Therapeutic Toxic Class

A)

Specific Substances

A)

1.2.1) MOLECULAR FORMULA
1) C8-H8-Hg-O2

Available Forms Sources

A)

1) Phenylmercuric acetate is used in herbicides and fungicides.
2) It was also used in the past as a vaginal contraceptive.

Life Support

A)

Clinical Effects

0.2.1)

A) Phenylmercuric acetate is an organic mercurial used as a fungicide, herbicide, slimicide, and preservative. Although it is an organic mercurial compound, studies in animals and reports of human exposures indicate that its effects are similar to those of inorganic mercurials.
B) This review is based on the properties of mercury compounds in general. Specific effects attributed to phenylmercuric acetate are identified.
C) ACUTE INORGANIC MERCURY POISONING - The principal concerns are sudden, profound circulatory collapse with tachycardia, hypotension and peripheral vasoconstriction, vomiting, and bloody diarrhea. Renal failure usually develops within 24 hours and may be life-threatening.

1) The brain is the critical organ for chronic inorganic mercury poisoning. Tremor and psychological changes such as increased irritability and sensitivity, may lessen xenophobia, insomnia, hallucinations, and mania.
2) ONSET - Toxicity may be delayed up to weeks following exposure.

0.2.3)

A) Sudden and profound circulatory collapse with tachycardia, weak and shallow pulse, hypotension and peripheral vasoconstriction can occur from ingestion of inorganic mercurials (HSDB , 1990).

0.2.4)

A) ACUTE EXPOSURE - Phenylmercuric acetate is a severe eye irritant.
B) CHRONIC EXPOSURE - Brown deposits of mercury in the lens and visual defects can occur. Gingivitis, fetid breath, and loosening of the teeth may occur with chronic exposure.

0.2.5)

A) Profound circulatory collapse with tachycardia and hypotension can occur from acute exposure to inorganic mercurials.

0.2.6)

A) Severe and potentially lethal pulmonary edema has been reported from inhalation of large amounts of elemental mercury. Mercuric salts could potentially act in a similar manner.

0.2.7)

A) Acute exposure may produce peripheral neuropathy and brain damage. The brain is the critical target organ for chronic mercury toxicity. Tremor, characteristic psychiatric changes, ataxia, peripheral neuropathy, and degeneration of higher brain functions appear with chronic exposure to inorganic mercurials.

0.2.8)

A) Vomiting, nausea, bloody diarrhea, and edema of the upper GI tract have occurred from ingestion of inorganic mercuricals.

0.2.9)

A) Liver necrosis may occur.

0.2.10)

A) Oligouria, anuria, and renal failure may occur from exposure to mercurials. Phenylmercuric acetate was 10 to 20 times more potent than mercuric acetate for inducing renal lesions in rats.

0.2.13)

A) Anemia occurs with chronic poisoning from inorganic mercurials.

0.2.14)

A) Severe skin irritation and burns may be seen with phenylmercuric acetate. Hypersensitivity reactions may rarely occur.

0.2.15)

A) Muscular weakness occurs with chronic poisoning from inorganic mercurials.

0.2.18)

A) Chronic exposure may cause mercurial erethism, a characteristic psychiatric syndrome involving short-term memory loss, increased irritability, xenophobia, apathy, and mania in extreme cases.

0.2.19)

A) Sensitization may rarely occur.

0.2.20)

A) Phenylmercuric acetate has induced severe neurological defects in humans from prenatal exposure.
B) The use of vaginal jelly containing phenylmercuric acetate has not been associated with birth defects.
C) Phenylmercuric acetate has been embryotoxic, fetotoxic, and teratogenic in animals.

0.2.21)

A) Phenylmercury acetate was not carcinogenic in mice.

0.2.22)

A) Phenylmercury acetate is hazardous by the inhalation, dermal, and oral routes.

Laboratory Monitoring

A)

B)

C)

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Treatment is symptomatic and supportive. If significant exposure has occurred, chelation therapy should be started as soon as possible, prior to development of symptoms. Breastfeeding should be halted immediately.

B) MANAGEMENT OF SEVERE TOXICITY

1) Supportive care is the mainstay of care. If significant exposure has occurred, chelation therapy should be started as soon as possible, prior to development of symptoms.

C) DECONTAMINATION

1) PREHOSPITAL: Dermal exposures should be washed off with soap and water. No other pre-hospital decontamination is indicated. Organic mercury spills should be contained and cleaned by qualified hazardous material abatement crews.
2) HOSPITAL: Most presentations are subacute or chronic exposures making gastrointestinal decontamination ineffective. However, given the dismal outcomes and limited therapeutic options, aggressive gastrointestinal decontamination including gastric lavage, activated charcoal and whole bowel irrigation is recommended for acute ingestions. Breastfeeding mothers should continue to pump breast milk and discard.

D) AIRWAY MANAGEMENT

1) Airway management may be necessary if a patient progresses to coma, if there is respiratory depression due to sensorimotor neuropathy, or if significant pneumonitis is present.

E) ANTIDOTE

1) None.

F) CHELATION

1) There is limited data suggesting that oral succimer (10 mg/kg every 8 hours for 5 days then twice daily for 2 weeks) can reduce mercury levels in the tissues. D-penicillamine (500 mg twice daily for 12 weeks) should be considered the second-line agent. Unithiol (2,3-dimercaptopropanol-sulfonic acid, DMPS) is available through compounding pharmacies in the United States. It is a water-soluble analog of BAL, and can be given orally or parenterally. It is considered a better mercury chelator than succimer. Unithiol is dosed as follows: IV: Day one 250 mg/kg every 3 to 4 hours, day two 250 mg every 4 to 6 hours, day three 250 mg every 6 to 8 hours, day four 250 mg every 8 to 12 hours, days five and six: 250 mg every 8 to 24 hours. ORAL: Initially 1200 mg to 2400 mg every 24 hours divided (100 mg or 200 mg every 2 hours), reduce to 100 mg to 300 mg every 8 hours as tolerated. Depending on the patient's clinical status, therapy may be changed to the oral route after the fifth day: 100 to 300 mg three times daily. Patients should be treated for 14 days or until there is no mercury detected in the urine. Dimercaprol (BAL; British Anti Lewisite) is CONTRAINDICATED because it increases brain organic mercury concentrations.

G) ENHANCED ELIMINATION

1) Hemodialysis, hemoperfusion, and exchange perfusion do not remove significant amounts of mercury after subacute or chronic organic mercury exposure. Hemodialysis in combination with L-cysteine infusion into the arterial blood has been shown to increase mercury clearance in chronic methylmercury intoxication, (L-cysteine converts methylmercury into a diffusible form) but it has not known if this improves outcomes.

