Endocrine disruptor

Female Sex Hormones Disruptors

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• Humans are exposed to thousands of chemicals used Humans are exposed to thousands of chemicals used in several anthropogenic processes.in several anthropogenic processes.

• Environmental factors that are under the focus of the Environmental factors that are under the focus of the scientific community include organic and chemical scientific community include organic and chemical solvents, pesticides, heavy metals, polychlorinated solvents, pesticides, heavy metals, polychlorinated biphenyls (PCBs) and other persistent organic biphenyls (PCBs) and other persistent organic pollutants (POPs). pollutants (POPs).


Introduction


• Among these agents, special concerns have been raised by endocrine disrupting chemicals (EDCs), which are hormonally active, synthetic or natural compounds that can interfere with the normal activity of endocrine system/tissue, most notably the reproductive endocrine axis.


Introduction


• Epidemiological and experimental studies have demonstrated reproductive alterations as a consequence of intrauterine and/or neonatal exposure to EDC.


Introduction


• Endocrine disruptor is:

An exogenous agent that interferes with synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body which are responsible for the maintenance of homeostasis, reproduction, development and/or behavior.


Definition


• Endocrine disruptors act on the endocrine Endocrine disruptors act on the endocrine system of humans and animals by mimicking, system of humans and animals by mimicking, blocking and/or interfering in some manner blocking and/or interfering in some manner with the natural instructions of hormones to with the natural instructions of hormones to cells.cells.


Mechanism of action


• Binding of EDs to hormone receptors, with resultant alteration in the transcription of messenger RNA, followed by altered gene expression, appears to be one mechanism by which EDs can alter endocrine function.

• Other mechanisms involve alteration in hormone synthesis, metabolism, and transport as well as effects mediated through changes in the hypothalamic–pituitary–gonadal axis.


Mechanism of action


• Chemicals can accumulate in fatty foods (meet, fish, eggs and dairy products)

• Some pesticides that have endocrine-disrupting effects may be present in food and in the home.

• Contaminants in drinking water may have endocrine-disrupting effects.


Routes of exposure to endocrine disruptors


• Occupational exposure to chemicals may put workers and their families at risk .

• Plastic medical and consumer products may leach dangerous chemicals.

• Some communities may suffer disproportionately from chemical

contamination.


Routes of exposure to endocrine disruptors


1.1. Adverse reproductive effects have been observed in male Adverse reproductive effects have been observed in male populations, wildlife, and laboratory animals as a populations, wildlife, and laboratory animals as a

consequence of exposure to hormonally active chemicals.consequence of exposure to hormonally active chemicals.

2.2. Chemicals could play a role in a number of reproductive Chemicals could play a role in a number of reproductive abnormalities in females.abnormalities in females.

3.3. Endocrine disrupting chemicals could be contributing to a Endocrine disrupting chemicals could be contributing to a population-wide decline in fertility.population-wide decline in fertility.


The hazardous effects


4. Exposure to dioxins, toxic byproducts of incineration and industrial processes, may be

associated with fewer male births.

5. Prenatal exposure to some chemicals is associated with deficits in IQ and memory, neurobehavioral

effects, and delayed neuromuscular development in children..




6. Endocrine disruptors may be associated with the development of cancers in hormone-

sensitive tissues.

7. Endocrine disruptors and the obesity epidemic.




A.A.DiethylstilbosterolDiethylstilbosterol (DES).(DES).

B.B.Polychlorinated biphenyls (PCBs).Polychlorinated biphenyls (PCBs).

C.C. Polybrominated biphenyls (PBB).Polybrominated biphenyls (PBB).

D.D.Chloroform.Chloroform.

E.E. Dioxins and furans.Dioxins and furans.

F.F. Pesticides Pesticides


Examples


A. Diethylstilbosterol (DES): Consider one of the most famous endocrine Consider one of the most famous endocrine

disruptors.disruptors. A synthetic estrogen prescribed to pregnant A synthetic estrogen prescribed to pregnant

women in the 1950s and 1960s to prevent women in the 1950s and 1960s to prevent miscarriage. miscarriage.

