MONOGRAPH FOR UKPID
MERCURY
ST Kolev
N Bates
National Poisons Information Service (London Centre)
Medical Toxicology Unit
Guy's & St Thomas' Hospital Trust
Avonley Road
London
SE14 5ER
UK
This monograph has been produced by staff of a National Poisons
Information Service Centre in the United Kingdom. The work was
commissioned and funded by the UK Departments of Health, and was
designed as a source of detailed information for use by poisons
information centres.
Peer review group: Directors of the UK National Poisons Information
Service.
1. SUBSTANCE/PRODUCT NAME
1.1 Origin of the substance
Naturally occurring. Mercury occurs in the Earth's crust, mainly in
the form of sulphides. The red sulphide, cinnabar, is the main
component of the mercury ores. It may contain up to 70% mercury.
Mercury is also released into the environment by human activities e.g.
combustion of fossil fuels, waste disposal and industrial activities.
Organic mercury compounds released into the environment are often
broken down to elemental mercury or mercuric compounds (Berlin, 1986).
1.2 Name
Elemental mercury. Inorganic mercury compounds.
1.2.1 Main brand names/main trade names
1.2.2 Generic name
Mercury (Hg).
Inorganic mercury compounds include: mercuric chloride (HgCl2),
mercurous chloride (Hg2Cl2), mercuric iodide red (HgI2), mercuric
oxide red, yellow (HgO), mercuric sulphide black, red (HgS), mercuric
nitrate (Hg(NO3)2, mercuric cyanide (Hg(CN)2)
1.2.3 Synonyms
Metallic mercury: hydrargyrum, hydrargyrum depuratum, mercure
(French), mercurio (Spanish, Italian), quecksilber (German),
quicksilver.
Synonyms of some inorganic mercuric compounds are:
Mercuric chloride (HgCl2): corrosive sublimate, mercury
bichloride, quecksilber chlorid (German), Sublimat (Czech), mercuric
bichloride, mercuric dichloride, mercury bichloride, mercury
dichloride, mercury (II) chloride, bichlorure de mercure (French),
bichloride of mercury, chloride rtutnaty (Czech), chlorure di
mercurique (French), cloruro di mercurio (Italian), cloruro mercurio
(Spanish), dichloromercury, mercury perchloride.
Mercurous chloride (Hg2Cl2): calomel, calomelanos, mild mercurous
chloride, mercury monochloride, mercury protochloride, mercury
subchloride, white precipitate.
Mercuric iodide, red: mercury biniodide.
Mercuric oxide red, yellow (HgO): red precipitate, yellow
precipitate.
Mercuric sulphide black, red (HgS): chinese red, cinnabar,
vermilion.
1.2.4 Common names/street names
Quicksilver.
1.3 Chemical group/family
Elemental mercury. Inorganic mercury compounds
1.4 Substance identifier and/or classification by use
1.5 Reference numbers
Metallic mercury CAS 7439-97-6
RTECS OV 4550000
EINECS 2311067
NCI C60399
UN 2809
Mercuric chloride (HgCl2) CAS 7487-94-7
RTECS OV 9100000
UN 1624
EINECS 2312998
NCI C60173
Mercurous chloride (HgCl2) CAS 7546-30-7
RTECS OV 8750000
EINECS 2314309
Mercuric iodide red (HgI2) CAS 7774-29-0
RTECS OW 5250000
UN 1638
EINECS 2318738
Mercuric oxide yellow (HgO) CAS 21908-53-2
RTECS OW 875000
UN 1641
EINECS 2446547
Mercuric sulphide red (HgS) CAS 1344-48-5
RTECS
EINECS 2156963
1.6 Supplier/importer/agent/ licence holder
Mercury and mercury compounds importers as listed in the UK importers
database (UKIM) are:
Seasafe Marine Clothing Ltd.
Tomita UK Ltd.
Alarmexpress Ltd
Philips Components Ltd Durham c/o Philips Impex Ltd
Hughes Microelectronics Europe Ltd
Sharp Manufacturing Company UK
1.7 Presentation
Some mercuric compounds used in laboratories are listed.
Mercuric iodide, red
Form crystalline
Mercurous mercury as Hg < 0.1%, Soluble mercury salts < 0.05 as Hg.
Pack sizes available: 25, 100 and 500 g.
Mercuric chloride
Form crystalline
Pack sizes available: 25, 100, 500 g and 1 kg.
Mercuric nitrate
Standardised solution 0.010 milliequivalents per ml
Pack sizes available: 100 ml.
1.8 Physico-chemical properties
Molecular weight
Mercury Hg = 200.59
Mercuric chloride HgCl2 = 271.5
Mercurous chloride Hg2Cl2 = 236.0
Mercuric iodide red HgI2 = 454.4
Mercuric oxide red HgO = 216.6
Mercuric sulphide red HgS = 232.7
Physical state
Metallic mercury: shiny, silvery white very mobile liquid, easily
divisible into globules, which readily volatiles on heating.
Mercuric chloride: crystals, powder of granules.
Mercurous chloride: powder.
Mercuric iodide, red: powder.
Mercuric oxide, red: crystalline powder of scales.
Mercuric oxide, yellow: powder.
Mercuric sulphide, red: powder, lumps, hexagonal crystals.
Colour
Metallic mercury: shiny, silvery white very mobile liquid.
Mercuric chloride: white.
Mercurous chloride: white.
Mercuric iodide, red: red.
Mercuric oxide, red: bright red or orange red.
Mercuric oxide, yellow: yellow or orange yellow.
Mercuric sulphide, red: bright red.
Odour
Odourless.
Solubility in water and organic solvents
Solubility in lipids in the order of 5-50 mg/L. Solubility in water
approximately 60 mg Hg/L at 24°C. Solubility of the inorganic mercury
salts is influenced by valence state and anionic component (Goyer,
1980). Mercuric salts like halides, sulphates and nitrates are water
soluble, sulphide and oxides are not (Berlin, 1986).
Metallic mercury: 20-30g/L in water, soluble in nitric acid, insoluble
in dilute hydrochloric acid, hydrogen bromide, hydrogen iodide and
cold sulphuric acid.
Mercuric chloride: 69g/L in water, 476g/L in boiling water, soluble in
ethanol, benzene, ether, glycerol, acetic acid, methanol, acetone,
ethyl acetate, slightly soluble in carbon disulphide and pyridine.
Mercurous chloride: 2 x 10-3 g/L in water, insoluble in alcohol and
ether.
Mercuric iodide, red: 0.06g/L, soluble in alcohol, ether, acetone,
ethyl acetate, carbon disulphide, alkali iodides and chloroform.
Mercuric oxide, red yellow: practically insoluble in water, soluble in
dilute hydrochloric acid and nitric acid, alkali cyanides or iodides,
slowly in solutions of alkali bromides, insoluble in alcohol.
Mercuric sulphide, red: practically insoluble in water.
Autoignition temperature
Not relevant.
Boiling point
Metallic mercury: 356.6°C
Mercuric chloride: 302°C
Mercurous chloride: NA
Mercuric iodide, red: about 300°C, sublimes
Mercuric oxide, red: NA
Mercuric oxide, yellow: NA
Mercuric sulphide, red: NA
Density
Metallic mercury: 13.59 g/cm2
Mercuric chloride: 5.4 g/cm2
Mercurous chloride: 7.15 g/cm2
Mercuric iodide, red: 6.28 g/cm2
Mercuric oxide, red: 11.14 g/cm2
Vapour pressure
Metallic mercury 2 x 10-3 mm at 25°C.
Relative vapour density
Metallic mercury volatile. A saturated atmosphere of mercuric vapour
contains approximately 18 mg Hg/m3 at 24°C.
Reactivity
Metallic mercury: reacts with ammonia, amines, acetylene and oxalic
acids to form compounds that are sensitive to mechanical shock. Reacts
with many metals except iron to form amalgams.
Mercuric chloride: incompatible with formates, sulphites,
hypophosphites, phosphates, sulphides, albumin, gelatin, alkalies,
alkaloid salts, ammonia, antimony and arsenic, bromides, borax,
carbonates, iron, copper, lead, silver salts.
Mercurous chloride: incompatible with bromides, iodides, alkali
chlorides, sulphates, sulphites, hydroxides, ammonia, cocaine,
cyanides, copper salts, hydrogen peroxides, iodine, lead salts, silver
salts and sulphides.
Mercuric oxide, yellow: incompatible with reducing agents.
Many mercury compounds decompose in light and should therefore be
stored in the dark.
1.9 Hazard/risk classification
1.10 Uses
Approximately 25% of the annual production of mercury is consumed by
the chloralkali industry, 20% is used in electrical equipment, 15% in
paints, 10% in measurement and control systems such as thermometers
and sphygmomanometers, 5% in agriculture, 3% in dentistry (dental
amalgam), and 2% in laboratories. The remaining 20% includes military
uses such as detonators, mercury containing catalysts, preservatives
in the paper-pulp industry, pharmaceuticals, in photography as an
intensifying agent and others (Korringa and Hagel, 1974).
Mercury was replaced as a preservative in emulsion paint in the UK by
substances such as ammonia and subsequently organic based
preservatives, over a period of years from the mid-fifties to the late
seventies.