H) PATIENT DISPOSITION

1) HOME CRITERIA: Patients with chronic exposures can be referred to outpatient healthcare providers for evaluation.
2) OBSERVATION CRITERIA: Asymptomatic or minimally symptomatic patients with chronic exposures already in healthcare facilities may be observed and referred to neurology or toxicology outpatient providers. All patients with acute exposures should be referred to a healthcare facility.
3) ADMISSION CRITERIA: All acute ingestions should be admitted. Patients with moderate or severe neurologic toxicity felt to be secondary to organic mercury warrant inpatient evaluation for neurology and toxicology consultation, whole blood quantification, and evaluation for possible chelation.
4) CONSULT CRITERIA: All cases with organic mercury toxicity should involve a toxicology and neurology consultants.

I) PITFALLS

1) Failure to fully appreciate the toxicity of significant organic mercury exposures during the latent phase may lead to delayed recognition of toxicity. Measurement of urine mercury when concerned for methylmercury toxicity is inappropriate since it is primarily cleared through the biliary tract resulting in a proportionally low urine mercury level. This may give false re-assurance when a low concentration is obtained.

J) PHARMACOKINETICS/TOXICOKINETICS

1) The organic mercurials are absorbed more completely (more than 90%) from the gastrointestinal tract than any other form of mercury because they are more lipid soluble. This lipid solubility allows passage across the blood-brain-barrier and the placenta. It is also concentrated in red-blood-cells. Organic mercurials are eliminated primarily through the biliary tract, then fecally with a significant amount of enterohepatic re-circulation. Less than 10% is cleared renally. Blood half-life is approximately 70 days.

K) DIFFERENTIAL DIAGNOSIS

1) Chronic arsenic poisoning may yield muscle weakness; however, the associate dermatologic effects are more prominent than in organic mercury poisoning. Chronic bismuth toxicity may result in a similar progressive neurotoxicity though, dermal changes are more common and black stools would be expected with chronic ingestion of bismuth. Medical etiologies such as progressive multi-focal leukoencephalopathy and cerebrovascular accidents should be considered.

0.4.4)

A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
B) Observe for development of clinical signs and symptoms and follow treatment recommendations in DERMAL EXPOSURE where appropriate.

0.4.5)

A) OVERVIEW

1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
2) Take precautions to avoid exposure of health care professionals and other individuals.
3) SYSTEMIC EFFECTS

a) Some chemicals can produce systemic poisoning by absorption through intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
b) Administration of chelators may be required. Provide supportive care.

Range Of Toxicity

A)

Clinical Effects

Summary Of Exposure

A)

B)

C)

1) The brain is the critical organ for chronic inorganic mercury poisoning. Tremor and psychological changes such as increased irritability and sensitivity, may lessen xenophobia, insomnia, hallucinations, and mania.
2) ONSET - Toxicity may be delayed up to weeks following exposure.

Vital Signs

3.3.1)

A) Sudden and profound circulatory collapse with tachycardia, weak and shallow pulse, hypotension and peripheral vasoconstriction can occur from ingestion of inorganic mercurials (HSDB , 1990).

3.3.4)

A) CIRCULATORY COLLAPSE - Sudden and profound circulatory collapse with tachycardia, hypotension and peripheral vasoconstriction can occur from acute inorganic mercury poisoning.

Heent

3.4.1)

A) ACUTE EXPOSURE - Phenylmercuric acetate is a severe eye irritant.
B) CHRONIC EXPOSURE - Brown deposits of mercury in the lens and visual defects can occur. Gingivitis, fetid breath, and loosening of the teeth may occur with chronic exposure.

3.4.3)

A) MERCURIALENTIS - Brown deposits of mercury in the lens cause opacity (Clayton & Clayton, 1981). This has occurred with long use of eyedrops containing phenylmercury acetate as a preservative (Grant, 1986).
B) VISUAL DEFECTS - Narrowing of the visual field and increase in the size of the blind spot are ophthalmic signs of chronic exposure to mercury ad its inorganic salts (Gmyrya et al, 1970). However, no changes in visual acuity were seen in patients using eyedrops containing phenylmercury acetate as a preservative (Grant, 1986).
C) ANIMAL STUDIES

1) Purulent conjunctivitis and atrophy of the iris were induced by phenylmercury acetate (as fermaset) in rabbit eyes after application 3 times per day for 1 to 5 days (Slem et al, 1972).
2) Phenylmercury acetate induced severe eye irritation in the rabbit in the Standard Draize Test (RTECS , 1990).

3.4.6)

A) CORROSION - Metallic taste, foul breath, loosening of the teeth, gingivitis, burning and intense salivation occur from oral exposure to inorganic mercury salts, as they are corrosive (HSDB , 1990).

Cardiovascular

3.5.1)

A) Profound circulatory collapse with tachycardia and hypotension can occur from acute exposure to inorganic mercurials.

3.5.2)

A) HYPOTENSIVE EPISODE

1) Sudden and profound circulatory collapse with tachycardia, hypotension and peripheral vasoconstriction can occur from acute inorganic mercury poisoning.

Respiratory

3.6.1)

A) Severe and potentially lethal pulmonary edema has been reported from inhalation of large amounts of elemental mercury. Mercuric salts could potentially act in a similar manner.

3.6.2)

A) ACUTE LUNG INJURY

1) Severe and potentially fatal pulmonary edema can occur from inhalation of mercury (ILO, 1983).

Neurologic

3.7.1)

A) Acute exposure may produce peripheral neuropathy and brain damage. The brain is the critical target organ for chronic mercury toxicity. Tremor, characteristic psychiatric changes, ataxia, peripheral neuropathy, and degeneration of higher brain functions appear with chronic exposure to inorganic mercurials.

3.7.2)

A) CENTRAL NERVOUS SYSTEM FINDING

1) Mercury crosses the blood-brain barrier (Blum & Manzo, 1985).

B) SECONDARY PERIPHERAL NEUROPATHY

1) A neurological syndrome resembling amyotrophic lateral sclerosis (Lou Gehrig disease) can occur even from acute exposure to mercury and its salts (Adams et al, 1983). The peripheral effects involve a dying-back axonopathy, followed by demyelinization. General loss of brain function may also occur (Folkl & Konig, 1983).

3.7.3)

A) ANIMAL STUDIES

a) Administration of BAL increased the distribution of phenylmercury acetate to the brain of mice (Berlin & Rylander, 1964).
b) Phenylmercury acetate, given at 15 mg/kg/day for 70 days intragastrically, induced degeneration of the sciatic nerve in rats (Slizewski, 1975).

Gastrointestinal

3.8.1)

A) Vomiting, nausea, bloody diarrhea, and edema of the upper GI tract have occurred from ingestion of inorganic mercuricals.

3.8.2)

A) VOMITING

1) Vomiting along with nausea and bloody diarrhea may occur from ingestion or inhalation of inorganic mercury salts (Clayton & Clayton, 1981).

B) EDEMA

1) Edema of the upper GI tract may occur.

Hepatic

3.9.1)

A) Liver necrosis may occur.

3.9.2)

A) HEPATIC NECROSIS

1) Liver necrosis may occur.

