Definitions in Toxicology

Definitions in Toxicology

Toxicology

The study of the adverse effects of a toxicant on living organisms. Toxicology is an applied science that incorporates biology, chemistry, physiology, pathology, physics, statistics, and sometimes immunology or ecology to help solve problems in forensic medicine, public health, industrial hygiene, veterinary medicine, pharmacy and pharmacology, as well as giving basic insight into how an organism functions.

Toxicant or Poison

Any agent capable of producing a deleterious effect in a biological system. As per Paracelsus’ axiom, all substances are potentially poisonous, it is the dosage that determines the toxicity.

Toxicity

Considering the above, this is the potential to cause damage to humans and experimental animals. Toxicity - the biological effect of a substance. In this context, toxicity and hazard are used interchangeably.

 

Adverse Effect (Response) 

Any change from an organism’s normal state. Producing a toxic adverse effect depends on the concentration of the active compound at the target site. Some of these changes may be short-lived, functional and relatively reversible at low dosages and become chronic and irreversible at higher dosages.

Hazard

This refers to a substance (or condition) which has some nonzero likelihood of causing damage to humans / animals under actual conditions of exposure or use. Hazard - the biological effects produced by substances (i.e., toxicity). Hazards pose risks only if the exposure is sufficiently high.

Risk

This term has many different meanings. In risk assessment it is often used to refer to likelihood of exposure multiplied by severity of impact. The answer is often categorical: negligible, low, medium, high, etc. (In epidemiology, it has the meaning of incidence proportion, i.e. the proportion of a cohort of workers affected when they are followed up over time.) Risk - Probability a substance will cause harm under specific conditions of use, i.e., a function of the hazard potential of an exposure to the substance.

Toxicokinetics

This is the study of the movement of toxic substance within the body. Toxicokinetics deals with absorption, distribution, biotransformation and excretion of chemicals / xenobiotics (substances "foreign" to the body). Toxicokinetics takes into consideration differences in susceptibility among individuals. The factors to consider in these processes are those of (1) bioavailability, (2) absorption, (3) distribution, (4) metabolism and (5) excretion and how they may be affected by genomic or environmental factors or combinations thereof. It also encompasses the relationship between the dose that enters the body and the level of the toxic substance in any biological sample.

Body burden

This is a concept related to bioavailability reflecting the total amount of a substance within the body at a point in time and depends upon total dosage, metabolism and elimination or excretion.

Toxicodynamics deals with the biochemical and physiological effects of chemicals to the body and mechanisms of their actions. The study of the relationship between the dose of the toxic substance that enters the body and the measured response or adverse effect.

Dose

The amount of chemical which has entered the body. Units of measure for dosage may vary but are usually given as milligrams of chemical per kilogram of body weight (mg/kg) or milligrams per meter square so that dosages can be compared. The quantitative dosage as well as temporal patterns, (schedule, duration and frequency), and how the route by which the dose is administered are all important parameters in predicting toxic effect.

LC50. Lethal concentration 50

A measure of dose response in an animal experiment. The inhaled dose at which 50 percent of laboratory animals are will die.

LD50. Lethal dose 50

A measure of dose response in an animal experiment. The ingested dose at which 50 percent of laboratory animals are will die.

Target Organ/Site

The target site refers to the location(s) at which adverse effects occur. Toxicity may be relatively specific to an organ system or even cell type therein but generally toxicity will occur at several sites. Patterns of physiologic response, (syndromes), may give clues as to toxic etiologies. An example would be lead which at very low dosages causes subtle neuropsychiatric effects which with ongoing exposure become permanent and which as dose increases will affect bone marrow hemoglobin production and renal function.

Storage Depot

A storage depot is a site or tissue which sequesters a toxin without a deleterious effect. Examples include sequestration of lead into the calcium hydroxyapatite matrix of bone cortex and DDT or other organochlorines entry and storage in fatty tissues. Such storage depots allow for decreased bioavailabity of a sequestered toxin, biologic persistence with chronic low level exposure, (equilibrium between the storage depot and blood stream), decreased excretion and biologic persistence.

