Health, Hormonal, and Reproductive Effects of Endocrine-Disrupting Chemicals in the Food Chain

 Dioxins, PCBs, Other Organochlorine Chemicals, etc.- Summary of Health Effects, Incidence, Areas Affected, and Sources (10-1-2000)

(editor: Bernard Windham, 12164 Whitehouse Rd, Tallahassee, 32311, ph 904-878-9024)

Introduction: the Rapidly Growing Problem of Endocrine Disrupting Chemicals in the Environment and Food Chain

The extent of the growing crisis in contamination of the environment and food chain by endocrine disrupting chemicals is reflected by the growing list of health advisories regarding eating fish and wildlife which should serve as a warning that similar bioaccumulation and effects are occurring in people as in fish and wildlife. For 1999 the U.S. EPA list of warnings that are in effect regarding toxic levels in fish or wildlife included over 52,000 U.S. lakes, 20% of total significant lakes, all Great Lakes, and approx. 7 % of all U.S. river miles(46). The number of health warnings rose again for mercury, PCBs. Dioxins, and DDT/DDE. In addition to the health advisories regarding the danger in eating fish and wildlife, there are widespread findings of hormonal and reproductive disorders/failures in wildlife caused by the toxic exposures(10,112), and this is also true in most urban and industrial coastal waters(117).

(there were approx. 50,000 warnings regarding mercury in water bodies in at least 42 states and 680 warnings in 35 states for PCBs. The FDA Action Level for mercury and PCBs respectively are 1ppm and 3 ppm in food, while the warning levels to limit consumption are .5 ppm and .2 ppm respectively. The EPA drinking water standard for PCBs is .5 micrograms per liter)

Large quantities of endocrine system disrupting chemicals that have adverse effects on the hormonal and reproductive systems of animals and humans have been released into the environment since WWII and are accumulating in the food chain, animals, and humans. These chemicals have been found to act as estrogens, anti-estrogens, androgens, anti-androgens, or to interfere with thyroid hormone, cortisol, insulin, or growth regulators. Evidence that they are having widespread catastrophic effects on wildlife and domestic animals is growing, and serious widespread effects on humans are now also being seen. A recent report by the National Research Council found that 50% of all pregnancies in the U.S. are now resulting in prenatal or postnatal mortality, significant birth defects, neurological conditions, or otherwise chronically unhealthy babies(1). Approximately 250,000 U.S. children are born each year with birth defects diagnosed at or shortly after birth. Birth defects are the leading cause of infant mortality in the United States. Congenital anomalies, sudden infant death syndrome, and premature birth combined account for more than 50% of all infant mortality.

TCDD dioxin is the most toxic of a class of organochlorine chemicals including chlorinated dibenzo-p-dioxins(CDDs),dibinzofurans(CDFs), polychlorinated biphenals(PCBs), brominated dibenzo-p-dioxins(BDDs), brominated dibenzofurans(BDFs), and polychlorinated pesticides. This group have been found to have hormonal effects that disrupt the endocrine system of wildlife and humans resulting in adverse effects on reproductive system development and hormones, fetal development, and the immune system at extremely low levels of exposure (10-12,32,91,112,113). Dioxins have been found to have both estrogenic and antiestrogenic effects depending on the organ or tissue affected. The toxic metals mercury, lead, and cadmium as well as phenols have also been found to have reproductive and endocrine system disrupting effects(10-12,32,5). Exposure to relatively low levels of these chemicals have been documented to have had catastrophic effects on populations of Beluga whales, alligators, turtles, mink, otters, bald eagles, osprey, cormorants, terns, herring gulls, migratory birds, chickens, lake trout, chinook and coho salmon, etc. throughout the U.S. and Canada (5-12,32,34).

Animals and human fetal development is dependent on hormonal levels at various phases of development and the endocrine, reproductive, neurological, and immune systems are all being impacted, often seriously or catastrophically. These chemicals are being found to have estrogenic effects(10) and/or antiandrogenic effects(48-50) on the hormonal/endocrine systems of fish, birds, and animals- resulting in effects at very low levels on the male and female reproductive organs and systems (9-12,32,34,104,107,112). Some of the effects are immediate and acute, but other effects are less obvious and are not recognized until years later or in the next generation. Male animals and humans in industrial countries appear to be becoming feminized through exposure to these estrogenic and antiandrogenic chemicals. Estrogenic chemicals cause cells to produce surplus levels of estrogen, which has been linked to breast cancer, testicular cancer, lowered sperm counts, and malformation/mutations of male sex organs, and a decreased number of successful male births(63,29,31,92,93,98,104-107,118). Studies have found that the combined synergistic effects of such estrogenic organochlorine chemicals such as endosulfan, dieldrin, toxaphene, and chlordane are much stronger than would be expected(63). Similar synergistic estrogenic effects were observed when small levels of estrogenic pesticides were combined with 2 types of PCBs(84).

Effects of Endocrine Disrupting Chemicals on Fish and Wildlife

The widespread effects observed in wildlife found to have accumulated these chemicals have now been confirmed in experimental animal studies, and a long list of additional chemicals that have estrogenic effects have been identified. Table 1 gives a list of 46 chemicals documented to have serious endocrine system disrupting effects- including 27 insecticides or fungicides, 8 herbicides, 3 toxic metals, and 7 industrial chemicals or by products(10). Very low levels of these chemicals are required to produce reproductive problems, birth defects, and development problems compared to even the low levels found to produce cancer. For example only 60 parts per billion(ppb) of DDE are required to cause antiandrogenic effects on male test animals. Lake Apopka alligators and many other populations including people have been found to have much higher levels. DDT is still a widely used chemical throughout the developing world and is dispersed all over the world by atmospheric and oceanic transport. Low levels of vinclozolin, a widely used fungicide, have similar anti-androgenic effects(49), and even lower levels of TCDD have endocrine disrupting effects on animals. The herbicide atrazine similarly blocks testosterone binding(87), and another group of common pesticides, pyrethrins, also have been found to have anti-androgenic effects(83) and to be the likely cause of enlarged breasts in men in some populations such as one in Haiti in 1981.

