ContentsENDOCRINE DISRUPTERS2INTRODUCTION21.DICHLORO DIPHENYL TRICHLOROETHAN [DDT]3INTRODUCTION3ENVIRONMENTAL FATE4OTHER HEALTH EFFECTS72.POLYCHLORINATED BIPHENOLS8INTRODUCTION8ENVIRONMENTAL FATE8EFFECT ON ENDOCRINE9OTHER HEALTH EFFECTS93.BISPHENOLS10INTRODUCTION10TYPES OF BISPHENOLS11BISPHENOL-A [BPA]11ENVIRONMENTAL FATE OF BISPHENOL-A12COMMERCIAL PRODUCTION AND USE OF BISPHENOL-A12EXPOSURE13HEALTH EFFECTS OF BISPHENOL-A134.PTHALATES16INTRODUCTION16PRODUCTION AND USE OF PTHALATES16ENVIRONMENTAL FATE OF PTHALATES17EXPOSURE17HEALTH EFFECTS OF PTHALATES18INFLUENCE ON THE ONSET OF PUBERTY IN GIRLS18

REFERENCES19

ENDOCRINE DISRUPTERSINTRODUCTION

Endocrine disruptors are chemicals that may interfere with the bodys endocrine system and produce adverse developmental, reproductive, neurological, and immune effects in both humans and wildlife. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls,DDTand other pesticides, andplasticizerssuch as bisphenol A. Endocrine disruptors may be found in many everyday products including plastic bottles, metal food cans, detergents, flame retardants, food, toys, cosmetics, and pesticides. The NIEHS supports studies to determine whether exposure to endocrine disruptors may result in human health effects including lowered fertility and an increased incidence ofendometriosisand some cancers. Research shows that endocrine disruptors may pose the greatest risk during prenatal and early postnatal development when organ and neural systems are forming.

Working of Endocrine disrupters

From animal studies, researchers have learned much about the mechanisms through which endocrine disruptors influence the endocrine system and alter hormonal functions.

Figure 1 Actions of endocrine disrupters after entering the cell.Endocrine disruptors can: Mimic or partly mimic naturally occurring hormones in the body like estrogens (the female sex hormone), androgens (the male sex hormone), and thyroid hormones, potentially producing overstimulation. Bind to a receptor within a cell and block the endogenous hormone from binding. The normal signal then fails to occur and the body fails to respond properly. Examples of chemicals that block or antagonize hormones are anti-estrogens and anti-androgens. Interfere or block the way natural hormones or their receptors are made or controlled, for example, by altering their metabolism in the liver.

1. DICHLORO DIPHENYL TRICHLOROETHAN [DDT]

INTRODUCTIONDDT is an organochlorine insecticide used mainly to control mosquito-borne malaria; use on crops has generally been replaced by less persistent insecticides [1] It was extensively used during the Second World War among Allied troops and certain civilian populations to control insect typhus and malaria vectors, and was then extensively used as an agricultural insecticide after 1945 [3]. DDT was banned for use in Sweden in 1970 and in the United States in 1972 [3]It is available in several different forms: aerosols, dustable powders, emulsifiable concentrates, granules and wettable powders [1,2]. It is reported to be compatible with many other pesticides and incompatible with alkaline substances [1]. Many insect pests may have developed resistance to DDT [1].

