[1] Principles of Toxicity

Toxicology

The scientific study of how toxicants/poisons and other substances cause harm

Etymology of Toxicology

“Toxicon” (poison) + “logos” (to study)

Forensic Toxicology

Involved with the process of solving what caused patient poisoning

Clinical Toxicology

Involved with the investigation of the effect(s) of an agent to patients, usually in a clinical setting

Nutritional Toxicology

Discusses known food/supplements and other products and their potential toxic effects

Reproductive Toxicology

Involved with understanding the effects of toxicants on the reproductive system of individuals

Development Toxicology

Involved with understanding the effects of toxicants on the development of an organism towards maturity and identifying in which developmental stages these effects occur

Teratology

Subsection of development toxicology focused on the effects of toxicants on the development of the human fetus

Veterinary Toxicology

Studies the effects of certain toxicants, poisons, and drugs on animals

Environmental Toxicology

Studies the effect of toxicants on the environment (i.e., pollutants)

Food Toxicology

Investigates the other components of food products that can cause toxicity (i.e., substances in processing methods such as coloring, pesticides)

Analytical Toxicology

Involved with the method development of analyses of toxicants

Aquatic Toxicology

Studies the effects of toxicants on aquatic environments

Ecotoxicology

Studies the effects of toxicants on the ecosystem

Formal Toxicology

Field focused on creating dossiers about certain substances. It is focused more on collecting information rather than the actual process of gathering data through scientific investigation or research

Genetic Toxicology

Studies the effects of toxicants/poisons/drugs on genes

Industrial Toxicology

Investigates what things in a work environment can cause toxicity to humans

Occupational Toxicology

Focuses on the effects of occupational hazards on people in the workplace

Regulation

Serves an executory role; focused on identifying/determining the upper and lower limits of toxic substances in products

Regulatory Toxicology

In charge of enforcing guidelines and policies based on the data provided through regulation toxicology. They validate the information that regulations passes on.

Toxicovigilance

In charge of monitoring/studying cases in the event that a toxicant is leaked

Toxicodynamics

Studies the effects of toxicants on the body

Toxicokinetics

Studies the effects of the body on the toxicant

Toxinology

Involved with the investigation of toxins (natural sources of poisons)

Toxicoepidemiology

Involved in monitoring the effects of a poison on a population that is exposed to it

Toxicant

Type of poison that usually refers to substances that are synthetic or chemicals not produced by nature

Toxin

Type of poison that refers to naturally occurring toxic substances

Types of Toxicants

Systemic, Organ-directed, Pollutant (toxic to the environment)

Endotoxin

Type of toxin released by microorganisms when their cells are lysed, usually proteinaceous in nature

Exotoxin

Type of toxin released by microorganisms without the need for cell lysis

Mycotoxin

Type of toxin released by fungi (i.e., spores)

Phytotoxin

Toxins from plants

Venom

Toxins from organisms of higher level of sentience/consciousness (basically animals)

Domestic/Household

Source of poisons such as cleaning materials (bleach, muriatic acid), sink de-cloggers (sodium hydroxide in high concentrations)

Agricultural/Horticultural

Source of poisons such as pesticides, vermicides, insecticides, and other similar substances

Industrial

Source of poisons such as smoke coming from industrial plants can become a source of poison

Commercial

Source of poisons such as packaging materials (i.e., plastic food packaging can release BPAs into food when heated)

Food/Drinks

Foods that are poisonous themselves, especially when its consumption is not regulated (source of poison)

Medicines

Source of poisons such as drugs that have narrow therapeutic indices

Environment, Plants and Animals

Other sources of poisons

Systemic

Classification of poisons (by effect) when the poison affects an organ but that organ is vital to the functions of the entire body

Corrosive

Classification of poisons (by effect) referring to agents that chemically destroy living tissue or other materials

Irritant

Classification of poisons (by effect) that causes irritation upon contact (or even through smell)

Miscellaneous

Classification of poisons (by effect) referring to domestic poisons, medicines, food contaminants, drugs of abuse

Accidental

Classification of poisons (by poisoning) when the poisoning is not deliberate (i.e., babies do not know what substances are dangerous)

Intentional

Classification of poisons (by poisoning) exemplified by the story of Giulia Tofana: Aqua Tofana

Occupational

Classification of poisons (by poisoning) characterized by exposure to toxicants due to hazardous occupations or work environments

1) by effects

2) by poisoning

2 Classification of Poisons

Toxicity

capacity of a substance to cause injury

Toxic Effects

undesirable effects caused by the poison

Side Effects

undesirable effects resulting from the normal pharmacologic action of drugs

Minoxidil

originally used for hypertension; now more frequently advertised for hair growth

Selective Toxicity

Toxicity to one organ or biological target but not harmful to another

Safety

Degree of certainty that the substance will not cause harm (assuming proper dosing and usage/administration)

Risk-to-Benefit Ratio

comparison of the risks and benefits associated with a medical intervention, including alternatives

LOW risk-to-benefit ratio

use of a toxic agent far outweighs its risk to cause harm

False; it is more preferable

True or False: treatment with a lower risk-to-benefit ratio is less preferable

Risk

Expected frequency (e.g., high/low risk) of the occurrence of a harmful effect

Risk Assessment

Quantitative assessment of the probability of harmful effect under given exposure conditions

Hazard

Qualitative description of the adverse effect of a chemical or physical agent regardless of dose or exposure

Hazard

a term that answers what type of poison a substance is (e.g., is it an irritant? What are its effects?)

