HEXACHLOROPHENE

Drugs in Pregnancy and Lactation.

"Official medicines" is the best online drugstore.

World’s leading meds delivered to your door – and you don’t even need a prescription! Only certified, first class drugs on offer! Buy more and spend less with our great discount system.

.


Name: HEXACHLOROPHENE
Class: Anti-infective
Risk Factor:    CM

Fetal Risk Summary

Hexachlorophene, a polychlorinated biphenol compound, is a topical antiseptic used primarily as a surgical hand scrub and as a bacteriostatic skin cleanser. Although no longer recommended, hexachlorophene has also been used as a douching agent and in feminine hygiene sprays. The drug is rapidly absorbed systemically following topical administration to injured skin, but percutaneous absorption also occurs across intact skin (1,2 and 3). Because of very rapid absorption, hexachlorophene should not be used on mucous membranes or injured skin (1,2).

Blood concentrations of the anti-infective have been documented in premature and full-term newborns who were bathed with hexachlorophene and in adults after chronic handwashing (3). Central nervous system toxicity has been observed following the topical use of hexachlorophene in burn patients and after intravaginal application (3).

Hexachlorophene crosses the human placenta (4,5). Newborn whole cord blood concentrations in one study ranged from 0.003 to 0.182 µg/g with a mean of 0.022 µg/g (1 µg/g = 1 ppm) (4). The source of the drug was thought to be from vaginal sprays used by the mothers and from preparation of the skin immediately before delivery. In a second study, a commercially available 3% emulsion of hexachlorophene was used as antiseptic lubricant for vaginal examinations during labor (5). At delivery, detectable maternal serum concentrations of the drug occurred in 12 of 28 women (range 0.142–0.942 µg/mL) and in the whole cord blood of 9 of 28 newborns (range 0.177–0.617 µg/mL). Because of the potential for toxicity, the authors recommended the use of alternative lubricants.

A number of studies have examined the reproductive toxicity of hexachlorophene in various animal species (6,7,8,9,10,11,12,13 and 14). A marked reduction in the sperm count was observed in male rats administered a single oral dose of 125 mg/kg (6). In pregnant rats, dose-related teratogenicity was demonstrated following acute and chronic oral dosing (6,7,8 and 9). No malformations resulted with relatively low doses (6,7 and 8), but high maternal doses were associated with cleft palate (8) and with microphthalmia, anophthalmia, and rib anomalies (9). Intravaginal administration of hexachlorophene in pregnant rats resulted in frequent microphthalmia, anophthalmia, wavy ribs, and less frequently, cleft palate in the offspring (10,11). Blood concentrations were 6–10 times higher after vaginal or oral administration than after dermal application (11). Oral doses of 6 mg/kg/day in pregnant rabbits produced defects of the ribs in a small percentage of exposed fetuses, indicating a minimal teratogenic response (9).

Three studies have described the distribution of hexachlorophene in the fetuses of pregnant mice, rats, and monkeys (12,13 and 14). In fetal mice, the drug selectively accumulated in the brain, optic vesicles, and neural tube in early gestation (12). During late gestation, high fetal concentrations were measured in the blood, liver, and intestine. A similar pattern of distribution during gestation was described in fetal monkeys (13). In both mice and monkeys, a partial blood-brain barrier was demonstrated to hexachlorophene in term fetuses (12,13). Hexachlorophene crossed the placenta in pregnant rats after both oral and dermal administration with concentrations detected in the placenta, amniotic fluid, and fetus (14).

Only one study has associated the routine use of hexachlorophene with human teratogenicity (15). The results of the investigation were summarized as a news item in a medical journal approximately a year before publication of the original study (16). In a retrospective analysis of the pregnancy outcomes among nurses who had washed their hands with hexachlorophene during the 1st trimester, 25 severe malformations were observed in 460 neonates (15). No major congenital defects were observed among 233 newborns delivered from similarly employed mothers who did not use hexachlorophene. The exposed nurses had worked at one of six Swedish hospitals between 1969 and 1975, and had washed their hands 10 to 60 times/day with either a 0.5% or 3% hexachlorophene liquid soap. Three of the hospitals also used a 0.3% or 0.5% hexachlorophene hand cream. Among the exposed group, 46 newborns, in addition to the 25 with major defects, had minor malformations for a total of 71 affected infants (15.4%). The major malformations included cleft lip and/or palate, microphthalmia, anal atresia and hypospadias, cystic kidneys, esophageal atresia and kidney defects, limb reductions, diaphragmatic hernia, neural tube defects, pulmonary stenosis, and cardiac defects. Minor mal- formations included dislocations of the hip, undescended testes, polydactyly, various foot anomalies, and mild cardiac defects. Eight (3.4%) minor malformations were observed in the control group.

Criticisms of this study on methodological grounds have been published (17,18). Most of the hexachlorophene-exposed nurses were selected because of an infant malformation, not on the basis of exposure to the drug, thus leading to a higher rate of malformations in the exposed group. The selection of the control group was also criticized and was considered, at least on statistical grounds, not to be representative of random selection (17). Concern was expressed over the identification of the minor defects and how diligently these defects were searched for at the various hospitals (18). Furthermore, another study evaluated delivery data on women working in Swedish hospitals from 1973–1975 and compared them with births in the general Swedish population during the same period (19). A cluster of malformed infants was found in 1973–1974 that was similar to that observed in the report associating defects with hexachlorophene. However, the rates of perinatal deaths and congenital malformations did not differ between 3,007 infants born to women heavily exposed to hexachlorophene in 31 hospitals and 1,653 infants born to women working in 18 hospitals where the antiseptic was not used at all or was used only sporadically (19).

