Toxicity
Encyclopedia
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
(cytotoxicity
Cytotoxicity
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are a chemical substance, an immune cell or some types of venom .-Cell physiology:...
) or an organ (organotoxicity), such as the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
(hepatotoxicity
Hepatotoxicity
Hepatotoxicity implies chemical-driven liver damage.The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure...
). By extension, the word may be metaphor
Metaphor
A metaphor is a literary figure of speech that uses an image, story or tangible thing to represent a less tangible thing or some intangible quality or idea; e.g., "Her eyes were glistening jewels." Metaphor may also be used for any rhetorical figures of speech that achieve their effects via...
ically used to describe toxic effects on larger and more complex groups, such as the family unit or society at large.
A central concept of toxicology
Toxicology
Toxicology is a branch of biology, chemistry, and medicine concerned with the study of the adverse effects of chemicals on living organisms...
is that effects are dose
Dose (biochemistry)
A dose is a quantity of something that may impact an organism biologically; the greater the quantity, the larger the dose. In nutrition, the term is usually applied to how much of a specific nutrient is in a person's diet or in a particular food, meal, or dietary supplement...
-dependent; even water can lead to water intoxication
Water intoxication
Water intoxication, also known as water poisoning, is a potentially fatal disturbance in brain functions that results when the normal balance of electrolytes in the body is pushed outside of safe limits by over-consumption of water....
when taken in large enough doses, whereas for even a very toxic substance such as snake
Snake
Snakes are elongate, legless, carnivorous reptiles of the suborder Serpentes that can be distinguished from legless lizards by their lack of eyelids and external ears. Like all squamates, snakes are ectothermic, amniote vertebrates covered in overlapping scales...
venom there is a dose below which there is no detectable toxic effect.
Types of toxicity
There are generally three types of toxic entities; chemical, biological, and physical:- ChemicalChemical substanceIn chemistry, a chemical substance is a form of matter that has constant chemical composition and characteristic properties. It cannot be separated into components by physical separation methods, i.e. without breaking chemical bonds. They can be solids, liquids or gases.Chemical substances are...
toxicants include inorganic substances such as leadLeadLead is a main-group element in the carbon group with the symbol Pb and atomic number 82. Lead is a soft, malleable poor metal. It is also counted as one of the heavy metals. Metallic lead has a bluish-white color after being freshly cut, but it soon tarnishes to a dull grayish color when exposed...
, mercuryMercury (element)Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...
, asbestosAsbestosAsbestos is a set of six naturally occurring silicate minerals used commercially for their desirable physical properties. They all have in common their eponymous, asbestiform habit: long, thin fibrous crystals...
, hydrofluoric acidHydrofluoric acidHydrofluoric acid is a solution of hydrogen fluoride in water. It is a valued source of fluorine and is the precursor to numerous pharmaceuticals such as fluoxetine and diverse materials such as PTFE ....
, and chlorineChlorineChlorine is the chemical element with atomic number 17 and symbol Cl. It is the second lightest halogen, found in the periodic table in group 17. The element forms diatomic molecules under standard conditions, called dichlorine...
gas, organic compoundOrganic compoundAn organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
s such as methyl alcoholMethanolMethanol, also known as methyl alcohol, wood alcohol, wood naphtha or wood spirits, is a chemical with the formula CH3OH . It is the simplest alcohol, and is a light, volatile, colorless, flammable liquid with a distinctive odor very similar to, but slightly sweeter than, ethanol...
, most medications, and poisons from living things. - Biological toxicants include bacteria and viruses that can induce disease in living organisms. Biological toxicity can be difficult to measure because the "threshold dose" may be a single organism. Theoretically one virusVirusA virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
, bacterium or wormWormThe term worm refers to an obsolete taxon used by Carolus Linnaeus and Jean-Baptiste Lamarck for all non-arthropod invertebrate animals, and stems from the Old English word wyrm. Currently it is used to describe many different distantly-related animals that typically have a long cylindrical...
can reproduce to cause a serious infectionInfectionAn infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
. However, in a host with an intact immune systemImmune systemAn immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
the inherent toxicity of the organism is balanced by the host's ability to fight back; the effective toxicity is then a combination of both parts of the relationship. A similar situation is also present with other types of toxic agentBiological agentA biological agent — also called bio-agent or biological threat agent — is a bacterium, virus, prion, or fungus which may cause infection, allergy, toxicity or otherwise create a hazard to human health. They can be used as a biological weapon in bioterrorism or biological warfare...
s. - Physical toxicants are substances that, due to their physical nature, interfere with biological processes. Examples include coalCoalCoal is a combustible black or brownish-black sedimentary rock usually occurring in rock strata in layers or veins called coal beds or coal seams. The harder forms, such as anthracite coal, can be regarded as metamorphic rock because of later exposure to elevated temperature and pressure...
dust and asbestosAsbestosAsbestos is a set of six naturally occurring silicate minerals used commercially for their desirable physical properties. They all have in common their eponymous, asbestiform habit: long, thin fibrous crystals...
fibers, both of which can ultimately be fatal if inhaled.
