Zinc and salts
| 1. NAME |
| 1.1 Substance |
| 1.2 Group |
| 1.3 Synonyms |
| 1.4 Identification numbers |
| 1.4.1 CAS number |
| 1.4.2 Other numbers |
| 1.5 Brand names, Trade names |
| 1.6 Manufacturers, Importers |
| 2. SUMMARY |
| 2.1 Main risks and target organs |
| 2.2 Summary of clinical effects |
| 2.3 Diagnosis |
| 2.4 First-aid measures and management principles |
| 3. PHYSICO-CHEMICAL PROPERTIES |
| 3.1 Origin of the substance |
| 3.2 Chemical structure |
| 3.3 Physical properties |
| 3.4 Other characteristics |
| 4. USES/CIRCUMSTANCES OF POISONING |
| 4.1 Uses |
| 4.2 High risk circumstance of poisoning |
| 4.3 Occupationally exposed populations |
| 5. ROUTES OF ENTRY |
| 5.1 Oral |
| 5.2 Inhalation |
| 5.3 Dermal |
| 5.4 Eye |
| 5.5 Parenteral |
| 5.6 Others |
| 6. KINETICS |
| 6.1 Absorption by route of exposure |
| 6.2 Distribution by route of exposure |
| 6.3 Biological half-life by route of exposure |
| 6.4 Metabolism |
| 6.5 Elimination by route of exposure |
| 7. TOXICOLOGY |
| 7.1 Mode of Action |
| 7.2 Toxicity |
| 7.2.1 Human data |
| 7.2.1.1 Adults |
| 7.2.1.2 Children |
| 7.2.2 Relevant animal data |
| 7.2.3 Relevant in vitro data |
| 7.2.4 Workplace standards |
| 7.2.5 Acceptable daily intake (ADI) and other guideline levels |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS |
| 8.1 Material sampling plan |
| 8.1.1 Sampling and specimen collection |
| 8.1.1.1 Toxicological analyses |
| 8.1.1.2 Biomedical analyses |
| 8.1.1.3 Arterial blood gas analysis |
| 8.1.1.4 Haematological analyses |
| 8.1.1.5 Other (unspecified) analyses |
| 8.1.2 Storage of laboratory samples and specimens |
| 8.1.2.1 Toxicological analyses |
| 8.1.2.2 Biomedical analyses |
| 8.1.2.3 Arterial blood gas analysis |
| 8.1.2.4 Haematological analyses |
| 8.1.2.5 Other (unspecified) analyses |
| 8.1.3 Transport of laboratory samples and specimens |
| 8.1.3.1 Toxicological analyses |
| 8.1.3.2 Biomedical analyses |
| 8.1.3.3 Arterial blood gas analysis |
| 8.1.3.4 Haematological analyses |
| 8.1.3.5 Other (unspecified) analyses |
| 8.2 Toxicological Analyses and Their Interpretation |
| 8.2.1 Tests on toxic ingredient(s) of material |
| 8.2.1.1 Simple Qualitative Test(s) |
| 8.2.1.2 Advanced Qualitative Confirmation Test(s) |
| 8.2.1.3 Simple Quantitative Method(s) |
| 8.2.1.4 Advanced Quantitative Method(s) |
| 8.2.2 Tests for biological specimens |
| 8.2.2.1 Simple Qualitative Test(s) |
| 8.2.2.2 Advanced Qualitative Confirmation Test(s) |
| 8.2.2.3 Simple Quantitative Method(s) |
| 8.2.2.4 Advanced Quantitative Method(s) |
| 8.2.2.5 Other Dedicated Method(s) |
| 8.2.3 Interpretation of toxicological analyses |
| 8.3 Biomedical investigations and their interpretation |
| 8.3.1 Biochemical analysis |
| 8.3.1.1 Blood, plasma or serum |
| 8.3.1.2 Urine |
| 8.3.1.3 Other fluids |
| 8.3.2 Arterial blood gas analyses |
| 8.3.3 Haematological analyses |
| 8.3.4 Interpretation of biomedical investigations |
| 8.4 Other biomedical (diagnostic) investigations and their interpretation |
| 8.5 Overall Interpretation of all toxicological analyses and toxicological investigations |
| 8.6 References |
| 9. CLINICAL EFFECTS |
| 9.1 Acute poisoning |
| 9.1.1 Ingestion |
| 9.1.2 Inhalation |
| 9.1.3 Skin exposure |
| 9.1.4 Eye contact |
| 9.1.5 Parenteral exposure |
| 9.1.6 Other |
| 9.2 Chronic poisoning |
| 9.2.1 Ingestion |
| 9.2.2 Inhalation |
| 9.2.3 Skin exposure |
| 9.2.4 Eye contact |
| 9.2.5 Parenteral exposure |
| 9.2.6 Other |
| 9.3 Course, prognosis, cause of death |
| 9.4 Systematic description of clinical effects |
| 9.4.1 Cardiovascular |
| 9.4.2 Respiratory |
| 9.4.3 Neurological |
| 9.4.3.1 CNS |
| 9.4.3.2 Peripheral nervous system |
| 9.4.3.3 Autonomic nervous system |
| 9.4.3.4 Skeletal and smooth muscle |
| 9.4.4 Gastrointestinal |
| 9.4.5 Hepatic |
| 9.4.6 Urinary |
| 9.4.6.1 Renal |
| 9.4.6.2 Others |
| 9.4.7 Endocrine and reproductive systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, ears, nose, throat: local effects |
| 9.4.10 Haematological |
| 9.4.11 Immunological |
| 9.4.12 Metabolic |
| 9.4.12.1 Acid-base disturbances |
| 9.4.12.2 Fluid and electrolyte disturbances |
| 9.4.12.3 Others |
| 9.4.13 Allergic reactions |
| 9.4.14 Other clinical effects |
| 9.4.15 Special risks |
| 9.5 Others |
| 9.6 Summary |
| 10. MANAGEMENT |
| 10.1 General principles |
| 10.2 Relevant laboratory analyses and other investigations |
| 10.2.1 Sample collection |
| 10.2.2 Biomedical analysis |
| 10.2.3 Toxicological analysis |
| 10.2.4 Other investigations |
| 10.3 Life supportive procedures and symptomatic treatment |
| 10.4 Decontamination |
| 10.5 Elimination |
| 10.6 Antidote treatment |
| 10.6.1 Adults |
| 10.6.2 Children |
| 10.7 Management discussion |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 11.2 Internally extracted data on cases |
| 11.3 Internal cases |
| 12. ADDITIONAL INFORMATION |
| 12.1 Availability of antidotes |
| 12.2 Specific preventive measures |
| 12.3 Other |
| 13. REFERENCES |
| 14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES |
CHEMICAL SUBSTANCES
1. NAME
1.1 Substance
Zinc
1.2 Group
Non-ferrous metal
1.3 Synonyms
zinc salts
zinc chloride
zinc sulphate
zinc acetate
1.4 Identification numbers
1.4.1 CAS number
7440-66-6
1.4.2 Other numbers
557-34-6
5970-45-6
7446-20-2
7646-85-7
7733-02-0
1.5 Brand names, Trade names
1.6 Manufacturers, Importers
2. SUMMARY
2.1 Main risks and target organs
Oral, Inhalation: Nausea, dyspnoea and chest pains.
