Biomonitoring Summary

Organochlorine Pesticides Overview

Organochlorine pesticides, an older class of pesticides, are effective against a variety of insects. These chemicals were introduced in the 1940s, and many of their uses have been cancelled or restricted by the U.S. EPA because of their environmental persistence and potential adverse effects on wildlife and human health. Many organochlorines are no longer used widely in the U.S., but other countries continue to use them. Hexachlorobenzene has been used primarily as a fungicide or biocide.

Organochlorine pesticides can enter the environment after pesticide applications, disposal of contaminated wastes into landfills, and releases from manufacturing plants that produce these chemicals. Some organochlorines are volatile, and some can adhere to soil or particles in the air. In aquatic systems, sediments adsorb organochlorines, which can then bioaccumulate in fish and other aquatic mammals. These chemicals are fat soluble, so they are found at higher concentrations in fatty foods. In the general population, diet is the main source of exposure, primarily through the ingestion of fatty foods such as dairy products and fish. Usage restrictions have been associated with a general decrease in serum organochlorine levels in the U.S. population and other developed countries (Hagmar et al, 2006; Kutz et al., 1991). Contaminated drinking water and air are usually minor exposure sources. Infants can be exposed through breast milk, and the fetus can be exposed in utero via the placenta. Workers can be exposed to organochlorines in the manufacture, formulation, or application of these chemicals. The FDA, U.S. EPA, and OSHA have developed standards for allowable levels of certain organochlorines in foods, the environment, and the workplace, respectively. Attributing human health effects to specific organochlorine chemicals is difficult because exposure to multiple organochlorine chemicals occurs often, and these chemicals may have similar actions.

The table shows selected parent organochlorines and their metabolites that can be measured in serum or urine. Measurements of these chemicals can reflect either recent or cumulative exposures, or both. Some of the metabolites can be produced from more than one pesticide. The level of a metabolite in a person's blood or urine may indicate exposure to the parent pesticide as well as to the metabolite itself.

Organochlorine Pesticides and Metabolites
Measured in the National Biomonitoring Program

Table of Phthalates and Urinary Metabolites Measured in the National Biomonitoring Program
Organochlorine pesticide (CAS number)	Serum pesticide or metabolite(s) (CAS number)	Urinary pesticide or metabolite(s) (CAS number)
Aldrin (309-00-02)	Aldrin (309-00-02) Dieldrin (60-57-1)
Chlordane (12789-03-6)	Oxychlordane (27304-13-8) trans-Nonachlor (3734-49-4)
Dichlorodiphenyltrichloroethanes	p,p'-DDT (50-29-3) p,p'-DDE (72-55-9) o,p'-DDT (789-02-6)
Dieldrin (60-57-1)	Dieldrin (60-57-1)
Endrin (72-20-8)	Endrin (72-20-8)
Heptachlor (76-44-8)	Heptachlor epoxide (1024-57-3)
Hexachlorobenzene (118-74-1)	Hexachlorobenzene (118-74-1)	Pentachlorophenol (87-86-5) 2,4,6-Trichlorophenol (88-06-2) 2,4,5-Trichlorophenol (95-95-4)
Hexachlorocyclohexanes	beta-Hexachlorocyclohexane (319-85-7) gamma-Hexachlorocyclohexane (58-89-9)	Pentachlorophenol (87-86-5) 2,4,6-Trichlorophenol (88-06-2) 2,4,5-Trichlorophenol (95-95-4)
Mirex (2385-85-5)	Mirex (2385-85-5)
Chlorophenols, including 2,4,5-Trichlorophenol (95-95-4) 2,4,6-Trichlorophenol (88-06-2)		2,4,5-Trichlorophenol (95-95-4) 2,4,6-Trichlorophenol (88-06-2)

Chlordane

CAS No. 57-74-9

Heptachlor

CAS No. 76-44-8

General Information

Chlordane and heptachlor are structurally related organochlorine pesticides and were used in the U.S. from the early 1950’s until the mid-1980’s. As a result of the manufacturing process, the technical grade product of each chemical contains 10%-20% of the other chemical, in addition to trace amounts of numerous other related compounds (ATSDR, 2007). Technical grade chlordane had contained 7% trans-nonachlor. Chlordane is not currently produced or used in the U.S. Since 1992, heptachlor use has been limited to treatment of fire ants near power transformers. Until 1988, chlordane was used to kill termites and other insects on agricultural crops, lawns, buildings, and in soil. Heptachlor was used as a soil and seed treatment and for termite control in and around buildings until 1988. Both pesticides are persistent in soils and sediments and have been detected in water from agricultural run-off and near production and disposal facilities (ATSDR, 1994, 2007). Heptachlor and chlordane are somewhat volatile and may be detected in the air and dust of buildings long after treatment for termite or insect control (Whitemore et al., 1994).

