Major Organic Pollutants 821 Organochlorine Insecticides 8211 Background

Organochlorine compounds are widely used as pesticides and are substantial environmental pollutants and carcinogens due to their extensive environmental release. Many pesticides are now suspected of being endocrine disruptors - chemicals that can lead to an increase in birth defects, sexual abnormalities and reproductive failure. An example is formed by the indications that polychlorobiphenyl pollution

Fig. 8.1 Organochlorine insecticide Dichlorodiphenyltrichloroethane (DDT)

of Swedish waters is linked to uterine occlusions and stenoses in female ringed seal, resulting in reproductive failure and, consequently, a rapid decrease of the seal population (Helle et al. 1976a, b). The insecticide dichlorodiphenyltrichloroethane (Fig. 8.1) has been banned in the developed world for many years, though is in widespread use in the developing world. Various dichlorodiphenyltrichloroethane metabolites have endocrine effects, including blocking the action of male hormones. Dichlorodiphenyltrichloroethane is metabolized in the body to dichlorodiphenyldi-chloroethylene, and both these compounds persist in the body fat. It is interesting to note that body fat concentrations in the USA have reduced from 15 mg/kg in 1955 to less than 5 mg/kg in 1980, though this is pretty high, due to the ban in dichlorodi-phenyltrichloroethane use (IEH 1995) . Many hormone-related effects on wildlife have been ascribed to dichlorodiphenyltrichloroethane, including thinning of eggshells, damage to male reproductive ability and behavioral changes (Colborn 1995; LeBlanc 1995). The two major metabolites of dichlorodiphenyltrichloroethane, p,p- dichlorodiphenyldichloroethylene and o,p- dichlorodiphenyltrichloroethane, have been detected in adipose tissue, breast milk and serum of individuals with no past record of occupational exposure or were living in areas where dichlorodiphe-nyltrichloroethane has not been used for years. This raised questions concerning chronic exposure to dichlorodiphenyltrichloroethane through food, which could increase the hazard of developing estrogen dependent tumors such as breast cancer. Another widely used organochlorine insecticide Chlordane, on occasion, has been reported in breast milk, as oxychlordane, the stable metabolite.

Metabolism

Biotransformation of organochlorine pesticides was observed in the microsomal fractions and whole cells of Saccharomyces cerevisiae expressing human cytochrome P450 3A4. As per the observation of Mehmood et al. (1996), hexachlo-robenzene and pentachlorobenzene were metabolised into pentachlorophenol which was further transformed into tetrachlorohydroquinone in both in vitro and in vivo studies.

There is particular concern about endocrine disrupting pesticides that are Lipophilic, resistant to metabolism, and able to bioconcentrate up the food chain. These substances become stored in body fats and can be transferred to the developing offspring via the placenta or via the egg. Animals feeding at the top of the food chain are at increased risk, particularly mammals because during breast feeding contaminants are again mobilized and transferred to the new born infant. Marine mammals may be most vulnerable, because not only do they carry large amounts of body fat, but also the oceans are the final sink for many persistent pollutants. Some persistent pollutants, including several pesticides, are carried in air and in water over several hundred miles, and so even wildlife and people living far away from where these substances are used are under significant threat. Some areas are especially vulnerable because these substances are redistributed to the colder northern regions in a process termed 'global redistillation' or the grasshopper effect. The United Nations Environment Programme Convention on persistent organic pollutants (2001) focused on 12 substances, including the following pesticides: aldrin, chlordane, dichlorodiphenyl-trichloroethane, dieldrin, endrin, heptachlor, mirex, and toxaphene. Ecological magnification in organisms of the food chain appears to be the most harmful environmental effect resulting from the general usage of organochlorine pesticides. Bioconcentration clearly results from two important properties; their lipid solubility and water insolubility i.e. a large lipid/water partition coefficient, and their resistance to degradation by multi function oxygenase enzymes (Hamelink et al.1971).

Toxicity

Organochlorine pesticides act primarily by altering the movement of ions across the nerve cell membranes, thus changing the ability of the nerve to fire. Organochlorines introduced into the environment since the early 1940s could threaten the reproductive potential of baleen whales and other cetaceans. In a study conducted by Colborn and Smolen (1996) on the effects of dichlorodiphenyltrichloroethane and polychlo-robiphenyl in humans, pinnipeds and other wildlife had shown that, the mechanisms of action of the organochlorines reveal their ability to affect developing organisms at very low concentrations during critical life stages: embryonic, fetal, and early postnatal. Exposure during early development can disrupt the organization of the endocrine, reproductive, immune and nervous systems, effecting irreversible damage that may not be expressed until the individuals reach adulthood. Administration of methoxychlor to the new born rat at a dose level of 0.5 mg/day caused accelerated puberty and accelerated loss of fertility. Similarly, new born female rats injected with 1 mg/day of o'p-dichlorodiphenyltrichloroethane on days 2-4 after birth had early onset of puberty and accelerated loss of fertility. Even doses as low as 1 mg/ day of either of these substances, given to pregnant female mice on days 11-17 of pregnancy, causes effects on the territorial behaviour of male offspring. However, dichlorodiphenyldichloroethylene induced eggshell thinning, one of the most well known effects noted in wildlife, is now not thought to result from dichlorodiphenyl-dichloroethylene binding to a sex hormone receptor.