Target organs: Liver, kidney and heart.
2.2 Summary of clinical effects
Inhalation: Zinc chloride inhalation has caused fatal
poisoning in individuals exposed during the generation of
chemical smoke. Severe respiratory inflammation was observed
in these patients, who developed fever and a pale cyanotic
colour. Death is due to acute pulmonary oedema,
bronchopneumonia or interstitial pulmonary fibrosis.
Oral: Poisoning following oral ingestion of zinc salts such
as zinc chloride is characterised by corrosion and
inflammation of the mucous membrane of the mouth and stomach,
which usually becomes white; ulceration of the stomach may
occur, often followed by perforation. Symptoms include
burning pains in the oesophagus and stomach, nausea and
vomiting, diarrhoea, hypotension, cold sweats and cramps in
the legs. Oesophageal or gastrointestinal stricture may
follow (Reynolds, 1982).
2.3 Diagnosis
The diagnosis depends on the history and the clinical
presentation. Blood and urine should be collected for
biomedical analysis, including serum measurements for
elemental zinc.
2.4 First-aid measures and management principles
Decontamination by emesis, gastric aspiration and lavage and
chelation with calcium disodium edetate. Seek medical
attention immediately and transfer patient to hospital.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Zinc is widely distributed and appears in almost all igneous
rocks. Occurs in calamine or zinc spar, sphalerite or zinc
blende, zincite, willemite, franklinite, zinc spinel or
gahnite. Zinc constitutes about 0.02% of the crust of the
earth.
3.2 Chemical structure
Chemical name: Zinc (metal)
Atomic weight: 65.37
Atomic number: 30
Valency: 2
Isotopes: 64 (48.89%)
66 (27.81%)
67 (4.11%)
68 (18.57%)
70 (0.62%)
Chemical name: Zinc chloride MW: 136.3
Chemical name: Zinc sulphate MW: 287.5 (Heptahydrate)
Chemical name: Zinc acetate MW: 219.5 (dihydrate)
(Budivari, 1989)
3.3 Physical properties
Zinc metal
Description: bluish-white, lustrous metal stable in dry
air; becomes coated with a white layer of basic
carbonate on exposure to moist air. Malleable when
heated to 100 to 150°C, at 210°C it becomes brittle and
pulverisable. Burns in air with a bluish-green flame.
Boiling Point: 906.1°C
Melting point: 419.4°C
Moh's hardness: 2.5.
Relative density: 7.14 (Water = 1)
Solubility: water, insoluble; dilute acids or alkalis in
all proportions at 20°C
Zinc chloride
Description: White or almost white, odourless,
deliquescent, caustic, crystalline powder or granules or
opaque white masses or sticks.
Melting point: about 260°C
Solubility: water 1 in 0.5
alcohol 1 in 1.5
glycerol 1 in 2
Zinc sulphate
Description: Odourless, colourless, transparent,
efflorescent crystals or white crystalline powder with
an astringent metallic taste. It is efflorescent in dry
air and loses 5 molecules of water of crystallisation
when slowly heated to 50°C, and a further molecule at
100°C.
Solubility: water 1 in less than 1
alcohol practically insoluble
glycerol 1 in 2.5
Zinc acetate
Description: Colourless or white crystals or granules
with a faint acetous odour and a sharp disagreeable
metallic taste. It effloresces slowly to form a basic
salt.
Melting point: 237°C
Relative density: 1.735
Solubility: water, 1 in 2.5
alcohol 1 in 30
3.4 Other characteristics
Zinc metal
Normal state of zinc (metal) at room temperature: solid
Colour: bluish - silvery metallic
Odour: odourless
Dangers associated with zinc powder: Powdered zinc presents
an explosion hazard. If it is stored in damp places, there is
a danger of spontaneous combustion. Residues from reduction
reactions may start a fire if thrown into combustible waste.
Possible chemical reactions in air: None.
Possible chemical reactions with other agents: Strong and
weak alkalis, forms hydrogen.
Electrical and thermal conductivity with possible
consequences: No data available.
Environmental risks: Affects microbial soil organisms,
reduces the synthetic activity of plant enzymes. Zinc
affects marine life, poisoning both plants and animals. Zinc
can cause a reduction in growth of certain aquatic plants;
this toxicity varies over several orders of magnitude for
aquatic plants dependent on their ability to concentrate zinc.
Because of the low toxicity of zinc, man-made emissions
probably do not present a serious environmental hazard unless
they are accompanied by more toxic metals such as cadmium.