Effects of Organochlorines and Other Endocrine-disrupters on Wildlife and Animals

Studies(5,6,7,8,9,10,11,12,32,45,,51,99) have found organochlorine chemicals to be the cause of widespread catastrophic effects on wildlife including:

(1) eggshell thinning, deformities and high mortality in birds and eagles of the Great Lakes area, West Coast, New England, Florida, etc.

(2) abnormal thyroid function in fish and birds of the Great Lakes area.

(3) abnormal hormone levels in birds, alligators, and mammals in the Great Lakes area, Florida, etc.

(4) decreased fertility in birds, fish, shellfish, otters, and minks in the Great Lakes area, west coast, Florida, etc.

(5) emasculation and feminization of male fish, birds, turtles, alligators, otters, minks, beluga whales, polar bears, and panthers in the Great Lakes area, Florida, west coast, Europe, Arctic.

(6) defeminization and masculation of female fish, gastropods, turtles, birds, and mammals in the Great Lakes area, Florida, west coast, Europe, etc.

(7) alteration of immune function in birds and mammals of the Great Lakes area

(8) birth defects and high infant mortality in mammals of the Great Lakes area

(9) behavioral changes in birds of the Great Lakes and west coast areas

(10) abnormal sex organs and intersexed birds, turtles, alligators, sturgeon, etc. in the Great Lakes, west coast, Florida, Mississippi and Missouri Rivers, etc.

(11) low testosterone levels and undescended testes in alligators and panthers in Florida

(12) strongly significant dose related relationship to endometriosis in monkeys.

(13)production of vitellogin, a female protein, by male fish living near sewer outfalls.

(14) doubled rate of testicular cancer and reproductive defects in military dogs used in Vietnam and their offspring.

Studies have found these chemicals to be the cause of large numbers of egg mortality, infant deformities, sexual abnormalities, and population decline among birds and fish eating animals in the Great Lakes area, Florida, Arkansas, Oregon, Mississippi River, Canada, Great Britain, etc.

(5-12,32,99,107). One type of deformity commonly caused among bird populations and in millions of commercially raised chickens exposed to low levels of dioxin or other dioxin-like chemicals is chick-edema disease, which causes twisted beaks, crooked legs, deformed claws and feathers, and other abnormalities(9). More than 50 horses and hundreds of birds, chickens, dogs, and cats died after a horse practice area was sprayed with oil contaminated with relatively low levels of dioxin at the Shenandoah Stables near Moscow Mills, Missouri(9).

The most extensive study of organochlorine related effects are the widespread cases of eggshell thinning, reproductive problems, and other health effects observed in the Great Lakes area as a result of DDT, PCBs, and dioxin levels for the last 3 decades. These effects have also been observed and studied in other more isolated cases. David Best of the U.S. Fish & Wildlife Service has been seeing increased deformities in eagles, high mortality, and reduced hatching rates(12). He indicates no successful reproduction in the Great Lakes area and that this area acts as a "black hole" for eagles migrating from other areas. He found eagle reproduction falls when PCBs in the body exceed 4 parts per million (ppm) or DDE levels exceeds 1 ppm. Much higher levels are common in the Great Lakes area, with PCBs in eggs found as high as 120 ppm. The levels of PCBs in Great Lakes fish has also been found to be the cause of reproductive system abnormalities and population declines in fish eating animals like otters and minks(12). PCBs have been found to cause developmental and reproductive effects on wildlife at levels similar to the average levels of PCBs found in human breast milk in industrial nations like the U.S.(34,45,116). PCBs have been shown to turn turtles that should have been males into "females" and females into feminized males at levels as low as 10 micrograms per egg.

T.M. Gross of the Univ. of Florida indicates PCBs appear to have synergistic effects with those of other estrogenic chemicals like dioxin, DDT, mercury, etc.(34) Dioxin has been found to have effects at extremely low levels(parts per trillion), but much less historic testing has been done for low levels of dioxin due to technical difficulty and expense. Some of the wildlife effects attributed to PCBs and DDT/DDE could have been contributed to by dioxins, though laboratory studies have confirmed each of these cause effects on animals of the types seen in wildlife at levels of the pollutants observed in wildlife.

Production of a female protein, vitelloginin, in males is turned on by estrogen and has a feminizing effect on the male reproductive system(77). Therefore vitellogenin production in males serves as a good marker for estrogenic chemical effects. Extremely high levels of vitelloginin and estrogen are being found in trout and carp in England, Wales, and other locations(51). The main sources appear to be ethynlestradiol(EE-the main estrogenic chemical in birth control pills) and nonylphenols, a breakdown chemical of alkylphenol polyethoylates which are widely used in dishwashing fluids, paints, pesticides, plastics, food wraps, etc. Nonylphenols have been found to cause proliferation of cancer cell growth(98). The main source of these in streams in the U.S. and other industrial countries appears to be sewage effluent, but they are also found in food and drinking water(78). Lab studies on animals find reproductive systems effects at levels similar to current levels of human exposure.