Heptachlor, chlordane, and their metabolites bioaccumulate in fatty animal tissues. Consequently, foods high in fat such as meat, fish, and dairy products are the usual sources of exposure to these chemicals in the general population. Both of these chemicals and their metabolites can cross the placenta and are excreted into breast milk, which results in exposure to the fetus and nursing infant (Dallaire et al., 2002; Rogan, 1996; Takahashi et al., 1981). Chlordane and heptachlor are absorbed after oral, dermal, and inhalation exposure. Chlordane is metabolized primarily to oxychlordane and to a lesser extent, to heptachlor. The major metabolite of heptachlor is heptachlor epoxide, which is also persistent in the body (ATSDR, 2007). Elimination of all these chemicals and their metabolites from the body occurs over months to years, and breast milk is a major excretion route in lactating women.

Human health effects from either chlordane or heptachlor at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Acute, high doses of either chlordane or heptachlor block inhibitory neurotransmitters and result in central nervous system toxicity, characterized by seizures and paralysis. In laboratory animal studies, chronic doses of heptachlor have produced liver enlargement and injury; both chlordane and heptachlor induced hepatic cytochrome P450 enzymes and increased the incidence of liver tumors (NTP, 1977a, 1977b; Smith, 1991). Chronic feeding studies with either chlordane or heptachlor have demonstrated reduced fertility, neonatal mortality, and alterations in immune function of offspring. Subtle neurodevelopmental effects have been observed rodents after prenatal exposure to heptachlor (IPCS, 2006). Epidemiologic studies have not demonstrated teratogenic or developmental effects (Baker et al., 1991; Le Marchand et al., 1986). No clear evidence of excessive cancer rates was demonstrated in human epidemiologic studies (ATSDR, 2007; IARC, 2001; Shindell and Ulrich, 1986). IARC considers chlordane and heptachlor as possibly carcinogenic to humans. OSHA has established occupational exposure criteria, and NIOSH and ACGIH have recommended workplace exposure levels for each pesticide. The U.S. EPA has established environmental criteria for chlordane and heptachlor, and the U.S. FDA established allowable residues of chlordane, heptachlor, and heptachlor epoxide in foods and bottled water. Information about external exposure (i.e., environmental levels) and health effects of chlordane and heptachlor is available from ATSDR at https://www.atsdr.cdc.gov/toxprofiles/index.asp. An assessment of heptachlor is available at http://www.inchem.org/documents/cicads/cicads/cicad70.htmexternal icon.

Biomonitoring Information

Serum oxychlordane and trans-nonachlor levels in NHANES 1999-2000, 2001-2002, and 2003-2004 subsamples were comparable to levels measured in Swedish women from 1996-1997 (CDC, 2009; Glynn et al., 2003). In serum samples obtained in between 1994 and1997 from Inuit women in different Arctic countries, the reported oxychlordane and trans-nonachlor geometric mean levels from Canada and Greenland groups were about threefold to fivefold higher than among females in NHANES 1999-2004 (CDC, 2009; van Oostdam et al., 2004). A small sample of Polish women had mean levels of oxychlordane and trans-nonachlor that were about fivefold lower than in females in the NHANES 2001-2002 subsample (CDC, 2009; Jaraczweska et al., 2006). Serum trans-nonachlor levels among females in the NHANES 1999-2001 subsample were about one half the levels obtained between 1994 and 1996 from women in New York (CDC, 2009; Wolff et al., 2000).

Levels of heptachlor epoxide among U.S. females in NHANES were approximately one tenth of the corresponding 90th percentile for a cohort of pregnant women in California studied from 1963 to1967 (CDC, 2009; James et al., 2002). Two episodes (one each in Arkansas and Hawaii) of inadvertent heptachlor contamination of dairy cattle feed occurred in the early-to-mid 1980’s, resulting in human exposure to heptachlor epoxide that was excreted into the milk. For the exposed persons drinking milk in the Arkansas episode, mean serum heptachlor epoxide and oxychlordane levels were about sevenfold and threefold higher, respectively, than the 90th percentile values of NHANES 1999-2000 (Stehr-Green et al., 1988). In the Hawaii episode, the mean serum heptachlor epoxide and oxychlordane levels were more than twice as high, respectively, than the 90th percentile values of NHANES 1999-2000 (Baker, 1991; CDC, 2009).

Finding a measurable amount of oxychlordane, trans-nonachlor, or heptachlor epoxide in serum does not imply that the level of oxychlordane, trans-nonachlor, or heptachlor epoxide causes an adverse health effect. Biomonitoring studies on levels of oxychlordane, trans-nonachlor, and heptachlor epoxide provide physicians and public health officials with reference ranges so that they can determine whether people have been exposed to higher levels of heptachlor and chlordane than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.

