Introduction to Toxicology and Important Definitions

Introduction to Toxicology

• Toxicology is the study of the adverse effects of chemicals on living organisms.
• Toxicologists examine the nature of these effects, including their cellular, biochemical, and molecular mechanisms of action, and assess the probability of their occurrence.

Toxicology Testing

• Toxicology testing, also known as safety testing or toxicity testing, is conducted to determine the degree to which a substance can damage a living or non-living organism.
• Acute toxicity tests involve a single dose in each animal on one occasion to determine gross behavior and LD50 or median lethal dose.
• Chronic tests involve dosing two species, one rodent and one non-rodent, daily for six months.
• Sub-acute tests involve dosing animals daily, starting at around expected therapeutic level and increasing stepwise every two to three days until toxic signs are observed.

Toxicants and Poisons

• Toxicants are substances that produce adverse biological effects of any nature, and may be chemical or physical in nature.
• Toxins are specific proteins produced by living organisms, such as mushroom toxins, which exhibit immediate effects.
• Poisons are toxicants that cause immediate death or illness when experienced in very small amounts.

Mechanisms of Toxicology

• Mechanistic toxicology identifies the cellular, biochemical, and molecular mechanisms by which chemicals exert toxic effects on living organisms.
• Descriptive toxicology is concerned with toxicity testing, which provides information for safety evaluation and regulatory requirements.
• Regulatory toxicology decides whether a drug or another chemical poses a sufficiently low risk to be marketed for a stated purpose.

Specialized Areas of Toxicology

• Environmental toxicology focuses on the impacts of chemical pollutants in the environment on biological organisms.
• Workplace drug testing is conducted for administrative purposes, and results are often used as evidence in court.
• Diagnostic or hospital (clinical) drug testing is conducted to assist in medical treatment.
• Forensic toxicological analysis is conducted for medical-legal purposes, including death and criminal investigations.

Toxic Effects

• The dose makes the poison, and all substances are poisons; there is none that is not a poison.
• The right dose differentiates a poison from a remedy, according to Paracelsus (1493–1541).
• Immediate toxic effects occur or develop rapidly after a single administration of a substance, whereas delayed toxic effects occur after the lapse of some period of time.
• Reversible toxic effects occur when a chemical produces pathological injury to a tissue, and the ability of that tissue to regenerate largely determines whether the effect is reversible or irreversible.

Interactions of Chemicals

• Additive effects occur when the combined effect of two chemicals is equal to the sum of the effects of each agent given alone.
• Synergistic effects occur when the combined effects of two chemicals are much greater than the sum of the effects of each agent given alone.

Spectrum of Undesired Effects

• Allergic reactions occur when a chemical combines with an endogenous protein to form an antigen (or immunogen), leading to an immunologically mediated adverse reaction to a chemical.