Figure 2 Chemical structure of DDTUnless otherwise specified, the toxicological, environmental effects and environmental fate and chemistry data presented here refer to the technical product DDT. Technical grade DDT is actually a mixture of three isomers of DDT, principally the p,p'-DDT isomer [ca. 85%], with the o,p'-DDT and o,o'-DDT isomers typically present in much lesser amounts [3.]Since Rachel Carsons Silent Spring, the fear that bioaccumulating substances might cause genetic mutations or cancer has resonated with the international developed community. Despite evidence that DDT does not cause permanent genetic mutations [1, 2], International treaties as recent at the Stockholm Convention on Persistent Organic Pollutants effective in 2004 [3] reference multigenerational consequences as a major selling point.ENVIRONMENTAL FATEBreakdown in Soil and GroundwaterDDT is very highly persistent in the environment, with a reported half life of between 2-15 years and is immobile in most soils. Routes of loss and degradation include runoff, volatilization, photolysis and biodegradation [aerobic and anaerobic] [3]. These processes generally occur only very slowly. Breakdown products in the soil environment are DDE and DDD, which are also highly persistent and have similar chemical and physical properties.Due to its extremely low solubility in water, DDT will be retained to a greater degree by soils and soil fractions with higher proportions of soil organic matter [5]. It may accumulate in the top soil layer in situations where heavy applications are [or were] made annually; e.g., for apples [2]. Generally DDT is tightly sorbed by soil organic matter, but it [along with its metabolites] has been detected in many locations in soil and groundwater where it may be available to organisms [5]. This is probably due to its high persistence; although it is immobile or only very slightly mobile, over very long periods of time it may be able to eventually leach into groundwater, especially in soils with little soil organic matter.Residues at the surface of the soil are much more likely to be broken down or otherwise dissipated than those below several inches [6]. Studies in Arizona have shown that volatilization losses may be significant and rapid in soils with very low organic matter content [desert soils] and high irradiance of sunlight, with volatilization losses reported as high as 50% in 5 months. In other soils [Hood River and Medford] this rate may be as low as 17- 18% over 5 years . Volatilization loss will vary with the amount of DDT applied, proportion of soil organic matter, proximity to soil-air interface and the amount of sunlight.Breakdown of Chemical in Surface WaterDDT may reach surface waters primarily by runoff, atmospheric transport, drift, or by direct application [e.g. to control mosquito-borne malaria] [3]. The reported half-life for DDT in the water environment is 56 days in lake water and approximately 28 days in river water. The main pathways for loss are volatilization, photodegradation, adsorption to water-borne particulates and sedimentation [3]. Aquatic organisms, as noted above, also readily take up and store DDT and its metabolites. Field and laboratory studies in the United Kingdom demonstrated that very little breakdown of DDT occurred in estuary sediments over the course of 46 days [5].DDT has been widely detected in ambient surface water sampling in the United States at a median level of 1 ng/L [part per trillion] [3,5].Breakdown of Chemical in VegetationDDT does not appear to be taken up or stored by plants to a great extent. It was not translocated into alfalfa or soybean plants, and only trace amounts of DDT or its metabolites were observed in carrots, radishes and turnips all grown in DDT-treated soils . Some accumulation was reported in grain, maize and riceplants, but little translocation occured and residues were located primarily in the roots [3].

EFFECTS ON ENDOCRINEStudies that have tried to link DDT levels in humans directly to endocrine effects were conducted in a much different way than those on other species. For one, the subject cannot be killed and dissected to look for more subtle variations in internal organ structure. Neither can one gather children and raise them in a laboratory. Therefore the studies that have been done about the effects of DDT on human subjects have been less controlled than their nonhuman counterparts. Researchers have looked for correlations between maternal serum concentrations of DDT and DDE during pregnancy and certain hormone regulated abnormalities [preterm labor, gonad formation, etc.] in their children. Scientist used blood collected almost 40 years ago from women who received prenatal care from university hospitals. They demonstrated a steadily increasing trend of preterm birth with serum DDE concentrations. The benefit of this method is the sample size. Because the blood has already been collected along with a record of the womens and childrens health, each additional sample is relatively little work. This allowed them to use a sample size of 2613 women. The disadvantage is not being able to identify an accurate control group. Preterm birth has been associated with several health factors besides DDT, including but not limited to smoking, weight, height, and age. Separating the effects of DDT from other physical and sociological factors proves to be challenging problem. Although the authors of this study attempt to address it, it is difficult to know if they accounted for all of the other environmental factors that could lead to the observed outcome. DDT was concluded to act as a lactation suppressant. Other associations have been even less conclusive than the ones addressed here, such as seaman count, menstrual cycle irregularity, and birth weight. Following is the figure of an ovary which has been at risk due to the frequent exposure to Environmental disrupters. [8]

Figure 3 Frequently observed ovarian malformations in rats following neonatal exposure to endocrine disruptors.

