National Toxicology Program

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. ¹

Names (NTP)

• Hexachlorophene
• 2,2'-METHYLENEBIS-3,4,6-TRICHLOROPHENOL (9CI)

Human Toxicity Excerpts

• IT CAN CAUSE CONTACT DERMATITIS IN SUSCEPTIBLE INDIVIDUALS OR WITH REPEATED APPLICATION IN HIGH CONCN, & CNS TOXICITY IF IT IS USED ON MUCOUS MEMBRANES OR OVER LARGE DERMATITIC AREAS. [American Medical Association, Council on Drugs. AMA Drug Evaluations. 2nd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1973., p. 662]**PEER REVIEWED**
  
• Neurologic symptoms in neonates after acute exposure probably result from cerebral edema. [Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1221]**QC REVIEWED**
  
• CARDIOVASCULAR DISTURBANCES, CONVULSIONS, AND RESPIRATORY ARREST HAVE BEEN REPORTED FOLLOWING ACCIDENTAL INGESTION OF HEXACHLOROPHENE DETERGENT EMULSION BY YOUNG CHILDREN OR APPLICATION OF HIGH CONCENTRATION (6%) TO CHILDREN. [American Medical Association, AMA Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc., 1977., p. 893]**PEER REVIEWED**
  
• ACUTE /ORAL/ TOXIC EFFECTS INCLUDING ANOREXIA, NAUSEA, VOMITING, ABDOMINAL CRAMPS, ASTHENIA, MIOSIS, ABSENCE OF LIGHT REFLEX, CEREBROSPINAL TRACT SIGNS, ELEVATED INTRACRANIAL PRESSURE, & DEATH. ... /FROM TOPICAL USE SEVERAL TIMES A DAY TO SKIN OR VAGINA OF ADULTS/ CONFUSION, DIPLOPIA, LETHARGY, TWITCHING, CONVULSIONS, RESP ARREST, & DEATH HAVE OCCURRED. [Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980., p. 969]**PEER REVIEWED**
  
• IN INFANTS ... /IT/ CAN CAUSE MYELINOPATHY & SPONGIFORM ENCEPHALOMALACIA AS RESULT OF TOPICAL APPLICATION. [Osol, A. (ed.). Remington's Pharmaceutical Sciences. 16th ed. Easton, Pennsylvania: Mack Publishing Co., 1980., p. 1102]**PEER REVIEWED**
  
• ... TWENTY-FIVE SEVERE MALFORMATIONS, SUCH AS EYE & CNS DEFECTS ... REPORTED AMONG 460 LIVE BIRTHS TO ... /SWEDISH HOSPITAL PERSONNEL EXPOSED TO HEXACHLOROPHENE SOAP (0.3-3%) 10-16 TIMES/DAY DURING PREGNANCY/, COMPARED WITH NO SEVERE MALFORMATIONS SEEN IN CONTROL GROUP OF 233 LIVE BIRTHS FROM UNEXPOSED MOTHERS. MINOR MALFORMATIONS WERE ALSO MORE FREQUENT IN ... EXPOSED GROUP. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 250 (1979)]**PEER REVIEWED**
  
• AN 8 DAY OLD NEONATE WAS ACCIDENTALLY FED ABOUT 10-15 ML HEXACHLOROPHENE (PHISOHEX) INSTEAD OF FORMULA. THE PATIENT SPIT UP MILKY FLUID IMMEDIATELY & HAD 3 WATERY BOWEL MOVEMENTS WITHIN AN HR. THREE WASHINGS WITH ISOTONIC SALINE WERE REQUIRED BEFORE CLEAR FLUID WAS OBTAINED. ACTIVATED CHARCOAL WAS THEN ADMIN BY NASOGASTRIC TUBE & LEFT IN THE STOMACH. JITTERINESS & EXCITABILITY INCREASED OVER THE FIRST 12 TO 18 HR, BUT WERE NOTABLY DIMINISHED BY DAY 3, & DISAPPEARED ENTIRELY BY THE TIME OF DISCHARGE AT AGE 14 DAYS, WHEN THE NEUROLOGIC EXAM WAS NORMAL. [HERSKOWITZ J, ROSMAN NP; J PEDIATR 94 (MAR): 495-6 (1979)]**PEER REVIEWED**
  
