ERHS 502 fundamentals of toxicology
final exam questions & answers 2024
thalidomide (use, MOA, effect) - ANSWERSused to treat morning sickness
creates oxidising (low GSH) environment that suppresses transcription factor NF-KB that you need to
turn on genes for growth (not able to reduce S-SG to bind to DNA with the free thiol) ---> NECROSIS
limb bud formation disrupted - imb atresia, regression /stunted vessels (malformed limbs)
note: need high GSH (reducing) environment to proliferate
(L21: developmental tox)
define developmental toxicity (how expressed, targets, mechanisms) - ANSWERSany
structural/functional alteration caused by enviro insult which interferes with homeostasis, normal
growth, differentiation, development, behavior
expressed as death of cells, structural malformations, functional deficits, developmental delays
targets fertilized egg/zygote, embryo during organogenesis, fetus in post-embryonic period of
histogenesis
mechanisms: mutations, chromosomal breaks, altered mitosis, altered nuclear integrity/function,
decreased energy supply
(L21: developmental tox)
,Karnofsky's law - ANSWERSany toxicant given to the right species at sufficient dose can cause embryonic
development disturbances (threshold effect, timing is crucial to chronicity)
(L21: developmental tox)
why is the embryo so vulnerable? - ANSWERS1. consists of undifferentiated cells with minimal detox and
repair mechanisms
2. normal differentiation requires proper spatial and temporal sequencing
3. sensitive cells to insults unique to cell movement, induction, or differentiation
4. absent/underdeveloped immune system to recognize self vs bad
**** organogenesis occurs in 1st trimester therefore very sensitive then to toxins
(L21: developmental tox)
retinoic acid (MOA, effect) - ANSWERSderivatives of retinol (including retinoic acid) bind to retinoid
receptors and control cell differentiation in many embryonic epithelial tissues preventing metaplasia
isotretinon (a retinoic acid) causes structural craniofacial abnormalities and head and limb effects
(L21: developmental tox)
diethylstilbesterol, DES (use, MOA, effects) - ANSWERSsynthetic non-steroidal estrogen used to prevent
miscarage
MOA: endocrine disruption
effects: genital tract abnormalities in offspring, 1st trimester exposure leads to daughters getting vaginal
clear cell carcinoma, sons get ependymal cysts and hypotrophic testes
, (L21: developmental tox)
cyclophosphamide (use, MOA, toxic agent, effect) - ANSWERSanti-neoplastic drug (chemotherapy),
nitrogen mustard in chemical warfare
MOA: produces single-strand breaks in DNA and DNA protein cross links (DNA adduct former) leading to
enhanced APOPTOSIS from p53 activation recruiting Bax
acrolein = toxic metabolite
effects: hydrocephaly, cleft palate, micrognathia, neural tube defects
(L21: developmental tox)
valproic acid (use, MOA, effect) - ANSWERSanticonvulsant
changes distribution of serotonin producing 5HT positive cells, loss of TH+ neurons, etiology uncertain
leads to spina bifida yelomeningocele (backbone/spinal canal dont close before birth, surgical repair
recommended)
(L21: developmental tox)
ethanol in fetus (MOA, effect) - ANSWERSMOA: neural tube closure phase of development affected with
mitochondrial dysfunction and oxidative stress with ROS (inhibits migration during the necessary time)
leading to fetal alcohol syndrome --- craniofacial dysmorphism (eye distance, cleft lip),
intrauterine/postnatal growth retardation, decreased IQ