Some of the Phthalates (plasticizers) which are the most widespread chemicals in the environment have also been found to be estrogenic, carcinogenic, and reproductive toxins in animal studies(51,79,99,109,110). The effects on the 2nd generation are more than on the generation exposed(79). While phthalates are found in fish in fresh or marine waters exposed to sewage(99), the most common human exposure is likely from food packaging where di-butyl phthalates(DBP) levels of 50 to 500 micrograms/kg are common(80)and DEHP is likewise common. Others include BHA (a commonly used food preservative), BBP (benzy butyl phthalate-found in construction adhesives and paper food wrapping), DEP(di-ethyl phthalate-found in nail polish, dyes, plastic food wraps), and DDP (diphenyl phthalate). These and other xenoestrogens also stimulated the growth of breast cancer cells in culture, and a strong case has been developed by studies that such chemicals are a significant factor in the rapid increase in breast cancer that has been observed(47,51,86). DBP is widespread in insect repellents, plastic plumbing pipes, and plastic food wraps. BBP is found in adhesives and paper products used in food wrapping. BBP is often found in levels exceeding 45 mg per kg in butter and margarine(52). Animal studies have confirmed that low levels of these chemicals alter sex hormone activities and studies in Puerto Rico indicate they are the likely cause of premature puberty in girls there, with cases occurring as early as 2 years of age(109). Fetal exposure during the first trimester of pregnancy appears to have the largest effect on fetal sex organ development. Women tested had relatively high levels of DEP and DBP. DEHP, BBP, DBP, DEP, and DINP have all been found to lower fetal testosterone levels in animal studies at low levels and to result in male reproductive defects (110). A federal scientific panel of the National Toxicology Program, NIEHS, concluded that these phthalates disrupt male reproductive development.

Another estrogenic chemical commonly found in food is bisphenol-A, which is leaching from plastic resins coating cans and baby bottles in supermarkets. About 50 % of cans surveyed had significant levels of BPA which has been shown to cause health problems(55). Beta-sitosterol, a phytoestrogenic chemical produced by tree bark and found in waters below paper mills, has been shown to affect the endocrine and reproductive systems of fish and animals below pulp plants(60). It has been found to significantly alter male and female reproductive hormones. Since sitosterol is found in the bark, much of this effect of pulp mills might be reduced by debarking pulp trees prior to grinding them up. However other chemicals which affect fish hormones such as dioxin are also found in pulp effluent. While some of the common phthalates of weakly estrogenic, they have also been found to have more adverse synergistic effects when combined with other chemicals found in the environment and food chain. For example, DEHP has been found to have synergistic effects with trichloroethylene and heptachlor for prenatal loss of fetus and maternal mortality in rats(81).

Organochlorines and Population Dieoffs of Marine Mammals

Catastrophic declines in mammals at the top of the marine food chain such as dolphins and seals throughout the world have been traced to buildup of these chemicals in fish and the animals at the top of the marine food chain(6,10). Fish in the North Sea and Baltic Sea have been found to have high levels of PCBs and dioxins, and a Dutch study found that seals eating fish from these areas have significantly damaged immune systems compared to seals eating less polluted fish. Over 20,000 harbor seals died in infectious epidemics in recent years(6).

Native groups eating these marine mammals have also been found to have high levels of PCBs and dioxins, and to have related health problems(27,37).

Organochlorines and Endocrine-disrupting Chemicals Effects in Florida

Florida is one of the states most at risk from organochlorine and endocrine-disrupting chemicals due to its large and growing population with much higher than average emissions and sources than most other states. Florida has the most incineration of any state (which is the number one source of dioxins and furans), and likewise has the highest per capita use of pesticides, herbicides, and fungicides, along with a large number of paper mills with dioxin in effluent. Widespread problems in wildlife populations in Florida related to such chemicals have already been documented. Little is known about the effects on humans in Florida as there has been virtually no testing of meat and dairy products, dioxin levels in humans or mother's milk, or of high risk populations as in some other states and countries where data is referenced.

Lake Apopka, Florida's 3rd largest lake, is polluted with organochlorine pesticides from a chemical spill of DDT and pesticide runoff from citrus farms and muck farms. Studies of bass, alligators, and turtles in Apopka found population densities less than 10 % that of less polluted lakes(7,8,12), with sexual infertility and sexual abnormalities of males appearing to be the main cause. Both alligators and bass were found to have abnormally high levels of estrogen and males to have very low levels of testosterone and very small penises. This has resulted in very low levels of successful reproduction, with sperm less males, intersexed gators with testes and ovaries, and gator eggs where 90% do not survive and the rest are sexual mutants(8,12,48). Dr. Guillette of the Univ. or Florida said that "if organochlorine chemicals are detrimental to embryos of other species, they are going to be detrimental to human embryos". Bass and other fish have also been found to be unable to reproduce and to be vanishing from other formerly highly productive Florida Lakes such as in the Ocklawaha chain of Central Florida(7). Like in Apopka, the cause of reproductive failure in the fish appears to be estrogenic effects of pesticides from runoff. The levels causing reproductive failure in fish and animals are more than 1000 times less than the level that current EPA standards for pesticide residues in food indicate is dangerous(7).

Similar findings have been seen in dioxin or organochlorine chemically contaminated fish and wildlife of the Great Lakes region, Mississippi River, and other areas throughout the U.S. and Canada, and in dioxin or pesticide contaminated Florida rivers (8,9,10,12,4,99). Animal studies have confirmed that PCBs have similar feminizing and sexual mutation effects, and that there are synergistic effects between different organochlorine congeners that produce effects at lower levels than for one toxic chemical alone(12,20). According to the U.S. EPA, there have been over 4000 listings of health bans or restrictions on eating fish due to food chain contamination in millions of lakes and rivers throughout the U.S., with over 30 states having such bans due to organochlorine chemical pollution(23 states including Florida with bans due to dioxin, 30 states for PCBs ,& 26 states for pesticides).

