Pesticides
CATEGORY*: depends upon compound. Many pesticides are Endocrine disruptors, several are IARC probable or possible, some are NTP reasonably anticipated
USED IN: Agricultural and household pest control
Triazine Herbicides: Atrazine
Triazine herbicides are the most heavily used agricultural chemicals in the United States. Triazines include atrazine, simazine, propazine and cyanazine. Although all have been shown to cause mammary cancer in laboratory rats (O’Connor, 2000), there is relatively little scientific data exploring the relationship between simazine or cyanazine and human breast cancer. The literature on atrazine is more substantial.
Atrazine was banned in the European Union in 2005 because of its high presence in drinking water, its demonstrated harmful effects on wildlife, and its potential health effects in humans. Atrazine is, however, still approved for use in the United States. More than 75 million pounds of atrazine are applied annually in the United States, primarily to control broadleaf weeds in corn and sorghum crops in the Midwest (EPA, 2008).
Elevated levels of atrazine are found each spring and summer in both drinking water and groundwater in agricultural areas (Hua, 2006; Miller, 2000; Villanuaeva, 2005). Atrazine is a known endocrine disruptor, causing dramatic damage to reproductive structures in frogs, fish and other wildlife (Hayes, 2003; Rohr, 2009).
High levels of triazines (primarily atrazine) in contaminated waters have been associated with an increased risk of breast cancer (Kettles, 1997), although not all ecological studies support these findings (Hunter, 2008). Because these studies tend to compare countywide average levels of atrazine contamination and incidence rates, it is difficult to understand clearly the difference in results.
Research in rodents has shown that atrazine exposure disrupts pituitary-ovarian function, resulting in decreases in circulating prolactin and luteinizing hormone levels, changes that contribute to the effects of this herbicide on increases in mammary tumors (Cooper, 2000; O’Connor, 2000). Atrazine also exerts endocrine-disrupting effects by increasing the activity of the enzyme aromatase (Fan, 2007; Sanderson, 2001), an enzyme that catalyzes (facilitates) the conversion of testosterone and other androgens to estrogens, including estradiol. Androgens are found naturally in women, although at lower levels than in men. The production of estrogens through the aromatase pathway, however, is of sufficient importance in the etiology of breast cancer that a current class of breast cancer drugs aims specifically to block the activity of aromatase.
Exposure to atrazine or mixtures of atrazine metabolites during gestation delays development of the rat mammary gland in puberty, widening the window of sensitivity to breast carcinogens (Enoch, 2007; Raynor, 2005). Similarly, exposure of rats late in pregnancy to a mixture of commonly formed metabolites of atrazine also leads to persistent changes in mammary gland development in pups exposed during gestation. These abnormalities persist into adulthood (Enoch, 2007). Exposure of rats with existing mammary tumors to atrazine increases the rate of cell proliferation in those tumors (Ueda, 2005).
Heptachlor
Heptachlor is an insecticide that was widely used in the United States throughout the 1980s, especially for termite control. In 1988, the U.S. EPA restricted use of heptachlor to certain applications for controlling fire ants, but agricultural use continued until 1993 because growers were allowed to use up existing stocks (Siegel, 1995). Heptachlor use was particularly high in Hawaii, where it was employed extensively on pineapple crops and consequently contaminated both local agricultural crops and dairy supplies. Breast cancer rates in Hawaii have increased dramatically for women of all ethnic groups over the past four decades (Maskarinec, 2006).
Heptachlor still contaminates both soil and humans. Its breakdown product, heptachlor epoxide (HE), is known to accumulate in fat, including breast tissue. Levels are highest in women ages 20 and older, but HE is also found in the bodies of adolescents 12 to 19 years old (CDC, 2005). Although HE does not act like estrogen, it affects the way the liver processes the hormones, thereby allowing levels of circulating estrogens to rise and increasing breast cancer risk. HE also has been shown to disrupt cell-to-cell communication in human breast cells in tissue culture (Dich, 1997) and to increase production of nitric oxide, a chemical that is found naturally in cells and is known to cause damage to DNA (Cassidy, 2005).