Inorganic mercury compounds have been used in medicine for centuries,
but their use has been greatly reduced because of their toxicity.
Mercuric chloride was used as a laxative and applied topically as an
antibacterial agent. It was also used in the treatment of syphilis
before the advent of antibiotics. Mercury compounds have been used as
an irrigation solutions in the management of carcinoma. Mercurials
have also been used as spermicides. Mercurius solubilis (Merc. Sol.) a
nitrated oxide of mercury is used in homoeopathic medicine.
Mercury compounds (particularly mercuric iodide) have been used in
skin lightening creams and soaps. Such products are banned but may be
found in imported products or those intended for sale overseas.
1.11 Toxicokinetics
1.11.1 Absorption
Oral: Metallic mercury is poorly absorbed after ingestion at a rate
related to the vaporisation (0.01%) and it is generally thought to be
of no toxicological consequence (Goyer, 1980), unless there is
significant delay in passage through the gastrointestinal tract or the
patient is exposed chronically. Inorganic soluble mercuric compound
are readily absorbed into the circulation e.g. mercurous chloride (up
to 10%) (WHO, 1991). A considerable proportion can remain fixed to the
intestinal mucosa and intestinal contents. Insoluble compounds undergo
oxidation to soluble absorbable compounds (Winship, 1985). Some
compounds which are particularly insoluble are poorly absorbed e.g.
cinnabar. However, chronic low dose exposure to these compounds may
lead to mercury intoxication (Kang-Yum and Oransky, 1992).
Inhalation: Mercury vapour is efficiently absorbed from the alveolar
air (about 80%) (WHO, 1991) due to the rapid diffusion of the vapour
through the alveolar membrane.
Dermal: Elemental mercury may be readily absorbed if applied to the
skin in suitable form. When applied as ointment, up to 31% of the
amount applied was excreted (Oehme, 1972). In animal studies up to 8%
of mercuric chloride applied to the skin was absorbed within 5 hours
(Berlin, 1986).
Vaginal: Mercury compounds presented in vaginal jellies are easily
absorbed and retained in the body (Oehme, 1972).
1.11.2 Distribution
Absorbed mercury passes into the circulation where about half of it is
bound to albumin in the plasma (in combination with sulphydryl
groups), the other half enters red blood cells. It is then rapidly
distributed to the tissues and within a few hours the highest
concentration is found in the kidneys. The liver, blood, spleen,
respiratory mucosa, small and large intestine, skin, salivary glands,
heart, skeletal muscle, brain and lungs contain decreasing amounts.
Mercury is stored in the bone, bone marrow and liver for a short time.
A special affinity for absorbed mercury in the frontal and basal
cerebral regions of the brain has been noted. A week after exposure
85-95% of all mercury in the body is stored in the kidney. With
continued absorption the concentration in the kidney increases.
Further absorption results in higher levels in other organs without
affecting renal levels (Winship, 1985).
Since organic mercury is concentrated in the erythrocytes and
inorganic is not, the ratio of the amount in the red blood cells and
plasma will indicate whether the patient has been exposed to organic
or inorganic mercury.
Mercury vapour crosses cell membranes much more rapidly than divalent
compounds, a significant amount of the vapour reaches the brain before
it is oxidised. Exposure to mercury vapour results in concentrations
in the brain which are 10 times higher than those following an
equivalent dose of inorganic mercuric salts (Winship, 1985).
The concentration of mercury in hair is about 300 times that in the
blood, and the most recent growth of hair reflects past blood mercury
levels.
All forms of mercury cross the placenta to the foetus. Foetal uptake
of elemental mercury in rats has been shown to be 10-40 times higher
than uptake after exposure to inorganic compounds probably because of
lipid solubility of mercury vapour (Goyer, 1980).
1.11.3 Biological half-life
Biological half-life for inorganic mercury is about 40 days. For
elemental mercury or mercury vapour the biological half-life is linear
with a range of values from 35 to 90 days. The biological half-life is
different for different organs. A fraction of the absorbed mercury
will remain in the body for a longer time (e.g. years in the brain)
(WHO, 1991).
1.11.4 Metabolism
Metallic mercury is oxidised to divalent mercury after absorption to
tissues and this is probably mediated by catalases. Inhaled mercury
vapour absorbed into red blood cells is transformed to divalent
mercury. However a proportion is also transformed as metallic mercury
to more distal tissues, particularly to the brain where
biotransformation may occur.
1.11.5 Elimination
Mercury is excreted mainly in the urine but considerable amounts are
also passed in the faeces through secretion by the gastrointestinal
tract, particularly in the colon, bile and saliva, gastric and
intestinal fluid. Mercuric mercury is also excreted by sweat,
lachrimal and mammary glands (Berlin, 1986). Excretion begins soon
after absorption and continues rapidly, with the tissue concentration
falling at different rates. The best mathematical model seems to be a
multicompartment model with at least two or more excretion rates and
with one small compartment including the brain. Most of the mercury is
excreted within a week but low levels may be found in the urine and
faeces for months. Small amounts may be retained in the brain for a
long period. Renal tissue tends to retain mercury, one week after
exposure 60-70% of mercury is still present. 60-70% of the mercury is
excreted as a sulphydryl mercury compound. The kinetics of clearance
from the body have shown three distinct phases. In the first, 35% of
the absorbed mercury with the half-time 3-4 days, accumulated in the
liver and was excreted into the faeces and transported into the
kidneys. In the second phase, 50% of the dose had a half-time of 30
days and was excreted in the urine following renal accumulation. The
remaining 15%, with a half time of 100 days, was accounted for by
renal excretion.
1.11.6 Special populations
No data available.
2. SUMMARY
3. EPIDEMIOLOGY OF POISONING
Occupational
Human exposure to inorganic mercury is mainly occupational, most
commonly associated with mercury vapour. It is often related to
specific working conditions e.g. mining, spillage of mercury compounds
on work clothes or in the working environment, handling of mercury
salts in the chemical industry and laboratories (Berlin, 1986; Bluhm
et al, 1992; Wide, 1986).
Accidental
Illicit gold extraction using mercury has also resulted in mercury
poisoning in adults and children (Shamley and Sack, 1989; Moromisato
et al, 1994). The mercury is mixed with quartz and gold, an amalgam is
formed with the gold and this is then heated until the mercury
evaporates off. Elevated levels of mercury were reported in 8 students
following exposure to mercury vapour during an experiment. Fourteen
others and the teacher had mercury levels below the normal
concentration (Anon, 1988).
There are several cases in the literature of mercury poisoning from
spillage of metallic mercury in the home and inappropriate cleaning up
of the chemical, particularly using a vacuum cleaner (Schwartz et al,
1992; McNeil et al, 1984; Muhlendahl, 1990; Bonhomme et al, 1996).
Mercury poisoning has also occurred from ingestion of a button battery
containing mercury (Mant et al, 1987). Toxicity has been reported
following exposure to mercury vapour from a broken mercury expansion
switch in a heating unit of an infant incubator (McLaughlin et al,
1980).
Medicinal and cosmetic use
Toxicity and deaths have occurred from the medicinal use of inorganic
mercury compounds (Rajagopal and Hamilton,1984; Laundy et al, 1984).
Poisoning has been reported following the use of mercury-containing
skin lightening creams and soaps (Lauwerys et al, 1987; Dept of
Pharmacology-Drug and Toxicology Information Service, 1990). Poisoning
has also been reported following the use of traditional remedies (Kew
et al, 1993; Perharic et al, 1994; Kang-Yum and Oransky, 1992).
There are rare reports of mercury poisoning following aspiration of
metallic mercury (Zimmerman, 1969). In some case only mild symptoms
have developed (Wallach, 1972; Janus and Klein, 1982; Tsuji et al,
1970).
Intentional
Metallic and inorganic salts of mercury have also been used as a means
of suicide (Winship, 1985), including deliberate intravenous,
intra-arterial injection (Vale and Proudfoot, 1995) and subcutaneous
injection (Hill, 1967).
Dental amalgam
Dental amalgam and the risk to human health has been the subject of
several reviews (Goering et al, 1992; Fung and Molvar, 1992; Enwonwu,
1987; Mjor, 1994; Halbach, 1994; Aposhian et al, 1992). As well as
mercury poisoning, dental amalgam has been claimed to cause multiple
sclerosis, leukaemia, rheumatoid arthritis and numerous other
disorders.
Dental amalgam contains about 50% mercury with silver, copper, zinc
and some other metals in small quantities. It has been used in
dentistry for over 150 years. Amalgam is manufactured to be inert and
biological inactive, but it is known that mercury vapour is given off
with chewing and brushing of teeth. This vapour is then inhaled and
swallowed. Uptake of mercury from dental amalgam has been demonstrated
in sheep (Boyd et al, 1991) and monkeys (Hahn et al, 1990). In man
postmortem studies have shown a higher concentration of mercury in the
brain and kidney of subjects with amalgam fillings than in those
without.
One of the most important points raised by these reviews is that the
effect of chronic low dose mercury exposure on man is not known. The
currently available evidence suggests that when reasonable precautions
are used dental amalgam is not a significant health hazard to dental
workers or patients. There is however a need for more research.
Table 1 gives the daily mercury retention in the general population
(WHO, 1991). This includes organic mercury but it is clear that dental
amalgam is the primary source of mercury in the general population.
