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Section B
Toxicokinetics and Predicting Risk Factors
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Sources of Lead
! Paint
- Paint chips fall to the ground and children place them in their
mouths; incorrectly referred to as pica (Latin for magpie)
! Gasoline
- Fumes fall to the ground and children eat soil
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Hand-to-Mouth
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Other Sources of Lead
! Drinking water (pipes)
! Paint
! Toys
! Occupation
! Floor dust
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Lead Toxicokinetics
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Factors Affecting Toxicokinetics
! Calcium (Ca) decreases lead absorption
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Milk Decreases Lead Absorption
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Demands for Ca Increase in Pregnancy and Lactation
Great chance for Pb
transfer to fetus/
nursing child
! Schematic illustration contrasting calcium homeostasis in human pregnancy and
lactation, as compared to normal. The thickness of arrows indicates a relative
increase or decrease with respect to the normal and non-pregnant state. Although
not illustrated, the serum (total) calcium is decreased during pregnancy, while the
ionized calcium remains normal during both pregnancy and lactation.
Source: Retrieved from http://www.endotext.org/pregnancy/pregnancy3/pregnancy3.htm
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Now the Problem ...
! Bone loss spills lead back into the blood
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Iron Deficiency Increases Internal Lead Burden
MORE INTESTINAL
IRON TRANSPORT
MORE INTESTINAL
Pb
TRANSPORT
(if iron is not
available)
Cognitive. Anemia.
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Pregnancy and Iron Absorption
Weeks of pregnancy
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Pregnancy: A Risk Factor
! Mother’s nutritional status changes—increases amount of Pb
absorbed, even though external exposure has not changed
! Great demand for iron
! Bone remodeling causes dumping of Pb into the blood
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Influences on the Transfer of Pb to the Fetus
Lead exposure pathway from mother to infant, using Mexico as an example
(adapted from Chuang et al. [60]).
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Brain Development
! Brain development composed for several processes occurring at different lengths of
time after fertilization. Brain regions develop at different periods of fetal
development.
! Why rodents might not be the best model to study xenobiotics
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In What Year Were Your Parents Born?
! Though students were raised with little Pb in their environment, exposure might have
nonetheless occurred
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Risk Factors for Lead Poisoning
! Nutrition—calcium- and iron-poor diets
- Intestinal transport through iron and calcium transporters
- Pregnancy increases amount of Pb absorbed even though
external exposure has not changed
- Pb hides in the bone
! Age
! Genetic polymorphisms
- ALAD2 allele for the 2-2 or 1-2 isozyme phenotype had median
blood lead levels 9 to 11 micrograms/dL greater than similarly
exposed individuals who were homozygous for the ALAD1 allele
—possible binding
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