Pure zinc is very slowly attacked by dilute sulphuric or
hydrochloric acid; the presence of a small amount of another
metal eg. copper, tin, lead, accelerates the action of the
acids. Slowly soluble in acetic acid; soluble in nitric
acid. Slowly soluble in ammonia water; readily soluble in
solutions of fixed alkali hydroxides with evolution of
hydrogen. Zinc has a standard electrode potential of +0.761
and is thus electropositive to most structural metals except
aluminium and magnesium, which is the basis for its use in
batteries and electrogalvanising of steel.
Zinc chloride
Normal state of zinc chloride at room temperature: solid
Colour: white or almost white
Odour: odourless
Dangers associated with zinc chloride: see Metal Fume Fever
monograph
Possible chemical reactions in air: none.
Electrical and thermal conductivity with possible
consequences: No data available
Environmental risks: as for metal.
Zinc sulphate
Normal state of zinc sulphate at room temperature: solid
Colour: colourless, transparent
Odour: odourless
Possible chemical reactions in air: none.
Electrical and thermal conductivity with possible
consequences: No data available.
Environmental risks: As for metal.
Zinc acetate
Normal state of zinc acetate at room temperature: solid
Colour: colourless or white
Odour: faint acetous odour
Possible chemical reactions in air: none.
Possible chemical reactions with other agents: No data
available.
Electrical and thermal conductivity with possible
consequences: No data available.
Environmental risks: As for metal.
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
As an ingredient or reagent in chemical processing and
the manufacture of household goods. Zinc sulphate is
used in agriculture and zinc phosphide as a rodenticide
(the toxic effects of zinc phosphide are principally due
to the release of phosphine). Zinc sulphate is also used
medicinally as a mineral supplement and the acetate and
sulphates are used as astringents and topical agents in
the treatment of skin ulcers (Simkin, 1976; IRPTC,
1985).
4.2 High risk circumstance of poisoning
Associated hazards in the metallurgy of zinc arise from the
presence of arsenic, cadmium, manganese, lead and possibly
copper and silver.
4.3 Occupationally exposed populations
Zinc plant workers, galvanisers, metal workers, farm workers,
paint workers, cosmetic workers.
5. ROUTES OF ENTRY
5.1 Oral
Zinc and its salts are poorly absorbed from the
gastrointestinal tract; only a small proportion of dietary
zinc is absorbed. Zinc is distributed widely throughout the
body and is excreted in the faeces with only traces appearing
in the urine, since the kidneys have little or no role in
regulating the content of zinc in the body. Ingestion of
soluble salts may cause nausea, vomiting and purging.
In one case, a 6 year-old child died after ingesting a zinc
chloride soldering solution.
5.2 Inhalation
Inhalation of fumes or dust may result in a sweet taste, dry
throat, cough, weakness, generalised aching, chills, fever,
nausea and vomiting. Zinc chloride fumes may be irritant to
skin and mucous membranes. Zinc phosphide may cause dyspnoea
and diarrhoea following inhalation of the dust.
5.3 Dermal
In various species, more than 2.5% of a topical dose is
absorbed through the skin. Chronic poisoning due to
occupational exposure to zinc chloride has been associated
with leg pains, fatigue, loss of appetite and loss of weight.
The patient's condition improved following removal from the
zinc source (du Bray, 1937).
5.4 Eye
Zinc dust and fine machinings are irritant and abrasive to the
eye. Many zinc salts, for example the chloride, are
extremely corrosive to ophthalmic tissues.
5.5 Parenteral
Accidental intravenous administration of 7.4 g of zinc
sulphate to a 72 year-old woman resulted in death after 47
days (Brocks et al., 1977).
5.6 Others
Dialysis: a 32 year old woman suffered severe nausea, vomiting
and fever on six occasions after home dialysis using water
which had been stored in a galvanised tank (Gallery et al,
1972).
Zinc phosphide introduced per vagina was followed by death
from renal failure after 92 hours (Santini, 1955).
6. KINETICS
6.1 Absorption by route of exposure
About 20 to 30% of the zinc ingested from the diet is absorbed
from the gastrointestinal tract. The amount absorbed from
foods can be influenced by the presence of phytic acid, which
makes zinc unavailable; and possibly by the intake of calcium,
although this is uncertain in man.
6.2 Distribution by route of exposure
Zinc is distributed widely throughout the body, and is
deposited relatively slowly in the skeleton, where it is
bound for long periods. Approximately 98% of the zinc in
normal human plasma is protein bound. The principal carrier
protein is albumin which binds about 80-85% of plasma zinc;
approximately 15% is bound to 2-macroglobulin, less than 2%
to retinol-binding protein and less than 1-2% of zinc is
free or ultrafiltrable (Giroux & Henkin, 1972; Whitehouse et
al., 1983; Chivers, 1984; Foote & Delves, 1984). Zinc is
found in high concentrations in the choroid plexus, prostate,
kidney, liver, lung, spleen, and brain (particularly the
cerebellum and hippocampus). Only small amounts are found in
the CSF, urine and serum. Reports of zinc concentration after
parenteral administration of a single dose indicate
substantial accumulation in the brain (Brocks, 1977).
Serum zinc concentrations in 17 healthy volunteers ranged from
0.566 to 1.02 mg/l, averaging 0.83 mg/l; plasma
concentrations did not significantly differ from those of
serum, although erythrocyte zinc concentrations averaged
12.25 mg/l in normal volunteers (Kosman & Henkin, 1979). Low
plasma zinc levels have been observed in dietary zinc
deficiency as well as in various other disease states (Prasad,
1979).
The mean plasma concentration of zinc is 960 µg/L in healthy
adults and 890 µg/L in healthy children.