In addition to seven Florida rivers and portions of St Andrew Bay and Perdido Bay that have been documented to be contaminated with dioxin, over 20,000 acres of St Joseph's bay have been found to be contaminated by dangerous levels of dioxin from 2.9 to 10.9 ppt in sediments of the bay(16). Dioxin was also found to be bioaccumulating in fish, crabs, and shellfish. The levels in bay sediments are similar to those in other areas studied where biomagnification occurred in adult cormorants, gulls, and mergansers to levels that caused birth defects and reproductive failure(16,19). A study of bioaccumulation of dioxin and PCBs in a bay in Lake Huron with sediment levels similar to those in St Josephs Bay found biomagnification occurred on a logarithmic scale as you go up the trophic food chain scale. The biomagnification at the fifth trophic level of fish eating birds was 31 times the sediment levels in TCDD-equivalence and 14.2 times for levels. These levels resulted in widespread birth defects and reproductive failures. A non-viable bald eagle egg had even higher levels, 1065 ppb TCDD-Eq and 58.9 ppm s. The source of the dioxin in St Josephs Bay is effluent from a pulp and paper mill. Due to the widespread contamination in the bay, which was one of the most pristine and productive fish, shellfish, and wildlife areas in Florida, the Fish & Wildlife Service has recommended that dioxin emissions into the bay should be eliminated by switching to a non-chlorine process that does not produce dioxins. They have also recommended more stringent controls on dioxin than currently exist in Florida. However these recommendations have not been approved by regulatory agencies.

In addition to the dioxins, other similar highly toxic and carcinogenic chlorinated organic chemicals have been found in the sediments of most bays and estuaries in Florida. A Dept. of Environmental Protection survey found polycyclic aromatic hydrocarbons(PAHs) in 70 percent of coastal sediments sampled, PCBs in 55% of sediments sampled, and chlorinated pesticides in 28% of sediments sampled(17). These chemicals have been identified in studies as being responsible for widespread fish cancer and fish disease by scientists who participated in a Congressional Hearing on "the fish cancer epidemic in the U.S."(44) According to Senator Breux, then chairman of the fisheries committee in summing up the conference: "What we are witnessing is a natural population that is trying to show us there is something very, very wrong with the environment."

In addition to bioaccumulation of toxic organic chemicals in fish and shellfish, the levels of highly toxic contaminants in much of the sediments sampled have been found to be toxic to marine biota and fauna in the area with many dead zones or areas with greatly reduced diversity resulting (the number of species found in sampling was less than 5 at 17% of Gulf Coast sites). Florida Gulf Coast estuarine sediments were found to be at levels toxic to marine organisms in 20 percent of areas sampled in 1992(22), and PAHs exceeded the EPA ERL criterion (total PAH>4 ppm)in 14 % of the sediments. Pesticides such as dieldrin, endrin, chlordane, and DDE(ERL=2.2ppb) exceeded the EPA criteria in 23-32 percent of sediments(21,22), and heavy metals such as mercury, chromium, nickel, lead, and cadmium exceeded the standard in 11 to 22 percent of sediments. The Effects Range Low(ERL) is the concentration of a contaminant that is above 10% of the ranked contaminant levels that resulted in toxic effects. Along with the many dioxin congeners, PCBs , chlorinated PAHs and pesticides found in the sediments of Panama City Harbor in St Andrew Bay, elevated levels of toxic metals and sulfides were also found(19). The sediments were found to be toxic to bottom feeding amphipods.( ERL=22.7ppb)

These chlorinated chemicals and toxic metals are also being found in fresh water sediments and are affecting fish and wildlife throughout Florida in drainage ponds, lakes, and other inland waters(41) and similarly in other states(114-117). Studies found widespread contamination of drainage ponds and lakes in Tallahassee and Orlando by PAHs and toxic metals from atmospheric deposition and runoff. In a survey of the Indian River Lagoon, PAHs were found to be up to 29.4 ppm with many sites above the ERL level and 2 sites above the AET level(22 ppm-level above which biological effects always occur)(24). PAHs are primarily the result of incomplete combustion of coal, oil, gas, and garbage. The Indian River survey also found phthalate esters from plasticizers and highly toxic levels of tributyltin(TBT) to be widely distributed in the lagoon(24) and referenced studies that have also found PCBs and chlorinated pesticides in the system. Pesticides in rivers, lakes, and coastal areas come primarily from agricultural or lawn runoff. TBT used in antifouling paints has been found to disrupt hormones controlling sexual development in mollusks at 10 parts per trillion resulting in reproductive failures and abnormalities(112).

Pyrogenic PAHs such as benzo(a)pyrene(ERL=.43ppm,dry weight) have been shown to be highly carcinogenic, mutagenic, and teratogenic to a wide variety of organisms (21,22,24,25,53), as well as estrogenic(51,112,114). PAHs are thought to be a major factor in the increased cancer rates found in industrial countries. In animal studies on mammals, PAHs have been shown to cause skin cancer, leukemia, breast cancer, lung cancer, lymph system cancer, and reproductive system cancers(25). They also cause cancers in fish and other marine organisms, along with causing high chick mortality and abnormalities in birds feeding in areas with high PAHs. PAHs have also been found to cause eye damage, cataracts, and reproductive toxicity(53).

PAHs are not very soluble and tend to concentrate in sediments, organic materials, and the plant or animal food chain. Aquatic invertebrates, fish, and amphibians collected in areas with high PAHs in sediments show elevated levels of tumors and disease(25,114). Lower molecular weight PAHs such as naphthalenes are more acutely toxic but less carcinogenic than the high molecular weight pyrogenic PAHs. Atmospheric emissions are responsible for at least 75% of pyrogenic PAHs in aquatic environments. The main sources of emissions are burning of organic materials in forest fires, incinerators, power plants, and home heating equipment. Car exhaust is a lesser but very widespread source as well. PAHs are found in plants grown in areas with high PAH deposition rates- in such cases fruits and vegetables may have up to 100 times normal levels.