Table 1.
Exposure source µg Hg/day absorbed
Dental amalgam 3.0-17.0
Fish or seafood 2.34
Other food 0.25
Water 0.0035
Air 0.001
Daily mercury retention in the general population (WHO, 1991)
4. MECHANISM OF ACTION/TOXICITY
4.1 Mechanism
Mercury compounds are highly potent but non-specific cellular poisons,
that influence many vital processes involving proteins. Mercury ions
are protein precipitants and as a result cause severe necrosis on
direct contact with tissue. They have affinity for a number of
cellular components essential for the function and survival of the
cell such as enzymes, membrane proteins, nucleic acids and mitotic
apparatus. Mercury interacts with sulphydryl groups and disulphide
bonds of the membrane, as a result of which specific membrane
transport is blocked and selective permeability of the membrane
altered. Mercuric compounds are also immunotoxic and some have been
shown to be strong sensitisers (Winship, 1985).
Table 2 outlines the differential characteristics of inorganic and
elemental exposure (from Young-Jin, 1994).
Table 2
Elemental mercury Inorganic mercury
Primary route of exposure Inhalation Oral, dermal
Primary tissue distribution CNS, kidney Kidney
Clearance Renal, GI Renal, GI
Clinical effects
CNS Tremor Tremor, erethism
Pulmonary +++ -
Gastrointestinal + +++ (corrosive)
Renal + +++
Acrodynia + ++
Differential characteristics of inorganic and elemental mercury
exposure (from Young-Jin, 1994)
4.2 Toxic dose
Ingestion of 0.5 g mercuric chloride usually results in serious
illness but rarely proves fatal. Doses of 1 g cause death in about 50%
of cases and more than 1.5 g in nearly all cases. The prognosis has
improved since the introduction of chelating agents (Bidstrup, 1964).
Toxic effects are usually evident within 10-15 minutes of ingestion
(Reynolds, 1983). Troen et al (1951) reported 18 cases of human
poisoning after oral ingestion of a single dose of mercuric chloride,
nine of which resulted in death. The lethal doses ranged from 29 mg/kg
body weight to at least 50 mg/kg body weight. The most common autopsy
findings in these cases were gastrointestinal lesions (ranging from
mild gastritis to severe necrotic ulceration of the mucosa) and renal
lesions that had resulted in renal failure.
Clinical features of mercury poisoning did not occur following
ingestion of 204g (15ml) of metallic mercury and all the mercury was
passed in the faeces within 3 days (Wright et al, 1980). An adult who
ingested about 3kg (220ml) of metallic mercury had elevated blood and
urine levels of mercury but he developed only mild effects; six months
later he returned with mild jaundice and impaired LFTs. In this case
the mercury was cleared from the gut within 10 days (Lin and Lim,
1993).
Acute mercury intoxication has been described after using 1/500 to
1/1000 solutions of mercuric chloride for peritoneal lavage (Laundy et
al, 1984).
A 17-year old woman developed acute mercury intoxication with renal
failure after inserting 1 g mercuric chloride tablet into her vagina
in order to induce abortion (Page et al, 1983).
Micromercuralism has been reported after long term exposure to mercury
concentration in the air of 0.05 mg/m3 (Berlin, 1986).
5. FEATURES OF POISONING
5.1 Acute poisoning
5.1.1 Ingestion
Critical organs are the kidney and the intestinal tract.
The corrosive effect of concentrated mercury salt solutions on the
mucous membranes of the gastrointestinal tract causes extensive
precipitation of proteins. Gastric pain and vomiting may ensue. As the
compound passes to the lower regions of the gut, general abdominal
pain and bloody diarrhoea with necrosis of the intestinal mucosae may
occur. This may lead to circulatory collapse and death. If the patient
survives the gastrointestinal tract damage renal failure due to
necrosis of the proximal tubular epithelium occurs within 24 hours.
Apart from the corrosive damage there may be also be local vasospasm
due to activation of the angiotensin system (Berlin, 1986).
5.1.2 Inhalation
Inhalation of mercury vapour is the most important route of uptake for
elemental mercury. The lung is the critical organ upon accidental
exposure to high concentrations of mercury vapour. Mercury vapour
causes erosive bronchitis and bronchiolitis with interstitial
pneumonitis. Victims usually develop respiratory insufficiency. These
symptoms may be combined with signs caused by effects on the CNS, such
as tremor or increased excitability. Workers acutely exposed (4-8 h)
due to an accident exhibited chest pain, dyspnoea, cough, haemoptysis,
and evidence of interstitial pneumonitis. The calculated elemental
mercury concentration was 1.1 to 44 mg/m3 (WHO, 1991).
5.1.3 Skin exposure
The soluble inorganic compounds of mercury are irritating to the skin
and mucous membranes; this effect is particularly marked with mercuric
chloride. Concentrations of 1-5% cause irritation, vesiculation and
corrosion of the skin. Dilute solutions may produce irritation of
sensitive skin. The water insoluble mercury compounds do not cause
immediate skin reactions, but this may develop slowly as the compound
is absorbed and the mercury ionised in the tissues.
Mercurous salts are less corrosive than mercuric compounds.
5.1.4 Eye contact
Mercurous and mercuric salts are corrosive to the eyes (Atterbury and
Olson, 1990), the latter more so.
5.1.5 Parenteral exposure
A 21 year old female injected metallic mercury subcutaneously into
both thighs. Her blood concentration of mercury was elevated but she
did not develop features of mercury poisoning (Hill, 1967).
Acute mercury intoxication has been described after using 1/500 to
1/1000 solutions of mercuric chloride for peritoneal lavage (Laundy et
al, 1984).
5.1.6 Other
No data.
5.2 Chronic poisoning
5.2.1 Ingestion
Cases of chronic poisoning with calomel (mercurous chloride) have been
described. Signs and symptoms similar to those of poisoning with mixed
exposure to mercury vapour and mercuric mercury were described. With
chronic exposure to inorganic mercury the kidney is the critical
organ. Symptoms such as increased salivation and inflammatory changes
in the gums and black lines on the teeth, due to precipitation of
mercuric sulphide can also appear. Two type of renal damage can occur:
1) a glomerular injury caused by the toxic effect of mercury on the
cells of the basal membrane of the glomeruli. An autoimmune reaction
is induced due to formation of antigen against the glomerular tissue,
and a nephrotic syndrome develops with proteinuria and the classical
signs of glomerulonephritis.
2) the other type of renal injury is tubular damage. Mercury
accumulation causes necrosis and damage of the distal and middle
portion of the proximal tubuli (Berlin, 1986).
5.2.2 Inhalation
Chronic inhalation of mercury vapour the major effects are on the
central nervous system. Early signs are not specific and have been
termed asthenic-vegetative syndrome or micromercuralism, with symptoms
such as weakness, fatigue, forgetfulness, anorexia, loss of weight,
and disturbance of gastrointestinal tract function. At higher exposure
levels, the characteristic mercurial tremor appears as a fine
trembling of the muscles, interrupted by coarse shaking movements
every few minutes. This begins peripherally in the fingers, eyelids,
and lips and has the characteristics of intentional tremor. In
progressive cases it may develop into generalised tremor involving the
entire body, with intermittent violent chronic spasms of the
extremities. This is often accompanied by changes in personality and
behaviour, with loss of memory, increased excitability (erethism)
severe depression, and even delirium and hallucinations. Another
characteristic feature of mercury vapour intoxication is severe
salivation and gingivitis (Goyer, 1980). Sporadic instances of
proteinuria and even nephrotic syndrome may occur.
EEG changes together with changes in visually evoke response in
chronically exposed workers have been reported. ALA D hydratase
activity in blood cells decreases and the cholinesterase activity in
plasma markedly decreases with the increasing mercury excretion in
urine. An increased frequency of aneuploidy in lymphocytes from
workers exposed to mercury vapour has been described. Symptoms of
poisoning may regress and disappear when exposure has ceased. However,
in severe cases with long term exposure, persistent sequelae related
to the nervous system are common. A long term exposure to mercury
concentration in the air of 0.1 mg/m3 or higher, the probability of
developing mercuralism increase.
Exposure to metallic mercury may rarely produce sensitation, for
example from amalgam teeth fillings.
5.2.3 Skin exposure
Typical manifestations are erythema and contact dermatitis. Ammoniated
mercury is a common cause. Mercury compounds give rise to a type IV
cell-mediated delayed hypersensitivity reaction. There have been a few
cases of allergic dermatitis among dental personnel (WHO, 1991).
An idiosyncratic hypersensitivity reaction has been described,
particularly in children. This syndrome called acrodynia or pink
disease, is characterised by a generalised body rash. Other symptoms
are: chills, swelling and irritation of the hands, feet, cheeks and
nose, usually followed by desquamation, loss of hair and ulceration,
hyperplasia and hyperkeratosis, irritability, sleeplessness, and
profuse perspiration which may lead to dehydration. The perspiration
is accompanied by dilated and enlarged sweat glands and desquamation
of the sole and palms. Once mercury exposure ceases, the signs
gradually disappear. Patients with acrodynia usually have increased
levels of mercury in the urine (> 50 mg/L) (Berlin, 1986).
