Health effects of persistent organic pollutants: the ...

Rev Environ Health 2011;26(1):61–69 © 2011 by Walter de Gruyter • Berlin • New York. DOI 10.1515/REVEH.2011.009

Health effects of persistent organic pollutants: the challenge for the Pacific Basin and for the world

David O. Carpenter* Institute for Health and the Environment, University at Albany, Rensselaer, NY, USA

Abstract Persistent organic pollutants include some organo-metals, such as methylmercury; lipophilic halogenated organics, such as dioxins, polychlorinated biphenyls, chlorinated pesticides, and polybrominated flame retardants; and perfluorinated compounds used as repellants. These compounds are resistant to degradation both in the environment and in the human body and tend to bioaccumulate within the food chain. Persistent organic pollutants cause a variety of adverse health effects, including cancer, immune system suppression, decrements in cognitive and neurobehavioral function, disruption of sex steroid and thyroid function, and at least some of them increase the risk of chronic diseases, such as hypertension, cardiovascular disease, and diabetes. Some compounds are byproducts of industry and combustion. Although the manufacture and use of most man-made chemicals has been reduced in recent years, the levels currently present in the population are still associated with an elevated risk of human disease. Others are still manufactured and used. These are dangerous chemicals that have contaminated even areas remote from the industrialized world, such as the polar regions. Keywords: chlorinated pesticides; dioxins; PBDEs; PCBs; perfluorinated compounds.

Introduction Persistent organic pollutants (POPs) pose a major public health threat to the world population, but that threat is perhaps even greater in the countries of the Pacific Basin than elsewhere for several reasons. Whereas most developed countries, including those in the Pacific Basin, stopped the manufacture and use of most POPs many years ago, many developing countries in Asia, Africa, and South America continued to use a variety of POPs until relatively recently, and in some cases even up to the present time. Thus, exposure levels for many POPs tend to be much higher in these regions. Whereas levels in humans are generally declining slowly, levels are usually higher in *Corresponding author: David O. Carpenter, Institute for Health and the Environment, University of Albany, Rensselaer, NY 12144, USA E-mail: [email protected]

developing countries. One example of this is shown in the changes over time in level of the pesticide dichlorodiphenyldichloro-ethylene (DDE) in human breast milk (Figure 1) (1). There are two very important considerations regarding POPs. The chemicals are persistent, both in the environment and in the human body. For example, dioxin has a half-life in the environment of from 10 to 100 years (2), and in the human body an average half-life of about 7–10 years (3, 4). Polychlorinated biphenyls (PCBs), depending upon the degree of chlorination of individual congeners, and chlorinated pesticides are also equally persistent. Whereas levels are certainly declining in the average human body since the period of manufacture and use (5), our knowledge of how dangerous these chemicals are is growing more rapidly than the ambient levels decline. The other major factor regarding POPs is that these are global contaminants spread by air transport and water. Whereas in the past many of these contaminants were found at local industrial sites, over time they have spread through volatilization, transport through water and dust, so that at present, the POPs are everywhere, even in the most remote regions of the earth that have no local sources. This is a particular problem in the polar regions, where the semi-volatile POPs have migrated primarily by air currents and have come out of the vapor phase in the cold regions by what has become known as the “grasshopper effect” (6, 7). The result is that some of the highest concentrations of POPs are found in the indigenous people of the Arctic, as discussed in greater detail below. However, POPs have also distributed into the food supply. This is especially the case for the fat-soluble POPs, which have bioaccumulated in all animal fat products. This problem has been made worse by the common practice of feeding waste animal fats back into feed for production livestock (8), a practice that only recycles POPs from previous times into the present food supply. Fish constitute another particular concern, as seafood is a major protein source throughout the world. But seafood everywhere, from inland lakes and rivers to the oceans, is contaminated with lipophilic POPs and with methylmercury, which in the extreme case makes certain kinds of seafood dangerous to eat at any level (9–11). In the Arctic, POPs have accumulated in marine mammals (12), whose fat constitutes a major food source for many indigenous peoples.

