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prn8099 - Number 34, June 2002

Food Scare

Acrylamides' toxic metabolite, glycidamide binds to DNA and cause genetic damage. Its monomer cause degenaration of peripheral nerves that is axonopathy.

A recent report from the Swedish National Food Administration (NFA) has drawn public attention to a substance known as "acrylamide" which according to a research done by a scientific group from the University of Stockholm, may be present in starchy foodstuff baked or heated to high temperatures.

Acrylamide is a chemical used in the manufacture of a number of consumer products, including textiles, contact lenses, appliances, building materials, cosmetic and soap preparations, food, and gelatin capsules (Kirk-Othmer V.6, 1979).

Human exposure to acrylamide is primarily occupational, however, the general public may be exposed through contaminated drinking water from polyacrylamide flocculants used in water treatment (Brown et al., 1980a; Howard, 1990). However, these are already strictly controlled by environmental regulations.

The toxicological effects of acrylamide in animal studies are well known. Its toxic metabolite, glycidamide binds to DNA and cause genetic damage. Its monomer causes degeneration of peripheral nerves, that is axonopathy. Acrylamide-induced axonopathy is characterised by loss of sensory input and impairment of motor nerves, which result in numbness and ataxia. At higher doses, the compound also affects the central nervous system. In addition, it has been reported that acrylamide induces carcinogenic, developmental and reproductive effects. However, an IARC (International Agency for Research in Cancer) Working Group of WHO (World Health Organisation) reported in 1994 that there were no adequate data available to evaluate the carcinogenecity of acrylamide in humans.

FAO's (Food and Agriculture Organisation) comment in the wake of the NFA's announcement is, 'It is too early to reach any firm conclusions on the unexpected finding of the toxic chemical acrylamide in fried and baked food,' and it added that it welcomed the suggestion by Swedish authorities to study the findings in coop­eration with international organisations and has already requested access to the data.

WHO has announced that it will organize an expert consultation as soon as possible to determine the full extent of the public health risk from acrylamide in food. WHO emphasized that several questions still need to be resolved before more definitive advice can be given. For example, is acrylamide taken up from food as readily as it is from water? If it is, what is the risk that this uptake will lead to harmful effects in humans?

The WHO informal expert consultation, planned to take place before the end of June, will look at these questions. Other topics that the consultation will consider are epidemiological data, levels in food in other countries, processing conditions that either increase or reduce those levels, and development of appropriate guidance to reduce exposure to acrylamide. Meanwhile, neither WHO nor FAO has changed their basic dietary advice on tak­ing more fibre-rich food and less fat-containing foods. 

Position statements: Single-dose activated charcoal

American Academy of Clinical Toxicology; European Association Of Poison Centres and Clinical Toxicologists


Overall, the mortality from acute poisoning is less than one percent. The challenge for clinicians managing poisoned patients is to identify promptly those who are most at risk of developing serious complications and who might potentially benefit, therefore, from gastrointestinal decontamination.

Single-dose activated charcoal therapy involves the oral administration or instillation by nasogastric tube of an aqueous preparation of activated char­coal after the ingestion of a poison.


Activated charcoal comes in direct contact with and adsorbs poisons in the gastrointestinal tract, decreasing the extent of absorption of the poison, thereby reducing or preventing systemic toxicity.

In Vitro Studies

Scores of compounds, including many drugs, have been shown to be adsorbed to activated charcoal to varying degrees.

Animal Studies

The administration of activated char­coal in animal studies has produced variable reduction in marker absorption.

Volunteer Studies

The results of 115 comparisons with 43 drugs indicate considerable variation in the absolute amount of char­coal used (0.5100 g) and the time of administration (up to 240 minutes after ingestion).

In these studies, when activated charcoal was administered 30 minutes or less following drug administration, the mean bioavailability was reduced by 69.1%. When activated charcoal was administered at 60 minutes following drug administration, the mean reduc­tion in bioavailability was 34.4%.

In 40 studies involving 26 drugs, using at least 50 g of activated charcoal, the mean reduction in drug absorption was 88.6% when charcoal was admin­istered up to 30 minutes after dosing; mean reduction at 60 minutes was 37.3%

Clinical Studies

There are no satisfactorily designed clinical studies assessing benefit from single-dose activated charcoal.