There are two possible reasons why the link between endocrine disruption, birth related problems, and gender related birth defects has been much more clearly demonstrated in nonhuman species. The first might be that the species being studied are actually more susceptible to the endocrine disrupting properties of DDT and its metabolites than humans are. The second possibility is that it is impossible to subject human subjects to substantial quantities of a toxin, force them to mate, and then kill and dissect their offspring. These methods that are used on animal subjects lead to much more comprehensive and conclusive results because they allow scientist to examine tissue and look for a causal relationships. However, statements such as the one quoted at the beginning of this paper from the Stockholm Convention on Persistent Organic Pollutants indicate that international policy makers are prepared to take leap from the scientific proof a correlation between DDT concentrations and hormonal induced effects in humans to the assumption of a causal relationship.OTHER HEALTH EFFECTSUnlike their land-loving relatives, aquatic invertebrates are quite sensitive to DDT, especially while these creatures are still very young. Some problems associated with DDT include reproductive/development impairment and nervous system disorders. At one time, DDT was used to control certain sea crustaceans, because it was so effective against these aquatic invertebrates.Organochlorine pesticides repress symbiotic nitrogen fixation resulting in low crop yields. Pesticides Pentachlorphenol,DDT and Methyl parathion interferes signaling from leguminous plants that are found in soil such as alfalfa,peas and soyabean to symbiotic soil bacteria.Humans and animals endocrine disruptions were seen that disrupts N2 fixation.Increased synthetic nitrogen fertilizers dependency,reduce soil fertility and unsustainable long-term crop yield occurs.At concentration above 236 mg DDT per kg of body weight, you'll die. Concentration of 6-10 mg/kg leads to such symptons as headache, nausea, vomiting, confusion, and tremors in human beings.Currently, there is much debate as to whether DDT can increase a woman's chance of breast cancer. [4]

2. POLYCHLORINATED BIPHENOLSINTRODUCTIONPCBs are a group of synthetic organic chemicals that can cause a number of different harmful effects. There are no known natural sources of PCBs in the environment. PCBs are either oily liquids or solids and are colorless to light yellow. Some PCBs are volatile and may exist as a vapor in air. They have no known smell or taste. PCBs enter the environment as mixtures containing a variety of individual chlorinated biphenyl components, known as congeners, as well as impurities. Because the health effects of environmental mixtures of PCBs are difficult toevaluate, most of the information in this toxicological profile is about seven types of PCB mixtures that were commercially produced. These seven kinds of PCB mixtures include 35% of all the PCBs commercially produced and 98% of PCBs sold in the United States since 1970. Some commercial PCB mixtures are known in the United States by their industrial trade name, Aroclor. For example, the name Aroclor 1254 means that the mixture contains approximately 54% chlorine by weight, as indicated by the second two digits in the name.