• THE USE OF PERITONEAL DIALYSIS WAS ASSESSED IN A CASE OF HEXACHLOROPHENE (PHISOHEX) INGESTION IN A 7 YR OLD BOY. APPROX 1 G WAS ACCIDENTALLY INGESTED INSTEAD OF AN ANTIDIARRHEAL MEDICATION. BLINDNESS & LETHARGY, FOLLOWED BY A CONVULSIVE EPISODE, DEVELOPED. PERITONEAL DIALYSIS WITH INPERSOL 1.5% WAS INITIATED, & ALIQUOTS OF THE FIRST 16 DIALYSATE EXCHANGES WERE ANALYZED. THE VALUES FOR THE CLEARANCE & AMT REMOVED OF HEXACHLOROPHENE CONSISTENTLY DEMONSTRATE THAT IT IS MINIMALLY ELIMATED BY PERITONEAL DIALYSIS. [BOEHM RM, CZAJKA PA; CLIN TOXICOL 14 (MAR): 257-62 (1979)]**PEER REVIEWED**
  
• Hexachlorophene resulted in human neurotoxicity when newborn infants, particularly premature infants, were bathed with the compound to avoid staphylococcal infections. Following skin absorption of this hydrophobic cmpd, hexachlorophene enters the nervous system and results in intramyelinic edema, splitting the intraperiod line of myelin in both the CNS and the PNS. Experimental studies with erythrocyte membranes show that hexachlorophene binds tightly to cell membranes, resulting in the loss of ion gradients across the membrane. [Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991., p. 421]**PEER REVIEWED**
  
• Poisoning by hexachlorophene, for example, by its liberal application to patients with burns or to infants, leads to circulatory failure, body temperature fluctuations and central nervous symptoms, including headache, twitching, convulsions and death. Some infants treated with high doses of hexachlorophene have died; premature infants and newborns appear to be most susceptible. The spongiform brain changes seen in animals were also observed in infants who died from overexposure to hexachlorophene. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 250 (1979)]**PEER REVIEWED**
  
• Severe malformations /were reported/ in children of hospital personnel who had been exposed to hexachlorophene soap during pregnancy as compared with children of a group of unexposed personnel: 4 severe and 6 slight malformations were observed in 82 babies born to the exposed group versus 1 slight malformation in 46 babies born to mothers not exposed to hexachlorophene. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 250 (1979)]**PEER REVIEWED**
  
• In a series of 10 cases of accidental ingestion the gastrointestinal symptoms included anorexia, nausea, vomiting, abdominal cramps and diarrhea. Dehydration was severe in some cases and associated with shock. Water and electrolyte derangements required vigorous treatment. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-195]**PEER REVIEWED**
  
• In 1974 a 7 year old boy was mistakenly given 45 ml of a 3% hexachlorophene emulsion orally in 3 days, causing him to become severely ill. On the 3rd day he was alert and well oriented, but "totally unable to see and could not distinguish light from dark." A day later, before respiratory arrest, "pupils were constricted and unreacting to light." At autopsy there was severe cerebral edema ("status spongiosus"), but most remarkably there was widespread severe disintegration and necrosis of myelin sheaths and axon cylinders of optic nerves, optic chiasm, and optic tracts. Although the lateral geniculate bodies did not show significant abnormality, the deepest layers of the calcarine fissure showed severe degeneration, and optic pathways anterior to the geniculate bodies "were frankly necrotic." [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 480]**PEER REVIEWED**
  
• Severe excoriation of skin and central nervous symptoms resulted from total body application of a 3% lotion on a newborn infant for several days. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-195]**PEER REVIEWED**
  
• Hexachlorophene exposure as a possible risk factor for nonHodgkins lymphoma (NHL) was discussed. The uses of & carcinogenic risk presented by hexachlorophene were described. Hexachlorophene, a polychlorinated bisphenol first developed in 1939 has been widely used as a detergent in soaps & as a disinfectant. 8 cases of NHL among medical personnel in the Swedish health care system who were occupationally exposed to hexachlorophene were summarized. 7 cases were female. The cases ranged in age from 32-67 yr & had used hexachlorophene for hand washes, disinfection & patient care. The apparent latency periods ranged from 14-28 yr. None of the cases had any etiological or suspected risk factors for NHL other than exposure to hexachlorophene. /Results suggest/ that the 8 cases are consistent with a causal relationship between hexachlorophene exposure & NHL. ... [Hardell L, Eriksson M; J Occupat Med 34 (8): 849-50 (1992)]**QC REVIEWED**
  
• Gastrointestinal disorders occur after ingestion of as little as 10 to 20 mg/kg. [Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1219]**QC REVIEWED**
  
