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Toxicology Final > Metal Toxicology > Flashcards

Metal Toxicology Flashcards

1
Q

What carries the environmental exposure for metals?

A

Air, water, soil, dust, and food

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2
Q

What are sources of occupational exposures?

A

Mining, refining, smelting, processing, pigment production, electroplating, and welding.

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3
Q

What types of metals in occupational exposure?

A

Mn, Cu, Fe, Be, Cr, Pb, and Ni

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4
Q

What are metals that are used in medicinal/ diet/ and dental exposure?

A

Mn: MRI enhancer, Hg: Vaccine Preservatives, and Fe & As.

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5
Q

What is a metal?

A

Electropositive elements with the tendency to lose electrons in chemical reactions.

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6
Q

What is a heavy metal?

A

Usually means the transition elements in the periodic table.

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7
Q

What are the heavy metals?

A

Fe, Cu, Pd, Cd, Hg, Pb, Ag

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8
Q

What is a metalloid?

A

Resembling a metal in at least one amphoteric form and conducting electricity more easily than true nonmetals.

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9
Q

What is an example of a metalloid?

A

Si, As, Se, In

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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.

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11
Q

Chemical forms in metals may change but not what?

A

the basic unit is neither created nor destroyed.

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12
Q

Catalytic function in active centers are seen in organic chemicals or metals?

A

In metals

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13
Q

What is not generally metabolized?

A

Iron

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14
Q

Metals have a long what?

A

biological life and lasting biological effect.

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15
Q

Metals persistently exist where?

A

ecosystem and prolonged exposure pattern.

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16
Q

What is the half life of As?

A

10hours

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17
Q

Toxicokinetics often reflects the total metals, but not what?

A

the specific forms of metals.

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18
Q

What are Lewis Acids?

A

Tendency to donate electron(s), and carry positive charge(s).

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19
Q

What are examples of Lewis Acids?

A

Li+, Mg 2+, Hg 2+, Cd 2+, Pb 2+

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20
Q

What is a Lewis Base?

A

Tendency to accept electrons, and carry negative charges.

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21
Q

What are examples of Lewis Bases?

A

F-, I-, SH-, CN-, RS-, NH3

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22
Q

What is the polarizability of soft acids?

A

High

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23
Q

What is the polarizability of hard acids?

A

Low

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24
Q

What is polarizability of a hard Base?

A

Low

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25
Q

What is the polarizability of a Soft Base?

A

High

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26
Q

What type of bond do hard acids form?

A

ionic

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27
Q

What type of bond does soft acids form?

A

Covalent

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28
Q

What type of bond do hard bases form?

A

ionic

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29
Q

What type of bond do soft bases form?

A

Covalent

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30
Q

Cu+ is a soft acid or soft base?

A

Soft acid

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31
Q

Ag+ is a soft acid or a soft base?

A

a soft acid

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32
Q

Au+ is a soft acid or soft base?

A

Soft acid

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33
Q

Cd 2+ is a soft acid or a soft base?

A

Soft acid

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34
Q

Hg 2+ is a soft acid or a soft base?

A

Soft acid

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35
Q

Hg+ is a soft acid or a soft base?

A

Soft acid

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36
Q

Ti + and Ti 3+ is a soft acid or a soft base?

A

Soft acid

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37
Q

Pb 2+ is a soft acid or a soft base?

A

Soft Acid

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38
Q

Ta and As is a soft acid or a soft base?

A

A soft acid

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39
Q

Te 4+ and Pt 4+ is a soft acid or a soft base?

A

Soft Acid

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40
Q

SH-, RS-,R2S,RSH is a soft acid or a soft base?

A

Soft bases

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41
Q

CN- and SCN- is a soft acid or a soft base?

A

Soft base

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42
Q

C=O is a soft acid or a soft base?

A

Soft base

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43
Q

RS-SeH a soft acid or a soft base?

A

soft base

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44
Q

S^2 is a soft acid or a soft base?

A

Soft base.

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45
Q

What is the mechanism of metal toxicities in vitro?

