HEAVY METAL

POISONING
Metals differ from other toxic substances
in that they are neither created nor
destroyed by humans. Nevertheless, their
utilization by humans influences the
potential for health effects in at least two
major
ways:
first, by environmental transport, that is,
by
human
or
anthropogenic contributions to air, water,
soil, and food, and second, by altering
the speciation or biochemical form
of the
1

COMPLEXATION AND CHELATION

THERAPY
Complexation is the formation of a metal ion complex in
which the metal ion is associated with a charged or
uncharged electron donor, referred to as a ligand.
The ligand may be monodentate, bidentate, or
multidentate; that is, it may attach or coordinate using
one, two or more donor atoms.
Chelating agents (drugs) vary in their specificity for toxic
metals.
Ideal chelating agents should be water-soluble, resistant
to biotransformation, able to reach sites of metal storage,
capable of forming nontoxic complexes with toxic metals,
and of being excreted from the body; they should also
have a low affinity for essential metals, particularly
calcium and zinc.
2

COMPLEXATION AND CHELATION THERAPY

BAL (British Anti-Lewisite)-(2,3-dimercaptopropanol Or
Dimercaprol)
DMPS(2,3-dimercapto-1-propanesulfonic acid)
DMSA(meso-2.3.-dimercaptosuccinic acid; succimer)
EDTA(ethylene diamine tetraacetic acid)
DTPA(diethylenetriaminepentaacetic acid)
Desferrioxamine
Dithiocarbamate (DTC)
Penicillamine and N-Acetylcysteine
Hemodialysis with Chelation

Major metallic toxicants:

Cadmium
Mercury
Magnesium
Lead
Arsenic
3

CADMIUM (Cd)
Physicochemical properties: Cd is a
soft, silver white metal, insoluble in
water, solved in nitric acid. Its vapours
are heavier than the air.
Cd usage and occupational risks: used
in the manufacture of plastics, alkaline
accumulators, production of Cd lamps, Cd
glass, galvanic coating, etc.
Routes of entry:

mainly by inhalation, often - by ingestion

(at wet extraction of Cd). In the organism Cd is mainly bound to the
metallothionein. It accumulates in liver and kidneys, and small parts
4

Cd poisoning
Elimination - mainly by urine and less by
the bile.
Pathogenesis:
Cd is bound to the sulphhydrate, aminoand carboxygroups and breaks the
activity of some enzymes.
Cd irritates directly mucous membranes
Cd has nephrotoxic effect.

ACUTE Cd POISONING
Rarely with occupational origin.
There are two forms:
1. Inhalation form with development of
pulmonary oedema
2. Gastrointestinal form with vomiting, nausea,
gripping pains in the epigastrium, in later
stages dehydration syndrome develops with
hemoconcentration, convulsions, collapses,
toxic hepatitis, hepatorenal syndrome, acute
toxic nephropathy.
6

CHRONIC CD POISONING
Critical organs are lungs and kidneys.
Respiratory system - irritative changes in the
upper respiratory tract, perforation of the nasal
septum, chronic rhinitis, emphysema,
pulmonary fibrosis.
Renal syndrome with proteinuria
Hepatic syndrome - tightness and pains in
the right hypochondrium, hepatomegaly, liver
dysfunctional with increased liver enzymes
Cardiovascular syndrome - mainly functional
disorders, hypertensive effects
Bone syndrome: osteoporosis, osteomalacia
with spontaneous fractures - at long-term
exposure above 20 years
7

STAGES OF CD EFFECTS
1. Cd carriers without subjective symptoms but
with elevated content of Cd in urine
2. Cd effect - irritative changes of the upper
respiratory tract, asthenic vegetative
syndrome, reticulocytosis, golden-yellowish Cd
ring at the base of the teeth - Cd lines,
increased Cd levels in urine
3. Stages Cd intoxication:
mild: gastrointestinal syndrome, proteinuria,
increased Cd levels
moderate: neurasthenic syndrome, gastro- 8

