b) in animals 3-14 days, the perineurial barrier to both peroxidases was not formed and peroxidase staining was observed in the periaxonal space and in the space between paranodal loops of myelin; c) intramyelinic vacuoles, induced by HCP in animals 7-14 days did not show peroxidase staining. HCP-induced intramyelinic vacuolation is due to the separation of the myelin lamellae at the intraperiod line; although these vacuoles are potential extensions of the extracellular space, they are not stained with the extracellular markers horseradish or microperoxidase.

Age Factors↗