Behind Endocrine Disruptors

Transcription

1 Behind Endocrine Disruptors Michele Lamse DiDiego, MS, RN, FNP Julia A. Eggert, PhD, RN, GNP Rosanne H. Pruitt, PhD, RN, FNP Lyndon L. Larcom, PhD 54 The Nurse Practitioner Vol. 30, No. 10

2 Endocrine Disruptors he increase in reproductive cancers and developmental problems over the past 70 years has led researchers to suspect environmental influences as a root cause. Evidence from wildlife and laboratory studies suggests that exposure to endocrine disruptors (EnDs) may be the cause. An EnD is a foreign substance or mixture that alters the function of the endocrine system. They can be found in food, water, soil, or air. Research into their possible role provides an opportunity to decrease modifiable risk factors. T etween 1973 and 1999, rates of prostate cancer rose 82.5% among African-Americans and 74.4% among Caucasians.1 The rate of hypospadias, a defect in the formation of the penis, doubled between 1970 and 1990;2 increases in related abnormalities such as cryptorchidism (undescended testes) and testicular cancer have been reported, as well as a decline in male fertility.3 Breast cancer risk has nearly tripled from a lifetime risk of 1 in 22 in the 1940s to 1 in 8 in The risk of breast cancer by 50 years of age increased from 24% in those born before 1940 to 67% in those born after.5 Neurologic problems, including autism and attention deficit hyperactivity disorder, B have increased significantly in the past 3 decades.6 In response to these statistics, scientists have begun to study environmental and lifestyle factors that contribute to disease. In particular, evidence from wildlife and laboratory studies suggests that exposure to EnDs may be related to reproductive cancers and developmental defects in humans. Research into the possible role of EnDs provides an opportunity to decrease modifiable risk factors for disease. Many plant and animal species are showing signs of ill health due to exposure to endocrine-disrupting chemicals. For example, fish in the Great Lakes, which are contaminated with polychlorinated biphenyls (PCBs) and other manthe Nurse Practitioner October

3 Selected Endocrine-Disrupting Chemicals 8 Compound Pesticides DDT, dieldrin, alachlor, atrazine, malathion, pentachlorophenol Persistent Nonpesticide Organochlorines Polychlorinated biphenyls Dioxins and furans Exposures/Uses Insecticides, fungicides, herbicides, wood preservatives Electrical capacitors, transformers, carbonless copy paper; produced during incineration, manufacturing of paper and plastic, and some chemicals lower levels. Rather than a linear distribution, some physiologically active systems have a U-shaped response curve: as the dose increases, so does the effect up to a certain concentration, then the effect decreases as the receptors saturate. Future research should determine the biologically active range of concentrations for compounds that act as EnDs. Persistent aromatic hydrocarbons Bisphenol A Phthalates Heavy Metals Lead, mercury, cadmium Phytoestrogens Industrial pollution, tobacco tar, charred foods Plastics: polycarbonate and polystyrene Commonly used in polyvinyl chloride and other plastic products; nail polish, hair spray, inks, adhesives Batteries, plastic stabilizers, pigments, thermometers, dentistry, pharmaceuticals, agricultural chemicals, antifouling paints Soy, grains, grain molds made chemicals, have numerous reproductive problems as well as abnormal swelling of the thyroid glands. Fish-eating birds in the Great Lakes area, such as eagles, terns, and gulls, have shown similar dysfunctions. This article will review recent studies on endocrine disruptors. This topic is especially important for advanced practice nurses so that they can educate patients about how to reduce exposure. Endocrine Disruptors An EnD is a foreign substance or mixture that alters the function of the endocrine system. They can be found in food, water, soil, or air. Endocrine disruptors work through a variety of mechanisms, including binding to hormone receptors to mimic natural hormones, blocking hormone receptors, or altering the production or metabolism of endogenous hormones. Effects from exposure to EnDs are more likely to occur when endogenous hormones are low, such as in utero and during childhood, although the effects may not appear until adulthood. Although EnDs are usually less potent than endogenous hormones, extremely low doses can produce a far greater effect than a high dose, depending on the time of exposure (see Table: Selected Endocrine-Disrupting Chemicals ). 2 Traditional toxicologic methods, which may not apply to hormones because they are physiologically active, 7 examine effects caused by large exposures, extrapolating them to Synthetic Estrogens Diethylstilbestrol (DES), a synthetic estrogen, was prescribed to pregnant women in the 1950s and 1960s to prevent miscarriage. Exposure in utero caused an increase in clear cell carcinoma in female offspring and increased rates of cryptorchidism and hypospadias in males. 1 Breast cancer rates increased for the women who took DES during pregnancy and for their female offspring. 8 Steroidal estrogens,listed as known carcinogens by the National Toxicology Program, 4 are used in oral contraceptives and post menopausal hormone replacement therapy (HRT). In the 2002 Women s Health Initiative study, a randomized trial with more that 16,000 women linked 5 years of using combination HRT to a 26% increase in the risk of breast cancer. 4 Recent use of oral contraceptives has been associated with a corresponding increase in breast cancer, although long-term use was not associated with increased risk. As women with long-term use of oral contraceptives reach menopause and the age of higher breast cancer risk, more information may become available regarding the long-term effects. 8 Conflicting evidence exists among scientists regarding hormones to promote growth in animals used for food. The European Union has restricted the use of six hormones, including 17 beta-estradiol, progesterone, and testosterone, citing health risks to consumers, although some scientists from the United States and Canada have argued that the use of hormones in livestock does not pose a health threat. 9 Heavy Metals During pregnancy, lead stored in the mother s bones is released along with calcium, and passes through the placenta into the fetus. Lead exposure can also occur via drinking water or dust from lead paint. Lead lowers brain metabolism and affects brain development by altering calcium flow, neurotransmitter activity, and the branching and myelina- 56 The Nurse Practitioner Vol. 30, No. 10