Genitourinary

3.10.1)

A) Oligouria, anuria, and renal failure may occur from exposure to mercurials. Phenylmercuric acetate was 10 to 20 times more potent than mercuric acetate for inducing renal lesions in rats.

3.10.2)

A) CRUSH SYNDROME

1) OLIGURIA/ANURIA - A large amount of the mercurial salt will become localized to the kidney producing a generalized increase in the permeability of the tubular epithelium; nephrotic syndrome occurs with oliguria and anuria requiring dialysis. Diagnosis should be based on elevated urinary excretion of mercury.

B) ACUTE RENAL FAILURE SYNDROME

1) Renal failure usually develops within 24 hours and is associated with albuminuria, epithelial cell casts, hematuria, glycosuria, and aminoaciduria.

3.10.3)

A) ANIMAL STUDIES

a) Phenylmercury acetate was less active than mercuric chloride in inducing proximal tubular damage in rats (Magos et al, 1982).
b) Phenylmercury acetate showed a similar distribution to mercuric chloride in the kidneys of rabbits: mercury accumulated in the collecting tubules, the proximal convoluted tublues, and the wide part of Henle's loops but not in the glomeruli (Bergstrand et al, 1958).

2) RENAL FUNCTION ABNORMAL

a) Chronic exposure can lead to impairment of kidney function, resulting in poor correlation between urinary mercury levels and body burden. Phenylmercury acetate was 10 to 20 times more potent than mercuric acetate for inducing renal lesions in female rats (Fitzhugh et al, 1950).
b) ADAPTATION - Repeated applications of low doses of phenylmercury acetate to rats induced resistance to higher doses with respect to renal damage (Solecki et al, 1989).

Hematologic

3.13.1)

A) Anemia occurs with chronic poisoning from inorganic mercurials.

3.13.2)

A) ANEMIA

1) Aryl mercury compounds such as phenylmercury acetate can cause anemia and leukopenia (HSDB , 1990).

Dermatologic

3.14.1)

A) Severe skin irritation and burns may be seen with phenylmercuric acetate. Hypersensitivity reactions may rarely occur.

3.14.2)

A) CHEMICAL BURN

1) Phenylmercuric acetate in concentrations of 0.1% and higher are primary irritants. Initially erythema and burning appear, followed by vesicles within 48 hours (Morris, 1960; Koby, 1972). In one case, pruritis and erythema developed 8 hours after a spill of phenylmercury acetate onto the skin, and vesicles began to form approximately 5 hours later (Sunderman et al, 1956).
2) Phenylmercury acetate induced severe skin irritation in humans during the Standard Draize Test (RTECS , 1990).

Musculoskeletal

3.15.1)

A) Muscular weakness occurs with chronic poisoning from inorganic mercurials.

3.15.2)

A) MUSCLE WEAKNESS

1) Muscular weakness occurs with chronic exposure to inorganic mercurials (HSDB , 1994).

Immunologic

3.19.1)

A) Sensitization may rarely occur.

3.19.2)

A) ACUTE ALLERGIC REACTION

1) Sensitization may rarely occur.

Reproductive

3.20.1)

A) Phenylmercuric acetate has induced severe neurological defects in humans from prenatal exposure.
B) The use of vaginal jelly containing phenylmercuric acetate has not been associated with birth defects.
C) Phenylmercuric acetate has been embryotoxic, fetotoxic, and teratogenic in animals.

3.20.2)

A) CONGENITAL ANOMALY

1) HUMAN TERATOGEN - Phenylmercuric acetate in contaminated pork consumed by American Indians induced severe or fatal neurological defects from prenatal exposure (Baranski, 1981).
2) No increase in malformations, cancers, Down's syndrome, or hyospadias occurred in 889 pregnancies where the parents had used spermacides containing phenylmercury acetate (Shapiro, 1982).
3) ANIMAL STUDIES

a) Fetotoxicity was observed in the rat, rabbit and hamster. A specific developmental abnormality of homeostasis occurred in the rat, rabbit and hamster. Other developmental abnormalities occurred in the rat and rabbit. Post-implantation mortality was observed in hamster and mammalian studies. Fetal death and specific developmental abnormalities in the musculoskeletal system were observed in the mouse. Specific developmental abnormalities in the central nervous system were detected in the hamster (RTECS , 1990).
b) Tail and neural tube defects were produced in fetal rats when phenylmercury acetate was given intravaginally between days 7 and 9 of gestation (Murakami, 1963).
c) Phenylmercury acetate was embryotoxic and teratogenic in hamsters, rats, and rabbits when given at doses ranging from 1/6 to 1/2 the LD50 (Dzierzawski, 1979).
d) Phenylmercury acetate (as falizan) was not teratogenic in chick embryos (Chakurov & Todorov, 1985).
e) Phenylmercury acetate induced delayed growth, CNS defects, cleft lip and palate, rib fusions, and syndactylia in hamsters when injected IV on day 8 of gestation (Gale & Ferm, 1971).

B) CASE SERIES

1) Lauwerys et al (1987) reported the case of a 3 month old with cataracts, anemia, and renal dysfunction resulting from mercury exposure during fetal life and the 1 month lactation period due to the extensive use of inorganic mercury containing soap by the mother.
2) A series of 81 infant-mother pairs were evaluated for identification of a dose-response relationship between methylmercury concentrations in single strands of maternal hair and observed effects in the child following an incident where methyl-mercury-treated seed grain was used in daily preparation of home baked bread and then consumed by the pregnant woman. Children of women with higher exposures to methylmercury during gestation were at greater risk for the development of neurologic findings and developmental delays (Marsh et al, 1987). No mercury concentrations were done in the children.

3.20.3)

A) PLACENTAL BARRIER

1) All forms of mercury move freely across the placenta, and fetal concentrations are at least as high as those in the mother (HSDB , 1990).
2) ANIMAL STUDIES

a) Phenylmercury acetate was found at lower concentrations in Syrian hamster embryos than in the dams when injected IV on day 8 of gestation (Gale & Hanlon, 1976). It was also partially blocked from transfer through the placenta in mice (Suzuki et al, 1967).

B) ABORTION

1) Increased spontaneous abortions, and menstrual dysfunction, have been reported in women exposed to mercury (Goncharuk, 1971; Panova & Ivanova, 1976; Goncharuk, 1977; Marinova, 1973).

C) CASE REPORTS

1) Lien et al (1983) reported a case of acute mercury inhalation toxicity in a pregnant woman. Twenty-six days after the exposure the child was born without clinical abnormalities, but with serum blood levels comparable with the mother's.

3.20.4)

A) BREAST MILK

1) Mercury is found in human breast milk (Mattison, 1983). Oral absorption of mercury is greater in infants than in adults (Barlow & Sullivan, 1982). A level of 4 mcg/L in breast milk is considered dangerous for infants (Mattison, 1983).
2) Gonzalez et al (1985) reported a correlation between total mercury concentrations measured in the hair of nursing neonates and their mothers to be significant.

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS62-38-4 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) IARC Classification

a) Listed as: Phenylmercury acetate
b) Carcinogen Rating: 2B

1) The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. This category is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group.

