Metal Toxicology Flashcards
1
Q
What carries the environmental exposure for metals?
A
Air, water, soil, dust, and food
2
Q
What are sources of occupational exposures?
A
Mining, refining, smelting, processing, pigment production, electroplating, and welding.
3
Q
What types of metals in occupational exposure?
A
Mn, Cu, Fe, Be, Cr, Pb, and Ni
4
Q
What are metals that are used in medicinal/ diet/ and dental exposure?
A
Mn: MRI enhancer, Hg: Vaccine Preservatives, and Fe & As.
5
Q
What is a metal?
A
Electropositive elements with the tendency to lose electrons in chemical reactions.
6
Q
What is a heavy metal?
A
Usually means the transition elements in the periodic table.
7
Q
What are the heavy metals?
A
Fe, Cu, Pd, Cd, Hg, Pb, Ag
8
Q
What is a metalloid?
A
Resembling a metal in at least one amphoteric form and conducting electricity more easily than true nonmetals.
9
Q
What is an example of a metalloid?
A
Si, As, Se, In
10
Q
What is common to both organics and metals?
A
1) Structural mimicry to essential body constituents.
2) Covalent bonding
3) Free radical formation
4) Bioaccumulation.
11
Q
Chemical forms in metals may change but not what?
A
the basic unit is neither created nor destroyed.
12
Q
Catalytic function in active centers are seen in organic chemicals or metals?
A
In metals
13
Q
What is not generally metabolized?
A
Iron
14
Q
Metals have a long what?
A
biological life and lasting biological effect.
15
Q
Metals persistently exist where?
A
ecosystem and prolonged exposure pattern.
16
Q
What is the half life of As?
A
10hours
17
Q
Toxicokinetics often reflects the total metals, but not what?
A
the specific forms of metals.
18
Q
What are Lewis Acids?
A
Tendency to donate electron(s), and carry positive charge(s).
19
Q
What are examples of Lewis Acids?
A
Li+, Mg 2+, Hg 2+, Cd 2+, Pb 2+
20
Q
What is a Lewis Base?
A
Tendency to accept electrons, and carry negative charges.
21
Q
What are examples of Lewis Bases?
A
F-, I-, SH-, CN-, RS-, NH3
22
Q
What is the polarizability of soft acids?
A
High
23
Q
What is the polarizability of hard acids?
A
Low
24
Q
What is polarizability of a hard Base?
A
Low
25
What is the polarizability of a Soft Base?
High
26
What type of bond do hard acids form?
ionic
27
What type of bond does soft acids form?
Covalent
28
What type of bond do hard bases form?
ionic
29
What type of bond do soft bases form?
Covalent
30
Cu+ is a soft acid or soft base?
Soft acid
31
Ag+ is a soft acid or a soft base?
a soft acid
32
Au+ is a soft acid or soft base?
Soft acid
33
Cd 2+ is a soft acid or a soft base?
Soft acid
34
Hg 2+ is a soft acid or a soft base?
Soft acid
35
Hg+ is a soft acid or a soft base?
Soft acid
36
Ti + and Ti 3+ is a soft acid or a soft base?
Soft acid
37
Pb 2+ is a soft acid or a soft base?
Soft Acid
38
Ta and As is a soft acid or a soft base?
A soft acid
39
Te 4+ and Pt 4+ is a soft acid or a soft base?
Soft Acid
40
SH-, RS-,R2S,RSH is a soft acid or a soft base?
Soft bases
41
CN- and SCN- is a soft acid or a soft base?
Soft base
42
C=O is a soft acid or a soft base?
Soft base
43
RS-SeH a soft acid or a soft base?
soft base
44
S^2 is a soft acid or a soft base?
Soft base.
45
What is the mechanism of metal toxicities in vitro?
Most metal ions will inhibit almost any enzyme when added at a sufficient amount.
46
What is the mechanism of metal toxicities in vivo?
One can see remarkably selective action even down to cellular and subcellular levels.
47
Metals are readily able to lose what?
electron in outer orbital.
48
What has high chemical reactivity?
Metals.
49
What type of acid/bases are metals?
Soft acid
50
What is the catalytic function of metals?
Transfer of e- and reusable.
51
Metals retain it's own identity?
Yes, hit and run
52
What is electropositive?
Metals
53
What do metals specifically form?
Specific complexes or chelates with endogenous ligands.
54
What are potential endogenous ligands?
Proteins, vitamins, porphyrins, polyamines, nucleic acids, amino acids, hydroxyl acids, conjugated diketones, hormones.
55
BPb: 10-25ug/dl show what type of symptoms?
Impaired learning abilities
56
BPb:35-50ug/dL
| (Children), 40-60ug/dL (adults) show what type of signs for mild toxicity?
Anemia, peripheral nerve dysfunction
57
BPb:35-50ug/dL
| (Children), 40-60ug/dL (adults) show what type of signs for Moderate toxicity?
Peripheral nerve dysfunction and reproductive toxicity
58
BPb:>70 ug/dL in children, >100 ug/dL in adults show what type of toxic signs?
Severe toxicity: Encephalopathy: seizure and brain hemorrhage and Lead line: blue-black on gingival tissue.
59
What was seen in chimney cleansing workers in Briton and the US?
Brain hemorrhages
60
What was seen in rats acutely exposed to high doses of Pb?
