SlideShare uma empresa Scribd logo
1 de 31



TERATOGENS
ENDOCRINE DISRUPTORS
In addition to genetic mutations that can affect
development, numerous environmental factors
can disrupt development
Abnormalities caused by exogenous
agents are called ‘disruptions’
Agents responsible for these disruptions are
called ‘teratogens’.


Rachel Carlson-1962-DDT- Destroying birds
egg



Lenz-1962- Thalidomide- a sedative drug used
to manage pregnancy- limb and ear
abnormalities in fetus



Rubella infection– 20,000 fetuses- blind deaf or
mentally retarded.
Human development is usually divided into two periods:
1) embryonic, 2) fetal
A teratogen is an agent
that can produce a
permanent alteration of
structure or function in
an organism exposed
during embyronic or fetal
life.
Many agents can
produce a teratogenic
effect under some
circumstances.


Nature of the agent
Dose
Route
Frequency of exposure
Duration of exposure


Gestational timing
Concurrent exposures
Concurrent illness
Genetic susceptibility
– Mother
– Fetus
Cell growth or proliferation
Cell death
Cell migration
Cell and tissue interactions
Disruptions
Principal mechanisms
– Gene mutation
– Chromosomal abnormalies

Before or after conception
Males and females both
affected
Birth Defects Caused
By Teratogenic
Exposures Are
Preventable.
Endocrine Disruptors
Any chemical agent in the environment that can alter
normal endocrine system actions leading to
deleterious effects on an organism or its progeny.
Disruptors may act directly or indirectly.
Direct acting disruptors are usually hormone
agonists or antagonists that interfere with
hormone actions on target cells.
Indirect acting disruptors alter hormone dynamics
in circulation, change hormone metabolism, or
interfere with hormone regulation.
1874

DDT synthesized

1881

PCB synthesized

1930-77 Widespread PCB use in transformers & as cutting oils
1938

DES synthesized

1942-72 Widespread DDT application in malaria control & agriculture
1941-54 FDA & USDA: DES approved for use in humans & animals
1959

DES produces cancer in experimental animals

1962

Publication of Silent Spring by Rachel Carson

1972

EPA bans DDT, FDA warnings on DES in pregnant women

1977

EPA bans PCBs

1979-95 Meetings & publications on estrogens in the environment
1995

EPA endocrine disruptor workshop; NAS/NRC panel meets

1996

Our Stolen Future, Colborn, Dumanoski & Myers, published;
FQPA passed & Safe Drinking Water Act amended

1998

International Conference on Endocrine Disruptors, Kyoto

1999

NRC report, Hormonally Active Agents in the Environment
Known Hormonal Classes
• Proteins & peptides

chemcases.com/olestra/
images/insulin.jpg

• Lipids (steroids, eicosanoids)
• Amino acid derived
(thyronines, neurotransmitters)

chem.pdx.edu/~wamserc/
ChemWorkshops/ gifs/W25_1.gif

• Gases (NO, CO)
website.lineone.net/~dave.cushman/
epinephrine.gif
Hormone Receptors are cellular proteins
that bind with high affinity to hormones &
are altered in shape & function by
binding; they exist in limited numbers.
Binding to hormone is noncovalent &
reversible.
Hormone binding will alter binding to
other cellular proteins & may activate
any receptor protein enzyme actions.
Membrane Receptors
Imbedded in target cell membrane; integral proteins/
glycoproteins; penetrate through membrane
For protein & charged hormones (peptides or
neurotransmitters)
3 major groups: Serpentine = 7 transmembrane
domains, Growth factor/cytokine = 1 transmembrane
domain, Ion channels

Nuclear Receptors
Nuclear proteins that usually act in pairs & bind to
specific Hormone Recognition Elements (HREs) =
sequences on the DNA in the promoter regions of
target genes
For small, hydrophobic molecules (steroids, thyroid
hormones)
Known Classes of Endocrine Disruptors
Estrogens

DES, o,p’-DDT, DEHP, bisphenol A

Anti-estrogens

hexachloro-4-biphenylol, luteolin

Anti-androgens

p,p’-DDE, vinclozolin

Progestogens

norethindrone, norgestrel

Adrenal toxins

o,p’-DDD, glycyrrhizic acid

Thyrotoxic agents

PCBs, goitrin

Aryl hydrocarbons

[often anti-estrogens] TCDD, PAH

Pancreatic toxins

azoxyglycosides, streptozotocin

Metals

cadmium, nickel, aluminum

Retinoids

vitamin A analogs
Endocrine Disruptors Include
Pesticides (herbicides, insecticides, …)
Plasticizers
Natural plant metabolites
Pharmaceuticals (contraceptives, drugs,…)
Detergents
Chemicals from cooking & burning
Antibiotics
Metals
Results of Disruptions
Inability to maintain homeostasis
Altered growth & development
Altered responses to external stimuli
Altered behavior
Suppressed gametogenesis
Elevated gestational losses
Induced neoplasiEmbryonic
malformation
a or carcinogenesis
Hormones & receptors co-evolve. It is common to have
several hormone receptors demonstrate varying affinity for
the same hormone. It is also common for one hormone to
have some affinity for several different receptor types.
Relative Affinities for Receptors of the Insulin Family to Family Members
Receptor

Relative Affinities

Insulin

Insulin >Proinsulin (10%) >IGF II >IGF I
>>Relaxin(~0)

IGF I

IGF I > IGF II >Insulin ~ Proinsulin

IGF II

IGF II = IGF I >>Insulin ~ Proinsulin

Relaxin

Relaxin >NGF >Proinsulin > IGF >>Insulin (~0)

