Class 6 Flashcards
What is regulatory toxicology?
Regulatory toxicology assesses the risk a drug or chemical poses to human health based on toxicity testing, which includes mechanistic and descriptive studies. It establishes safe exposure standards and guidelines.
Define the blood-brain barrier (BBB).
The BBB is a selective membrane that protects the brain from potentially harmful substances while allowing essential nutrients to pass through. It’s formed by brain capillary endothelial cells, pericytes, and astrocytic endfeet, making up the neurovascular unit (NVU).
How do substances cross the BBB?
Substances can cross the BBB through various methods, including paracellular diffusion, transcellular passive diffusion, carrier-mediated transcytosis, adsorptive-mediated transcytosis, and receptor-mediated transcytosis.
What role do efflux transporters play in the BBB?
Efflux transporters protect the brain by pumping various molecules out of brain cells or across the cell membranes of the BCECs that form the BBB back into the bloodstream, e.g., p-glycoprotein.
Efflux transporters are like the body’s bouncers at the cell’s exit doors. Their job is to pick up stuff inside the cell that shouldn’t be there—like waste, toxins, or even some medicines—and kick it out.
What is neurotoxicity testing?
Neurotoxicity testing evaluates whether a chemical can induce neurotoxicity, using both in vitro and in vivo methods to assess changes in behavior, neurochemistry, neurophysiology, and neuropathology.
What are heavy metals?
Heavy metals are naturally occurring elements with a high atomic weight, found throughout the Earth’s crust. Some are essential nutrients (e.g., copper, iron, zinc), while others (e.g., lead, mercury, arsenic) have no known biological function and can be toxic.
How are humans exposed to heavy metals?
Exposure to heavy metals can come from natural sources (e.g., soil erosion, volcanic eruptions) and human activities (e.g., industrial processes, agriculture, domestic use).
Describe the toxicokinetics of lead.
Lead is absorbed into the body via oral, inhalation, and dermal routes, accumulating in bones and tissues. It crosses the BBB potentially through transporters like DMT1 and ATP-dependent calcium pumps, with its half-life in blood being 30 days and in bones 30 years.
What are the neurotoxic effects of lead exposure?
Lead exposure can result in cognitive impairments, executive function and attention deficits, and increased aggression. It interferes with calcium signaling pathways, affecting neurotransmitter release and myelination.
What are early symptoms of lead exposure in children?
Early symptoms include lethargy, abdominal cramps, irritability, headache, and in severe cases, encephalopathy and hallucinations.
What role does regulatory toxicology play in preventing neurotoxicity?
Regulatory toxicology assesses risks to human health from chemicals, establishes safety levels, and implements guidelines for safe exposure to prevent neurotoxicity.
Describe the ADME process for lead in the body.
Lead is absorbed (primarily through oral and inhalation routes), distributed to organs like bones and blood, cannot be metabolized (accumulates over time), and is excreted very slowly, primarily through urine and feces.
Besides the BBB, name another protective barrier in the brain.
The blood-CSF barrier, which controls the movement of substances between the blood and the cerebrospinal fluid (CSF), is another critical protective barrier.
What are behavioral indicators of neurotoxicity?
Indicators include alterations in motor activity, changes in sensations (touch, sight, sound), and impairments in learning, memory, and attention.
What is Developmental Neurotoxicity (DNT), and why is it important?
DNT refers to adverse effects on the development of nervous system structures and functions due to exposure to toxic substances, highlighting the vulnerability of the developing brain to environmental toxins.
What is the significance of NOELS and NOAELS in the context of neurotoxicity studies?
NOELS (No Observed Effect Levels) and NOAELS (No Observed Adverse Effect Levels) are determined during toxicity testing to identify doses of substances that do not cause observable toxic effects, providing a basis for establishing safety standards.
Explain how paracellular diffusion and transcellular diffusion differ in the context of crossing the Blood-Brain Barrier.
Paracellular diffusion involves the passage of substances between endothelial cells, while transcellular diffusion involves the movement through the cells themselves, impacting how various substances can cross the BBB.
How does the body’s deficiency in nutrients like calcium and iron influence lead’s ability to enter the brain?
A deficiency in calcium or iron can increase the expression of transporters such as ATP-dependent calcium pumps and DMT1, respectively, enhancing lead’s ability to cross the BBB and enter the brain.
What are the main sources of environmental exposure to lead?
Environmental exposure to lead primarily comes from industrial emissions, contaminated water due to lead pipes, lead-based paints, and lead-acid batteries.
What role do efflux transporters play in protecting the brain from neurotoxic substances?
Efflux transporters, such as p-glycoprotein, pump various molecules out of brain cells or across the endothelial cell membranes of the BBB back into the bloodstream, thereby helping to protect the brain from neurotoxic substances.
Describe the impact of lead exposure on executive function and attention in children
Lead exposure has been associated with impairments in executive function and attention, evidenced by increased rates of arrest and aggressive behaviors in populations with higher blood lead levels.