TREATMENT
1. Antidotal therapy
CaNa2EDTA (calcium disodium
versenate)- amp. 10% 10 ml, 1.0 g/daily
during 6 days. A control on urine is performed
concerning albumin and cadmium content in
urine.
D-penicillamin - caps. 250 mg, 2,0 g/daily
for 10 days with control of blood pressure
concerning the number of leucocytes and
thrombocytes
9

WORK ABILITY EXPERTISE

In Cd carriers - hospital treatment, vitamin therapy
When Cd effect is established - antidote therapy is
applied and temporary disability
In Cd intoxication permanent change of work
without contact with Cd or other toxic substances is
necessary.
When structural damages (emphysema, hepatitis,
nephropathy, bone disorders) are diagnosed an
appropriate therapy is applied with permanent change
of work without toxic exposure. The percent loss of
working ability depends on the degree and severity
poisoning and the structural organic damages.
10

MANGANESE (Mn) POISONING

Physicochemical properties. Mn is a grey

metal, oxidized in the air, soluble in acids.
It is easily bound to iron, copper, silicon,
sulphur, phosphorus, etc.
Use and occupational risk. It is used for
the production of ferromanganese, ferrous
steel, etc. Exposed to Mn are workers
producing alloyed steel, welders, those
engaged in non-ferrous metallurgy, mining,
textile, etc.
Route of entry - by inhalation, few amount
by ingestion and through skin.
11

BIOTRANSFORMATION AND
ELIMINATION OF MN
The highest percentage of Mn in blood is in
erythrocytes, tightly bound as Mn porphirine
and in serum it is bound to globulin.
Mn accumulates in liver, brain, kidneys,
hypophysis, hair, retina, dark skin. It passes
through hematoencephalic barrier and
placenta.
Mn is eliminated mainly by the bile and gastrointestinal tract and significantly less by urine.

MECHANISMS OF Mn ACTION
Manganese is a neurotropic
poison. It affects directly the extra
pyramid structures (pallidum,
substantia nigra, corpus striatum)
and causes Parkinson's syndrome.
It shows affinity to the thiol groups
and forms complex compounds
with methionine, cysteine, cystine

CLINICAL FINDINGS

Acute Mn poisoning :
Chronic Mn poisoning - stages:
1. Mn carriers have no subjective
complaints, but only increased
content of Mn in blood and urine
2. Mn effect is characterized with
elevated Mn absorption and asthenic
vegetative syndrome with dystonia.
3. Mn intoxication

Mn INTOXICATION
It is divided in:
a) Early stage commonly with functional disorders
like astheno-vegetative syndrome, autonomic
gastro-intestinal events
b) Stage of microfocal symptoms with
depression syndrome, coordination disorders,
sensory impairments, affection of the pyramid
routes, etc.
c) Advanced stage: Parkinson's syndrome with
increased extra pyramid muscle tone,
hypokinesia and akinesia, aphonic speech and
disarthria, disgraphia, most frequently
micrographia, tremor, hyper salivation,
hyperhydrosis, diencephalic manifistation, etc. 15

DIAGNOSIS
It is based on:
Objective document about occupational contact with
Mn
Increased levels of Mn in biological media (a correlation
relationship between Mn concentrations in the air of
the working environment and its content in urine)
Differential diagnosis
The Mn induced Parkinsonism should be differentiated
from Parkinsons syndromes due to encephalitis,
trauma, drugs, psychotropic medications,
atherosclerosis, toxic agents - CO, Hg, Pb, parathion,
etc.
16