3.21.2)

A) Phenylmercury acetate was not carcinogenic in mice.

3.21.4)

A) LACK OF EFFECT

1) LACK OF EFFECT

a) Phenylmercury acetate was not carcinogenic in mice (HSDB , 1990).
b) Mercury was not carcinogenic in mice at a level of 5 ppm in the drinking water (Schroeder & Mitchener, 1975).

Genotoxicity

A)

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Obtain whole blood mercury levels, 24 hour urine collection for mercury, baseline BUN, creatinine, urinalysis and electrolytes.
B) NORMAL RANGE - Mercury levels rarely exceed 1.5 mcg/dL.
C) NORMAL URINE EXCRETION - Without chelation therapy, rarely exceeds 50 mcg/24hrs of mercury.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Normal whole blood mercury levels rarely exceed 1.5 mcg/dL in unexposed individuals. Normal levels are approximately 0.5 mcg/dL (Skerfving & Vostal, 1972). Levels of 4 to 220 mcg/dL have been lethal (HSDB , 1990).
2) For organic mercurials such as phenylmercury acetate, the toxic blood level is >20 mcg/dL (HSDB , 1990).
3) Most commonly used analytical methods do not distinguish between inorganic and organic mercury in the blood (Zenz, 1988). The use of blood mercury levels after acute exposure should be considered with the knowledge that a single seafood meal will elevate levels for 20 to 30 hours (Kershaw et al, 1980; Sherlock et al, 1984). Specific analysis of inorganic mercury in the blood did correlate with the level of exposure in workers exposed chronically (Yoshida, 1985).
4) In acute exposures, elevation of blood-mercury level to ranges of 25 to 50 mcg/dL (1246.2 to 2492.5 nmol/L) precede elevations in urinary excretion because of the body's capacity to store mercury (Cherian et al, 1978).
5) Blood mercury levels did not correlate with indicators of toxicity in chronically exposed workers (Rosenman et al, 1986).

4.1.3)

A) URINARY LEVELS

1) Normal urine excretion rarely exceeds 15 mcg/L (74.7 nmol/L) in unexposed individuals. Normal levels are approximately 0.5 mcg/L, with the upper limit of normality being 20 mcg/L (Clayton & Clayton, 1981). Levels of 0.1 to 0.5 mg Hg/L (100 to 500 mcg/L) are considered significantly elevated (Sittig, 1985).
2) Spot urine levels are inconsistent due to diurnal variation. The interpretation of these levels is most accurate when samples are taken at the same time of day and corrected for creatinine. Because proteinurea and glycosuria cause specific gravity changes, correction using this method is less accurate than the creatinine method. Patients with kidney damage should be excluded (Calder et al, 1984).
3) Monitoring of spot urine mercury levels did correlate with occurrence of neuropsychological toxicity and motor nerve conduction velocity in 42 chronically exposed workers (Rosenman et al, 1986).
4) Urine 24-hour delta ALA levels are invaribly elevated to the ranges of 3 to 10 mg/liter in chronic poisoning cases. Although urinary levels as high as 2000 mcg/L have been seen without symptoms, levels greater than 100 mcg/L may need careful behavioral and neurological evaluation (Adams et al, 1983).
5) Workers chronically exposed to mercury vapor exhibited preclinical renal toxicity at spot urine mercury levels of greater than 50 mcg/g creatinine (Roels et al, 1985).
6) Collection of a 24-hour urine sample, followed by challenge with D-penicillamine for 4 days, has been used to document mercury body burden (Ishihara et al, 1974).

4.1.4)

A) OTHER

1) ELECTROPHYSIOLOGICAL TESTING

a) Nerve conduction velocity studies in workers chronically exposed to inorganic mercury are informative for evaluation of mercury toxicity. Slowing of the median motor nerve correlated with both increased blood and urine mercury levels and an increased number of neurologic symptoms (Singer et al, 1987).

2) PULMONARY FUNCTION TESTS

a) If respiratory tract irritation is present, it may be useful to monitor pulmonary function tests.

3) MONITORING

a) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.

Radiographic Studies

A)

1) If respiratory tract irritation is present, monitor chest x-ray.

Methods

A)

1) SUMMARY - Blood, urine, hair and nails can be analyzed for mercury content.
2) HAIR - Single hair strands can be analyzed by x-ray fluorescence (XRF) spectrometry without destroying the hair sample (Toribara et al, 1982). An average rate of uniform hair growth is 1.1 cm/month (Shahristani & Shihab, 1974).
3) STOMACH CONTENTS - A method for the determination of toxic quantities of mercury was reported in simulated stomach contents by energy dispersive x-ray fluorescence (EDXRF). The lower limit of detection was 10 micrograms/milliliter in simulated stomach contents (soup) (Winstanley et al, 1987). This method may not detect mercury at quantities near a normal value.
4) URINE AND BLOOD - Samples can be analyzed for mercury using flameless atomic absorption. The range of detection is 0.003 to >0.3 mg/L for urine and 0.5 to 450 mcg/dL for blood (HSDB , 1994).
5) PHARMACEUTICAL PREPARATIONS - Phenylmercuric acetate was analyzed in pharmaceutical preparations by high-performance liquid chromatography, using a mobile phase of methanol-acetonitrile-0.005 M KH2PO4 in water (1:4:5). The complex with 6-mercaptopurine was detected at 293 nm (Parkin, 1986).
6) NOTE - Most analytical methods detect total mercury and make no distinction between inorganic and organic mercury.

a) Phenylmercuric acetate can be separated from other organic and inorganic mercury compounds using thin-layer chromatography (Furuno et al, 1976).
b) Phenylmercuric acetate can also be analyzed by gas chromatography (Klaue & Hanika, 1984).

7) ENVIRONMENTAL SAMPLES - Mercury can be analyzed in environmental samples by flameless atomic absorption spectrometry with a detection limit of 0.12 to 10 mcg Hg/L in water and industrial waste (Association of Official Analytical Chemists, 1982).

a) Selective ion exchange chromatography can also be used to analyze total mercury in water (Clechet & Eschalier, 1984).
b) Cold vapor techniques have been used to analyze mercury in water and wastewater according to EPA Method 245. Method 7471 is used for solid or semisolid waste, and method 7470 for liquid waste (EPA, 1983) 1986).
c) Mercury can be analyzed in fish by flameless atomic absorption after digestion of the sample with hyrdochloric and nitric acid in a special apparatus connected to the spectrophotometer (Association of Official Analytical Chemists, 1982b).
d) Phenylmercuric acetate in seeds and water was extracted with chloroform, concentrated by evaporation, and identified using paper chromatography with an acetone-water (70-30) solvent system (Prameela Devi & Nanda Kumar, 1984).

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) All acute ingestions should be admitted. Patients with moderate or severe neurologic toxicity felt to be secondary to organic mercury warrant inpatient evaluation for neurology and toxicology consultation, whole blood quantification, and evaluation for possible chelation.

