Chlordane in human

SAFETY PROFILE Confirmed carcinogen with experimental carcinogenic data. A poison by ingestion, skin contact, intraperitoneal, and intravenous routes. Human mutation data reported. Acute exposure and chronic doses have caused liver damage. See also closely related chlordane. In humans, a dose of 1-3 g can cause serious symptoms, especially where liver impairment is the case. Acute symptoms include tremors, convulsions, kidney damage, respirator)" collapse, and death. When heated to decomposition it emits toxic fumes of Cl . 

Epidemiological and Human Dosimetry Studies. Several epidemiological studies have investigated the cancer and noncancer effects of chlordane in humans exposed in their homes or occupationally in the manufacture of chlordane or in its application as a pesticide (Alvarez and Hyman 1953 Brown 1992 Cantor et al. 1992 Ditraglia et al. 1981 Kawano and Tatsukawa 1982 MacMahon et al. 

Polychlorinated Pesticides. A once substantial but now diminished use for DCPD is in the preparation of chlorinated derivatives for further use or synthesis into pesticide compounds (see Insectcontrol technology). Soil permanence and solubiUty of the products in human fatty tissues have considerably restricted the use of these compounds. The more prominent chlorinated pesticides were aldrin, dieldrin, chlordane, and heptachlor, all of which use hexachorocyclopentadiene as a starting material. Aldrin and dieldrin are no longer used in the U.S. Chlordane and heptachlor are stiU produced, but only for export use. 

Chlordane is readily absorbed by warm-blooded animals through skin, diet, and inhalation. It is quickly distributed in the body and tends to concentrate in liver and fat (WHO 1984). Up to 75% of a single oral dose of chlordane administered to rats and mice was absorbed in the gut, and up to 76% of an aerosol dose was absorbed in the respiratory tract (Nomeir and Hajjar 1987). Rabbits absorbed 33% in the gut following oral administration (USEPA 1988). Chlordane residues in mammals were usually not measurable 4 to 8 weeks after cessation of exposure (Ingle 1965). Chlordane persistence in human serum and whole body was estimated at 88 days and 21 days, respectively this compares to a Tb 1/2 of about 23 days in rats fed chlordane for 56 days (USEPA 1980). 

Chlordane levels in human blood were comparatively elevated among individuals living in residences treated with chlordane during the past 5 years, and in termite control operators. Oxychlordane levels were usually significantly higher than /ra/u-nonachlor, except among those who consumed large quantities of fish (Wariishi et al. 1986 Wariishi and Nishiyama 1989). 

HUMANS, Homo sapiens 100 pg/L 25-50 mg/kg BW 100 mg/kg BW Suicidal female swallowed 6 g chlordane, equivalent to 104 mg/kg BW Reduced growth and altered cell morphology in human cell cultures (USEPA 1980) Acute lethal oral dose (WHO 1984) Fatal (IARC 1979) Death in 9 days (WHO 1984)... 

Past chlordane use, coupled with atmospheric transport as the major route of dissemination, produced global contamination of fish and wildlife resources and human populations. The chemical and its metabolites were frequently detected in all species examined, but usually at low concentrations. Residues in fish muscle sometimes exceeded the U.S. Food and Drug Administration action level of 0.3 mg/kg fresh weight recommended for human health protection. In general, chlordane in animals is highest near areas where the chemical has been applied to control termites concentrations are highest in fat and liver, especially in predatory species. 

Wariishi, M. and K, Nishiyama. 1989. Observations on the progress of chlordane contamination in humans by blood and sebum analysis. Arch. Environ. Contam. Toxicol. 18 501-507. 

Miyazaki, T., et al. Chlordane residues in human milk, Bull. Environ. Contam. Toxicol., 25,518, 1980. 

Savage EP, Keefe TJ, Tessari JD, et al. 1981. National study of chlorinated hydrocarbon insecticide residues in human milk, USA I. Geographic distribution of dieldrin, heptachlor, heptachlor epoxide, chlordane, oxychlordane, and mirex. Am J Epidemiol 113(4) 413-422. 

There are few studies that specifically describe the effects of heptachlor or heptachlor epoxide in humans following exposure via the oral, inhalation, or dermal routes. There are data on the health effects of chlordane from occupational studies of pesticide applicators and manufacturers, and from studies of people who consumed food contaminated with chlordane and heptachlor. Chlordane is a pesticide that is structurally similar to heptachlor, and technical-grade preparations may contain... 

No studies were located regarding death in humans after oral exposure to heptachlor or heptachlor epoxide. However, since heptachlor is a major component of the insecticide chlordane, chlordane poisoning can be considered when evaluating heptachlor toxicity data. In the case study of a woman who ingested 6 g of chlordane with suicidal intent and died 9.5 days following ingestion, no information was presented on the composition of the chlordane. Therefore, the amount of heptachlor exposure is unknown, and the effect of other components of chlordane cannot be ruled out (Derbes et al. 1955). 

No studies were found correlating levels to which humans were exposed with actual body burdens. However, an attempt was made to correlate blood levels of chlordane, which may contain from 6% to 30% heptachlor, to duration of occupational exposure. Blood samples from 51 male pest control operators who were occupationally exposed to chlordane were tested for the presence of chlordane and its metabolites trans-nonachlor, oxychlordane, and heptachlor epoxide. The blood of 19 male workers with no experience spraying chlordane was also tested as a control. Heptachlor epoxide was detected (from not detectable to 1.6 ppb) in 20% of the blood samples from pest control operators exposed to chlordane (concentration not reported). The total chlordane in the blood was low but demonstrated sizable correlation with the number of spraying days and the amount of chlordane sprayed (Saito et al. 1986). 

