Developmental Toxicity Flashcards
Development is characterized by 5 things
- size
- biochemistry
- physiology
- form
- functionality
developmental toxicology is the study of 5 things
- developmental exposure
- pharmacokinetics - how exposure affects via metabolism
- mechanisms
- pathogenesis - how the disease affects tissue
- outcomes related to adult effects
teratology is the study of
congenital abnormalities and abnormal formations
Wilson’s Principles of Teratology: 1. Susceptibility to teratogenesis depends on the genotype of the conceptus and a manner in which this interacts with adverse environmental factor
genetics interact with the fetal environment
Wilson’s Principles of Teratology: 2. Susceptibility to teratogensis varies with the developmental stage at the time of exposure to an adverse influence
time of exposure is very important in determine type and incidence of malformation
Wilson’s Principles of Teratology: 3. Teratogenic agents act in specific ways (mechanism) on developing cells and tissues to initiate sequences of abnormal developmental events (pathogenesis)
specific teratogenic agents produce distinctive malformation patterns
Wilson’s Principles of Teratology: 4. The access of adverse influences to developing tissues depends on the nature of the influence
the developmental toxicant must access the target
Wilson’s Principles of Teratology: 5. Four manifestations of deviant development are death, malformation, growth retardation and functional deficit
manifestations of developmental toxicity include death, malformation, growth retardation and functional deficit
a single toxicant may cause several effects by different mechanisms
Wilson’s Principles of Teratology: 6. Manifestations of deviant development increase in frequency and degree as dosage increases, from no-effect to the totally lethal level
there is a threshold below which there is no fetal damage
dose-response differed from other forms of toxicity
mechanism: cellular - level events that initiate the process leading to
abnormal development
mutations, chromosomal breaks, altered mitosis, altered uncle acids, decreased energy supplies
pathogenesis: compress the cell, tissue or organ level that ultimately manifest in
abnormality
thalidomide was used for
sleep aid and morning sickness
Malformations from Thalidomide
severe limb defects
absence of ears, deafness,
who wouldn’t approve thalidomide through the FDA?
Dr. France Kelsey
maternal factors affecting development (6 of them)
1 genetics 2 diseases 3 nutrition 4 stress 5 placental toxicity 6 maternal toxicity
Diethylstilbestrol, why was it used?
synthetic non steroidal estrogen to prevent miscarriage
theory of critical window
exposure outside the critical window will not affect structure
some of the windows of susceptibility: fertilization
some of the windows of susceptibility:
some of the windows of susceptibility: bastocyst
death
some of the windows of susceptibility: gastrulation
malformation of the eye, brain and face, malformation of neural plate
some of the windows of susceptibility: morphogenesis
acquisition of position and shape
some of the windows of susceptibility: organogensis
creation of organs and structures
some of the windows of susceptibility: fetal period / body growth
- Miniature structures
- Further differentiate organs and tissues
- Neuronal differentiation
some of the windows of susceptibility: juvenile development
Infertility, breast cancer
• Changes in secondary sex characteristics and sex hormones
some of the windows of susceptibility: nervous system development
- Spans gastrulation THROUGH late adolescence
* Disruption is usually undetected until adolescence
epidemiological events
dutch famine
dioxin exposure
baker hypothesis says that if a fetus is faced with limited nutritional resources it will
adopt metabolic chances to enhance postnatal success in anticipated every
results in long-term permeant changes
predictive adaptive response
model, developmental trajectory taken by an organism during a period of developmental plasticity in response to perceived environmental cues
ethanol
FAS
craniofacial dysmorphism
growth retardation
heart murmur
tobacco smoke
leading cause of environmental induced development disease and morbidity spontaneous abortion perinatal deaths SIDS low brith weight risk of obesity hypertension
cocaine
premature labor and delivery altered prosencphalic development decreased birthweight poor feedings irritability SIDS seizures
Retinoid
excess vit a
malformation of face, limbs, heart, CNS and skeleton
Valproic Acid
anti epileptic drugs
causes spina bifida
3 parts of modern safely assessment
- lab animal testing
- surveillance of human population
- alert clinical awareness
reproductive epidemiology is the study of associates between
specific exposures of the father or pregnant mother and the fetus and outcome of the pregnancy
Paternal Factors can effect
birth defects, spontaneous abortions, childhood cancers, onset diseases
what are things that the father can do that will affect fetus
drugs, radiation, enivormental chemicals, diet
can test what of the fathers?
sperm quality and characteristics
sperm quality
