toxicity

Toxicity is the degree to which a substance is able to damage an exposed organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell (cytotoxicity) or an organ (organotoxicity), such as the liver (hepatotoxicity). By extension, the word may be metaphorically 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 is that effects are dose-dependent; even water can lead to water intoxication when taken in large enough doses, whereas for even a very toxic substance such as snake 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:

• Chemicals include inorganic substances such as lead, mercury, asbestos, hydrofluoric acid, and chlorine gas, organic compounds such as methyl alcohol, most medications, and poisons from living things.

• Biological toxic entities include those bacteria and viruses that are able to induce disease in living organisms. Biological toxicity can be complicated to measure because the "threshold dose" may be a single organism. Theoretically one virus, bacterium or worm can reproduce to cause a serious infection. However, in a host with an intact immune system 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 agents.

• Physically toxic entities include things not usually thought of under the heading of "toxic" by many people: direct blows,^{[citation needed]} concussion,^{[citation needed]} sound and vibration,^{[citation needed]} heat and cold,^{[citation needed]} non-ionizing electromagnetic radiation such as infrared and visible light,^{[citation needed]} and ionizing radiation such as X-rays and alpha, beta, and gamma radiation.

Toxicity can be measured by the 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 probability of an outcome for a given individual in a population. One such measure is the LD₅₀. 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 wide 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 assess the toxicity of chemical mixtures than of single, pure chemicals because each component display its own toxicity and components may interact to produce enhanced or diminished effects. Common mixtures include gasoline, cigarette smoke, and industrial waste. 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 labeled. 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 unifing these countries as early as 2008^[1][2]

Global Classification looks at three areas: Physical Hazards (explosions and pyrotechnics)^[3], Health Hazards^[4] and Environmental Hazards.^[5]

Health Hazards^[4]

Separates out the types of toxicities where substances may cause lethality to the entire body, lethality to specific organs, major/minor damage, or cause cancer wherein the cancer is what causes the damage and/or lethality. It should be noted that 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 broken 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 the be lethal.

1. Oral
   1. Category 1: LD50 ≤ 5 mg/kg of bodyweight
   2. Category 2: LD50 ≤ 50 mg/kg of bodyweight
   3. Category 3: LD50 ≤ 300 mg/kg of bodyweight
   4. Category 4: LD50 ≤ 2000 mg/kg of bodyweight
   5. Category 5: LD50 ≤ 5000 mg/kg of bodyweight
   6. Substances beyond category 5 are not defined, though they cannot legally be defined as orally toxic.
2. Dermal
   1. Category 1: LD50 ≤ 50 mg/kg of bodyweight
   2. Category 2: LD50 ≤ 200 mg/kg of bodyweight
   3. Category 3: LD50 ≤ 1,000 mg/kg of bodyweight
   4. Category 4: LD50 ≤ 2,000 mg/kg of bodyweight
   5. Category 5: LD50 ≤ 5,000 mg/kg of bodyweight
   6. Substances beyond category 5 are not defined, though they cannot legally be defined as dermally toxic.
3. Inhalation – Gases
   1. Category 1: LC50 ≤ 100 ppmV
   2. Category 2: LC50 ≤ 500 ppmV
   3. Category 3: LC50 ≤ 2,500 ppmV
   4. Category 4: LC50 ≤ 20,000 ppmV
   5. Category 5: not defined though is expected to have an equivalent of category 5 oral and dermal
4. Inhalation – Vapours
   1. Category 1: LC50 ≤ 0.5 mg/l
   2. Category 2: LC50 ≤ 2.0 mg/l
   3. Category 3: LC50 ≤ 10 mg/l
   4. Category 4: LC50 ≤ 20 mg/l
   5. Category 5: not defined though is expected to have an equivalent of category 5 oral and dermal
5. Inhalation – Dust and Mists
   1. Category 1: LC50 ≤ 0.05 mg/l
   2. Category 2: LC50 ≤ 0.5 mg/l
   3. Category 3: LC50 ≤ 1.0 mg/l
   4. Category 4: LC50 ≤ 5 mg/l
   5. Category 5: not defined though is expected to have an equivalent of category 5 oral and dermal

