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Toxicology Final > Part 2 reproductive Tox > Flashcards

Part 2 reproductive Tox Flashcards

1
Q

What are the markers of physiologic damage for the Seminal Sperm tissue?

A

Sperm number, structure, motility, viability, agglutination, penetration, and egg interaction.

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2
Q

What are non reproductive tract fluids?

A

Blood, urine, saliva, and cerebrospinal fluid.

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3
Q

What is significant in temporal fluctuations?

A

blood

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4
Q

What is good for cumulative exposure?

A

Urine

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5
Q

What is an ultrafiltrate of plasma?

A

Saliva

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6
Q

What is limited by blood CSF/Brain barrier?

A

CSF

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7
Q

What shows the status of sperm/accessory organs?

A

Semen

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8
Q

What is cycle Specific and bacteria?

A

Vaginal Secretions

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9
Q

What 3 reproductive fluids are cycle-specific?

A

Cervical Secretions, Uterinel Luminal fluid, and tubal secretions.

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10
Q

What is only in stimulated cycles?

A

Follicular fluid

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11
Q

What is limited by autolysis?

A

Menstrual cycle.

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12
Q

What are the markers of physiologic damage of the testes tissue?

A

Histopathology

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13
Q

What are the markers of physiologic damage of seminal sperm?

A

Sperm number, structure, Motility, Viability, Agglutination, penetration, and egg interaction.

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14
Q

What are the markers of physiologic damage of other seminal parameters?

A

Physical characteristics, immature germ cells, chemical composition.

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15
Q

What are the seminal parameters of the chemical composition of sperm?

A

Normal and toxic materials, sertoli cells, leydig cells, and accessory glands.

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16
Q

What are the markers of physiologic damage of blood?

A

Hormone Levels

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17
Q

What are markers of physiologic damage for mother’s urine?

A

early pregnancy.

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18
Q

What are markers of genetic damage for testes (biopsy)?

A

Cytogenetic analyses of cells in mitosis and meiosis I, and II.

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19
Q

What are markers of genetic damage for Sperm?

A

Sperm cytogenetics, Sperm DNA and protein adducts, gene mutation, and sperm aneuploidy.

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20
Q

What are markers of genetic damage of Immature germ cells?

A

Spermatid Micronuclei

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21
Q

What are the markers of genetic damage for offspring tissue?

A

Cytogenetics, DNA sequencing, Protein mutations, Restriction-Length DNA polymorphism, RNAse digestion…

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22
Q

What are markers of genetic damage for mother’s urine?

A

Detection of early fetal loss.

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23
Q

What are potential markers for CNS?

A

Neurotransmitters.

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24
Q

What are potential markers for the pituitary?

A

LH, FSH,Prolactin, TSH, and growth hormone.