Types of POPs that pose concern for human health At least three major categories of POPs pose concern for human health: the organometals that bind to protein, especially

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Carpenter: Persistent organic pollutants

the organomercurials; the lipophilic contaminants like dioxins, PCBs, polybrominated diphenyl ethers (PBDEs) and chlorinated pesticides; and the persistent non-lipophilic compounds, such as the perfluorinated compounds used as repellents. Of course, toxicity does not require that a substance be persistent. Substances that are present and leach from common industrial products, such as many volatile organic compounds, phthalates, and bisphenol A, are also found throughout the food supply and in the bodies of many of the world’s populations. These compounds have known adverse endocrine and neurological effects (13–15). Even though not characterized by persistence, their use on an everyday basis means that individuals are constantly exposed, and therefore the health concerns are similar to those of persistent compounds. Nevertheless, the health effects of this category of chemicals will not be discussed here. We must recognize that chemicals that impair human health also affect animals in similar fashions. Indeed, wildlife serves as a very important sentinel for effects of these agents on humans (16). Thus, some information on animal health will also be presented below.

Methylmercury and other organometals Mercury is an element that has toxicity in both the elemental and the inorganic forms. When inorganic mercury gets into an aquatic environment, however, the element is methylated by microorganisms, and the products, of which methylmercury is the most abundant, are sufficiently lipophilic so that they bioaccumulate and bioconcentrate in seafood. The result is dangerously elevated levels of methylmercury in many

species of fish. Almost all fish have some methylmercury, but levels are particularly elevated in large, carnivorous species. The United States Environmental Protection Agency (U.S. EPA) and the U.S. Food and Drug Administration (U.S. FDA) (17) have recommended no consumption of four species of marine fish (shark, tilefish, king mackerel, and swordfish) because of dangerous levels of methylmercury. Tuna is also a concern, whether as sushi, steaks or canned. Levels of methylmercury in tuna also trigger restrictive consumption advisories, especially for children and women of reproductive age. The advisories are more restrictive for canned white or albacore tuna, which comes from larger fish, than for ‘light’ tuna, which comes from smaller fish that have not had as much time to bioaccumulate mercury (18). These observations indicate that the oceans are contaminated with mercury, and that methylmercury is both formed there and bioaccumulates in large carnivorous fish. The problem is not limited to marine fish. Many fresh water fish are also contaminated, especially large carnivorous fish. The degree of contamination various with local sources of mercury input into the water body, as well as the pH of the water, as acidity promotes conversion to methylmercury (19). In New York, very restrictive consumption advisories for most freshwater fish are in place for women of reproductive age and children because of the health effects of methylmercury that are discussed below (20). The sources of mercury input into water bodies are varied. Some are natural, such as volcanic activity and leaching of mercury from rocks and soils. Some are from local industrial activity, such as mining (21). But the major preventable source comes from fossil fuel combustion, especially burning of coal. Fossil fuel combustion also produces nitrogen oxides

Figure 1 Mean total DDT compounds in breast milk reported by region and year of study, with spline fit. Reproduced from (1) with permission.


(NOx) and sulfur oxides (SOx), both of which contribute to acid rain and reduced pH of water bodies. Because acidity promotes the methylation of mercury, fish from lakes and streams of lower pH will have larger concentrations of methylmercury (22). As shown in Figure 2, the largest coal consumption comes from China, followed by the United States (23). Asia is the largest contributor of anthropogenic mercury emissions (Figure 3) (24), generating over half of the global releases (25). These releases come not only from coal combustion but also from mercury and gold mining, zinc smelting, chlorine-alkali production, waste incineration, and from various industries. The emissions are both elemental mercury in a vapor phase and inorganic mercury bound to particulates. Whereas the particulates can travel some distance, the vapor phase elemental mercury is the greater problem because it can travel across continents and deposit very far from the source of production. Although fish consumption is the major source of exposure to methylmercury, Qiu et al. (26) have reported that methylmercury accumulates in rice grown near an abandoned

Figure 2

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mercury mine in Guizhou, China. Because rice constitutes such an important part of the diet in much of Asia, this finding raises important concerns. In the Guizhou region, rice is a more significant source of methylmercury than fish consumption (27).

Dioxins/furans, PCBs, chlorinated pesticides and PBDEs The production and use of most of these chemicals (the “dirty dozen”) was outlawed by the Stockholm Convention of 2004, which has been signed by over 160 countries. The only exception was for the use of dichlorodiphenyltrichloroethane (DDT) in countries that have a major problem with malaria because DDT is by far the most effective anti-mosquito pesticide known, and malaria remains a deadly disease in tropical countries. The recent amendment to the Stockholm Convention expanded this list to include other chlorinated pesticides, the PBDEs and several other compounds (28).

