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National Research Council (US) Committee on Toxicology. An Assessment of the Health Risks of Seven Pesticides Used for Termite Control. Washington (DC): National Academies Press (US); 1982.

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An Assessment of the Health Risks of Seven Pesticides Used for Termite Control.

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EXECUTIVE SUMMARY

BACKGROUND

Seven pesticides are registered with the Environmental Protection Agency (EPA) for control of subterranean termites: chlordane, heptachlor, 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 has 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 chlordane. As a result, the Air Force in 1978 asked the National Research Council's Committee on Toxicology, in the Board on Toxicology and Environmental Health Hazards, Commission on Life Sciences, to review the toxicity data on chlordane 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 termiticides (NRC, 1977a, b). However, neither of these studies involved an assessment of the possible health risks associated with airborne exposure of the termiticides.

The Committee on Toxicology (NRC, 1979) concluded that it “could not 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 µg/m3, which was pragmatically determined on the basis of known concentrations 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 also suggested that a prospective epidemiologic study of persons exposed to chlordane in military housing would help substantially in making a risk assessment.

In 1980, the Comptroller General of the United States (GAO, 1980) recommended that the EPA initiate a formal risk-benefit review of chlordane to determine whether its registered uses for subsurface termite control should be limited or canceled and whether the health of people living in housing treated with chlordane is being adversely affected. In response to these recommendations, the EPA has initiated a risk-benefit 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 1980 prohibiting further application of chlordane for buildings with subslab or intraslab ducts. It also recommended that, where the risk and extent of possible termite damage in existing structures are considered unacceptable, studies be undertaken to determine the feasibility of sealing subslab or intraslab ducts and of renovating heating and cooling systems to use aboveground and above-slab ducts.

As a second step in the review of chlordane, the Department of Defense, through the Armed 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 assessment 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 limits for the other pesticides.

HEALTH EFFECTS OF THE SPECIFIC PESTICIDES

CYCLODIENES (CHLORDANE, HEPTACHLOR, ALDRIN, AND DIELDRIN)

The principal pesticides used for control of subterranean termites are the chlorinated cyclodienes--chlordane, heptachlor, aldrin, and dieldrin. These all had widespread use as pesticides until the mid-1970s, 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 humans to cyclodienes can produce central nervous system symptoms characterized by headache, blurred vision, dizziness, involuntary muscle movements, tremors, and seizures. Data on chronic exposure at low airborne concentrations are limited. A recent epidemiologic study of workers producing chlordane suggested that exposure has no long-term effects. However, because of shortcomings in the study and the suggestion of a trend in standard mortality ratios for deaths due to cancer in workers with increasing length of employment, more complete data are needed before firm 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 tumorigenic response in Osborne-Mendel rats. Central nervous system effects--such as hyperexcitability, tremors, and convulsions--have also occurred in laboratory animals fed 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 all persistent in the environment, they can be effective as termiticides for up to 20 yr after application.

LINDANE

Lindane is the gamma isomer of hexachlorocyclohexane. It has had widespread application as a pesticide, but its use has been severely restricted in the last several years. As a termiticide, it is primarily sprayed on the soil, and it persists in the environment for approximately 10 yr. Lindane has also been used widely in the treatment of scabies and for louse infestation.

In humans, lindane 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 lindane has produced diarrhea, hypothermia, hyperirritability, incoordination, and convulsions. Long-term exposure has produced nervous symptoms and fatty degeneration of the liver. Results of carcinogenicity tests in rodents have not been consistent, with both positive and negative results reported. However, it appears that the liver is one of the target organs after chronic exposure.

PENTACHLOROPHENOL

Pentachlorophenol 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-lived 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 loss of appetite, respiratory difficulties, anesthesia, hyperpyrexia, sweating, dyspnea, and coma. Animals exposed to pentachlorophenol had pathologic changes in the liver and kidneys, in addition to symptoms associated with uncoupling of oxidative phosphorylation. There was no evidence of a carcinogenic effect in mice and rats given pentachlorophenol orally for 1-2 yr. Embryotoxicity and fetotoxicity have been observed in offspring of rats given purified or commercial pentachlorophenol.

CHLORPYRIFOS

Chlorpyrifos 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.

Chlorpyrifos is in a different chemical class from the other termiticides discussed here, and its toxic effects also differ. The principal effect in humans and animals exposed for short periods is a reduction in plasma and red-cell cholinesterase activity. These changes have occurred after oral, dermal, and inhalation exposure.

There is no information on effects of long-term exposure of humans. Rats, mice, and 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 RECOMMENDATIONS

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 health 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.

COMPARISON OF CARCINOGENIC RISK

Information is insufficient to determine whether carcinogenesis is the critical biologic end point in humans exposed to these pesticides, but available animal data allow some useful comparisons of carcinogenic risk. The four cyclodienes and lindane have been tested for carcinogenicity under similar experimental protocols. Each compound has produced hepatocellular carcinomas in male mice, and this end point can be used for comparing carcinogenicity.

The ED10 (dosage producing an incidence of liver tumors 10 percent above background) was calculated to make comparisons. ED10 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 basis of the ED10s, heptachlor, aldrin, and dieldrin had approximately the same carcinogenic activity and were more potent than chlordane; lindane had about one-sixth the activity of chlordane. The calculated ED10s for dietary aldrin, dieldrin, heptachlor, chlordane, and lindane were 3.1, 3.6, 5.0, 16, and 103 ppm, respectively. The upper 95 percent confidence bounds on lifetime cancer risk expressed as the probability of cancer after a lifetime consumption of 1 L of water per day containing the compound at a concentration of 1 µg/L have also been estimated.