6.3.1.2) HOME CRITERIA/ORAL

A) Patients with chronic exposures can be referred to outpatient healthcare providers for evaluation.

6.3.1.3) CONSULT CRITERIA/ORAL

A) All cases with organic mercury toxicity should involve a toxicology and neurology consultants.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Asymptomatic or minimally symptomatic patients with chronic exposures already in healthcare facilities may be observed and referred to neurology or toxicology outpatient providers. All patients with acute exposures should be referred to a healthcare facility.

Monitoring

A)

B)

C)

Oral Exposure

6.5.1)

A) Dermal exposures should be washed off with soap and water. No other pre-hospital decontamination is indicated. Organic mercury spills should be contained and cleaned by qualified hazardous material abatement crews.

6.5.2)

A) SUMMARY: Most presentations are subacute or chronic exposures, making gastrointestinal decontamination ineffective. However, given the dismal outcomes and limited therapeutic options, aggressive gastrointestinal decontamination including gastric lavage, activated charcoal and whole bowel irrigation is recommended for acute ingestions. Abdominal x-ray may be useful in evaluating the need for gastric lavage. Breastfeeding mothers should continue to pump breast milk and discard.
B) ACTIVATED CHARCOAL

1) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

2) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

C) GASTRIC LAVAGE

1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).

a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.

2) PRECAUTIONS:

a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.

3) LAVAGE FLUID:

a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.

4) COMPLICATIONS:

a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).

5) CONTRAINDICATIONS:

a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.

D) WHOLE BOWEL IRRIGATION

a) WHOLE BOWEL IRRIGATION/INDICATIONS: Whole bowel irrigation with a polyethylene glycol balanced electrolyte solution appears to be a safe means of gastrointestinal decontamination. It is particularly useful when sustained release or enteric coated formulations, substances not adsorbed by activated charcoal, or substances known to form concretions or bezoars are involved in the overdose.

1) Volunteer studies have shown significant decreases in the bioavailability of ingested drugs after whole bowel irrigation (Tenenbein et al, 1987; Kirshenbaum et al, 1989; Smith et al, 1991). There are no controlled clinical trials evaluating the efficacy of whole bowel irrigation in overdose.

b) CONTRAINDICATIONS: This procedure should not be used in patients who are currently or are at risk for rapidly becoming obtunded, comatose, or seizing until the airway is secured by endotracheal intubation. Whole bowel irrigation should not be used in patients with bowel obstruction, bowel perforation, megacolon, ileus, uncontrolled vomiting, significant gastrointestinal bleeding, hemodynamic instability or inability to protect the airway (Tenenbein et al, 1987).
c) ADMINISTRATION: Polyethylene glycol balanced electrolyte solution (e.g. Colyte(R), Golytely(R)) is taken orally or by nasogastric tube. The patient should be seated and/or the head of the bed elevated to at least a 45 degree angle (Tenenbein et al, 1987). Optimum dose not established. ADULT: 2 liters initially followed by 1.5 to 2 liters per hour. CHILDREN 6 to 12 years: 1000 milliliters/hour. CHILDREN 9 months to 6 years: 500 milliliters/hour. Continue until rectal effluent is clear and there is no radiographic evidence of toxin in the gastrointestinal tract.
d) ADVERSE EFFECTS: Include nausea, vomiting, abdominal cramping, and bloating. Fluid and electrolyte status should be monitored, although severe fluid and electrolyte abnormalities have not been reported, minor electrolyte abnormalities may develop. Prolonged periods of irrigation may produce a mild metabolic acidosis. Patients with compromised airway protection are at risk for aspiration.

6.5.3)

A) MONITORING OF PATIENT

1) A basic metabolic panel including renal function tests should be followed since toxicity may be delayed.
2) Whole blood mercury levels are the preferred diagnostic test. Blood should be collected in a trace heavy metal free container approved by the appropriate reference laboratory. The whole blood mercury should be speciated to inorganic and organic fractions. Patients should abstain from fish meals for 1 week prior to testing. Levels of 10 to 15 mcg/L are common in patients eating several fish meals per week. Levels over 200 mcg/L have been associated with symptoms.
3) Hair testing is useful in documenting a remote exposure only, but it has no role in quantification of the exposure.
4) Obtain 24-hour urine collection for long-chain aryl or alkyl mercury compounds (eg, phenylmercury). Urinary mercury levels are NOT useful for determining methylmercury (a short-chain alkyl mercury compound) exposure, since approximately 90% of methyl mercury is cleared through biliary and gastrointestinal tract.
5) Chest x-ray should be obtained for inhalational exposures. Serial visual field testing and neuropsychiatric testing is useful for chronic toxicity monitoring.

B) CHELATION THERAPY

1) Chelation should be performed with one of the following drugs in severe poisonings.
2) All of the effective complexing agents administered to facilitate removal of mercury from the body contain sulfhydryl groups (Clarkson, 1990).

C) SUCCIMER

1) EFFICACY

a) Succimer is an effective mercury chelator with minimal side effects (Clarkson, 1990; Graziano, 1986; Graziano et al, 1978; Graziano et al, 1985; Kosnett et al, 1989). It has been shown to increase urinary mercury excretion and decrease brain levels of mercury in experimental animal models of methyl mercury poisoning (Aaseth & Friedheim, 1978; Kostyniak, 1983; Magos et al, 1978).

1) One study (n=24) evaluated urinary mercury excretion before and after DMSA therapy in healthy fish eaters (two groups 1 to 2 fish servings per week or 3 or more servings per week) and non-fish eaters, to determine whether urine mercury excretion after DMSA would rise above baseline levels to a greater extent in fish eaters. In all patients, blood mercury concentrations and 12-hour urine mercury and creatinine excretions were obtained before and after DMSA therapy (30 mg/kg). Although fish eaters had higher baseline blood mercury concentrations than non-fish eaters (p=0.001), the baseline urinary mercury excretion did not differ between groups (explained by the predominant excretion of alkylmercury in bile as opposed to predominant urinary excretion of inorganic mercury). DMSA therapy increased median urinary mercury excretion in all groups, which was highest in fish eaters (p=0.04). The authors concluded that a simple rise in chelated mercury excretion over baseline excretion is not a reliable diagnostic indicator of mercury poisoning (Ruha et al, 2009).

b) In a rat model of methyl mercury poisoning, DMSA therapy begun after the onset of functional neurologic disturbances prevented the progression of cerebellar damage, reduced brain mercury content, and was associated with some improvement in neurologic findings compared with untreated rats (Magos et al, 1978).

2) SUCCIMER/DOSE/ADMINISTRATION

a) PEDIATRIC: Initial dose is 10 mg/kg or 350 mg/m(2) orally every 8 hours for 5 days (Prod Info CHEMET(R) oral capsules, 2011).

