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Norris: The Adrenal Glands 6. Toxicology and Risk Assessment 7.

Organizational and activational effects of estrogenic endocrine disrupting chemicals

Dickerson and Ernest E. Smith: Introduction to the Science of Toxicology 8. Dixon and Clyde F. Martin: Probablistic Risk Assessment 9. Representative EDCs in Animals Giesy, K. Kannan, Alan L.


  • Why this growing concern about endocrine disruption and its relation to some chemicals??
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Blankenship, Paul D. Jones, and J. Guillette, Jr. Kools, Mark P. Gunderson, and Dieldrich S. Vajda and David O. Gross and R. Heath Rauschenberger: Triazines Appendices. Several drugs, cosmetics and pesticides act as the activators and suppressors of this enzyme. This carefully-compiled critical review is expected to increase public awareness regarding the threats resultant of the perturbations of this enzyme and to motivate researchers for further investigation of this field.

J Steroid Biochem Mol Biol. Maternal thyroid hormones are essential for adequate fetal neurodevelopment during the first half of pregnancy. Within the quantifiable range, median was There were no significant associations with other hormones of the thyroid profile or with clinical diagnosis. Environ Res. Ovarian cancer OC is a relatively fatal female reproductive malignancy.

Since the underlying causes are uncertain, it brings us to believe that both genetic and external factors contribute toward development of this lethal disorder. Exposure to endocrine-disrupting chemicals EDCs in the form of occupational usage of pesticides, fungicides, herbicides, plasticizers, cosmetics, and so on is potentially carcinogenic and their ability to cause epigenetic modifications has led us to hypothesize that they may play a catalytic role in OC progression.

In response to synthetic chemicals, animal models have demonstrated disturbances in the development of ovaries and steroid hormonal levels but in humans, more research is required. The present review is an attempt to address the impact of EDCs on the hormonal system and gene methylation levels that may lead to malfunctioning of the ovaries which may consequently develop in the form of cancer.

It can be concluded that endocrine disruptors do have a potential carcinogenicity and their high proportions in human body may cause epigenetic modifications, prompting ovarian surface epithelium to grow in an abnormal manner.

Reprod Sci. A number of pesticides are suspected or proved to act as endocrine disruptor compounds EDCs. In the present survey of the literature, we try to define the main issues to be considered to classify individual pesticides as EDC or not. Recent findings demonstrate that such endocrine-disrupting chemicals, termed "obesogens", can promote adipogenesis and cause weight gain. Animal models and epidemiological studies have shown that an especially sensitive time for exposure is in utero or the neonatal period.

In summarising the actions of obesogens, it is noteworthy that as their structures are mainly lipophilic, their ability to increase fat deposition has the added consequence of increasing the capacity for their own retention. This has the potential for a vicious spiral not only of increasing obesity but also increasing the retention of other lipophilic pollutant chemicals with an even broader range of adverse actions.

This might offer an explanation as to why obesity is an underlying risk factor for so many diseases including cancer. Curr Obes Rep. The prevalence of type-2 diabetes has dramatically increased worldwide during the last few decades. While lifestyle factors sedentariness, noxious food , together with genetic susceptibility, are well-known actors, there is accumulating evidence suggesting that endocrine disrupting chemicals EDCs may also play a pathophysiological role in the occurrence of metabolic diseases. Both experimental and epidemiological evidence support a role for early and chronic exposure to low doses of chemical pollutants with endocrine and metabolic disrupting effects.

Most are present in the food chain and accumulate in the fat mass after absorption. More prospective, longitudinal studies are needed to determine the importance of such environmental risk factors.

Endocrine Disrupting Compounds – Problems and Challenges

C R Biol. Eligible studies were selected from an electronic literature search from the PUBMED database from January to February and associated references in published studies. Data have been grouped according to the studied pollutants in order to synthetize their impact on follicular development and follicular atresia and the molecular pathways involved. Ninety-seven studies appeared to be eligible and were included in the present study, even though few directly address POI.

