1: INTRODUCTION
2: PROPERTIES AND ENVIRONMENTAL BEHAVIOUR OF POPs
3.1 CHEMISTRY
3.2 TOXICOLOGY
Persistent organic pollutants (POPs) are organic compounds that, to a varying degree, resist photolytic, biological and chemical degradation. POPs are often halogenated and characterised by low water solubility and high lipid solubility, leading to their bioaccumulation in fatty tissues. They are also semi-volatile, enabling them to move long distances in the atmosphere before deposition occurs.
Although many different forms of POPs may exist, both natural and anthropogenic, POPs which are noted for their persistence and bioaccumulative characteristics include many of the first generation organochlorine insecticides such as dieldrin, DDT, toxaphene and chlordane and several industrial chemical products or byproducts including polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (dioxins) and dibenzo-p-furans (furans). Many of these compounds have been or continue to be used in large quantities and, due to their environmental persistence, have the ability to bioaccumulate and biomagnify. Some of these compounds such as PCBs, may persist in the environment for periods of years and may bioconcentrate by factors of up to 70,000 fold.
POPs are also noted for their semi-volatility; that property of their physico-chemical characteristics that permit these compounds to occur either in the vapour phase or adsorbed on atmospheric particles, thereby facilitating their long range transport through the atmosphere.
These properties of unusual persistence and semi-volatility, coupled with other characteristics, have resulted in the presence of compounds such as PCBs all over the world, even in regions where they have never been used. POPs are ubiquitous. They have been measured on every continent, at sites representing every major climatic zone and geographic sector throughout the world. These include remote regions such as the open oceans, the deserts, the Arctic and the Antarctic, where no significant local sources exist and the only reasonable explanation for their presence is long-range transport from other parts of the globe. PCBs have been reported in air, in all areas of the world, at concentrations up to 15ng/m3; in industrialized areas, concentrations may be several orders of magnitude greater. PCBs have also been reported in rain and snow.
POPs are represented by two important subgroups including both the polycyclic aromatic hydrocarbons and some halogenated hydrocarbons. This latter group includes several organochlorines which, historically, have proven to be most resistant to degradation and which have had wide production, use and release characteristics. These chlorinated derivatives are generally the most persistent of all the halogenated hydrocarbons. In general, it is known that the more highly chlorinated biphenyls tend to accumulate to a greater extent than the less chlorinated PCBs; similarly, metabolism and excretion is also more rapid for the less chlorinated PCBs than for the highly chlorinated biphenyls.
Humans can be exposed to POPs through diet, occupational accidents and the environment (including indoor). Exposure to POPs, either acute or chronic, can be associated with a wide range of adverse health effects, including illness and death.
Laboratory investigations and environmental impact studies in the wild have implicated POPs in endocrine disruption, reproductive and immune dysfunction, neurobehavioural and disorders and cancer. More recently some POPs have also been implicated in reduced immunity in infants and children, and the concomitant increase in infection, also with developmental abnormalities, neurobehavioural impairment and cancer and tumour induction or promotion. Some POPs are also being considered as a potentially important risk factor in the etiology of human breast cancer by some authors.
2. PROPERTIES AND ENVIRONMENTAL BEHAVIOUR OF POPs
The behaviour and fate of chemicals in the environment is determined by their chemical and physical properties and by the nature of the environment. The chemical and physical properties are determined by the structure of the molecule and the nature of the atoms present in the molecule. Depending on the structure of the molecule, these physical and chemical properties span a large range of values. Compounds may be of very low persistence, of low toxicity and be immobile. These compounds are unlikely to present a risk to the environment or to human health. At the other end of the scale are those compounds that are persistent, mobile and toxic and it is this range of the distribution where the toxic and lipophilic POPs are found. Environmental behaviour and exposure are strongly related. Thus, the risk of exposure to a substance will be much lower if the substance is not persistent and the risk, if any, will be localized unless the substance has properties which allow its movement to distant locations.
It must be recognized that relatively few substances possess the necessary properties to make them POPs. In fact, if the range of these properties were presented as a distribution, only those compounds at the extreme ends of the distribution would express the degree of persistence, mobility and toxicity to rank them as POPs (Figure 2).
Some substances may be very persistent in the environment (i.e., with half-lives (t½) greater than 6 months). The nature of this persistence needs to be clarified - it is the length of time
the compound will remain in the environment before being broken down or degraded into other and less hazardous substances. Dissipation is the disappearance of a substance and is a combination of at least two processes, degradation and mobility. It is not an appropriate measure of persistence as mobility may merely result in the substance being transported to other locations where , if critical concentrations are achieved, harmful effects may occur.