Toxic metals like mercury and cadmium have high levels of emissions in Florida and have also been found to have estrogenic effects at very low levels(10,5). Mercury appears to be responsible for feminization and reproduction problems of beluga whales and polar bears in the Arctic and panthers in Florida(12,40,NIEHS 29). In recent years 67% of male panther cubs born have had undescended testicles, low testosterone levels, abnormal sperm, and very high estrogen levels. Recent tests show some males have estrogen levels twice as high as testosterone levels and some females have higher testosterone levels than estrogen levels(12). Levels of mercury in Florida are also sufficient to have contaminated lakes and bays in Florida to levels where fish in over half the lakes and streams tested have levels of mercury dangerous to wildlife or humans eating the fish, and where birds and panthers in South Florida are dying as a result of mercury levels in the fish(5,40). Panthers eat racoons and other fish predators.

Health Effects of Dioxins and Related Chemicals on Humans

Dioxin is the most acutely toxic chemical and the most potent carcinogen ever tested according to the U.S. Center for Disease Control(5,9). Dioxin causes cancer, birth defects, learning disabilities, endometriosis, depression and behavioral problems, lower sperm counts and other sexual abnormalities, atherosclerosis and heart disease, and damage to the immune system, endocrine system, liver, skin, and neuromuscular system (1-4,9,10,11,29,32,36,37,38,45, 92,95,96,98,106,112). Industrial pesticide plant workers exposed to dioxin have been found to be more than 3 times as likely to die from cancer and more than 2.5 times as likely to die from ischemic heart disease as workers of similar characteristics working in a nearby gas plant(61). They also have been found to have disruption of the male reproductive system(104). And the risk of dying was found to be dose related- increasing directly with increased exposure to dioxins and furans. Seafood from the Baltic Sea has been found to be highly contaminated with dioxins, and those eating such seafood regularly have been found to have dioxin levels comparable to workers that have been found to have adverse health effects(104).

Dioxin along with other related organochlorine chemicals are very widespread in the environment and food chain in all areas of the country and is found in the blood, semen, breast milk, and fatty tissues of humans throughout the country (4,11,26,33,38). Infants receive the highest dose and are also the most vulnerable(11,33). Mercury, dioxins and PCBs all disrupt the activity of thyroid hormones, which are essential for normal neurological growth and development(38,66,74,76,108,5). Pregnant women who suffer from hypothyroidism (underactive thyroid) have a four-times greater risk for miscarriage during the second trimester than those who don't, and women with untreated thyroid deficiency were four-times more likely to have a child with a developmental disabilities and lower I.Q. (74)

PCBs are distributed widely in the environment and cross the placenta to cause in utero injury to the developing brain (75.5). Development of the fetus is most sensitive and prenatal exposure results in developmental delays, impaired cognitive function, hyperactivity, and attention deficit disorder(75.2,75.5,95,96,4). Large numbers of people are being adversely affected by dioxins and other members of its chemical family, and very small levels of dioxin cause serious adverse health effects. Dioxin is still found in the bodies and sperm of Vietnam veterans 20 years after exposure (average of 49 ppt in 1987 compared to 5 ppt for controls), and Vietnam veterans' children have experienced much higher levels of birth defects such as spina bifida and cleft palate along with much higher levels of leukemia, prostate cancer, colon cancer, male breast cancer, ischemic heart disease, motor neuron disease, and learning disabilities than normal(5,11,105). An Australian Government study of children of Vietnam veterans found higher levels of adrenal gland cancer, acute myeloid leukemia, and non-Hodgkins lymphoma than in the general population(105). Most Americans are exposed to unhealthy levels of dioxin through normal daily consumption of food according to a recent study(101). According to the report, children exposed to dioxins in utero during critical periods of development appear to be the most sensitive and vulnerable to the toxic effects. Dioxin exposure has been associated with IQ defects, increased prevalence of withdrawn/depressed behavior, adverse effects on attentional processes, an increase in hyperactive behavior in children, disrupted sexual development, birth defects and damage to the immune system(75.5,101).

Furans, PCBs, DDT/DDE, and other organochlorine pesticides such as endosulfan, methoxychlor, dicofol, and lindane have also been shown to be endocrine-disrupting chemicals that have health effects and adverse reproductive impacts on wildlife similar to dioxins (4,10,11,12,82,85,112). Polyaromatic hydrocarbons(PAHs) and toxic metals like mercury, cadmium, and lead also are highly neurotoxic and strong cancer promoters- in addition to being endocrine-system disrupting chemicals(5,10,112,113). PAHs and PCBs have both been found to be among the most toxic and widespread contaminants, with both ranked in the top 10 of toxics adversely affecting the most people by U.S. EPA/ATSDR. PAHs are increasing in lake and reservoir sediments and streams in urban areas(41) and in many bays(114,116,117). PAHs come primarily from petroleum and combustion of fossil fuels. PAHs have been documented to cause genetic damage, malformations, reproductive failures, and reduced growth rates in fish embryos at levels as low as 0.7 ppb(114). PCBs have similar affects on mollusks (116). PCBs also have been found to be strong promoters of cancer, with those having over 1 ppm in blood serum having 4.5 times greater risk of non-Hodgkin's lymphoma, the rate of occurrence of which has increased by a factor of 2.5 since 1950(90). It is conjectured that this is due to PCBs known suppression of the immune system. The FDA Action Level for PCBs in meat(fat) is 3 ppm.

PCBs, dioxins, and mercury have been found to interfere with transport of thyroid hormone which is necessary for normal growth and development(38,66,74,108,5). Higher levels of PCBs in breast milk were found to be correlated with lower levels of thyroid hormone in infants(76,108). A relationship has been demonstrated between decreased thyroid in infants and increased risk of neurological disorders. Humans are accumulating PCBs since they bioaccumulate and the food chain contains PCB s. Fish collected nationwide show residues at a level of .53 ppm, and many marine species have levels thousands of times higher(72). A group of killer whales living off coastal British Columbia averaged 250 ppm PCBs while the females averaged 60 ppm since the majority of PCBs in a mother has been found to be transfered to the calf or infant via lactation(72). Inuit mothers in the Arctic have extremely high levels of PCBs in their milk due to a diet high in fish(37).