Historical (A and B) and projected (C and D) coal consumption by region. Reproduced from (23) with permission.

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Figure 3 2005 Mercury emissions by region. Asia responsible for two-thirds of estimated global emissions. Reproduced from (24) with permission.

Unlike the other lipophilic POPs, dioxins and furans have never been manufactured intentionally; rather, the latter are products of combustion and byproducts of some chemical manufacturing processes. Dioxins and especially furans are produced whenever substances containing chlorine are burned at relatively low temperatures. Thus, even a forest fire results in formation of some dioxins and furans. Incineration is a major source of these compounds, unless the incineration is at a temperature sufficiently high to destroy the products after they are formed (29, 30). As the amount of plastic in the waste stream increases, the formation of dioxins becomes more likely. Unfortunately, incineration in many countries is not conducted to prevent production and release of dioxins and furans. As developed countries have tightened the releases of dioxins from incinerators, a major source of dioxin formation is backyard burning of household wastes (31), a practice still very common in rural areas. In many countries, the combustion of wastes is the rule rather than the exception, and even municipal landfills are frequently burned to reduce the volume. As a consequence, exposure to and health hazards from dioxin remain a global problem, and the exposure is greater in developing countries that lack the regulation of dioxin formation that is common in more developed countries. The other major source of dioxin was as a byproduct of manufacture of certain herbicides, primarily 2,4,5-trichlorophenoxyacetic acid. Although these were widely used in many countries, the most significant exposure was in Vietnam in the 1960–1970s. The U.S. Air Force sprayed some 77 million liters of herbicides in Vietnam in an effort to kill foliage that prevented them from seeing North Vietnamese troops, including 49.3 million liters of Agent Orange, a code name for an herbicide that contained dioxin (32). To this day, Vietnamese civilians living in the south have elevated levels of dioxins, and as a consequence suffer from a marked elevation in several diseases, including birth defects (33), cancer (34), and likely a number of other diseases that unfortunately have not been adequately investigated. PCBs and chlorinated pesticides were intentionally manufactured and were useful products. PCBs were used as

insulators in electrical transformers, as hydraulic fluids, as solvents in paints and caulk, and had many other uses (35). The chlorinated pesticides (DDT, hexachlorobenzene, chlordane, mirex, toxaphene, hexachlorocyclohexane, and others) were potent agents against a variety of insect pests. However, the production of most of these chemicals was stopped in developed countries in the late 1970s and 1980s after they were found to be persistent in the environment. Rachael Carson, in her 1962 book entitled “Silent Spring” (36), brought the world’s attention to the plight of eagles and hawks as a consequence of DDT exposure. DDT is an endocrine disruptor and caused eggshell thinning, especially in birds that consumed contaminated fish. The result was a drastic decline in the reproductive capacity of these birds, which has only recently been reversed as levels of DDT have declined. The reproductive capacity of many other aquatic animals, and animals that ate fish, was also impaired by exposure to POPs, including marine mammals (37), polar bears (38), mink (39), alligators (40), and small birds (41). Cook et al. (42) found that exposure to dioxin and dioxin-like compounds was responsible for the drastic decline of lake trout in the U.S. Great Lakes because of direct damage to the embryos and sac fry. Despite these compounds not being manufactured recently, they still remain at levels that pose hazards to wildlife and humans. For example, in the Great Lakes in the U.S., the levels of PCBs in fish have essentially plateaued at concentrations that are still in excess of those deemed safe for human consumption (43). Such levels persist because the rates of inputs into the lakes from air transport and being carried through sediments in rivers balances the rates of degradation and volatilization from the lakes (44). PCBs are a major concern in older buildings where they were used as solvents for caulk and paint. In India, a typical merchant ship when dismantled for scrap has been found to contain 250–800 kg of PCBs in the paint and machinery (45). The PBDEs pose an even more serious problem because not only are they hazardous and persistent, but also they are still in use globally. PBDEs are structurally similar to PCBs, but have bromines rather than chlorines. The compounds were also useful. They were used as flame retardants in a great variety of products ranging from upholstery to clothing to computers. Like PCBs, PBDEs were manufactured as commercial mixtures of congeners containing various average numbers of bromines, usually with an average of five, eight or ten bromines. Although much less is known about the health hazards from PBDEs, the lower brominated congeners appear to be the more toxic (46, 47). The production of PBDEs has been stopped in Europe, and the manufacture of all but the deca PBDEs has been voluntarily stopped in the U.S. Fortunately, the levels of PBDEs are much lower in Asia at present than in Western Europe and the U.S. In Western countries, the major route of exposure to PBDEs appears to be house dust, which poses a particular problem in causing exposure to toddlers, who are crawling on the floor (48). Another very important route of exposure is breast-feeding. In California, the levels of PBDEs in breast milk appear to be increasing exponentially (49). Because of the similarity of structure to PCBs, PBDEs will likely be found to have similar health effects.


