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OCR for page 1
EXECUT IVE SUGARY
BACKGROUNI)
Seven pesticides are registered with the Environmental Protection
Agency (EPA) for control of subterranean termites: chlordane,
hepeachlor, aldrin, dieldrin, lindane, pentachlorophenol, and
chlorpyrifos. Chlordane is the most widely used of this group ~ and
heptachlor the second most widely used. Before 1974, chlordane and
aldrin accounted for 55 percent and 40 percent of market sales,
respectively. The use of aldrin was drastically reduced after EPA
cancellation hearings. However, because of recent increases in the
price of chlordane, the use of aldrin to control termites is
increasing, and it may soon account for 25 percent of the market.
Dieldrin and lindane, although effective as termiticides, have rarely
been used for this purpose. Pentachlorophenol is generally used for
special applications, such as wood impregnation, and rarely for
controlling subterranean termites. Chlorpyrifos is a newer product
and only recently teas been marketed for the control of subterranean
termites.
Chlordane has been the pesticide of choice for termite control in
military housing. There now are several reports of the presence of
airborne chlordane in military housing long after application; such
findings have caused concern over adverse health effects among
residents. The problem has been related primarily to housing built on
poured concrete slabs with heating and cooling ducts in or below the
slabs. Contamination has occurred when the ducts cracked or when
exterminators accidentally pierced the ducts during application of
ch lordane. As a resul t, the Air Force in 19 78 asked the National
Research Council's Committee on Toxicology, in the Board on Toxicology
and Environmental Health Bssards, Commission on Life Sciences, to
review the toxicity data on chiortane and to suggest an airborne
concentration that could be used as a guideline in deciding whether
the housing should be vacated. Two National Research Council
committees had previously conducted detailed reviews on chlordane and
some of the other tenmiticides (NBC, 1977a,b). However, neither of
these studies involved an assesement of the possible health risks
associated with airborne exposure of the ten~iticides.
The Committee on Toxicology (NRC, 1979) concluded that it "could
noe determine a level of exposure to chlordane below which there would
be no biologic effect under conditions of prolonged exposure of
families in military housing." However, it did suggest an interim
airborne concentration of 5 ~g/m3, which was pragmatically
determined on the basis of "own concentratione of chlordane in the
military housing, a review of reported health complaints of residents
of contaminated housing, and a comparison with the acceptable daily
intake derived from long~term animal feeding studies. The Committee
al so suggested that a prospective epidemiologic study of persons
exposed to chlordane in military housing would help substantially in
making a risk assesament.
— 1 —
OCR for page 2
In 1960, the Comptroller General of ache United States (GAO, 1980)
recommended that the EPA initiate a fon"1 risk-benefit review of
chlordane to determine whether its registered uses for subsurface
termite control should be 1 limited or canceled and whether the heal th
of people living in housing treated with chlordane is being adversely
affected. In response to these recommendations, the EPA has initiated
a risk-benefie review of all seven pesticides registered for control
of subterranean termites.
Faced with recurring exposures of personnel to chlordane in
military housing, the Department of Defense issued an order in May
198V prohibiting further applicat on of chlordane for buildings with
subelab or intraelab ducts. It also recommended chat, where the risk
and extent of possible termite damage in existing structures are
considered unacceptable, studies be undertaken to determine the
feasibility of sealing subelab or intraslab ducts and of renovating
heating and cooling systems to use aboveground and above-alab ducts.
As a second step in the review of chlortane, the Department of
Defense, through the Anmet Forces Pest Management Board, requested in
1981 an independent review of the seven pesticides by the National
Research Council's Committee on Toxicology. Specifically, the
Committee was asked to evaluate the key information on the toxic
effects of the pesticides; make a comparative assesament of the
human~health risks associated with exposure to the pesticides; review
the previously recommended exposure limit for airborne chlordane; and,
if there are sufficient data, suggest airborne exposure 1 imits for the
other pestic ides .