• May cause asthma. /from table/ [Rom, W.N. (ed.). Environmental and Occupational Medicine. 2nd ed. Boston, MA: Little, Brown and Company, 1992., p. 424]**QC REVIEWED**
  
• Hexachlorophene is a potent neurotoxicant. It causes brain edema and spongy degeneration of white matter. This neurotoxicity can be seen after acute or chronic exposures, either by skin absorption or ingestion. The nervous system symptoms are complex. Lethargy is an early manifestation, following by muscular weakness, muscular fasciculation, irritability, cerebral edema, and paralysis, leading to coma and death. Seizures commonly occur in more severe cases. Blindness and optic atrophy have been reported following exposure to hexachlorophene. [U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 204]**QC REVIEWED**
  

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Non-Human Toxicity Excerpts

• ... IN POULTRY ... THERAPEUTIC DOSES (35-45 MG/KG BODY WT) MAY CAUSE A DROP IN EGG PRODN ... LARGER AMT (200 MG/KG) INCR RESPIRATION RATE & CAUSE OTHER SIGNS OF ACUTE TOXICITY. ... DOSES OF 40 MG/KG BODY WT ... /CAUSED/ TRANSIENT SIGNS OF TOXICITY IN 2 & DEATH IN 1, OF 6 CATTLE TREATED. ... IN CALVES FED MILK FROM BUCKETS ALSO USED FOR 9.6% HEXACHLOROPHENE, 7/20 ANIMALS DIED AFTER SHOWING MUSCULAR TREMORS, NYSTAGMUS, OPISTHOTONOS & STIFFNESS OF LEGS. [Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 96]**PEER REVIEWED**
  
• IN ... FDA STUDIES, ... IT WAS FOUND THAT 2 WK AFTER ONSET OF EXPOSURE, RATS FED 500 PPM (25 MG/KG/DAY) ... SHOWED WEAKNESS IN ... HINDQUARTERS, WHICH PROGRESSED TO PARALYSIS. MICROSCOPIC EXAMINATION OF BRAIN & SPINAL CORD ... REVEALED A PARTICULAR EDEMA OF WHITE MATTER RESEMBLING SPONGY DEGENERATION OF WHITE MATTER IN INFANTS. WHEN THE ANIMALS WERE REMOVED FROM THE POISONED DIET, THEY RECOVERED GRADUALLY OVER A PERIOD OF WEEKS. SIMILAR ... /SYMPTOMS WERE/ NOTED IN MONKEY. [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1783]**QC REVIEWED**
  
• ORAL ADMIN OF HEXACHLOROPHENE TO RATS CAUSES DEGENERATION OF SPERMATOGENIC CELLS. IN SHEEP ... 2500 MG/KG FOLLOWED 2 DAYS LATER BY DOSE OF 50 MG/KG HAS ALSO CAUSED EXTENSIVE DAMAGE TO SPERMATOGONIA; AFTER 21 DAYS THERE WAS NEITHER SPERM IN EPIDIDYMIS NOR SPERMATOGENESIS. [Casarett, L.J., and J. Doull. Toxicology: The Basic Science of Poisons. New York: MacMillan Publishing Co., 1975., p. 271]**PEER REVIEWED**
  
• ... APPLIED TO DORSAL SKIN OF GROUPS OF 50 RANDOM-BRED /8 WK OLD FEMALE SWISS MICE AT 10, 5, & 1 MG/ TWICE/WK FOR LIFE ... CAUSED SKIN ULCERATION, NECROSIS, INFLAMMATION ... /&/ NEUROLOGICAL SYMPTOMS. ABOUT 25% OF TREATED ANIMALS AT ALL DOSE LEVELS DIED WITHIN 40 WK ... VERSUS 5% OF CONTROLS; 60 WK AFTER START OF TREATMENT, 50-65% OF TREATED ... HAD DIED, COMPARED WITH 10% OF CONTROLS. IN TREATED GROUPS, TUMORS DEVELOPED IN 10/50 (15 TUMORS), 14/50 (17 TUMORS) & 15/50 (19 TUMORS) ANIMALS, RESPECTIVELY; 20/50 CONTROLS DEVELOPED TOTAL OF 29 TUMORS. AMONG TREATED ... ONLY 1 BENIGN SKIN PAPILLOMA DEVELOPED. LYMPHOMAS, LUNG ADENOMAS, LIVER HEMANGIOMAS & OTHER TUMORS OCCURRED SPORADICALLY WITH SIMILAR FREQUENCIES IN TREATED & EXPTL GROUPS. (THE WORKING GROUP NOTED THAT LIFESPAN WAS GREATLY REDUCED IN ALL EXPTL GROUPS). [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 248 (1979)]**PEER REVIEWED**
  