Figure 4 Chemical structure of PCBs Because they don't burn easily and are good insulating materials, PCBs were used widely as coolants and lubricants in transformers, capacitors, and other electrical equipment. The manufacture of PCBs stopped in the United States in August 1977 because there was evidence that PCBs build up in the environment and may cause harmful effects. Consumer products that may contain PCBs include old fluorescent lighting fixtures, electrical devices or appliances containing PCB capacitors made before PCB use was stopped, old microscope oil, and old hydraulic oil. [9]ENVIRONMENTAL FATEBreakdown in surface waterIn surface waters, PCBs are present in substantial quantities in sediments. Indeed, PCBs tend to attach to the surface of organic matter, clay, and micro-particles that are still suspended in the water or have already settled down. They can remain buried in sediments for a long time and be slowly released into the water and evaporate into air. Releases through water into air occur especially when it is warm and when PCB concentrations in sediment are high as this keeps the PCB levels in water elevated.Breakdown in AirPCBs present in air can deposit on land when it rains or snows [wet deposition], or when they attach to particulate matter, such as dust or soot, that settles on the ground [dry deposition]. It is also possible that PCBs could be transported by insects which have come into contact with them. [10]EFFECT ON ENDOCRINEThe preponderance of the biomedical data from human and laboratory mammal studies provide strong evidence of the toxic potential of exposure to PCBs. Information on health effects of PCBs is available from studies of people exposed in the workplace, by consumption of contaminated rice oil. Health effects that have been associated with exposure to PCBs in humans and/or animals include liver, thyroid, dermal and ocular changes, immunological alterations, neurodevelop- mental changes, reduced birth weight, reproductive toxicity, and cancer. Direct evidence linking PCB exposures to thyroid morbidity in humans is limited. The risk for goiter was significantly increased among the Yu-Cheng cohort, indicating the possibility of excess thyroid disease in an adult population that experienced relatively high exposures to mixtures of PCBs and polychlorinated dibenzofurans [PCDFs]. Increased thyroid gland volume among workers and nearby residents of a PCB production facility is also observed.There is suggestive evidence that PCBs can produce both agonistic and antagonistic estrogenic responses. A wide variability of responses observed across PCB type and assays indicates the involvement of multiple mechanisms. The specific mechanism of action appears to vary, with competitive binding to estrogen receptors being congener/metabolite specific. Anti-estrogenic activities appear to be morestrongly associated with PCBs that are Ah receptor agonists, whereas hydroxylated metabolites of PCBs seem to be at least partly responsible for responses to PCBs that may involve changes in estrogen receptor-dependent physiological processes.OTHER HEALTH EFFECTSDermal lesions including skin irritation, chloracne, and pigmentation of nails and skin have been observed in humans following occupational exposure to PCBs, and from the accidental ingestion of rice oil contaminated with high concentrations of PCBs, chlorinated dibenzofurans [CDFs] and other halogenated chemicals.Ocular effects including hypersecretion of the Meibomian glands, abnormal pigmentation of the conjunctiva, and swollen eyelids have also been observed in humans occupationally exposed to PCBs. These ocular alterations almost always accompany chloracne. Ocular effects may continue to appear after exposure has ceased, possibly as a result of accumulation of the causative agent in skin adipose. Chronic- duration oral exposure studies in monkeys showed that adverse dermal and ocular effects can occur at dose levels as low as 0.005 mg/kg/day.The neurological effects of PCBs have been extensively investigated in humans and animals. Substantial data suggest that PCBs play a role in neurobehavioral alterations observed in newborns and young children of women with PCB burdens near background levels. In general, the observed alterations are subtle. In some studies, those alterations were found to disappear as the children grow older [24 years old], while other studies have reported neurobehavioral deficits still present in 11-year-old children mostly due to in utero exposure to PCB.There are indications of altered immune status in adult and infant human populations that were orally exposed to mixtures of PCBs and other chemicals. The most conclusive findings were in the Yusho and Yu-Cheng populations that experienced the highest levels of PCB exposure and least complex exposure mixture.Reproductive effects of PCBs have been studied in a variety of animal species, including Rhesus monkeys, rats, mice and mink. Rhesus monkeys are generally regarded as the best laboratory species for predicting adverse reproductive effects in humans. Potentially serious effects on the reproductive system were seen in monkeys and a number of other animal species following exposures to PCB mixtures. Most significantly, PCB exposures were found to reduce the birth weight, conception rates and live birth rates of monkeys and other species and PCB exposure reduced sperm counts in rats. Effects in monkeys were long-lasting and were observed long after the dosing with PCBs occurred.EPA uses a weight-of-evidence approach in evaluating the potential carcinogenicity of environmental contaminants. EPA's approach permits evaluation of the complete carcinogenicity database, and allows the results of individual studies to be viewed in the context of all of the other available studies. Studies in animals provide conclusive evidence that PCBs cause cancer. Studies in humans raise further concerns regarding the potential carcinogenicity of PCBs. Taken together, the data strongly suggest that PCBs are probable human carcinogens.[11]