NGF

NGF (only)

Promiscuity often occurs with opioids & steroids. Progestins
can bind glucocorticoid receptors. Clomiphene binds
estrogen receptors & demonstrates mixed anti-estrogenic &
estrogenic actions. Cyproterone acetate is a progestin &
anti-androgen. TCDD is an anti-estrogen & thyroid agonist.
Synthetic enzyme inhibitor
Agonist or antagonist binding to receptor
Alteration of normal dose-response relationships

www.pharmacist.com/images
/estrogen_molecule.gif
17β-Estradiol

www.ac-nantes.fr/peda/
disc/scphy/dochtml/3ieme/ch
ouroug/images/molecule.gif
Diethylstilbesterol
Biologically available (free) hormone
levels vary due to:
Changes in synthesis
Changes in secretion
Changes in degradation
Changes in binding proteins
Age
Gender
Developmental stage
Reproductive status
Stage of temporal rhythm

so…, alterations at any process or
stage changes free hormone levels.
Hormone Transport or Secretion Kinetics
Enterohepatic Metabolism
Feedback loops, Neural controls

users.rcn.com/jkimball.ma.ultranet/Biolog
www.fst.rdg.ac.uk/courses/
yPages/H/hypothalamic_feedback.gif
fs916/lect5/l5b.gif
www.nurse-prescriber.co.uk/
Modified from D.J. Liska, The
Detoxification Enzyme Systems,
www.thorne.com/altmedrev/
fulltext/detox3-3.html.
Human Sperm
Suppression

From the Study of
Scottish Male
Reproductive Health
www.link.med.ed.ac.uk/
HEW/repro/default.htm
Disruption of Sex Determination

Stages
sensitive to
hormonally
active
agents
Diethylstilbestrol
*SAX TOXICITY EVALUATION: THR: Poison by intraperitoneal and subcutaneous
routes. Moderately toxic by ingestion and other routes. A human carcinogen and
teratogen by many routes. It causes skin, liver and lung tumors in exposed
humans as well as uterine and other reproductive system tumors in the female
offspring of exposed women. An experimental carcinogen, neoplastigen,
tumorigen and teratogen by various routes. A transplacental carcinogen.
Glandular system effects by skin contact. Human reproductive effects by
ingestion. Implicated in male impotence and enlargement of male breasts. Other
experimental reproductive effects. Mutagenic data.

Bis (2-ethylhexyl) phthalate
New Jersey Department of Health and Senior Services
Cancer Hazard
* Bis (2-Ethylhexyl) Phthalate may be a CARCINOGEN in humans. It has
been shown to cause liver cancer in animals…
Reproductive Hazard
* Bis (2-Ethylhexyl) Phthalate may be a TERATOGEN in humans since it
has been shown to be a teratogen in animals.
* Bis (2-Ethylhexyl) Phthalate may damage the testes...
Impacts
on Cancer
Rates

www.link.med.ed.ac.uk/
HEW/repro/default.htm

Breast Cancer Risks. Reference group
(R) vs quartiles of dieldrin exposure
(adapted from Høyer et al. 1998 in Our
Stolen Future Website: www.ourstolen
future.org/ Images/graphs/breast%20
cancer%20dieldrin%20risk.jpg). Vertical
bars = 95% confidence interval. Dose
response is significant (p = 0.01).
Endocrine disruptors or hormonally active
agents have been with us for millennia as
elements of plants and cooking. The new
abundance of synthetic compounds has
unleashed a wave of new challenges to our
physiology, including the endocrine system.
The impacts are as pleiotropic as endocrine
actions are. Not surprisingly they involve
altered reproductive success, growth, and
cancer risks because of endocrine controls or
inputs in these processes. Due care will help
minimize impacts, but some increased risks
are here permanently.

Mais conteúdo relacionado

Mais procurados

Molecular basis of fertilization
Molecular basis of fertilizationMolecular basis of fertilization
Molecular basis of fertilizationTeketel23
 
hormonal control of pregnancy
hormonal control of pregnancyhormonal control of pregnancy
hormonal control of pregnancysrijon ghosh
 
HORMONAL REGULATION OF OVULATION,PREGNANCY,PARTURITION
HORMONAL REGULATION OF OVULATION,PREGNANCY,PARTURITIONHORMONAL REGULATION OF OVULATION,PREGNANCY,PARTURITION
HORMONAL REGULATION OF OVULATION,PREGNANCY,PARTURITIONSudarshan Gokhale
 
Structure of human sperm and ovum
Structure of human sperm and ovumStructure of human sperm and ovum
Structure of human sperm and ovumAsif Rozindar
 
Fertilization process
Fertilization processFertilization process
Fertilization processUE
 
In-Vitro Fertilization
In-Vitro FertilizationIn-Vitro Fertilization
In-Vitro FertilizationSonia John
 
Gonadal hormone
Gonadal hormoneGonadal hormone
Gonadal hormoneAtai Rabby
 
Translational Regulation of Development
Translational Regulation of DevelopmentTranslational Regulation of Development
Translational Regulation of DevelopmentSyed Muhammad Khan
 
Placental endocrinology
Placental endocrinologyPlacental endocrinology
Placental endocrinologyjasminthaha
 
Embryonic induction
Embryonic inductionEmbryonic induction
Embryonic inductionNaveen Gul
 
Intracytoplasmic sperm injection(2)
Intracytoplasmic sperm injection(2)Intracytoplasmic sperm injection(2)
Intracytoplasmic sperm injection(2)Mian Numan
 