In adults representative of industrial workers, the average
zinc concentration of eight organs and tissues were (µg/g of
ash):
kidney 4900 ± 140
liver 3800 ± 110
heart 2800 ± 67
pancreas 2400 ± 70
aorta 1900 ± 70
lung and spleen (each) 1400 ± 35, 29
brain 820 ± 34
(Schroeder & Nason, 1967)
There are few data on normal values of zinc in blood and
urine. Vallee (1962) reported values in human serum of 109 to
130 µg/100 ml, similar to those of iron; whole blood zinc,
880 ± 200 µg/100 mL; and red cell zinc, 1440 ± 270 µg/100 mL.
This value for whole blood is in fair agreement with the
value of 580 µg/100 mL obtained by mass spectrometry.
The normal or therapeutic value in blood is 68 to 136
microgram/100 ml and, in the CSF, 20 to 60 µg/kg/litre.
Similarly, Schroeder et al. (1967) estimated urinary excretion
estimated at less than 500 µg/day, close to the 150 µg/L
obtained by mass spectroscopy.
Whole blood and plasma zinc concentrations in healthy brass
foundry workers were noted to be 46% and 22% higher,
respectively, than in healthy control subjects; the
investigator concluded that excess zinc that is not
immediately excreted is stored in erythrocytes (Hamdi, 1969).
The volume of distribution has not been not fully established.
Serum levels of zinc are modified by many diseases, including
cancer, wound healing and atherosclerosis.
6.3 Biological half-life by route of exposure
5 to 16 months (whole body) (IRPTC, 1985)
6.4 Metabolism
Zinc occurs in the body in two different protein combinations:
i) as a metalloenzyme in which Zn is an integral part of an
important enzyme system, such as carbonic anhydrase for the
regulation of CO2 exchange, and
ii) as a metal - protein complex in which Zn is loosely bound
to a protein, which acts as its carrier and transport
mechanism in the body (metallothionine).
6.5 Elimination by route of exposure
In man, most of the average dietary intake of 10 - 15 mg Zn is
excreted in the faeces. Of the amount absorbed, about 20% is
excreted in the daily urine and up to 60% is excreted in the
faeces (Prasad, 1979). The kidneys have little or no role in
the regulation of zinc content in the body. Normal urine
zinc concentrations are from 0.3 to 0.4 mg/24 hours (231 to
641 µgs/day), but may increase to as much as 2.1 mg/24 hours
in patients with albuminaemia (Vallee, 1957), or up to 22-fold
with chelation therapy. Intestinal excretion appears to
regulate body zinc content under normal conditions. Urinary
zinc concentrations of 0.6 to 0.7 mg/l were observed in
workers exposed to zinc oxide at levels of 3 to 5 mg/m3
(ACGIH, 1971). Healthy brass foundry workers exposed to zinc
fumes excreted zinc in the urine at an average rate of 0.4
mg/24 hours (range 0.3 to 0.6), and increase of only 14% over
normal control subjects (Hamdi, 1969). Sweat can represent a
sizeable route of zinc excretion, according to Prasad et al
(1963); depending on climatic conditions, zinc loss in sweat
can range from 1150 ± 300 microgram/L in temperate climates to
2300 to 12, 700 microgram in 2 to 11 litres/day in hot
climates.
7. TOXICOLOGY
7.1 Mode of Action
Zinc is an essential trace element, however an excessive
exposure of the body to zinc leads to disturbances of the
functional state of individual organs and systems.
Intoxication is manifested by the reduction in the content of
free -SH- groups in serum; reduced activity of hepatic
arginase; and reduced prothrombin index (IRPTC, 1985).
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
Inhalation
The minimum concentration of zinc dust that is
toxic after exposure for 30 minutes is 4,800
mg/3.
Metal fume fever caused by zinc oxide fumes is
covered in a separate monograph.
Parenteral
When zinc chloride is administered parenterally,
zinc depresses the central nervous system,
causing tremors and paralysis in the
extremities.
Ingestion
Zinc chloride: The lethal dose of the various
zinc salts have not been defined, but a few
grams of the chloride have been lethal in an
adult, although recovery has occurred after
ingestion of 90 grams.
Zinc sulphate: Fatalities have been reported
following the ingestion of 10 to 30 g of zinc
sulphate. Intravenous infusion of 7.4 g of zinc
sulphate over 60 hours was fatal in a 72 year-
old woman (Brocks et al, 1977).
Zinc phosphide: Systemic toxicity is
principally due to the release of phosphine.
Ingestion of 4 to 5 grams of zinc phosphide has
caused death on two occasions (Frketic et al.,
1957; Gilli, 1948), but patients have survived
ingestion of 25 grams (Paszko, 1961) and 50
grams (Simonovic, 1954). Doses in the region
of 100 mg daily appear to be harmless,
(Phillips, 1882), but as little as 30 mg causes
nausea (British Pharmaceutical Codex, 1979).
7.2.1.2 Children
As for adults.
7.2.2 Relevant animal data
Acute oral toxicity:
Zinc sulphate heptahydrate, LDLO (rat, oral)
2200 mg/kg
Zinc acetate dihydrate, LDLO (rat, oral) 2460 mg/kg
Zinc phosphide, LD50 (rat, oral) 40 mg/kg
Acute toxicity parenteral route:
(inorganic zinc salts are highly toxic)
zinc sulphate heptahydrate, LD50 (IV) 40 mg/kg; and LDLO
49 mg/kg
zinc chloride LD50 (IV) 30 mg/kg.
The acute toxicity of zinc salts administered
subcutaneously appears to be intermediate between that
following intravenous and oral administration:
zinc sulphate heptahydrate LDLO (rat, s/c) 330 mg/kg.
No experimental data are available on zinc oxide, which
accounts for most industrial exposure.
The acute toxicity of organic derivatives of zinc are
similar to those of the inorganic compounds.
LD50 (rat, oral) 1400 mg/kg
LD50 (rat, i/p) 23 mg/kg
The lethal intravenous dose for rats is 60 to 90 mg/kg.
7.2.3 Relevant in vitro data
No data available.
7.2.4 Workplace standards
Current threshold limit value for exposure to fumes of
zinc chloride is 1 mg/m3. A zinc content of more than
15 ppm markedly impairs the potability of drinking
water (WHO, 1963).