Analytical toxicology is a branch of analytical chemistry concerned with the identification and assay of toxic chemicals and their metabolites in biological and environmental materials.

Applied Toxicology - This includes the various aspects of toxicology as they apply in the field or the development of new methodology or new selective toxicants for early application in the field setting.

Behavioral toxicology deals with the effects of toxicants on animal and human behavior, which is the final integrated expression of nervous function in the intact animal. This involves both the peripheral and central nervous systems, as well as effects mediated by other organ systems, such as the endocrine glands.

Biochemical and molecular toxicology consider events at the biochemical and molecular levels, including enzymes that metabolize xenobiotics, generation of reactive intermediates, interaction of xenobiotics or their metabolites with macromolecules, gene expression in metabolism and modes of action, and signaling pathways in toxic action.

Clinical toxicology

Clinical toxicology deals with diagnosis and treatment of the normal diseases or effects caused by toxic substances of exogenous origin i.e. xenobiotics.

Descriptive toxicology

Descriptive toxicology deals with toxicity tests on chemicals exposed to human beings and environment as a whole.

Environmental toxicology

Environmental toxicology deals with the potentially deleterious impact of chemicals, present as pollutants of the environment, to living organisms.

Environmental toxicology is concerned with the movement of toxicants and their metabolites and degradation products in the environment and in food chains and with the effect of such contaminants on individuals and, especially, populations. Because of the large number of industrial chemicals and possibilities for exposure, as well as the mosaic of overlapping laws that govern such exposure, this area of applied toxicology is well developed.

Ecotoxicology

Ecotoxicology has evolved as an extension of environmental toxicology. It is concerned with the toxic effects of chemical and physical agents on living organisms, especially in populations and communities with defined ecosystems.

Forensic toxicology

Forensic toxicology closely related to clinical toxicology. It deals with the medical and legal aspects of the harmful effects of chemicals on man, often in post mortem material, for instance, where there is a suspicion of murder, attempted murder or suicide by poisoning.

Forensic toxicology concerns the medicolegal aspects, including detection of poisons in clinical and other samples.

Industrial toxicology is a specific area of environmental toxicology that deals with the work environment and constitutes a significant part of industrial hygiene.

Mechanistic toxicology

Mechanistic toxicology deals with the mechanism of toxic effects of chemicals on living organisms. This is important for rational treatment of the manifestations of toxicity (e.g. organophosphate poisoning reversed by oximes), prediction of risks (e.g. organophosphate poisoning leads to accumulation of acetyl choline activate muscarinic and nicotinic receptors respiratory failure) & facilitation of search for safer drugs (e.g. Instead of organophosphates, drugs which reversibly bind to cholinesterase would be preferable in therapeutics)

Nutritional toxicology deals with the effects of diet on the expression of toxicity and with the mechanisms of these effects.

Occupational toxicology

Occupational toxicology Deals with chemical found in the workplace

E.g. – Industrial workers may be exposed to these agents during the synthesis, manufacturing or packaging of substances

– Agricultural workers may be exposed to harmful amounts of pesticides during the application in the field.

Predictive toxicology

Predictive toxicology studies about the potential and actual risks of chemicals /drugs. This is important for licensing a new drug/chemical for use.

Regulatory toxicology

Regulatory toxicology studies whether the chemical substances has low risk to be used in living systems

E .g - Food and drug administration regulates drugs, food, cosmetics medical devices & supplies in USA.

- Environmental protection agency regulates pesticides, toxic chemicals, hazardous wastes and toxic pollutants in USA

- Occupational safety and health administration regulates the safe conditions for employees in USA

- Drug administration & control authority (DACA) – regulates drugs, cosmetics and medical devices &supplies in Ethiopia.

Toxicoepidemiology - Epidemiology as it applies to toxicology, is of great importance as it deals with the relationship between chemical exposure and human / animal disease in actual populations rather than in experimental settings.

Toxicopathology - Toxicologic pathology is the branch of pathology that deals with the effects of toxic agents manifested as changes in subcellular, cellular, tissue, or organ morphology.