TREATMENT

Etiological (antidote);
-CaNa2EDTA (calcium disodium versenate) 10% 10 ml (1,0 g) by one ampoule daily in 5% of
500 ml Glucose solution i.v. guttatim or in stream
of 20-40 ml 5%, 10% of glucose solution in three
consecutive days;
The manganese excretion in urine is daily
observed. The medication course could be
repeated.
-D-penicillamin (tablets of 250 mg) by 1-2 g/daily
for 5 days
Antiparkinsonic drugs (dopaminergic)
Vitamin therapy (Vit B1, Vit B6, Vit B12, Vit C etc.)
Other symptomatic and supportive drugs
17

WORK ABILITY EXPERTISE

In mild, moderate or severe stages
the contact with Mn must be stopped.
In mild degree the patients are able to
work
In moderate or severe degrees the
work ability is reduced according to the
clinical manifestations.
Parkinson's syndrome induces
completely and permanently lost work
ability.

LEAD
INTOXICATION
Pb - inorganic, dusts and fumes, mist
Tetraethyl lead, Tetramethyl lead
Pb does not serve any useful biologic function in
humans.
Physicochemical properties of Pb: a soft
malleable, blue-gray metal, with high density
and soluble in acid medium.
Pb occur in many ores; it is concentrated through
wet grinding and flotation prior to smelting.
Another source is the removing from lead scrap.
Exposure limits are determined in standards.
19

LEAD
INTOXICATION

Risk occupations: Manufacture of storage batteries,

accumulators and painting production; chemical

and building industry; lead alloys (chiefly with An
and Stannum) in pipes and cable sheathing,
isolder and electrical applications, paints, plastics
as pigment and stabilizer; Pb glazes of ceramics;
in crystal glass; for shielding of radioactivity;
ammunition, bronze, in blast furnace building,
polygraphic, metallurgic, electronic industry, etc.
Tetraethyl and tetramethyl Pb are used as
antiknock agents in gasoline.
20

Occupational and Environmental

Exposure
Inhalation (40%), and ingestion (when eating or
smoking at the working place 5-10%) and through
skin in contact with organic solvents containing Pb
are potential routes of Pb exposure in mining
particulary the more soluble carbonate and sulfate
ores.
Grinding and sintering operation generate high levels of
Pb dust and fumes. Workers engaged in the
reclamation of Pb from secondary sources have
potential exposure to Pb as well as other metal
contaminants.
21

Occupational and Environmental

Exposure
Exposure is a constant hazard in the manufacture of Pb
batteries. Paint and pigment manufacturers are
exposed to Pb additives. Painters may also be
exposed, especially during fine spray-painting
operations. Torch burning to remove Pb-based paints
generates lead fumes. Welders and brazers may be
exposed to Pb alloys fluxes, coatings. Glass-makers,
pottery workers, workers in munitions plants and rifleranges.
Environmental exposure may occur near Pb smelters
due to air, soil, water contamination. From car
exhausts, low-income housing, of tap water from Pb
pipes in old homes.
22

Absorption and Metabolism

Absorption - Inhalation and ingestion are the
primary routes.
Metabolism In the blood stream, the majority of
absorbed Pb is bound to Er. The free diffusible
plasma fraction is distributed to brain, kidney, liver,
skin, skeletal muscles, where it is readily
exchangeable. Bone constitutes the major site of
deposition of absorbed Pb, where it is incorporated
into the bony matrix similar to Ca.
Intracellularly, Pb binds to sulfhydryl groups and
interferes with numerous cellular enzymes, including
those involved in haem synthesis. This binding
accounts for the presence of Pb in hair and nails.
Pb also binds to mitochondrial membranes and
interferes with protein and nucleic acid synthesis.
23

Pb
Biotransformation
Pb accumulates in bones, liver, kidneys,
aorta, etc. During alcohol consumption,
infections the accumulated Pb is
released from the internal organs and
manifests its toxic effect. Pb crosses the
blood-brain barrier and placenta.
Elimination: mainly by urine (75-80%),
less by gastro-intestinal tract (about
15%) and by hairs, nails, sweat (8%).
24