3. BISPHENOLSINTRODUCTIONBisphenol-A [BPA] and other bisphenols are found in polycarbonate plastics and epoxy resins. Polycarbonate plastics are often used in consumer goods and containers that store food and beverages, such as water bottles. Bisphenol A [BPA] is an important industrial chemical that is used primarily to make polycarbonate plastic and epoxy resins, both of which are used in a wide variety of applications. For example, polycarbonate is used in eyeglass lenses, medical equipment, water bottles, digital media [e.g. CDs and DVDs], cell phones, consumer electronics, computers and other business equipment, electrical equipment, household appliances, safety shields, construction glazing, sports safety equipment, and automobiles1. Among the many uses for epoxy resins are industrial floorings, adhesives, industrial protective coatings, powder coatings, automotive primers, can coatings and printed circuit boards. [13]TYPES OF BISPHENOLS There are many types of bisphenols, including bisphenol [A, AB, AF, B, BP, C, E, F, G, M, S, P, PH, TMC, and Z]. However, Bisphenol A is the most popular representative of this group, often simply called "bisphenol". Bisphenol A [BPA] is an important industrial chemical that is used primarily to make polycarbonate plastic and epoxy resins, both of which are used in a wide variety of applications. [12]

Figure 4 chemical structure of bisphenolsBISPHENOL-A [BPA] Bisphenol A is a pseudo-persistent chemical, which despite its short half-life is ubiquitous in the environment because of continuous release. Properties: Formed by the condensation of phenol with acetone, BPA has a low vapor pressure, high melting point and moderate solubility. It is thus expected to have low volatility. BPA is considered to have low or moderate hydrophobicity and thus a modest capacity for bioaccumulation. Bisphenol A is a nonsteroidal xenoestrogen that exhibits approximately 104 the activity of estradiol. [17] Release: Release can occur during chemical manufacture, transport, and processing. Post-consumer releases are primarily via effluent discharge from municipal wastewater treatment plants, leaching from landfills, combustion of domestic waste, and the natural breakdown of plastics in the environment.

BISPHENOL-A IN THE ENVIRONMENT Bisphenol A has become ubiquitous in the environment within the past 80 years because of its presence in a multitude of products including food and beverage packaging, flame retardants, adhesives, building materials, electronic components, and paper coatings. As demand for these products has increased, so has BPA production. BPA in water and suspended solids- Many studies have quantified BPA levels in various aqueous media, including fresh and marine surface waters, treatment plant influents and effluents, and groundwater. Levels of BPA in landfill leachate can be very high; studies in Japan reported concentrations of 5400 mg/L [Yamadaet al., 1999] and 17,200 mg/L BPA in sediments and soils- The primary source of BPA in soils is the land-application of sewage sludge or biosolid. BPA in biota- Compared to non-biotic environmental compartments, relatively little environmental BPA occurs in biota. At low doses, BPA is biodegraded or metabolized, so bioaccumulation generally occurs only with high doses. [16,17]

