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Biomonitoring Summary

Organochlorine Pesticides Overview


General Information

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
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)


Hexachlorocyclohexane

CAS No. 608-73-1

beta-Hexachlorocyclohexane

CAS No. 319-85-7

gamma-Hexachlorocyclohexane (Lindane)

CAS No. 58-89-9

General Information

Hexachlorocyclohexane (HCH), formerly referred to as benzene hexachloride, exists in several isomeric forms, including alpha, beta, gamma, and delta. The gamma isomer, commonly known as lindane, can be used as an insecticide and has been used to kill soil-dwelling and plant-eating insects. The other isomers can be formed during the synthesis of lindane, and have been used either as fungicides or to synthesize other chemicals. Technical grade HCH is a mixture of all four isomers, containing about 64% alpha and 10%-15% gamma isomers. It is no longer produced or sold in the U.S. In 2006, the U.S. EPA cancelled agricultural uses of lindane (ATSDR, 2005). Lindane (1%) lotion and shampoo are available by prescription for single-use application to treat human scabies and head lice.

HCH isomers, particularly alpha and gamma have been detected widely in air, soil, water, and sediment as a result of historic production and use. As pesticide applications of HCH were increasingly restricted or eliminated, environmental levels declined. Lindane has a half-life of about two weeks in soils and water. HCH does not bioaccumulate to an appreciable extent in plants (ATSDR, 2005). However, HCH isomers are lipophilic, so they can accumulate in fatty tissues of animals. General population exposure to HCH is through the diet. The U.S. FDA pesticide monitoring program has shown a temporal decline in the detection of lindane, from 6% of samples in 1982-1984 to 2% in 1994 (FDA, 2010; Gunderson 1988). Pesticide applicators or agricultural workers could be exposed to HCH by inhalation and dermal pathways.

HCH isomers are absorbed after inhalation, ingestion, or dermal exposure. Distribution is mainly to fatty tissues. After dermal application of lindane 1% lotion, the serum half-life was about 20 hours among children (Ginsburg et al., 1977). The beta isomer accumulates in fatty tissues and is metabolized more slowly, resulting in a half-life of about seven years. HCH isomers are metabolized to chlorophenol metabolites that are excreted in the urine (Angerer et al., 1983). HCH crosses the placenta and is also excreted in breast milk (Radomski et al., 1971; Rogan, 1996; Saxena et al., 1981).

Human health effects from HCH isomers at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Acute high dose toxicity in rodents affects the central nervous system, producing decreased activity, ataxia, and seizures. When animals were chronically fed lindane at high doses, enlarged livers, hepatic enzyme induction, and nephropathy developed (IPCS, 2002). Acute high doses of lindane after ingestion or excessive skin application of the 1% lotion have produced seizures in humans, probably by blocking inhibitory neurotransmitters in the central nervous system. Workers who directly handled HCH have complained of headache, paresthesias, tremors, and memory loss (Nigam et al., 1986). OSHA and ACGIH have established workplace standards and guidelines, respectively, for lindane. U.S. EPA has established a drinking water standard, and FDA has established a bottled water standard and food residue tolerances for lindane. IARC classifies hexachlorocyclohexane isomers as possibly carcinogenic to humans, and NTP classifies hexachlorocyclohexane isomers as reasonably anticipated to be human carcinogens. More information about external exposure (i.e., environmental levels) and health effects is available from the U.S. EPA at http://www.epa.gov/pesticides and from ATSDR at http://www.atsdr.cdc.gov/toxprofiles/index.asp.

Biomonitoring Information

Because of its longer half-life, beta-HCH may be detected in a higher percentage of the general population than are the other HCH isomers. Studies of general populations have shown declining beta-HCH levels since the 1970s (ATSDR, 2005; Kutz et al., 1991; Link et al., 2005; Radomski et al., 1971; Stehr-Green, 1989; Sturgeon et al., 1998). Additional factors associated with higher beta-HCH levels include rural residence, older age, male sex, and a diet that includes meat (Becker et al., 2002; Kutz et al., 1991; Stehr-Green, 1989).

In NHANES 1999-2000, 2001-2002, and 2003-2004, serum levels of lindane were generally below the limits of detection, which were considerably lower (as much as twentyfold) than mean levels reported in small studies of adults in Spain (Botella et al., 2004) and India (Bhatnagar et al., 2004). In recent years, studies in populations with environmental exposure have reported lindane levels below the limit of detection in most persons (Anderson et al., 1998; Bates et al., 2004; Becker et al., 2002). In population-based studies of New Zealand adults and German adults and children, the maximum and 95th percentile beta-HCH values, respectively, were similar to the 95th percentiles in comparable groups in NHANES 1999-2004. In an earlier (1996-1997) sample of German children, aged 9-11 years, the 95th percentile of beta-HCH levels was twofold to threefold higher than the 95th percentile of 12-19 year olds in the comparable NHANES 2001-2002 survey period (Link et al., 2005). In a small study of adults who consumed sport fish from the Great Lakes, the median beta-HCH levels were similar or slightly higher than the 95th percentile in U.S. adults in NHANES 1999-2004 (Anderson et al., 1998). A study of Swedish women aged 54 years and older reported a median beta-HCH level that was slightly higher than the geometric mean for women reported in the NHANES 1999-2000 survey period (Glynn et al., 2003). Beta-HCH and lindane levels in workers involved in HCH production have been more than 1000-fold higher than the 95th percentile and limit of detection (lipid adjusted), respectively, in U.S. adults in NHANES 1999-2004 (Nigam et al., 1986; Radomski et al., 1971).