Veterinary toxicology is the diagnosis and treatment of poisoning in animals other than humans, particularly livestock and companion animals, but not excluding feral species. Other important concerns of veterinary toxicology are the possible transmission of toxins to the human population in meat, fish, milk, and other foodstuffs and the care and ethical treatment of experimental animals.

Based on the organ/system effect

1. Cardiovascular toxicology

2. Renal toxicology

3. Central nervous system toxicology

4. Gastrointestinal toxicology

5. Respiratory toxicology etc.

Organ toxicity considers effects at the level of organ function (neurotoxicity, hepatotoxicity, nephrotoxicity, etc.).

Carcinogenesis includes the chemical, biochemical, and molecular events that lead to the large number of effects on cell growth collectively known as cancer.

Teratogenesis includes the chemical, biochemical, and molecular events that lead to deleterious effects on development.

Mutagenesis is concerned with toxic effects on the genetic material and the inheritance of these effects.

Measurement of Toxicants and Toxicity. These important aspects deal primarily with analytical chemistry, bioassay, and applied mathematics; they are designed to provide the methodology to answer certain critically important questions. Is the substance likely to be toxic? What is its chemical identity? How much of it is present? How can we assay its toxic effect, and what is the minimum level at which this toxic effect can be detected? A number of important fields are included:

Toxicity testing involves the use of living systems to estimate toxic effects. It covers the gamut from short-term tests for genotoxicity such as the Ames test and cell culture techniques to the use of intact animals for a variety of tests from acute toxicity to lifetime chronic toxicity. Although the term “bioassay” is used properly only to describe the use of a living organism to quantitate the amount of a particular toxicant present, it is frequently used to describe any in vivo toxicity test.

Structure-activity studies are concerned with the relationship between the chemical and physical properties of a chemical and toxicity and, particularly, the use of such relationships as predictors of toxicity. Quantitative Structure-Activity Relationship (QSAR) – A method of modeling the relationship between biological activity and the structure of organic chemicals.

 

Common Toxicology Terms

Absolute lethal concentration (LC100) - Lowest concentration of a substance in an environmental medium which kills 100% of test organisms or species under defined conditions. This value is dependent on the number of organisms used in its assessment.

Absolute lethal dose (LD100) - Lowest amount of a substance which kills 100% of test animals under defined conditions. This value is dependent on the number of organisms used in its assessment.

Absorbed dose (of a substance) - Amount of a substance absorbed into an organism or into organs and tissues of interest.

Absorption - In biology, this is the process of active or passive transport of a substance into an organism - in the case of a mammal or human being, this is usually through the lungs, gastrointestinal tract, or skin.

Absorption coefficient - Ratio of the absorbed amount of a substance to the administered amount. With respect to exposure by way of the respiratory tract, the coefficient is the ratio of the absorbed amount to the amount of the substance (usually particles) deposited (adsorbed) in the lungs.

Acceptable daily intake (ADI) - Estimate of the amount of a substance in food or drinking water, expressed on a body mass basis (usually mg/kg body weight), that can be ingested daily over a lifetime by humans without appreciable health risk. A standard body mass of 60 kg is used to calculate the daily intake per person, 

Acceptable risk - Probability of suffering disease or injury which is considered to be sufficiently small to be “negligible.”

Accidental exposure - Unintended contact with a substance or change in the physical environment.

Accumulation - Successive additions of a substance to a target organism, or organ, or to part of the environment, resulting in an increasing amount or concentration of the substance in the organism, organ, or environment.  ACCUMULATION  – The build-up of chemical in the organism as a result of repeated, or long term exposure.

Action level - Concentration of a substance in air, soil, water or other defined medium at which specified emergency counter-measures should be taken.

Active ingredient - In any pesticide product, the component that kills, or otherwise controls, target pests. Pesticides are regulated primarily on the basis of active ingredients.

