492 HEXACHLOROPHENE
Neff, J. M., Lane, J. M., Pert, J. H., et al.: Compli-cations of smallpox vaccination. I. National sur-vey in the United States, 1963. New Eng. J. Med., 276:125, 1967.
Neff, J. M., Levine, R. H., Lane, J. M., Ager, E. A., Moore, H., Rosenstein, B. J., Millar, J. D.,
and Henderson, B. A.: Complications of small-pox vaccination, United States, 1963. II. Results
obtained by four statewide surveys. PEDIATRICS,
39:916, 1967.
Neff, J. M.: The case for abolishing routine child-hood smallpox vaccination in the United States. Amer. J. Epidemiol., 93:245, 1971.
Public Health Service Recommendation on Small-pox Vaccination. Morbidity and Mortality: 20:
339, 1971.
HEXACHLOROPH
ENE
Y
ET another chemical widely used by thepopulation has been discovered to be
potentially dangerous. Hexachlorophene
was first synthesized in 1939 and found to
have both bactericidal and fungicidal prop-erties, but its toxicity has only been
appre-ciated in the last few years. Probably the
most alarming aspects are that the chemical is not only neurotoxic but is also readily ab-sorbed from the skin.
Although muscle twitching and coma
were observed 3 years ago in burn patients treated with hexachlorophene, these
obser-vations were not actually responsible for
the recent toxicity studies which have fo-cused attention on this subject and raised
many important questions. These studies,
begun in 1970 at the FDA Division of Pesti-cide Chemistry and Toxicology in Atlanta, were related to the use of hexachlorophene as a fungicide on citrus fruits and a number
of vegetables, including cucumbers,
toma-toes, and potatoes. Rats fed
hexachioro-phene daily developed cerebral edema and
cystic spaces in the white matter of the
brain and spinal cord. The findings were
presented at the Society of Toxicology
meeting in March of 1971 and the implica-tions immediately became apparent,
partic-ularly for the newborn. Blood levels were
determined in infants given daily baths
with hexachlorophene in a 3% emulsion
and reported in the Lancet in August 1971.
In some cases these levels were nearly 50%
of those associated with neurotoxicity in the
rats which had been fed the chemical.
The FDA immediately notified the
Academy Committee on the Fetus and
Newborn of these developments and
pro-posed a warning statement. The initial reac-tion of the Committee at its meeting in Oc-tober of 1971 was that more information
was needed and the experiments in rats
might not be relevant to the human.
Conse-quently the Committee did not agree to
en-dorse the statement at that time.
Shortly thereafter, results of testing the
effect of skin washing with
hexachloro-phene in newborn monkeys became
avail-able. The animals were washed daily with
one teaspoonful of a detergent containing 3% hexachlorophene which was subsequent-ly washed off. After 90 days all of six
ani-mals showed extensive lesions in the brain
and spinal cord, and two had papilledema.
No lesions were detected in five control
animals. The experiments left a number of
questions unanswered. The amount of
hexachiorophene used in the small animals,
which weighed only approximately 400 gm
at birth, was proportionally greater per unit
of body surface than is customarily used in
the human infant. There might be
differ-ences in absorption due to the number of
sweat glands in the skin of the monkey,
some of the chemical might have been
licked from the skin, and there also might
have been difficulties in washing the
ma-terial off because of hair. There was no
indication as to how rapidly these lesions
developed nor whether they might be
COMMENTARIES
493
Despite these questions the Academy
Com-mittee agreed unanimously that the
warn-ing statement of the FDA should be
endorsed and promptly sent to all physicians.
A summary of the Committee statement
appeared in the January issue
(
Pimwrmcs,49:4, 1972) and the full statement appears
on page 625 of this issue.