The perfluorinated compounds, perfluorooctane sulfonate (PFOS), perfluorooctanonic acid (PFOA), and related compounds, had wide usage as water and stain repellants and in manufactured products, such as Teflon. The perfluorinated compounds differ from the POPs mentioned above in that the former are not lipophilic. However, the perfluorinated compounds are very persistent and bind to proteins rather than accumulating in fat (50). The perfluorinated compounds are widely distributed in the environment and in essentially all living animals including humans. The toxicity of these compounds is not as well understood as the more legacy POPs but the perfluorinated compounds are clearly toxic, at least for the nervous and thyroid systems (51, 52).

Human health effects of POPs The POPs cause many adverse health effects and may alter the function of almost every organ system. These compounds do so by a variety of mechanisms, from induction of enzymes to altered gene regulation to exhibiting endocrine activity and changes in nervous system function. Most POPs and other pesticides are not directly mutagenic, but do cause DNA damage indirectly via the generation of reactive oxygen species (53, 54). Many POPs are considered probable human carcinogens, and dioxin is ranked as a known human carcinogen by the World Health Organization (55). The carcinogenic potential of some of the newer POPs has not been investigated in detail, but of the compounds described above, only the organomercurial compounds are unlikely to be carcinogenic. The organochlorines are usually considered non-mutagenic carcinogens (56, 57), although some have reported mutagenic activity of some PCBs or their metabolites (58). Numerous reports have described elevated risks of various specific cancers as a result of exposure to POPs, but PCBs and dioxins likely increase the risk of all forms of cancer. Less is known about the carcinogenic potency of specific chlorinated pesticides, although in general they also function as non-mutagenic carcinogens. A large body of evidence indicates the ability of dioxins, PCBs, chlorinated pesticides, and methylmercury to adversely affect the central nervous system, resulting in reduced IQ and such changes in behavior as reduced attention span and ability to deal with frustration (59, 60). Spanish children exposed to DDT show significant decrements in verbal, memory, quantitative and perceptual-performance as compared with less exposed children (61). Studies of Taiwanese children prenatally exposed to PCBs and furans indicate that the effects on IQ are not reversible (62). The mechanisms responsible for the effects of nervous system function are not well understood, but both dioxin-like (63) and non-dioxin like (64) congeners reduce long term potentiation, an electrophysiological monitor of cognitive function, in rodent brains. Although prenatal and early life exposure has been best studied, convincing evidence points to reduced cognitive function in adults exposed to PCBs (65, 66). DDT exposure has also been associated with adverse neurobehavioral development (67, 68).