Acute - Short-term exposure or effect. In experimental toxicology, “acute” refers to studies of two weeks or less in duration (often less than 24 hours)

Acute effect - Effect of short duration and occurring rapidly (usually in the first 24 hours or up to 14 days) following a single dose or short exposure to a substance.

Acute exposure - Contact with a substance that occurs once or for only up to 14 days.

Acute toxicity - Adverse effects occurring within 14 days after administration of a single dose (or exposure to a given concentration) of a test substance or after multiple doses (exposures), usually within 24 hours.

Acute toxicity – adverse effects arising from a single exposure or short term exposure to a chemical.

Acute toxicity test - Experimental animal study to determine what adverse effects occur in a short time, within 14 days after a single dose of a substance or after multiple doses.

Adaptation - Changes in an organism that have no irreversible disruptions in response to changing environmental conditions.

Added risk - Difference between the incidence of an adverse effect in a treated group (of organisms or a group of exposed humans) and a control group (of the same organisms or the spontaneous incidence in humans).

Addiction - To function normally, the body relies on a substance and there is a physical dependency on the substance as well. If that substance is taken away, it causes withdrawal, that is accompanied by a characteristic set of signs and symptoms.

Additive effect - Consequence which follows exposure to two or more physio-chemical agents which act jointly, but do not interact - commonly, the total effect is the simple sum of the effects of separate exposure to the agents under the same conditions. Substances of simple similar action may show dose or concentration addition. An additive effect is the overall consequence which is the result of two chemicals acting together and which is the simple sum of the effects of the chemicals acting independently.

Adsorption - Enrichment (positive adsorption, or briefly adsorption) of one or more components in an interfacial layer.

Adverse effect - Change in physiology, development or lifespan of an organism which results in impairment of functional capacity or impairment of capacity to compensate for additional stress or increase in susceptibility to the harmful effects of other environmental influences.

Adverse event - Occurrence which causes an adverse effect.

Air particulates - Total suspended particulate matter found in the atmosphere as solid particles or liquid droplets. Chemical composition of particulates varies widely, depending on location and time of year. Airborne particulates include windblown dust, emissions from industrial processes, smoke from the burning of wood and coal, and motor vehicle or non-road engine exhausts.

Air pollution - Substances that are present in the air that interfere with the health, welfare or comfort of individuals. These substances also cause harm to the environment and result from human activity or natural processes.

Air quality standards - The level of pollutants prescribed by regulations that may not be exceeded during a given time in a defined area.

Air toxics - Any air pollutant for which a national ambient air quality standard (NAAQS) does not exist (i.e., excluding ozone, carbon monoxide, PM-10, sulfur dioxide, nitrogen oxide) that may reasonably be anticipated to cause cancer, developmental effects, reproductive dysfunctions, neurological disorders, heritable gene mutations, or other serious or irreversible chronic or acute health effects in humans.(1)

Allergen – a substance which causes an allergic reaction.

Allergy – an adverse reaction which is caused by an over-stimulation of the immune system in response to a specific allergen, which is otherwise harmless and would be normally tolerated by the majority of those who come in contact with it.

Application Factor (AF) – An empirically derived “safe” concentration of a chemical.

Aquatic toxicology is the study of the effects of manufactured chemicals and other anthropogenic and natural materials and activities on aquatic organisms at various levels of organization, from sub-cellular through individual organisms to communities and ecosystems. Aquatic toxicology is a multidisciplinary field which integrates toxicology, aquatic ecology and aquatic chemistry.

Baseline toxicity – Refers to narcosis which is a depression in biological activity due to toxicants being present in the organism.

Bioaccumulate - Absorption of a toxic substances by an organism at a rate that is greater than the rate at which the substance is lost.

Bioconcentration Factor (BCF) – The ratio of the average chemical concentration in the tissues of the organism under steady-state conditions to the average chemical concentration measured in the water to which the organisms are exposed.

Biomarkers - There are three general categories of Biomarkers: Biomarkers of Exposure, Biomarkers of Susceptibility, and Biomarkers of Effect.