Pb
distribution
and
accumulation
in bones, liver,
kidneys,
aorta, etc.
25

Excretion of Pb
Excretion is slow over time, primary through the
kidney. Fecal excretion, sweat, and epidermal
exfoliation are other routes. The half-life of Pb is
long, estimated 5 - 10 years.
Tetraethyl and tetramethyl Pb are converted
to the trialkyl metabolites that are responsible
for toxicity. The fat solubility of this compounds
is responsible for the accumulation in central
nervous system. Alkyl Pb compounds are
ultimately converted to inorganic Pb and are
excreted in the urine.
26

Pathogenesis
Anaemia develops - acquired
sideroblastic, hypochromic,
hypersideremic.
directly affects Erithrocytes,
destroying there structures and
forms, shortening there life

27

CLINICAL FINDINGS

Asthenic vegetative syndrome functional disorders of the autonimc

nervous system
Gastrointestinal syndrome - loss of
appetite, metal taste, dyskinesia,
nausea and development of lead
colic, constipation, arterial
hypertension, bradycardia, umbilical
pain.
28

CLINICAL FINDINGS
Hepatic syndrome (functional
disorders of different degree up to the
development of toxic hepatitis - the
transition to cirrhosis is rarely met.)
Encephalo-polyneurotic syndrome
(paresis and paralysis, positive
symptom of weakness of upper
limbs).

29

CLINICAL FINDINGS

Eye disorders
Blood syndrome (sideroblastic anaemia,
reticulocytosis, increased number of
basophile stippled erythrocytes).
Cardio-vascular syndrome
(bradycardia, hypotonia, early
atherosclerosis with myocardial disorders)
Stigmata of Pb intoxication: typical
distinct Pb line in the gum a grey blue
pigmentation of the gum especially near
carious teeth; Pb face with pale grey
colour as a result of skin vessels spasm)
30

STAGES OF LEAD POISONING

1. Lead carriers - preclinical stage without complaints,
but gum changes, higher Pb content in blood and
urine, increased daily urine content of lead.
2. Lead effect asthenic vegetative and blood
syndrome.
3. Mild degree - blood syndrome, gastro-intestinal
syndrome dyskinesia of the biliary and intestinal
tracts, spastic colitis, functional liver disorders, and
no lead colic.
4. Moderate degree - blood syndrome, toxic hepatitis,
gastro-intestinal disorders including lead colic, Pb
polyneuropathy.
5. Severe degree Pb encephalopathy - epilepsy,
toxic hepatitis, gastro-intestinal - lead colic, motor
form of polyneuropathy, anemia
31

DIAGNOSIS

Occupational risk with lead exposure

Laboratory constellation with increased
content of Pb in blood and urine,
reticulocytosis, increased number of
basophilic stippled erythrocytes.

32

Essentials of Diagnosis
Inorganic Pb- acute effects:
Abnormal pain (collic)
Encephalopathy
Hemolysis
Acute renal failure

33

Essentials of Diagnosis
Inorganic Pb- chronic effects:
Anemia
Peripheral neuropathy (Nerve conduction studies
may reveal delayed motor conduction velocities
even without overt peripheral neuropathy )
Fatigue and asthenia
Arthralgias and myalgias
Neurobehavioral disorders and chronic
encephalopathy
Gout and gouty nephropathy
Chronic renal failure Proximal renal injury may
result in aminoaciduria, glucosuria, phosphaturia,
hyperuricemia.
Liver involvement may be suggested by mild
34
elevations of serum aminotransferases.

Alkyl lead compounds:

Fatigue
Headache
Nausea and vomiting
Neuropsychiatric complaints
(memory loss, difficulty in
concentrating)
Delirium, seizures, coma
35

Laboratory findings
Anemia is a frequent manifestation.
It is usually normochromatic. Normal Felevels in sera.
Increased red cells turnover and frank
hemolysis
present, with basophilic stippling of
the Er and reticulocytosis.