Mais procurados (20)

Teratogenesis
TeratogenesisTeratogenesis
Teratogenesis
 
Teratogenesis
TeratogenesisTeratogenesis
Teratogenesis
 
Molecular basis of fertilization
Molecular basis of fertilizationMolecular basis of fertilization
Molecular basis of fertilization
 
hormonal control of pregnancy
hormonal control of pregnancyhormonal control of pregnancy
hormonal control of pregnancy
 
HORMONAL REGULATION OF OVULATION,PREGNANCY,PARTURITION
HORMONAL REGULATION OF OVULATION,PREGNANCY,PARTURITIONHORMONAL REGULATION OF OVULATION,PREGNANCY,PARTURITION
HORMONAL REGULATION OF OVULATION,PREGNANCY,PARTURITION
 
Structure of human sperm and ovum
Structure of human sperm and ovumStructure of human sperm and ovum
Structure of human sperm and ovum
 
Fertilization process
Fertilization processFertilization process
Fertilization process
 
Implantation
ImplantationImplantation
Implantation
 
In-Vitro Fertilization
In-Vitro FertilizationIn-Vitro Fertilization
In-Vitro Fertilization
 
Primordial Germ Cells
Primordial Germ CellsPrimordial Germ Cells
Primordial Germ Cells
 
Biological clock
Biological clockBiological clock
Biological clock
 
Development of gonads
Development of gonadsDevelopment of gonads
Development of gonads
 
Fate map
Fate mapFate map
Fate map
 
2. gastrulation
2. gastrulation2. gastrulation
2. gastrulation
 
Gonadal hormone
Gonadal hormoneGonadal hormone
Gonadal hormone
 
Translational Regulation of Development
Translational Regulation of DevelopmentTranslational Regulation of Development
Translational Regulation of Development
 
Placental endocrinology
Placental endocrinologyPlacental endocrinology
Placental endocrinology
 
Embryonic induction
Embryonic inductionEmbryonic induction
Embryonic induction
 
Organogenesis
OrganogenesisOrganogenesis
Organogenesis
 
Intracytoplasmic sperm injection(2)
Intracytoplasmic sperm injection(2)Intracytoplasmic sperm injection(2)
Intracytoplasmic sperm injection(2)
 

Destaque

Nuestro futuro robado. La amenaza de los disruptores endócrinos
Nuestro futuro robado. La amenaza de los disruptores endócrinos Nuestro futuro robado. La amenaza de los disruptores endócrinos
Nuestro futuro robado. La amenaza de los disruptores endócrinos Ramón Copa
 
Endocrine Disruptors by @toxipedia
Endocrine Disruptors by @toxipediaEndocrine Disruptors by @toxipedia
Endocrine Disruptors by @toxipediaDES Daughter
 
Prenatal Development, Birth, and Newborns’ Readiness for Life
Prenatal Development, Birth, and Newborns’ Readiness for LifePrenatal Development, Birth, and Newborns’ Readiness for Life
Prenatal Development, Birth, and Newborns’ Readiness for LifeMark Anthony Castillo
 
ContaminacióN Por Plaguicidas
ContaminacióN Por PlaguicidasContaminacióN Por Plaguicidas
ContaminacióN Por Plaguicidasgaliciabadillo
 
Fetal Alcohol Syndrome
Fetal Alcohol SyndromeFetal Alcohol Syndrome
Fetal Alcohol SyndromeTejas Shah
 
The Toxicology of Personal Care Products & Cosmetics
The Toxicology of Personal Care Products & CosmeticsThe Toxicology of Personal Care Products & Cosmetics
The Toxicology of Personal Care Products & CosmeticsAdrian Tam
 
7 drugs in pregnancy2010
7 drugs in pregnancy20107 drugs in pregnancy2010
7 drugs in pregnancy2010obsgyna
 
Alternatives to animals in toxicity testing
Alternatives to animals in toxicity testingAlternatives to animals in toxicity testing
Alternatives to animals in toxicity testingSandhya Talla
 

Destaque (20)

Endocrine disruptors and DDT
Endocrine disruptors and DDTEndocrine disruptors and DDT
Endocrine disruptors and DDT
 
Zika general presentation 18 feb 2016
Zika general presentation 18 feb 2016Zika general presentation 18 feb 2016
Zika general presentation 18 feb 2016
 
Productos quimicos 2013
Productos quimicos 2013Productos quimicos 2013
Productos quimicos 2013
 
Nuestro futuro robado. La amenaza de los disruptores endócrinos
Nuestro futuro robado. La amenaza de los disruptores endócrinos Nuestro futuro robado. La amenaza de los disruptores endócrinos
Nuestro futuro robado. La amenaza de los disruptores endócrinos
 
Prenatal development
Prenatal developmentPrenatal development
Prenatal development
 
Fetal development
Fetal developmentFetal development
Fetal development
 
Endocrine Disruptors by @toxipedia
Endocrine Disruptors by @toxipediaEndocrine Disruptors by @toxipedia
Endocrine Disruptors by @toxipedia
 
Prenatal Development, Birth, and Newborns’ Readiness for Life
Prenatal Development, Birth, and Newborns’ Readiness for LifePrenatal Development, Birth, and Newborns’ Readiness for Life
Prenatal Development, Birth, and Newborns’ Readiness for Life
 
ContaminacióN Por Plaguicidas
ContaminacióN Por PlaguicidasContaminacióN Por Plaguicidas
ContaminacióN Por Plaguicidas
 