HEALTH EFFECTS OF THE SPECIFIC PESTICIDES
CYCLODIENES (CHLORDANE, HEPTAC~OR, ALDRIN, AND DIELDRIN )
The principal pesticides uset for control of subterranean termites are
the chlorinated cyclodienes--chlordane, beptachlor, aldrin, and
dieldrin. These all bad widespread use as pesticides until the
mid-1970e, when cancellation hearings were held by the EPA. Their use
since then has been severely limited, although their registration for
control of termites was retained.
Acute or chronic exposure of humane to cyclodienes can produce
central nervous system symptoms characterized by headache, blurred
vision, dizziness, involuntary muscle movements, tremors, and
seizures. Date on chronic exposure at low airborne concentrations are
Whited. ~ recent epidemiologic study of workers producing chlordane
suggested that exposure has no long-term effects. However, because of
abortcominge in the study and the suggestion of a trend in standard
mortality ratio. for deaths due to cancer in workers with increasing
length of employment, more complete Thea are needed before fin
conclusions can be reached with regard to the long-term human~health
risks of chlordane and the other cyclodienes.
All four cyclodienes produced hepatocellular carcinomas in B6C3F1
mice; there was not a significant eumorigenic response in
— 2 —
OCR for page 3
Osborne~Mendel rats. Central nervous System effect8--such as
hyperexcitability, tremors, and convulsions--have also occurred in
laboratory animals ted the cyclodiene termiticides. The cyclodienes
are deposited in the body in fat, with biologic retention half lives
on the order of days to several weeks.
Because these compounds are al 1 persistent in the environment,
they can oe effective as termiticides for up to 20 yr after
appl ication.
L INDANE
Lindane is the gaunt isomer of hexachlorocyclohexane. It has had
widespread appl ication as a pesticide, but its use has been Severely
restricted in the last several years. As a termiticide, it is
primarily sprayed on the ~oil, and it persists in the environment for
approximately 10 yr. Lindane has al so been used widely in the
treatment o f scabies and for 1 ous e infes tat ion.
In humans, 1 indane exerts its toxic action on the central nervous
system. Signs of poisoning include tremors, ataxia, convulsions, and
prostration. In severe cases of acute poisoning, violent tonic and
clonic convulsions have occurred. Acute exposure of animals to
1 indane has produced diarrhea, hypothermia, hyperirritability,
incoordination, and convulsions. Long-term exposure has produced
nervous symptoms and fatty degeneration of the 1 iver. Results of
carcinogenicity tests in rodents have not been consistent, with both
positive and negative resul to reported. However, z: appears that the
1 iver is one of the targe t organs at ter chronic exposure.
PE NTACHLOROPHEN()L
Pentachlorophenal is a wood preservative. As a termiticide, it is
applied rarely to soil, but mainly directly to termite-infested wood.
It is not as long-1 ived in the environment as the cyclodienes; its
effectiveness as a termiticide after a single application lasts about
3 yr.
Symptoms of pentachlorophenol intoxication in humans include lose
of appetite, respiratory difficulties, anesthesia, hyperpyrexia,
sweating, dyspnea, and coma. ADiDIal8 exposed to pentachlorophenol had
pathologic changes in the liver and kidneys, in addition to symptoms
associated with uncoupling of oxitative phosphorylation. There was no
evidence of a carcinogenic effect in mice ant rats given
pentachlorophenol orally for 1-2 yr. Embryotoxicity and fetotoxicity
have been observed in offspring of rats given purified or commercial
pentach 1 oropenol .
CHLORPYRIFOS
l
Cblorpyrifos is an organophosphate pesticide with a wide variety of
applications; only in recent years has it been used as a subsurface
termiticide. Its effectiveness in controlling termites after a single
application lasts about 4-10 yr.
— 3 —
OCR for page 4
C1hlorpyrifos is in a different chemical class from the other
termiticides discussed here, and its toxic effects also differ. The
principal effect in has and animals exposed for shore periods is a
reduction in plasma ant red-cell cholinesterase activity. These
changes have occurred af ter oral, termal, ant inhalation exposure .