In certain circumstances skin absorption may be responsible for the
occurrence of systemic chronic toxicity. When applied as ointment, up
to 31% of the amount applied was excreted (Oehme, 1972). In animal
studies up to 8% of the mercuric chloride applied to the skin was
absorbed within 5 hours (Berlin, 1986).
5.2.4 Eye contact
Mercurialentis is the name given to an unusual appearance of the
anterior surface of the lens seen in people exposed to mercury. The
change in the lens consists of greyish or light-to-coffee brown
granular discoloration, detected by slit-lamp examination. The change
is bilateral and symmetrical, and the visual activity is unaffected.
It has been seen in people who have had prolonged exposure. It was
suggested that mercury is absorbed through the cornea circulates in
the aqueous humour, and precipitates on the anterior surface of the
lens. Mercurialentis is a manifestation of exposure but not necessary
of toxic absorption (Winship, 1985).
5.2.5 Other
Subcutaneous injection of metallic mercury resulted in the development
of tender fluctuant abscess with surrounding erythema. Between 0.5 and
1 ml mercury was recovered in each side of injection. No symptoms or
signs of mercury poisoning developed. However, the blood and urine
mercury concentration were within the range encountered in chronic
mercury poisoning (Hill, 1967).
5.3 Systematic description of clinical effects
5.3.1 Cardiovascular
Acute:
Tachycardia with dull heart sounds and a gallop rhythm have been
reported secondary to severe pneumonitis after acute exposure to
mercury vapour (Berlin, 1986).
Chronic:
EEG changes have been recorded in chronically exposed workers (Berlin,
1986).
5.3.2 Respiratory
Acute:
The lung is the critical organ in acute accidental exposure to high
concentrations of mercury vapour. Mercury vapour causes erosive
bronchitis and bronchiolitis with interstitial pneumonitis. Chest
pain, dyspnoea, cough, haemoptysis, and evidence of interstitial
pneumonitis have been reported (WHO, 1991), atelectasis, emphysema,
haemorrhage and pneumothorax often follow (Winship, 1985). The cause
of death is progressive respiratory failure. The mortality rate is
higher in children than adults (Moutinho et al, 1981; Moromisato et
al, 1994).
Aspiration of metallic mercury may result in severe pulmonary toxicity
or death (Zimmerman, 1969). In some case only mild symptoms have
developed (Wallach, 1972; Janus and Klein, 1982; Tsuji et al, 1970).
5.3.3 Neurological
Chronic:
Most information focuses on effects on the CNS following occupational
exposure. Characteristic signs are tremor, motor disturbances and
mental deterioration. The most common psychiatric signs and symptoms
are depression, irritability, and exaggerated response to stimulation,
with excessive shyness, loss of confidence, vague fears, insomnia,
emotional instability, forgetfulness and confusion. In advanced cases
there may be loss of memory, hallucinations or intellectual
deterioration, suicidal melancholia, or even manic-depressive
psychoses. Tremors are common, a fine static tremor of the fingers,
eyelids, lips and tongue develops and may progress to the arms and
legs. The tremor may cause deterioration of the handwriting and the
ability to perform other manipulative tasks. Intention tremor have
also been reported. Slurred speech may developed.
Four out of nine workers exposed to mercury vapour had clinical signs
suggesting involvement of the peripheral nervous system in addition to
the features of chronic poisoning. Electromyographic changes
consistent with denervation were demonstrated in eight. Sensory
effects are uncommon with poisoning by inorganic salts. However,
constriction of visual fields, difficulties in counting objects at a
low illumination and poor depth and colour perception have been
reported in a patient with chronic mercury poisoning.
5.3.4 Gastrointestinal
Acute:
The gastrointestinal system is usually affected after acute exposure
to inorganic mercury compounds (e.g. mercuric chloride). One of the
earliest symptoms is metallic taste, followed by thirst, severe
abdominal pain, vomiting and diarrhoea. The toxic effects are usually
evident within 10-15 minutes of ingestion (Reynolds, 1983). Ashen
discoloration of the mouth and pharynx are seen. Stomatitis develops
in about 24 hours. Colitis with prolonged haemorrhagic diarrhoea may
also occur.
Chronic:
Excessive salivation with loosening of the teeth is a sign of advanced
poisoning, as is a blue line along the gum margin (Winship, 1985).
5.3.5 Hepatic
Chronic:
Disturbed liver function with raised serum alkaline phosphatase have
been reported in 6 out of 70 patients following chronic use of
ammoniated mercury ointment (Klaassen, 1980).
5.3.6.1 Renal
Acute:
Renal failure due to necrosis of the proximal tubular epithelium
typically occurs within 24 hours after acute exposure to inorganic
mercury compounds. Apart from the corrosive damage there may also be a
local vasospasm due to activation of the angiotensin system (Berlin,
1986).
Chronic:
With chronic exposure to inorganic mercury the kidney is the critical
organ. Symptoms such as increased salivation and inflammatory changes
in the gums and black lines on the teeth, due to precipitation of
mercuric sulphide can also appear. Two type of renal damage can occur:
1) a glomerular injury caused by the toxic effect of mercury on the
cells of the basal membrane of the glomeruli. An autoimmune reaction
is induced due to formation of antigen against the glomerular tissue,
and a nephrotic syndrome develops with proteinuria and the classical
signs of glomerulonephritis.
2) tubular damage may also occur. Mercury accumulation causes necrosis
and damage of the distal and middle portion of the proximal tubuli
(Berlin, 1986).
WHO (1976) states that effects of elemental mercury on the kidney had
been reported only at doses higher than those associated with the
onset of the CNS toxicity sign and symptoms. Since then several new
studies have been carried out, and kidney effects have been seen at
lower exposure levels (WHO, 1991).
5.3.7 Endocrine and reproductive systems
Enlargement of the thyroid gland has been reported but the incidence
in relation to exposure to mercury is uncertain (Winship, 1985).
5.3.8 Dermatological
The soluble inorganic compounds of mercury are irritating to the skin
and mucous membranes; this effect is particularly marked with mercuric
chloride. Concentrations of 1 to 5% cause irritation, vesication, and
corrosion of the skin and mucous membranes, and much more diluted
solutions may produce irritation to sensitive skin. Typical
manifestations are erythema and contact dermatitis. Ammoniated mercury
is commonly implicated (WHO, 1991).
5.3.9 Eye, nose, throat: local effects
Acute:
Mercurous and mercuric salts are corrosive to the eyes (Atterbury and
Olson, 1990), the latter are more corrosive. Concentrations of 1 to 5%
cause irritation, vesication, and corrosion of the skin and mucous
membranes, and much more diluted solutions may produce irritation.
Chronic:
Mercurialentis is the name given to an unusual appearance of the
anterior surface of the lens seen in people exposed to mercury. The
change in the lens consists of greyish or light-to-coffee brown
granular discoloration, detected by slit-lamp. The change is bilateral
and symmetrical, and the visual activity is unaffected. It has been
seen in people who have had prolonged exposure. It has been suggested
that mercury is absorbed through the cornea circulates in the aqueous
humor, and precipitates on the anterior surface of the lens.
Mercurialentis is a manifestation of exposure but not necessary of
toxic absorption (Winship, 1985).
5.3.10 Haematological
Chronic:
Anaemia may follow chronic exposure to inorganic and metallic mercury.
Leucopenia, eosinophilia and thrombocytopenia have been reported
rarely. Aplastic anaemia and death from bone marrow suppression have
also been described (Winship, 1985).
5.3.11 Immunological
Experimental studies on animals have shown that inorganic mercury may
induce auto-immune glomerulonephritis in all species tested but not in
all strains, indicating a genetic predisposition (WHO, 1991).
5.3.12 Metabolic
Acute:
Metabolic, acid base and fluid and electrolyte disturbances may
developed secondary to severe vomiting and diarrhoea, or to acute
renal failure after acute poisoning with inorganic mercury salts.
5.3.12.3 Others
No data.
5.3.13 Allergic reactions
Erythema and contact dermatitis may occur. Ammoniated mercury is
commonly implicated. Mercury compounds give rise to a type IV
cell-mediated delayed hypersensitivity reaction. There have been a few
cases of allergic dermatitis among dental personnel (WHO, 1991).
Allergic reactions have been reported with dental amalgam. Symptoms
may occur within hours to several days after placement of amalgam
restorations. Symptoms may be limited to areas of contact or be
generalised, including eczema, urticaria and wheals on the face. Other
symptoms reported include dryness and soreness of the throat and
mouth, fever, hives, swelling of lips, tongue and mucosa. Most effects
are self-limiting and resolve within 2 weeks (Fung and Molvar, 1992).
5.13.14 Other
An idiosyncratic hypersensitivity reaction has been described,
particularly in children. This syndrome called acrodynia or pinks
disease, is characterised by generalised erythematous body rash. Other
symptoms are chills, swelling and irritation of the hands, feet,
cheeks and nose, usually followed by desquamation, loss of hair and
ulceration, hyperplasia and hyperkeratosis, irritability,
sleeplessness and profuse perspiration which may lead to dehydration.
The perspiration is accompanied by dilated and enlarged sweat glands
and desquamation of the sole and palms. Once mercury exposure ceases,
the signs gradually disappear. Patients with acrodynia usually have
increased levels of mercury in the urine (> 50 mg/L) (Berlin, 1986).