One study of symptomatic patients who received activated charcoal and some form of gastric evacuation (gastric lavage, ipecac, gastric aspiration) showed that patients receiving gastric aspiration and activated charcoal were less likely to be admitted to an intensive care unit.


Based on volunteer studies, activated char­coal is more likely to produce benefit if administered within 1 hour of poison ingestion.

The administration of activated charcoal may be considered if a patient has ingested a potentially toxic amount of a poison up to 1 hour following ingestion.

Activated charcoal may be considered more than 1 hour after ingestion, but there are insufficient data to support or exclude its use.

Dosage Regimen

The optimal dose of activated charcoal for poisoned patients is unknown, though available data imply a dose-response relationship that favors larger doses.

Data derived from animal and human volunteer studies have little relevance to the clinical situation because these experimental studies were performed in fasting animals and human subjects who ingested a known quantity of drug.

The United States Pharmacopeia (USP DI, 1997) recommends the following oral dosage regimen.

Children up to one year of age:1 g/kg

Children 1 to 12 years of age:25 to 50 g

Adolescents and adults:25 to 100 g

Constipation has not been observed after the administration of a single dose of activated charcoal.


An unprotected airway.

A gastrointestinal tract not anatomically intact.

When activated charcoal therapy may increase the risk and severity of aspiration (e.g., hydrocarbons with a high aspiration potential).


Few serious adverse effects or complications from the use of single-dose activated charcoal have been reported in poisoned patients. Following the administration of aqueous activated charcoal, emesis occurs infrequently. However, the incidence of emesis appears to be greater when activated charcoal is administered with sorbitol. With inadequate airway management, pulmonary aspiration has occurred following the administration of activated charcoal. Aspiration of charcoal containing povidone has led occasionally to major respiratory problems. Corneal abrasions may occur upon direct ocular contact.

(Full text of this article can be obtained from the National Poison Centre, USM, Penang, or from http://clintox.org/PosJStatements/Intro.html


Poison Content Toxicity Profile Management

Nail hardener/nail strengtheners

Toluene, Ethyl Acetate, Acetone, Isopropanol (Information of Toluene, Acetone, and Alcohol have been described earlier in PRN8099, Number 32 & 33, February & April 2002

Ingestion (Ethyl Acetete)

Low in toxicity with small volume

May cause mild mucous membrane irritation

Eye/Skin Exposure

May cause conjunctival irritation

Prolonged dermal contact may cause dryness and cracking


Gastric lavage in ingestion

Symptomatic and supportive


Irrigate with copious amount of tepid water or saline for 15 minutes

Wash skin thoroughly with water

Skin whiteners/spots remover

Hydroquinone with concentration from 2% to 5%


Moderately or severely toxic depending on amount of ingestion

May cause dypsnea, cyanosis, GI distress, convulsion and hemolytic anaemia in ingestion of between 5-15 gm

Eye/skin Exposure

May result in corneal injury

May cause mild irritation to inflammation and burns in hypersensitive individuals


Dilution with milk or water

Activated charcoal

Gastric lavage

Symptomatic and supportive


Irrigate eyes with copious amount of tepid water or saline for at least 15 minutes

Wash skin thoroughly with water

Lipstick, Facial make-ups, Eye make-ups (except black eye make-ups which may coantain lead)

Waxes, oil, fats


Relatively non-toxic


Symptomatic and supportive

Skin whiteners/spots remover

Waxes, water, fats in surfactants (Alcohol, if present, is in a concentration of <10%)


May cause mild gastrointestinal discomfort

Eye Exposure

Minor irritation


Symptomatic and supportive


Rinse with copious amount of tepid water for 15 minutes


Review on
Management of Mercury Toxicity
by Dr Syed Azhar Syed Sulaiman, PharmD,
Clinical Pharmacy Discipline,
School of Pharmaceutical Sciences,Universiti Sains Malaysia.


Mercury is a naturally occurring metal that has several forms. The metallic mercury is a shiny, silver-white, odorless liquid. If heated, it is a colorless, odorless gas.