Fetal Alcohol Syndrome
Fetal Alcohol SyndromeFetal Alcohol Syndrome
Fetal Alcohol Syndrome
 
Teratogenic antibiotics
Teratogenic antibioticsTeratogenic antibiotics
Teratogenic antibiotics
 
The Toxicology of Personal Care Products & Cosmetics
The Toxicology of Personal Care Products & CosmeticsThe Toxicology of Personal Care Products & Cosmetics
The Toxicology of Personal Care Products & Cosmetics
 
Mutagens and their actions
Mutagens and their actionsMutagens and their actions
Mutagens and their actions
 
Teratogenesis
TeratogenesisTeratogenesis
Teratogenesis
 
Teratogen Drugs
Teratogen DrugsTeratogen Drugs
Teratogen Drugs
 
Teratogens
TeratogensTeratogens
Teratogens
 
7 drugs in pregnancy2010
7 drugs in pregnancy20107 drugs in pregnancy2010
7 drugs in pregnancy2010
 
Thalidomide
ThalidomideThalidomide
Thalidomide
 
Mutagen
MutagenMutagen
Mutagen
 
Alternatives to animals in toxicity testing
Alternatives to animals in toxicity testingAlternatives to animals in toxicity testing
Alternatives to animals in toxicity testing
 

Semelhante a Teratogens

Endocrine disruptors
Endocrine disruptorsEndocrine disruptors
Endocrine disruptorsAjay Dominic
 
Endocrine disruptor
Endocrine disruptorEndocrine disruptor
Endocrine disruptorraj kumar
 
Prescribing in pregnancy
Prescribing in pregnancyPrescribing in pregnancy
Prescribing in pregnancyYogesh Patel
 
EndocrineDisruptors_Upload.pdf
EndocrineDisruptors_Upload.pdfEndocrineDisruptors_Upload.pdf
EndocrineDisruptors_Upload.pdfSaeYen
 
Drug safety (1)
Drug safety (1)Drug safety (1)
Drug safety (1)drmcbansal
 
Reproductive toxicology
Reproductive toxicologyReproductive toxicology
Reproductive toxicologysyeddastagir9
 
Session 5: How Environmental Toxins are Linked to Metabolic Disorders and Chr...
Session 5: How Environmental Toxins are Linked to Metabolic Disorders and Chr...Session 5: How Environmental Toxins are Linked to Metabolic Disorders and Chr...
Session 5: How Environmental Toxins are Linked to Metabolic Disorders and Chr...Center for Environmental Health
 
Environmental Pollution And Reproductive Health Paper
Environmental Pollution And Reproductive Health  PaperEnvironmental Pollution And Reproductive Health  Paper
Environmental Pollution And Reproductive Health PaperShradha Diwan
 
Informe de riesgos emergentes sobre disruptores endocrinos
Informe de riesgos emergentes sobre disruptores endocrinos Informe de riesgos emergentes sobre disruptores endocrinos
Informe de riesgos emergentes sobre disruptores endocrinos ainia centro tecnológico
 
An introductiontoendocrinology
An introductiontoendocrinologyAn introductiontoendocrinology
An introductiontoendocrinologyAmour Massoud
 
Ask Dr Safety about Reproductive Toxins
Ask Dr Safety about Reproductive ToxinsAsk Dr Safety about Reproductive Toxins
Ask Dr Safety about Reproductive ToxinsDIv CHAS
 
People Safe: The Link Between Declining Fertility & Environmental Contami...
People Safe: The Link Between Declining Fertility & Environmental Contami...People Safe: The Link Between Declining Fertility & Environmental Contami...
People Safe: The Link Between Declining Fertility & Environmental Contami...abowes23
 
Endocrine Disruptors Chemicals
Endocrine Disruptors ChemicalsEndocrine Disruptors Chemicals
Endocrine Disruptors ChemicalsAbeer Ansari
 
LiChing Sheng aresty poster-final
LiChing Sheng aresty poster-finalLiChing Sheng aresty poster-final
LiChing Sheng aresty poster-finalLi Ching Sheng
 
Reproductive Toxicology: History and State of Regulatory Science
Reproductive Toxicology: History and State of Regulatory ScienceReproductive Toxicology: History and State of Regulatory Science
Reproductive Toxicology: History and State of Regulatory ScienceJoseph Holson
 
Molecular basis of aging and longevity
Molecular basis of aging and longevityMolecular basis of aging and longevity
Molecular basis of aging and longevityGualbertoJrLantaya
 
ENDOCRINE_DISRUPTORS.pptx
ENDOCRINE_DISRUPTORS.pptxENDOCRINE_DISRUPTORS.pptx
ENDOCRINE_DISRUPTORS.pptxDavidSutton43
 

Semelhante a Teratogens (20)

Endocrine disruptors
Endocrine disruptorsEndocrine disruptors
Endocrine disruptors
 
Endocrine disruptor
Endocrine disruptorEndocrine disruptor
Endocrine disruptor
 
Prescribing in pregnancy
Prescribing in pregnancyPrescribing in pregnancy
Prescribing in pregnancy
 
EndocrineDisruptors_Upload.pdf
EndocrineDisruptors_Upload.pdfEndocrineDisruptors_Upload.pdf
EndocrineDisruptors_Upload.pdf
 
Drug safety (1)
Drug safety (1)Drug safety (1)
Drug safety (1)
 
Reproductive toxicology
Reproductive toxicologyReproductive toxicology
Reproductive toxicology
 
Session 5: How Environmental Toxins are Linked to Metabolic Disorders and Chr...
Session 5: How Environmental Toxins are Linked to Metabolic Disorders and Chr...Session 5: How Environmental Toxins are Linked to Metabolic Disorders and Chr...
Session 5: How Environmental Toxins are Linked to Metabolic Disorders and Chr...
 