5.4 At risk groups
5.4.1 Elderly
No special risk as human exposures are mainly occupational.
5.4.2 Pregnancy
Sikorski et al (1987) reports a high frequency of foetal malformations
among the children of dental staff. Of 117 pregnancies in the mercury
exposed group, 28 pregnancies in 19 women led to spontaneous abortion
(19 cases) and stillbirth (3 cases) and congenital malformations (5
cases of spina bifida and one case of intra-atrial defect). In non
exposed controls, there were 7 cases of adverse pregnancy outcome in
five women out of a total 63 pregnancies (30 women). Another study
investigated the Swedish National registers for birth records. There
was no tendency towards an elevated rate of malformations, abortions
or stillbirth among dentists dental nurses and dental technicians.
On balance it would seem likely that there is risk of teratogenicity
or foetal toxicity following maternal exposure to mercury vapour or
inorganic salts.
5.4.3 Children
Acute mercury vapour inhalation is reported to have a higher mortality
rate in children than in adults (Moutinho et al, 1981; Moromisato et
al, 1994).
In addition to the features of acute and chronic poisoning recorded in
adults, an idiosyncratic reaction has been described in children. This
syndrome called acrodynia or pink disease, is characterised by general
body rash. Other symptoms are chills, swelling and irritation of the
hands, feet, cheeks and nose, usually followed by desquamation, loss
of hair and ulceration, hyperplasia and hyperkeratosis, irritability,
sleeplessness, and perfuse perspiration which may lead to dehydration.
The perspiration is accompanied by dilated and enlarged sweat glands
and desquamation of the sole and palms. Once mercury exposure ceases,
the signs gradually disappear. Patients with acrodynia usually have
increased levels of mercury in the urine (> 50 mg/L) (Berlin, 1986).
Renal tubular acidosis has been described in children. This disorder
was caused by exposure to mercuric salts from application of an
ointment containing ammoniated mercury. (Berlin, 1986).
5.4.4 Enzyme deficiencies
No data available.
5.4.5 Enzyme induced
No data available.
5.4.6 Occupations
Exposure to mercury vapour occurs in a variety of industries: in
mercury mining, levels as high as 5mg/m3 have been reported (Berlin,
1986), chloralkali factories range 10-50mg/m3, (WHO, 1991)
instrument manufacturing, physics and medical laboratories, some
exposure may also occur in dental surgeries.
Common operations in which exposure to inorganic mercury may occur are
as follows:
1) During use as a liquid cathode in electrolytic production of
chlorine and caustic soda from brine.
2) During manufacture of inorganic and organic compounds for use as
pesticides, antiseptics, germicides. Also miscellaneous applications
as chemical intermediate.
3) Preparation of amalgams in dentistry, in chemistry processing and
jewellery manufacture.
4) Manufacturing of mildew-proof paints and marine anti-fouling
agents.
5) Manufacturing of batteries, lamps (fluorescent and mercury), power
tubes, tungsten-molybdenum wire and rods.
6) Manufacturing of inorganic salts for use as catalysts in the
production of urethanes, vinyl chloride monomers and other chemicals.
7) Manufacturing of instruments (e.g. thermometers, barometers with
mercury as a working fluid).
8) Manufacturing of explosives and fireworks.
9) During use as a conductor during construction and maintenance of
military and nuclear power systems, in mercury-stem boilers, and in
air rectifiers.
10) During use and manufacturing of compounds for the pulp and paper
industry as a control for biological growths.
11) During roasting and smelting operations, extraction of silver and
gold, mining and subsequent refining of ore containing cinnabar
(Aronow, 1990).
5.4.7 Others
No data available.
6 MANAGEMENT
6.1 Decontamination
Inhalation
Immediately remove victim from exposure and give oxygen if available.
After spill of metallic mercury, carefully clean up all liquid and
discard contaminated carpeting or porous tile, or arrange for
professional toxic cleanup with self contained vacuum system. Do
not vacuum with home vacuum cleaner; this may disperse liquid
mercury, increasing its airborne concentration.
Ingestion of liquid mercury
Because liquid mercury usually passes through the gastrointestinal
tract system without being absorbed gut decontamination is not
required. Following a very large intentional ingestion, particularly
in a patient with multiple blind loops of bowel or intestinal
perforation, there is a risk of chronic intoxication. Whole gut
lavage, or even surgical removal may be necessary depending on X-ray
evidence of large pockets of mercury.
Ingestion of inorganic mercuric salts
Perform gastric lavage. Do not induce emesis because of risk of
serious corrosive injury. Whole bowel irrigation may be considered.
Arrange for endoscopic examination if corrosive injury is suspected.
6.2 Supportive care
Inhalation of mercury vapour
Give supplemental oxygen and observe closely for several hours for
development of acute pneumonitis and pulmonary oedema.
Ingestion of mercuric salts
Anticipate severe gastroenteritis and treat shock aggressively with IV
fluid replacement. Treat renal failure supportively; it is usually
reversible, but haemodialysis may be required for 1-2 weeks.
Allergic reactions to dental amalgam
Allergic reactions from dental amalgams usually respond to
antihistmines. In patients unresponsive to antihistamine therapy
removal of the fillings is recommended.
6.3 Monitoring
With acute mercury vapour inhalation symptoms of pneumonitis may be
delayed for several hours; a chest X-ray and arterial blood gases may
show early signs of toxicity.
Monitor electrolytes, fluid balance and renal function. Obtain blood
and urine mercury levels. Collection of 24 hour urine mercury is
useful in determining body burden.
6.4 Antidotes
Chelation therapy should not be started until the gut has been
emptied of mercury or it may enhance mercury absorption.
For serious systemic intoxication DMPS (dimercaptopropanesulphonic
acid) is the treatment of choice. It should be given IV in seriously
ill patients and orally in those with less severe effects or in those
with chronic mercury toxicity.
Dosage - adults:
Parenteral - slow injection over 3-5 minutes
Day 1: 250mg IV every 3-4 hours,
Day 2: 250mg every 4-6 hours,
Day 3: 250mg every IV/IM every 6-8 hours,
Day 4: 250mg every IV/IM every 8-12 hours.
Following days: according to patient's clinical condition 250-750mg
parenterally or change to oral medication.
Children:
Parenteral - slow injection over 3-5 minutes
Day 1: 5mg/kg 6 times daily,
Day 2: 5mg/kg 6 times daily,
Day 3, 4, etc: 5mg/kg 1-3 times daily.
Oral - acute poisoning
Adults: 1.2-2.4g daily in divided doses (e.g. 12 times 100-200mg/24
hours).
Children: 5mg/kg daily in divided doses.
Oral - chronic poisoning
Adults: 300-400mg/day in divided doses. The dose can be increased in
severe poisoning.
Children: 5mg/kg daily in divided doses.
DMSA (succimer, 2-3 dimercaptosuccinic acid) has been used
successfully as an oral chelating agent in a limited number of
patients with mercury poisoning (Bluhm et al, 1992; Fournier et al,
1988; Graziano, 1986) and could be used in patients sensitive to DMPS.
Dosage: Orally 30 mg/kg body weight daily for 5 days, then 20 mg/kg
for 14 days.
Dimercaprol (BAL) is another alternative. Dosage: 3-5 mg/kg IM every
4-6 hours for several days. Decisions on tapering the dose or ending
the administration will depend on blood and 24-hour urine mercury
concentration. After initial course of BAL, a oral chelating agent may
be used. BAL injections are said to be painful.
Penicillamine has also been used. Dosage: 100 mg/kg 24 hr (up to 1 g)
in 4 divided doses. If treatment is to continue longer, the dose
should be reduces to 35 mg/kg/24 hr. Animal experiments and some
clinical experience indicate that N-acetyl-D, L-penicillamine (NAP) is
more specific chelating agent for mercury. There is little human
experience to support this finding.
6.5 Elimination techniques
There is no role for dialysis, haemoperfusion, or repeat dose
activated charcoal in mercury poisoning. However, dialysis may be
required for supportive treatment of renal failure, and it may
slightly enhance removal of the mercury-chelator complex in patients
with renal failure. Haemodialysis clearance of the mercury-BAL complex
is about 5 mL/minute (Atterbury and Olson, 1990).
6.6 Management controversies
The use of dimercaprol (BAL) has been questioned in recent years with
the advent of the less toxic hydrophilic BAL analogues DMSA and DMPS.
Enhanced brain deposition may result from BAL treatment due to
lipophilicity of the metal complex formed with dimercaprol. This has
been described with inorganic arsenic and mercury. Experimental models
using oral administration of mercuric mercury in mice showed that DMPS
was superior to the other chelators in preventing mortality. Both DMSA
and DMPS were superior to dimercaprol and NAP in alleviating acute
toxicity, especially in the brain. Another study compared the
potential to mobilise mercury and the incidence of drug induced
toxicity of two chelating agents, DMSA and NAP (N-acetyl-D,
L-penicillamine), after acute exposure to metallic mercury in man.