1) The dosing interval is then increased to every 12 hours for the next 14 days. A repeat course may be given if indicated by elevated blood levels. A minimum of 2 weeks between courses is recommended, unless blood lead concentrations indicate the need for prompt retreatment.
2) Succimer capsule contents may be administered mixed in a small amount of food (Prod Info CHEMET(R) oral capsules, 2011).

b) ADULT: Succimer is not FDA approved for use in adults, however it has been shown to be safe and effective when used to treat adults with poisoning from a variety of heavy metals (Fournier et al, 1988). Initial dose is 10 mg/kg or 350 mg/m(2) orally every 8 hours for 5 days (Prod Info CHEMET(R) oral capsules, 2011).

1) The dosing interval then is increased to every 12 hours for the next 14 days. A repeat course may be given if indicated by elevated blood levels. A minimum of 2 weeks between courses is recommended, unless the patient's symptoms or blood concentrations indicate a need for more prompt treatment (Prod Info CHEMET(R) oral capsules, 2011).

3) MONITORING PARAMETERS

a) The manufacturer recommends monitoring liver enzymes and complete blood count with differential and platelet count prior to the start of therapy and at least weekly during therapy (Prod Info CHEMET(R) oral capsules, 2011).
b) Succimer therapy did not worsen preexisting borderline abnormal liver enzyme levels in a prospective evaluation of 15 children with lead poisoning (Kuntzelman & Angle, 1992).

4) SUCCIMER/ADVERSE EFFECTS: The following adverse events have occurred in children and adults during clinical trials: nausea, vomiting and diarrhea; transient liver enzyme elevations; rash, pruritus; drowsiness and paresthesia. Events reported infrequently include: sore throat, rhinorrhea, mucosal vesicular eruption, thrombocytosis, eosinophilia, and mild to moderate neutropenia (Prod Info CHEMET(R) oral capsules, 2011).
5) ODOR: Succimer has a sulfurous odor that may be evident in the patient's breath or urine (Prod Info CHEMET(R) oral capsules, 2005).
6) HYPERTHERMIA: One adult developed acute severe hyperthermia associated with hypotension; rechallenge resulted in hyperthermia with shaking chills and hypertension (Marcus et al, 1991).
7) AVAILABLE FORMS: Succimer (Chemet (R)), 100 mg capsules (Prod Info CHEMET(R) oral capsules, 2011).

D) PENICILLAMINE

1) EFFICACY

a) Penicillamine has been shown to increase urinary mercury excretion (Pierce et al, 1972) and decrease blood mercury levels (Bakir et al, 1976) in patients poisoned with methyl mercury.
b) In a group of patients with chronic methyl mercury poisoning, penicillamine therapy was associated with a mercury half-life of 26 days compared with half lives of 65 and 61 days in untreated and placebo treated controls, respectively (Clarkson et al, 1981).

2) USUAL ADULT DOSE

a) 1 to 1.5 g/day given orally in 4 divided doses (Nelson, 2011).

3) USUAL PEDIATRIC DOSE

a) 15 to 30 mg/kg/day in 3 to 4 divided doses. Initially, a small dose may be given to minimize side effects and then increased gradually (eg, 25% of the desired dose in week 1, 50% in week 2, and the full dose by week 3) (Caravati, 2004; Prod Info DEPEN(R) titratable oral tablets, 2009).

4) ADVERSE REACTIONS

a) COMMON SIDE EFFECTS/CHRONIC DOSING: Fever, anorexia, nausea, vomiting, diarrhea, abdominal pain, proteinuria, and myalgia(Prod Info DEPEN(R) titratable oral tablets, 2009).

1) SERIOUS ADVERSE EFFECTS: Nephrotic syndrome, hypersensitivity reactions, leukopenia, thrombocytopenia, aplastic anemia, agranulocytosis, cholestatic hepatitis, and various autoimmune responses (Prod Info DEPEN(R) titratable oral tablets, 2009; Feehally et al, 1987; Kay, 1986).

5) DURATION OF THERAPY

a) Administer d-penicillamine for 3 to 10 days with daily monitoring of urinary excretion of mercury. If urine mercury falls rapidly, body burden is probably small. Wait 10 days and repeat after a baseline collection to determine if there is a rise on re-chelation therapy indicating further body burden.
b) Repeated courses of D-penicillamine may be required. Regular follow-up of blood and urine mercury levels will establish need for treatment.

6) CAUTIONS

a) Patients allergic to penicillin products may have cross-sensitivity to penicillamine (Prod Info DEPEN(R) titratable oral tablets, 2009).
b) Monitor for proteinuria and hematuria; heavy metals may also cause renal toxicity (Prod Info DEPEN(R) titratable oral tablets, 2009).
c) Monitor CBC with differential, platelet count, and hepatic enzymes (Prod Info DEPEN(R) titratable oral tablets, 2009).
d) CROSS-REACTIVITY: The use of penicillamine in a patient with penicillin allergy is controversial.

1) While positive penicillamine skin tests have been reported in 2.5 to 10 percent of patients with history of penicillin allergy, the risk of rash or anaphylaxis in these patients is unknown. One such patient did not react when challenged with oral penicillamine (Bell & Graziano, 1983).

7) PREGNANCY

a) Penicillamine is considered FDA pregnancy category D(Prod Info CUPRIMINE(R) oral capsules, 2004); it should be avoided if possible in pregnant patients.
b) Use of penicillamine throughout pregnancy has been associated with connective tissue abnormalities, hydrocephalus, cerebral palsy, cardiac and great vessel anomalies, webbing of fingers and toes, and arthrogryposis multipex (Linares et al, 1979; Solomon et al, 1977; Anon, 1981; Beck et al, 1981; Rosa, 1986). However, the teratogenic effect when used in low doses or for short periods of time, as in metal chelation, has yet to be determined.

8) IMPAIRED RENAL FUNCTION

a) Anuria or other evidence of renal dysfunction makes therapy with d-penicillamine dangerous as the main route of elimination of this complex is renal.

E) UNITHIOL

1) DMPS/INDICATIONS: Chelating agent for heavy metal toxicities associated with arsenic, bismuth, copper, lead and mercury (Blanusa et al, 2005).
2) DMPS/DOSING

a) ACUTE TOXICITY

1) ADULT ORAL DOSE:

a) 1200 to 2400 mg/day in equally divided doses (100 to 200 mg 12 times daily) (Prod Info DIMAVAL(R) oral capsules, 2004).

2) ADULT INTRAVENOUS DOSE (Arbeitsgruppe BGVV, 1996; Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013):

a) If oral DMPS therapy is not feasible or in severe toxicity, it may be given intravenously.
b) ADMINISTRATION: DMPS should be injected immediately after breaking open the ampule and should not be mixed with other solutions. DMPS should be injected slowly over 3 to 5 minutes. The opened ampules cannot be reused.
c) First 24 hours: 250 mg intravenously every 3 to 4 hours (1500 to 2000 mg total).
d) Day two: 250 mg intravenously every 4 to 6 hours (1000 to 1500 mg total).
e) Day three: 250 mg intravenously every 6 to 8 hours (750 to 1000 mg total).
f) Day four: 250 mg intravenously every 8 to 12 hours (500 to 750 mg total).
g) Subsequent days: 250 mg intravenously every 8 to 24 hours (250 to 750 mg total).
h) Depending on the patient's clinical status, therapy may be changed to the oral route.

