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) |
||
Dichlorodiphenyltrichloroethane (DDT)
CAS No. 50-29-3
General Information
Dichlorodiphenyltrichloroethane (DDT) has been used widely as a broad spectrum insecticide in agriculture and for control of vector-borne diseases. It was produced and used in the U.S. after World War II until 1972, when virtually all use of it was banned. It is still used in some countries, particularly for endemic vector and malaria control. DDT was used at one time as a treatment for head and body lice. DDT usually refers to the technical product, which is a mixture containing p,p'-DDT (65%-80%), o,p'-DDT (15%-21%), p,p'-DDD (4% or less), and trace amounts of several related compounds. DDT is converted in the environment to other more stable chemical forms, including 1,1'-(2,2-dichloroethenylidene)-bis[4-chlorobenzene] (DDE) and 1,1'-dichloro-(2,2-bis(p-chlorophenyl) ethane (DDD). These chemicals are highly persistent in soil, sediments, air, and water, as well as in plant and animal tissues. The biodegradation half-life of DDT in soil varies from 2 to 15 years, depending on conditions.
In the general U.S. population, food, particularly meat, fish, and dairy products, continues to be the primary source of DDT exposure, although DDT and DDE intakes have decreased over time (FDA, 2010; Gunderson, 1988). Food imported from countries that still use DDT may contain the chemical or its residues. DDT can be absorbed after ingestion, inhalation, or dermal exposure. In the body, DDT is converted to DDE and several other metabolites. DDT and DDE are distributed to all body tissues with the highest concentrations found in adipose tissues (ATSDR, 2002; Smith, 1991). Only a small proportion of DDT is metabolized and excreted (Smith, 1991). DDT and DDE can cross the placenta, resulting in fetal exposure. Both chemicals are excreted in breast milk, resulting in exposure to nursing infants (Rogan, 1996).
Human health effects from DDT at low environmental doses or at biomonitored levels from low environmental exposures are unknown. In high dose, accidental exposures, overt signs of acute human toxicity include vomiting, tremor, and seizures. Experimental human dosing studies conducted over an 18 month period and during which doses well above environmental levels were given did not demonstrate overt clinical abnormalities (ATSDR, 2002; Hayes et al., 1956). In laboratory animals, both DDT and DDE may induce specific cytochrome P450 isozymes (Nims et al., 1998). DDT may bind to estrogen receptors (Chen et al., 1997); and o,p'-DDD and p,p'-DDE can produce anti-androgenic effects (Gray et al., 2001). Animal studies reported reduced fertility, premature delivery, reproductive organ abnormalities, and altered behavior after neonatal exposure (Eriksson and Talts, 2000; Gray et al., 2001). Reproductive effects in humans affecting birth weight, fertility, and duration of lactation, have not been consistently demonstrated (Beard, 2006; Gladen and Rogan, 1995; Jusko et al., 2006), although the risk for preterm delivery may be related to maternal DDE levels (Longnecker et al., 2001). Epidemiologic studies of children with environmental exposure to DDT and DDE have not demonstrated neurologic or developmental abnormalities (Gladen et al., 2004; Jusko et al., 2006; Longnecker et al., 2002; Mariussen and Fonnum, 2006). Several reviews of cancer epidemiologic studies have concluded that a link between DDT and breast cancer is inconclusive (Beard, 2006; Calle et al., 2002; Snedeker, 2001). Studies of DDT exposure and pancreatic cancer, lung cancer, and leukemia have also been inconclusive (ADSDR. 2002; Beard, 2006). It is difficult to attribute outcomes in human studies solely to DDT because of potential co-exposure to other persistent organohalogen chemicals (e.g., polychlorinated biphenyls, other organochlorines, dioxins and furans).
A workplace standard for DDT has been established by OSHA and a guidance established by ACGIH. IARC classifies DDT (p,p'-DDT) as a possible human carcinogen. NTP considers DDT as being reasonably anticipated to be a human carcinogen. More information about external exposure (i.e., environmental levels) and health effects is available from the U.S. EPA at https://www.epa.gov/pesticides and from ATSDR at https://www.atsdr.cdc.gov/toxprofiles/index.asp.