DMSA was able to increase the excretion of mercury to a greater extent
than NAP. In animal studies, DMSA was also shown to have greater
activity than NAP in mobilising mercury from a toxic site (Houeto et
al, 1994)
A number of reports have indicated that in the treatment of acute
mercury poisoning by dialysis little mercury is removed even with
prior use of dimercaprol, except in the first few hours after
exposure, therefore dialysis has usually been employed only in cases
with renal failure. Other records, however, indicate then when
potentially toxic doses have been taken, haemodialysis concurrent with
dimercaprol administration may remove 10 to 15% of the ingested
mercury and, even more importantly, relieve the kidneys and treat any
uraemia caused by reversible kidney damage. Limited experience
suggests an advantage of starting dialysis within the first 24 hr
before maximal renal concentration can occur on the second day. This
also may assist in controlling fluid and electrolyte imbalance as
circulatory collapse accentuates the toxic tubular lesions (Aronow,
1990).
7 CASE DATA
Case 1: Intentional ingestion - mercury salts
A 17-year-old woman with psychological problems leading to four
previous drug overdoses deliberately ingested a mouthful of mixed
chemicals which she obtained as pure crystals from the laboratory
where she worked. They were thought to comprise aniline hydrochloride
and salts of barium, cadmium, lead, mercury, selenium and thallium in
unknown proportions. She presented 7 hours later with vomiting and
corrosive oral damage. Her face was flushed but there were no other
abnormalities. She was treated with BAL and calcium disodium edetate,
but became anuric within 16 hours. Her blood pressure remained normal.
Haemodialysis was started at 24 hours in an attempt to remove chelated
heavy metal. The results of the analysis taken during the first day of
admission were available after 4 days and showed an extremely high
mercury concentration in whole blood (1200 mg/L) measured by the cold
vapour atomic absorption method. No other heavy metal was found at a
concentration above normal. Calcium disodium edetate was therefore
withdrawn, and BAL and dialysis was continued. The dose of BAL used
was 100 mg IM 4 hourly during the first day, followed by 75 mg twice
daily for the next 24 days. The patient then declined to accept the
drug for 10 days, after which she was given 75 mg daily for a further
3 days. A renal biopsy showed severe tubular necrosis. She remained
virtually anuric for 31 days and received a total of 180 hours
dialysis during this period. Her renal function improved and the
plasma mercury fell, dialysis became unnecessary, when the level had
reached a concentration of approximately 100 mg/L. There were no other
manifestations of mercury poisoning except for a mild normochromic
anaemia and a transient elevation of her serum transaminase
concentrations. Three months later her creatinine clearance was 56
ml/min (Newton et al, 1983).
Case 2 and 3: Acute occupational inhalation - mercury vapour
Two men, aged 35 and 50 years old weighing 75 and 108 kg, were exposed
to mercury at work. They were jewellers and accidentally inhaled smoke
containing mercury vapour produced during the melting of a gold block.
The patients were exposed to the vapour for about half an hour. They
presented with moderate headache, spreading pain, nausea, lumbar pain,
gingival pain and shortness of breath at rest. The EEGs were
characterised by slow alpha activity. The ECGs were normal. No CNS,
EEG or nerve conduction velocity changes nor urological and
cardiovascular symptoms were found. The patients had no evidence of
any chronic respiratory disorder and arterial blood gas analysis was
normal. Chelation therapy was given for 10 days. BAL was given
initially (50 mg in the first injection, then 3 mg/kg 4 hourly for 2
days and then 3 mg/kg 6 hourly for 2 days). This was followed with
oral DMSA (30 mg/kg), due to the painful nature of the intramuscular
injections of BAL. Samples of plasma and urine were taken from the
patients every 24 hour over a period of 10 days. The maximum plasma
concentrations in the first sample were 239.5 mg/L and 93.3 mg/L in
patient 1 and 2 respectively. They remained at a plateau of about 50
mg/L (patient 1) and 25 mg/L (patient 2). The serum creatinine and
urea remained normal. In spite of the fact that high concentrations of
mercury persisted in the plasma, no further symptoms were observed at
any time in either patient during the 10 days BAL and DMSA were given.
Observations were not made after the 10 day period (Houeto et al,
1994).
Case 4: Chronic accidental inhalation - mercury vapour
A 33 month old girl was admitted for anorexia, weight loss, light
sensitivity and eczema, starting 4 months previously. She had
widespread severely itching eczema and pink, sweating and scaling
palms. She was ill-tempered and preferred to lie in bed or to be taken
around in a small buggy. Acrodynia was suspected, and raised mercury
concentrations was found in the urine. After 2 weeks of chelation
therapy with DMPS (30 mg twice daily) the child's eczema and mood
began to improve. After 4 months of therapy all symptoms had
disappeared and mercury excretion was normal. Subsequently it was
discovered that the mercury poisoning in this child was caused by
mercury from a broken thermometer spilled on the carpet (Muhlendahl,
1990).
Case 5: Accidental ingestion - mercuric chloride
A 23 month old boy ingested an unknown quantity of mercuric chloride
powder (a skin preparation) that he found on the lower shelf of a
chemist's shop. Vomiting was induced (method not stated) and within 5
minutes his tongue and lips were seen to be swollen. On admission
within an hour of ingestion the oedema and ulceration were so
extensive that there was a risk of compromising the airway. However, a
tracheostomy was not thought necessary. He was treated with
dimercaprol 6mg/kg IM every 6 hours for 48 hours then half that dose
for a further 48 hours. He was also given antibiotic cover and
hydrocortisone. On admission the urea was 8.7mmol/L and creatinine
43µmol/L. The blood mercury level on admission was 4.5 mg/L (urine
30.4 mg/L). This had decreased to 0.95 mg/L (urine 8.5 mg/L) by the
next day, 0.69 mg/L (urine 0.4 mg/L) on day 5 and 0.30 mg/L (urine
0.24 mg/L) by day 8. He suffered only mild renal impairment, this may
have been due to prompt treatment. By day 8 he was able to swallow
soft food without difficulty. He made a full recovery but the blood
mercury level only returned to normal after more than 100 days (Stack
et al, 1983).
Case 6: Chronic dermal absorption - acrodynia
A baby boy (2.15kg) developed nappy rash at the age of two weeks. The
rash did not improve with cream prescribed by the family doctor and
the mother began using Conotrane (hygraragaphen 0.05%). The baby
became fretful and refused feeds. He began to vomit and his stools
became watery. There was considerable erythema of the whole body with
irritability, photophobia and watering of the eyes. Once it was
discovered that the cream contained a mercury compound it was realised
that he was suffering from acrodynia (pink disease). The urine mercury
concentration was 120 µg/ml (Rajagopal and Hamilton, 1984).
Case 7: Chronic accidental inhalation - mercury vapour
A three year old boy was admitted to hospital with weight loss (2kg in
2 months) and acrodynia. A few days before admission he began to
experience difficulty in walking. High mercury levels were found in
the blood and urine. His parents and older and younger sisters all had
elevated mercury levels. His two year old sister had been admitted to
hospital 2 months earlier with a nephrotic syndrome of unknown cause.
The only symptom in his 6 year sister was aesthenia. His parents were
asymptomatic. According to the parents no mercury containing objects
had been broken in the house. An ozone analyser was used to determine
the source of the mercury. There was widespread contamination, with
the highest concentration in hose of the vacuum cleaner and in the
carpet of the children's room. Very high levels were found in the dust
of the vacuum cleaner (3020 and 5984 µg/g of dust). Dust in the garage
at ground level and the children's room at air level were 40 µg/g and
4.24 µg/m3 respectively. Extensive decontamination of the house was
undertaken and 4 months later the mercury levels were decreased. All
the family had at least one course of chelation therapy with DMSA and
the clinical signs disappeared (Bonhomme et al, 1996).
Case 8: Fatal accidental aspiration - metallic mercury
A 48 year old man was admitted to hospital for reevaluation and
treatment of Hodgkin's disease. Radiation therapy was begun on the
retroperitoneal area and was well tolerated. However, during the sixth
week of therapy he became unwell with nausea, vomiting, diarrhoea,
fever, cramping and abdominal pain and abdominal distension. X-ray
examination revealed distended, small bowel loops with multiple
air-fluid levels. A Miller-Abbott tube was passed into the proximal
ileum and 10ml of metallic mercury was placed in the bag. He began to
improve over the following 4 days. The tube was then removed but the
mercury bag ruptured while in the nasopharynx. The patient immediately
began to cough and expectorated about 4ml of mercury. X-ray
examination revealed considerable amounts of mercury in the stomach,
duodenum and throughout the trachea, major bronchi and over both lung
fields. An additional 5ml of mercury was removed by postural drainage,
chest tapping and forced coughing. A repeat X-ray 3.5 hours later
showed an increased amount of mercury in the left lung and a more
diffuse alveolar spread in the right lung. The patient remained well
for 12 hours, but then became pyrexial and irritable. By the next day
he was incontinent of urine and faeces with weakness and abdominal
pain. A mild cough produced small amounts of mercury-containing
sputum. There was no mercury excretion in the 24 hour urine specimen.
During the following 48 hours his temperature rose, he became confused
and continued to complain of weakness and abdominal pain. A repeat
urinary mercury determination was negative. He developed leucocytosis
and albuminuria. Dimercaprol was started 72 hours after aspiration
occurred. Four days after aspiration his symptoms persisted and he
developed hypotension which responded to volume expansion. He
developed an increasingly severe cough which produced bloody sputum.