Neurotoxicity. The only human data on neurotoxicity come from case reports of occupational exposures to chlordane in which the route was not specified, and for which the effects could not be related directly to heptachlor or heptachlor epoxide alone (Dadey and Kammer 1953). Signs of neurotoxicity, such as irritability, salivation, lethargy, dizziness, labored respiration, muscle tremors, and convulsions, were reported. No data exist describing neurologic effects in animals following inhalation exposure of any duration. Acute and intermediate oral studies in animals provide support for the supposition that the neurotoxicity of chlordane seen in humans may be due in part to heptachlor or heptachlor epoxide. Although there are no reasons to suspect that neurotoxic effects... 

Biomarkers of Exposure and Effect. Exposure to heptachlor and heptachlor epoxide is currently measured by determining the level of these chemicals in the blood or adipose tissue in living organisms (Curley et al. 1969 Klemmer et al. 1977 Radomski et al. 1968). This measure is specific for both heptachlor and heptachlor epoxide. Heptachlor epoxide is also a metabolite of chlordane, and thus its presence is not specific for exposure to heptachlor alone. However, in the absence of stable chlordane residues (e.g., nonachlor and oxychlordane), the heptachlor epoxide would most likely have been derived from heptachlor. Because heptachlor is believed to be converted rapidly in the body to heptachlor epoxide, it is impossible to determine whether the exposure was to one or the other of these two compounds. Heptachlor and heptachlor epoxide accumulate in adipose tissue and are released slowly over long periods of time. Therefore, it is not possible to accurately identify whether the exposure was recent or what the duration of exposure was. However, the ratio of heptachlor epoxide to heptachlor increases over time and therefore may be used as a biomarker of possible exposure to heptachlor. The sensitivity of the methods for identifying these compounds in human tissue appears to be only sufficient to measure background levels of heptachlor epoxide in the population. Additional biomarkers of exposure to heptachlor would be helpful at this time. 

In human case reports, chlordane exposure has been linked to neuroblastoma, aplastic anemia, and acute leukemia, but only circumstantially. In a 1987 report, 25 new cases of blood dyscrasia, including leukemias, production defects, and thrombocytopenic purpura (generally after home termite treatment with chlordane/heptachlor), were reported. The authors noted the rarity of many of the conditions and, hence, the difficulty of finding statistically significant results. 

Trany-nonachlor, a major component of technical chlordane, was frequently found as the major chlordane residue in humans, whereas oxychlordane was the major component in rats fed technical chlordane (Nomeir and Hajjar 1987). Trany-nonachlor is converted efficiently by rat liver microsomes to trany-chlordane, but this ability is lacking in humans, resulting in the accumulation of ran -nonachlor in humans (Nomeir and Hajjar 1987). 

One excess cancer per million (10 ) is associated with lifetime exposure to chlordane in drinking water at concentrations as low as 0.027 pg/L, the most conservative estimate. A lifetime health advisory computation was not possible because chlordane is a probable human carcinogen (USEPA 1988). 

Environmental. The high lipophilicity of the cydodienes and the prolonged persistence of dieldrin and heptachlor epoxide (soil half-lives 2—10 yr) have resulted in severe environmental contamination. These compounds are bioaccumulated from water to fish up to 100,000- to 300,000-fold and are ubiquitous in human fat and milk. Oxychlordane [26880-48-8], mirex, and chlordecone are also bioaccumulative. The cydodienes are extremely toxic to fish with LC5Qs (ppm) to trout and bluegill of endrin, 0.001-0.002 endosulfan, 0.001-0.003 diddrin, 0.003-0.015 aldrin, 0.006-0.01 heptachlor, 0.03-0.026 and chlordane, 0.022—0.095. The LD5Qs to pheasant and mallard are aldrin 16.8 and 520, dieldrin 79 and 381, and endrin 1.6 and 5.6 mg/kg. As indicated by their rat oral LD - s, they are also extremdy toxic to small mammals in fact, endrin has been used as a rodenticide (see Pesticides). Compounds, eg, aldrin and heptachlor, which have unsubstituted double bonds, readily add oxygen to form epoxides in plant and animal tissues and are preferentially concentrated and stored in animal fats. Aldrin epoxide (dieldrin) and heptachlor epoxide are more stable (half-lives on alfalfa of seven to eight days) than aldrin and heptachlor (half-lives on alfalfa of less than one day). 

Evidence is similar for humans but limited, and includes male sterility, spontaneous abortions in human females, premature human fetuses, severe neurologic and CNS effects, blood dyscrasias, hepatotoxicity, accumulation of organohalogen pesticides in human lipid tissue—and, perhaps even more important, their presence in human breast milk, whence they can continue to exert influences on growth, development and hormonal, CNS and enzyme systems. Aldrin, dieldrin, chlordane, chlordecone (Kepone), heptachlor epoxide, hexachlorobenzene (HCB) and Mirex are all excreted via breast milk in the human female. This is also true for the related PCBs and PBBs that resist biodecomposition and maintain persistent residence in mammalian tissues. For them, excretion via breast milk may constitute the main—if not sole—elimination route. 

The production of chlordane was reduced from. 3.5 to 4.0 million pounds in 1986 to 100,000 to 1 million pounds in 1991 (ATSDR, 1994a). More than 63 million kg of chlordane were produced and used in the United States, mostly after 1960 before sales and its use were suspended in 1988 (Dearth Hites, 1991a,b). Restrictions were imposed on the use of chlordane in 1979 because of its potential human carcinogenicity. After this time chlordane was used mainly for underground termite control and in building construction (Dearth Hites, 1991a,b). In Japan, chlordane was only permitted for the control of termites and powder post beetles (Miyazaki et al., 1980). USEPA cancelled its registration for commercial... 

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