One important property of POPs is that of semi-volatility. This property confers a degree of mobility through the atmosphere that is sufficient to allow relatively great amounts to enter the atmosphere and be transported over long distances. This moderate volatility does not result in the substance remaining permanently in the atmosphere where it would present little direct risk to humans and organisms in environment. Thus, these substances may volatilize from hot regions but will condense and tend to remain in colder regions. Substances with this property are usually highly halogenated, have a molecular weight of 200 to 500 and a vapour pressure lower than 1000 Pa.
In order to concentrate in organisms in the environment, POPs must also possess a property that results in their movement into organisms. This property is lipophilicity or a tendency to preferentially dissolve in fats and lipids, rather than water. High lipophilicity results in the substance bioconcentrating from the surrounding medium into the organism. Combined with environmental persistence and a resistance to biological degradation, lipophilicity also results in biomagnification through the food chain. Biomagnification results in much greater exposures in organisms at the top of the food chain.
3. CHEMISTRY AND TOXICOLOGY.CHEMISTRY AND TOXICOLOGY
3.1 Chemstry
POPs are, by definition, organic compounds that are highly resistant to degradation by biological, photolytic or chemical means. POPs are often halogenated and most often chlorinated. The carbon-chlorine bond is very stable towards hydrolysis and, the greater the number of chlorine substitutions and/or functional groups, the greater the resistance to biological and photolytic degradation. Chlorine attached to an aromatic (benzene) ring is more stable to hydrolysis than chlorine in aliphatic structures. As a result, chlorinated POPs are typically ring structures with a chain or branched chain framework. By virtue of their high degree of halogenation, POPs have very low water solubility and high lipid solubility leading to their propensity to pass readily through the phospholipid structure of biological membranes and accumulate in fat deposits.
Halogenated hydrocarbons are a major group of POPs and, of these, the organochlorines are by far the most important group. Included in this class of organohalogens are dioxins and furans, PCBs, hexachlorobenzene, mirex, toxaphene, heptachlor, chlordane and DDT. These substances are characterized by their low water solubility and high lipid solubility and, like many POPs, are noted for their environmental persistence, long half-lives and their potential to bioaccumulate and biomagnify in organisms once dispersed into the environment.
Although some natural sources of organochlorines are known to exist, most POPs originate almost entirely from anthropogenic sources associated largely with the manufacture, use and disposition of certain organic chemicals. In contrast, HCB, dioxins and furans are formed unintentionally in a wide range of manufacturing and combustion processes.
As pointed out above, POPs are typically semi-volatile compounds, a characteristic that favours the long-range transport of these chemicals. They can thus move over great distances through the atmosphere. Volatilisation may occur from plant and soil surfaces following application of POPs used as pesticides.
Halogenated, and particularly chlorinated organic compounds have become entrenched in contemporary society, being utilized by the chemical industry in the production of a broad array of products ranging from polyvinyl chloride (millions of tonnes per year) to solvents (several hundreds of thousands of tonnes) to pesticides (tens of thousands of tonnes) and speciality chemicals and pharmaceuticals (thousands of tonnes down to kilogram quantities). In addition, both anthropogenic and non-anthropogenic sources also lead to production of undesirable by-products and emissions often characterized by their persistence and resistance to breakdown (such as chlorinated dioxins). As noted above, organochlorine compounds have a range of physico-chemical properties. In the environment, organochlorines can be transformed by a variety of microbial, chemical and photochemical processes. The efficiency of these environmental processes are largely dependent on the physico-chemical properties of the specific compound and characteristics of the receiving environment.
Cyclic, aromatic, cyclodiene-type and cyclobornane type chlorinated hydrocarbon compounds, such as some chlorinated pesticides, with molecular weights greater than 236 g/mol have been noted for their ability to accumulate in biological tissues, and to particularly concentrate in organisms that occupy positions in the upper trophic levels; not surprisingly, these compounds are also known for their persistence in the environment. Compounds included in this class often share many physico-chemical characteristics and include some of the earliest organochlorine pesticides such as DDT, chlordane, lindane, heptachlor, dieldrin, aldrin, toxaphene, mirex and chlordecone. Conversely, the lower molecular weight chlorinated hydrocarbons (less than 236 g/mol) may include a number of alkanes and alkenes (dichloromethane, chloropicrin, chloroform) and are often associated with little acute toxicity, reversible toxicological effects and relatively short environmental and biological half-lives. Bioavailability, that proportion of the total concentration of a chemical that is available for uptake by a particular organism, is controlled by a combination of chemical properties of the compound including the ambient environment and the morphological, biochemical and physiological attributes of the organism itself.