Ultimately, more than 300 cases of CCA have Ultimately, more than 300 cases of CCA have been documented in women exposed in utero to been documented in women exposed in utero to DES.DES.


Examples


B. Polychlorinated biphenyls (PCBs): Uses:

• paints.paints.• Lubricants.Lubricants.• Wood floor finishes.Wood floor finishes.• Coatings of electrical wiring.Coatings of electrical wiring.• Plastic water and baby bottles, food Plastic water and baby bottles, food

and beverage can linings and dental and beverage can linings and dental sealants ate the most commonly sealants ate the most commonly encountered uses of this chemical.encountered uses of this chemical.


Examples


Hazardous effects:1.1. The The childrenchildren born to these prenatally exposed born to these prenatally exposed

mothers have the following more than unexposed mothers have the following more than unexposed ones:ones:

1. Sperm with abnormal morphology, reduced with abnormal morphology, reduced motility, and reduced strength.motility, and reduced strength.

2.2. Intrauterine growth retardation (Intrauterine growth retardation (IUGRIUGR).).

3.3. Abnormal skin Abnormal skin pigmentationpigmentation..

4.4. Delayed, developmental Delayed, developmental milestonesmilestones..

5.5. Lower Lower (IQs).(IQs).


Examples


2. women2. women who had eaten who had eaten PCB-contaminated fishPCB-contaminated fish from the from the Great Lakes before and during pregnancy documented Great Lakes before and during pregnancy documented dose-related delays in development and dose-related delays in development and reductions in intellect in their infants in the absence of reductions in intellect in their infants in the absence of any overt symptoms.any overt symptoms.


Examples


C. Polybrominated biphenyls (PBB):

• PBBs are used as flame retardants of the brominated flame retardant group. They are added to plastics used in products such as home electrical appliances, textiles, plastic foams etc. to make them difficult to burn.


Examples


perinatal PBB exposure was associated with perinatal PBB exposure was associated with earlier pubertal stage in breastfed girls.earlier pubertal stage in breastfed girls.

Possible mechanisms for the action of PBBs in Possible mechanisms for the action of PBBs in relation to puberty include alteration of relation to puberty include alteration of endocrine feedback loops and alteration of endocrine feedback loops and alteration of circulating hormone levels (Figure 1).circulating hormone levels (Figure 1).


Examples



Examples

Figure 1


D. Chloroform:Uses:

• production of the refrigerant.production of the refrigerant.

• Air conditioning.Air conditioning.


Examples


Hazardous effects:• Rickets.Rickets.

• Induce asthma.Induce asthma.

• incidence of PCO.incidence of PCO.


Examples


E.Dioxins and furans :Uses:

• Animal feed.Animal feed.

• Wood preservation. Wood preservation.

• Dioxins occurs when heating our food in Dioxins occurs when heating our food in the microwave using plastic containers.the microwave using plastic containers.


Examples


Hazardous effects:• High heat and plastics releases dioxins into the High heat and plastics releases dioxins into the

food and ultimately into the cells of the body. food and ultimately into the cells of the body. • Dioxins are carcinogens and highly toxic to the Dioxins are carcinogens and highly toxic to the

cells of our bodies.cells of our bodies.

• Recurrent abortion.Recurrent abortion.• IUGR.IUGR.• IUFD.IUFD.


Examples


Definition.Definition. Routes of exposure.Routes of exposure. Results of exposure.Results of exposure.


F.Pesticides


• Definition:Definition:

Pesticides are ‘substances used to prevent, destroy, repel any pest

ranging from insects, animals and weeds to microorganisms.


Pesticides


• In Egypt, pesticides are typically applied to cotton crops (about10000 to 60000 tons) from

May to September.

• Safety measures are generally poorly applied and workers (12000 workers) lack proper knowledge

or training in safe handling of these chemicals


Pesticides


Routes of exposure:Routes of exposure:

1-1- Oral Exposure. Exposure.

2- 2- Dermal Exposure. Exposure.

3- 3- Inhalation Exposure. Exposure.