In the light of these new toxicity studies the question of introducing still another
iat-rogenic disease must be considered. It
might be argued that, because
hexachloro-phene has been used for newborn skin care
over such a long period, without any
abnor-mal neurological signs having been
de-tected and without any pathological
evi-dence of neurotoxicity, the chemical as
presently applied is completely safe. One
does not have to search far, however, to
find examples of iatrogenic disease which
has eluded the eye of even watchful physi-cians. Those caring for newborn infants are particularly alert to this tragic possibility. It
was many years before the relationship be-tween oxygen toxicity and retrolental
fibro-plasia was recognized; similar delays were
experienced in associating chioramphenical
with the “grey baby syndrome” and only a
carefully controlled study on the use of pro-phylactic antibiotics revealed the cause and effect relationship between sulfa drugs and
kernicterus. Problems arising from the use
of DDT might also be cited as another
ex-ample. For years this chemical was univer-sally used in large quantities before its rela-tionship to aplastic anemia was recognized, and arguments as to the relative benefits and risks still rage.
Prophylactic skin care with
hexachioro-phene was introduced because of an
epi-demic of a virulent staphylococcus. The ep-idemic, first recognized in the late 1940’s and early ‘50’s and world-wide, occurred si-multaneously in hospitals in Europe, North
series, maternity, and surgical wards. The
staphylococcus appears to spread
princi-pally by hand transfer from personnel but
air transfer of the organisms probably also
plays some role. The first reported
success-ful use of hexachlorophene in a 3%
emul-sion for the reduction of staphylococcal in-fection in a nursery appeared in 1952 in the
Canadian Medical Journal. Since that time
there have been numerous communications,
many claiming hexachiorophene to he
effective in reducing the incidence of
nur-sery infection and colonization, but some reporting failure.
It is widely believed that this last
epi-demic was caused by the development of a
new strain of staphylococcus which was
resistant to antibiotics and which had
ac-quired unusually virulent and lethal
prop-erties. Some authorities related the appear-ance of this new strain to the widespread use of antibiotics. In the historical perspec-tive of staphylococcal disease, there is some
evidence to indicate an episodic nature of
outbreaks. A severe epidemic in the
new-born was reported in 1904 in the American
Journal of Obstetrics and Gynecology;
an-other was reported in 1929. The cause of
this wave-like incidence of disease is not
known. Nor is the waxing and waning of
virulence which is seen to occur in a
num-ber of bacteria understood. The widespread incidence of disease occurring simultane-ously and the evidence of prior epidemics which have occurred in a wave-like fashion suggest more the spread of a viral disease
in a susceptible population, rather than a
bacterial infection alone. Thus, at the
mo-ment it can be stated with a fair degree of
certainty that the cause for the rise and de-cline of the recent staphylococcal epidemic
is not known. While this decline has
coin-cided with an increase in the use of
hexa-EnsTon’s NoTE: This was the position of the Academy when the April issue of PEDIATRICS went to press, March 13, 1972. See also page 625, this issue.
494 HEXACHLOROPHENE
disease and in the carrier state when
hexa-chlorophene washing was introduced on a
regular basis, the overall role of
hexachloro-phene has been difficult to evaluate because
many other changes in newborn care were
introduced at the same time.
Thus in reviewing all the available infor-mation, the Academy Committee on the
Fe-tus and Newborn concluded that the daily
prophylactic use of hexachlorophene-con-taming solutions on a routine basis could
not be recommended for asymptomatic in-fants. This in no way precludes its use for treatment of specific infections, or if there is
an outbreak of staphylococcal disease. It
is unlikely, however, that such treatment
will interrupt a true outbreak with an
epi-demic strain. The Committee has also wished to reemphasize that the main source
of infection is hand contact and breaks in
technique. Meticulous attention to hand
washing before and after handling each
infant is essential. Other important
mea-sures include local treatment of the
um-bilical cord and nares with bacitracin or
neomycin.
In this era of chemotherapeutics the new
information on
the
potential toxicity of hexachiorophene indicates the importanceof constant surveillance and evaluation of
nursery procedures. Many of our time
hon-ored practices, even the caring of infants in incubators, are being scrutinized and ques-tioned. This is a period of rapid change and advance. If optimal care is to be provided, flexibility and revision are essential.
L. STANLEY JAMES, M.D., Chairman
Committee on Fetus and Newborn
American Academy of Pediatrics
630 West 168th Street