Generally, excretion of organic pollutants is facilitated through the metabolic conversion to more polar forms. Because of their resistance to degradation and breakdown, the POPs are not easily excreted and those pollutants (e.g. toxaphene, PCBs etc.) most resistant to metabolism and disposition tend to accumulate in organisms and through the food chain. Notably, some organic pollutants may also be converted to more persistent metabolites than the parent compound, as is the case with the metabolic conversion of DDT to DDE. Similarly, the rapid metabolic conversion of aldrin to its extremely environmentally persistent metabolite dieldrin, is also noteworthy.
3.2.1 Environment
If analysed for in tissues or environmental samples, some POPs will almost always be found. As is the case with many environmental pollutants, it is most difficult to establish causality of illness or disease that is directly attributable to exposure to a specific persistent organic pollutant or group of POPs. This difficulty is further underscored by the fact that POPs rarely occur as single compounds and, individual field studies are frequently insufficient to provide compelling evidence of cause and effect in their own right. More to the point, however, is the fact that the significant lipophilicity of these compounds means that POPs are likely to accumulate, persist and bioconcentrate and could, thus, achieve toxicologically relevant concentrations even though discrete exposure may appear limited.
Experimentally, POPs have been associated with significant environmental impact in a wide range of species and at virtually all trophic levels. While acute effects of POPs intoxication have been well documented, adverse effects associated with chronic low level exposure in the environment is of particular concern. Noteworthy in this context is the long biological half life of POPs in biological organisms thereby facilitating accumulation of seemingly small unit concentrations over extended periods of time. For some POPs, there is some experimental evidence that such cumulative low level exposures may be associated with chronic non-lethal effects including potential immunotoxicity, dermal effects, impairment of reproductive performance and frank carcinogenicity.
Immunotoxicity in association with exposure to different POPs has been reported by several authors. Investigators have demonstrated immune dysfunction as a plausible cause for increased mortality among marine mammals and have also demonstrated that consumption of persistent organic pollutant contaminated diets in seals may lead to vitamin and thyroid deficiencies and concomitant susceptibility to microbial infections and reproductive disorders. Investigators have also noted that immunodeficiency has been induced in a variety of wildlife species by a number of prevalent POPs, including TCDD's, PCBs, chlordane, HCB, toxaphene and DDT.
Exposure to POPs has been correlated with population declines in a number of marine mammals including the common seal the harbour porpoise, bottle-nosed dolphins and beluga whales from the St. Lawrence River. More notably, a clear cause and effect relationship has been established between reproductive failure in mink and exposure to some POPs.
The scientific literature has demonstrated a direct cause and effect relationship in mink and ferrets between PCB exposure and immune dysfunction, reproductive failure, increased kit mortality, deformations and adult mortality. Similarly, investigators have also demonstrated a convincing correlation between environmental concentrations of PCBs and dioxins with reduced viability of larvae in several species of fish. Noteworthy as well is a report suggesting significant reproductive impairment in a number of Great Lakes species described as top level predators dependent on the Great Lakes aquatic food chain. Supporting this is the observation that wildlife, including stranded carcasses of St. Lawrence beluga whales, with reported high incidence of tumours have contained significantly elevated concentrations of PCBs mirex, chlordane and toxaphene. A 100% incidence of thyroid lesions in coho, pink and chinook salmon sampled in the Great Lakes over the last two decades has also been reported to be associated with increased body burdens of POPs.
3.2.2 Human health
As noted for environmental effects, it is also most difficult to establish cause and effect relationships for human exposure of POPs and incident disease. As with wildlife species, humans encounter a broad range of environmental exposures and frequently to a mixture of chemicals at any one time. Much work remains to be done on the study of the human health impact of exposure to POPs, particularly in view of the broad range of concomitant exposing experienced by humans.
The weight of scientific evidence suggests that some POPs have the potential to cause significant adverse effects to human health, at the local level, and at the regional and global levels through long-range transport.
