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|
|Organochlorine pesticide (CAS number)||Serum pesticide or metabolite(s) (CAS number)||Urinary pesticide or metabolite(s) (CAS number)|
|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)||
|Mirex (2385-85-5)||Mirex (2385-85-5)|
CAS No. 118-74-1
Hexachlorobenzene (HCB) was used from the 1930's to the 1970's in the U.S. primarily as a fungicide and seed treatment until the U.S. EPA cancelled its use in 1984. Although it is not manufactured as an end-product in the U.S., HCB may be created as either a by-product or an impurity in the manufacturing process for certain chemicals and pesticides.
Hexachlorobenzene has entered the environment as a result of industrial activities and pesticide applications, and has been detected in soil, air, water, and sediment (Barber et al., 2005). It is a persistent chemical and bioaccumulates in both aquatic and terrestrial food chains (ATSDR, 2002). The general population may be exposed to HCB through diet, particularly by consuming fish, wildfowl, or game taken from areas with HCB contamination, and foods with a high fat content. The FDA dietary surveys have shown that over time, HCB has been detected in fewer foods since the 1980s (FDA, 2010; Gunderson, 1988). Workers in chemical manufacturing industries may be exposed to HCB via inhalation or dermal pathways.
HCB is well absorbed after oral administration, distributes widely throughout the body, and accumulates in fatty tissues where it persists for years. HCB is slowly metabolized, and elimination occurs by renal and fecal routes; breast milk is an additional route of elimination in nursing women. Urinary metabolites include pentachlorophenol (PCP), 2,4,5-trichlorophenol (2,4,5-TCP) and 2,4,6-trichlorophenol (2,4,6-TCP) (To-Figueras et al., 1997); these metabolites can also be produced after exposure to other chlorinated compounds (Kohli et al., 1976). Therefore, measuring HCB in serum is a specific indicator of exposure to the parent chemical.
Human health effects from HCB at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Chronic feeding studies in animals have demonstrated kidney injury, immunologic abnormalities, reproductive and developmental toxicities, and liver and thyroid cancers (ATSDR, 2002). In humans, very high, acute doses produce central nervous system depression and seizures. HCB interferes with normal heme synthesis, which is manifested by increased delta-aminolevulinic acid synthase activity and decreased uroporphyrinogen decarboxylase activity. With chronic exposure, a consequence of these heme abnormalities is a condition known as acquired porphyria cutanea tarda. This condition, as well as hypertrichosis, arthritis, thyromegaly, anorexia, and weakness, were seen in an epidemic of poisoning in Turkey that occurred from 1955 to 1959 when HCB-treated seed grain was diverted for bread production. Infants were exposed transplacentally and through breast milk, and many died before 2 years of age (Peters et al., 1982; Schmid, 1960).
IARC classifies hexachlorobenzene as possibly carcinogenic to humans, and NTP classifies hexachlorobenzene as reasonably anticipated to be a human carcinogen. ACGIH has developed workplace exposure limits for HCB. The U.S. EPA has established a drinking water standard, and the FDA has established a bottled water standard for HCB. 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#E.
Serum concentrations reflect the body burden of HCB. HCB levels were generally below the limits of detection in the NHANES 1999-2000 and 2001-2002 subsamples (CDC, 2009). As a result of the lower limit of detection in NHANES 2003-2004, more HCB levels were quantified. Age-related increases of HCB in body fat and serum have been consistently noted in general population studies (Becker et al., 2002; Bertram et al., 1986; Glynn et al., 2003). In a representative sample of the 1998 German adult population, HCB levels were directly related to age, and the geometric mean concentration of HCB in whole blood was 0.44 g/L, lower than the limit of detection (on a lipid adjusted basis) in NHANES 1999-2000 and 2001-2002, but approximately five times higher than the overall geometric mean level in 2003-2004 (Becker et al., 2002; CDC, 2009). In the 1976-1980 NHANES subsample, HCB detection in serum also was proportional to age, but overall, only 4.9% of participants had quantifiable levels (Stehr-Green, 1989). In Spain, factory workers chronically exposed to HCB and residents near the factory had serum HCB levels that were 150 to 50 times higher, respectively, than the limits of detection (on a whole weight basis) in NHANES 1999-2000 and 2001-2002 (CDC, 2009; Herrero et al., 1999). Residency near industrial or agricultural areas has been associated with higher serum HCB levels (Barber et al., 2005; Bradman et al., 2006). Over the past two decades, however, declines in background HCB levels ranging from around 50%-90% have been documented in studies using cord blood (Dallaire et al., 2002; Lackman, 2002) and among children (Link et al., 2005); the more recent values in these studies were similar to the lipid adjusted limit of detection in NHANES 1999-2000 and 2001-2002 (CDC, 2009; Dallaire et al., 2002; Lackmann, 2002; Link et al., 2005).
Finding a measurable amount of hexachlorobenzene in serum does not imply that the level of the hexachlorobenzene causes an adverse health effect. Biomonitoring studies on levels of HCB provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of hexachlorobenzene than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.
Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for hexachlorobenzene update [online]. September 2002.
Available at URL: http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=627&tid=115. 12/28/12
Barber JL, Sweetman AJ, van Wijk D, Jones KC. Hexachlorobenzene in the global environment: emissions, levels, distribution, trends and processes. Sci Tot Environ 2005;349:1-44.
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.
Bertram HP, Kemper FH, Muller C. Hexachlorobenzene content in human whole blood and adipose tissue: experiences in environmental specimen banking. IARC Sci Publ 1986;77:173-82.
Bradman A, Schwartz JM. Fenster L, Barr DB, Holland NT, Eskenazi B. Factors predicting organochlorine pesticide levels in pregnant Latina women living in a United States agricultural area. J Exp Sci Environ Epidemiol 2007;17:388–99.
Centers for Disease Control and Prevention (CDC). Fourth National Report on Human Exposure to Environmental Chemicals. 2009. [online] Available at URL: http://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.
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
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.
Herrero C, Ozalla D, Sala M, Otero R, Santiago-Silva M, Lecha M, et al. Urinary porphyrin excretion in a human population highly exposed to hexachlorobenzene. Arch Dermatol 1999;135(4):400-4.
Kohli J, Jones D, Safe A. The metabolism of higher chlorinated benzene isomers. Can J Biochem 1976;54(3):203-8.
Lackmann GM. Polychlorinated biphenyls and hexachlorobenzene in full-term neonates. Reference values updated. Biol Neonate 2002;81(2):82-5.
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.
Peters HA, Gocmen A, Cripps DJ, Bryan GT, Dogramaci I. Epidemiology of hexachlorobenzene-induced porphyria in Turkey: clinical and laboratory follow-up after 25 years. Arch Neurol 1982;39(12):744-9.
Schmid R. Cutaneous porphyria in Turkey. N Engl J Med 1960;263:397-8.
Stehr-Green, PA. Demographic and seasonal influences on human serum pesticide residue levels. J Toxicol Environ Health 1989;27:405-21.
To-Figueras J, Sala M, Otero R, Barrot C, Santiago-Silva M, Rodamilans M, et al. Metabolism of hexachlorobenzene in humans: association between serum levels and urinary metabolites in a highly exposed population. Environ Health Perspect 1997;105(1):78-83.