Zinc chloride fumes:
TLV-TWA: 1 mg/m3 (ACGIH, 1989).
TLV-STEL: 2 mg/m3 (ACGIH, 1989).
Zinc sulphate:
2 mg/m3 (Dreisbach, 1987).
7.2.5 Acceptable daily intake (ADI) and other guideline levels
A dietary intake of 15 to 20 mg/day has been recommended
(Vallee, 1957).
7.3 Carcinogenicity
Zinc metal and dust are carcinogenic (IRPTC, 1985). Zinc
appears to be potentially carcinogenic only when a high
concentration of insoluble material has caused necrosis and
is followed by a regenerative response (Walters & Roe, 1975).
No indication exists that occupational exposure to zinc
increases the incidence of any type of cancer. Zinc may,
however, sustain tumour growth (Léonard et al., 1986).
7.4 Teratogenicity
Zinc appears not to be teratogenic except perhaps at very high
doses, but it can modify the teratogenic potential of other
metals. Teratogenicity in animals varies according to the
species (Léonard et al., 1986).
Zn pyrithione [1-hydroxy-2-(1H)-pyridinethione] is a broad
spectrum antifungal and antimicrobial agent found in
formulations that come into contact with skin, and in
shampoos and hairdressings as an anti-dandruff agent.
Because more than 2.5% is absorbed through the skin in various
species, its teratogenicity has been evaluated in the pig
(Wedig et al., 1976) and in the rabbit (Nolen et al., 1975).
There was no evidence of any teratogenic or embryotoxic
effect was observed in either case. The relevance of this to
other zinc compounds uncertain.
7.5 Mutagenicity
Studies on the mutagenicity of zinc strongly suggest that
zinc does not represent a mutagenic risk. Zinc chloride does
not affect DNA synthesis in vitro. In bacterial mutagenicity
tests, zinc sulphate is not mutagenic (Léonard et al., 1986).
7.6 Interactions
It has been suggested that concurrent administration of a zinc
salt might diminish the effect of penicillamine (Lyle, 1976).
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
No data available
8.3.3 Haematological analyses
Complete blood count
Blood film
Haematocrit
Prothrombin time
Liver function tests
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their
interpretation
High levels of zinc lead to microcytic anaemia with a reduced
prothrombin time. The excretion of zinc is increased in
patients with albuminaemia. Serum concentrations of zinc can
be used in the diagnosis of poisoning. Urinalysis may reveal
haematuria and proteinuria. Urine volume may be reduced.
Blood urea nitrogen and creatinine levels are elevated in the
presence of renal damage.
8.5 Overall Interpretation of all toxicological analyses and
toxicological investigations
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Zinc salts of strong mineral acids are irritating to the
gastrointestinal tract, and when ingested they act as
emetics. The emetic concentration in water is 675 to
2280 ppm. The onset of symptoms occurs within half to
one hour. Zinc ion, however, is ordinarily too poorly
absorbed to induce acute systemic effects.
Ingestion of soluble salts may cause nausea, vomiting
and purging. After large doses have been ingested,
fatal collapse may occur as a result of serious damage
to the buccal and gastroenteric mucous membranes.
Residual nephritis, and strictures of the oesophagus
and pyloric end of the stomach may occur. Zinc sulphate
also produces a burning pain in the mouth and throat,
and hyperglycaemia has been reported in one fatal case.
Mass poisonings from drinking acidic beverages made in
galvanised containers have been recorded. Fever, nausea,
vomiting, stomach cramps, and diarrhoea occurred 3 to
12 hours following ingestion (Callender & Gentkow,
1988).
The threshold concentration of taste for zinc salts is
15 ppm.
Except for their irritant action, inorganic zinc
compounds are relatively non-toxic by mouth.
9.1.2 Inhalation
Inhalation of fumes may result in a sweet taste, dry
throat, cough, weakness, generalised aching, chills,
fever, nausea and vomiting. Zinc chloride fumes damage
mucous membranes and are irritant to skin.
Metal fume fever is a brief, self-limiting illness
characterised by fever, chills, myalgia, vomiting and
prostration which is usually due to inhaling fumes of
zinc oxide. This syndrome should be distinguished from
the severe necrotising bronchitis and bronchopneumonia
which can follow inhalation of bronze powder (70%
copper, 30% zinc stearate), and from the severe and
often lethal damage to the mucosa of the respiratory
tract produced by zinc chloride fumes.
9.1.3 Skin exposure
Zinc salts of strong mineral acids are astringent,
corrosive to the skin, and irritating to the
gastrointestinal tract if swallowed. Skin contact,
especially with zinc dichromate can cause
papulovesicular lesions with exfoliation. Zinc chloride
has been implicated in contact dermatitis (IRPTC,
1985).
9.1.4 Eye contact
Corneal damage results in epithelial erosion and stromal
opacification of the cornea sometimes accompanied by
anterior subcapsular lens changes. These effects are
due to the precipitation of protein caused by zinc.
Lens opacities can result from exposure to high
concentrations of zinc salt, and may be associated with
reduced intraocular pressure and deposition of pigment
on the posterior surface of the cornea. Symptoms
sometimes resemble severe acute attacks of closed-angle
glaucoma.
9.1.5 Parenteral exposure
Inorganic zinc salts are highly toxic after parenteral
administration. Following accidental intravenous
administration of 7.4 g of zinc sulphate to a 72-year-
old woman, the serum zinc concentration was 41.8 mg/l;
hypotension, pulmonary oedema, vomiting, diarrhoea,
jaundice, and renal failure developed and she died
after 47 days (Brocks et al., 1977).
9.1.6 Other
No data available.
9.2 Chronic poisoning
9.2.1 Ingestion
Chronic ingestion of low doses of zinc salts is
associated with anaemia (Chunn, 1973), including
hypochromic (Porter et al., 1977) and sideroblastic
anaemia (Broun et al., 1990). Treatment was ineffective
until zinc ingestion was stopped.