3) PEDIATRIC ORAL DOSE (Arbeitsgruppe BGVV, 1996; Blanusa et al, 2005):

a) There are insufficient clinical data regarding the pediatric use of DMPS. It should be used only if medically necessary.
b) Initial dose: 20 to 30 mg/kg/day orally in many equal divided doses.
c) Maintenance dose: 1.5 to 15 mg/kg/day.

4) PEDIATRIC INTRAVENOUS DOSE (Arbeitsgruppe BGVV, 1996; Blanusa et al, 2005; Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013):

a) There are insufficient clinical data regarding the pediatric use of DMPS. It should be used only if medically necessary.
b) If oral DMPS therapy is not feasible or in severe toxicity, it may be given intravenously.
c) ADMINISTRATION: DMPS should be injected immediately after breaking open the ampule and should not be mixed with other solutions. DMPS should be injected slowly over 3 to 5 minutes. The opened ampules cannot be reused.
d) First 24 hours: 5 mg/kg intravenously every four hours (total 30 mg/kg).
e) Day two: 5 mg/kg intravenously every six hours (total 20 mg/kg).
f) Days three and four: 5 mg/kg intravenously every 8 to 24 hours (total 5 to 15 mg/kg).

b) CHRONIC TOXICITY

1) ADULT DOSE

a) 300 to 400 mg/day orally (in single doses of 100 to 200 mg). The dose may be increased in severe toxicity (Arbeitsgruppe BGVV, 1996; Prod Info DIMAVAL(R) oral capsules, 2004).

c) DMPS/ADVERSE REACTIONS

1) Chills, fever, and allergic skin reactions such as itching, exanthema or maculopapular rash are possible (Hla et al, 1992; Prod Info DIMAVAL(R) oral capsules, 2004). Cardiovascular effects such as hypotension, nausea, dizziness or weakness may occur with too rapid injection of DMPS. Hypotensive effects are irreversible at very high doses (300 mg/kg) (Prod Info DIMAVAL(R) oral capsules, 2004; Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013).

3) SOURCES

a) DMPS is not FDA-approved, but is available outside of the US from Heyl Chem-pharm Fabrik in Germany (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013; Prod Info DIMAVAL(R) oral capsules, 2004). In the US it may be obtained from some compounding pharmacies.

4) EFFICACY

a) In a group of patients with chronic methyl mercury poisoning, DMPS therapy was associated with a mercury half life of 10 days compared with half lives of 65 and 61 days in untreated and placebo treated controls, respectively (Clarkson et al, 1981).
b) In a patient with acute methyl mercury ingestion, DMPS was more effective than penicillamine in increasing urinary mercury excretion (Lund et al, 1984).

5) ADVERSE REACTIONS

a) SKIN REACTIONS: Urticaria, maculopapular rash, and erythema multiforme (Hla et al, 1992).

F) N-ACETYL-PENICILLAMINE

1) DOSE: Oral N-acetyl penicillamine (NAP) 250 mg to 500 mg, 4 times a day for 6 to 10 days (30 mg/kg/day in children) has been associated with increased urinary mercury excretion (Kark et al, 1971; Hryhorczuk et al, 1982; Gledhill & Hopkins, 1972).
2) AVAILABILITY: NAP is still considered experimental and is not generally available as a medicinal preparation.
3) EFFICACY

a) In the Iraq outbreak of methyl mercury poisoning from fungicide-treated wheat NAP was equally effective as d-penicillamine; both resulted in mercury blood half-life of 24 to 26 days, while untreated patients had mean half-lives of 61 to 65 days (Clarkson et al, 1981).
b) NAP has been shown to increase urinary excretion of mercury and decrease brain levels of mercury in animal models of methyl mercury poisoning (Aaseth & Friedheim, 1978; Zimmer & Carter, 1979; Aaseth & Friedheim, 1978).

G) EXPERIMENTAL THERAPY

1) THIOL RESIN - EFFICACY

a) In a group of patients with chronic methyl mercury poisoning, thiolated resin therapy was associated with a mercury half life of 20 days compared with half lives of 65 and 61 days in untreated and placebo treated controls, respectively (Clarkson et al, 1981).
b) Mercaptostarch, a thiol resin, has been shown to increase fecal elimination of methyl mercury in a mouse model (Aaseth & Friedheim, 1978).

H) DIMERCAPROL

1) BAL therapy has been shown to increase brain mercury levels in experimental animal models of methyl mercury (Berlin et al, 1965; Zimmer & Carter, 1979) and phenylmercuric acetate poisoning (Berlin & Rylander, 1964a). It is CONTRAINDICATED in methyl mercury poisoning (Clarkson, 1990).

I) ACETYLCYSTEINE

1) NAC therapy has been shown to reduce methyl mercury-induced fetal mortality and teratogenicity in rodent models (Ornagi et al, 1993).
2) Dialysis performed with n-acetylcysteine infused into the blood as it entered the dialyzer at a rate to produce a 10 millimolar concentration, produced a mean dialysance of 13 milliliters/minute and was associated with a 40-fold increase in urinary mercury excretion in a patient with acute methyl mercury ingestion (Lund et al, 1984).
3) STUDY: Methyl mercury poisoned mice were administered NAC in their drinking water (10 mg/mL) starting at 48 hours after poisoning. NAC-treated mice excreted from 47% to 54% of the radio-labelled mercury in their urine over the next 48 hours, as compared to 4% to 10% excretion in untreated mice. Excretion of inorganic mercury was not affected by oral NAC (Ballatori et al, 1998).

Inhalation Exposure

6.7.1)

A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

6.7.2)

A) SUPPORT

1) Treat pulmonary irritation and systemic effects.
2) Inhalation of alkyl mercury compounds may produce irritation of the mucous membranes. The irritation generally disappears shortly after cessation of exposure (Skerfving & Vostal, 1972).
3) Inhalation of some volatile organic mercury compounds may produce systemic toxicity. Phenyl mercury acetate containing latex paint may release mercury vapors (Agocs et al, 1990; CDC, 1990).

a) Acute inhalation exposure to mercury vapor from can produce local pulmonary effects, systemic effects and elevated urine mercury concentrations (Levin et al, 1988; Agocs et al, 1990). Chelation may be required.

B) MEASUREMENT OF RESPIRATORY FUNCTION

1) PULMONARY FUNCTION: Mild interstitial lung disease has been noted in acute mercury vapor exposure. Pulmonary function tests and chest x-ray may be of value in patients with significant exposure.

C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

6.8.1)

A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).
B) Observe for development of clinical signs and symptoms and follow treatment recommendations in DERMAL EXPOSURE where appropriate.