There is no information on effects of long-eenm exposure of
humans. Rats, mice, ant dogs have been given chlorpyrifos in the diet
for up to 2 yr. At the dosages tested, the only effect observed was a
decrease in cholinesterase activity.
CONCLUSIONS AND RECO - ENDATIONS
To evaluate the risks associated with exposure to the seven pesticides
that are available for controlling subsurface termites and to assess
which of them, if any, are most appropriate for use in military
housing from the standpoint of health risks, the Committee has
considered several factors. These include heal th effects themselves
and environmental end points that influence potential airborne
concentrations, such as vapor pressure, persistence in the
environment, and amount of material that needs to be applied for
optimal effectiveness.
COHI?ARISON OF CARCINOGENIC RISK
Information is insufficient to determine whether carcinogenesis is the
critical biologic end point in h''~s exposed to these pesticides, but
available animal data al low some useful comparisons of care inogenic
risk. The four cyclodienes and lindane have been testes for
c arc inogenic i ty under ~ imi 1 ar experimental pro tocol ~ . Each c ompound
has produced hepatocellular carcinomas in male mice, and this end
point can be used for comparing carcinogenicity.
The EDlo (dosage producing an incidence of liver eumore 10
percent above background) was calculated to make comparisons. EDlo
was chosen because it is the lowest effective dosage that can be
estimated with satisfactory precision, owing to the size of the
experimental groups.
On the oasis of the Edits, heptachlor, aldrin, and d~eldrin had
approximately the same carcinogenic activity and were more potent than
calordane; lindane had about one~sixth the activity of chlordane. Ibe
calculated EDlo. for dietary aldrin, dieldrin, heptachlor,
chlordane, and lindens were 3.1, 3.6, 5.0' 16, and 103 ppm,
respectively. me upper 95 percent conf idence bounds on 1 if etime
cancer rick expressed as the probability of cancer after a lifetime
consumption of 1 L of weeer per day containing the compound at a
concentration of 1 ug/L have also been estimated.
A 1 imitation in interpreting the results of the bioassays is that
the route of exposure was the diet, whereas the primary route of
exposure of humane to these pesticides applied for termite control is
inhalation. However, given this limitation, and on the basis of the
EDlo. and the upper conf idence bounds on 1 if etime cancer risk, the
— 4 —
OCR for page 5
ranking from greatest to least risk would be: aldrin, dieldrin >
heptachior ~ chlordane ~ lindane.
The carcinogenic potential of chiorpyrifos was investigated in
C0-1 mice; there did not appear to be any tumors related to
administration of th is pesticide. Direc t c omparis on with the
chlorinated hydrocarbons is not possible, because a different test
protocol and a different strain of mice were used. However, using the
highes t dosage in the chlorpyrifos study, 15.8 ppm, and the same
experimental conditions, one could es timate the proportion of animals
that woul d be expected to have tenors af ter exposure to the other
pesticides. On the basis of this analysis, chlordane ant 1 indane
would be expected to yield negative results if tested under the same
conditions as chlorpyrifos. Obviously, one cannot predict from these
data the carcinogenicity of chlorpyrifos at higher dosages.
Data on the care inogenicity of pentachlorophenol are not adequate
for comparisons with the other termiticides.
OVERALL ASSESSMENT OF RISKS
Because chlordane is the most widely used termiticide in military
housing, the Committee used it as the reference material in making
comparisons. The four cyclodiene eermiticides are 8 imilar in overal
heal th risks; each exerts toxic effects on the central nervous
system. Al though the data on aldrin, dieldrin, and heptachlor suggest
a greater carcinogenic risk than that of chlordane, the Committee toes
not believe that these differences alone are sufficient to make one
cyclodiene more desirable than another. The effectiveness of the
cyclodienes as termiticides is fairly comparable, and they all persist
in the environment for about 20 yr after application. Aldrin and
dieldrin are less volatile than chlordane. Therefore, although
chiordane has a smaller carcinogenic risk, the possibility of greater
airborne concentrations might result in a greater hazard than would be
expected from health data alone.
