Graph 2  Comparison of Dose-Response Curves for Two Substances

(Created 12/02) 
UNL Environmental Health and Safety · (402) 472-4925 · http://ehs.unl.edu 
to environment antagonism); temperature; air pressure. 
• Routes of Exposure. Biological results can be different for the same dose, depending on 
whether the chemical is inhaled, ingested, applied to the skin, or injected. Natural barriers 
impede the intake and distribution of material once in the body. These barriers can 
attenuate the toxic effects of the same dose of a chemical. The effectiveness of these 
barriers is partially dependent upon the route of entry of the chemical.
• Interspecies Variation. For the same dose received under identical conditions, the 
effects exhibited by different species may vary greatly. A dose which is lethal for one 
species may have no effect on another. Since the toxicological effects of chemicals on 
humans is usually based on animal studies, a test species must be selected that most 
closely approximates the physiological processes of humans.
• Intraspecies Variations. Within a given species, not all members of the population 
respond to the same dose identically. Some members will be more sensitive to the 
chemical and elicit response at lower doses than the more resistant members which 
require larger doses for the same response.
• Age and Maturity. Infants and children are often more sensitive to toxic action 
than younger adults. Elderly persons have diminished physiological capabilities 
for the body to deal with toxic insult. These age groups may be more susceptible 
to toxic effects at relatively lower doses.
• Gender and Hormonal Status. Some chemicals may be more toxic to one gender 
than the other. Certain chemicals can affect the reproductive system of either the 
male or female. Additionally, since women have a larger percentage of body fat 
than men, they may accumulate more fat-soluble chemicals. Some variations in 
response have also been shown to be related to physiological differences between 
males and females.
• Genetic Makeup. Genetic factors influence individual responses to toxic 
substances. If the necessary physiological processes are diminished or defective 
the natural body defenses are impaired. For example, people lacking in the G6PD 
enzyme (a hereditary abnormality) are more likely to suffer red blood cell damage 
when given aspirin or certain antibiotics than persons with the normal form of the 
enzyme.
• State of Health. Persons with poor health are generally more susceptible to toxic 
damage due to the body's decreased capability to deal with chemical insult.
• Environmental Factors. Environmental factors may contribute to the response for a 
given chemical. For example, such factors as air pollution, workplace conditions, living 
conditions, personal habits, and previous chemical exposure may act in conjunction with 
other toxic mechanisms.
• Chemical Combinations. Some combinations of chemicals produce different effects 
from those attributed to each individually:
• Synergists: chemicals that, when combined, cause a greater than additive effect. 
For example, hepatotoxicity is enhanced as a result of exposure to both ethanol 
and carbon tetrachloride.
• Potentiation: is a type of synergism where the potentiator is not usually toxic in 
itself, but has the ability to increase the toxicity of other chemicals. Isopropanol, 

(Created 12/02) 
UNL Environmental Health and Safety · (402) 472-4925 · http://ehs.unl.edu 
for example, is not hepatotoxic in itself. Its combination with carbon tetrachloride, 
however, increases the toxic response to the carbon tetrachloride.
• Antagonists: chemicals, that when combined, lessen the predicted effect. There 
are four types of antagonists.
1. functional: Produces opposite effects on the same physiologic function. 
For example, phosphate reduces lead absorption in the gastrointestinal 
tract by forming insoluble lead phosphate.
2. chemical: Reacts with the toxic compound to form a less toxic product. 
For example, chelating agents bind up metals such as lead, arsenic, and 
mercury.
3. dispositional: Alters absorption, metabolism, distribution, or excretion. 
For example, some alcohols use the same enzymes in their metabolism:
ethanol--------> acetaldehyde-------> acetic acid
methanol------> formaldehyde------> formic acid
The aldehydes cause toxic effects (hangover, blindness). Ethanol is more 
readily metabolized than methanol, so when both are present, methanol is 
not metabolized and can be excreted before forming formaldehyde. 
Another dispositional antagonist is Antabuse which, when administered to 
alcoholics, inhibits the metabolism of acetaldehyde, giving the patient a 
more severe prolonged hangover.
4. receptor: Occurs when a second chemical either binds to the same tissue 
receptor as the toxic chemical or blocks the action of receptor and thereby 
reduces the toxic effect. For example, atropine interferes with the receptor 
responsible for the toxic effects of organophosphate pesticides.

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