ENVIRONMENTAL FATE OF BISPHENOL-A The vast majority of BPA produced, greater than 99.9%, is consumed at manufacturing sites to make products such as polycarbonate plastic or epoxy resins [Staples et al, 1998]. Bisphenol A dust [particulates] is controlled by workplace practices and engineering design and is not a significant contributor to environmental exposures. The relatively small amount of vapor released to the atmosphere is rapidly degraded by sunlight. Low levels may be released to the environment in the effluent water from biological wastewater treatment plants. A study using guidelines of the Organization for Economic Cooperation and Development demonstrated that bisphenol A meets its criteria for classification as "readily biodegradable." [18]COMMERCIAL PRODUCTION AND USE OF BISPHENOL-A In 1953, Dr. Hermann Schnell of Bayer in Germany and Dr. Dan Fox of General Electric in the United States independently developed manufacturing processes for a new plastic material, polycarbonate, using BPA as the starting material. Commercial production began in 1957 in the United States and in 1958 in Europe. About this same time, epoxy resins were developed with the versatility to meet a wide range of industrial and consumer needs. Commercial production of BPA began in the 1950s when large-scale uses for polycarbonate plastic and epoxy resins were developed and has grown worldwide along with the continued growth of the uses for these materials. Up to 6 billion pounds of BPA is produced globally per year. [16]EXPOSURE Varnishes used for the inner coatings of food cans are mostly based on epoxy resins or vinylic organosols. The epoxy resins are produced from bisphenol A and bisphenol F and they also contain BADGE or BFDGE as stabilizing components. [14] At higher temperatures [sterilization, microwave heating], the resin can decompose and, as a results, the migration of bisphenols from packaging to food can be more intensive and rapid. A similar situation can be encountered, for example, in the case of imperfectly thermally stabilized can lacquers. Thus, the major human exposure route to bisphenols is via ingestion of contaminated food and water, with over 90% of adults in many countries having detectible amounts in their urine. [12] FDA is continuing its research and monitoring of studies to address uncertainties raised about BPA [15] The U.S. EPA has established the safe daily intake of BPA to be 50 g/kg body weight/d based on the assumption that the main source of exposure is oral through food ingestion. [19] HEALTH EFFECTS OF BISPHENOL-A Endocrine Disruption and Bisphenol-A Bisphenol A exhibits extremely weak hormonal activity in test tube assays, such as those utilizing yeast or human breast cancer cells. Effects have also been observed in compromised laboratory animals at high doses of bisphenol A. However, reproduction and development are not affected by relatively high levels of bisphenol A in multi-generational studies, which are designed to detect disruptions in normal hormone activity [doses are compared to the extremely low levels of possible consumer exposure].[18] Prenatal Exposure to BPA and alterations in Reproductive System Perinatal exposure to environmentally relevant BPA doses results in morphological and functional alterations of the male and female genital tract and mammary glands that may predispose the tissue to earlier onset of disease, reduced fertility and mammary and prostate cancer. [20] Estrogenic Activity of Bisphenol A Estrogenic activity was mainly identified in ovariectomozed rats or in even less relevant in vitro models. In addition, estrogenic activity was seen in animals administered large doses of BPA or animals exposed via only experimental routes of exposure, such as intraperitoneally or subcutaneously. [18] General Toxicity The toxicology of bisphenol A [BPA] has been extensively studied over the past several decades. Some studies have focused on the potential of BPA to act as an estrogen. These studies have shown that BPA possesses estrogenic activity in special experimental systems, however, it is not yet clear how relevant these studies are to human health. Thus, the use of these studies in estimating the NOEL for the toxicity of BPA is inappropriate at this time. [18] Studies of BPA effects on wildlife have demonstrated few clear trends. Terrestrial wildlife is likely to experience low exposures of BPA, and few studies have examined environmentally relevant doses. However, some invertebrate, fish, and amphibian species appear to be susceptible to low exposures of BPA, and benthic organisms may be exposed to higher concentrations of BPA because of elevated sediment levels. 11 studies that show measurable effects in wildlife at or near environmentally relevant concentrations [0.08e12.5 mg/L]. It is important to note that many wildlife populations are likely affected by environmental BPA concentrations in specific high exposure locations. [17]

4. PTHALATESINTRODUCTIONPhthalates are a group of chemicals used as plasticizers, which provide flexibility and durability to plastics such as polyvinyl chloride [PVC]. Phthalates are a family of compounds made from alcohols and phthalic anhydride. Phthalates are dialkyl or alkyl aryl esters of 1,2 benzenedicarboxylic acid. Phthalates in pure form are usually clear liquids, some with faint sweet odors and some with faint yellow color. Plastics that contain phthalates are commonly used in applications that include building materials, clothing, cosmetics, perfumes, food packaging, toys, and vinyl products. With respect to health effects, phthalates are often classified as endocrine disruptors or hormonally active agents [HAAs] because of their ability to interfere with the endocrine system in the body.

Figure 5 chemical structure of PthalatesThe general chemical structure of phthalates [R and R' = CnH2n+1]PRODUCTION AND USE OF PTHALATES They are oily, colorless, odorless liquids that do not evaporate readily. Often called plasticizers, phthalates are used in the manufacture of plastics, including polyvinyl chloride plastics [PVC]. Phthalates can prolong the lifespan or durability of plastics and increase the flexibility of some plastics. They can be found in hundreds of products such as toys, vinyl flooring, herbal pill coating, and plastic shower curtains. In addition, phthalates are also used as solvents. Phthalates are used in a variety of cosmetic products, such as nail polishes, perfumes, skin moisturizers and shampoos to enhance penetration and hold scent and/or color. Phthalates are ubiquitous in the environment. Uses of the various phthalates depend in part on their molecular weight: Higher molecular weight phthalates, DEHP, DiDP, and DiNP, are the phthalates produced in highest volume for use in construction material, clothing, childrens toys, and household furnishings. Relatively low molecular weight phthalates, DBP, DEP, DMP, tend to be used as solvents and in adhesives, waxes, inks, cosmetics, insecticides, and pharmaceuticals. [23