This was eventually produced in such large amounts that the airway
could not be kept clear. He became tachypnoeic, cyanotic and comatose,
and died 110 hours after aspiration of the mercury. During this time
only 8.2ml of the mercury had been recovered. Permission for a
postmortem was denied (Zimmerman, 1969).
Case 9: Intentional ingestion - metallic mercury
A 17 year male ingested approximately 205g (15ml) of metallic mercury
and presented to hospital about 2 hours later. He was well on
admission and a gastric lavage was performed. All investigations were
normal. An X-ray 4 hours after ingestion showed mercury in the stomach
and small intestine. By three weeks all the mercury had been passed in
the faeces. He remained well and serial urine mercury levels were
normal (all less than 15 µg) (Wright et al, 1980).
Case 10: Chronic inhalation exposure plus acute intentional
ingestion - metallic mercury
A 42 year old man presented to hospital after ingesting approximately
3kg (220ml) of metallic mercury. He had worked since the age of 13
repairing thermometers, barometers, sphygomanometers and related
instruments. In the last 2 years he had developed mild hand tremor,
forgetfulness, fatigue and irritability. He was given a gastric lavage
and cathartics. He complained of abdominal discomfort. An X-ray
revealed mercury in the stomach and small intestine. By 2 weeks most
of the mercury had passed in the faeces. An ophthalmological
examination was normal. Neuropsychiatric and psychological evaluation
revealed poor concentration and a defect in recent memory. An EEG
showed diffuse cortical dysfunction. He was treated with penicillamine
for 7 days. Blood and urine mercury levels 3 days after chelation
therapy were 116.9 µg/L and 22.9 µg/L. Six months after ingestion he
returned to hospital with mild jaundice and impaired liver function
which resolved over the next 6 months (Lin and Lam, 1993).
Case 11: Acute ingestion - button battery
A two year old girl arrived in hospital within two hours of ingestion
of a button battery containing mercury. The battery was visible on
X-ray in the upper stomach. An X-ray the following day was unchanged
but on the second day the battery was observed to be in two halves
surrounded by radiopaque material. More radiopaque material was
visible in the small bowel. The child remained asymptomatic. A
gastrotomy was performed to remove the mercury salts from the stomach,
areas of ulceration and bleeding were observed. The two halves of the
battery casing were removed via an enterotomy from 60 cm beyond the
pylorus. A blood mercury concentration at this time was 95 µL (normal
<4 µg/L) and the urine mercury concentration 60 µg/L (normal <20
µg/L). Two days later the blood concentration was 230 µg/L and the
urine 100 µg/L. Dimercaprol by IM injection was used as a chelating
agent. Six days post-operatively the blood mercury concentration was
340 µg/L (urine 600 µg/L). At this time she had been vomiting
intermittently but this became more persistent at nine days and an
abdominal X-ray revealed small bowel obstruction. Radiopaque material
was visible in the caecal region. A laparoptomy was performed and the
obstruction was found to be due to adherence of the proximal jejunum
to the abdominal wall. Multiple small ulcers were seen in the caecum.
One week after the second operation no mercury was seen on X-ray and
the blood mercury concentration was 25 µg/L. She was discharged and
six weeks later the blood mercury concentration was down to 7 µg/L
(Mant et al, 1987).
Case 12: Acute fatal inhalation in a child- mercury vapour
A 7 month old girl, her 3.5 year old brother and her father were
admitted to hospital with a 12 history of fever, vomiting and
dyspnoea. The family's six month old kitten had died the previous
evening. Postmortem examination of the cat revealed diffuse pleural
effusions and pneumonitis. The father and brother recovered over a 2-3
day period but the girl became increasingly dyspnoeic and was
transferred to another hospital. On admission coarse breathing sound
were heard bilaterally and heart sound were dull with a gallop rhythm.
On the evening of the onset of effects the patient's father had been
heating a metal thought to be lead on the kitchen stove. The kitten,
brother and sister were all playing in the kitchen at the time. Black
fumes were produced and the windows were opened. Analysis of the
melted metal revealed it to be an amalgam of mercury and tin with
smaller amounts of lead and zinc. The child was started in oxygen
therapy but over the following three days the oxygen requirement was
gradually increased. She had persistent metabolic acidosis and the
pulmonary interstitial marking became more prominent. Blood mercury on
the fourth day after exposure was 35 µg/L. Urine mercury excretion on
the same day was 400 µg/24 hours, on the 5th day 130 µg/24 hours and
on the 6th day 230 µg/24 hours. She was given methylprednisolone,
sodium bicarbonate and penicillamine. On the 7th hospital day she
developed increasing dynspnoea leading to apnoea. A chest X-ray
revealed bilateral pneumonthorax with complete collapse of the right
upper and left lower lobe. Despite adequate reexpansion, severe
acidosis, coma and convulsions occurred and she died six hours later.
At postmortem abnormalities were almost exclusively confined to the
lungs. The mercury level in the brain was 2.9 µg/L, lung 5.2 µg/L,
liver 5.1 µg/L and kidney 12.2 µg/L. In the family cat the level of
mercury in the lung was 18 µg/L and in the kidney 12 µg/L (Moutinho et
al, 1981).
8 ANALYSIS
8.1 Agent/toxin/metabolite
Mercury can be measured in blood and urine. For inorganic and
elemental mercury urine mercury determination is preferred.
8.2 Sample containers to be used
Blood (10ml) in hard plastic or glass container with anticoagulant
(heparin or EDTA).
Urine (20ml) for random sample use sterile universal, for 24 hour
sample collect in acid washed (nitric acid) hard plastic bottle.
8.3 Optimum storage conditions
8.4 Transport of samples
8.5 Interpretation of data
Normal levels: Blood <10µg/L (<50nmol/L)
Urine <20µg/L (<100nmol/L)
Toxic levels: Blood >35µg/L (>175nmol/L)
Urine >150µg/L (>750nmol/L)
8.6 Conversion factors
Metallic mercury 1 mg3 = 0.12ppm
1µg/L = 4.985nmol/L
8.7 Other recommendations
9 OTHER TOXICOLOGICAL DATA
9.1 Carcinogenicity
Inorganic mercury is generally not considered to be carcinogenic in
humans (WHO, 1991). However, some data have suggested possible
carcinogenicity of mercury in some occupationally exposed groups.
9.2 Genotoxicity
WHO (1976) did not report any studies showing that inorganic mercury
was genotoxic in humans. However, some data have since been reported
suggesting possible genotoxic effects of inorganic mercury.
9.3 Mutagenicity
DNA synthesis in animals exposed to mercury leads to the accumulation
of the metal in the cell nuclei. The affinity of mercury for nuclear
material was found to be considerable, binding largely to the
chromatin. Mercuric chloride has been shown to cause depression of
mouse leukaemic cells (Nakazawa et al, 1975). Reduction of DNA
replication in Chinese hamster ovary cells has also been observed.
Treatment of mice with mercuric chloride in vivo did not demonstrate
an increased frequency of chromosomal aberrations in bone marrow cells
or in spermatogonia (Poma et al, 1981). It seems likely that mercury
poses a risk of mutagencity in heavily exposed individuals.
9.4 Reprotoxicity
Six out of nine male workers accidentally exposed to mercury vapour
(concentration 44.3 mg/m3 for less than 8 hours) developed acute
mercury poisoning. During a follow up lasting several years they
showed signs of chronic poisoning. A loss of libido which persisted
for at least several years, was reported in all six cases. In a study
carried out at a US Department of Energy plant that used very large
quantities of metallic mercury, reproductive outcomes were studied
among 247 male workers exposed to mercury vapour. No association was
demonstrated between mercury exposure and decreased fertility,
increased rates of major malformations of the offspring, or serious
childhood diseases (WHO, 1991).
There have been reports of menstrual disturbances in women exposed
industrially or in dentistry to mercury vapour. A number of reports
suggested that inorganic mercury compounds cause spontaneous abortion.
During a 4 year period 17% of 168 exposed workers in a mercury ore
smelting plant had experienced spontaneous abortion (average exposure
80 mg mercury/m3), compared with 5% among 178 controls. Toxaemia
during pregnancy was reported in 35% of the exposed and 2% of the
unexposed workers. On the other hand, De Rosis et al (1985), revealed
no difference in the age standardised rate of spontaneous abortions
between mercury exposed and unexposed females. Two other studies on
female dental staff also reported no increased abortion rate when
compared with age standardised controls.
9.5 Teratogenicity
Studies on animals revealed that after brief exposure to elemental
mercury vapour the mercury easily penetrates the placentar barrier
(Greenwood et al, 1972). After equal exposure of pregnant rats, the
foetal uptake was 10-40 times higher after exposure to mercury vapour
than to mercury salts. In contrast, the placentar content of mercury
after exposure to elemental mercury was only 40% of that after
injected inorganic salts. The teratogenic effects of inorganic mercury
has been investigated in the rat: increased resorption and abnormality
rates were found, the malformations consisted of limbs and eye
defects. Embryological, teratogenic and foetotoxic effects have also
been demonstrated in the hamster; resorption rates were increased and
growth retardation was seen in surviving foetuses. Malformations
included: exencephaly, encephalocoele, anophthalmia, cleft lip and
palate, rib fusions and syndactyly (Gale et al, 1982).