A limitation in interpreting the results of the bioassays is that the route of exposure was the diet, whereas the primary route of exposure of humans to these pesticides applied for termite control is inhalation. However, given this limitation, and on the basis of the ED10s and the upper confidence bounds on lifetime cancer risk, the ranking from greatest to least risk would be: aldrin, dieldrin > heptachlor > chlordane > lindane.

The carcinogenic potential of chlorpyrifos was investigated in CD-1 mice; there did not appear to be any tumors related to administration of this pesticide. Direct comparison with the chlorinated hydrocarbons is not possible, because a different test protocol and a different strain of mice were used. However, using the highest dosage in the chlorpyrifos study, 15.8 ppm, and the same experimental conditions, one could estimate the proportion of animals that would be expected to have tumors after exposure to the other pesticides. On the basis of this analysis, chlordane and lindane 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 carcinogenicity 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 termiticides are similar in overall health risks; each exerts toxic effects on the central nervous system. Although the data on aldrin, dieldrin, and heptachlor suggest a greater carcinogenic risk than that of chlordane, the Committee does 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 chlordane 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 chlordane 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 from that of chlordane to any 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 pentachlorophenol nor chlorpyrifos has been shown to be carcinogenic, although they were not tested under the same conditions as the other termiticides. There are no data on humans, but pentachlorophenol has been shown to be embryotoxic and fetotoxic in rats. Chlorpyrifos differs from the other termiticides in being an organophosphate. Its toxicity is related primarily to effects on cholinesterase activity. Although the risk of chronic effects of pentachlorophenol and chlorpyrifos 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.

RECOMMENDATIONS

Guidelines for Airborne Exposure

The airborne exposure limits suggested here are intended to provide guidance in estimating the health risks of the pesticides in military housing. These are not standards like 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 that 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 reflect 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 termiticides 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. The suggested guidelines for airborne exposure should be reviewed 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 µg/m3. This 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, and in the absence of definitive information on the health risks in humans and animals associated with various degrees of exposure to airborne chlordane, the Committee concludes that there are no new data that justify a change in the guideline of 5 µg/m3 and suggests that it continue to be used. Because of the shortcomings of current data and in view of the Committee's request that more definitive data be developed, the airborne concentration of 5 µg/m3 should be regarded as an interim guideline for exposures not exceeding 3 yr. This 3-yr period is suggested with the expectation that it will provide adequate time for the needed health data to begin developing.

Heptachlor, Aldrin, Dieldrin. The best available data for quantitatively comparing health risk are from the National Cancer Institute (NCI) mouse bioassays. On the basis of the ED10s estimated from these tests, heptachlor is approximately 3 times as carcinogenic and aldrin and dieldrin 5 times as carcinogenic as chlordane. Using these data, the Committee suggests interim guidelines for airborne heptachlor and airborne aldrin/dieldrin of 2 and 1 µg/m3, respectively, for exposures not exceeding 3 yr.

Lindane. Carcinogenicity data on lindane are equivocal. Therefore, the Committee does not believe 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 lindane 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 guideline for airborne exposure.

Chlorpyrifos. The Committee on Toxicology previously suggested a guideline for airborne chlorpyrifos of 100 µg/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 offer the best available information from which to derive a guideline. Because the population in military housing is more heterogeneous than that in submarines, the Committee suggests an interim guideline of 10 µg/m3 for exposures not exceeding 3 yr.

Research Recommendations

The Committee strongly recommends that more definitive human-health 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 termiticides 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:

  • Long-Term Animal-Inhalation Studies. The primary route of human exposure is inhalation, and there is a minimum of information on such exposure. Differences between routes of administration could modify the relative or absolute risks 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 tissues, and teratogenic and reproductive effects. Studies on the mechanisms of carcinogenicity (particularly for the cyclodienes) and neurotoxicity of these termiticides should also be undertaken. In addition, the role of metabolism in influencing their toxic effects needs to be examined further. If resources are insufficient for the testing of all seven materials, it is suggested that testing begin with chlordane, aldrin, and 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 quantitative analytic data were available to the Committee only on chlordane; some preliminary data were available on aldrin and dieldrin. It is suggested that a program be undertaken to determine the airborne concentrations of the termiticides under conditions similar to those now used. This program should be conducted over a sufficient period to delineate the effects of such variables as time and temperature.
  • 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 that, at a minimum, a biologic monitoring program be undertaken as a first step in a comprehensive analysis of the human health effects of chlordane. Concentrations of chlordane 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 signs of anemia and diseases of blood-forming tissues. Neurologic symptoms appear to be the most sensitive indicator of exposure in humans. It might be possible to develop a retrospective case-control study of those with suggestive neurologic symptoms and appropriate matched controls (neighbors, unaffected siblings, etc.), including correlation with concentrations of the termiticides in tissues and in indoor air. Any of the other termiticides for which there are sufficient data on exposure in military housing should be investigated in a similar fashion.
Copyright © National Academy of Sciences.
Bookshelf ID: NBK217619

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