Environmental Pollution And Reproductive Health Paper
Environmental Pollution And Reproductive Health  PaperEnvironmental Pollution And Reproductive Health  Paper
Environmental Pollution And Reproductive Health Paper
 
Informe de riesgos emergentes sobre disruptores endocrinos
Informe de riesgos emergentes sobre disruptores endocrinos Informe de riesgos emergentes sobre disruptores endocrinos
Informe de riesgos emergentes sobre disruptores endocrinos
 
An introductiontoendocrinology
An introductiontoendocrinologyAn introductiontoendocrinology
An introductiontoendocrinology
 
Ask Dr Safety about Reproductive Toxins
Ask Dr Safety about Reproductive ToxinsAsk Dr Safety about Reproductive Toxins
Ask Dr Safety about Reproductive Toxins
 
People Safe: The Link Between Declining Fertility & Environmental Contami...
People Safe: The Link Between Declining Fertility & Environmental Contami...People Safe: The Link Between Declining Fertility & Environmental Contami...
People Safe: The Link Between Declining Fertility & Environmental Contami...
 
Endocrine Disruptors Chemicals
Endocrine Disruptors ChemicalsEndocrine Disruptors Chemicals
Endocrine Disruptors Chemicals
 
LiChing Sheng aresty poster-final
LiChing Sheng aresty poster-finalLiChing Sheng aresty poster-final
LiChing Sheng aresty poster-final
 
Webinar 1 slides 2
Webinar 1 slides 2Webinar 1 slides 2
Webinar 1 slides 2
 
Reproductive Toxicology: History and State of Regulatory Science
Reproductive Toxicology: History and State of Regulatory ScienceReproductive Toxicology: History and State of Regulatory Science
Reproductive Toxicology: History and State of Regulatory Science
 
EDC Michael Hansen
EDC Michael  HansenEDC Michael  Hansen
EDC Michael Hansen
 
Molecular basis of aging and longevity
Molecular basis of aging and longevityMolecular basis of aging and longevity
Molecular basis of aging and longevity
 
Letrozole Final
Letrozole FinalLetrozole Final
Letrozole Final
 
ENDOCRINE_DISRUPTORS.pptx
ENDOCRINE_DISRUPTORS.pptxENDOCRINE_DISRUPTORS.pptx
ENDOCRINE_DISRUPTORS.pptx
 

Último

Housewife Call Girls Hsr Layout - Call 7001305949 Rs-3500 with A/C Room Cash ...
Housewife Call Girls Hsr Layout - Call 7001305949 Rs-3500 with A/C Room Cash ...Housewife Call Girls Hsr Layout - Call 7001305949 Rs-3500 with A/C Room Cash ...
Housewife Call Girls Hsr Layout - Call 7001305949 Rs-3500 with A/C Room Cash ...narwatsonia7
 
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...Miss joya
 
Call Girls Service Nandiambakkam | 7001305949 At Low Cost Cash Payment Booking
Call Girls Service Nandiambakkam | 7001305949 At Low Cost Cash Payment BookingCall Girls Service Nandiambakkam | 7001305949 At Low Cost Cash Payment Booking
Call Girls Service Nandiambakkam | 7001305949 At Low Cost Cash Payment BookingNehru place Escorts
 
Call Girls In Andheri East Call 9920874524 Book Hot And Sexy Girls
Call Girls In Andheri East Call 9920874524 Book Hot And Sexy GirlsCall Girls In Andheri East Call 9920874524 Book Hot And Sexy Girls
Call Girls In Andheri East Call 9920874524 Book Hot And Sexy Girlsnehamumbai
 
Glomerular Filtration and determinants of glomerular filtration .pptx
Glomerular Filtration and  determinants of glomerular filtration .pptxGlomerular Filtration and  determinants of glomerular filtration .pptx
Glomerular Filtration and determinants of glomerular filtration .pptxDr.Nusrat Tariq
 
Call Girls Thane Just Call 9910780858 Get High Class Call Girls Service
Call Girls Thane Just Call 9910780858 Get High Class Call Girls ServiceCall Girls Thane Just Call 9910780858 Get High Class Call Girls Service
Call Girls Thane Just Call 9910780858 Get High Class Call Girls Servicesonalikaur4
 
call girls in munirka DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in munirka  DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️call girls in munirka  DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in munirka DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️saminamagar
 
Call Girl Bangalore Nandini 7001305949 Independent Escort Service Bangalore
Call Girl Bangalore Nandini 7001305949 Independent Escort Service BangaloreCall Girl Bangalore Nandini 7001305949 Independent Escort Service Bangalore
Call Girl Bangalore Nandini 7001305949 Independent Escort Service Bangalorenarwatsonia7
 
Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...
Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...
Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...narwatsonia7
 
Call Girls Jp Nagar Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Jp Nagar Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Jp Nagar Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Jp Nagar Just Call 7001305949 Top Class Call Girl Service Availablenarwatsonia7
 
Glomerular Filtration rate and its determinants.pptx
Glomerular Filtration rate and its determinants.pptxGlomerular Filtration rate and its determinants.pptx
Glomerular Filtration rate and its determinants.pptxDr.Nusrat Tariq
 
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Availablenarwatsonia7
 
Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...
Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...
Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...Miss joya
 