Biomonitoring Information
DDE persists in the body longer than DDT, so serum DDE levels may be an indicator of historic exposure and may be higher than DDT levels in the same person. In general, levels of DDT and DDE increase as a person ages as a result of cumulative exposure (ATSDR, 2002; Smith, 1991). Since the 1970's, mean serum levels of DDT and DDE in the U.S. population declined by about fivefold to tenfold (Anderson et al., 1998; Stehr-Green, 1989). Declining DDE levels over time have also been observed in the German population, and the most recent median levels for German adults and children are similar to comparable levels in NHANES (Becker et al., 2002; CDC, 2009; Heudorf et al., 2003; Link et al., 2005). Median DDE levels among a population-based sample of Swedish women in 1996-1997 were similar to females in the NHANES 1999-2000 subsample (CDC, 2009; Glynn et al., 2003). A study of New Zealand adults sampled in 1996-1997 reported median DDE levels that were about threefold higher than the median for adults in the NHANES 1999-2000 subsample (Bates et al., 2004; CDC, 2009). In a population-based sample of men and women from eastern Slovakia, the lipid-adjusted geometric mean levels of DDT and DDE were each fivefold to tenfold higher than the 95th percentile and geometric mean levels, respectively, for males and females in the NHANES 1999-2000 subsample (CDC, 2009; Pavuk et al., 2004).
Compared to females in the NHANES 1999-2000 subsample, mean DDE levels were about fivefold higher among women of southern Spain exposed by virtue of nearby agriculture (Botella et al., 2004; CDC, 2009). A small study of Indian men with background exposure reported mean serum DDT and DDE levels that were around fiftyfold higher than the 95th percentile for DDT and tenfold to twentyfold higher than the geometric mean DDE levels among U.S. males in NHANES (Bhatnagar et al., 2004; CDC, 2009). Consumers of Great Lakes sport fish had mean serum DDE levels that were only slightly higher than nonconsumers, 309 versus 268 ng/g lipid, which is similar to the overall geometric mean of 260 ng/g lipid in the NHANES 1999-2000 subsample (Bloom et al., 2005; CDC, 2009). High mean levels of whole blood DDT (about 3,860 ng/L) and DDE (about 14,490 ng/L) were found many years ago in a study of pesticide workers in Argentina (Radomski et al., 1971). Workers involved in production or application of DDT developed neurologic abnormalities associated with blood levels around 100-300g/L, considerably higher than levels in NHANES (Smith, 1991).
In the NHANES 1999-2000, 2001-2002 and 2003-2004 subsamples, serum levels of o,p'-DDT were below the limits of detection (CDC, 2009). In a subsample of NHANES II (1976-1980) participants, less than one percent had detectable serum levels of o,p'-DDT (Stehr-Green, 1989).
Finding a measurable amount of p,p'-DDT, o,p'-DDT, or p,p'-DDE in serum does not imply that the level of the chemical causes an adverse health effect. Biomonitoring studies on levels of DDT and DDE provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of DDT or DDE 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 DDT, DDE, and DDD [online]. September 2002. Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=81&tid;=20. 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):279-289.
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;54:1431-1443.
Beard J. DDT and human health. Sci Tot Environ 2006;355:78-89.
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;72:261-265.
Bloom MS, Vena JE, Swanson MK, Moysich KB, Olson JR. Profiles of ortho-polychlorinated biphenyl congeners, dichlorodiphenyldichloroethylene, hexachlorobenzene, and Mirex among male Lake Ontario sportfish consumers: the New York State Angler cohort study. Environ Res 2005;97(2):178-192.
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.
Calle EE, Frumkin H, Henley SJ, Savitz DA, Thun MJ. Organochlorines and breast cancer risk. CA Cancer J Clin 2002;52:301-309.