Skin Corrosion and Irritation

Skin corrosion and irritation are determined though skin patch test analysis which looks at the severity of the damage done, when it is incurred, 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 average damage (less severe than corrosion) within 72 hours of application or for three consecutive days after application within a 14 day period; or, inflammation that 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

Eye Damage and Irritation

Serious eye damage involves tissue damage or decay of vision which does not fully reverse in 21 days.

Eye irritation involves changes to the eye which do fully reverse within 21 days.

Respiratory or Skin Sensitization

Substances determined to cause to the majority of test subjects either breathing hypersensitivity through inhalation or allergic responses from dermal application.

Germ Cell mutagenicity

Substances that can cause mutations to germ cells in an adult which can be passed to progeny.

Carcinogenicity

Substances that can induce cancer or the likeliness of cancer to occur.

Reproductive Toxicity

Adverse effects in sexual function and fertility in adults and/or development of the offspring. Where a substance can do either or both, though is not lethal to the adult.

Specific Target Organ Toxicity

Substances which can cause adverse effects to a specific organ through single or multiple exposures

Aspiration Hazard

Direct/indirect ingestion or inhalation of a solid or liquid which can enter the lungs and cause sickness, damage or death.

Environmental Hazards^[5]

Environmental hazards tend to focus on degradability, bioaccumulation and aquatic toxicity.

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.

Acute aquatic toxicity levels

Acute toxicity generally involves short-term exposure to adult species.

• 1. Category Acute 1: Fish (LC50) and/or crustacea (EC50) and/or aquatic plants ≤ 1.0 mg/l
• 2. Category Acute 2: Fish (LC50) and/or crustacea (EC50) and/or aquatic plants >1 - ≤ 10 mg/l
• 3. Category Acute 3: Fish (LC50) and/or crustacea (EC50) and/or aquatic plants >10 - ≤ 100 mg/l

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.^[6]

Chronic aquatic toxicity levels

Chronic toxicity involves an analysis of long-term exposure, including life cycle stages. This method of analysis has less standardized testing and less data.

• 1. Category Chronic 1: Fish (LC50) and/or crustacea (EC50) and/or aquatic plants ≤ 1.0 mg/l
• 2. Category Chronic 2: Fish (LC50) and/or crustacea (EC50) and/or aquatic plants >1 - ≤ 10 mg/l
• 3. Category Chronic 3: Fish (LC50) and/or crustacea (EC50) and/or aquatic plants >10 - ≤ 100 mg/l
• 4. Category Chronic 4: Substances which do not easily dissolve in water and have no acute toxicity values recorded

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 can cause irreversible side effects.

Etymology

Look up toxicity in Wiktionary, the free dictionary.

"Toxic" and similar words came from Greek τοξον = "bow (weapon)" via "poisoned arrow," which came to be used for "poison" 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 = "bow-toothed" from the shape.

See also

• Agency for Toxic Substances and Disease Registry (ATSDR)
• Biological activity
• Biological warfare
• California Proposition 65 (1986)
• Carcinogen
• Drunkenness
• Indicative limit value
• List of highly toxic gases
• Mutagen
• Nephrotoxicity
• Neurotoxicity
• Ototoxicity
• Paracelsus
• Physiologically-based pharmacokinetic modelling.
• Poison
• Reference dose
• Registry of Toxic Effects of Chemical Substances (RTECS) - toxicity database
• Soil contamination
• Teratogen
• Toxic tort
• Toxication
• Toxicophore
• Toxin

References

External links

• Agency for Toxic Substances and Disease Registry
• Chemical and Other Safety Information – Oxford University
• Whole Effluent, Aquatic Toxicity Testing FAQ

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