Toxicology

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Toxicology Definition: Toxicology is the study of the adverse effects of chemical, physical or biological agents on living organisms and the ecosystem, including the prevention and amelioration of such adverse effects. Modern toxicology uses chemicals as tools to understand molecular/cellular biology.

[edit] Discussion

Toxicity is the adverse end product of a series of events that is initiated by exposure to chemical, physical or biological agents. Toxicity can manifest itself in a wide array of forms, from mild biochemical malfunctions to serious organ damage and death. These events, any of which may be reversible or irreversible, include absorption, transport, metabolism to more or less toxic metabolites, excretion, interaction with cellular macromolecules and other modes of toxic action. Toxicology integrates the study of all of these events, at all levels of biological organization, from molecules to complex ecosystems. The broad scope of toxicology, from the study of fundamental mechanisms to the measurement of exposure, including toxicity testing and risk analysis, requires an extensively interdisciplinary approach. This approach utilizes the principles and methods of other disciplines, including molecular biology, chemistry (analytical, organic, inorganic and biochemistry), physiology, medicine (veterinary and human), computer science and informatics.[1]

[edit] History

Toxicology is arguably the oldest scientific discipline, as the earliest humans had to recognize which plants were safe to eat. Humans are exposed to chemicals both deliberately and inadvertently. Most exposure of humans to chemicals is via naturally occurring compounds consumed in the diet from food plants.

[edit] Role of Toxicology In Drug development

[edit] What Do Toxicologists Do?

Most Toxicologists work to assess and understand how chemicals affect living systems.

• Develop mechanistic understanding of effects
• Ensure safer chemical products
• Develop safer drugs & medicines
• Determine risks from chemical exposures
• Develop treatments for chemical exposures
• Ensure a safe food and water supply
• Forensics

[edit] Who are Toxicologists?

Toxicology involves integration of information from many different areas of expertise. People working in toxicology can also be called:

• Biochemists
• Chemists
• Pathologists
• Cancer Researchers
• Veterinarians
• Medical Doctors
• Cell and Molecular Biologists
• Engineers
• Mathematicians
• Statisticians
• Lab Technicians
• Animal Care Providers

[edit] Major areas of specialization in toxicology

• Mechanistic toxicology (basic biology and chemistry)‏
• Descriptive toxicology (testing)‏
• Regulatory toxicology (rule making and compliance)‏
• Risk assessment (modeling)‏
• Translational and clinical (applying basic research to patient care)‏

[edit] Exposure

Sources of exposure to chemicals

• Environmental, including home and school
• Occupational
• Therapeutic
• Dietary
• Accidental
• Deliberate

In order for a chemical to produce a biological effect, it must first reach a target individual (exposure pathway). Then the chemical must reach a target site within the body (toxicokinetics). Toxicity is a function of the effective dose (how much) of a foreign chemical (xenobiotic) at its target site, integrated over time (how long). Individual factors such as body weight will influence the dose at the target site.

[edit] Route of Exposure

The route (site) of exposure is an important determinant of the ultimate dose—different routes may result in different rates of absorption.

• Dermal (skin)‏
• Inhalation (lung)‏
• Oral ingestion (Gastrointestinal)‏
• Injection

The route of exposure may be important if there are tissue-specific toxic responses. Toxic effects may be local or systemic

[edit] Time of Exposure

How long an organism is exposed to a chemical is important. Duration and frequency contribute to dose. Both may alter toxic effects.

• Acute Exposure = usually entails a single exposure
• Chronic Exposures = multiple

[edit] Dose (The Key Concept in Toxicology)

“All things are poisonous, only the dose makes it non-poisonous.” [Father of Modern Toxicology, Paracelsus—1564]

Dose alone determines toxicity. All chemicals—synthetic or natural—have the capacity to be toxic. All Interactions between chemicals and biological systems follow a Dose-Response Relationship.

[edit] Dose-Response Relationship

• A key concept in Toxicology is the quantitative relationship between the concentration of a xenobiotic in the body and the magnitude of the biological effect it produces.
• The magnitude of the effect of a xenobiotic is usually a function of the amount of xenobiotic to which a person is exposed (i.e., “The Dose Makes the Poison”).
• In any given population, there will be a range of sensitivities to a xenobiotic. It is extremely useful to know what is the average sensitivity of a population to a xenobiotic, and what the average dose required to elicit a toxic response will be.

The magnitude of the toxic response is proportional to the concentration (how much) of the chemical at the target site. The concentration of a chemical at the target site is proportional to the dose. Four important processes control the amount of a chemical that reaches the target site.

• Absorption
• Tissue distribution
• Metabolism
• Excretion