Measuring Toxicity
Toxicity can be measured by its effects on the target (organism, organ, tissue or cell). Because individuals typically have different levels of response to the same dose of a toxin, a population-level measure of toxicity is often used which relates the probabilities of an outcome for a given individual in a population. One such measure is the . When such data does not exist, estimates are made by comparison to known similar toxic things, or to similar exposures in similar organisms. Then "safety factors" are added to account for uncertainties in data and evaluation processes. For example, if a dose of toxin is safe for a laboratory rat, one might assume that one tenth that dose would be safe for a human, allowing a safety factor of 10 to allow for interspecies differences between two mammals; if the data are from fish, one might use a factor of 100 to account for the greater difference between two chordate classes (fish and mammals). Similarly, an extra protection factor may be used for individuals believed to be more susceptible to toxic effects such as in pregnancy or with certain diseases. Or, a newly synthesized and previously unstudied chemical that is believed to be very similar in effect to another compound could be assigned an additional protection factor of 10 to account for possible differences in effects that are probably much smaller. Obviously, this approach is very approximate; but such protection factors are deliberately very conservative and the method has been found to be useful in a deep variety of applications.Assessing all aspects of the toxicity of cancer-causing agents involves additional issues, since it is not certain if there is a minimal effective dose for carcinogens, or whether the risk is just too small to see. In addition, it is possible that a single cell transformed into a cancer cell is all it takes to develop the full effect (the "one hit" theory).
It is more difficult to determine the toxicity of chemical mixtures than a pure chemical, because each component displays its own toxicity, and components may interact to produce enhanced or diminished effects. Common mixtures include gasoline
Gasoline
Gasoline , or petrol , is a toxic, translucent, petroleum-derived liquid that is primarily used as a fuel in internal combustion engines. It consists mostly of organic compounds obtained by the fractional distillation of petroleum, enhanced with a variety of additives. Some gasolines also contain...
, cigarette smoke
Tobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
, and industrial waste
Industrial waste
Industrial waste is a type of waste produced by industrial activity, such as that of factories, mills and mines. It has existed since the outset of the industrial revolution....
. Even more complex are situations with more than one type of toxic entity, such as the discharge from a malfunctioning sewage treatment plant, with both chemical and biological agents.
Global classifications of toxicity
For substances to be regulated and handled appropriately they must be properly classified and labelled. Classification is determined by approved testing measures or calculations and have determined cut off levels set by governments and scientists. While currently many countries have different regulations regarding the types of tests, amounts of tests and cut off levels, the implementation of Global Harmonization will begin unifying these countries as early as 2008.Global Classification looks at three areas: Physical Hazards (explosions and pyrotechnics), Health Hazards and Environmental Hazards.
Health hazards
The types of toxicities where substances may cause lethality to the entire body, lethality to specific organs, major/minor damage, or cause cancer. These are globally accepted definitions of what toxicity is. Anything falling outside of the definition cannot be classified as that type of toxicant.Acute toxicity
Acute toxicity looks at lethal effects following oral, dermal or inhalation exposure. It is split into five categories of severity where Category 1 requires the least amount of exposure to be lethal and Category 5 requires the most exposure to be lethal. The table below shows the upper limits for each category.| Category 1 | Category 2 | Category 3 | Category 4 | Category 5 | |
|---|---|---|---|---|---|
| Oral: measured in mg/kg of bodyweight | 5 | 50 | 300 | 2 000 | 5 000 |
| Dermal: LD50 measured in mg/kg of bodyweight | 50 | 200 | 1 000 | 2 000 | 5 000 |
| Gas Inhalation: LC50 measured in ppmV | 100 | 500 | 2 500 | 20 000 | Undefined |
| Vapour Inhalation: LC50 measured in mg/L | 0.5 | 2.0 | 10 | 20 | Undefined |
| Dust and Mist Inhalation: LC50 measured in mg/L | 0.05 | 0.5 | 1.0 | 5.0 | Undefined |
Note: The undefined values are expected to be roughly equivalent to the category 5 values for oral and dermal administration.
Other methods of exposure and severity
Skin corrosion and irritation are determined though a skin patch test analysis. This examines the severity of the damage done; when it is incurred and how long it remains; whether it is reversible and how many test subjects were affected.Skin corrosion from a substance must penetrate through the epidermis into the dermis within four hours of application and must not reverse the damage within 14 days. Skin irritation shows damage less severe than corrosion if: the damage occurs within 72 hours of application; or for three consecutive days after application within a 14 day period; or causes inflammation which lasts for 14 days in two test subjects. Mild skin irritation minor damage (less severe than irritation) within 72 hours of application or for three consecutive days after application.