4 tion of nerve cells. Children exposed to lead exhibit short attention spans, aggression, poor language skills, and hyperactivity. 10 Mercury, released from burning fossil fuels such as coal, is biomagnified in the food chain. A recent study estimates that 60,000 children are born in the United States with neurologic problems that could lead to difficulties in school performance because of methylmercury exposure in utero. It is estimated that one in 10 women have mercury levels high enough to cause these effects. 6 Since a major source of mercury is canned tuna, pregnant women and children are encouraged to limit their consumption to once a week. 11 Pesticides Pesticides include herbicides, fungicides, insecticides, DDT (dichlorodiphenyltrichloroethane) and its metabolite DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene). Classified as a reasonably anticipated human carcinogen by the National Toxicology Program, DDT was used for 30 years to control insects until it was banned by the Environmental Protection Agency (EPA) in However, DDT is still produced and used in 18 countries around the world, chiefly for malarial control. 4 As late as 2003, the Centers for Disease Control and Prevention found clearly measurable levels of DDE in people 12 to 19 years of age. 12 Continued exposure may be due to residues of DDT/DDE in food and fat stores, which can be passed on to offspring. While several studies attempting to show a link between DDT/DDE and breast cancer have been inconclusive, some have measured levels at times of diagnosis rather than exposure, while others have not considered the effect over time or the multiplied effects from combinations of chemicals. 4 Dieldrin Rather than measuring pesticide levels at time of diagnosis, researchers in Denmark compared levels of the pesticide dieldrin in serum that had been collected 20 years ago, finding that women with the highest serum levels of dieldrin had double the risk of breast cancer. 13 Alachlor and Atrazine Alachlor is classified as a probable human carcinogen by the EPA, while atrazine exhibits antiestrogenic activity and may inhibit enzymatic conversion of testosterone. Researchers compared semen quality between men in rural Missouri, where pesticide use is high, and in urban Minnesota, where pesticide use is low. When correlating levels of eight pesticides in the urine to semen quality, researchers found reduced sperm concentration and motility related to the levels of alachlor and atrazine. 14 In addition to the negative effects on those who work with them directly, these pesticides can affect entire communities through drinking water. Industrial Chemicals Polychlorinated Biphenyls (PCBs) Organochlorines, a class of chemicals found in approximately 15,000 compounds including PCBs and DDTs, persist in the environment, accumulate in humans, and may act as carcinogens or EnDs. Researchers have found immune system changes, neurologic and motor delays, and learning problems in children exposed to background levels of PCBs in utero. 2,10 Testing adipose tissue rather than serum represents cumulative exposure, allowing for distinctions among the 209 types of PCBs. Because organochlorines are concentrated in adipose tissue, levels of PCBs in this tissue are 200 to 1,000 times higher than in serum. A recent study compared breast adipose tissue between 217 Researchers have found immune system changes in children exposed to background levels of PCBs in utero. women with breast cancer and 214 women as controls. Researchers found a clear association between some types of PCBs and breast cancer risk. 15 Polybrominated biphenyls (PBB) An accidental addition of PBB, a fire retardant, to animal feed in Michigan led to illness when the meat or dairy products were ingested. Farm families were the most affected. 1 In a longitudinal study, early onset of menstruation was observed among girls who were exposed to PBBs both in utero and as breast-fed infants. 1 Dioxin (2,3,7, 8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin) Dioxin, a group of highly toxic chemicals released from manufacturing and incineration processes, has been linked to cancer, birth defects, learning disabilities, infertility, endometriosis, and immune suppression. 4,6,10 Dioxin is ubiquitous, persisting in the environment, becoming incorporated in plants and algae, and accumulating in the food web. Often, studies of EnDs do not allow enough time for their effects to develop after exposure. However, in 1976, The Nurse Practitioner October