Mercury combines with other elements, such as chlorine, sulfur, or oxygen, to form inorganic mercury compounds or "salts," which are usually white powders or crystals. Mercury also combines with carbon to make organic mercury compounds. The most common one, methyl mercury, is produced mainly by microscopic organisms in the water and soil. More mercury in the environment can increase the amounts of methyl mercury that these small organisms make.

Mercury is present in numerous chemical forms. Elemental mercury itself is toxic and cannot be broken down into less hazardous compounds. Elemental or inorganic forms can be transformed into organic (especially methylated) forms by biological systems. Not only are these methylated mercury compounds toxic, but highly bioaccumulative as well. The increase in mercury as it rises in the aquatic food chain results in relatively high levels of mercury in fish consumed by humans. Widespread poisoning of Japanese fisherman and their families occurred in Minamata, Japan in the 1950's as a result of consumption of methyl mercury contam­inated fish.

Metallic mercury is used to produce chlorine gas and caustic soda, and is also used in thermometers, dental fillings, and batteries. Mercury salts are sometimes used in skin lightening creams and as antiseptic creams and ointments.

In the 1940s and 1950s, mercury became known as the product that caused acrodynia, also known as Pink Disease. Manifestations of acrodynia include pain and erythema of the palms and soles, irritability, insomnia, anorexia, diaphoresis, photo­phobia, and rash.

Some of the more recent exposures include Minamata Bay in Japan (1960), mercury contaminated fish in Canada, treated-grain in Iraq (1960, 1970). and, in the US (1996), a beauty cream product from Mexico called "Crema de Belleza-Manning."

Mercury poisoning usually is misdiagnosed because of the insidious on­set, nonspecific signs and symptoms, and lack of knowledge within the medical profession. Mercury is found in many industries such as battery, thermometer, and barometer manufacturing. Mercury can be found in fungicides used in the agricultural industry. Before 1990, paints contained mercury as an antimildew agent. In medicine, mercury is used in dental amalgams and various antiseptic agents.

How does mercury toxicity occur?

Mercury in any form is toxic. The difference lies in how it is absorbed, the clinical signs and symptoms, and the response to treatment modalities. Mercury poisoning can result from vapor inhalation, ingestion, injection, or absorption through the skin.

Elemental mercury (Hg) is found in liquid form, which easily vaporizes at room temperature and is well absorbed (80%) through inhalation. Its lipid-soluble property allows for easy passage through the alveoli into the bloodstream and red blood cells (RBCs). Once inhaled, elemental mercury is mostly converted to an inorganic divalent or mercuric form by catalase in the erythrocytes. This inorganic form has similar properties to inorganic mercury (e.g., poor lipid solubility, limited permeability to the blood brain barrier, and excretion in feces). Small amounts of nonoxidized elemental mercury continue to persist and account for central nervous system toxicity.

Elemental mercury as a vapor has the ability to penetrate the CNS, where it is ionized and trapped, attributing to its significant toxic effects. Elemental mercury is not well absorbed by the GI tract and, therefore, when ingested (e.g., thermometers), is only mildly toxic.

Inorganic mercury, found mostly in the mercuric salt form (e.g., batteries), is highly toxic and corrosive. It gains access to the body orally or dermally and is absorbed at a rate of 10% of that ingested. It has a nonuniform mode of distribution secondary to poor lipid solubility and accumulates mostly in the kidney, causing significant renal damage. Although poor lipid solubility characteristics limit CNS penetration, slow elimination and chronic exposure allow for significant CNS accumulation of mercuric ions and subsequent toxicity. Chronic dermal exposure to inorganic mercury also may lead to toxicity.

Excretion of inorganic mercury, as with organic mercury, is mostly through feces. Renal excretion of mercury is considered insufficient and attributes to its chronic exposure and accumulation within the brain, causing CNS effects.