• Biomarkers of Exposure have the ability to identify if exposure to a drug or foreign substance has occurred, and the route or pathway of exposure, Biomarkers of Exposure can be measured in the body of an organism (animal or human) or in the environment. This is also referred to as biomonitoring.
• Biomarkers of Susceptibility evaluate an individual’s susceptibility to drugs, chemicals, and environmentally mediated disease that may arise from genetic causes or from nongenetic factors such as age, disease state, diet, or dietary supplementation.
• Biomarkers of Effect may be either early events on the direct pathway to disease or toxic end points or predictors of disease or toxicity outside the direct pathway.

Although biomarkers can indicate events or changes that are not harmful, toxicologists use biomarkers chiefly to determine if exposure has occurred and whether exposure may lead to toxic effects. Also, toxicologists are continually evaluating animals, humans, and the environment to look for more and better biomarkers that represent the earliest signs of exposure. That way, toxicologists and public health professionals can use this information to determine if exposure mitigation efforts are needed.

Biomagnify - the tendency of a substance to increase in concentration as it proceeds up the food chain from prey to the top consumer. Biomagnification – The process by which the concentration of a chemical in the tissues of an organism increases as it passes through several levels in the food web.

Biomonitoring - is the analysis of human bodily fluids and tissues for purposes of measuring people’s exposure to chemicals.

Biomonitoring - a direct measure of human exposure to substances. Biomonitoring involves measuring actual levels of exposure within the body which can help to make risk assessments far more accurate. (Mackinac Center for Public Policy)

Biomonitoring – The consistent use of living organisms to analyze environmental changes over time.

Carcinogen – a substance that is capable of causing cancer.

Carcinogenesis – the process of the development of a cancer.

Chronic toxicity – adverse health effects arising from continuous or intermittent exposure to low concentrations of chemical over a lifetime.

Corrosive – a chemical that causes irreversible alterations or destruction in living tissue at the site of contact.

Cumulative exposure – a summation of all the exposures that have been undergone by an organism during a specified period of time.

Critical Body Residue (CBR) – An approach that routinely examines whole-body chemical concentrations of an exposed organism that is associated with an adverse biological response.

Developmental toxicology – adverse toxic effects in the developing embryo or foetus

DNEL – derived no effect level. This is the dose above which exposure may give rise to adverse effects.

Dose – the amount of chemical administered. It is a measure of exposure.

Dose –response – the relationship between the dose of a chemical and the degree/severity of the resulting effect.

Effluent – Liquid, industrial discharge that usually contain varying chemical toxicants.

Endocrine Disruptor - generally, a substance that interacts with one or more components of the endocrine system to cause adverse effects.

Endocrine Modulator - An endocrine modulator is a compound or chemical that changes the function of the endocrine system, which makes and controls the hormones in the body. Thus, endocrine modulators can change how these hormones are formed and how they behave. The endocrine system has many components, located virtually all over the body, and these components include the hypothalamus, pituitary, pineal, thyroid, and parathyroid glands, the kidney, heart, stomach, and intestines, along with fat cells, testes, and ovaries. The endocrine system is contrasted to the exocrine system, which is comprised of salivary glands, sweat glands, and some gastrointestinal glands. Thus, compounds which act as endocrine modulators can have far-reaching consequences if they obstruct crucial bodily functions such as child-bearing, body temperature regulation, bone density, and organ function.

End point – a specific biological effect or response which is used as an indicator of the effect of the chemical on the organism.

Etiology - Science dealing with the cause or origin of disease.

Exposure - in health matters, a measurement of the level at which one encounters any substance. Exposure – contact with a chemical. The most common routes are inhalation, skin contact and also by oral ingestion.

Gavage – oral feeding by a tube.

Genotoxic – chemicals that cause hereditary mutations as a result of directly interacting with the DNA.

Genotoxic carcinogens – chemicals causing cancer as a result of directly interacting with dna.

Hazard –the inherent ability of a chemical to cause an adverse effect

Hazardous air pollutants - Air pollutants that may reasonably be expected to cause or contribute to irreversible illness or death as defined under the Clean Air Act. These pollutants include asbestos, beryllium, mercury, benzene, coke-oven emissions or radionuclides, and vinyl chloride.

