Target Organ Toxicology - Final exam practice

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PFAS – exposure, adverse health effects and mechanisms of toxicity.

1. Exposure to PFAS.

a) Who are at risk of PFAS poisoning?

b) Which is the main route of PFAS exposure in humans and why?

c) Describe the ADME properties of PFAS

2. PFAS exposure may cause several adverse health effects.

a) Name three of the main target organs or organ systems for PFAS.

b) State the level of evidence regarding the target organs/organ systems (from 2a) for humans and animals, respectively, and describe the properties of these organs/organ systems that make them targets for adverse effects of PFAS.

c) Is there a unifying principle for adverse effects of PFAS in different target organs? If so, describe such principle.

d) Describe and compare the adverse health effects of acute intoxication (single exposure) versus chronic intoxication (repeated exposure) of PFAS.

3. Toxicity mechanisms.

For two of the target organs stated in 2a, give a detailed description of one adverse effect of PFAS in each organ and one mechanism of action mediating this effect (known or suggested). The mechanisms should include a chain of molecular, cellular and tissue-level events, be clearly connected to the adverse effect at an organ level, and to an adverse outcome at an individual level. Potential gaps in the chain of events should be discussed.

Clarification. Per target organ: 1 adverse effect and 1 mechanism. OBS, the mechanisms must differ from each other.

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1.
a) Human living near facilities manufacturing fluoropolymer, occupationally exposed workers and chirldren are at risk of PFAS poisoning (1, p3-4).
b) 
The main route of PFAS exposure are food and water ingestion, dust ingestion. This is because PFAS with low volatility is very stable and hard to break down, they can migrate from paper packaging and wrapping into food and accumulate in soil and water (1, p3).
c)
Absorption:
PFAS can be absorbed efficiently through oral exposure according to animal data, also can be absorbed via inhaltaion and dermal exposure (1, p559-563). 
Distribution:
PFAS distributed preferentially in liver, kidneys, and blood (1, p565-569). PFAS binds to proteins like albumin in blood (1, p564). PFAS can reach fetus and nursing infants (1, p575).
Metabolism:
PFAS are not metabolized in the body and remain chemically unchanged regardless of the exposure route (1, p578-579).
Excretion:
Elimination rates are not affected obviously by absorption route (1, p579). PFAS elminate mainly via urine, with smaller amounts through feces and breast milk, and maybe accelerated by menstruation in younger women (1, p579, p603). Biliary excretion of PFAS is inefficient due to biliary reasorption (1, p580). Elimination rate vary based on sex, age, type of PFAS, chain length and branching (1, p582-585). In human, half-life of PFAS range from hours to years (1, p582-585).

2.
a) Liver, Reproductive system and Immune system (1, p30-31)
b) 


Reference list
1. ATSDR report on PFAS, 2021