Organic mercury can be found in 3 forms, aryl and short and long chain alkyl compounds. Organic mercurials are absorbed more completely from the GI tract than inorganic salts are; this is because of intrinsic properties, such as lipid solubility and mild corrosiveness (although much less corrosive than inorganic mercury). Once absorbed, the aryl and long chain alkyl compounds are converted to their inorganic forms and possess similar toxic properties to inorganic mercury. The short chain alkyl mercurials are readily absorbed in the GI tract (90-95%) and remain stable in their initial forms. Alkyl organic mercury has high lipid solubility and is distributed uniformly throughout the body, accumulating in the brain, kidney, liver, hair, and skin. Organic mercurials also cross the blood brain barrier and placenta and penetrate erythrocytes, attributing to neurological symptoms, teratogenic effects, and high blood to plasma ratio, respectively.

Methyl mercury has a high affinity for sulfhydryl groups, which at­tributes to its effect on enzyme dysfunction. One enzyme that is inhibited is choline acetyl transferase, which is involved in the final step of acetylcholine production. This inhibition may lead to acetyl­choline deficiency, contributing to the signs and symptoms of motor dysfunction.

Excretion of alkyl mercury occurs mostly in the form of feces (90%), secondary to significant enterohepatic circulation. The biological half-life of methyl mercury is approximately 65 days. Organic mercury is found most commonly in antiseptics, fungicides, and industrial run-off.

What are the causes of the toxicity?

There are few reasons that contributed to mercury toxicity, which can be divided into, elementary, inorganic and organic toxicity as listed below:

  • Causes of elemental mercury toxicity include barometers, batteries, bronzing, calibration instruments, chlor-aiki production, dental amalgams, electroplating, fingerprinting products, fluorescent and mercury lamps, infrared detectors, the jewelry industry, manometers, neon lamps, paints, paper pulp production, photography, silver and gold production, semiconductor cells, and thermometers.
  • The causes of inorganic mercury toxicity include antisyphilitic agents, acetaldehyde production, chemical laboratory work, cosmetics, disinfectants, explosives, embalming, fur hat processing, ink manufacturing, mercury vapor lamps, mirror silvering, the perfume industry, photography, spermicidal jellies, tattooing inks, taxidermy production, vinyl chloride production, and wood preservation.
  • The causes of organic mercury toxicity include antiseptics, bactericidals, embalming agents, the farming industry, fungicides, germicidal agents, insecticidal products, laundry products, diaper products, paper manufacturing, pathology products, histology products, seed preservation, and wood preservatives.
  • Another cause of organic mercury toxicity is thimerosal, an additive preservative used in vaccines to prevent bacterial contamination. The most commonly used vaccines that contain Thimerosal are for diphtheria-tetanus-whole cell pertussis (DTP), Haemophilus influenzae (HIB), and hepatitis B.

What are the clinical presentations for mercury toxicity?

The diagnostic approach for patients with suspected mercury toxicity begins with a thorough history that includes occupations, hobbies, and levels of seafood intake. All toxic presentations, whether acute, chronic, or sub acute, are difficult diagnoses because multiple organ systems are affected (e.g., CNS, kidney, mucous membranes) and can mimic a variety of other diseases. If no such history exists, clinical suspicion can be confirmed by laboratory analysis.

The clinical presentation of mercury toxicity can manifest in a variety of ways, depending on the nature of the exposure, the intensity of the exposure, and the chemical form. Acute toxicity usually is related to the inhalation of elemental mercury or ingestion of inorganic mercury. Exposure to organic mercury leads to chronic toxicity and, occasionally, acute toxicity.