ENVIRONMENTAL FATE OF PTHALATES Phthalates are synthesized in massive amounts to produce various plastics and have become widespread in environments following their release as a result of extensive usage and production. This has been of an environmental concern because phthalates are hepatotoxic, teratogenic, and carcinogenic by nature. Numerous studies indicated that phthalates can be degraded by bacteria and fungi under aerobic, anoxic, and anaerobic conditions. [22]EXPOSURE All populations of people, domestic animals, and wildlife regularly encounter opportunities for exposure to phthalates because of their widespread use. Ingestion, inhalation, intravenous injection tubing and solutions, and skin absorption are potential pathways of exposure. Food: Phthalates can be released into aqueous solution foods during microwaving in plastic containers [24]. Water: Phthalates are found in ground water and drinking water. Infant formula and milk: Some phthalates occur as contaminants in consumer milk and ready-to-use baby formulas based on cows milk. [25] Medications and nutritional supplements: Pharmaceutical preparations intended to treat diseases of the gastrointestinal tract, such as ulcerative colitis and colorectal cancer, are often coated with a polymer that allows the drug to be delivered directly to the colon or small intestine. This polymer may contain plasticizer phthalates such as DBP and DEP. Polymer toys softened with phthalates are a source of potential oral exposure in children. Indoor air and house dust Vapors emitted from building materials, furniture and household fragrances are potential indoor sources of phthalate exposures. Cosmetics and personal care products: Phthalates are used in a variety of cosmetic and personal care products, such as nail polishes, perfumes, hairsprays, skin moisturizers and shampoos. In one study, the levels of selected phthalates were measured in 102 branded hair sprays, perfumes, deodorants, and nail polishes. Medical devices: A variety of medical devices used to deliver medical care such as bags and tubing for intravenous fluids, nutritional formulas, blood transfusions, and dialysis are made of PVC plastics softened with phthalates, usually DEHP. DEHP can leach out from these products [23]HEALTH EFFECTS OF PTHALATES ENDOCRINE DISRUPTION Phthalates are capable of binding to the estrogen receptor. In breast cancer cells, some phthalates have weak estrogenic effects and some have weak anti-estrogenic effects in the presence of 17beta-estradiol. Phthalates have been linked to adverse reproductive effects in male pubertal and adult rodents exposed in utero and during lactation, such as reduction in the weights of reproductive organs and a reduction in sperm count. [26] There is also some evidence of reproductive toxicity in adult female rodents exposed to DEHP, such as prolonged estrous cycles and lowered circulating estradiol levels [27] In one human study, infant boys born to mothers with high phthalate urine levels were more likely to have smaller penises and scrotums and incomplete testicular descent [17]. Boys born to mothers with the highest levels of phthalates were four to ten times more likely to have reduced genital development.

INFLUENCE ON THE ONSET OF PUBERTY IN GIRLS One study in Puerto Rico found that girls with premature breast development [younger than 8 years] had higher blood levels of several phthalates than a control group of girls without premature breast development [29]

Phthalates are found in young children and in human amniotic fluid [30]. There is evidence in rodents and humans that in utero exposure to phthalates adversely affects reproductive development [26] [28]

Results from several studies have shown significant levels of phthalates in breast milk [31]. In a study of Danish and Finnish women, phthalate monoesters were found in breast milk with large variations. Interestingly, levels of some phthalate esters in German women were higher than in Canadian mothers, indicating a regional exposure to specific phthalates.