• TOPICAL EXPOSURE OF NEONATAL RATS TO 3% HEXACHLOROPHENE SOLN CAUSED REDUCED FERTILITY IN 7 MO OLD MALES, DUE TO INABILITY TO EJACULATE. ... ADMIN OF 500 MG/KG DIET OR 20-30 MG/KG/DAY BY GAVAGE TO RATS CAUSED SOME MALFORMATIONS (ANGULATED RIBS, CLEFT PALATE, MICRO- & ANOPHTHALMIA) & REDUCTION IN LITTER SIZE. THESE DOSAGES APPROACHED THOSE THAT RESULTED IN MATERNAL DEATH. A 45% SUSPENSION ... APPLIED INTO VAGINA OF PREGNANT RATS CAUSED MATERNAL TOXICITY & MALFORMATIONS IN OFFSPRINGS (HYDROCEPHALY, MICRO- & ANOPHTHALMIA, WAVY RIBS, UROGENITAL DEFECTS). IN RABBITS, ORAL DOSE OF 6 MG/KG BODY WT/DAY CAUSED LOW FREQUENCY OF RIB MALFORMATIONS. SC INJECTION OF 12.5 OR 25 MG/KG BODY WT/DAY ... TO MICE ON DAYS 3-8, 7-12 OR 11-17 OF GESTATION CAUSED FETAL RESORPTIONS BUT NO MALFORMATIONS. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 249 (1979)]**PEER REVIEWED**
  
• BESIDES IRREVERSIBLE LOSS OF VISUAL FACULTY IN BEAGLE DOGS FROM 3 & 10% OINTMENT OF HEXACHLOROPHENE APPLIED DERMALLY OVER PERIOD OF 12 WK, A PERMANENT MYDRIASIS, PERIPAPILLARY EXUDATIONS, & OTHER ALTERATIONS OF OCULAR FUNDUS & OPTIC NERVOUS SYSTEM WERE OBSERVED. [STABEN P; TOXICOL LETT 5 (1): 77-82 (1980)]**PEER REVIEWED**
  
• IN XVII/G MICE INJECTED SC AT BIRTH OR RECEIVING HEXACHLOROPHENE FROM MOTHER'S MILK, INCIDENCE OF TUMORS WAS NOT STATISTICALLY INCR. WHEN FED TO MALE SPRAGUE-DAWLEY RATS IN A PROTEIN & VITAMIN DEFICIENT DIET & TO C57BL & XVII/G MICE IN A COMPLETE DIET FOR LIFETIME, NO SIGNIFICANT CARCINOGENIC EFFECTS WERE OBSERVED AFTER 2 YR. NO EFFECTS WERE OBSERVED IN C57BL MICE THAT RECEIVED HEXACHLOROPHENE TRANSPLACENTALLY. [RUDALI G, ASSA R; CANCER LETT 5 (6): 325-32 (1978)]**PEER REVIEWED**
  
• HEXACHLOROPHENE DID NOT INDUCE REVERSE MUTATIONS IN SALMONELLA TYPHIMURIUM G46 IN HOST-MEDIATED ASSAY USING MALE ALBINO RATS THAT RECEIVED 100 OR 200 MG/KG DIET FOR 90 DAYS. DOMINANT LETHAL TESTS WITH MALE MICE TREATED WITH SINGLE IP INJECTIONS OF 2.5 OR 5.0 MG/KG BODY WT ... WERE NEG. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 250 (1979)]**PEER REVIEWED**
  
• THE CYTOTOXIC EFFECT ON THE CORNEAL SURFACE OF RABBITS OF 5 PRESERVATIVES USED IN CONTACT LENS SOLUTIONS OR EYE COSMETICS WAS INVESTIGATED BY SCANNING ELECTRON & LIGHT MICROSCOPY. HEXACHLOROPHENE HAD THE MOST PRONOUNCED EFFECTS: A NEARLY COMPLETE LOSS OF THE TWO TOP LAYERS, WHILE THE THIRD CELL LAYER WAS STILL INTACT. [DORMANS JA M, VAN LOGTEN MJ; TOXICOL APPL PHARMACOL 62 (2): 251-61 (1982)]**PEER REVIEWED**
  