These effects were found when exposure occured at different times throughout the lifetime from the prenatal to the adult period, possibly due to different mechanisms. The main mechanism seemed to be an increase in atresia of pre-antral follicles. Environmental pollutants are probably a cause of POI. Health officials and the general public must be aware of this environmental effect in order to implement individual and global preventive actions. Environ Health. The safety, including the endocrine disruptive capability, of glyphosate-based herbicides GBHs is a matter of intense debate.

Authors evaluated the estrogenic potential of glyphosate, commercial GBHs and polyethoxylated tallowamine adjuvants present as co-formulants in GBHs. Commercial GBH formulations or their adjuvants alone did not exhibit estrogenic effects in either assay. Food Chem Toxicol. Endocrine disrupting chemicals are ubiquitous chemicals that exhibit endocrine disrupting properties in both humans and animals. Female reproduction is an important process, which is regulated by hormones and is susceptible to the effects of exposure to endocrine disrupting chemicals.

Disruptions in female reproductive functions by endocrine disrupting chemicals may result in subfertility, infertility, improper hormone production, estrous and menstrual cycle abnormalities, anovulation, and early reproductive senescence. This review summarizes the effects of a variety of synthetic endocrine disrupting chemicals during adult life. The chemicals covered in this review are pesticides organochlorines, organophosphates, carbamates, pyrethroids, and triazines , heavy metals arsenic, lead, and mercury , diethylstilbesterol, plasticizer alternatives di- 2-ethylhexyl phthalate and bisphenol A alternatives , 2,3,7,8-tetrachlorodibenzo-p-dioxin, nonylphenol, polychlorinated biphenyls, triclosan, and parabens.

This review focuses on the hypothalamus, pituitary, ovary, and uterus because together they regulate normal female fertility and the onset of reproductive senescence.


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  • Endocrine Disruption?

The literature shows that several endocrine disrupting chemicals have endocrine disrupting abilities in females during adult life, causing fertility abnormalities in both humans and animals. J Endocrinol. Endocrine disrupting chemicals EDCs comprise a group of chemical compounds that have been examined extensively due to the potential harmful effects in the health of human populations. During the past decades, particular focus has been given to the harmful effects of EDCs to the reproductive system. The estimation of human exposure to EDCs can be broadly categorized into occupational and environmental exposure, and has been a major challenge due to the structural diversity of the chemicals that are derived by many different sources at doses below the limit of detection used by conventional methodologies.

Animal and in vitro studies have supported the conclusion that endocrine disrupting chemicals affect the hormone dependent pathways responsible for male and female gonadal development, either through direct interaction with hormone receptors or via epigenetic and cell-cycle regulatory modes of action.

Despite promising discoveries, a causal relationship between the reproductive disorders and exposure to specific toxicants is yet to be established, due to the complexity of the clinical protocols used, the degree of occupational or environmental exposure, the determination of the variables measured and the sample size of the subjects examined. Future studies should focus on a uniform system of examining human populations with regard to the exposure to specific EDCs and the direct effect on the reproductive system.

Environ Toxicol Pharmacol. Urine and serum samples were collected concurrently from participants. Urine was analyzed for levels of specific- and non-specific metabolites of organophosphates OPs , pyrethroids, select herbicides, and fungicides. Serum was analyzed for total and free testosterone. Linear regression analyses revealed significant negative relationships between total testosterone and the herbicide 2,4-dichlorophenoxyacetic acid 2,4-D after controlling for covariates e.

Positive significant associations were found between some OP pesticides and total testosterone. Due to the small sample size and the observational nature of the study, future investigation is needed to confirm our results and to elucidate the biological mechanisms.

Arch Environ Occup Health. Use of pesticides results in indirect effects on human health. We aimed to evaluate implications of toxicological effects of subchronic chlorpyrifos exposure on reproductive function in male rats. Animals were gavaged with 2. An increase in liver weight resulted in reduced sperm counts and sperm motility and an increase in sperm abnormalities. Our results demonstrated that prolonged exposure of CPF induces spermatogenesis damage, possibly through interference with sex hormones and AchE enzyme resulting in reduction of fertility.