  • Acute exposure caused by inhaled elemental mercury can lead to pulmonary symptoms. Initial signs and symptoms, such as fever, chills, shortness of breath, metallic taste, and pleuritic chest pain, may be confused with metal fume fever. Other possible symptoms could include stomatitis, lethargy, confusion, and vomiting.
  • Recovery is usually without sequela, but pulmonary complications of inhaled toxicity may include interstitial emphysema, pneumatocele, pneumothorax, pneumomediastinum, and interstitial fibrosis. Fatal ARDS has been reported following elemental mercury inhalation.
  • Chronic and ntense acute exposure causes cutaneous and neurological symptoms. The classic triad found in chronic toxicity is tremors, gingivitis, and erethism (i.e., a constellation of neuropsychiatric findings that includes insomnia, shyness, memory loss, emotional instability, depression, anorexia, vasomotor disturbance, uncontrolled perspiration, and blushing).
  • Additional findings may include head­ache, visual disturbance (eg, tunnel vision), peripheral neuropathy, salivation, insomnia, and ataxia.
  • Without a complete history, mercury toxicity, especially in elderly individuals, can be misdiagnosed as Parkinson disease, senile dementia, metabolic encephalopathy, depression, or Alzheimer disease.
  • Elemental mercury has poor Gl absorption and, therefore, oral or rectal exposure to elemental mercury from a thermometer should have no toxic effect. Dental amalgams also contain elemental mercury. Dental professionals who are in contact with amalgam must follow specific guidelines to avoid exposure to toxic amounts of aerosolized elemental mercury. Patients with dental amalgam fillings have slightly elevated levels in their urine, but these findings have not correlated with any systemic disease.
  • Inorganic mercury or mercuric salt exposure mainly occurs through the oral and Gl tract. Its corrosive properties account for most of the acute signs and symptoms of inorganic mercury or mercuric salt toxicity. The acute presentation can include ashen-gray mucous membranes secondary to precipitation of mercuric salts, hematochezia, vomiting, severe abdominal pain, and hypo-volemic shock. Systemic effects usually begin several hours postingestion and may last several days. These effects include metallic taste, stomatitis, gingival irritation, foul breath, loosening of teeth, and renal tubular necrosis leading to oliguria or anuria.
  • All forms of mercury are toxic to the fetus, but treated most readily passes through the placenta. Even with an asymptomatic patient, maternal exposure can lead to spontaneous abortion or retardation.

Clinical Updates
Acute Renal Failure(ARF) from Hemoglobinuric and Interstitial Nephritis Secondary to Iodine and Mefenamic Acid
Author(s): Sinniah R, Lye W C
Source: Clin Nephrol, Vol 55, Iss 3, Pg 254-258, Yr 2001.
Abstract: A unique case presentation of ARF from hemoglobinuric and acute interstitial nephritis secon­dary to suicidal ingestion of potassium iodide solution and also ingestion of a few mefenamic acid tab­lets. These agents led to potentation of the renal injury from hemoglobinuric tubulopathy, probably from the iodine, and renal dysfunction from alteration of renal perfusion, and induction of acute interstitial nep­hritis from mefenamic acid, leading to ARF which was reversible by hemodialysis and supportive therapy.
Hypokalemic Metabolic Acidosis Attributed to Cough Mixture Abuse
Author(s): Wong K M; Chak W L; Cheung C Y; Chan Y H; et.al
Source: Am J Kidney Dis, Vol 38, Issue 2, Pg 390-394, Yr 2001.
Abstract: This report describes a patient with mixed normal anion gap hyperchloremic metabolic and respiratory acidosis associated with hypokalemia attributed to cough mixture abuse. Metabolic acidosis was likely related to ammonium chloride, whereas respiratory acidosis was probably related to the hypokalemia on the respiratory muscles, causing hypoventilation. Hypokalemia was caused by a transcellular shift of potassium induced by ephedrine and pseudoephedrine.
Acute Nicotine Poisoning Associated with a Traditional Remedy for Eczema
Author(s): Davies P; Levy S; Pahari A; Martinez D
Source: Arch Dis Child, Vol 85, Issue 6, Pg 500-502, Yr 2001
Abstract: A case of severe acute nicotine poisoning in an 8 year old boy with moderate eczema after topical application of a traditional remedy from a book published in Bangladesh. Symptoms consistent with nicotine poisoning developed within 30 minutes of application of the remedy. The child subse­quently improved with supportive care and was discharged after 5 days with no neurological sequelae.
An Unusual Presentation of Opioid-Like Syndrome in Pediatric Valproic Acid Poisoning.
Author(s): Espinoza 0. et.al.
Source: Veterinary and Human Toxicology, Vol 43, Issue 3, Pg 178-179, Yr 2001.
Abstract: A case report of a 3 year-old boy who accidentally poisoned himself with valproic acid. Clinical features included profound coma, depressed respiration and miosis responsive to naloxone, gastric lavage, and activated charcoal and a saline cathartic. The patient fully recovered and was discharged 24 h after the admission.





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