• The effects of hexachlorophene (HCP) on amino acid profiles in the brain of mice were studied. Six adult male Indian grey mice received an oral dose of 60 mg/kg/day of HCP dissolved in corn oil for seven consecutive days. Control animals were given corn oil alone. Free amino acids in brain were analyzed using HPLC. Repeated HCP treatments produced significant increases in the levels of the neutral amino acids glutamine, threonine, phenylalanine, leucine, isoleucine, and valine in mouse brain compared with the control animals. A 162% elevation of glutamine was observed following HCP treatment. This elevation was associated with increased glutamine synthetase and decreased glutaminase activity levels. The levels of the acidic amino acids glutamic acid and aspartic acid, and the glutamic acid/glutamine ratio as well as the glutamic acid and aspartic acid/gamma-amino butyric acid ratios were significantly decreased. Gamma-aminobutyric acid, alanine, and glycine concentrations were increased. [Prasad GV et al; Arch Environ Contam Toxicol 16: 631-6 (1987)]**PEER REVIEWED**
  
• Bathing of the abdomen of puppies with pustular dermatitis and of the mammary glands of the dam with a hexachlorophene preparation has resulted in generalized tremors which increased during excitement and disappeared during sleep. The signs developed about 10 days after the use of the preparation and persisted for about two weeks. One of the puppies which was killed had pronounced vacuolation of the white matter of the brain and spinal cord. Fatal intoxication has been reported in puppies which sucked mammary glands which had been bathed in a preparation containing 3% of hexachlorophane and after eating a bar of soap containing 2% of this material. The clinical signs reported include diarrhoea, vomiting, hypersalivation, tachypnoea and depression. [Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988., p. 96]**PEER REVIEWED**
  
• Therapeutic doses of hexachlorophane can produce fatalities among pregnant or under-nourished sheep. Affected sheep show clinical signs of diarrhoea, depression, recumbency and anorexia and post-mortem evidence of fatty degeneration of the liver. ... Severe lesions are seen in sheep which appear clinically normal at the time of death. Rams may develop atrophy of the semeniferous epithelium of the testes. [Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988., p. 96]**PEER REVIEWED**
  
• The principal anticestodal use of hexachlorophene in the USA has been for control of chicken tapeworms, especially Raillietina cesticillus. A single oral dose of 30-60 mg/kg after an overnight fast removes most of these tapeworms. Up to a 30% drop in egg production may be expected following treatment. Combination of hexachlorophene and nicotine sulfate or phenothiazine make it possible to deworm poultry for the tapeworms and ascarids simultaneously. [Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University Press, 1982., p. 859]**PEER REVIEWED**
  
• Some biochemical actions of hexachlorophene include uncoupling of oxidative phoshorylation with resulting hyperthermia and inhibition of cytochrome oxidase, lactic dehydrogenase, and succinoxidases of liver, kidney, and heart cells. ... In developing rats, hexachlorophene (10 mg/kg/day) does not seem to affect brain adenosine triphosphate, phospholipid, sterol, protein, or deoxyribonucleic acid or ribonucleic acid concentrations. Hexachlorophene causes osmotic swelling of erythrocyte membranes by altering their permeability to sodium and potassium. [Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University Press, 1982., p. 983]**PEER REVIEWED**
  
• A study was made of deviations in the profiles of hepatic amino acids after repeated exposure of mice to hexachlorophene (HCP). Male mice (Mus booduga) were administered HCP orally at 20 40 or 60 mg/kg per day ln corn oil; on day eight total body weights and liver somatic indices and dry weights were measured. In another experiment HCP was given for 7 days at 60 mg/kg per day after which livers were obtained and analyzed for free amino acid concentratlons and enzyme activities. Dose dependent reductions In food consumption and body weight were observed with HCP treatment. Wet and dry liver weights were reduced only at the highest dose and liver somatic indices were increased dose dependently with 40 and 60 mg/kg HCP. Hyperthermia and hind limb weakness progressing to paralysis occurred in mice treated with 60 mg/kg HCP for 7 days. There was a general trend toward increased free amino acid levels in livers of treated mice. Hepatic levels of free neutral amino acids increased significantly with HCP treatment. Aspartic acid levels declined and glutamic acid levels increased significantly. Liver transaminases and glutamate-dehydrogenase showed decreased specific activities. Glutamine-synthetase was not significantly altered and glutaminase decreased significantly. ... [Rajendra W et al; J Environ Sci Health. Part B: Pest Food Contam Agric Wastes 23 (4): 409-26 (1988)]**QC REVIEWED**
  