Dieldrin and Aldrin
From the 1950s until 1970, the pesticides dieldrin and aldrin (which breaks down to dieldrin, the active ingredient) were widely used for crops including corn and cotton. Because of concerns about damage to the environment and, potentially, to human health, the EPA in 1975 banned all uses of aldrin and dieldrin except in termite control; the EPA banned these pesticides altogether in 1987 (ATSDR, 2010). Thus, most of the human body burden of this chemical comes either from past exposures or lingering environmental contamination.
One body burden study showed a clear relationship between breast cancer incidence and dieldrin exposure. Conducted by the Copenhagen Center for Prospective Studies in collaboration with the CDC, the study examined a rare bank of blood samples taken from women before development of breast cancer (Hoyer, 1998). During the late 1970s and early 1980s, blood samples were taken from approximately 7,500 Danish women ranging in age from 30 to 75. In 2000, researchers looking at blood samples of 240 women from the original study who had later been diagnosed with breast cancer detected organochlorine compounds in most of the samples. They found dieldrin, which has exhibited estrogenic activity during in vitro assays, in 78 percent of the women who were later diagnosed with breast cancer. Women who had the highest levels of dieldrin long before cancer developed had more than double the risk of breast cancer compared to women with the lowest levels. This study also showed that exposure to dieldrin correlated with the aggressiveness of breast cancer: Higher levels of dieldrin were associated with higher breast cancer mortality (Hoyer, 2000).
Like many other pesticides found in the environment, dieldrin has been shown to be an endocrine disruptor, both by stimulating estrogen-regulated systems and by interfering with androgen-regulated pathways. Addition of dieldrin to human breast cancer (MCF-7) cells in vitro stimulated their growth and proliferation (Andersen, 2002; Soto, 1994). The exposure of normal (non-cancerous) human breast epithelial cells to mixtures of organochlorine pesticides, including dieldrin and aldrin, as well as DDT/DDE at levels found in the environment, led to greater induction of cellular processes linked to cancer than exposures to any of the chemicals individually (Valeron, 2009).
Treatment of mice prenatally and neonatally to environmentally relevant doses of dieldrin increased the number and size of mammary tumors. These effects may have been mediated through changes in the cellular expression of the growth factor BDNF and cell-signal receptor Trks. Both of these were elevated in tumors from the dieldrin-treated animals (Cameron, 2009).
Other Pesticides
A case-control study of 128 Latina agricultural workers newly diagnosed with breast cancer in California identified three pesticides—chlordane, malathion and 2,4-D—associated with an increased risk of the disease. Scientists found that the risks associated with use of these chemicals were higher in young women and in those with early-onset breast cancer than in unexposed women (Mills, 2005).
Researchers from the National Cancer Institute studied the association between pesticide use and breast cancer risk in farmers’ wives in the Agricultural Health Study. This large prospective cohort study enrolled more than 30,000 women in Iowa and North Carolina. Researchers found evidence of increased incidence of breast cancer in women using 2,4,5-trichlorophenoxypropionic acid (2,4,5-TP) and possibly in women using dieldrin and captan, although the small number of cases among those who had personally used pesticides precluded firm conclusions. Incidence was also modestly elevated in women whose homes were closest to areas of pesticide application (Engel, 2005).
A recent study of farmers and their families shows that young children of farmers using 2,4,5-TP on their farms had high levels of the pesticide in their urine samples soon after the chemical had been applied to the fields (Alexander, 2007). This is of concern given the evidence of increased susceptibility of children and young adolescents to the carcinogenic effects of chemicals.
*For chemicals that have been shown to be carcinogens, we provide classifications from two authoritative bodies: the International Agency for Research on Cancer (IARC, an international body) and the National Toxicology Program (NTP, a division of the U.S. Department of Health and Human Services). We have categorized endocrine-disrupting compounds where the body of peer-reviewed research indicates a strong foundation for doing so.