Pesticide-Induced Diseases: Endocrine Disruption

Therefore, awareness programs on handling CPF pesticides to enhance safety warrant minimization of its hazards. Environ Sci Pollut Res Int. Linuron is a widely used herbicide; its toxicity on the male reproductive system has been recognized. The current study was designed to explore the molecular mechanism underlying linuron-induced reproductive toxicity.

Tissues from male offspring rats were collected for pathological examination and microarray gene expression profiling. There were evident damages in seminiferous tubules and abnormal morphology in mesenchymal cells in samples from linuron-exposed animals. Microarray analysis indicated that the expressions of testosterone synthesis-associated genes, i. These data indicate that linuron upon entering male offspring body can directly or indirectly interact with the androgen production and function; linuron-induced alteration in genes encoding testosterone synthesis is likely a major factor in linuron-induced male reproductive toxicity.

Animal studies suggest that exposure to pesticides may alter thyroid function; however, few epidemiologic studies have examined this association. Study evaluated the relationship between individual pesticides and thyroid function in men enrolled in a substudy of the Agricultural Health Study, a cohort of licensed pesticide applicators. Self-reported lifetime pesticide use was obtained at cohort enrolment Intensity-weighted lifetime days were computed for 33 pesticides, which adjusts cumulative days of pesticide use for factors that modify exposure eg, use of personal protective equipment.

Sufficient evidence existed in the scientific literature to identify 34 of these 95 chemicals as potential EDCs, including biogenic and synthetic hormones, pharmaceuticals, and personal care products. The fact that we detect EDCs in the environment alone does not indicate that they are an environmental health concern. Although detection is an important component of environmental assessment, controlled studies of the toxicological effects of the levels and mixtures of EDCs that we find in environmental settings are essential. EDCs are stressors with the potential to impact the reproductive potential or behavioral responses of animals and to increase the susceptibility of populations to significant deterioration.

These effects can include:.

Some of these responses are reversible if exposure is eliminated, but other anatomical, physiological and genetic alterations are permanent. There is compelling evidence that endocrine systems of certain fish and wildlife have been affected by exposure to EDCs in the environment. The exposure to EDCs and indicators of endocrine disruption such as intersex, the presence of female characteristics in males or male characteristics in females has been documented together in the same places in fish species across the Nation and in many countries across the world, including the United Kingdom, Denmark, South Africa, Germany and more.

A national USGS study of sex hormones and intersex biomarkers in common carp in the mids indicated the potential for widespread endocrine disruption in fish and the need for more detailed cause-and-effect studies Goodbred et al. Fish are highly susceptible to endocrine disruption because they can live in waters with sustained levels of EDCs.

Conclusive demonstration of the cause and effect relation between exposure to EDCs and endocrine disruption in the environment has remained elusive until recently. Recent studies have demonstrated conclusively that EDC levels in the environment have the potential to severely impact a fish population.

Kidd et al. USGS studies in Boulder Creek, Colorado, demonstrated significantly different indicators of endocrine disruption in fish populations upstream and downstream of a low head dam, which separates upstream waters minimally affected by development from downstream waters enriched in wastewater effluent Vajda et al. Investigations of fish health in the Potomac River were initiated in in response to recurring fish kills and high incidence of fish lesions. Since then, the USGS and the FWS have identified high levels of intersex in bass and have recently identified evidence that endocrine disruption may contribute to impaired immune response and increased susceptibility to other stressors Blazer et al.

We are continuing to explore whether a linkage exists between EDCs and these fish kills and lesions. Studies into the effects of EDCs on wildlife examined a wide range of species in many environments and locations, including river otters in Oregon; alligators and panthers in Florida; barn swallows in the lower Mississippi River, Louisiana; reptiles in Arizona; polar bears and eiders in Alaska; sturgeon along the middle Mississippi River in Illinois, Missouri, and Iowa; mussels and paddlefish in Ohio; common loons in Maine; terns and cormorants in New York; cormorants in Michigan; and amphibians in Texas.