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Many chlorinated POPs function as endocrine-disruptive chemicals. Dioxin and compounds that bind to the aryl hydrocarbon receptor (AhR) have anti-estrogenic activity because they induce the P450 enzymes that metabolize estrogen. Exposure to dioxin (69) and PCBs (70) has resulted in a reduced percentage of male births, and increased time to pregnancy (71). Exposure to dioxins results in more feminized play behavior in both boys and girls (72). Most PCBs, polybrominated biphenyls, and several pesticides have estrogenic activity because of weak binding to the estrogen receptor (73). This estrogenic activity leads to precocious puberty in girls (74), a lengthened menstrual cycle (75), and may increase risk of breast cancer (76). Several POPs also have anti-androgenic activity, causing a reduction in production of male sex hormones (77, 78). Dioxins, PCBs, PBDEs, and some pesticides also interfere with thyroid hormone function and do so by action of several sites (79). The structure of thyroid hormone, with two benzene rings containing iodines, shows a clear similarity to dioxins and PCBs having similar rings containing chlorines. PBDEs, with bromines around the rings, also suppress thyroid function (80). DDT exposure has been reported to increase risk of male genital anomalies (81), impaired semen quality (82), as well as breast cancer in young women (83). Recently, it has become clear that exposure to several of the chlorinated POPs increases the risk of development of type 2 diabetes, a disease of insulin function (84). Remarkably, this increased risk occurs at very low concentrations and appears not to show a linear dose-response curve (85). The strongest relations appear to be with DDE and hexaclorobenzene, but PCBs also significantly increase the risk (86, 87). Because type 2 diabetes is a disease of the insulin receptor, the mechanisms behind this relationship are not known, but probably are a result of gene induction. Obesity is often considered to be the major risk factor for diabetes. The studies of Lee et al. (84), however, found that obese persons who do not have elevated levels of POPs do not have an increased risk of diabetes. Because obesity is usually a consequence of excessive consumption of animal fats, and because it is the animal fats that contain the POPs, perhaps the concentration of POPs is the critical factor in promoting diabetes. In addition, recent evidence indicates that obesity risk is increased by exposure to a variety of contaminants, including PCBs, dioxins, DDE, hexachlorobenzene, phthalates, and bisphenol A (88–91). Whereas life-style factors, such as diet and exercise, or lack thereof, are certainly important, the results of those studies strongly indicate that diabetes is an environmentally induced disease and suggest that environmental exposures may even be risk factors for obesity itself. Strong evidence also shows that exposure to POPs increases the risk of cardiovascular disease (92, 93) and hypertension (94). Dioxins and PCBs are known to stimulate the synthesis of serum lipids (95), which may be one part of the mechanism resulting in cardiovascular disease, but the evidence also indicates that dioxin-like chemicals cause a direct damage to endothelial cells, which promotes atherosclerotic changes (96). The lipophilic POPs are also substances that alter immune system function. Indeed, a massive die-off of seals in Europe

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Figure 4 The Grasshopper effect. Modified from (24) with permission.

has been attributed to immune system suppression resulting from exposure to PCBs and other POPs (97, 98). Immunosuppression in terns and gulls secondary to exposure to organochlorines pollutants has also been reported (99, 100). Recent studies have shown that exposure to PCBs in early human life reduces the ability of the body to respond to immunizations (101). Figure 4 (24) illustrates the “grasshopper” effect, whereby semi-volatile contaminants like DDT and its metabolites, other organochlorines pesticides, PCBs, and dioxin-like chemicals migrate to the polar regions. This effect results in exposures in both animals and humans who live in the Arctic and Antarctic regions having extremely elevated levels in their bodies. Recent reviews have documented elevated exposure of essentially all form of Arctic wildlife, demonstrating the effects of vitamin levels, endocrine systems, reproductive hormones, reproductive organs, immune system function, organ pathology (especially kidney) and bone structure, as well as effects on the neurological system and behavior (102). The concern increases with the level in the food supply. For example polar bears, who feed primarily on seal fat, have exceptionally high levels of persistent organics (103), such that the animals show impaired fertility, immunosuppression, and altered endocrine function (104, 105). Humans, also at the top of the food chain, show similar effects. Inuit infants and preschool children are at increased risk of respiratory tract, ear and gastrointestinal infections (106, 107), probably primarily due to prenatal exposure to PCBs and DDE. Although levels of some of the legacy contaminants have gone down somewhat or at least are no longer increasing, the levels of the brominated flame retardants and the perfluorinated compounds are increasing (108, 109). The greatest challenge we face today is climate change, which will have an impact on life all over the earth. But the impact is likely to be greater in the polar regions than anywhere else. There is not only the issue of melting sea ice, and the impact this will have on both the human and polar bear populations who depend upon ice for hunting seals, but also the consequences related to thawing permafrost. Global

warming will increase the release and volatilization of semivolatile compounds, both in temperate regions and in the Arctic itself. Thus the migration of contaminants to the Arctic will continue to pose greater risk than elsewhere as long as we have these persistent chemicals in the overall environment. As temperatures rise, the way of life of the inhabitants of the Arctic is severely threatened (110), both as a result of the effect of warming on the ability to practice traditional methods of hunting and as a consequence of increasing contamination with POPs. The injustice of these twin threats should be a factor in motivating governments to take action to reduce sources of contaminants that migrate to the Arctic and to take urgent action to reduce the greenhouse gas releases that are the cause of climate change.

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