Organochlorine and Endocrine-disrupting Chemicals Effects on Humans

The first generation of humans widely exposed to synthetic chlorinated organic chemicals in the womb began reaching reproductive age in the 1970s. Lab experiments and studies of human exposures have demonstrated that exposures of fetuses to endocrine-disrupting chemicals can profoundly disturb organ differentiation and development of the endocrine, immune, neurological, and reproductive systems of the fetus(4,10,11,13,20,28,29,32). Many chemicals that have estrogenic effects that disrupt the endocrine system have been identified (see Table 1), as well as a large group of chemicals that affect the reproductive systems of male fish and animals through antiandrogenic effects (47,48,49,50).

Studies have found mother's pass hormone-mimicking chemicals to a fetus or child through blood before birth and through breast feeding after birth, with widespread serious consequences including size, behavior, and intellectual development(10,29,31,33,38,75.5,91).

International data from industrial countries using thousands of men show average sperm densities have fallen over 40% along with an additional drop in sperm volume of 20% and increased sperm abnormalities in the last 50 years (over 50% decline in overall sperm counts) (10,29,31,92,98). Researchers at the National Institute of Health found that the average decline in the U.S. has been about `1.5% with an even larger decline in Europe(93). The declines vary geographically but the largest declines have been seen in urban areas. A study of sperm counts at a Paris sperm bank found a large decline of 33% in sperm density over the last 20 years in a group of men followed in a carefully controlled study, with the decline averaging over 2.5 % per year and an increase in abnormal sperm of 0.7% per year(NEJM,31). Researchers at Florida State Univ. reported similar findings(4). Since 1970 significant reductions in the proportion of boys to girls born have been documented in Denmark, Netherlands, U.S. Canada, Sweden, Germany, Norway, and Finland. Researchers suspect that disruption of normal male fetal development by environmental pollutants is the cause of these problems and trends(93). Steroidal hormones such as estradiol, testosterone, and progesterone that are given to the majority of beef and dairy cows also appear to be an increasing factor, with levels in meat products testing at up to 30 times normal levels of such hormones(94). Heavy use by the U.S. meat industry of such hormones led to the European Union banning imports of U.S. beef in 1988. Such practices are banned in Europe.

Occupational exposure to certain pesticides have been found to result in reduced sperm counts and infertility(65). There has been a more than 200% increase in male reproductive problems such as cryptorchidism (undescended testicles), hypospadias, abnormal sperm, and testicular cancer in the U.S. and England since 1969(10,29,31,92,93,98). In a group of London men, these problems were also accompanied by significant increases in sperm abnormalities including a twelvefold increase in the number of men producing mostly abnormal sperm in the 1980s compared to the 1970s(29). A factor in this increase appears to be increased estrogenic chemicals in river drinking water in the London area. During this period there has also been a significant increase in breast cancer, testicular cancer, and prostrate cancer in the U.S., and an over 400% increase in ectopic pregnancies (outside the womb) and increased endometriosis in women. Follow up studies and laboratory animal studies have confirmed a relation of these conditions with hormone mimicking estrogenic chemicals such as DES, dioxin, PCBs, DDT, etc. which have been increasing widely distributed in the environment since the 1950s.

A strong case has been developed that xenoestrogens in the food chain are a major factor in the increase in breast cancer in the U.S. and industrial countries(51,86,98). 16-alpha-hydroxyestrone, a metabolite of the human estrogen estradiol, has been found to be strongly linked to breast cancer. Xenoestrogenic chemicals have been found to promote breast cancer by several mechanisms- including: promotion of the bad 16-alpha form of estrogen as opposed to the good 2-alpha form; binding to estrogen receptors and inducing proliferative signals to cells; generation of new blood vessels that aid tumor growth; damaging DNA. Corn oil and polyunsaturated or hydrogenated fats also appear to have such estrogenic effects, while indole-3-carbinol found in plants of the broccoli family and soy products retard cancer by favoring the 2-alpha form of estrogen(51). A synergistic effect of low levels of estrogenic chemicals has also been documented. Mixtures of low levels of organochlorine chemicals were found to cause a significantly greater proliferation of tumor cells than when exposed individually. This could also explain why the distribution of toxic-waste sites in the U.S. closely parallels the sites of highest breast cancer mortality(59) and increased birth defects().

Women tested in a gynecological clinic with endometriosis and antihyroidal antibodies had significantly higher levels of PCBs than controls on average(100). Organochlorine compounds also have been documented to adversely affect the immune system, resulting in increased allergic sensitivities and diseases such as eczema(102).

Several populations of boys in Taiwan and Michigan have been monitored whose mothers were exposed to endocrine system disrupting chemicals such as dioxin and PCBs through contaminated rice oil and eating meat grown with contaminated feed or PCBs from Lake Michigan fish(10,11,75,75.5,88,96,108). These boys have developmental, psychomotor, and cognitive disfunction, along with reproductive system deformities and problems similar to some of the animal populations. The Michigan groups effects were found to be related in a dose-dependent manner to umbilical cord serum level. Another group whose mothers ate 2 to 3 fish per month from Lake Michigan prior to birth were found to have lower birth weight, growth retardation, low IQS, and cognitive, motor, and behavioral deficits compared to a control group. The group having high level of PCBs later was found to display disruptive and intractable behavior. The group with the highest prenatal exposure to PCBs had average IQ 6 points below controls and other persistent harmful developmental effects(88,75.5). Other studies on children with prenatal exposure to PCBs or DDT/DDE have found similar neurological problems and learning disabilities(36,53,75,88),some in populations with no known special exposure. Studies indicate at least 5% of the babies born in the U.S. are exposed to quantities of PCBs sufficient to cause neurological effects, learning disabilities, and behavioral problems. According to EPA and other studies this is true for an even higher percentage due to toxic metals such as lead, mercury, and cadmium(5).