All of these investigations involved wildlife and habitat sampling to determine how animals were being exposed to EDCs and provided suggested management actions to alleviate the documented impacts from these toxic compounds. In , the FWS began investigating the potential reproductive effects of EDCs on wildlife with studies on the endangered Florida panther and polar bears and their prey. To date, the FWS has funded and participated in 23 studies that specifically looked at the effects of EDCs on wildlife across the country.

Many of these studies have been directly associated with endangered species recovery actions or threats to the recovery of listed species. These studies typically included management recommendations for the removal of threats from contaminants or other corrective actions to alleviate the impacts of EDCs on wildlife. Exposure to certain EDCs results in a variety of adverse reproductive effects in wildlife. Alterations in the differentiation, growth and function of wildlife reproductive organs can result from perinatal and neonatal exposure to EDCs. Examples of effects include smaller than normal sexual organs in male alligators, ambiguous gonads in amphibians and altered sex behavior in birds Fry, ; Guillette, LJ, et al.

Results from the preliminary river otter study correlated concentrations of known EDCs with observed underdevelopment of juvenile male reproductive organs. In an expanded study, Grove found significant inverse relationships between EDC concentrations in the liver and size and mass of reproductive organs.

Two Sisters on a Mission.

Some of these changes appear to be carried into adulthood as a permanent effect. If the EDC-related reduction in testes size found in juvenile male river otters is permanent, then fertility could potentially be reduced as well. Regional differences existed in river otter contaminant body burdens, with otters from heavily populated and industrialized regions, as well as from areas of intensive agriculture, having significantly higher liver concentrations of many contaminants.

While focusing on the environmental effects of EDCs, we understand that information that we provide on the occurrence of EDCs in drinking water has great value to those evaluating the human health significance of EDCs in the environment. Environmental Protection Agency EPA to provide additional information on these chemicals in drinking water.

Similarly, effects studies conducted on animals may also contribute to an understanding of the potential impacts on human health. Growing public awareness has prompted significant public interest regarding potential adverse health effects and actions they can take to mitigate release of these chemicals to the environment. As a result, pharmaceutical take-back programs are emerging across the country to reduce the amount of unused drugs that are flushed down toilets to our streams. Furthermore, industries are inquiring about the treatment technologies and best management practices that are most effective at removing trace organic chemicals from surface and ground waters and solid and liquid wastes Phillips et al.

Information that we can provide on the comparative performance of alternative treatment technologies enables industries to invest resources wisely on a voluntary basis. The FWS has also joined with corporate partners to engage the public in reducing the amount of EDCs in the environment and helping everyone to become a better steward of our environment. In March , a memorandum of understanding was signed to help protect the Nation's fish and wildlife resources from the improper disposal of unwanted medication, some of which are EDCs.

The EPA's Endocrine Disruptor Screening Program EDSP is currently proceeding in three areas: 1 performing scientific and technical testing needed to validate the endocrine disruptor screens and tests; 2 setting priorities for selecting chemicals for initial screening and testing; and 3 developing the policies and procedures the Agency will use to require testing.

USGS researchers are collaborating with EPA to evaluate the effectiveness of a new multigenerational assay protocol in generating data applicable to the EPA's risk assessment modeling and to evaluate the sensitivity of the endpoints currently used for detection of EDC exposure and effect. The USGS is working on providing technical assistance for the National Wildlife Refuge System on total maximum daily loads TMDLs of chemical contaminants, such as those responsible for endocrine disruption in effluent water. This technical assistance will use geospatial information and a risk assessment approach that will enable Refuges to manage water quality and reduce impacts of potential EDCs.

FWS facilities have a regular maintenance schedule and annual facility assessment programs to ensure contaminants are properly disposed of and the facilities remain in an adequate state of repair. In addition, FWS has developed a contaminant assessment database for its National Wildlife Refuges to identify and address threats posed from contamination on refuges and is completing a similar database for its National Fish Hatchery System.