Serious eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
damage involves tissue damage or degradation of vision which does not fully reverse in 21 days. Eye irritation involves changes to the eye which do fully reverse within 21 days.
Other categories of toxicity
- Respiratory sensitizers cause breathing hypersensitivity when the substance is inhaled.
- A substance which is a skin sensitizer causes an allergic responseAllergic responseAn allergic response is a hypersensitive immune reaction to a substance that normally is harmless or would not cause an immune response in everyone. An allergic response may cause harmful symptoms such as itching or inflammation or tissue injury....
from a dermal application. - CarcinogenCarcinogenA carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
s induce cancer, or increase the likelihood of cancer occurring. - Reproductively toxic substances cause adverse effects in either sexual function or fertilityFertilityFertility is the natural capability of producing offsprings. As a measure, "fertility rate" is the number of children born per couple, person or population. Fertility differs from fecundity, which is defined as the potential for reproduction...
to either a parent or the offspring. - Specific-target organ toxins damage only specific organs.
- Aspiration hazards are solids or liquids which can cause damage through inhalation.
Environmental hazards
Environmental hazards tend to focus on degradability, bioaccumulation and aquatic toxicity.Mapping environmental hazards
There are many environmental health mapping tools. TOXMAPTOXMAP
TOXMAP is a geographic information system from the United States National Library of Medicine that uses maps of the United States to help users visually explore data from the United States Environmental Protection Agency's Toxics Release Inventory and Superfund programs...
is a Geographic Information System (GIS) from the Division of Specialized Information Services of the United States National Library of Medicine
United States National Library of Medicine
The United States National Library of Medicine , operated by the United States federal government, is the world's largest medical library. Located in Bethesda, Maryland, the NLM is a division of the National Institutes of Health...
(NLM) that uses maps of the United States to help users visually explore data from the United States Environmental Protection Agency
United States Environmental Protection Agency
The U.S. Environmental Protection Agency is an agency of the federal government of the United States charged with protecting human health and the environment, by writing and enforcing regulations based on laws passed by Congress...
's (EPA) Toxics Release Inventory
Toxics Release Inventory
The Toxics Release Inventory is a publicly available database containing information on toxic chemical releases and other waste management activities in the United States.-Summary of requirements:...
and Superfund
Superfund
Superfund is the common name for the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 , a United States federal law designed to clean up sites contaminated with hazardous substances...
programs. TOXMAP is a resource funded by the US Federal Government. TOXMAP's chemical and environmental health information is taken from NLM's Toxicology Data Network
(TOXNET) and PubMed
PubMed
PubMed is a free database accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine at the National Institutes of Health maintains the database as part of the Entrez information retrieval system...
, and from other authoritative sources.
Aquatic toxicity
Aquatic toxicity testing submerges key indicator species of fish or crustacea to certain concentrations of a substance in their environment to determine the lethality level. Fish are exposed for 96 hours while crustacea are exposed for 48 hours. While GHS does not define toxicity past 100 mg/l, the EPA currently lists aquatic toxicity as “practically non-toxic” in concentrations greater than 100 ppm.| Exposure | Category 1 | Category 2 | Category 3 |
|---|---|---|---|
| Acute | ≤ 1.0 mg/L | ≤ 10 mg/L | ≤ 100 mg/L |
| Chronic | ≤ 1.0 mg/L | ≤ 10 mg/L | ≤ 100 mg/L |
Note: A category 4 is established for chronic exposure, but simply contains any toxic substance which is mostly insoluble, or has no data for acute toxicity.
Factors influencing toxicity
Toxicity of a substance can be affected by many different factors, such as the pathway of administration (whether the toxin is applied to the skin, ingested, inhaled, injected), the time of exposure (a brief encounter or long term), the number of exposures (a single dose or multiple doses over time), the physical form of the toxin (solid, liquid, gas), the genetic makeup of an individual, an individual's overall health, and many others. Several of the terms used to describe these factors have been included here.acute exposure: a single exposure to a toxic substance which may result in severe biological harm or death; acute exposures are usually characterized as lasting no longer than a day.
chronic exposure: continuous exposure to a toxin over an extended period of time, often measured in months or years; it can cause irreversible side effects.
Etymology
"Toxic" and similar words came from GreekGreek language
Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...
τοξον = "bow (weapon)
Bow (weapon)
The bow and arrow is a projectile weapon system that predates recorded history and is common to most cultures.-Description:A bow is a flexible arc that shoots aerodynamic projectiles by means of elastic energy. Essentially, the bow is a form of spring powered by a string or cord...
" via "poisoned arrow", which came to be used for "poison
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....