Finding a measurable amount of HCH isomers in serum does not imply that the level of HCH isomers causes an adverse health effect. Biomonitoring studies on levels of HCH isomers provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of HCH isomers 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 hexachlorocyclohexanes update [online]. August 2005. Available at URL: http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=754&tid=138. 12/28/12

Anderson HA, Falk C, Hanrahan L, Olson J, Burse VW, Needham LL, et al. Profiles of Great Lakes critical pollutants: a sentinel analysis of human blood and urine. The Great Lakes Consortium. Environ Health Perspect 1998;106(5):279-89.

Angerer J, Maass R, Heinrich R. Occupational exposure to hexachlorocyclohexane. VI. Metabolism of gamma-hexachlorocyclohexane in man. Int Arch Occup Environ Health 1983;52(1):59-67.

Bates MN, Buckland SJ, Garrett N, Ellis H, Needham LL, Patterson DG Jr, et al. Persistent organochlorines in the serum of the non-occupationally exposed New Zealand population. Chemosphere 2004;54:1431-43.

Becker K, Kaus S, Krause C, Lepom P, Schulz C, Seiwert M, et al. German Environmental Survey 1998 (GerES III): environmental pollutants in blood of the German population. Int J Hyg Environ Health 2002;205:297-308.

Bhatnagar VK, Kashyap R, Zaidi SS, Kulkarni PK, Saiyed HN. Levels of DDT, HCH, and HCB residues in human blood in Ahmedabad, India. Bull Environ Contam Toxicol 2004;72:261-5.

Botella B, Crespo J, Rivas A, Cerrillo I, Olea-Serrano MF, Olea N. Exposure of women to organochlorine pesticides in Southern Spain. Environ Res 2004;96:34-40.

Food and Drug Administration (FDA). FDA Pesticide Program Residue Monitoring: 1993-2008. [online]. Updated 10/27/2010. Available at URL: http://www.fda.gov/Food/FoodSafety/FoodContaminantsAdulteration/Pesticides/ResidueMonitoringReports/default.htm. 12/18/12

Ginsburg CM, Lowry W, Reisch JS. Absorption of lindane ( benzene hexachloride) in infants and children. J Pediatr 1977;91:998-1000.

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.

Gunderson EL. FDA total diet study, April 1982 to 1984, dietary intakes of pesticides, selected elements, and other chemicals. J Assoc Off Anal Chem 1988;71(6):1200-9.

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 Programme on Chemical Safety (IPCS). Pesticide residues in food-2002-Joint FAO/WHO meeting on pesticide residues. Lindane. 2002. available at URL: http://www.inchem.org/documents/jmpr/jmpmono/2002pr08.htm. 4/21/09

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

Link B, Gabrio T, Zoellner I, Piechotowski I, Paepke O, Herrman T, et al. Biomonitoring of persistent organochlorine pesticides, PCD/PCDFs and dioxin-like PCBs in blood of children from South West Germany (Baden-Wuerttemberg) from 1993-2003. Chemosphere 2005;58:1185-1201.

Nigam SK, Karnik AB, Majumder SK, Visweswariah K, Raju GS, Bai KM, et al. Serum hexachlorocyclohexane residues in workers engaged at a HCH manufacturing plant. Int Arch Occup Environ Health 1986;57(4):315-20.

Radomski JL, Astolfi E, Deichmann WB, Rey AA. Blood levels of organochlorine pesticides in Argentina: occupationally and nonoccupationally exposed adults, children and newborn infants. Toxicol Appl Pharmacol 1971;20(2):186-93.

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

Saxena MC, Siddiqui MKJ, Bhargava AK, Krishna Murti CR, Kutty D. Placental transfer of pesticides in humans. Arch Toxicol 1981;48:127-34.

Stehr-Green, PA. Demographic and seasonal influences on human serum pesticide residue levels. J Toxicol Environ Health 1989;27:405-21.

Sturgeon SR, Brock JW, Potischman N, Needham LL, Rothman N, Brinton LA, et al. Serum concentrations of organochlorine compounds and endometrial cancer risk (United States). Cancer Causes and Control 1998;9(4):417-24.


 
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