The carcinogenic risk of lindane is considerably less than that of
chlortane on the basis of the mouse bioassay; other biologic end
points, such as effects on the central nervous system, do not suggest
that its toxicity differs fro. that of chlordane to arty great degree.
However, lindane is several times more volatile than chlordane and
would have to be applied more often to be as effective. Therefore,
there is a potential for greater airborne concentrations.
Neither pentachloropenol nor chlorpyrifo. has been shown to be
carcinogenic, although they were not tested under the same conditions
as the other te~iticides. There are no data on bumans, but
peneachloropt~enol has been obown to be embryotoxic and f etotoxic in
rats. Chlorpyrifo. differs from the other tenniticites in being an
organophosphate. Its toxicity is related primarily to ef facts on .
cholinesterase activity. Although the risk of chronic effects of
pentachlorophenol and chlorpyrifo. may not be as great as that of
chlordane, there is a potential for acute effects. Because these
materials need to be applied more often than chlordane to be as
effective, there is a potential for higher airborne concentrations,
which could increase the likelihood of acute effects.
— 5 —
OCR for page 6
RECOMMENDAT IONS
Guidelines for At ro`, rho l;x~s~re
The airborne exposure ~ imits suggested here are intended to provide
guidance in estimating the health risks of the pesticides in military
housing. These are not standards 1 ike those suggested by the
Occupational Safety and Health Administration, and they do not
guarantee absolute safety. Given the available data and the fact that
under conditions of prolonged exposure of families in military housing
there may be persons, such as young children, who in general are more
susceptible to environmental insults, the Committee concluded thee it
could not determine a level of exposure to any of the termiticides
below which there would be no biologic effects. The exposure limits
were derived on the basis of health considerations and ref lees the
combined judgment of the Committee members; the feasibility of
achieving the suggested airborne concentrations was not taken into
account. However, every effort should be made to minimize exposure to
the greatest extent feasible. In deciding which, if any, of the
termiticites are most appropriate for use in military housing, one
should take into account not only the toxicity and suggested airborne
exposure limits, but also other factors that would influence the
extent of exposure and hazard. Some of these factors are discussed
briefly in this report; they include vapor pressure, persistence In
the environment, and amount of material that needs to be applied. One
suggested guidelines for airborne exposure should be retrieved again as
soon as additional health-effects data become available.
Chlordane. The Committee on Toxicology in 1979 suggested an interim
guideline for airborne chlordane in military housing of 5 ~g/~3.
mid was derived pragmatically on the basis of known concentrations of
chlordane in military housing, a review of reported health complaints,
and consideration of data from long-term animal-feeding studies.
After an extensive review of the available literature on chlordane,
ant in the absence of definitive information on the health risks in
humane and anioale associated with various degrees of exposure to
airborne chiordane, the Committee concludes that there are no new data
that justify a change in tt~e guideline of 5 ug/m3 and suggests that
it continue to be used. Because of the shortcomings of current data
and in view of the Co~ittee's request that more definitive data be
developed, the airborne concentration of 5 ~g/~3 should be regarded
as an inter). guideline for exposures not exceeding 3 yr. This 3-yr
period is sugges ted with the expectation that i t wil 1 provide adequate
the for the nested health data to begin developing.
Heptachlor, Al drin, Dieldrin. The best available data f or
quantitatively comparing health risk are from the National Cancer
Institute (NCI) mouse bioassaye. On the basis of the EDlo.
estimated from these tests, heptachlor is approximately 3 times as
carcinogenic and aldrin and dieldrin 5 times as carcinogenic as
chlortane. Using these data, the Committee suggests interim
— 6 —
OCR for page 7
guidelines for airborne heptachlos. and airborne aldrin/dieldrin of 2
and 1 ug/m3, respectively, for exposures not exceeding 3 yr.
Lindane. Carcinogenic ity data on 1 indane are equivocal . Therefore,
the Committee does not bet ieve that this information should be used as
a basis for suggesting a guideline for airborne exposure to lindane
relative to exposure to chlordane. In the absence of other data for
quantitative estimation of the risks of exposure to airborne lintane
and because lindane is not now used to control termites in military
housing, the Committee does not suggest a guideline for airborne
exposure.