The recent discovery that human sperm count is declining worldwide at a rate of 1 x 10(6) sperm/(mL year) suggests common exposure to estrogen-like chemicals during prenatal and early postnatal development (Colborn and Smolen 1996). This raises concern for other top predator species that also share the same exposure. Recent years has expressed concern a propos the potential endocrine disruptive means of chemicals that persist in nature and build up in body tissues. Some chemicals are thought to act as estrogen mimics because they antagonize the effect of estradiol in vitro by interacting with the estrogen receptor and because their toxicity in vivo resembles the effects of premature estrogen exposure (Cooper and Kavlok 1997; Turner and Sharpe 1997). Accordingly, the developing male reproductive tract is a target for unfortunate xeno estrogen exposure that could lead to infertility later in adulthood. Moreover, wildlife studies representing damaged reproductive function in environments, where levels of xeno estrogens are high, have stirred up research into their endocrine disrupting effects (Bolger et al. 1998; Colborn et al. 1993 ; Ramamoorthy et al. 1997; Shekhar et al. 1997). Though in vitro and in vivo assays of estrogenicity have revealed that certain chemicals act as estrogens, the likelihood that some chemicals may wield their effects by interfering with the binding of androgens to the androgen receptor is still an 'orphan' issue that gained moderately petite consideration (Timothy et al. 2000). Grippingly p,p9- dichlorodiphenyldichloroethylene, one of the most abundant organo-chlorine compounds in the environment which is proved not to bind, or very poorly bind, to the estrogen receptor, has been observed to perform as an anti androgen (Kelce et al. 1995, 1997) ; Lindane is a persistent organochlorine pesticide, the oestrogenic properties of which have been demonstrated in several systems, including the production of vitellogenin (egg yolk protein) and zona radiata (egg shell protein) in primary hepatocyctes from Atlantic salmon Salmo salar (Celius et al. 1999). Lindane has also been shown to damage human spermatozoa at concentrations as low as those found in female genital tract secretions (Silvestroni and Palleschi 1999) and its presence in the breast milk has been observed (Lyons 1999).

Eggshell thinning due to dichlorodiphenyldichloroethylene has also affected populations of bald eagles (Haliaeetus leucocephalusyr). The mechanism for eggshell thinning although previously thought to be caused by the estrogenic effects of dichlorodiphenyldichloroethylene is now proposed to involve the inhibition of prostaglandin synthesis in the eggshell gland muscosa (Bowerman et al. 2000; Lundholm 1997). Additional reports of dichlorodiphenyltrichloroethane effects in birds include decreased egg hatchability in eastern bluebirds (Sialia sialis) (Bishop et al. 2000). Eggs from alligators from Lake Apopka in Florida are known to contain residues of organochlorine pesticides including toxaphene, dieldrin, dichlorodiphenyldichloro-ethylene and chlordane, as well as polychlorobiphenyls (Heinz et al. 1991). Several studies have described adverse reproductive effects to the alligator population on this lake including increased embryo mortality (Woodward et al. 1993) and morphological and endocrine abnormalities in juvenile alligators. (Guillette et al. 1994; Gross et al. 1995). Dichlorodiphenyldichloroethylene also has been shown to cause sex reversal in alligators and red-eared slider turtles (Trachemys scripta elegans)

following the treatment of eggs at early embryonic stages and at incubation temperatures necessary for the production of male offspring.

Major ecological effects of organochlorine compounds include interference with reproductive success of organisms high on the food chain, especially fish eating birds (osprey, pelicans, falcons and eagles). Ortho and para isomers of dichlorodi-phenyltrichloroethane have estrogenic effects and they compete with estradiol for binding to estrogen receptors in uterine cytosol. Estrogenic and enzyme inducing properties of dichlorodiphenyltrichloroethane cause changes in steroid metabolism. Organochlorine compounds also alter ability of birds to mobilize Ca to produce strong egg shells. Once the ecological impact of these pesticides was documented, they were banned from use in many countries. They are still used in some developing countries, though, because of their efficiency in controlling diseases an increasing food production. Examples of effects of dichlorodiphenyltrichloroethane contamination in marine mammals include low reproductive success and declining populations of harbor seals in the Dutch Wadden Sea (Reijnders 1980; 1986; 1990), premature pupping in California sea lions (Gilmartin et al. 1976), and immune and reproductive impairment in Baltic ringed and gray seals (Bergman and Olsson 1985; Roos et al. 1998). Concentrations of persistent organic pollutants in Arctic species reflect their position in the food web. For example, eggs of top prey species such as white tailed sea eagles had higher concentrations than did species lower in the food web. Studies of Canadian seabirds have shown that eiders, which overwinter in contaminated waters, have a higher contaminant load than do birds overwintering in clean waters. In mammals, concentrations in marine species are higher than in terrestrial species and highest in top predators at the end of long food chains, for example, in polar bears (de March et al. 1998).

New Mothers Guide to Breast Feeding

New Mothers Guide to Breast Feeding

For many years, scientists have been playing out the ingredients that make breast milk the perfect food for babies. They've discovered to day over 200 close compounds to fight infection, help the immune system mature, aid in digestion, and support brain growth - nature made properties that science simply cannot copy. The important long term benefits of breast feeding include reduced risk of asthma, allergies, obesity, and some forms of childhood cancer. The more that scientists continue to learn, the better breast milk looks.

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