Sikorski et al (1987) revealed a high frequency of malformations among
dental staff. Of 117 pregnancies in the mercury exposed group, 28
pregnancies in 19 women led to reproductive failure, with spontaneous
abortion (19 cases) and stillbirth (3 cases) and congenital
malformations (5 cases of spina bifida and one case of intra-atrial
defect). In non exposed controls, there were 7 cases of adverse
pregnancy outcome in five women out of a total 63 pregnancies (30
women). Another study investigated the Swedish National registers for
birth records. There was no tendency towards an elevated rate of
malformations, abortions or stillbirth among dentists dental nurses
and dental technicians.
On balance it would seem likely that there is risk of teratogenicity
or foetal toxicity following maternal exposure to mercury vapour or
inorganic salts.
9.6 Acceptable daily intake (ADI)
The Food and Agriculture Organisation WHO Expert Committee allocated a
provisional tolerable weekly intake for adults of 0.3 mg/person or
0.005 mg/kg.
9.7 AOEL
In the UK the occupational exposure standards of mercury and mercury
compounds (except mercury alkyls) are 0.05 mg (as Hg) per m3 long
term and 0.15 mg (as Hg) per m3 short term.
In the USA the permissible and recommended exposure limits for
inorganic mercury are 0.1 mg/m3 (maximum long term) and 0.05 mg/m3
(long term).
9.8 Relevant animal data
Evidence of damage to brain, kidney, heart and lungs in rabbits
exposed acutely to metallic mercury vapour at a concentration of 29
mg/m3 have been reported. The LD50 for inorganic mercury lies
between 10 and 40 mg/kg body weight for all compounds tested. For
mercuric chloride, a value of about 10 mg/kg body weight has been
observed after parenteral administration to mice. The features of
acute toxicity usually consisted of shock, cardiovascular collapse,
acute renal failure and severe gastrointestinal damage (WHO, 1991).
WHO (1976) in evaluating a number of experimental studies on animals,
concluded that both reversible and irreversible effects may be caused
by mercury and its compounds. Microscopically detectable changes have
been seen in the organs of dogs, rabbits and rats exposed to
concentrations of mercury vapour ranging from about 100 to 30 000
mg/m3 for different period of time. Severe damage was noted in
kidneys and brains at mercury concentration of about 900 mg/m3 after
an exposure period of about 12 weeks. After exposure of dogs to 100 mg
mercury/m3 for 7 days, 5 days /week, over a period of 83 weeks, no
microscopically detectable effects were seen, and tests revealed no
abnormalities in the kidney function. In two studies tremor and
behavioural effects were observed in rabbits and rats after several
weeks exposure to mercury vapour at levels of several mg/m3,
although there were no morphological changes in the brain.
During the last 10-20 years, great attention has been paid to effects
of inorganic mercury on the immune system. A number of studies have
been evaluated and it is concluded that depending on the animal strain
tested, either auto-immunity or immunosupression may be observed (WHO,
1991).
Selenium has been found to affect the distribution of mercuric mercury
in many animal species. As a consequence of this redistribution
decreased toxicity has also been observed. Mercury forms a
mercury-selenium protein complex with selenium. This complex can be
identified in plasma and blood cells. Given together with selenium,
mercury is retained longer in the blood, and as a consequence lessens
accumulation in the kidney. The mercury taken up by the kidney is
bound to the protein-selenium complex, binding to metallothionein is
diminished or negligible on administration of equivalent amounts of
selenium. Studies of selenium interaction with mercury have mainly
been done on animals. Selenium metabolism in man is different from
that in most animals. Observations in workers exposed to mercury
vapour indicate, however, that there is a remarkable relationship
between selenium concentrations and mercury concentrations in organs
such as brain, thyroid and pituitary. Transport of mercury over the
placental membranes is also inhibited (Berlin, 1986).
9.9 Relevant in vitro data
Mercuric chloride has been shown to cause depression of mouse
leukaemic cells (Nakazawa et al, 1975). Reduction of DNA replication
in Chinese hamster ovary cells has also been established. Treatment of
mice with mercuric chloride in vivo did not demonstrate an increased
frequency of chromosomal aberrations in bone marrow cells or in the
spermatogonia (Poma et al, 1981).
10. ENVIRONMENTAL DATA
10.1 Ecotoxicological data
Solubility in water
Elemental mercury: approximately 60 mg Hg/L at 24°C.
Volatilisation
Metallic mercury is rather volatile. A saturated atmosphere of
mercuric vapour contains approximately 18 mg Hg/m3 at 24°C.
LC50
The 96 hour LC50 varies between 33 and 400 mg/L for freshwater fish
and are higher for seawater fish.
10.2 Behaviour
Adsorption onto soil
In an experimentally set-up, the pH and chloride concentration in
soils was changed and the effect on the sorption of mercury
determined. With no chloride there was only a small effect of pH
between 4 and 6; sorption decreased at higher pH. Addition of chloride
had minimal effect at higher pH and decreased sorption at low pH.
Between pH 4 and 5.8, the effect of mercury sorption was entirely due
to changes in the HgOH+ concentration in solution.
Heavy metals were found in 2 to 5 fold higher concentrations near
roadside soils than in soils some distance removed from the road. The
typical roadside concentration of mercury was 0.12 mg/kg of soil
(Poisindex, 1995).
10.3 Biodegradation
Environmental fate
Mercury vapour is converted to soluble forms and deposited by rain
into soil and water. The atmospheric residence time for mercury vapour
is up to 3 years, where soluble forms have a residence time of only a
few weeks. The change in specification of mercury from inorganic to
methylated forms is the first step in the aquatic biotransformation
process. This can occur non-enzymatically or through microbial action
(WHO, 1991).
Abiotic transformation
The change in specification of mercury from inorganic to methylated
forms is the first step in the aquatic biotransformation process.
Experiments performed without the presence of any bacteria showed that
transfer of methyl groups occurs non-enzymatically.
Aerobic/anaerobic
It has been shown that cell extracts of a strictly anaerobic
methanogenic bacterium effectively converted inorganic mercury into
methylmercury .
Microbial
About 37 consortia were isolated in the presence of mercury chloride.
These strains retained between 82 and 90% of the total mercury
influent in fixed bed experiments. The retention mechanism was the
reduction in ionic mercury to metallic mercury (Poisindex, 1995).
Half-life in water, soil and vegetation
Water: The half-life of mercury can vary considerably, depending on
whether biological and non-biological mechanisms are involved.
Artificial decontamination of bottom sediments has cleaned up Minimata
Bay and the nearby Yatsushiro Sea, to a large extend accelerating the
natural process by an estimated 31.5 years. The natural
decontamination of the Yatsushiro Sea is estimated to have a half-life
of 9.5 years. The decontamination of the Ottawa River, where only
natural processes were involved, was found to have a half-life of 1.5
years.
Vegetation: Low levels of uptake of inorganic mercury from the soil by
plants have been reported.
10.4 Environmentally important metabolites
The change in specification of mercury from inorganic to methylated
forms is the first step in the aquatic biotransformation process. This
can occur non-enzymatically or through microbial action (WHO, 1991).
10.5 Hazard warnings
Aquatic life
Fish take up metallic mercury and retain it in the tissues,
principally as methylmercury, although most of the environmental
mercury to which they are exposed is inorganic. The source of
methylation is uncertain, but there is strong indication that
bacterial action leads to methylation in aquatic systems. Elimination
time is slow in fish (with half lives in the order of months or years)
and from other aquatic organisms (WHO, 1991).
10.5.1 Bees
No data available.
10.5.2 Birds
Sea birds and those feeding in estuaries are most at risk of mercury
poisoning. The form of retained mercury is variable and depends on the
species, organ and geographical site.
10.5.3 Mammals
Bioaccumulation: An experimental study was carried out with six sheep
which were given 4 mg inorganic mercury in their feed for 28 days. The
results suggest that the long term ingestion of mercury leads to a
chronic effect on the production of farm animals. High tissues
concentrations of mercury have been found in a number of wild animals.
10.5.4 Plants
Barley was used to assess plant-availability, tissue concentration and
genotoxicity of mercury from the solid waste deposited of a
chloralkali plant. Roots were found to take up most of the mercury,
bioconcentration in the straw was minimal and accumulation of mercury
in the grain did not increase with increased mercury in the soil,
indicating a restriction of transport function (Poisindex, 1995).
10.5.6 Protected species
Inorganic mercury is toxic to micro-organisms, aquatic life, insects,
birds and mammals, therefore, a number of protected species would be
at risk if exposed to toxic doses. High tissues concentrations of
mercury have been found in a number of wild animals.
AUTHORS
ST Kolev
N Bates
National Poisons Information Service (London Centre)
Medical Toxicology Unit
Guy's & St Thomas' Hospital Trust
Avonley Road
London
SE14 5ER
UK
This monograph was produced by the staff of the London Centre of the
National Poisons Information Service in the United Kingdom. The work
was commissioned and funded by the UK Departments of Health, and was
designed as a source of detailed information for use by poisons
information centres.
Peer review was undertaken by the Directors of the UK National Poisons
Information Service.
March 1996
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