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Section C: Bone Marrow Cellular
Structure
and Hematopoiesis
Hematopoiesis
Š Divided into lymphopoiesis and
myelopoiesis( myeloid cells)
Š Involves the development and
differentiation of various blood and
immune cell populations originating from a
common stem cell.
Š The development and differentiation of
blood cells is controlled by a spectrum of
cytokines and colony stimulating factors
derived from the stromal cell population
Bone Marrow
Hematopoiesis
Lymphopoiesis
Myelopoiesis
Section D: Relationship between
Benzene Biotransformation and
Toxicity
NORMAL
BONE MARROW
GENETIC
DAMAGE
APLASTIC
ANEMIA
(ABNORMAL)
REPAIR (?)
CLONAL
PROLIFERATION
LEUKEMIA
Possible pathways relating benzene exposure to
acute myelogenous leukemia (after Kekule, 1865)
Benzene: Phase I & II Biotransformation
Benzene: Phase I & II Biotransformation
A Tale of Two Organs
Hydroquinone Toxicokinetics
HYDROQUINONE
BENZOQUINONE
Quinone
Reductase
(QR)
GSH
HYDROQUINONE
MACROMOLECULAR
INTERACTIONS
CONJUGATION
SULFATE
GLUCURONIDES
BQ-GSH CONJUGATE
Bone Marrow Macrophages,
Fibroblastoid Stromal Cells
61
HEPATIC
CYP2E1
BONE MARROW
GSH AND QR
HIGH
LOW
HIGH
HIGH
LOW
LOW
LOW
HIGH
SUSCEPTIBILITY
TO BENZENE
HEMATOXICITY
Year
Guideline
1941
1947
1948
1957
1963
1969
1971
1974
1987
1989
1995
100 ppm (8-hr TWA)
50 ppm (8-hr TWA)
35 ppm (8-hr TWA)
25 ppm (8-hr TWA)
25 ppm (ceiling value)
10 ppm (8-hr TWA)
10 ppm (8-hr TWA)
25 ppm (ceiling value)
1 ppm (8-hr TWA)
Proposed 0.1ppm (8-hrTWA)
Proposed 0.3ppm (8-hrTWA)
Source
U.S. DOL
ACGIH
ACGIH
ACGIH
ACGIH
ACGIH
OSHA
OSHA
OSHA
ACGIH
ACGIH
19711995
Recommended occupational exposure limit for benzene
Benzene Exposures and
Theoretical Risk in the U.S.
Activity
Smoking
Passive smoking
Outdoors
Driving car
Filling gas tank
Occupational
Other personal
Drinking water at the
current MCL
Intake
(μg/day)
Cases/Year
1,800
50
120
40
10
10,000
150
10
500
50
150
40
5
10
200
0.01