Ahmedabad Call Girls CG Road 🔝9907093804 Short 1500 💋 Night 6000
Ahmedabad Call Girls CG Road 🔝9907093804  Short 1500  💋 Night 6000Ahmedabad Call Girls CG Road 🔝9907093804  Short 1500  💋 Night 6000
Ahmedabad Call Girls CG Road 🔝9907093804 Short 1500 💋 Night 6000aliya bhat
 
Dwarka Sector 6 Call Girls ( 9873940964 ) Book Hot And Sexy Girls In A Few Cl...
Dwarka Sector 6 Call Girls ( 9873940964 ) Book Hot And Sexy Girls In A Few Cl...Dwarka Sector 6 Call Girls ( 9873940964 ) Book Hot And Sexy Girls In A Few Cl...
Dwarka Sector 6 Call Girls ( 9873940964 ) Book Hot And Sexy Girls In A Few Cl...rajnisinghkjn
 
Call Girls Service In Shyam Nagar Whatsapp 8445551418 Independent Escort Service
Call Girls Service In Shyam Nagar Whatsapp 8445551418 Independent Escort ServiceCall Girls Service In Shyam Nagar Whatsapp 8445551418 Independent Escort Service
Call Girls Service In Shyam Nagar Whatsapp 8445551418 Independent Escort Serviceparulsinha
 
Call Girls Service in Bommanahalli - 7001305949 with real photos and phone nu...
Call Girls Service in Bommanahalli - 7001305949 with real photos and phone nu...Call Girls Service in Bommanahalli - 7001305949 with real photos and phone nu...
Call Girls Service in Bommanahalli - 7001305949 with real photos and phone nu...narwatsonia7
 
Call Girl Koramangala | 7001305949 At Low Cost Cash Payment Booking
Call Girl Koramangala | 7001305949 At Low Cost Cash Payment BookingCall Girl Koramangala | 7001305949 At Low Cost Cash Payment Booking
Call Girl Koramangala | 7001305949 At Low Cost Cash Payment Bookingnarwatsonia7
 
High Profile Call Girls Jaipur Vani 8445551418 Independent Escort Service Jaipur
High Profile Call Girls Jaipur Vani 8445551418 Independent Escort Service JaipurHigh Profile Call Girls Jaipur Vani 8445551418 Independent Escort Service Jaipur
High Profile Call Girls Jaipur Vani 8445551418 Independent Escort Service Jaipurparulsinha
 
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbai
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service MumbaiLow Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbai
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbaisonalikaur4
 

Último (20)

Housewife Call Girls Hsr Layout - Call 7001305949 Rs-3500 with A/C Room Cash ...
Housewife Call Girls Hsr Layout - Call 7001305949 Rs-3500 with A/C Room Cash ...Housewife Call Girls Hsr Layout - Call 7001305949 Rs-3500 with A/C Room Cash ...
Housewife Call Girls Hsr Layout - Call 7001305949 Rs-3500 with A/C Room Cash ...
 
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...
College Call Girls Pune Mira 9907093804 Short 1500 Night 6000 Best call girls...
 
Call Girls Service Nandiambakkam | 7001305949 At Low Cost Cash Payment Booking
Call Girls Service Nandiambakkam | 7001305949 At Low Cost Cash Payment BookingCall Girls Service Nandiambakkam | 7001305949 At Low Cost Cash Payment Booking
Call Girls Service Nandiambakkam | 7001305949 At Low Cost Cash Payment Booking
 
Call Girls In Andheri East Call 9920874524 Book Hot And Sexy Girls
Call Girls In Andheri East Call 9920874524 Book Hot And Sexy GirlsCall Girls In Andheri East Call 9920874524 Book Hot And Sexy Girls
Call Girls In Andheri East Call 9920874524 Book Hot And Sexy Girls
 
Glomerular Filtration and determinants of glomerular filtration .pptx
Glomerular Filtration and  determinants of glomerular filtration .pptxGlomerular Filtration and  determinants of glomerular filtration .pptx
Glomerular Filtration and determinants of glomerular filtration .pptx
 
Call Girls Thane Just Call 9910780858 Get High Class Call Girls Service
Call Girls Thane Just Call 9910780858 Get High Class Call Girls ServiceCall Girls Thane Just Call 9910780858 Get High Class Call Girls Service
Call Girls Thane Just Call 9910780858 Get High Class Call Girls Service
 
call girls in munirka DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in munirka  DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️call girls in munirka  DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in munirka DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
 
Call Girl Bangalore Nandini 7001305949 Independent Escort Service Bangalore
Call Girl Bangalore Nandini 7001305949 Independent Escort Service BangaloreCall Girl Bangalore Nandini 7001305949 Independent Escort Service Bangalore
Call Girl Bangalore Nandini 7001305949 Independent Escort Service Bangalore
 
Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...
Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...
Russian Call Girls Chickpet - 7001305949 Booking and charges genuine rate for...
 
Call Girls Jp Nagar Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Jp Nagar Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Jp Nagar Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Jp Nagar Just Call 7001305949 Top Class Call Girl Service Available
 
Glomerular Filtration rate and its determinants.pptx
Glomerular Filtration rate and its determinants.pptxGlomerular Filtration rate and its determinants.pptx
Glomerular Filtration rate and its determinants.pptx
 
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Available
 
Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...
Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...
Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...
 
