what are the factors that influence the toxicity when exposed to an environmental pollutant?
3.2: Factors Affecting Toxicity
- Folio ID
- 317813
Factors Influencing Toxicity
In some instances, individuals can take unpredictable reactions, or idiosyncratic responses, to a drug or other substance. An idiosyncratic response is uncommon, and it is sometimes incommunicable to understand whether it is the result of a genetic predisposition or has some other cause such equally the condition of the immune organisation. Information technology could outcome in an abnormally small or brusque, or abnormally large or long response to the drug or other substance. Or, the response could be qualitatively different than what has been observed in nearly other individuals.
The toxicity of a substance usually depends on the following factors:
- Form and innate chemical activity
- Dosage, peculiarly dose-fourth dimension relationship
- Exposure route
- Species
- Life stage, such as infant, immature adult, or elderly adult
- Gender
- Ability to be absorbed
- Metabolism
- Distribution within the body
- Excretion
- Wellness of the individual, including organ function and pregnancy, which involves physiological changes that could influence toxicity
- Nutritional status
- Presence of other chemicals
- Circadian rhythms (the time of day a drug or other substance is administered)
Factors Related to the Substance
Course and Innate Chemical Activeness
The form of a substance may have a profound bear upon on its toxicity especially for metal elements, also termed heavy metals. For example, the toxicity of mercury vapor differs profoundly from methyl mercury. Another example is chromium. Cr3+ is relatively nontoxic whereas Cr6+ causes skin or nasal corrosion and lung cancer.
The innate chemical activeness of substances also varies greatly. Some can speedily damage cells causing firsthand cell expiry. Others slowly interfere only with a cell's function. For example:
- Hydrogen cyanide binds to the enzyme cytochrome oxidase resulting in cellular hypoxia and rapid death.
- Nicotine binds to cholinergic receptors in the cardinal nervous organisation (CNS) altering nerve conduction and inducing gradual onset of paralysis.
Dosage
The dosage is the most important and disquisitional factor in determining if a substance will be an astute or a chronic poisonous substance. Virtually all chemicals can be astute toxicants if sufficiently large doses are administered. Often the toxic mechanisms and target organs are different for astute and chronic toxicity. Examples are:
| Toxicant | Acute Toxicity | Chronic Toxic Effects |
|---|---|---|
| Ethanol | CNS depression | Liver cirrhosis |
| Arsenic | Gastrointestinal damage | Skin/liver cancer |
Table \(\PageIndex{one}\). Examples of astute and chronic toxicity
Exposure Road
The way an individual comes in contact with a toxic substance, or exposure route, is important in determining toxicity. Some chemicals may be highly toxic by one route but not by others. 2 major reasons are differences in absorption and distribution within the body. For case:
- Ingested chemicals, when absorbed from the intestine, distribute outset to the liver and may be immediately detoxified.
- Inhaled toxicants immediately enter the general blood circulation and can distribute throughout the body prior to existence detoxified by the liver.
Different target organs often are affected by different routes of exposure.
Figure \(\PageIndex{1}\). Ingestion
(Image Source: ORAU, ©)
Figure \(\PageIndex{two}\). Inhalation
(Paradigm Source: ORAU, ©)
Absorption
The ability to be absorbed is essential to systemic toxicity. Some chemicals are readily captivated and others are poorly captivated. For instance, nearly all alcohols are readily captivated when ingested, whereas in that location is virtually no absorption for nigh polymers. The rates and extent of absorption may vary greatly depending on the course of a chemical and the route of exposure to information technology. For case:
- Ethanol is readily absorbed from the alimentary canal just poorly absorbed through the skin.
- Organic mercury is readily absorbed from the gastrointestinal tract; inorganic lead sulfate is non.
Factors Related to the Organism
Species
Toxic responses tin vary substantially depending on the species. Most differences between species are attributable to differences in metabolism. Others may be due to anatomical or physiological differences. For example, rats cannot vomit and miscarry toxicants before they are absorbed or cause astringent irritation, whereas humans and dogs are capable of vomiting.
Selective toxicity refers to species differences in toxicity between 2 species simultaneously exposed. This is the basis for the effectiveness of pesticides and drugs. For example:
- An insecticide is lethal to insects only relatively nontoxic to animals.
- Antibiotics are selectively toxic to microorganisms while virtually nontoxic to humans.
Life Stage
An individual'southward age or life stage may be important in determining his or her response to toxicants. Some chemicals are more than toxic to infants or the elderly than to young adults. For example:
- Parathion is more toxic to young animals.
- Nitrosamines are more carcinogenic to newborn or young animals.
Figure \(\PageIndex{three}\). An individual's life phase can impact that person'south response to toxicants
(Paradigm Source: iStock Photos, ©)
Gender
Gender can play a large role in influencing toxicity. Physiologic differences betwixt men and women, including differences in pharmacokinetics and pharmacodynamics, can affect drug activity.
In comparison with men, pharmacokinetics in women generally can be impacted by their lower body weight, slower gastrointestinal motility, reduced intestinal enzymatic activity, and slower kidney function (glomerular filtration rate). Delayed gastric emptying in women may consequence in a need for them to extend the interval betwixt eating and taking medications that crave assimilation on an empty tum. Other physiologic differences between men and women too exist. Slower renal clearance in women, for instance, may upshot in a need for dosage adjustment for drugs such as digoxin that are excreted via the kidneys.
In general, pharmacodynamic differences between women and men include greater sensitivity to and enhanced effectiveness, in women, of some drugs, such equally beta blockers, opioids, and some antipsychotics.
Studies in animals likewise take identified gender-related differences. For instance:
- Male person rats are 10 times more sensitive than females to liver damage from DDT.