After ingestion of 660 mg zinc sulphate daily for over a
year, profound hypochromic macrocytic anaemia,
associated cardiac failure, and copper deficiency
developed. Treatment consisted of slow transfusion of
packed cells, copper sulphate 4 mg daily, and the
withdrawal of the zinc sulphate. The blood picture was
normal four weeks later (Porter et al., 1977).
Chronic anaemia unresponsive to iron in three children
was attributed to zinc poisoning, resulting from the
children chewing metal toys of a zinc alloy. When the
toys were withdrawn, the children responded to
conventional treatment with iron (Chunn, 1973).
Broun et al. (1990) reported on two cases on
sideroblastic anaemia from chronic ingestion of zinc
salts. In the first case, a 31-year-old man who had
been ingesting coins for the past 12 years on the basis
of a delusional belief that they would protect him from
harm. In the second case, a 48-year-old man had been
taking zinc supplements daily for the past two years.
The anaemia in both patients resolved, with improvement
of their presenting symptoms once the zinc cause was
removed (Broun et al., 1990).
9.2.2 Inhalation
Inhalation is associated with zinc fume fever (see
separate monograph).
Within 4 to 12 hours after exposure to freshly formed
fumes, the first sign is an unusual metallic taste, or
some alteration of familiar tastes such as tobacco
smoke. This is accompanied by dryness and irritation
of the throat, with coughing and dyspnoea, feelings of
weakness and fatigue, pains in the muscles and joints,
and general malaise, similar to the prodromal syndrome
of influenza. Fever then drops, associated with
alternating chills. Body temperature is usually around
102 F, but may reach 104 F, with febrile shivering or
rigors, accounting for the trade terms of "brass
founders ague," "brass chills," spelter shakes," and
"zinc chills". The subject sweats profusely while the
body temperature begins to fall, occasionally
associated with convulsions. Severe pain in the chest,
aggravated by difficult breathing, has been described.
Clinical and symptomatic recovery is usually complete
in 24 to 48 hours. Rapid development of tolerance is
another characteristic feature of Zinc Fume Fever, but
it is lost equally quickly: a zinc or brass worker may
experience fume fever on his first day back at work
rather than during subsequent consecutive days of
exposure but re-exposure even on consecutive days may
lead to repeated attacks (McCord, 1960).
Extensive fibrosis of the lung, resulting in the death,
of a worker who had been employed for 29 years in a
zinc stearate factory has been reported (Uotila & Noro,
1957). The exposure must have been extremely high,
because in the long years of exposure of workers to
zinc stearate in a large US rubber factory, no adverse
effects of any kind were experienced (McCormick, 1971).
Gastrointestinal disturbances consisting of pressure in
the stomach region, nausea, and weakness, suggestive of
gastric or duodenal ulcers, have occurred in workers
employed for years in galvanising; in torch cutting of
galvanised metal parts (Kapp, 1934); in welding
galvanised iron sheets; and in brass foundry work (Hamdi,
1969).
9.2.3 Skin exposure
Repeated applications of zinc solutions to the skin may
cause erythematous, papular and granulomatous reactions
in susceptible individuals. One case of exposure to
zinc chloride has been associated with leg pains,
fatigue, weight loss and anorexia; the symptoms
resolved after removal from the source of contamination.
9.2.4 Eye contact
No data available.
9.2.5 Parenteral exposure
No data available.
9.2.6 Other
A 32-year-old woman developed severe nausea, vomiting
and fever on six occasions after home dialysis using
water which had been stored in a galvanised tank. The
plasma zinc concentration 36 hours after the sixth home
dialysis was 7 mg/l and fell slowly after dialysis for
six weeks in hospital to 1.58 mg/l. The red cell zinc
concentrations were respectively 35 and 12.3 mg/l
(normal 10 to 14 mg/l). No further episodes occurred
when the domestic water was deionised before use.
(Gallery et al., 1972).
9.3 Course, prognosis, cause of death
Death usually occurs within 6 to 12 hours following ingestion
(IPRTC, 1985), and is due to pulmonary oedema and cardiac,
respiratory and hepatic failure. There are no recorded
studies of death following acute inhalation but the time
course would be similar to that after oral ingestion. If the
patient is asymptomatic at the end of 72 hours, recovery is
likely. However, death may occur up to one week after
poisoning.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Cardiac failure due to anaemia, hypotension, cardiac
arrhythmias, shock, circulatory collapse, premature
atrial beats.
9.4.2 Respiratory
Cyanosis, severe retrosternal pain, widespread
consolidation of the lungs, pulmonary oedema, areas of
haemorrhaging, and extensive necrosis and numerous
punctate cysts, adult Respiratory Distress Syndrome
(Hjortso et al., 1988), severe respiratory failure,
severe coughing and dyspnoea, asthma, metal fume fever,
decrease in FEV1.
9.4.3 Neurological
9.4.3.1 CNS
CNS depression, lethargy, somnolence,
depression.
9.4.3.2 Peripheral nervous system
Myalgias
9.4.3.3 Autonomic nervous system
No data available.
9.4.3.4 Skeletal and smooth muscle
Leg pains have been reported following possible
transdermal absorption of zinc chloride.
9.4.4 Gastrointestinal
Gastroenteritis, nausea and vomiting, corrosion of
gastric mucosa, diarrhoea, haemorrhagic gastric erosion
(Moore, 1978), substernal pain, strictures of the
oesophagus and pyloric end of the stomach. Zinc
sulphate produces a burning pain in the mouth and
throat, with severe burns.
9.4.5 Hepatic
Jaundice, alkaline phosphatase, amylase, lipase and
hepatic metallo-thionein elevation.
9.4.6 Urinary
9.4.6.1 Renal
Oliguria, residual nephritis
9.4.6.2 Others
No data available.