Ahmedabad Call Girls CG Road 🔝9907093804 Short 1500 💋 Night 6000
Ahmedabad Call Girls CG Road 🔝9907093804  Short 1500  💋 Night 6000Ahmedabad Call Girls CG Road 🔝9907093804  Short 1500  💋 Night 6000
Ahmedabad Call Girls CG Road 🔝9907093804 Short 1500 💋 Night 6000
 
Dwarka Sector 6 Call Girls ( 9873940964 ) Book Hot And Sexy Girls In A Few Cl...
Dwarka Sector 6 Call Girls ( 9873940964 ) Book Hot And Sexy Girls In A Few Cl...Dwarka Sector 6 Call Girls ( 9873940964 ) Book Hot And Sexy Girls In A Few Cl...
Dwarka Sector 6 Call Girls ( 9873940964 ) Book Hot And Sexy Girls In A Few Cl...
 
Call Girls Service In Shyam Nagar Whatsapp 8445551418 Independent Escort Service
Call Girls Service In Shyam Nagar Whatsapp 8445551418 Independent Escort ServiceCall Girls Service In Shyam Nagar Whatsapp 8445551418 Independent Escort Service
Call Girls Service In Shyam Nagar Whatsapp 8445551418 Independent Escort Service
 
Call Girls Service in Bommanahalli - 7001305949 with real photos and phone nu...
Call Girls Service in Bommanahalli - 7001305949 with real photos and phone nu...Call Girls Service in Bommanahalli - 7001305949 with real photos and phone nu...
Call Girls Service in Bommanahalli - 7001305949 with real photos and phone nu...
 
Call Girl Koramangala | 7001305949 At Low Cost Cash Payment Booking
Call Girl Koramangala | 7001305949 At Low Cost Cash Payment BookingCall Girl Koramangala | 7001305949 At Low Cost Cash Payment Booking
Call Girl Koramangala | 7001305949 At Low Cost Cash Payment Booking
 
High Profile Call Girls Jaipur Vani 8445551418 Independent Escort Service Jaipur
High Profile Call Girls Jaipur Vani 8445551418 Independent Escort Service JaipurHigh Profile Call Girls Jaipur Vani 8445551418 Independent Escort Service Jaipur
High Profile Call Girls Jaipur Vani 8445551418 Independent Escort Service Jaipur
 
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbai
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service MumbaiLow Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbai
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbai
 