- Female person rats are twice as sensitive to parathion as are male rats.
Figure \(\PageIndex{4}\). Gender symbols for female person (left) and male (right)
(Image Source: iStock Photos, ©)
Metabolism
Metabolism , also known as biotransformation, is the conversion of a chemical from ane form to another by a biological organism. Metabolism is a major factor in determining toxicity. The products of metabolism are known every bit metabolites. There are two types of metabolism:
- Detoxification
- Bioactivation
In detoxification , a xenobiotic is converted to a less toxic form. This is a natural defense machinery of the organism. Generally, detoxification converts lipid-soluble compounds to polar compounds.
In bioactivation , a xenobiotic may be converted to more reactive or toxic forms. Cytochrome P-450 (CYP450) is an instance of an enzyme pathway used to metabolize drugs. In the elderly, CYP450 metabolism of drugs such as phenytoin and carbamazepine may be decreased. Therefore, the effect of those drugs may exist less pronounced. CYP450 metabolism also can exist inhibited by many drugs. Adventure of toxicity may be increased if a CYP450 enzyme-inhibiting drug is given with 1 that depends on that pathway for metabolism.
At that place is awareness that the gut microbiota tin bear upon the toxicity of drugs and other chemicals. For example, gut microbes tin can metabolize some ecology chemicals and bacteria-dependent metabolism of some chemicals can attune their toxicity. Also, environmental chemicals tin alter the composition and/or the metabolic activity of the gastrointestinal bacteria, thus contributing in a meaningful style to shape an individual'southward microbiome. The study of the consequences of these changes is an emerging area of toxicology.
Learn more nigh human exposure to pollutants and their interaction with the GI microbiota.
Larn more about the microbiome and toxicology.
Distribution Within the Body
The distribution of toxicants and toxic metabolites throughout the body ultimately determines the sites where toxicity occurs. A major determinant of whether a toxicant will damage cells is its lipid solubility. If a toxicant is lipid-soluble, it readily penetrates cell membranes. Many toxicants are stored in the body. Fat tissue, liver, kidney, and os are the most common storage sites. Blood serves every bit the main avenue for distribution. Lymph also distributes some materials.
Excretion
The site and rate of excretion is another major factor affecting the toxicity of a xenobiotic. The kidney is the primary excretory organ, followed by the gastrointestinal tract, and the lungs (for gases). Xenobiotics may also be excreted in sweat, tears, and milk.
A large volume of blood serum is filtered through the kidney. Lipid-soluble toxicants are reabsorbed and concentrated in kidney cells. Impaired kidney function causes slower elimination of toxicants and increases their toxic potential.
Health Condition
The health of an individual or organism tin play a major role in determining the levels and types of potential toxicity. For case, an individual may have pre-existing kidney or liver affliction. Sure conditions, such as pregnancy, also are associated with physiological changes in kidney function that could influence toxicity.
Nutritional Status
Diet (nutritional status) tin be a major cistron in determining who does or does non develop toxicity. For example:
- Consumption of fish that take captivated mercury from contaminated water can event in mercury toxicity; an antagonist for mercury toxicity is the food selenium.
- Some vegetables tin accumulate cadmium from contaminated soil; an antagonist for cadmium toxicity is the nutrient zinc.
- Grapefruit contains a substance that inhibits the P450 drug detoxification pathway, making some drugs more than toxic.
Find out more about nutrition and chemic toxicity here.
Circadian Rhythms
Circadian rhythms tin play a role in toxicity. For example, rats administered an immunosuppressive drug had astringent toxicity in their intestines vii hours after calorie-free onset compared to controls and to other times in the day. The rats had changes in their digestive enzyme activeness and other physiological indicators at this dosing time.
Find out more nigh circadian rhythm and gut toxicity here.
Other Factors
Presence of Other Chemicals
The presence of other chemicals, at the same time, earlier, or afterward may:
- Decrease toxicity (animosity)
- Add to toxicity (additivity)
- Increase toxicity (synergism or potentiation)
For example:
- Antidotes used to counteract the effects of poisons function through animosity (atropine counteracts poisoning past organophosphate insecticides).
- Alcohol may enhance the issue of many antihistamines and sedatives.
- A synergistic interaction between the antioxidant butylated hydroxytoluene (BHT) and a sure concentration of oxygen results in lung damage in the course of interstitial pulmonary fibrosis.
Information on boosted examples of lung damage from chemical interactions tin exist institute here.
Cognition Check
ane. A target organ is an organ that:
- Reply
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A target organ is an organ in which a substance exerts a toxic issue.
2. What are the important factors that influence the degree of toxicity of a substance?
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3. Metabolism, or biotransformation, of a xenobiotic:
- Answer
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May result in detoxification or bioactivation
Metabolism of a xenobiotic results in either detoxification, which converts the xenobiotic to a less toxic form, or bioactivation, which converts the xenobiotic to more reactive or toxic forms. For instance, a xenobiotic itself might not be carcinogenic, but a metabolite of the xenobiotic might be.
4. An antibody administered to humans kills bacteria in the torso simply does not damage human being tissues. This is an instance of:
- Answer
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Selective Toxicity
Selective toxicity refers to differences in toxicity between ii species simultaneously exposed, much similar the antibiotic in this instance.
- Answer
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A major determinant of whether or not a poison will damage cells is its lipid solubility. If a toxicant is lipid-soluble, it readily penetrates prison cell membranes.
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Source: https://chem.libretexts.org/Bookshelves/Environmental_Chemistry/Toxicology_MSDT/6:_Principles_of_Toxicology/Section_3:_Toxic_Effects/3.2:_Factors_Affecting_Toxicity
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