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25
What are potential markers for steroids?
Estradiol, estrone, progesterone, testosterone, androstenedione.
26
What are potential markers for regulatory factors?
Relaxin, Prolactin, plasminogen activator, inhibinm oocyte maturation inhibitor, luteinization inhibitor.
27
What are potential markers for the fallopian tube?
Secretory proteins
28
What are the potential markers for the uterus?
Prolactin, Prostaglandins.
29
What are potential markers for the cervix?
mucus.
30
What are potential markers for the vagina?
Secretory proteins
31
What are the guideline for biomarkers in reproductive tox in regards to laboratory animals and humans?
Baseline values established.
32
Sensitivity and Specificity is a guideline for what?
biomarkers in reproductive toxicology.
33
What are the 4 factors that influence the toxicity of gonadotoxicants?
1) Pharmacokinetics/Toxicokinetics. 2) Biotransformation 3) Repair Mechanism 4) Alcohol and Drug Abuse.
34
What are the pharmacokinetic/toxicokinetic considerations for absorption route?
Oral, Inhaling, dermal, vaginal.
35
What are the pharmacokinetic/toxicokinetic considerations for absorption Ka?
Low-dose, Long-term exposure.
36
What are the pharmacokinetic/toxicokinetic considerations for distribution property?
Lipophilicity
37
What are the pharmacokinetic/toxicokinetic considerations for Distribution binding?
Tissue vs Plasma protein binding.
38
What are the pharmacokinetic/toxicokinetic considerations for distribution barriers?
Blood-testis, blood-brain, blood placental.
39
What are the pharmacokinetic/toxicokinetic considerations for distribution Vb?
Medium to large Vb
40
What are the pharmacokinetic/toxicokinetic considerations for metabolism Detoxification?
Phase II conjugation and endogenous protective molecules.
41
What are the pharmacokinetic/toxicokinetic considerations for metabolism bioactivation?
P450 system and epoxidase.
42
What are the pharmacokinetic/toxicokinetic considerations for Elimination T (1/2)?
Reflects metabolism and excretion.
43
What are the pharmacokinetic/toxicokinetic considerations for elimination clearance (CLs)?
Hepatic, renal, and placental.
44
What occurs to absorption in regards to pharmacokinetic changes during pregnancy?
Increased Ventilation, peripheral blood flow. Increased GI residence time Decreased in GI motility
45
What occurs to Distribution in regards to pharmacokinetic changes during pregnancy?
Increased cardiac output, plasma, and water volume. Increased in body fat. Decrease in Plasma proteins.
46
What occurs to Metabolism in regards to pharmacokinetic changes during pregnancy?
Placental and Hepatic
47
What occurs to Excretion in regards to pharmacokinetic changes during pregnancy?
Increased ventilation, renal blood flow, filtration rate. Increased maternal-placenta-fetus exchange Increased flow to uterus, placenta, fetal volume. changes in pH gradient.
48
In pregnant women what occurs to Vb and Vd?
Blood volume increases and Vd increases.
49
In pregnant women what occurs to tissue volume and vd?
Vt increases and Vd increases
50
In pregnant women ________ plasma protein binding leads to a _____ free fraction of chemical in blood.
Low, high
51
What is Fb and Vd in low plasma protein binding leads to a high free fraction of chemical in blood?
increase in Fb and Increase in Vd
52
In Valproic acid what is important to know in regards to Cmax and AUC?
Cmax is much more important that AUC for the valproic acid.
53
What is the toxicity relevant to peak concentration?
Cmax
54
What is the toxicity relevant to total exposure?
AUC
55
What type of toxicants that the Cmax is more important than AUC?
Valproic Acid and Caffeine
56
What type of toxicants that the AUC is more important than Cmax?
Cyclophosphamide, Retinoic acid, 2-methoxyacetic acid.
57
VCH can metabolize through what?
P450 enzyme
58
VCD effects the size of the ovary how?
It shrinks it/makes it smaller.
59
Where is VCH mainly metabolized?
In the liver
60
How does VCH get to the ovaries?
It's metabolites are transported to ovaries and cause the damage.
61
What is DNA repair mechanism?
Induce unscheduled DNA synthesis to repair damaged DNA
62
What is the mechanism of protein replacement?
Increase protein production to replace the destroyed proteins.
63
The use of illicit drugs by pregnant women may do what?
disrupt placental metabolism and exacerbate the effects of smoking.
64
What uses lead that can lead to reproductive toxicity?
Construction material, alloys, pigments, batteries, plastics, electronic devices, etc...
65
What is the gonadtoxicity in lead for males?
Reduced sperm count, compromised sperm motility, altered sperm morphology.
66
What is the gonadtoxicity for lead induced toxicity in females?
Luteolysis, inhibition of implantation.
67
What is the mechanism of gonadotoxicity?
Act on spermatogenesis processes, impair leydig cells, directly damage reproductive tract.
68
What types usages are there for TCDD induced reproductive toxicity?
A contaminant in herbicides (DDT) Extremely toxic with LD50s of 0.022 and 0.045mg/kg for male and female rats, respectively.
69
What is the gonadotoxicity in males for the TCDD induced reproductive toxicity?
Decrease testis weight and spermatogenesis, cause abnormal testicular morphology.
70
What is the gonadotoxicity in females in regards to TCDD reproductive toxicity for females?
Reproduce fertility, alter menstrual cycle, and cause inability to conceive and carry a pregnancy.
71
What is the general mechanism for gonadotoxicity for TCDD?
Inhibit testosterone biosynthesis and two antiestrogenic action.
72
What is the first antiestrogenic action?
antagonize estrogen effect in target organs ( by a decrease in estrogen receptor number)
73
What is the second antiestrogenic action?
Accelerate the metabolism of steroids ( by inducing P-450 in liver and target cells).
74
What were the observation on ovary in regard to TCDD treatments?
Ovary was much smaller.
75
What is an indication of sexual dysfunction?
Decreased libido; impotence.
76
What is an indicator of sperm abnormalities?
Decreased number and motility; abnormal morphology
77
What is an indicator of sub fecundity dysfunction?
Abnormal gonads, ducts of external genitalia: abnormal pubertal development; infertility of male or female origin; amenorrhea;anovulatory cycles;delay in conception.
78
What is an indicator for dysfunction in illness during pregnancy and parturition?
toxemial hemorrhage.
79
Early fetal loss to 28 weeks is an indicator of what?
possible reproductive dysfunction
80
Late fetal loss after 28 weeks and still birth is an indicator of what?
a possible reproductive dysfunction.
81
Intrapartum death/death in first week is an indicator of what?
possible reproductive dysfunction.
82
What are markers of physiologic damage for the testes?
histopathology

Toxicology Final (7 decks)

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