For some POPs, occupational and accidental high-level exposure is of concern for both acute and chronic worker exposure. The risk is greatest in developing countries where the use of POPs in tropical agriculture has resulted in a large number of deaths and injuries. In addition to other exposure routes, worker exposure to POPs during waste management is a significant source of occupational risk in many countries. Short-term exposure to high concentrations of certain POPs has been shown to result in illness and death. For example, a study in the Philippines showed that in 1990, endosulfan became the number one cause of pesticide-related acute poisoning among subsistence rice farmers and mango sprayers. Occupational, bystander and near-field exposure to toxic chemicals is often difficult to minimize in developing countries. Obstacles in managing workplace exposure are in part due to poor or non-existent training, lack of safety equipment, and substandard working conditions. As well, concerns resulting from near-field and bystander exposure are difficult to identify due to inadequacies in monitoring of the ambient environment and inconsistencies in medical monitoring, diagnosis, reporting and treatment. These factors contribute to a lack of epidemiological data. Earliest reports of exposure to POPs related to human health impact include an episode of HCB poisoning of food in south-east Turkey, resulting in the death of 90% of those affected and in other exposure related incidences of hepatic cirrhosis, porphyria and urinary, arthritic and neurological disorders. In another acute incident in Italy in 1976, release of 2,3,7,8-TCDD to the environment resulted in an increase of chloracne. The US EPA is currently reviewing dioxin related health effects especially for the non-carcinogenic endpoints such as immunotoxicity, reproductive disorders and neurotoxicity.
Such frank expressions of effects are not as common in the case of exposure to lower concentrations derived from the environment and the food chain. Laboratory and field observations on animals, as well as clinical and epidemiological studies in humans, and studies on cell cultures collectively demonstrate that overexposure to certain POPs may be associated with a wide range of biological effects. These adverse effects may include immune dysfunction, neurological deficits, reproductive anomalies, behavioural abnormalities and carcinogenesis. The scientific evidence demonstrating a link between chronic exposure to sublethal concentrations of POPs (such as that which could occur as a result of long-range transport) and human health impacts is more difficult to establish, but gives cause for serious concern. Swedish investigations have reported that dietary intake of PCBs, dioxins and furans may be linked to important reductions in the population of natural killer cells (lymphoytes), while other reports have suggested that children with high organochlorine dietary intake may experience rates of infection some 10-15 times higher than comparable children with much lower intake levels. The developing fetus and neonate are particularly vulnerable to POPs exposure due to transplacental and lactational transfer of maternal burdens at critical periods of development. It has also been reported that residents of the Canadian Arctic, and who exist at the highest trophic level of the Arctic aquatic food chain, have PCB intake levels in excess of the acceptable daily intake, and that may place this population at special risk for reproductive and developmental effects. In another report, children in the northern Quebec region of Canada who have had significant exposure to PCBs, dioxins and furans through breast milk also had a higher incidence of middle ear infections than children who had been bottle fed. Most authors, however, conclude that the benefits of breast feeding outweighs the risks.
Studies of carcinogenesis associated with occupational exposure to 2.3.7.8-TCDD also seem to indicate that extremely high-level exposures of human populations do elevate overall cancer incidence. Laboratory studies provide convincing supporting evidence that selected organochlorine chemicals (dioxins and furans) may have carcinogenic effects and act as strong tumour promoters.
More recently, literature has been accumulating in which some researchers have suggested a possible relationship between exposure to some POPs and human disease and reproductive dysfunction. Researchers have suggested that the increasing incidence of reproductive abnormalities in the human male may be related to increased estrogen (or estrogenic type) compound exposure in vitro, and further suggest that a single maternal exposure during pregnancy of minute amounts of TCDD may increase the frequency of cryptorchidism in male offspring, with no apparent sign of intoxication in the mother. Associations have been made between human exposure to certain chlorinated organic contaminants and cancers in human populations. Preliminary evidence suggests a possible association between breast cancer and elevated concentrations of DDE. While the role of phytoestrogens and alterations in lifestyle cannot be dismissed as important risk factors in the dramatic increase in estrogen dependent breast cancer incidence, correlative evidence suggesting a role for POPs continues to mount. This latter theory has been supported in a report that noted that levels of DDE and PCBs were higher for breast cancer case patients than for control subjects, noting that statistical significance was achieved only for DDE. While a causal relationship between organochlorine exposure and malignant breast disease remains far from proven, the possibility that chronic low level exposure, when coupled with the known bioaccumulative properties of POPs, may even contribute in some small way to overall breast cancer risk has extraordinary implications for the reduction and prevention of this very important disease.