LESSON PLANNER

Course: Pharm D
Year/Semester: Fourth Year Pharm D
Batch: 2021-2027
Academic year & Month: 2025 January
Subject: Clinical Toxicology
Lesson No: 4.6
Chapter/unit: 8
Title of the topic: Introduction, Pharmacokinetics and Sources of Arsenic

Learning objectives: To learn about the Forms, Groups, Pharmacokinetics and Sources
related to Chronic Poisoning with Arsenic.
Introduction:
 Arsenic is a naturally found silver gray, brittle, crystalline metalloid that is a significant
toxin worldwide found in the earth's crust having a concentration of 1.8 ppm.
 It can be existing in 3 allotropic forms.
a) Yellow (Alpha)
b) Black (Beta)
c) Gray (Gamma)
 The Environmental Protection Agency (EPA) and the World Health Organization
(WHO), set the safe contaminant level of arsenic in drinking water to be less than 10 ppb
(0.010mg/L).

 Arsenic is classified as a human carcinogen by IARC (International Association for

 For soluble trivalent arsenic compounds, approximately 95% of the ingested dose is
absorbed from the gastrointestinal (GI) tract.
  Airborne arsenic in the workplace is generally in the form of arsenic trioxide. The
amount of arsenic absorbed by inhalation has not been determined precisely, but it is
thought to be within 60% to 90%. Smaller particles are deposited more deeply in the
respiratory tract.
 Dermal absorption is generally negligible, although toxic systemic effects have resulted
from rare occupational accidents where either arsenic trichloride or arsenic acid was
splashed on workers' skin.
 After absorption it is redistributed to the liver, lungs, intestinal wall, and spleen, where it
binds to the sulfydryl groups of tissue proteins.
 Arsenic is absorbed into the blood stream at the cellular level and is taken up by Red
blood cells, White blood cells, and Other cells that reduce arsenate to arsenite.
 The primary method of metabolizing arsenic in humans is methylation.
 Arsenic is excreted in the urine primarily through the kidneys. Humans excrete a mixture
of inorganic, monomethylated, and dimethylated (but not trimethylated) forms of arsenic.
The pentavalent metabolites MMA V and DMA V are less toxic than arsenite or arsenate.
 Other less important routes of elimination of inorganic arsenic include Feces,
Incorporation into hair and nails Skin desquamation, and Sweat.
 Two to four weeks after exposure ceases, most of the arsenic remaining in the body is
found in keratin-rich tissues such as hair, nails, skin and a lesser extent in bones and
teeth.
 Arsenic exhibit broader carcinogenic potential by the inhalation, oral, and perhaps the
dermal route.
 Arsenic replaces phosphorus in the bone where it may remain for years. It gets deposited
also in hair. While arsenic does not cross the blood-brain barrier easily, it crosses the
placenta readily, it can give rise to intrauterine death of the foetus and is teratogenic. In
less severe intoxications it can cause respiratory distress of the newborn due to
pulmonary haemorrhage and hyaline membrane formation.
 The half-life of inorganic arsenic in humans is about 10 hours.
Natural and Industrial sources:
1. Volcanoes
2. Byproduct of smelting process
 3. Paints, dyes
4. Coal-fired power plants
5. Hardening metal alloys and purifying industrial gases (removal of sulfur).
6. Glass manufacturing
7. Drinking water and Soil
Arsenic Products:
1. Algaecides
2. Desiccants used in mechanical cotton harvesting
3. Herbicides
4. Pesticides
Arsenic is and has been used medicinally:
1. Induction and consolidation chemotherapy for acute promyelocytic leukemia and other
cancers.
2. Traditional remedies from a number of Asian countries.
3. Naturopathic or homeopathic remedies.
4. “Fowlers solution,” which is 1% arsenic trioxide, was used historically to treat skin
conditions such as psoriasis and eczema.
5. Arsphenamin (Salvarsan) was the first effective cure for syphilis until replaced by
antibiotics after World War II.
Arsenic may be found in foods:
1) Seafood (especially bivalves [clams, oysters, scallops, mussels], crustaceans [crabs, lobsters],
and certain cold water and bottom feeding finfish, and seaweed/kelp.
 The organic forms of arsenic found in seafood (mainly arsenobetaine and arsenocholine,
also referred to as “fish arsenic”) are generally considered to be nontoxic, and are
excreted in urine within 48 hours of ingestion.
 However, inorganic forms of arsenic have been found in some types of seaweed (Recent
literature suggests hijiki seaweed has very high levels of inorganic arsenic).
Arsenic Compounds:
 Arsenic compounds can be classified into three major groups:
a) Inorganic
b) Organic
 c) Arsine gas

Inorganic:
 Arsenic combines with oxygen, chlorine and sulfur to create inorganic arsenic
compounds. These compounds may occur naturally in soil and rock. They also occur due
to agriculture and industrial process such as mining, smelting and manufacturing.
 Arsenic enters the air and land from wind-blown dust. It can get into ground water from
runoff and leaching.
 Inorganic arsenic compounds are highly toxic and have been linked to cancer.
Organic:
 Arsenic in plants and animals combines with carbon and hydrogen to create organic
arsenic compounds. Seafood such as fish and shellfish contain organic compounds.
However, most of the arsenic in organic compounds is in a form that’s much less toxic
than inorganic compounds.
Arsine gas:
 Arsine gas is a non-irritating, colorless and nearly tasteless gas.
 Arsine gas, the most toxic arsenical (acute exposures), is used commercially in the
microelectronics industry, and it is encountered accidentally in metallurgical and mining
processes.
 Arsine gas is used in the production of semiconductors, although substitutes of lower
toxicity such as tributylarsine have also been used.
 Arsine forms when acid or other reducing substances are added to arsenic-containing
compounds, such as metals in which arsenic is a low level contaminant. Arsine gas
produces a clinical syndrome very different from other arsenic compounds.
 At low levels, arsine is a potent hemolysin, causing dose-dependent intravascular
hemolysis.
 At high levels, arsine produces direct multisystem cytotoxicity.
The relative toxicity of an arsenical depends primarily on:
a) Inorganic or organic form
b) Valence state
c) Solubility
 d) Physical state and purity
e) Rates of absorption and elimination

References:
1. Principles of toxicology: environmental and industrial applications / edited by Phillip L.
Williams, Robert C. James, Stephen M. Roberts. —2nd ed. Chapter 14.6, Page No. 336.
2. Arsenic toxicity, National Library of medicine, National center for biotechnology
information, Matthew Kuivenhoven; Kelly Mason.
3. Pillay VV. Comprehensive Medical Toxicology. 2nd edn, 2008. Paras Medical Publisher,
Hyderabad, India. 10.- Chapter 9, Page No. 79-83

4. Kim Gehle, CDC/ATSDR Author, U.S. Department of Health and Human Services,
Agency for Toxic Substances and Disease Registry, Division of Toxicology and Human
Health Sciences Environmental Medicine Branch. Arsenic Toxicity CSEM (Case Studies
in Environmental Medicine); 2013.
Summary:
 Prolonged arsenic exposure causes skin and lung cancer and may cause other internal
cancers as well. Human exposure may involve inhalation of arsenic dusts; ingestion of
arsenic in water, food, or soil; or dermal contact with dust, soil or water. The Biological
Fate, Physiologic Effects, Forms, Groups and Sources of Arsenic poisoning were defined
well in this session.

Preview of Next Lesson: We are going to learn about Clinical Symptoms and management
of chronic poisoning with Arsenic.

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