" in scientific language, as the usual Classical Greek word ('ιον) for "poison" would transcribe as "io-", which is not distinctive enough. In some biological names, "toxo-" still means "bow", as in Toxodon
Toxodon
Toxodon is an extinct mammal of the late Pliocene and Pleistocene epochs about 2.6 million to 16,500 years ago. It was indigenous to South America, and was probably the most common large-hoofed mammal in South America at the time of its existence....
= "bow-toothed" from the shape.
See also
- Agency for Toxic Substances and Disease RegistryAgency for Toxic Substances and Disease RegistryThe Agency for Toxic Substances and Disease Registry is a federal public health agency within the United States Department of Health and Human Services. The agency focuses on minimizing human health risks associated with exposure to hazardous substances...
(ATSDR) - Biological activityBiological activityIn pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or pharmacophore but can be modified by the other...
- Biological warfareBiological warfareBiological warfare is the use of biological toxins or infectious agents such as bacteria, viruses, and fungi with intent to kill or incapacitate humans, animals or plants as an act of war...
- California Proposition 65 (1986)California Proposition 65 (1986)Proposition 65 is a California law passed by direct voter initiative in 1986 by a 63%-37% margin...
- CarcinogenCarcinogenA carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
- DrunkennessDrunkennessAlcohol intoxication is a physiological state that occurs when a person has a high level of ethanol in his or her blood....
- Indicative limit valueIndicative limit valueIn the law of the European Union, indicative limit values, more exactly indicative occupational exposure limit values , are human exposure limits to hazardous substances specified by the Council of the European Union based on expert research and advice.They are not binding on member states but must...
- List of highly toxic gases
- MutagenMutagenIn genetics, a mutagen is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level. As many mutations cause cancer, mutagens are therefore also likely to be carcinogens...
- NephrotoxicityNephrotoxicityNephrotoxicity is a poisonous effect of some substances, both toxic chemicals and medication, on the kidneys. There are various forms of toxicity. Nephrotoxicity should not be confused with the fact that some medications have a predominantly renal excretion and need their dose adjusted for the...
- NeurotoxicityNeurotoxicityNeurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue. This can eventually disrupt or even kill neurons, key cells that transmit and process...
- OtotoxicityOtotoxicityOtotoxicity is damage to the ear , specifically the cochlea or auditory nerve and sometimes the vestibular system, by a toxin. It is commonly medication-induced; ototoxic drugs include antibiotics such as the aminoglycoside gentamicin, loop diuretics such as furosemide, and platinum-based...
- ParacelsusParacelsusParacelsus was a German-Swiss Renaissance physician, botanist, alchemist, astrologer, and general occultist....
- Physiologically-based pharmacokinetic modellingPhysiologically-based pharmacokinetic modelling-What is a PBPK model?:Physiologically based pharmacokinetic modeling is a mathematical modeling technique for predicting the absorption, distribution, metabolism and excretion of synthetic or natural chemical substances in humans and other animal species...
. - PoisonPoisonIn the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....
- Reference doseReference doseA reference dose is the United States Environmental Protection Agency's maximum acceptable oral dose of a toxic substance. Reference doses are most commonly determined for pesticides...
- Registry of Toxic Effects of Chemical Substances (RTECS) - toxicity database
- Soil contaminationSoil contaminationSoil contamination or soil pollution is caused by the presence of xenobiotic chemicals or other alteration in the natural soil environment....
- Teratogen
- Toxic leaderToxic leaderA toxic leader refers to a person who has responsibility over a group of people or an organization, and who abuses the leader-follower relationship by leaving the group or organization in a worse-off condition than when s/he first found them...
- Toxic tortToxic tortA toxic tort is a special type of personal injury lawsuit in which the plaintiff claims that exposure to a chemical caused the plaintiff's injury or disease.-Different types:...
- Toxic workplaceToxic workplace-Overview:In the context of a toxic workplace, a toxic employee is a worker who is motivated by personal gain , uses unethical, mean-spirited and sometimes illegal means to manipulate and annoy those around them; and whose motives are to maintain or increase power, money or special status or divert...
- ToxicationToxicationToxication is the process of metabolism in which the metabolite of a compound is more toxic than the parent drug or chemical. A parent drug or chemical that was previously non-toxic may be called a protoxin.Toxication may involve:...
- ToxicophoreToxicophoreA toxicophore is a feature or group within a chemical structure that is thought to be responsible for the toxic properties, either directly or via metabolic activation....
- ToxinToxinA toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
- Toxica, a disambiguation page
External links
- Agency for Toxic Substances and Disease Registry
- Chemical and Other Safety Information – Oxford University
- Whole Effluent, Aquatic Toxicity Testing FAQ
- TOXMAP Environmental Health e-Maps from the United States National Library of Medicine
- Toxseek: meta-search engine in toxicology and environmental health