Diaminobenzidine staining blood cells showed that in control rats the reaction was confined to blood vessels in brain (B)
61
What was seen in the extravascular staining in rats acutely exposed to rats?
an extensive extravascular staining in Pb-treated rats
| C
62
What does lanthanum lack?
ability to penetrate the blood-brain barrier
63
What are the dark strains seen in the endothelial barrier?
seen exclusively alongside the inner cerebral capillary in control rats.
64
What does chronic exposure to lead in drinking water for 6 weeks cause?
The invasion of lanthanum stains in brain parenchyma outside of the capillary.
65
What occurs in lead poisoning?
Anemia
66
Pb covalently binds to what?
The enzyme and inhibits its activity
67
Pb inhibits what?
The heme biosynthesis.
68
What is the first toxic metalloid for which biochemical mechanism of action has been clearly elucidated?
Arsenic
69
Arsenic is the first toxic metalloid for which what?
a biochemical mechanism of action has been clearly elucidated.
70
What did studies show in 1940 in respect to As?
exposure to trivalent organic arsenic compounds causes an increase in plasma pyruvate levels.
71
What is the mechanism for arsenic?
it covalently binds to alpha lipoic acid and its 2-(SH) groups and inactivates pyruvate dehydrogenase.
72
What are two examples that imitate endogenous essential metals?
Pb vs Ca and Mn vs Fe
73
What are two examples of metals that imitate endogenous oxyanions?
Arsenate vs phosphate and chromate vs sulfate
74
What are examples of metals that imitate endogenous ligands?
MeHg vs Methoinine.
75
Imitation of endogenous useful materials often follow what?
essential metal pathway
76
Imitation of endogenous useful materials often interfere with what?
Essential metal function.
77
What is Arsenic usually present in biological systems as?
arsenate
78
What is arsenate?
an oxyanion having a structure similar to phosphate.
79
Where is Hexavalent chromium?
normal present in biological fluids as chromate.
80
What is an oxyanion resembling a sulfate anion?
hexavalent chromium
81
What type of metals are we exposed to environmentally?
As, Pb, Mn, Hg, Cd
82
How is ATP synthesized?
Synthesized from 3-phosphogluceraldehyde and phosphate through the stable intermediate 1,3-diphosphoglycerate.
83
The substitution of arsenate for phosphate produces what?
An unstable acyl arsenate intermediate that rapidly hydrolyzes without ATP.
84
What metal is toxic purified enzymes and DNA, but not to intact cells?
Cr(III)
85
What metal is toxic to intact cells, but not to purified enzymes and DNA?
Cr(VI)
86
What is Cr(III) toxic to?
purified enzymes and DNA, but not intact cells.
87
What is Cr(VI) toxic to?
Toxic to intact cells, but not to purified enzymes and DNA.
88
What does Cr(VI) gain entry to?
the cell by the anion carrier that transports sulfate across the membrane.
89
What occurs inside the cell to Cr (VI)?
It is reduced to Cr(III) form.
90
MeHg-Cysteine complex is structurally very similar to what?
to the large neutral amino acid, methionine.
91
MeHg is transported across what?
the blood brain barrier by this carrier present in the endothelial membrane.
92
What is interchangeable in Iron regulatory protein-I and aconitase, and Mn-Fe interaction?
The active center of IRP1 and aconitase is interchangeable.
93
IRP1 can bind to what?
the iron responsible elements (IRE) in some mRNAs.
94
Mn replaces Fe when & where?
ACO1 and decreases ATP production.
95
What alters Fe metabolism in IRP1
3Fe-4S-Mn
96
Mn exposure induces what?
over expression of transferrin receptor.
97
What occurs when Mn exposure induces over expression of transferrin receptor?
Leads to cellular overload of Fe.
98
Cd exposure does what?
increases metallothionein (MT) biosynthesis.
99
What are examples of metals that induce endogenous proteins or macromolecules?
Mn and Cd.
100
Cadmium will accumulate high where?
in the liver
101
Where will cadmium damage?
will cause severe kidney damage.
102
One cigarette contains what?
1-2mg of Cd, 0.1-0.2 mg inhaled
103
What is the absorption of Cd?
Oral and Respiratory bioavailability.
104
What is the Oral bioavailability of Cd?
5-8%
105
What is the Respiratory bioavailability of Cd?
15-30%
106
What is the distribution of Cd?
Primary intracellular distribution.
107
Liver is the major storage organ for Cd due to what?
an induction of and binding to MT
108
What is the elimination route for Cd?
Biliary excretion, also in urine, biological t1/2:10-30 years in human.
109
Describe the MT structure?
Primary: single chain and snd/3rd: tightly folded chain.
110
MT soluble cytoplasmic protein does what?
stores physiological Zn and Cu.
111
One MT molecule binds how many Cd?
7 Cd ions.
112
Cd induces what?
metallothionein in liver
113
Transport of Cd-MT complex to where?
renal proximal tubular.
114
What complex causes renal damage?
Breakdown products of Cd-MT complex
115
Breakdown products of Cd-MT complex cause what?
renal damage.
116
What is the general rule of biotransformation?
Most of the metal ions are not metabolized, neither bioactivated nor biodeactivated.
117
What are examples of some metals that don't get bioactivated or biodeactivated?
Pb, Cd, Zn.
118
What is the exception of biotransformation?
Certain metals undergo metabolism.
119
What metals are the exception to biotransformation?
As (De-activation); Hg, MeHg (activation).