9.4.7 Endocrine and reproductive systems
Hyperglycaemia has been noted in one fatal ingestion;
hyperamylasaemia.
9.4.8 Dermatological
Zinc dichromate and other salts may cause
papulovesicular lesions with exfoliation.
9.4.9 Eye, ears, nose, throat: local effects
Epithelial erosion, stromal opacification, anterior
subcapsular lens changes, lens opacities, reduced
intraocular pressure, taste disturbances, erythematous
uvula.
9.4.10 Haematological
Hypochromic macrocytic anaemia, copper deficiency,
thrombocytopenia, sideroblastic anaemia.
9.4.11 Immunological
No data available.
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
Metabolic acidosis and hypocalcemic tetany.
9.4.12.2 Fluid and electrolyte disturbances
Dehydration, pallor, weakness
9.4.12.3 Others
Circulatory collapse, impaired copper
absorption
9.4.13 Allergic reactions
Contact allergic dermatitis. Fume fever on repeated
exposure.
9.4.14 Other clinical effects
No data available.
9.4.15 Special risks
There is a suggestion that low serum zinc
concentrations during pregnancy might be a sign of
zinc deficiency with associated risks to mother and
child. Zinc crosses the placenta and can accumulate
in foetal brain and liver (IRPTC, 1985).
9.5 Others
No data available.
9.6 Summary
10. MANAGEMENT
10.1 General principles
From inhalation: Treat pulmonary oedema. Give prednisone
25 to 50 mg orally per day, or an equivalent dose of
another oral corticosteroid, to reduce tissue response to
inhaled metal fumes. Gradually decrease the dose as the
patient improves. Treat metal fume fever by bed rest and
give aspirin for fever and pain.
Except for zinc chloride, which is corrosive, gastric
decontamination by emesis, aspiration or gastric lavage
should be considered after ingestion of zinc salts unless
contraindicated. Demulcents may be given provided mucosal
damage is not present. Activated charcoal should then be
administered.
Absorbed zinc may be removed by chelation by dimercaprol or
calcium disodium edetate. Management is otherwise
symptomatic, with particular emphasis on monitoring cardiac
function since myocardial damage is the principal cause of
death.
Fluid replacement
Replace fluid loss with 5% glucose in saline, treat the
metabolic acidosis and hypocalcemic tetany if present.
Pain
Relieve pain with meperidine or morphine sulphate.
Anuria
Observe for and treat anuria and liver damage.
Cardiac damage
Death is probably due to cardiac damage.
10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
Usual blood and urine sampling for biomedical
analysis (zinc serum levels are clinically useful).
Collect in plastic where possible, keep cool and
tightly closed, until analysed. Traditional vacuum
tubes not specifically labelled for trace element
analysis can contain substantial amounts of
extraneous zinc. During treatment urine samples may
be clinically useful. Clean, unused plastic
containers are appropriate for the collection and
storage of urine and tissue samples prior to zinc
determinations (Breitschwerdt et al, 1986).
10.2.2 Biomedical analysis
Routine blood and urine analysis should be performed.
Hepatic function tests.
Blood glucose.
10.2.3 Toxicological analysis
Hepatic function tests.
Blood glucose (for hypoglycaemia).
10.2.4 Other investigations
Monitor FEV1, other pulmonary function tests
10.3 Life supportive procedures and symptomatic treatment
Following respiratory exposure, move patient to fresh air.
Monitor for respiratory distress. Emergency airway support
and 100% humidified supplemental oxygen with assisted
ventilation may be needed. If a cough or difficulty in
breathing develops, evaluate for respiratory tract
irritation, bronchitis, pneumonitis. All patients: support
respiratory and cardiovascular function.
Exposed eyes should be irrigated with copious amounts of
water at room temperature for at least 15 minutes. If
irritation, pain, swelling and lacrimation occur after 15
minutes of irrigation, an ophthalmologic examination should
be performed. Rinsing with 0.05 M neutral sodium edetate
may help prevent or reverse a portion of the protein
precipitation caused by zinc salts in the eye.
Skin exposure: wash the exposed area thoroughly with soap
and water. A physician may need to examine the area if
irritation or pain persists after washing.
10.4 Decontamination
Zinc chloride is highly corrosive and emesis or gastric
lavage should be avoided after oral ingestion. Zinc
sulphate is much less corrosive.
After ingestion of zinc sulphate, the stomach should be
emptied by emesis, aspiration and lavage, unless the
patient is already vomiting, or if there is evidence of
oral mucosal burns, and demulcents such as milk or white of
egg should be given freely.
With more corrosive salts, dilute rapidly with water or
milk. Immediately dilute with 4 to 8 ounces (120 to 240 mL)
of milk or water (not to exceed 15 mL/kg in a child).
Emesis may be indicated in substantial recent ingestions of
zinc sulphate unless the patient is obtunded, comatose or
convulsing, or is at risk of doing so based on the history.
Emesis is most effective if initiated within 30 minutes of
ingestion.
If emesis is unsuccessful following two doses of ipecac, the
decision to lavage or otherwise attempt to decontaminate
the gut should be made on an individual basis. In zinc
phosphide poisoning, it has been suggested that 0.5 grams
of copper sulphate (as a 1% aqueous solution) may be
administered: this has the theoretical benefit of
preventing absorption by forming insoluble copper phosphide
but evidence of efficacy is lacking (Gosselin et al, 1984)
and the administration of copper salts may be hazardous.
Whole bowel irrigation successfully removed 50 tablets each
containing 500 mg zinc sulphate from the bowel of a 16 year-
old (Burkhart et al, 1990). The patient was asymptomatic
throughout the procedure, and stool guaiac tests were
negative. The only adverse effect associated with whole
bowel irrigation was an increase in serum chloride
concentration from 105 to 127 mEq /L.
For total cover/immersion, use copious amounts of
water/detergent to remove surface metal dust.
Eye Contact
Flood affected eye(s) with copious amounts of lukewarm,
gently running water for at least 15 minutes. During this
time hold apart occasionally the upper and lower eyelid(s).