36

Laboratory findings
Blood lead levels are an indication of recent
exposure (days or weeks).
The current standard requires that Pb levels
be maintained < 40g/dL
Altered haem synthesis, evidenced by an
increase in protoporphyrin measured
as either free erythrocyte protoporphyrin
(FEP) begins when blood Pb levels exceed
40 g/ dL.
The enzyme Delta-aminolevulinic acid
dehydratese (delta-ALAD) is inhibited by Pb
and Delta-aminolevulinic acid is
37
increased the urine test.

Laboratory findings
Measurement of chelatable Pb may
assist in the diagnosis;
CaNa2 EDTA (Calcium disodium versenate)
Pbmobilization test is an indication of the
total body burden and, when abnormally
high, suggests that chelation therapy should
be initiated.
A 24-hour urine (using the proper acidwashed polypropylene bottles) is collected
for Pb before and after i.v. giving a CaNa2
EDTA dose of 30 mg/kg body weight.;
infusion over 1h in 250 mL of 20% dextrose.
38

Medical examination of lead - exposed

workers
1. Medical and occupational history (focusing on Pb
exposure history)
2. Physical examination (focusing on gums,
gastrointestinal, hematologic, renal, reproductive
problems.
3. Blood pressure measurement
4. Blood testing: Blood lead level; Protoporphyrin;
Haemoglobin; Hematocrit; Peripheral smear;
Serum iron; Serum creatinine; ASAT; ALAT; Deltaaminolevulinic acid in urine
5. Neurological examination (focusing on
neurological problems)
39
6. Psychological tests

TREATMENT
The first step is removal from exposure.
The decision about whether chelation
therapy.
Symptomatic therapy
1.Etiological (Antidote)
CaNa2EDTA - 10% of 10 ml amp in serum or
glucose solution by 1,0 g daily i. v. during
three consecutive days. This course may be
repeated two times with three days break if
the Pb exposure is high.In the administration
of therapy with CaNa2EDTA the following is
observed: content of iron, zinc, copper in
urine, possible presence of proteinuria.

TREATMENT
Succimer (chemet) caps. 350 mg - 2,1 g/daily at equal
administrations per 8 hours during 5 days, after that the
dose is reduced to 1,4 e/daily, Therapy course - 7 to
10 days (at lower degree of lead exposure). It is
obligatorily to determine the level
D-penicillamin (Cuprenil) tabl. 250 mg, 2,0 g daily in
four applications. Therapy course - 7 days. An
(preventive therapy).
BAL (2,3-dimercaptopropanol) is also a clinically useful chelating agent.
2.Spasmolitics as an additional therapy at lead colics
(Atropine sulf., Buscolysin, Spasmalgon etc.),
hepatoprotective therapy (levulose solutions, Carsil 3x2
tabl. etc.), etc.
3.Vitamin therapy (Vit B1, Vit B6, Vit C)

41

PREVENTION
Technological prevention - automation and
pressurization of the production processes, local and
general ventilation, wet cleaning, use of personal
protective equipment. Regular conduction of preliminary
and periodic medical check-ups.
Workplace hygiene (Clean areas for eating, no smoking,
showering and cleaning of work)
Technological and machine innovations
Ventilation in working rooms
Medical prevention
Medical examinations and laboratory tests for workers
(periods are according laws and standards)
Medical examinations before accepting in the work place
(new labours)
42

MERCURY POISONING (Hg)

Physicochemical properties. Hg is a liquid metal
Its vapours are seven times heavier than the air,
they are easily volatile.
Portal of entry in the organism - by inhalation
and skin contact, rarely - ingestion (when eating or
smoking the working places)
Usage and occupational risk: in production of
mercury and quartz lamps, amalgams, manufacture
of thermometers, barometers, manometers ,etc.
43

 Biotransformation. Hg is bound to erythrocytes. It

can also be found in the blood plasma. It is a
cumulative poison, mostly accumulates in kidneys
and liver, where bounds to low-molecular-weight
protein - metallothionein. Hg crosses the blood-brain
barrier and placenta. It has affinity to the sulfhydryl
groups of the cellular enzymes and proteins.
Elimination: mainly in urine, feces, and few
amounts in sweat.
Mechanism of action: Hg is a neurotropic poison.