Pentachlorophenol. Because of the wide use of pentachlorophenol in
ways other than as a termiticide, because it is not now used to
control termites in military housing, because of its complex toxicity,
and in the absence of definitive data on effects of long-term exposure
to airborne pentachlorophenol, the Committee does not suggest a
guide 1 ine f o r a irborne exposure .
Ch lorpyrifos. The Commit tee on Toxicology previously suggested a
guideline for airborne chlorpyrifos of 100 1lg/m3, applicable for
90-d continuous exposure of Navy personnel in submarines. That
guideline was based on data from ingestion. In the absence of data on
effects of long-term exposure to airborne chlorpyrifos, the Committee
concludes that the ingestion studies of fer the best available
information from which to derive a guideline. Because the population
in military housing is more heterogeneous than that in submarines, the
Co ~ ittee suggests an interim guideline of 10 ~g/m3 for exposures
no t exceeding 3 yr.
Research Recommendations
The Committee s trongly recommends that more def initive human-heal th
data be developed for a fuller assessment of the risks of exposure to
these termiticides. With increasing reports of human exposure to some
of these termiticites in military and civilian housing, a clearer
understanding of the potential risks becomes even more important. To
provide a stronger data base on which to compare these materials more
fully, the following research is recommended:
· Lon~Term Animal-Inhalation Studies. The primary route of human
exposure is inhalation, ant there is a minimum of information on such
exposure. Differences between routes of administration could modify
the relative or absolute rises of these materials. Therefore,
long-term inhalation studies of the seven termiticides are
recommended. Biologic end points to investigate in these studies
include neurotoxicity, carcinogenicity, effects on blood-forming
t issues, and teratogenic ant reproductive ef fects. Studies on the
mechanisms of carcinogenicity (particularly for the cyclodienes) ant
neurotoxicity of these termiticides should also be untereaken. In
addition, the role of metabolism in influencing their toxic effects
— 7 —
OCR for page 8
need e to be examined further. If resources are insufficient for the
testing of all seven materials, it is suggested that testing begin
with chlordane, aidrin, ant some of the noncyclodiene compounds, such
as lindane and chlorpyrifos.
· Airborne Monitoring. An important consideration in assessing
health hazards is knowledge of likely exposure concentrations.
Published quantiteeive analytic data were available to the Committee
only on chlordane; some preliminary data were available on altrin and
dieldrin. It is suggested that a program be undertaken to determine
the airborne concentrations of the termiticides under conditions
~ imilar to those now used. This program should be conducted over a
sufficient period to delineate the effects of such variables as time
and t emperature.
0 Epidemiology Data. In several episodes in recent years, people
have been exposed to chlordane in military housing. This group can be
followed more readily than the general population, because their
health records and whereabouts are more easily traced. It is
recommended teat, at a minimum, a biologic monitoring program be
undertaken as a first step in a comprehensive analysis of the human
health ef fects of culordane. Concentrations of chlortane and its
metabolites in fat, blood, and urine of persons who lived in military
housing where chlordane was applied should be measured. Comparisons
of these concentrations before and after exposure would provide some
information on extent of exposure and on whether chlordane has
accumulated in the body. The health status of these persons should
also be investigated. In particular, investigators should look for
signs of neurotoxicity~-such as seizures, movement disorders, tremors,
and chorea--and for ~ igns of anemia and diseases of blood-forming
tissues. Neurologic symptoms appear to be the most sene~tz~e
indicator of exposure in humans. It might be possible to develop a
retrospective case~control study of those with suggestive necrologic
symptoms and appropriate matched conerole (neighbors, unaffected
siblings, etc.), including correlation with concentrations of the
termiticides in tissues and in indoor air. Any of the other
teraiticides for which there are sufficient data on exposure in
military housing should be investigated in a si~lar fashion.
— 8 —
Representative terms from entire chapter:
airborne exposure