5 Health Risks of Plastics 20 Plastic Type Polyethylene terephthalate h (PETE or PET) Where Found Clear containers, e.g. soda bottles, bottled water Possible Health Risk May release phthalates, a suspected carcinogen Recommendations Do not reuse High-density polyethylene (HDPE) Opaque or translucent plastics e.g. milk bottles None known Good choice for reuse Polyvinylchloride (PVC) Some cling wraps (PVC plus phthalates or adipates) A source of dioxin and phthalates exposure Avoid use Low-density polyethylene (LDPE) Many food storage bags None known Good choice for reuse Polypropylene (PP) Some food storage containers, (Rubbermaid, Ziploc, Gladware, Tupperware) None known Good choice for reuse Polystyrene (PS) Foam containers, plastic cutlery May leach styrene, a possible human carcinogen Do not reheat food in Styrofoam Other (usually polycarbonate) Lining in food cans, dental sealants, 95% baby bottles May leach BPA, bisphenol A Avoid use or wash with mild detergent, rinse well serum was collected from 981 females between 1 and 40 years of age after an accident at a pesticide factory in Seveso, Italy, in which dioxin was released. An ongoing longitudinal study is comparing serum levels with breast cancer incidence. There was no statistically significant increase in breast cancer incidence or mortality in follow-up studies at 10, 15, and 20 years of age. However, after 22 years of age, 15 women were diagnosed with breast cancer, a statistically significant increase. When serum dioxin levels were compared, researchers found a twofold increase in breast cancer risk associated with a tenfold increase in serum dioxin. Considered an early finding because the number of cases is small, the most sensitive individuals in this study (those who were in utero or before menarche at time of exposure) have not reached the age of maximum risk for breast cancer. 16 Plastics Bisphenol A (BPA) Bisphenol A, a flame retardant and a resin used for plastic food containers, bottles, dental sealants, and linings in metal cans, can migrate from the plastic into food, especially at high temperatures, such as when canned food is heat processed or plastic dishes are heated in a microwave (see Table: Health Risks of Plastics ). Leaching increases with repeated use of BPA-containing plastic products. 17 Rodents exposed as fetuses to BPA at very low doses had alterations in the tissue development of the mammary glands, reduced sperm production, increased prostate gland weight, 58 The Nurse Practitioner Vol. 30, No. 10 accelerated growth, and early puberty in females. 17 Phthalates Certain phthalates, chemicals used to make plastics softer and more flexible, given to pregnant laboratory animals induced a syndrome similar to testicular dysgenesis (decreased sperm counts, testicular cancer, cryptorchidism and hypospadias) in male offspring. 18 The mechanism appears to be suppression of endogenous testosterone production by the fetal testes. Levels of phthalate metabolites measured in humans were significant in relation to decreased semen quality in men, endometriosis in women, and shorter gestation periods. 18 Researchers in Puerto Rico found that girls with precocious puberty who were developing breasts before 8 years of age had higher levels of several phthalates than girls with no evidence of early puberty. Phthalates were evaluated since water, infant formula, and other foods are imported to Puerto Rico in plastic containers. 4 Phytoestrogens Phytoestrogens are estrogen mimics that occur naturally in some plants. Some research suggests that they may protect against breast cancer, citing the higher soy diet of Asian women and their lower rate of breast cancer compared to American women. The typical Asian diet contains less fat and more fiber than the typical American diet, which may also be beneficial. Laboratory research with genistein, a soy