CLINICAL FINDINGS

High levels of mercury in urine

Asthenic vegetative syndrome headache, vertigo, decreased work
ability, feeling of fear, insomnia,
memory loss, increased anger, tremor of
hands, the so-called mercury erethism,
psychogenic and cerebellum
manifestations.
Polyneuropathy and
encephalopathy may also occur.
45

CLINICAL FINDINGS
Gastro-intestinal syndrome: unpleasant,
sweetish, metal taste in the mouth, increased
salivation - up to a few litres in the twenty-fourhour period - the so-called mercury ptyalism; in
other cases, on the contrary a dry mouth is
observed; abdominal pain, vomiting, nausea chronic gastritis and colitis.
The Hg pharyngitis - the so-called Kussmaul's
sign or throat. Inflammatory processes in the
oral cavity are manifested - gingivitis, stomatitis.
A Hg line - bluish purple pigmentation from Hg
sulphide may be present on the teeth or gums.
46

CLINICAL FINDINGS

Cardio-vascular syndrome - it has most

frequently functional character - cardialgia,
tachycardia, etc.
Renal syndrome - mercury nephrosis and
glomerulonephritis may also occur.
Skin damage - on the bare parts of the body
chronic dermatitis or eczema may develop.
Eye disorders - Atkinson's syndrome - the
colour of the cornea is changed to dark pinkbrown.
47

Stages of mercury poisoning

1. Mercury carrier - in the urine increased

content of Hg, mercury line on the gums and
no objective clinical findings.
2. Mercury effect - asthenic vegetative,
neurotic syndrome with changes in the oral
cavity, increased level of Hg in urine, inhibited
activity of carboanhydrase.
nervous system effects,.
3. Micromercurism - expressed manifestations
of tremor, disorders of coordination,
gastrointestinal syndrome, strongly inhibited
activity of the carboanhydrase
4. Severe degree - organic disorders of the
48
central nervous system, encephalopathy

Diagnosis. Differential
diagnosis
Diagnosis - proved occupational risk,
clinical course of the intoxication,
Atkinson's syndrome, mercury content in
urine.
Differential diagnosis. The differential
diagnosis is with the diseases of the
nervous, gastro-intestinal systems, renal
diseases with non-occupational origin.

49

TREATMENT
1.Antidote (Unithiol - 5 ml amp. by 1 amp.
daily, a treatment course from 5 to 10days
Succimer (caps. 350 mg by 2,1 g/daily at
equal administrations per 8 hours during 5
days. Depending on the excretion of mercury
in urine, the dose of
Succimer can be reduced to 1,4 g/daily, 2
times per 12 hours during 2 weeks.
The therapy with Succimer is an alternative to
that with Unithiol. A therapy with Succimer can
be applied after treatment with Unithiol, but
not earlier than 4 weeks from the Unithiol
administration.
50

TREATMENT
Na thiosulfuricum (10-20% - 10 ml,
therapy course of 5 days. It is applied in
the absence of Unithiol and Succimer.
2.Vitamin therapy (Vit Bu Vit B6, Vit C).
3. Symptomatic treatment - in the
early phases tranquilizers, in more
advanced stages - antidepressants,
neurotrophics, vessel dilators).