References

Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for chlordane [online]. May 1994. Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=355&tid=62. 12/28/12

Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for heptachlor and heptachlor epoxide [online]. August 2007. Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=746&tid=135. 12/28/12

Baker DB, Loo S, Barker J. Evaluation of human exposure to the heptachlor epoxide contamination of milk in Hawaii. Hawaii Med J 1991;50(3):108-18.

Centers for Disease Control and Prevention (CDC). Fourth National Report on Human Exposure to Environmental Chemicals.2009. [online] Available at URL: https://www.cdc.gov/exposurereport/. 12/28/12

Dallaire F, Dewailly E, Laliberte C, Muckle G, Ayotte P. Temporal trends of organochlorine concentrations in umbilical cord blood of newborns from the lower north shore of the St. Lawrence River (Quebec, Canada). Environ Health Perspect 2002;110(8):835-8.

Glynn AW, Granath F, Aune M, Atuma S, Darnerud PO, Bjerselius R, et al. Organochlorines in Swedish women: determinants of serum concentrations. Environ Health Perspect 2003;111:349-55.

Hagmar L, Wallin E, Vessby B, Jonsson BA, Bergman A, Rylander L. Intra-individual variations and time trends 1991-2001 in human serum levels of PCB, DDE and hexachlorobenzene. Chemosphere 2006;64(9):507-13.

International Agency for Research on Cancer (IARC). International Agency for Research on Cancer (IARC) – Summaries & Evaluations. Chlordane and heptachlor [online]. Vol. 79, 2001. Available at URL: http://www.inchem.org/documents/iarc/vol79/79-12.htmlexternal icon. 12/28/12

International Programme in Chemical Safety (IPCS). Concise International Chemical Assessment Document 70 Heptachlor [online]. 2006. Available at URL: http://www.inchem.org/documents/cicads/cicads/cicad70.htmexternal icon. 12/28/12

James RA, Hertz-Picciotto I, Willman E, Keller JA, Charles MJ. Determinants of serum polychlorinated biphenyls and organochlorine pesticides measured in women from the child health and development study cohort, 1963-1967. Environ Health Perspect 2002;110:617-24.

Jaraczewska K, Lulek J, Covaci A, Voorspoels S, Kaluba-Skotarczak A, Drews K, et al. Distribution of polychlorinated biphenyls, organochlorine pesticides and polybrominated diphenyl ethers in human umbilical cord serum, maternal serum and milk from Wielkopolska region, Poland. Sci Tot Environ 2006;372:20-31.

Kutz FW, Wood PH, Bottimore DP. Organochlorine pesticides and polychlorinated biphenyls in human adipose tissue. Rev Environ Contam Toxicol 1991;120:1-82.

LeMarchand L, Kolonel LN, Siegel BZ, Dendle WH. Trends in birth defects for a Hawaiian population exposed to heptachlor and for the United States. Arch Environ Health, 1986;41:145–8.

National Toxicology Program (NTP). Bioassay of chlordane for possible carcinogenicity. Natl Cancer Inst Carcinog Tech Rep Ser 1977a;8:1-123. Available at URL: https://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr008.pdfpdf iconexternal icon. 12/28/12

National Toxicology Program (NTP). Bioassay of heptachlor for possible carcinogenicity. Natl Cancer Inst Carcinog Tech Rep Ser 1977b;9:1-109. Available at URL: https://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr009.pdfpdf iconexternal icon. 12/28/12

Rogan WJ. Pollutants in breast milk. Arch Pediatr Adolesc Med 1996;150:981-90.

Shindell S and Ulrich S. Mortality of workers employed in the manufacture of chlordane: an update. J Occup Med 1986;28:497-501.

Smith AG. Chlorinated Hydrocarbon Insecticides. In Hayes WJ, Jr and Laws ER, Jr, Eds. Handbook of Pesticide Toxicology, Vol. 2 Classes of Pesticides. New York, Academic Press, Inc. 1991 pp. 731-915.

Stehr-Green P, Wohlleb JC, Royce W, Head SL. An evaluation of serum pesticide residue levels and liver function in persons exposed to dairy products contaminated with heptachlor. JAMA 1988;259(3):374-7.

Takahashi W, Saidein D, Takei G, Wong L. Organochloride pesticide residues in human milk in Hawaii, 1979-1980. Bull Environ Contam Toxicol 1981:27:506-11.

Van Oostdam JC, Dewailly E, Gilman A, Hansen JC, Odland JO, Chashchin V, et al. Circumpolar maternal blood contaminant survey, 1994-1997 organochlorine compounds. Sci Total Environ 2004;330:55-70.

Wolff MS, Berkowitz GS, Brower S, Senie R, Bleiweiss IJ, Tartter P, et al. Organochlorine exposures and breast cancer risk in New York City women. Environ Res 2000;84:151-61.

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Content source: Centers for Disease Control and Prevention