• Effect of repeated oral administration of hexachlorophene (HCP) on glycolytic and oxidative pathways was studied in the rat brain. The rats were divided into three batches of six. The first batch was treated with paralytic dose (60 mg/kg/day) of HCP for 7 days. The second batch of animals was treated with sublethal dose 18 mg/kg/day for 7 days. The third batch of animals was served as the age matched controls which received vehicle (corn oil) only. The glycolytic and oxidative metabolism of carbohydrates was significantly inhibited ln the brain of rat during HCP treatment and the inhibition was more pronounced in paralytic dose treatment as compared to sublethal dose treatment. The inhibition of NADP-isocitrate dehydrogenase coupled with glucose 6-phosphate dehydrogenase indicates reduced generation of NADPH2 and pentoses for the synthesis of fatty acids and nucleotides. [Ralendra W et al; J Environ Sci Health B 27 (6): 751-8 (1992)]**QC REVIEWED**
  
• Cerebral ammonia glutamate and related metabolite patterns in mice were observed during hexachlorophene (HCP) induced neurotoxicity. Male mice were given HCP intragastrically at sublethal doses of 60 mg/kg/day for 1 week. Most symptoms of HCP intoxication were neurological in nature. Hind limb weakness in mice was noted within 3 to 5 days and progressed to paralysis after 5 days of treatment. Drowsiness, listlessness and weight loss were noted after 6 to 7 days. Blood and brain ammonia levels rose following 7 days of HCP treatment. A conspicuous rise was noted in glutamine and gamma-amino-butyric-acid (GABA) levels as well as depletion of glutamate levels In brain. The glutamine/glutamic acid ratios of brain were high in intoxicated mice presumably due to the reversible fixation of excess ammonia as glutamine. /Results suggest/ that while the accumulation of ammonia in the brain of HCP intoxicated mice cannot at present be explained. It may have significant implications for the neurotoxicity of HCP since ammonia does affect the brain function in a multifaceted fashion. Accumulation of GABA and increased GABA/glutamic acid ratios suggest a depressed state of the brain perhaps contributing to the expression of HCP neurotoxicity. [Prasad GV et al; Bull Environ Contam Toxicol 38 (4): 561-4 (1987)]**PEER REVIEWED**
  
• Seven cell specific marker enzymes in brain and optic nerve and morphological evaluation by light microscopy were used to characterize the neurotoxicity associated with exposure of rats to hexachlorophene (HCP); 40 mg/kg/day, po, for 9 days). In vitro exposure to HCP at concn up to 100 uM had no direct inhibitory effect on the marker enzymes, validating their use in evaluating brain function in vivo. Rats exhibited a reduction in body weight gain, weakness, and ataxia of the hind limbs by the ninth day of HCP exposure. At 24 hr following the last day of exposure to HCP, the activities of the three neuron specific enzymes, glutamic acid decarboxylase, tyrosine hydroxylase, and choline acetyltransferase, In rat brain were unchanged from those of the vehicle treated control group. Of the two astroglial enzyme markers measured, a small but significant increase was observed In the activity of nonneuronal enolase In the cerebellum and glutamine synthetase in the hippocampus of HCP-treated rats. The optic nerve appeared to be the most sensitive tissue iln that the activity of both the astroglial marker, nonneuronal enolase, and the myelin marker, 2',3'-cyclic nucleotide phosphohydrolase, was significantly decreased following HCP exposure. This decrease in enzyme activity is consistent with the histological observations demonstrating extensive vacuolization and edema in the optic nerve after exposure to HCP. [Kung MP et al; Fundam Appl Toxlcol 11 (3): 519-27 (1988)]**QC REVIEWED**
  
• ... /Rats/ were divided into two groups, the experimental group received HCP at a daily dose of 20 mg/kg po for 53 consecutive days whereas the control group received an equivalent amount of the vehicle only. HCP produced no change ln 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 produced 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 ln the sciatic nerve, hippocampus and optic nerve, respectively. [Kung MP et al; Neurotoxicol 10 (2): 201-10 (1989)]**PEER REVIEWED**
  