A

Most metal ions will inhibit almost any enzyme when added at a sufficient amount.

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46
Q

What is the mechanism of metal toxicities in vivo?

A

One can see remarkably selective action even down to cellular and subcellular levels.

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47
Q

Metals are readily able to lose what?

A

electron in outer orbital.

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48
Q

What has high chemical reactivity?

A

Metals.

49
Q

What type of acid/bases are metals?

A

Soft acid

50
Q

What is the catalytic function of metals?

A

Transfer of e- and reusable.

51
Q

Metals retain it’s own identity?

A

Yes, hit and run

52
Q

What is electropositive?

A

Metals

53
Q

What do metals specifically form?

A

Specific complexes or chelates with endogenous ligands.

54
Q

What are potential endogenous ligands?

A

Proteins, vitamins, porphyrins, polyamines, nucleic acids, amino acids, hydroxyl acids, conjugated diketones, hormones.

55
Q

BPb: 10-25ug/dl show what type of symptoms?

A

Impaired learning abilities

56
Q

BPb:35-50ug/dL

(Children), 40-60ug/dL (adults) show what type of signs for mild toxicity?

A

Anemia, peripheral nerve dysfunction

57
Q

BPb:35-50ug/dL

(Children), 40-60ug/dL (adults) show what type of signs for Moderate toxicity?

A

Peripheral nerve dysfunction and reproductive toxicity

58
Q

BPb:>70 ug/dL in children, >100 ug/dL in adults show what type of toxic signs?

A

Severe toxicity: Encephalopathy: seizure and brain hemorrhage and Lead line: blue-black on gingival tissue.

59
Q

What was seen in chimney cleansing workers in Briton and the US?

A

Brain hemorrhages

60
Q

What was seen in rats acutely exposed to high doses of Pb?

A

Diaminobenzidine staining blood cells showed that in control rats the reaction was confined to blood vessels in brain (B)

61
Q

What was seen in the extravascular staining in rats acutely exposed to rats?

A

an extensive extravascular staining in Pb-treated rats

C

62
Q

What does lanthanum lack?

A

ability to penetrate the blood-brain barrier

63
Q

What are the dark strains seen in the endothelial barrier?

A

seen exclusively alongside the inner cerebral capillary in control rats.

64
Q

What does chronic exposure to lead in drinking water for 6 weeks cause?

A

The invasion of lanthanum stains in brain parenchyma outside of the capillary.

65
Q

What occurs in lead poisoning?

A

Anemia

66
Q

Pb covalently binds to what?

A

The enzyme and inhibits its activity

67
Q

Pb inhibits what?

A

The heme biosynthesis.

68
Q

What is the first toxic metalloid for which biochemical mechanism of action has been clearly elucidated?

A

Arsenic

69
Q

Arsenic is the first toxic metalloid for which what?

A

a biochemical mechanism of action has been clearly elucidated.

70
Q

What did studies show in 1940 in respect to As?

A

exposure to trivalent organic arsenic compounds causes an increase in plasma pyruvate levels.

71
Q

What is the mechanism for arsenic?

A

it covalently binds to alpha lipoic acid and its 2-(SH) groups and inactivates pyruvate dehydrogenase.

72
Q

What are two examples that imitate endogenous essential metals?

A

Pb vs Ca and Mn vs Fe

73
Q

What are two examples of metals that imitate endogenous oxyanions?

A

Arsenate vs phosphate and chromate vs sulfate

74
Q

What are examples of metals that imitate endogenous ligands?

A

MeHg vs Methoinine.

75
Q

Imitation of endogenous useful materials often follow what?

A

essential metal pathway

76
Q

Imitation of endogenous useful materials often interfere with what?

A

Essential metal function.

77
Q

What is Arsenic usually present in biological systems as?

A

arsenate

78
Q

What is arsenate?

A

an oxyanion having a structure similar to phosphate.

79
Q

Where is Hexavalent chromium?

A

normal present in biological fluids as chromate.

80
Q

What is an oxyanion resembling a sulfate anion?

