Toxicology:
Not another MT thingy!
History & Milestones
Year
|
Development
|
Early 1500s
|
Paracelsus provides a scientific basis for
understanding poisons.
|
1809
|
F. Magendie reports on the mechanisms of action of arrow poisons.
|
1830–40
|
Orfila devises methods for detecting poisons, thereby proving that
poisoning had taken place and establishing the field of forensic toxicology.
|
1920s–30s
|
Delayed neurotoxicity in individuals who consume ‘bootleg liquor,’
in particular, ‘ginger jake’, contaminated with tri-o-cresyl phosphate.
|
1945
|
R. A. Peters, L. A. Stocken, and R. H. S. Thompson develop British
anti-Lewisite (BAL) as an antidote for arsenic.
P. Muller introduces and studies DDT and related organochlorine
compounds.
|
1952
|
G. Schrader introduces and studies organophosphorus compounds.
|
1950s
|
Over 200 cases of severe neurological disease reported in
individuals consuming fish contaminated with methyl mercury in Minimata,
Japan.
|
1984
|
Approximately 2000 die in Bhopal, India, from acute lung disease associated
with methylisocyanate release.
|
Historically, toxicology laid the foundation
of therapeutics and experimental medicine. Toxicology continues to develop and
expand from the past century by assimilating techniques and knowledge from
branches of biology, chemistry, physics and mathematics. Recently, a new field
was added to toxicology which is the relevance of this discipline to security
evaluation and risk assessment.
Scope
and Definition
Toxicology
is defined as the branch of medical science that deals with poisons,
which are substances that causes a detrimental effect when administered, either
by accident or by plan, to a living organism especially to humans. By principle,
toxicology also includes the study of harmful effects brought about by substantial
phenomena, such as radiation, noise, and so on. Toxicology has
also been defined as the study of the unfavorable effects of xenobiotics that has evolved from ancient poisoners.
In practice, however, many complications exist beyond these plain definitions,
both in bringing more accurate definition to the meaning of poison and to the quantification
of toxic effects.
Fate and effect of toxicants in the body.
Areas of Toxicology
Graphical
representation of the interconnections between different areas of toxicology.
Mechanistic toxicology
is concerned with the identification and understanding of cellular,
molecular, and biochemical mechanisms by which chemicals bring about toxic
effects on living organisms.
Descriptive toxicology deals directly with toxicity testing, which provides information for safety evaluation and regulatory requirements. The appropriate toxicity tests in cell culture systems or experimental animals are intended to yield information to evaluate risks posed to humans as well as the environment from contact to specific chemicals.
Regulatory toxicology has the sole responsibility for deciding, on the starting point of data provided by descriptive and mechanistic toxicologists, whether a chemical or a drug poses a sufficiently low risk to be marketed for a declared purpose or consequent human or environmental exposure resulting from its use.
Descriptive toxicology deals directly with toxicity testing, which provides information for safety evaluation and regulatory requirements. The appropriate toxicity tests in cell culture systems or experimental animals are intended to yield information to evaluate risks posed to humans as well as the environment from contact to specific chemicals.
Regulatory toxicology has the sole responsibility for deciding, on the starting point of data provided by descriptive and mechanistic toxicologists, whether a chemical or a drug poses a sufficiently low risk to be marketed for a declared purpose or consequent human or environmental exposure resulting from its use.
Sources of toxicants
Exposure Classes.
Exposure classes include toxicants in food, air, water, and soil as well as
toxicants characteristic of domestic and occupational settings.
Use Classes. Use classes include drugs of abuse, therapeutic drugs, agricultural chemicals, food additives and contaminants, metals, solvents, combustion products, cosmetics, and toxins. Some of these, such as combustion products, are the products of use processes rather than being use classes.
Routes
- Ü Gastrointestinal tract (ingestion)
- Ü Lungs (inhalation),
- Ü Skin (topical, percutaneous, or dermal)
- Ü Parenteral (other than intestinal canal) routes.
Toxic agents
- Ü Pesticides/herbicides/fungicides
- Ü Metals
- Ü Industrial chemicals
- Ü Vapors and gases
- Ü Naturally occurring toxins
- Ü Drugs
Toxicity Screening
- 1. Acute toxicity
- Ø administration of progressively larger single doses up to the lethal dose
- Ø “No-Effect” dose – largest dose at which a specific toxic effect is NOT seen
- Ø Minimum Lethal Dose – smallest amount of the drug that can kill a study animal
- Ø LD50 – dose that kills half of the experimental animal population
- 2. Subacute / chronic toxicity
- Ø administration of multiple doses to detect any adverse effects
Mutagenicity
Ø detection of possible ability to induce
genetic alteration (mutation)
Carcinogenicity
Ø detection of possible ability to induce
abnormal clonal uncontrolled proliferation of genetically altered cells
Teratogenicity
Ø detection of possible deleterious effects
on the developing fetus
Most Common Causes of Poisoning
Circa
1964
|
|
Death
|
Disability
|
•
Barbiturates
•
Carbon monoxide
•
Phenols; Cresols
•
Methanol
•
Ethanol
•
Cyanide
•
Arsenic fluoride
•
Mercury
•
Salicylates
|
•
Ethanol
•
Barbiturates
•
Lead
•
Arsenic
•
Salicylates
•
Carbon monoxide
•
Methanol
•
Antihistamines
•
Nonbarbiturate
hypnotics
•
phenothiazines
|
Food poisoning in the Philippines
- Salmonella - raw/contaminated
meat, poultry, meat, egg yolks
- Campylobacter – meat & poultry
- Shigella – raw, ready to eat produce
- Cryptosporidium – water, fruit, salad vegetables
- E. coli – contaminated water, beef
(fecal)
- Yersinia – inadequately cooked / raw pork
- Listeria – inadequately cooked/raw pork
- Vibrio – oysters
& other shellfish
- Cyclospora – imported fresh produce
Come bitter
pilot, now at once run on
The dashing rocks
thy seasick weary bark!
Here’s to my
love! O true apothecary!
Thy drugs are
quick. Thus with a kiss I die.
(Romeo and
Juliet, act 5, scene 3)
Thank you and
watch out for my next post! J
References:
Klaassen,
Curtis. Casarett & Doull’s Toxicology the Basic Science of Poisons, 7th
edition
McQueen,
Comprehensive Toxicology 2nd edition
Hodgson,
Ernest. A Textbook of Modern Toxicology 4th edition