• ... Hexachlorophene (HCP) can affect myelin formation or integrity leading to intramyelinic edema & vacuolation in the CNS through an unknown mechanism. These studies were conducted to investigate the direct dose dependent effects of HCP on myelin membrane markers in cultured oligodendrocytes isolated from 4-7-day-old rat pups & cultured in vitro for up to 5 wk. Two wk old oligodendrocyte cultures were exposed to 0, 0.24 or 0.74 uM HCP for 48 hr. At 48 hr & again at 5, 12 & 19 days after the end of dosing the myelin markers, galactosylceramide (GalC) myelin basic protein (MBP) & 2',3', -cyclic nucleotide 3 phosphohydrolase (CNPase) were quantified by ELISA or histochemical techniques. DNA was measured to estimate total cell mass & astrocyte contamination was determined by an ELISA procedure using anti-glial fibrillary acidic protein (GFAP) as the primary antibody. Because of the use of a selective culture medium astrocyte contamination was initially low & continued to decr from wk 2 to 4 as determined by GFAP binding. CNPase, GalC & MBP levels were similar in control & low dose (0.24 uM HCP) cultures with a general incr in MBP & CNPase over time. Cultures exposed to 0.74 uM HCP showed a decr in GalC proportional to decr DNA content with time, but levels of MBP & CNPase incr after dosing & were always > the corresponding levels in control or low dose cultures. These studies suggest a direct dose related toxic effect of HCP accompanied by a stimulation of MBP & CNPase but not a GalC production in the membranes of the recovering OLG following removal of HCP. [Amacher DE, Schomaker SJ; Toxicol In Vitro 8 (1): 1-11 (1994)]**QC REVIEWED**
  
• When neonatal rats are washed with Phisohex containing 3% hexachlorophene during the first 8 days of life ..., they are significantly less fertile when mated at maturity. At 11 months of age the treated males exhibit mounting & intromission but no ejaculation. However, the epididymis of these animals contains large numbers of motile spermatozoa. Thus, the CNS-integrated ejaculatory reflex appears to be permanently damaged in these animals. [Thomas, J.A., K.S. Korach, J.A. McLachlan. Endocrine Toxicology. New York, NY: Raven Press, Ltd., 1985., p. 313]**QC REVIEWED**
  

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Human Toxicity Values

• None found

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Non-Human Toxicity Values

• LD50 RAT MALE ORAL 6 MG/KG [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 248 (1979)]**PEER REVIEWED**
  
• LD50 RAT FEMALE ORAL 56 MG/KG [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 248 (1979)]**PEER REVIEWED**
  
• LD50 RAT WEANLING ORAL 120 MG/KG [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 248 (1979)]**PEER REVIEWED**
  
• LD50 RAT SUCKLING (10 DAYS OLD) ORAL 9 MG/KG [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 248 (1979)]**PEER REVIEWED**
  
• LD50 Rat oral 187 mg/kg [Gump WS; J Soc Cosmet Chem 20: 173-84 (1969)]**PEER REVIEWED**
  
• LD50 Rat oral 67 mg/kg [Chung HL et al; Chinese Med J 82: 691-701 (1963)]**PEER REVIEWED**
  
• LD50 Rat Female Wistar oral 63-87 mg/kg [Nakaue HS et al; Toxicol Appl Pharmacol 24: 239-49 (1973)]**PEER REVIEWED**
  
• LD50 Rat Male Wistar oral 58-87 mg/kg [Nakaue HS et al; Toxicol Appl Pharmacol 24: 239-49 (1973)]**PEER REVIEWED**
  
• LD50 Rat skin 1840 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1783]**QC REVIEWED**
  
• LD50 Rat ip 22 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1783]**QC REVIEWED**
  
• LD50 Rat subcutaneous 14,700 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1783]**QC REVIEWED**
  
• LD50 Mouse oral 67 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1783]**QC REVIEWED**
  
• LD50 Mouse skin 270 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1783]**QC REVIEWED**
  
• LD50 Mouse ip 20 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1783]**QC REVIEWED**
  

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Absorption, Distribution and Excretion

• Hexachlorophene was administered intraperitoneally to rats and rabbits. Excretion of this chemical was slow, most (48-83%) excreted unchanged in the feces. [Menzie, C.M. Metabolism of Pesticides-Update III. Special Scientific Report- Wildlife No. 232. Washington, DC: U.S.Department of the Interior, Fish and Wildlife Service, 1980., p. 323]**PEER REVIEWED**
  