A

hexavalent chromium

81
Q

What type of metals are we exposed to environmentally?

A

As, Pb, Mn, Hg, Cd

82
Q

How is ATP synthesized?

A

Synthesized from 3-phosphogluceraldehyde and phosphate through the stable intermediate 1,3-diphosphoglycerate.

83
Q

The substitution of arsenate for phosphate produces what?

A

An unstable acyl arsenate intermediate that rapidly hydrolyzes without ATP.

84
Q

What metal is toxic purified enzymes and DNA, but not to intact cells?

A

Cr(III)

85
Q

What metal is toxic to intact cells, but not to purified enzymes and DNA?

A

Cr(VI)

86
Q

What is Cr(III) toxic to?

A

purified enzymes and DNA, but not intact cells.

87
Q

What is Cr(VI) toxic to?

A

Toxic to intact cells, but not to purified enzymes and DNA.

88
Q

What does Cr(VI) gain entry to?

A

the cell by the anion carrier that transports sulfate across the membrane.

89
Q

What occurs inside the cell to Cr (VI)?

A

It is reduced to Cr(III) form.

90
Q

MeHg-Cysteine complex is structurally very similar to what?

A

to the large neutral amino acid, methionine.

91
Q

MeHg is transported across what?

A

the blood brain barrier by this carrier present in the endothelial membrane.

92
Q

What is interchangeable in Iron regulatory protein-I and aconitase, and Mn-Fe interaction?

A

The active center of IRP1 and aconitase is interchangeable.

93
Q

IRP1 can bind to what?

A

the iron responsible elements (IRE) in some mRNAs.

94
Q

Mn replaces Fe when & where?

A

ACO1 and decreases ATP production.

95
Q

What alters Fe metabolism in IRP1

A

3Fe-4S-Mn

96
Q

Mn exposure induces what?

A

over expression of transferrin receptor.

97
Q

What occurs when Mn exposure induces over expression of transferrin receptor?

A

Leads to cellular overload of Fe.

98
Q

Cd exposure does what?

A

increases metallothionein (MT) biosynthesis.

99
Q

What are examples of metals that induce endogenous proteins or macromolecules?

A

Mn and Cd.

100
Q

Cadmium will accumulate high where?

A

in the liver

101
Q

Where will cadmium damage?

A

will cause severe kidney damage.

102
Q

One cigarette contains what?

A

1-2mg of Cd, 0.1-0.2 mg inhaled

103
Q

What is the absorption of Cd?

A

Oral and Respiratory bioavailability.

104
Q

What is the Oral bioavailability of Cd?

A

5-8%

105
Q

What is the Respiratory bioavailability of Cd?

A

15-30%

106
Q

What is the distribution of Cd?

A

Primary intracellular distribution.

107
Q

Liver is the major storage organ for Cd due to what?

A

an induction of and binding to MT

108
Q

What is the elimination route for Cd?

A

Biliary excretion, also in urine, biological t1/2:10-30 years in human.

109
Q

Describe the MT structure?

A

Primary: single chain and snd/3rd: tightly folded chain.

110
Q

MT soluble cytoplasmic protein does what?

A

stores physiological Zn and Cu.

111
Q

One MT molecule binds how many Cd?

A

7 Cd ions.

112
Q

Cd induces what?

A

metallothionein in liver

113
Q

Transport of Cd-MT complex to where?

A

renal proximal tubular.

114
Q

What complex causes renal damage?

A

Breakdown products of Cd-MT complex

115
Q

Breakdown products of Cd-MT complex cause what?

A

renal damage.

116
Q

What is the general rule of biotransformation?

A

Most of the metal ions are not metabolized, neither bioactivated nor biodeactivated.

117
Q

What are examples of some metals that don’t get bioactivated or biodeactivated?

A

Pb, Cd, Zn.

118
Q

What is the exception of biotransformation?

A

Certain metals undergo metabolism.

119
Q

What metals are the exception to biotransformation?

A

As (De-activation); Hg, MeHg (activation).

Toxicology Final (7 decks)

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