REFERENCES1. Royal Society of Chemistry. 1991 [as updated]. The Agrochemicals Handbook, Royal Society of Chemistry Information Services, Cambridge, UK.2. Meister, R.T. [ed.] 1992. Farm Chemicals Handbook '92, Meister Publishing Co., Willoughby, OH.3. Agency for Toxic Substances and Diseases Registry [ATSDR]/US Public Health Service, Toxicological Profile for 4,4'-DDT, 4,4'-DDE, 4, 4'-DDD [Update]. 1994. ATSDR. Atlanta, GA.4. http://people.chem.duke.edu/~jds/cruise_chem/pest/effects.html 5. Van Ert, M. and Sullivan, J.B. 1992. Organochlorine Pesticides In Sullivan, J.B. and Krieger, G.R., Hazardous Materials Toxicology, Clinical Principles of Environmental Health. Williams & Wilkins, Baltimore, MD.6. World Health Organization [WHO]. 1989. Environmental health Criteria 83, DDT and its Derivatives--Environmental Effects. World Health Organization, Geneva.7. Matsumura, F. 1985. Toxicology of Insectides. Second Edition. Plenum Press, New York, NY.8. Heather B. Patisaul, Heather B. Adewale. 2009 Long-Term Effects of Environmental Endocrine Disruptors on Reproductive Physiology and Behavior9. www.atsdr.cdc.gov/toxprofiles/tp17.pdf10. http://www.greenfacts.org/en/pcbs/l-2/2-biomagnification.htm#2 11. http://www.epa.gov/wastes/hazard/tsd/pcbs/pubs/effects.htm12. http://www.cyclicor.com/products/cycli-clear-tm/background.aspx13. BISPHENOL A: INFORMATION SHEET-PDF14. Determination of Bisphenol A, Bisphenol F, Bisphenol A Diglycidyl Ether and Bisphenol F Diglycidyl Ether Migrated from Food Cans using Gas Chromatography-Mass Spectrometry- PDF15. http://www.fda.gov/Food/IngredientsPackagingLabeling/FoodAdditivesIngredients/ucm064437.htm16. Endocrine Disruptors in Plastic: Bisphenol A & Phthalates BY Carol Kwiatkowski, PhD Executive Director, The Endocrine Disruption Exchange- PDF17. Journal of Environmental Management- Bisphenol A exposure, effects, and policy: A wildlife perspective- PDF18. http://www.bisphenol-a.org/esafety/enfate.html19. Endocrine-Disrupting Chemicals -An Endocrine Society Scientific Statement- PDF20. Endocrine disruptors and reproductive health: the case of bisphenol-A. BY Maffini MV1, Rubin BS, Sonnenschein C, Soto AM. PDF21. http://www.epa.gov/teach/chem_summ/phthalates_summary.pdf22. Phthalates biodegradation in the environment BY Da-Wei Liang & Tong Zhang & Herbert H. P. Fang & Jianzhong He PDF 23. BREAST CANCER & THE ENVIRONMENT RESEARCH CENTERS Early Life Exposure to Phthalates and Breast Cancer Risk in Later Years FACT SHEET on PHTHALATES-PDF 24. Jen J, Liu T, Determination of phthalate esters from food-contacted materials by on-line microdialysis and liquid chromatography, J Chromatogr A, 1130[1]:28-33, 2006.25. Mortensen GK, et al., Determination of phthalate monoesters in human milk, consumer milk, and infant formula by tandem mass spectrometry [LC-MS-MS], Anal Bioanal Chem, 382[4]:1084-92, 200526. Dalsenter P, et al., Phthalate affect the reproductive function and sexual behavior of male Wistar rats, Hum Exp Toxicol, 25[6]:297-303, 2006.27. Davis BJ, Maronpot R R, Heindel JJ, Di-[2-ethylhexyl] phthalate suppresses estradiol and ovulation in cycling rats, Toxicol Appl Pharmacol, 128:216223, 1994.28. Swan SH, et al., Decrease in anogenital distance among male infants with prenatal phthalate exposure, Environ Health Perspect, 113[8]:1056-61, 2005.29. Coln I, Caro D, Bourdony CJ, Rosario O, Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development, Environ Health Perspect 108[9]:895-900, 2000.30. Latini G, et al., Exposure to Di[2-ethylhexyl]phthalate in humans during pregnancy. A preliminary report, Biol Neonate, 83[1]:22-4, 2003.31. Zhu J, et al., Phthalate esters in human milk: concentration variations over a 6-month postpartum time, Environ Sci Technol, 40[17]:5276-81, 2006.