Another similar well documented case is the experience with DES( a synthetic estrogenic chemical used to prevent spontaneous abortions from 1948 to 1971). Daughters whose mothers took DES have been found to suffer reproductive organ disfunction, abnormal pregnancies, lowered fertility, immune system disorders, and depression(10). These effects are similar to those documented for animal populations with similar exposures to endocrine-disrupting chemicals.

The rate of depression and other similar neurological problems has increased substantially since 1945(54). In a given year approximately 13% of women and 6% of men suffer major depression in the 1990s(54), and over 20% of all US children have their learning ability adversely affected by endocrine system disrupting chemicals including toxic metals (62). Many of the organochlorine chemicals and toxic metals have been found to adversely affect the levels of brain neurotransmitter uptake of serotonin, dopamine, acetylcholine, and norepinephrine which control the brain and body's neurologic functions. Low levels of serotonin have been shown to result in depression, anger, anxiety, aggression, violence, insomnia, obesity, sexual deviance, and other impulse disorders(62).

EPA conducts an annual survey of chemicals building up in the adipose (fatty) tissue of humans autopsied throughout the U.S. and has found levels of dioxin and organochlorine chemicals found in scientific studies to cause serious harm to wildlife and humans(10,11,26). The average body burden in the U.S. is 9 parts per trillion (ppt), and the average dietary background exposure level of CDDs, CDFs, and PCBs is 200 to 400 picograms TEQ/ day (3 to 6 pg TEQ/ kilogram/day) (pico=1 trillionth). A group suffering from Chronic Fatigue Immune Dysfunction Syndrome was found to have significantly higher levels of organochlorine chemicals than a matched control group(57). The CFIDS group averaged 100% higher levels of DDT and hexachlorobenzen than the controls. They were also found to have a chemical in their blood similar in structure to pesticides and which appeared to have been caused by mutation of natural body bacteria. The breasts of Quebec area women with breast cancer and other groups of women with breast cancer have been found to have much higher levels of DDE than those without estrogen responsive cancer(37,51). There is now a strong case that estrogenic chemicals are a significant factor in the increase in hormone responsive cancers(4,51).

Relatively high concentrations of dioxins and furans have been documented in human milk in industrial countries such as those of Europe(33). The average daily dose of infants through breast milk is 60 pg TEQ/kg body weight/day- 10 to 20 times that of average adult exposure levels. In a recent study of infants with average dioxin levels in this general range, the infants were divided into a high exposure and low exposure group based on mother's blood level before birth(38). Total thyroxine and mean thyrotropin levels were somewhat higher at birth for high exposure group infants than for the low exposure group, but were significantly higher at 11 weeks old after both groups were breast fed. Both prenatal and post natal exposures appear to produce abnormal thyroid hormone levels and affect thyroid system function. Thyroid system function has broad effects on developing infants. Studies have found that the timing of fetal exposures is as important to effects as the magnitude of the dose; very low maternal exposures in critical window periods of fetal development can catastrophic effects(66,74).

Scientific studies on animals have found as a result of dietary intake of dioxin-like compounds- at dietary intake of 1 to 1.5 parts per trillion: altered enzyme induction response and altered lymphocytes in mice(11); at dietary intake of 4 to 25 ppt: chloracne in rabbits, endometriosis and decreased object learning ability in monkeys, skin tumor promotion in mice, increased reproductive disorders in fetally exposed male rats, and immune system deficiency (enhanced viral susceptibility)(11,67); general inability of monkeys to produce viable offspring at 25-50ppt dietary intake(11,68); decreased fertility in mice at 100 ppt(69); physical birth defects in mice at 1-4 ppt(70); and lower testosterone levels in rats at 15 ppb(71) In terms of body burden of dioxin-like compounds studies found: altered enzyme induction, altered lymphocytes, and enhanced viral susceptibility in animals at body burdens of 7 ppt(11); decreased human testis size and altered glucose tolerance at 14 ppt(11), decreased monkey object learning ability at 19ppt body burden; mortality to lake trout eggs at 65 ppt, mortality to chicken embryo at 250 ppt egg wt, and mortality to rainbow trout embryos at 400 ppt(72). These study results and body burden information do not include the many other endocrine-disrupting or estrogenic chemicals not included in the EPA study of dioxin-like chemicals. Thus many are currently exposed to levels of endocrine-disrupting chemicals already proven to cause serious adverse effects.

The currently used EPA and DEP risk assessment for dioxin and dioxin-like chemicals has been found to be greatly flawed and inaccurate due to the use of 1970s fish consumption data(44.1 grams/week) and failure to take into account the high risk of children, pregnant women, and groups that consume more than average amount of fish such as Native Americans, sport fishermen's families, etc. (3,7,10,14). The average health risk from eating fish has more than quadrupled since the 1970s and is much higher for groups eating more than the average amount of fish. According to a state survey, Florida adults eat an average of 253 grams per week of fish and 69 grams per week of shellfish(23). Additionally the EPA risk assessment does not include the endocrine-disrupting and reproductive system effects on humans, domestic animals, and wildlife that have been widely documented. Similarly the EPA currently does not include any of the endocrine system mediated effects discussed in this paper or food chain source effects in air emission risk assessments used in setting air emission regulations- even though EPA scientists have pointed out that these effects that are not taken into account represent over 90% of health risk to humans(4,14,42,43).

Sources

The U.S. uses over 178 billion kilogram of synthetic organic chemicals per year(196 million tons), of which approx. 318 million kg is pesticides(35). The largest source of dioxins, furans, PCBs, PAHs, mercury, and cadmium is air emissions. Dioxins and furans are chlorinated pollutants that can form during combustion of materials containing chlorine or in several industrial activities(30). Approx. 90% of dioxins and furans are from air emissions, with incinerators and cement kilns being the largest sources(64,30,3,11,33). Total emissions are approx. 12,500 kg per year(64), with municipal incinerators responsible for approx. 28% of known emissions and cement kilns 25%. Incinerators have been found to produce from 514 to 5140 ng TEQ PCDD/DF gas emissions per ton of MSW(58). Likewise about 90 % of PCBs in the Great Lakes come from air emissions(34). PCBs historically were primarily used in electrical equipment.