Dermal Exposure

6.9.1)

A) DERMAL DECONTAMINATION

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

B) PERSONNEL PROTECTION

1) In cases of significant exposure prehospital decontamination should occur outside the medical facility if possible since the wash may contaminate medical personnel and cause them to become poisoned.
2) Remove all contaminated clothing, seal into bags, and treat as hazardous waste. The person performing decontamination may be protected by wearing rubber gloves, disposable shoe covers, and a rubber apron.
3) All medical personnel should wear protective clothing, including respirators if significant amounts of dust are present, to prevent secondary contamination.

6.9.2)

A) BURN

1) APPLICATION

a) These recommendations apply to patients with MINOR chemical burns (FIRST DEGREE; SECOND DEGREE: less than 15% body surface area in adults; less than 10% body surface area in children; THIRD DEGREE: less than 2% body surface area). Consultation with a clinician experienced in burn therapy or a burn unit should be obtained if larger area or more severe burns are present. Neutralizing agents should NOT be used.

2) DEBRIDEMENT

a) After initial flushing with large volumes of water to remove any residual chemical material, clean wounds with a mild disinfectant soap and water.
b) DEVITALIZED SKIN: Loose, nonviable tissue should be removed by gentle cleansing with surgical soap or formal skin debridement (Moylan, 1980; Haynes, 1981). Intravenous analgesia may be required (Roberts, 1988).
c) BLISTERS: Removal and debridement of closed blisters is controversial. Current consensus is that intact blisters prevent pain and dehydration, promote healing, and allow motion; therefore, blisters should be left intact until they rupture spontaneously or healing is well underway, unless they are extremely large or inhibit motion (Roberts, 1988; Carvajal & Stewart, 1987).

3) TREATMENT

a) TOPICAL ANTIBIOTICS: Prophylactic topical antibiotic therapy with silver sulfadiazine is recommended for all burns except superficial partial thickness (first-degree) burns (Roberts, 1988). For first-degree burns bacitracin may be used, but effectiveness is not documented (Roberts, 1988).
b) SYSTEMIC ANTIBIOTICS: Systemic antibiotics are generally not indicated unless infection is present or the burn involves the hands, feet, or perineum.
c) WOUND DRESSING:

1) Depending on the site and area, the burn may be treated open (face, ears, or perineum) or covered with sterile nonstick porous gauze. The gauze dressing should be fluffy and thick enough to absorb all drainage.
2) Alternatively, a petrolatum fine-mesh gauze dressing may be used alone on partial-thickness burns.

d) DRESSING CHANGES:

1) Daily dressing changes are indicated if a burn cream is used; changes every 3 to 4 days are adequate with a dry dressing.
2) If dressing changes are to be done at home, the patient or caregiver should be instructed in proper techniques and given sufficient dressings and other necessary supplies.

e) Analgesics such as acetaminophen with codeine may be used for pain relief if needed.

4) TETANUS PROPHYLAXIS

a) The patient's tetanus immunization status should be determined. Tetanus toxoid 0.5 milliliter intramuscularly or other indicated tetanus prophylaxis should be administered if required.

B) OBSERVATION REGIMES

1) Carefully observe patients with SKIN exposure for the development of any systemic signs or symptoms

C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

A)

1) Hemodialysis, hemoperfusion, and exchange perfusion do not remove significant amounts of mercury after subacute or chronic organic mercury exposure. Hemodialysis in combination with L-cysteine infusion into the arterial blood has been shown to increase mercury clearance in chronic methylmercury intoxication, (L-cysteine converts methylmercury into a diffusible form) but it has not known if this improves outcomes.

B)

1) Hemodialysis has not been shown to reduce a significant amount of the total body burden following acute or chronic ingestion but should be considered early in severely symptomatic patients with diminished urine output (Sauder et al, 1988).

C)

1) Peritoneal dialysis and BAL therapy were associated with a mercury clearance rate of 0.07 to 0.68 mL/minute in a 3-month-old with mercury toxicity from mercaptomerin therapy (Robillard et al, 1976).

D)

1) Hemofiltration has not been studied for organic mercury poisoning. Hemofiltration, begun on the fourth day after overdose of 7 grams of mercuric chloride, removed 1.926 mg of mercury per 24 hours (McLauchlan, 1991).

E)

1) In a dog model Extracorporeal Regional Complexing Hemodialysis (ERCH), using DMSA or cysteine via arterial infusion, produced mercury clearance rates of 25 milliliters/minute and 17 milliliters/minute, respectively (Kostyniak et al, 1977; Kostyniak, 1982).
2) ERCH - using cysteine as the complexing agent increased mercury clearance in 2 patients with chronic methyl mercury intoxication (Bakir et al, 1980).

F)

1) Exchange transfusion performed on 3 children with chronic methyl mercury intoxication was estimated to remove 6% of the body burden, compared with 1% within 24 hours by natural excretion (Bakir et al, 1980).

Abstracts

Range Of Toxicity

Summary

A)

Minimum Lethal Exposure

A)

1) Phenylmercury acetate is an extremely toxic substance. The estimated lethal human oral dose is in the range of 5 to 50 mg/kg (between 7 drops and 1 teaspoon for a 150-pound person) (EPA, 1985).
2) The average lethal dose for organic mercurial compounds is about 100 mg (Baselt, 1988).

Maximum Tolerated Exposure

A)

1) Atmospheric levels exceeding 0.01 milligram/cubic meter organic mercury may be toxic. Maximum tolerated oral concentrations are unknown; acute toxicity occurred following absorption of 60 to 90 milliliters of mercurial fungicides. The daily "safe" limit for methylmercury contaminated fish is 0.03 milligram.

B)

1) A single acute ingestion of 45 milligrams of methylmercury resulted in whole blood levels of 1930 and 1007 nanograms/milliliter 2 and 24 hours after ingestion, but did not result in symptoms of toxicity (Lund et al, 1984).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) ACUTE

a) TOXIC MERCURY LEVELS - Levels of 4 to 220 micrograms/deciliter have been lethal (HSDB , 1994).
b) TOXIC PHENYLMERCURIC ACETATE LEVELS - For organic mercurials such as phenylmercuric acetate, the toxic blood level is >20 micrograms per deciliter (HSDB , 1994).

Workplace Standards

A)

1) Not Listed

B)

1) Not Listed

C)

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Phenylmercuric acetate
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 2B ; Listed as: Phenylmercury acetate

a) 2B : The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. This category is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group.

4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D)

1) Not Listed

Toxicity Information

7.7.1)

A) References: RTECS, 1990

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 13 mg/kg

2) LD50- (ORAL)MOUSE:

a) 13,250 mcg/kg

3) LD50- (SUBCUTANEOUS)MOUSE:

a) 12 mg/kg

4) LD50- (ORAL)RAT:

a) 22 mg/kg

Pharmacology Toxicology

Toxicologic Mechanism

A)

B)

Physicochemical

Physical Characteristics

A)

Molecular Weight

A)

Other

A)

1) Currently not available (CHRIS , 2002)

Animal Toxicology

References

General Bibliography

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