Obtain medical attention immediately.
Skin Contact
Rinse the affected area(s) with copious amounts of lukewarm,
gently running water for at least 15 minutes. Remove
contaminated clothing and shoes. Wash/thoroughly clean all
clothing before re-using or discard. If skin irritation
exists, seek medical attention.
10.5 Elimination
See 10.6 Antidote treatment; diuresis may be required if
renal failure occurs.
10.6 Antidote treatment
10.6.1 Adults
Administration of sodium calcium edetate by mouth and
intravenously has been suggested.
Dimercaprol 2.3 mg/kg bodyweight intramuscularly
every four hours for four doses, then daily for 6
days (Murphy, 1970) was effective in a 16 year old
boy (see case study).
Injury due to splashes of zinc chloride in the eye
can be treated by immediate irrigation with neutral
disodium edetate solution 0.05M.
10.6.2 Children
Administer calcium disodium edetate or dimercaprol to
symptomatic patients suspected to have excess body
zinc burden.
A 13 month-old boy was given calcium disodium edetate
180 mg (15 mg/kg) intravenously following accidental
ingestion of 30 mL of a moss killer solution
containing 13% zinc chloride. The serum zinc
concentration decreased from 10,020 micrograms/l
prior to chelation to 1,450 micrograms/l after
chelation. A marked improvement of his mental
status was also noted after chelation therapy (Hedtke
et al, 1989).
In a 16 month-old boy who swallowed soldering flux,
chelation with calcium EDTA and dimercaprol starting
75 hours after ingestion was ineffective in
enhancing zinc clearance. Dimercaprol (12 mg/kg) and
calcium EDTA (1 g/m2) were given daily divided into
four doses for 5 days. Blood zinc levels had
declined from 10,199 to 1,600 micrograms/l prior to
chelation and decreased only from 1,600 to 870
micrograms/l after chelation (McKinney et al, 1991).
Calcium EDTA lowers serum zinc to normal levels
(Chobanian, 1981; Potter, 1981) and, in the rat,
EDTA has been shown to increase urinary excretion
greatly (Millar et al, 1954).
10.7 Management discussion
Gastric lavage may be beneficial in patients exposed to non-
corrosive salts of zinc but it should not be used for
corrosive salts such as zinc chloride. Activated charcoal
is useful to adsorbing zinc.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
A 16 year-old boy ingested 12 g of elemental zinc in an
attempt to promote wound healing. Lethargy occurred 3 days
after ingestion, and blood zinc concentrations were
elevated. Treatment with dimercaprol 2.3 mg/kg body weight
intramuscularly every four hours for 4 injections, then once
daily for 6 days, resulted in clinical improvement and a
fall in zinc concentrations. (Murphy, 1970).
A 13 month-old boy accidentally ingested 30 mL of a moss
killer solution containing 13% zinc chloride, and developed
spontaneous vomiting, erythematous uvula, lethargy,
somnolence, frequent premature atrial beats, hyperglycaemia,
elevated alkaline phosphatase, oliguria, hyperamylasemia,
and a large superficial burn to the greater curvature of the
stomach. He was treated with intravenous fluids and 15
mg/kg of calcium disodium edetate. His mental status
improved dramatically and he was discharged after a day of
additional observation. (Hedtke et al, 1989).
Two persons survived the acute ingestion of zinc chloride
after developing serum levels of 1.46 and 19.4 mg/l;
symptoms included lethargy, nausea, vomiting and erosion of
the gastrointestinal mucosa. Administration of calcium
EDTA reduced the serum zinc concentration to normal
(Chobanian, 1981; Potter, 1981).
A six year old child died of corrosive gastritis and hepatic
necrosis 9 days after ingesting a zinc chloride soldering
solution (Jacobziner and Raybin, 1962). Hyperglycaemia has
been reported after a dose of zinc sulphate from which the
patient subsequently died (Dreisbach, 1987).
A 31 year-old man presented to the Emergency Department with
nausea, vomiting and abdominal pain. The patient was a
chronic paranoid schizophrenic who admitted to ingesting
coins for the past 12 years on the basis of a delusional
belief that they would protect him from harm. Coin-like
structures in his stomach and abdomen were noted on X-ray.
He was hospitalised and given intravenous fluids and
analgesics. At admission he had a haemoglobin of 9.3 g/dl;
over the next 8 days it fell to a low of 6.6 g/dl at which
time he was given a transfusion. The rest of his blood
results indicated sideroblastic anaemia. A gastroscopy was
performed on the 14th day, at which time a large number of
coins were found and removed from his stomach. The serum
zinc level preoperatively was greater than 45.9 micromol/l
(normal 9.2 to 23.0 micromol/l). Both the zinc level and
the anaemia returned to normal over the next four months
(Broun et al, 1990).
A 48 year-old man presented with a 6-month history of
chronic fatigue, and a blood screen notable for
sideroblastic anaemia. The patient reported taking zinc
supplements daily for the past two years. His serum zinc
level was 36.4 micromol/l. Two weeks after stopping the
zinc, his anaemia had resolved (Broun et al, 1990).
11.2 Internally extracted data on cases
To be added by the centre.
11.3 Internal cases
To be added by the centre.
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes
12.2 Specific preventive measures
Respiratory Protection: Use self contained breathing
apparatus (in fire).
Gloves: Rubber or plastic.
Protective clothing: suitable to prevent repeated or
prolonged skin contact, e.g., coveralls, etc.
Eyes: Wear suitable eye protection.
12.3 Other
No data available
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14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESSES
Authors: Peter Hayes, MPharm, BPharm, MRPharmS, MCPP, MBIM.
Trudi Patricia Martin, BPharm, MPharm, MPS.
Department of Pharmacy
University of Queensland
Brisbane QLD 4072
Australia
Tel: 61-7-3653191
Fax: 61-7-3653194
Date: February, 1994