6 Pesticide Contamination in Fruits and Vegetables Foods with Consistently High Levels of Pesticides Apples Bell peppers Celery Cherries Imported grapes Nectarines Peaches Pears Potatoes Red raspberries Spinach Strawberries Foods with Consistently Low Levels of Pesticides Asparagus Avocados Bananas Broccoli Cauliflower Corn (sweet) Kiwi Mangos Onions Papaya Pineapples Peas (sweet) Based on over 100,000 tests by the United States Department of Agriculture and the Food and Drug Administration for pesticides on 46 popular fruits and vegetables. 19 phytoestrogen, yielded mixed results depending on dosage and timing. High doses of genistein inhibited breast cancer cells, while low doses stimulated their proliferation. Hence, more information is needed before making dietary recommendations about phytoestrogens. 4 Patient Education Healthcare professionals, in particular nurse practitioners, who educate patients on primary care and prevention, need to be aware of the potential health risks from EnDs and assist patients in reducing exposure, especially children, adolescents, and women of childbearing age. General steps include changing consumer and dietary habits and supporting changes in public policy. Specific recommendations include: Vary intake of produce to limit exposure to pesticides. Wash all produce, and peel those with waxy residue (see Table: Pesticide Contamination in Fruits and Vegetables ). Eat lower on the food chain, (i.e. produce or grains), or animals that do not eat meat. Choose meats, eggs, and dairy products that are hormonefree and organic. Choose lean cuts of meat and trim visible fat. Consult for recommendations for limiting fish consumption. Use traps or hotels for insects rather than spraying, and avoid areas freshly sprayed with pesticides for a few days. Use glass or ceramic containers rather than plastic for food storage and heating. Minimize contact of cling wraps to food, especially meats and cheeses. Determine if your drinking water contains lead. Consult the EPA water safety hotline at Avoid dust from lead-based paint. Support public polices to provide funding for independent research and to place the burden on corporations rather than consumers to prove a product is safe and to label products. REFERENCES 1. Landigran P, Anjali G, Droller DB: Assessing the effects of endocrine disruptors in the National Children s Study. Environmental Health Perspectives 2003;111(13): World Wildlife Fund: Chemicals that compromise life: A call to action. Available at: Accessed April 23, Dolk H, Vrijheid M, Scott JES, et al: Toward the effective surveillance of hypospadias.environmental Health Perspectives 2004;112: Evans N (Ed.): State of the Evidence: What is the connection between chemicals and breast cancer? [Brochure] San Francisco: The Breast Cancer Fund and Breast Cancer Action, (Original work published 2002) 5. King MC, Marks JH, Mandell JB: Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 2003;302(24 Oct): Krulewitch CJ: Environmental health and pregnancy. J Midwife Women Health 2001;46:6. 7. Welshons WV, Thayer KA, Judy BM, et al: Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity. Environmental Health Perspectives 2003;111(8): Brody JG, Rudel RA: Environmental pollutants and breast cancer. Environmental Health Perspectives 2003;111(8): Elliott I: European Union tightens ban on growth hormones. Feedstuffs 2002;74(52): Steingraber S: Having Faith: An ecologist s journey to motherhood. Cambridge, Massachusets: Perseus Publishing, Pastorik AM: Methylmercury poison: Is it just another fish story? The Nurse Practitioner 2004;29(4): Centers for Disease Control and Prevention, Second National Report on Human Exposure to Environmental Chemicals. Available at cdc.gov/exposurereport. Accessed June 30, Johnson-Thompson MC, Guthrie J: Ongoing research to identify environmental risk factors in breast carcinoma. Cancer 2000; 88, Swan SH, Kruse RL, Liu F, et al: Semen quality in relation to biomarkers of pesticide exposure. Environmental Health Perspectives 2003;111(12): Aronson KJ, Miller AB, Woolcott CG, et al: Breast adipose tissue concentrations of polychlorinated biphenyls and other organochlorines and breast cancer risk. Cancer Epidemiol Biomarkers Prevent , Warner M, Eskenazi B, Mocarelli P, et al: Serum dioxin concentrations and breast cancer risk in the Seveso women s health study. Environmental Health Perspectives 2002;110(7): Schonfelder G, Wittfoht W, Hopp H, et al: Parent bisphenol A accumulation in the human maternal-fetal-placental unit. Environmental Health Perspectives 2002;110(11):A Sharpe RM, Irvine DS: How strong is the evidence of a link between environmental chemicals and adverse effects on human reproductive health? Br Med J 2004;328: Environmental Working Group. Report card: Pesticides in Produce. Available at Accessed June 30, Green Guide: Plastics for kitchen use. Available at Accessed January 19, ABOUT THE AUTHORS Michele Lamse DiDiego is a Family Nurse Practitioner in Mariposa, Calif. At Clemson University, Clemson, S.C., Dr. Eggert is an Assistant Professor in the School of Nursing and Coordinator of the RN-BS Program. Dr. Pruitt is a Professor and Director of the School of Nursing. Dr. Larcom is a Professor of Microbiology and Physics. The Nurse Practitioner October