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
Chen CW, Hurd C, Vorojeikina DP, Arnold SF, Notides AC. Transcriptional activation of the human estrogen receptor by DDT isomers and metabolites in yeast and MCF-7 cells. Biochem Pharmacol 1997;53(8):1161-1172.
Eriksson P, Talts U. Neonatal exposure to neurotoxic pesticides increases adult susceptibility: a review of current findings. Neurotoxicol 2000;21(1-2)37-48.
Food and Drug Administration (FDA). FDA Pesticide Program Residue Monitoring: 1993-2008. [online]. Updated 10/27/2010. Available at URL: https://www.fda.gov/Food/FoodSafety/FoodContaminantsAdulteration/Pesticides/ResidueMonitoringReports/default.htm. 12/18/12
Gladen BC, Rogan WJ. DDE and shortened duration of lactation in a northern Mexican town. Am J Public Health 1995;85:504-508.
Gladen BC, Klebanoff MA, Hediger ML, Katz SH, Barr DB, Davis MD, et al. Prenatal DDT exposure in relation to anthropometric and pubertal measures in adolescent males. Environ Health Perspect 2004;112(17):1761-1767.
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;111:349-355.
Gray LE Jr, Ostby J, Furr J, Wolf CJ, Lambright C, Parks L, et al. Effects of environmental antiandrogens on reproductive development in experimental animals. Hum Reprod Updat 2001;7(3):248-264.
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):1200-1209.
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):507-513.
Hayes WJ, Jr., Durham WF, Cueto C, Jr. The effect of known repeated oral doses of chlorophenothane (DDT) in man. JAMA 1956;162:890-897.
Heudorf U, Angerer J, Drexler H. Current internal exposure to pesticides in children and adolescents in Germany: blood plasma levels of pentachlorophenol (PCP), lindane (ϒ-HCH), and dichloro(diphenyl)ethylene (DDE), a biostable metabolite of dichloro(diphenyl)trichloroethane (DDT). Int J Hyg Environ Health 2003;206:485-491.
Jusko TA, Koepsell TD, Baker RJ, Greenfield TA, Willman EJ, Charles MJ, et al. Maternal DDT exposures in relation to fetal and 5-year growth. Epidemiology 2006;17(6):692-700.
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.
Longnecker MP, Klebanoff MA, Zhou H, Brock JW. Association between maternal serum concentration of the DDT metabolite DDE and preterm and small-for-gestational-age babies at birth. Lancet 2001;358:110-114.
Longnecker MP, Klebanoff MA, Brock JW, Zhou H, Gray KA, Needham LL, et al. Maternal serum level of 1,1-dichloro-2,2-bi(p-chlorophenyl)ethylene and risk of cryptorchidism, hypospadias, and polythelia among male offspring. Am J Epidemiol 2002;155(4):313-322.
Mariussen E, Fonnum F. Neurochemical targets and behavioral effects of organohalogen compounds: an update. Crit Rev Toxicol 2006;36:253-589.
Nims R, Lubet R, Fox S, Jones CR, Thomas PE, Reddy AB, et al. Comparative pharmacodynamics of CYP2B induction by DDT, DDE, and DDD in male rat liver and cultured rat hepatocytes. J Toxicol Environ Health Part A 1998;53:455-477
Pavuk M, Cerhan JR, Lynch CF, Schecter A, Petrik J, Chovancova J, et al. Environmental exposure to PCBs and cancer incidence in eastern Slovakia. Chemosphere 2004;54:1509-520.
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):186-193.
Rogan WJ. Pollutants in breast milk. Arch Pediatr Adolesc Med 1996;150:981-990.
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.
Snedeker SM. Pesticides and breast cancer risk: a review of DDT, DDE, and dieldrin. Environ Health Perspect 2001;109:35-47.
Stehr-Green, PA. Demographic and seasonal influences on human serum pesticide residue levels. J Toxicol Environ Health 1989;27:405-421.