• ... /FROM/ USE OF 3% HEXACHLOROPHENE SOLN AS BODY & HAND SOAP, BLOOD LEVELS RANGED FROM LESS THAN 0.005-0.38 MG/L BLOOD, COMPARED WITH MEAN BASELINE CONCN IN 30 CONTROL PEOPLE OF 0.02 MG/L BLOOD. AFTER PROLONGED USE OF SOAP CONTAINING 0.75% HEXACHLOROPHENE, LEVELS RANGED FROM 0.02-0.14 MG/L BLOOD ... USE OF MOUTHWASH CONTAINING 0.5% HEXACHLOROPHENE FOR 3 WK PRODUCED LEVELS OF 0.02-0.12 MG/L BLOOD. IN STUDY OF RANDOMLY SELECTED HOSPITAL PT ... BLOOD LEVELS RANGED FROM 0 TO 0.12 MG/L, WITH MEAN LEVEL OF 0.03 MG/L. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 244 (1979)]**PEER REVIEWED**
  
• PERCUTANEOUS ABSORPTION OF HEXACHLOROPHENE THROUGH HUMAN FOREARM SKIN IS 3% OF DOSE. /FROM TABLE/ [The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 2: A Review of the Literature Published Between 1970 and 1971. London: The Chemical Society, 1972., p. 132]**PEER REVIEWED**
  
• IN RATS, UP TO 55% OF DERMALLY APPLIED HEXACHLOROPHENE IS ABSORBED IN 24 HR. DERMAL ABSORPTION IS ENHANCED BY DIMETHYLSULFOXIDE & DERMATITIS OR SKIN ABRASIONS. ... IN CATS BLOOD LEVEL PEAKS AT OR BEFORE 12 HR & SUBSIDES TO VERY LOW LEVEL 24 HR AFTER DOSAGE. ... MOST OF CMPD IS ELIMINATED FROM MAMMALIAN BODY IN SEVERAL DAYS. [Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University Press, 1982., p. 983]**PEER REVIEWED**
  
• SAMPLES OF ADIPOSE TISSUE OBTAINED FROM NECK DURING ROUTINE SURGERY CONTAINED MEAN CONCN OF 0.01 MG/KG TISSUE; ABDOMINAL FAT OBTAINED AT AUTOPSY CONTAINED 0.04 MG/KG TISSUE. IN ANOTHER STUDY, HEXACHLOROPHENE WAS DETECTED AT LEVELS OF 0-80 UG/KG ADIPOSE TISSUE. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 244 (1979)]**PEER REVIEWED**
  
• PLACENTAL TRANSFER ... HAS BEEN DEMONSTRATED IN RATS. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V20 249 (1979)]**PEER REVIEWED**
  
• WHEN HEXACHLOROPHENE WAS FED TO A COW, THE INTACT MATERIAL WAS EXCRETED VIA URINE (0.24%) & FECES (63.8%). [Menzie, C. M. Metabolism of Pesticides, An Update. U.S. Department of the Interior, Fish, Wild-life Service, Special Scientific Report - Wildlife No. 184, Washington, DC: U.S. Government Printing Office, l974., p. 221]**PEER REVIEWED**
  
• HEPATIC FUNCTION IS IMPORTANT DETERMINANT IN REMOVAL OF HEXACHLOROPHENE. WITHIN 3 HR AFTER ADMIN, 50% WAS EXCRETED IN BILE OF RATS. PRETREATMENT WITH PHENOBARBITAL ENHANCED PLASMA DISAPPEARANCE & DOUBLED RATE AT WHICH IT & ITS METABOLITES WERE EXCRETED INTO BILE. 2/3 HEPATECTOMY DECR RATE OF REMOVAL OF HEXACHLOROPHENE FROM PLASMA & DECR RATE OF EXCRETION INTO BILE TO APPROX 1/3 THAT OF CONTROL ANIMALS. [KLAASSEN CD; TOXICOL APPL PHARMACOL 49 (1): 113-7 (1979)]**PEER REVIEWED**
  
• Generally, clinical effects do not correlate well with blood hexachlorophene levels & no safe /blood/ level has been determined for premature infants. [Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1221]**QC REVIEWED**
  
• Rats given HCP intraperitoneally excreted about 5% of the dose in urine and none as CO2. More than 70% of the material was excreted in feces. Whereas urine contained HCP only as a conjugate, probably the glucuronide, feces contained HCP both free and conjugated. [Menzie, C.M. Metabolism of Pesticides-Update III. Special Scientific Report- Wildlife No. 232. Washington, DC: U.S.Department of the Interior, Fish and Wildlife Service, 1980., p. 323]**PEER REVIEWED**
  

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Metabolism/Metabolites

• HEXACHLOROPHENE YIELDED HEXACHLOROPHENE-BETA-D-GLUCURONIDE IN RAT & RABBIT. /FROM TABLE/ [Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. H-3]**QC REVIEWED**
  

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TSCA Test Submissions

• None found

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Footnotes

¹ Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.