Pesticides


Hazardous effects:

• Reproductive effects:Reproductive effects:effects on the reproductive system or on effects on the reproductive system or on the ability to produce healthy offspring. the ability to produce healthy offspring.

• Teratogenic:Teratogenic:Causes birth defects if used it during their Causes birth defects if used it during their

pregnancy . pregnancy .


Pesticides


Hazardous effects:

• Carcinogenic:Carcinogenic:

produces cancer in living animal tissues. produces cancer in living animal tissues.

• Oncogenic effects:Oncogenic effects: tumor-forming effects tumor-forming effects (not necessarily cancerous.)(not necessarily cancerous.)


Pesticides


• Mutagenic effects:Mutagenic effects:is the production of changes in genetic is the production of changes in genetic structure.structure. permanent effects on genetic permanent effects on genetic

material that can be inherited. material that can be inherited.

• Neurotoxicity:Neurotoxicity:poisoning of the nervous system, including poisoning of the nervous system, including

the brain.the brain.


Pesticides


• ImmunosuppressionImmunosuppression::

blocking of natural responses of the blocking of natural responses of the immune system responsible for protecting immune system responsible for protecting

the body.the body.


Pesticides


– The aberrant production of ovarian steroid hormones (progesterone, E2, and androgens) can disrupt normal folliculogenesis.

– It follows that environmental agents and pathogens that mimic the actions of ovarian steroids via the activation of steroid hormone receptors, could disrupt follicle development and/or ovulation.


Effects on the ovary and female reproductive function


– This is of interest because certain endocrine disruptors can function as ER agonists and/or antagonists, depending on the specific ER isoform targeted.




Estrogenic endocrine disruptors:Estrogenic endocrine disruptors: Methoxychlor and HPTE.Methoxychlor and HPTE. Bisphenol ABisphenol A Diethylstilbestrol (DES).Diethylstilbestrol (DES).

Anti-androgenic endocrine disruptors:Anti-androgenic endocrine disruptors: Vinclozolin.Vinclozolin. DDE.DDE.




Estrogenic endocrine disruptors:Estrogenic endocrine disruptors: Methoxychlor and HPTE.Methoxychlor and HPTE. Bisphenol ABisphenol A Diethylstilbestrol (DES).Diethylstilbestrol (DES).




Methoxychlor and HPTEUses ::

Methoxychlor is an organochlorine Methoxychlor is an organochlorine pesticide, , which is currently used as a replacement for which is currently used as a replacement for DDT. DDT.




Methoxychlor and HPTE

Hazardous effects:

• Have weak Have weak estrogenic and and antiandrogenic activities, and these effects are thought to be activities, and these effects are thought to be mediated through the estrogen and androgen mediated through the estrogen and androgen receptors.receptors.




Bisphenol A:Uses:

• Production of epoxy resins(Production of epoxy resins( الصقة الصقة مادة مادةالبالس;;;تيك و البالس;;;تيك للمع;;;ادن و and polycarbonate and polycarbonate ((للمع;;;ادن

plastics in many plastics in many food and drink packaging applications. applications.

• Coating metal products such as food such as food cans, bottle tops and water supply pipes.cans, bottle tops and water supply pipes.

• Dental treatment contain Bisphenol-A. contain Bisphenol-A.• Optical glasses.




Diethylstilbestrol : Uses:

• For the treatment of recurrent miscarriage.For the treatment of recurrent miscarriage.

• In clinical trials and In clinical trials and veterinary prescriptions for the treatment of urinary for the treatment of urinary incontinence in dogs.incontinence in dogs.

• For the treatment of advanced breast and For the treatment of advanced breast and prostate cancer.prostate cancer.




Anti-androgenic endocrineAnti-androgenic endocrine disruptorsdisruptors:: Vinclozolin.Vinclozolin. DDE.DDE.