Hypersensitivity – the state in which an individual reacts following exposure to a substance with allergic effects  after having been exposed (sensitised).

Immediately Dangerous to Life or Health (IDLH). IDLH is defined as a condition "that poses a threat of exposure to airborne contaminants when that exposure is likely tocause death or immediate or delayed permanent adverse health effects or prevent escape from such an environment. The purpose of establishing an IDLH exposure level is to ensure that the worker can escape from a given contaminated environment in the event of failure of the respiratory protection equipment.

In vitro – latin for “in glass”. Studies which use tissue, cellular or subcellular extracts from a living organism.

In vivo – studies which are carried out in living organisms.

Irritant – a chemical causing a localised inflammatory reaction to skin or mucous membranes at the site of contact.

KOW – The octanol-water partition coefficient which represents the ratio of the concentration of octanol to the concentration of chemical in the water.

LC₅₀  – lethal concentration 50%. This is the concentration which causes death in 50% of the test population.

LOAEL – lowest observable adverse effect level.  This is the lowest dose in the study which causes an observable adverse effect.

Lowest Observed Effect Concentration (LOEC) – The lowest test concentration that has a statistically significant effect over a specified exposure time.

Lethal dose low (LD_LO): The lowest dose, other than LD50of a substance introduced by any route, other than inhalation, which has been reported to have caused death in humans

or animals.

Lethal dose fifty (LD50): A calculated dose of a substance which is expected to cause the

death of 50 percent of an entire defined experimental animal population. It is determined from the exposure to the substance byany route other than inhalation.

Lethal concentration low (LC_LO): The lowest concentration of a substance in air, other than LC50, which has been reported to cause death in humans or animals.

Lethal concentration fifty (LC50): A calculated concentration of a substance in air, exposure to which for a specified length of time is expected to cause the death of 50 percent of an entire defined experimental animal population.

Maximum Acceptable Toxicant Concentrations (MATC) – An estimated value that represents the highest “no-effect” concentration of a specific substance within the range including the NOEC and LOEC.

Median Lethal Concentration (LC50) – The chemical concentration that is expected to kill 50% of a group of organisms.

Mode of Action – A set of common behavioral or physiological signs that represent a type of adverse response.

Mechanism of Action – The detailed events that take place at the molecular level during an adverse biological response.

Neurotoxin – a chemical that causes adverse effects in the nervous system.

NOAEL – no observed adverse effect level. This is the largest dose in a given study that does not cause an adverse effect.

Non genotoxic carcinogen – chemical carcinogens that cause cancer by effects other than direct damage to the genetic material.

No Observed Effect Concentration (NOEC) – The highest test concentration for which no effect is observed relative to a control over a specified exposure time.

PBT - a material that is considered to be persistent in the environment, Bioaccumulative, and toxic to fish and wildlife. Phthalates are often improperly referred to as PBTs although they do not have the same characteristics that genuine PBT materials possess.

Primary irritant – a chemical that causes an inflammatory reaction on first contact.

Reference dose (RfD) - An exposure level defined by the Environmental Protection Agency as “a numerical estimate of a daily oral exposure to the human population, including sensitive subgroups such as children, that is not likely to cause harmful effects during a lifetime.”

Senstisation – the immune process by which  individuals become hypersensitive to a substance to which they are exposed. Subsequent exposure can lead to the development of an allergic response.

Teratogen – a chemical agent causing adverse effects in the normal embryonic development without causing lethality in the foetus or maternal toxicity.

The Three Rs—Reduce, refine and replace.

Toxic dose low (TD_LO): The lowest dose of a substance introduced by any route, other than inhalation, over any given period of time, and reported to produce any toxic effect in humans or to produce tumorigenic or reproductive effects in animals.

Toxic concentration low (TCLO): The lowest concentration of a substance in air to which humans or animals have been exposed for any given period of time that has produced any toxic effect in humans or produced tumorigenic or reproductive effects in animals.