According to the U.S. EPA, Minnesota Pollution Control Agency, and World Health Organization, the main source of dioxins in humans are contaminated dairy and beef products, along with fish and other parts of the food chain contaminated by emissions from incinerators and other combustion of chlorine compounds (3,11,14,15,30,33,42,43). Widespread emissions containing large amounts of dioxins, mercury, cadmium and other toxics result from the over 6000 medical waste incinerators, municipal incinerators, hazardous waste incinerators, and sewer sludge incinerators. Significant portion of hospital waste are chlorine based plastics or compounds, MSW incinerators are the second largest source, and 40% of the waste burned in hazardous waste incinerators is chlorine compounds that produce large amounts of dioxin emissions.

The largest cause of dioxin emissions in incinerators is combustion of PVC plastics which are extremely widespread in building materials and hospital equipment(3,11). Burning 1 kilogram of PVC produces approx. 50 micrograms of dioxin. The large amounts of dioxin emissions in Europe and serious health effects have caused many European countries to phase out or reduce PVC usage in packaging and other applications. Some dairy farms in areas around incinerators have also had to be closed due to high levels of dioxins in the milk. In addition to dioxin emissions, combustion of PVC produces over 75 other toxic emissions including vinyl chloride, PCBs, chlorobenzene, benzene, hydrogen chloride, lead, cadmium, etc. HCl and other emissions cause acid rain, metal corrosion, and destruction of the ozone layer. Significant levels of dioxin is found in incinerator ash which has been found to produce dangerous levels of exposure to workman, in addition to the exposure to toxic metals in the ash. Workers and others exposed to ash or ash piles have had a high incidence of serious neurological problems. PVC feedstock plants also emit large amounts of dioxin with high cancer rates among workers and those living around the plant. Additionally the PVC in buildings causes many deaths or serious injuries from building fires that emit dioxins and other toxic gases.

While the majority of dioxins in the food chain including fish come from atmospheric sources, high dioxin or PCB levels are also found in fish in localized areas near industrial effluent sources such as pulp mills, where fish have been found to have dangerous levels of dioxin and reproductive abnormalities in 7 Florida rivers. Approx. 110 grams of dioxin is released by U.S. paper mills into rivers and steams each year. This is a small fraction of that released by incinerators according to EPA(30). Other sources of dioxins include incinerator ash, diesel vehicles, manufacturing of chlorine-rich chemicals, wood burning, and paper making(30).

Government Actions to Ban or Restrict Chlorinated Chemicals

Due to the growing and well documented serious health problems being seen in animal and human populations, many Government agencies, public health, and environmental organizations have called for phasing out or severely limiting the use of chlorinated chemicals(28,13). The International Joint Commission on the Great Lakes, the 1992 Paris Commission for the Prevention of Marine Pollution, and many U.S. or international environmental organizations have called for phasing out chlorinated chemicals. The Society of Environmental Toxicology and Chemistry has called for restricting or banning chlorinated chemicals that are highly toxic, persistent, and bioaccumulative. These include dioxins, furans, PCBs, and many chlorinated pesticides. The Canadian Government announced that Canada is moving aggressively to implement this policy. Germany and other European countries have placed severe restrictions on use of chlorinated chemicals and plastics such as PVC, Studies also show that use of chlorine dioxide by paper mills rather than chlorine for bleaching would greatly reduce dioxin emissions, as most European countries have done(30). In the U.S., the American Public Health Association has called for strict regulations and phaseout or cutbacks in all non-essential chlorinated chemicals, and the U.S. EPA has recommended examining chlorines impact on health and the environment- with the possible goals of banning or restricting it use.

A recent study has found that Trichlorophenols(TCPs) can be biodegraded in some situations by a combination of hydrogen peroxide and a catalyst

(2,9,16,23-tetra sulfopha thalocyanine)(56).

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Persistent Organohalogens

Dioxins and furans PBBs PCBs Hexachlorobenzene Octachlorostyrene Pentachlorophenol

Pesticides

2,4,5-T 2,4-D alachlor aldicarb d-trans allethrin amitrole atrazine benomyl

beta-HCH carbaryl chlordane chlozolinate-cyhalothrin cis-nonachlor cypermethrin DBCP DDT DDE/DDT metabolites

dicofol dieldrin endosulfan esfenvalerate ethylparathion fenvalerate h-epoxide heptachlor iprodione kelthane kepone ketoconazole lindane linurone malathion mancozeb maneb methomyl methoxychlor metiram metribuzin mirex nitrofen oxychlordane permethrin procymidone sumithrin

synthetic pyrethroids toxaphene trans-nonachlor tributyltin oxide trifluralin

vinclozolin zineb ziram

Phthalates

Di-ethylhexyl phthalate (DEHP) Butyl benzyl phthalate (BBP) Di-n-butyl phthalate (DBP) Di-n-pentyl phthalate (DPP) Di-hexyl phthalate (DHP) Di-propyl phthalate (DprP)

Dicyclohexyl phthalate (DCHP) Diethyl phthalate (DEP)

Other Compounds

Styrene dimers and trimers Benzo(a)pyrene ethane dimethane sulphonate

tris-4-(chlorophenyl)methane tris-4-(chlorophenyl)methanol

Heavy Metals

Mercury Lead Cadmium

Pollutants shown to bind to hormone receptors (or to interfere

with receptor binding) without further confirmation of endocrine disrupting effects

2,4-dichlorophenol Cyanazine Diethylhexyl adipate

Benzophenone N-butyl benzene 4-nitrotoluene