Teratogens

  • 2. In addition to genetic mutations that can affect development, numerous environmental factors can disrupt development Abnormalities caused by exogenous agents are called ‘disruptions’ Agents responsible for these disruptions are called ‘teratogens’.
  • 3.  Rachel Carlson-1962-DDT- Destroying birds egg  Lenz-1962- Thalidomide- a sedative drug used to manage pregnancy- limb and ear abnormalities in fetus  Rubella infection– 20,000 fetuses- blind deaf or mentally retarded.
  • 4. Human development is usually divided into two periods: 1) embryonic, 2) fetal
  • 5. A teratogen is an agent that can produce a permanent alteration of structure or function in an organism exposed during embyronic or fetal life.
  • 6. Many agents can produce a teratogenic effect under some circumstances.
  • 7.  Nature of the agent Dose Route Frequency of exposure Duration of exposure
  • 8.  Gestational timing Concurrent exposures Concurrent illness Genetic susceptibility – Mother – Fetus
  • 9. Cell growth or proliferation Cell death Cell migration Cell and tissue interactions Disruptions
  • 10. Principal mechanisms – Gene mutation – Chromosomal abnormalies Before or after conception Males and females both affected
  • 11. Birth Defects Caused By Teratogenic Exposures Are Preventable.
  • 12.
  • 14. Any chemical agent in the environment that can alter normal endocrine system actions leading to deleterious effects on an organism or its progeny. Disruptors may act directly or indirectly. Direct acting disruptors are usually hormone agonists or antagonists that interfere with hormone actions on target cells. Indirect acting disruptors alter hormone dynamics in circulation, change hormone metabolism, or interfere with hormone regulation.
  • 15. 1874 DDT synthesized 1881 PCB synthesized 1930-77 Widespread PCB use in transformers & as cutting oils 1938 DES synthesized 1942-72 Widespread DDT application in malaria control & agriculture 1941-54 FDA & USDA: DES approved for use in humans & animals 1959 DES produces cancer in experimental animals 1962 Publication of Silent Spring by Rachel Carson 1972 EPA bans DDT, FDA warnings on DES in pregnant women 1977 EPA bans PCBs 1979-95 Meetings & publications on estrogens in the environment 1995 EPA endocrine disruptor workshop; NAS/NRC panel meets 1996 Our Stolen Future, Colborn, Dumanoski & Myers, published; FQPA passed & Safe Drinking Water Act amended 1998 International Conference on Endocrine Disruptors, Kyoto 1999 NRC report, Hormonally Active Agents in the Environment
  • 16. Known Hormonal Classes • Proteins & peptides chemcases.com/olestra/ images/insulin.jpg • Lipids (steroids, eicosanoids) • Amino acid derived (thyronines, neurotransmitters) chem.pdx.edu/~wamserc/ ChemWorkshops/ gifs/W25_1.gif • Gases (NO, CO) website.lineone.net/~dave.cushman/ epinephrine.gif
  • 17. Hormone Receptors are cellular proteins that bind with high affinity to hormones & are altered in shape & function by binding; they exist in limited numbers. Binding to hormone is noncovalent & reversible. Hormone binding will alter binding to other cellular proteins & may activate any receptor protein enzyme actions.
  • 18. Membrane Receptors Imbedded in target cell membrane; integral proteins/ glycoproteins; penetrate through membrane For protein & charged hormones (peptides or neurotransmitters) 3 major groups: Serpentine = 7 transmembrane domains, Growth factor/cytokine = 1 transmembrane domain, Ion channels Nuclear Receptors Nuclear proteins that usually act in pairs & bind to specific Hormone Recognition Elements (HREs) = sequences on the DNA in the promoter regions of target genes For small, hydrophobic molecules (steroids, thyroid hormones)
  • 19. Known Classes of Endocrine Disruptors Estrogens DES, o,p’-DDT, DEHP, bisphenol A Anti-estrogens hexachloro-4-biphenylol, luteolin Anti-androgens p,p’-DDE, vinclozolin Progestogens norethindrone, norgestrel Adrenal toxins o,p’-DDD, glycyrrhizic acid Thyrotoxic agents PCBs, goitrin Aryl hydrocarbons [often anti-estrogens] TCDD, PAH Pancreatic toxins azoxyglycosides, streptozotocin Metals cadmium, nickel, aluminum Retinoids vitamin A analogs
  • 20. Endocrine Disruptors Include Pesticides (herbicides, insecticides, …) Plasticizers Natural plant metabolites Pharmaceuticals (contraceptives, drugs,…) Detergents Chemicals from cooking & burning Antibiotics Metals
  • 21. Results of Disruptions Inability to maintain homeostasis Altered growth & development Altered responses to external stimuli Altered behavior Suppressed gametogenesis Elevated gestational losses Induced neoplasiEmbryonic malformation a or carcinogenesis
  • 22. Hormones & receptors co-evolve. It is common to have several hormone receptors demonstrate varying affinity for the same hormone. It is also common for one hormone to have some affinity for several different receptor types. Relative Affinities for Receptors of the Insulin Family to Family Members Receptor Relative Affinities Insulin Insulin >Proinsulin (10%) >IGF II >IGF I >>Relaxin(~0) IGF I IGF I > IGF II >Insulin ~ Proinsulin IGF II IGF II = IGF I >>Insulin ~ Proinsulin Relaxin Relaxin >NGF >Proinsulin > IGF >>Insulin (~0) NGF NGF (only) Promiscuity often occurs with opioids & steroids. Progestins can bind glucocorticoid receptors. Clomiphene binds estrogen receptors & demonstrates mixed anti-estrogenic & estrogenic actions. Cyproterone acetate is a progestin & anti-androgen. TCDD is an anti-estrogen & thyroid agonist.
  • 23. Synthetic enzyme inhibitor Agonist or antagonist binding to receptor Alteration of normal dose-response relationships www.pharmacist.com/images /estrogen_molecule.gif 17β-Estradiol www.ac-nantes.fr/peda/ disc/scphy/dochtml/3ieme/ch ouroug/images/molecule.gif Diethylstilbesterol
  • 24. Biologically available (free) hormone levels vary due to: Changes in synthesis Changes in secretion Changes in degradation Changes in binding proteins Age Gender Developmental stage Reproductive status Stage of temporal rhythm so…, alterations at any process or stage changes free hormone levels.
  • 25. Hormone Transport or Secretion Kinetics Enterohepatic Metabolism Feedback loops, Neural controls users.rcn.com/jkimball.ma.ultranet/Biolog www.fst.rdg.ac.uk/courses/ yPages/H/hypothalamic_feedback.gif fs916/lect5/l5b.gif www.nurse-prescriber.co.uk/
  • 26. Modified from D.J. Liska, The Detoxification Enzyme Systems, www.thorne.com/altmedrev/ fulltext/detox3-3.html.
  • 27. Human Sperm Suppression From the Study of Scottish Male Reproductive Health www.link.med.ed.ac.uk/ HEW/repro/default.htm
  • 28. Disruption of Sex Determination Stages sensitive to hormonally active agents
  • 29. Diethylstilbestrol *SAX TOXICITY EVALUATION: THR: Poison by intraperitoneal and subcutaneous routes. Moderately toxic by ingestion and other routes. A human carcinogen and teratogen by many routes. It causes skin, liver and lung tumors in exposed humans as well as uterine and other reproductive system tumors in the female offspring of exposed women. An experimental carcinogen, neoplastigen, tumorigen and teratogen by various routes. A transplacental carcinogen. Glandular system effects by skin contact. Human reproductive effects by ingestion. Implicated in male impotence and enlargement of male breasts. Other experimental reproductive effects. Mutagenic data. Bis (2-ethylhexyl) phthalate New Jersey Department of Health and Senior Services Cancer Hazard * Bis (2-Ethylhexyl) Phthalate may be a CARCINOGEN in humans. It has been shown to cause liver cancer in animals… Reproductive Hazard * Bis (2-Ethylhexyl) Phthalate may be a TERATOGEN in humans since it has been shown to be a teratogen in animals. * Bis (2-Ethylhexyl) Phthalate may damage the testes...
  • 30. Impacts on Cancer Rates www.link.med.ed.ac.uk/ HEW/repro/default.htm Breast Cancer Risks. Reference group (R) vs quartiles of dieldrin exposure (adapted from Høyer et al. 1998 in Our Stolen Future Website: www.ourstolen future.org/ Images/graphs/breast%20 cancer%20dieldrin%20risk.jpg). Vertical bars = 95% confidence interval. Dose response is significant (p = 0.01).
  • 31. Endocrine disruptors or hormonally active agents have been with us for millennia as elements of plants and cooking. The new abundance of synthetic compounds has unleashed a wave of new challenges to our physiology, including the endocrine system. The impacts are as pleiotropic as endocrine actions are. Not surprisingly they involve altered reproductive success, growth, and cancer risks because of endocrine controls or inputs in these processes. Due care will help minimize impacts, but some increased risks are here permanently.