True

True or False: A higher dose of the poison is needed to cause harmful effect as a consequence of continuous exposure to a small dose

Acceptable Risk

Probability of suffering from disease or injury during exposure is considered small but acceptable to the individual 

Acceptable Exposure

Unintentional contact with the chemical or physical agent that results in harmful effects

Margin of Exposure (MOE)

Ratio of the No Observed Adverse Effect Level (NOAEL) for critical effect to the theoretical/predicted exposure dose

Threshold Limit Values (TLV)

The airborne concentration of a substance that represents the conditions under which it is believed that nearly all workers may be repeatedly exposed to without adverse effects

Reversible Toxicity

Can be cured upon treatment; short duration [Duration of Effects]

Irreversible Toxicity

Persists throughout an individual’s lifespan; permanent damage [Duration of Effects]

Immediate Toxicity

Toxic effects develop soon after exposure [Duration of Effects]

Delayed Toxicity

The onset of toxic effects is delayed (i.e., an hour after exposure) [Duration of Effects]

Cumulative Toxicity

It is progressive; produced by the summation of incremental injury due to successive exposure [Duration of Effects]

False; it occurs through chronic exposure (slow and gradual)

True or False: Cumulative toxicity occurs through acute exposure to a toxic substance

Host, Poison, Environment

3 Factors Affecting Toxicity

1. size/ weight

2. age

3. species/ strain

4. food intake

5. drug intake

6. physiological factors

7. idiosyncratic reactions

Examples under Host [Factors Affecting Toxicity]

Idiosyncratic reactions

the unique reaction of individuals to certain agents

• Physical state (i.e., volatility)

• Chemical properties (i.e., a substance’s convertibility to a toxic form)

• Route and rate of administration

• Drug-drug interaction

• Tolerance

Examples under Poison [Factors Affecting Toxicity]

• Presence of other organisms of same/different species

• Humidity

Examples under Environment [Factors Affecting Toxicity]

Short-term Toxicity

Long-Term Toxicity

2 Classification of Frequency of Exposure

Short-Term Toxicity

acute toxicity; toxicity effect is seen shortly after exposure (1 day)

Long-Term Toxicity

toxicity effect is seen long after exposure

28 days

Effects of subacute toxicity typically show after how many days?

90 days

Effects of subchronic toxicity typically show after how many days?

> 90 days

Effects of chronic toxicity typically show after how many days?

Inhalation, Ingestion, Skin absorption

Routes of Toxicity Exposure

Concentration

Amount of the substance within the formulation/solution

Dose

Amount of substance in a biological target

mg/Kg bodyweight

Dose unit of expression

Graded Dose Response

The intensity of response in an individual

Quantal Dose Response

The percentage of individuals with a response or no response within the population

Sigmoidal

The response curve for Graed Dose Response is almost always ___ in shape due to pharmacokinetics/dynamics

Lethal Dose Concentration (LD₅₀)

Concentration of a substance that kills 50% of the population

Absolute Lethal Dose Concentration (LD₁₀₀)

Concentration of a substance that kills 100% of the population

Derived No-Effect Level (DNEL)

Level of exposure to a substance above which humans should not be exposed to

No Observed Effect Level (NOEL)

Highest dose/concentration under defined conditions of exposure that causes no effect on the morphology, functional capacity, growth, development, or life span of animals

No Observed Adverse Effect Level (NOAEL)

Highest dose/concentration under defined conditions of exposure that causes no adverse effect on the morphology, functional capacity, growth, development, or life span of animals

Adverse effect

Beyond the limit in No Observed Adverse Effect Level (NOAEL), what can be observed?

Lowest Observed Adverse Effect Level (LOAEL)

Lowest dose/concentration under defined conditions of exposure causes adverse effect on the morphology, functional capacity, growth, development, or life span of animals

Affinity

the strength of chemical attraction attraction between a drug and its biological target, such as a receptor or enzyme

High Affinity

Explanation: Because the drug binds so well (high affinity) = the body only needs a tiny amount (a low dose) to fill the targets and take effect.

A dose is said to have ___ to a receptor when a low dose causes a sizable effect

Efficacy

the maximal response a drug can produce