51

Arsenic poisoning
Arsenic is released during the smelting process of copper, zinc,
tin, and lead
It is an irritant to the skin and may cause eczematous dermatitis
and arsenical keratosis usually on the palms and soles on contact
Chronic toxic effects include megaloblastic bone marrow
suppression and liver enlargement
Normal blood concentration is 223 g/L and urine levels are 5
50 g/d.
Biological monitoring of arsenic is usually conducted by
measuring total arsenic in the hair, nails, or urine
52

Arsenic poisoning
Arsenic is particularly difficult to characterize as a
single element because its chemistry is so complex and
there are many different arsenic compounds.
It may be trivalent or pentavalent and is widely
distributed in nature. The most common inorganic
trivalent arsenic compounds are arsenic trioxide,
sodium arsenite, and arsenic trichloride. Pentavalent
inorganic compounds are arsenic pentoxide, arsenic
acid, and arsenates, such as lead arsenate and calcium
arsenate.
Organic compounds may also be trivalent or
pentavalent,
such as arsanilic acid, or may even occur in methylated
forms as a consequance of biomethylation by
organisms in soil, fresh water, and seawater.
53

Toxicokinetics
About 80 to 90 percent of a single dose of
arsenite[As(III) or arsenate As(V)] has been
shown
to
be
absorbed
from
the
gastrointestinal
tract
of
humans
and
experimental animals.
Arsenic compounds of low solubility (e.g.,
arsenic selenide,lead arsenide, and gallium
arsenide) are absorbed less efficiently than
dissolved arsenic
Skin can be a route of exposure to arsenic, and
systemic toxicity has been reported in persons
having extensive acute dermal contact with
solutions of inorganic arsenic
54

Biotransformation
The metabolism and potential for toxicity
of arsenic is complicated by in vivo
transformation of inorganic forms by
methylation to monomethyl arsenic (MMA)
and dimethyl arsenic (DMA).
The methylation of arsenic compounds
involves both oxidation states of the element.
The liver is the major site for methylation. A
substantial fraction of absorbed As(V) is
rapidly reduced to AS(III), most of which is
then methylated to MMA or DMA.
55

Mechanisms of Toxicity
It has been known for some years that
trivalent compounds of arsenic are the
principal toxic forms and that pentavalent
arsenic compounds have little effect on
enzyme activity.
A number of sulfhydryl-containing proteins
and enzyme systems have been found to be
altered by exposure to arsenic.
Some of these can be reversed by addition
of an excess of a monothiol such as
glutathione.
56

Toxicology
Ingestion of large doses (70 to 180 mg) of
arsenic may be fatal. Symptoms of acute illness,
possibly leading to death,consist of fever, anorexia,

hepatomegaly, melanosis, and cardiac arrhythmia,

with changes in electrocardiograph results that may
point to eventual cardiovascular failure.
Other features include upper respiratory tract
symptoms, peripheral neuropathy, and gastrointestinal,
cardiovascular, and hematopoietic effects.
Acute ingestion may be suspected from damage to
mucous membranes, such as irritation, vesicle
formation, and even sloughing.
57

Reproductive Effects and

Teratogenicity
High doses of inorganic arsenic
compounds given to pregnant experimental
animals produced various malformations,
somewhat dependent on time and route of
administration, in fetuses and offspring.
However, no such effects have been noted
in humans with excessive occupational
exposures to arsenic compounds. Arsenic
readily crosses the placenta in women
without known exposure to arsenic.
58

Carcinogenicity
In humans, chronic exposure to arsenic
induces a series of characteristic changes
in skin epithelium, proceeding from
hyperpigmentation to hyperkeratosis.
Diffuse or spotted hyperpigmentation, the
initial nonmalignant cutaneous effect, can
first appear within 6 months to 3 years of
chronic ingestion at concentrations in
excess of approximately 0.4 mg/kg/day.

59

Treatment
Treatment is symptomatic, with particular
attention to fluid volume replacement and
support of blood pressure with pressor agents.
For acute symptoms, dimercaprol may be
given (3 mg/kg intramuscularly every 4 hours)
until symptoms subside, followed by oral
penicillamine.
Succimer(2,3-dimercaptosuccinic acid) is also
thought to be effective. For chronic exposures,
dimercaprol and/or penicillamine may also be
used
60