Vinclozolin:Uses:

• fungicide to control various types of rot to control various types of rot caused by Botrytis spp., Sclerotinia spp, caused by Botrytis spp., Sclerotinia spp, and other types of mold and blight and other types of mold and blight causing organisms, raspberries causing organisms, raspberries ( التوت onions, succulent beans, and turf on ) onions, succulent beans, and turf on (ال;برىال;برىgolf courses, commercial and industrial golf courses, commercial and industrial sites. sites.

• on ornamental plants ( on ornamental plants ( (( الزينة الزينة نباتات ..نباتات




DDE:• Another compound possessing anti-Another compound possessing anti-

androgen activity is the DDT metabolite androgen activity is the DDT metabolite 1,1- dichloro- 2, 2- bis(p- chlorophenyl) 1,1- dichloro- 2, 2- bis(p- chlorophenyl) ethylene.ethylene.




Hazardous effects:• Clear cell adenocarcinoma (CCA) of the Clear cell adenocarcinoma (CCA) of the

vagina and cervix .vagina and cervix .• Irregular uterine bleeding.Irregular uterine bleeding.• Recurrent abortion.Recurrent abortion.• Intrauterine growth retardation.Intrauterine growth retardation.• Abnormalities within the reproductive, Abnormalities within the reproductive,

cardiovascular, neuroendocrine, and cardiovascular, neuroendocrine, and immune systems.immune systems.




• Eat lower on the food chain.Eat lower on the food chain.• Eat Eat deep-water fish (avoid sword fish, tuna

and shark and all farm raised fish)• In general, substitute In general, substitute natural products for products for

synthetic products whenever possible. products whenever possible.• Eat Eat fresh organic products as meat and milk products as meat and milk

free from rBGH (Recombinant Bovine Growth free from rBGH (Recombinant Bovine Growth Hormone).Hormone).

• Buy products at your local Farmers' Market or Buy products at your local Farmers' Market or join a buying club.join a buying club.

• Use Use fewer processed, , prepackaged foods foods whenever possible.whenever possible.


Measures to lower the exposure to endocrine disruptors


• AvoidAvoid smoke. smoke.• AvoidAvoid use chemicals or any pesticides.use chemicals or any pesticides.• AvoidAvoid use makeup, hair sprays & coloring use makeup, hair sprays & coloring

products or nail polish products or nail polish (enjoy your own body (enjoy your own body and not the image that the media says)and not the image that the media says)

• AvoidAvoid use strong chemicals, glues, paints, use strong chemicals, glues, paints, nail polish and remover, floor & carpet nail polish and remover, floor & carpet cleaners.cleaners.

• AvoidAvoid heat food or eat hot food in plastic heat food or eat hot food in plastic containers, even the ones frozen dinners containers, even the ones frozen dinners now come in.now come in.




• AvoidAvoid canned foods unless absolutely a canned foods unless absolutely a must.must.

• AvoidAvoid products with hydrogenated, products with hydrogenated, partially hydrogenated fats and oelestra (a partially hydrogenated fats and oelestra (a synthetic fat substitute).synthetic fat substitute).

• AvoidAvoid stay in places that smell of stay in places that smell of chemicals.chemicals.

• Do notDo not give young children soft plastic give young children soft plastic toys, since these leach potential endocrine toys, since these leach potential endocrine disrupting chemicals.disrupting chemicals.




• Endocrine disruptors (sometimes also referred to as hormonally active agents) are exogenous substances that act like hormones in the endocrine system and disrupt the physiologic function of endogenous hormones.


Conclusions


• Endocrine disrupting compounds encompass a variety of chemical classes, including hormones, plant constituents, pesticides, compounds used in the plastics industry and in consumer products, and other industrial by-products and pollutants.


Conclusions


• Human exposure to pesticides can occur directly from occupational, agricultural and household use, and indirectly through the diet. Significant diet exposure starts early in postnatal life with breastfeeding, as underscored by the evidence that high levels of organochlorine pesticides have been detected in breast milk.


Conclusions


• In epidemiological studies, exposure to pesticides has been associated with menstrual cycle disturbances, reduced fertility, prolonged time-to-pregnancy, spontaneous abortion, stillbirths, and developmental defects.


Conclusions


Endocrine disruptor

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