In summary, one report has suggested that heavy use of hexachlorophene during the 1st trimester may cause birth defects in exposed offspring, but several criticisms have been directed at this study on methodological grounds. Moreover, in nonprimate animal species, only very high levels (i.e., those approaching maternal toxicity) of hexachlorophene are teratogenic. These considerations, coupled with the absence of confirming reports in humans, suggest a lack of an association between routine handwashing with hexachlorophene and human congenital malformations. Because of other toxicities, use of the antiseptic on mucous membranes, such as in the vagina, or on injured skin should be avoided.

Breast Feeding Summary

Hexachlorophene has been detected in the milk of lactating rats following a single oral dose of 10 mg/kg on the 2nd postpartum day (14). Detectable milk concentrations of hexachlorophene were found 1 hour after the dose.

In humans, hexachlorophene has been measured in milk following the presumed use of the antiseptic as a nipple wash between nursings (20). The specific history of hexachlorophene use by the women was not available. Six samples of milk were found to have a range of hexachlorophene levels from trace (<2 ppb) to 9.0 ppb (1 ng/g = 1 ppb). The authors concluded that the milk concentrations of hexachlorophene found in their study were too low to present a risk to a nursing infant. The American Academy of Pediatrics has not found any reports describing signs or symptoms in a nursing infant or effect on lactation after use of the drug, but notes that nipple washing with hexachlorophene may contaminate the milk (21).

"Official medicines" is the best online drugstore.

World’s leading meds delivered to your door – and you don’t even need a prescription! Only certified, first class drugs on offer! Buy more and spend less with our great discount system.

References

  1. American Hospital Formulary Service. Drug Information 1997. Bethesda, MD:American Society of Health-System Pharmacists, 1997:2716–8.
  2. Product information. pHisoHex. Sanofi Winthrop Pharmaceuticals, 1993.
  3. Lockhart JD. How toxic is hexachlorophene? Pediatrics 1972;50:220–35.
  4. Curley A, Hawk RE, Kimbrough RD, Nathenson G, Finberg L. Dermal absorption of hexachlorophene in infants. Lancet 1971;2:296–7.
  5. Strickland DM, Leonard RG, Stavchansky S, Benoit T, Wilson RT. Vaginal absorption of hexachlorophene during labor. Am J Obstet Gynecol 1983;147:769–72.
  6. Thorpe E. Some pathological effects of hexachlorophene in the rat. J Comp Pathol 1967;77:137–42.
  7. Gaines TB, Kimbrough RD. The oral and dermal toxicity of hexachlorophene in rats. Toxicol Appl Pharmacol 1971;19:375–6.
  8. Oakley GP, Shepard TH. Possible teratogenicity of hexachlorophene in rats (abstract). Teratology 1972;5:264.
  9. Kennedy GL Jr, Smith SH, Keplinger ML, Calandra JC. Evaluation of the teratological potential of hexachlorophene in rabbits and rats. Teratology 1975;12:83–8.
  10. Kimmel CA, Moore W Jr, Stara JF. Hexachlorophene teratogenicity in rats. Lancet 1972;2:765.
  11. Kimmel CA, Moore W Jr, Hysell DK, Stara JF. Teratogenicity of hexachlorophene in rats. Comparison of uptake following various routes of administration. Arch Environ Health 1974;28:43–8.
  12. Brandt I, Dencker L, Larsson Y. Transplacental passage and embryonic-fetal accumulation of hexachlorophene in mice. Toxicol Appl Pharmacol 1979;49:393–401.
  13. Brandt I, Dencker L, Larsson KS, Siddall RA. Placental transfer of hexachlorophene (HCP) in the marmoset monkey (Callithrix jacchus). Acta Pharmacol Toxicol 1983;52:310–3.
  14. Kennedy GL Jr, Dressler IA, Keplinger ML, Calandra JC. Placental and milk transfer of hexachlorophene in the rat. Toxicol Appl Pharmacol 1977;40:571–6.
  15. Halling H. Suspected link between exposure to hexachlorophene and malformed infants. Ann NY Acad Sci 1979;320:426–35.
  16. Check W. New study shows hexachlorophene is teratogenic in humans. JAMA 1978;240:513–4.
  17. Källen B. Hexachlorophene teratogenicity in humans disputed. JAMA 1978;240:1585–6.
  18. Janerich DT. Environmental causes of birth defects: the hexachlorophene issue. JAMA 1979;241:830–1.
  19. Baltzar B, Ericson A, Källen B. Pregnancy outcome among women working in Swedish hospitals. N Engl J Med 1979;300:627–8.
  20. West RW, Wilson DJ, Schaffner W. Hexachlorophene concentrations in human milk. Bull Environ Contam Toxicol 1975;13:167–9.
  21. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.

Index

Q&A about Hexachlorophene

Ahmed A
How could hexachlorophene gets toxic while used for diaper rash in children?
Fredrick Carley
It was used underarm. I guess the benefits outweigh the drawbacks.
Fri3ndlY
Where can I buy hexachlorophene?
I have found out that this can be used as a skin allergy prevention and would like it to stop heat rash when I go on holiday
old know all
From the pharmacy counter in the chemists. You'll have to convince the pharmacist you're not going to drink it.
Nina T
hexachlorophene and glycerol tristearate.?
Is there any site that will give me thorough information on hexachlorephene( about it's structure, social effects, environmental effects, use in local industry, etc.)?

Can you also tell me any website or book that would give me information on the synthesis of glycerol tristearate?

Please help soon, it is for a major chem project that I have to hand in next week!!!!
NONAME
Hexachlorophene: go here --> http://www.pesticideinfo.org/Detail_Chem...

glyceryl tristearate: go here --> http://www.springerlink.com/content/x538...

good luck =O)