Toxicant, toxin, and poison are often used interchangeably

in the literature; however, they are different.

Toxicologists primary goal: to establish a quantitative
relationship between toxic exposure and degree of
effect.
Dose-response curve.
Toxicant concentration in the exposure medium.
Assumption: direct relationship of ambient toxicants
concentration to the dose accummulated by the
organism.
However, extraneous factors may significantly affect the
relationship.
By varying the bioavailability of a toxicant.
By altering its metabolism.
Once absorbed, how toxic a xenobiotic will be?
Biotic factors (on the host).
Abiotic factors (environmental).
Intrinsic toxicity.
Dose.
Exposure conditions.

Taxonomic group.
Variation among species.
Variation within species.
Age/body size.
Gender.
Nutrition.
Variation among species:
A substance harms one species at a given dose may not
be toxic to another species.
Example: silicosis on human (miners), did not affect
mules.

Variation within species:
Individuals may vary greatly in their sensitivity to a
toxicant.
Some very sensitive, others resistant.
Example: aspirin some are hypersensitive, but no
indication of adverse effects in most people at
common levels used.
Sensitivity to toxic chemicals can be equated
with taxonomic relationship.
Reasonable extrapolation may be made within
species, genera, and families.
Significant influence on toxic response.
Calibration of drug dosage to age or weight.
Life stages:
Animal larvae are more sensitive; eggs are more resistant (egg
membrane protection).
Babies & small children are more sensitive (immune system less
developed).
Elderly people are more sensitive (immune system less
efficient).
Small animals are more sensitive
Larger surface area : volume ratio.
Fast chemical uptake per unit weight, higher ventilatory and
metabolic rates.
Gender
Differences in sex hormones (androgen and
estrogen) influence the response to xenobiotics.
Differences in the level of enzymes production.
Nutrition
Good nutrition maintain immune system.
Poorly nourished people are less susceptible to xenobiotics.
Overweight animals (and possibly human) develop more
cancers and cardiovascular diseases.


Biotic factors (on the host).
Abiotic factors (environmental).
Intrinsic toxicity.
Dose.
Exposure conditions.

Temperature
pH and alkalinity
Salinity
Hardness
Chemical mixtures
Dissolved organic carbon

Ectothermic metabolism increases approximately
twofold for every 10C change in temperature.
Changes in metabolism may affect chemical toxicity.
Reected by changes in respiratory rate, chemical
absorption, detoxication, and excretory rates
Usually the correlation between temperature and
toxicity is positive.
Most toxicants exhibit a 2-4x increase in toxicity for every
10C change in temperature.
Probably relate to the increased metabolism of the
compound.


A negative effect of elevated temperature: increase
of oxygen usage.
Thermal death may be the result of tissue anoxia.
Thus, the toxicity of chemicals that increase metabolic
demand or inhibits oxygen uptake and utilization may be
enhanced at higher temperatures.
In water exacerbated by lower oxygen solubility
higher temperatures.
The solubility of many toxic chemicals may increase
at elevated temperatures.
Temperature changes are likely to have effects on
enzyme activity (or inhibition thereof).


pH affects chemical toxicity in a variety of ways.
Hydrogen ions in aquatic environment.
pH<5 detrimental, usually by increasing the
permeability of the gill epithelium, causing the loss
of important electrolytes.
Inuence the toxicity of trace metals, by affecting
their chemical speciation in water or by competing
with metals for sites on biological membranes.
Source of acid conditions in aquatic ecosystem:
Acid mine drainage.
Fossil fuel burning (atmospheric sulphuric acid).
The vulnerability to acid input may be
greatly affected by the buffering capacity of
the water.
This buffering capacity is referred to as
alkalinity.
Mainly a function of CO
3
2-
, HCO
3-
, OH
-
content.
Also phosphates, borates, silicates, some organics.

Optimal salinity may vary from species to species.
Outside its optimal salinity, organisms may be more
susceptible to toxic stress.
Metals such as Cd, Cu, Ag, and Zn, the effect of
salinity on their bioavailability is related to their
chemical speciation.
Example: The most bioavailable form of cadmium is the
free cadmium ion (Cd
2+
), which predominates in
freshwater.
In increasingly saline media, cadmium forms chloride
complexes such as CdCl
+
and CdCl
2
which are less
available and, therefore, less toxic.

Water hardness principal components: Ca
2+
and Mg
2+
.
Hardness alone has no effect on the speciation of other
cations such as metals.
It is usually correlated with pH and alkalinity.
There is evidence that hardness affects the toxicity of
organic surfactants.
But data are variable and often confounded by pH differences.
The correlation among hardness, alkalinity, and pH
often makes it difcult to differentiate the effects.
Some studies showed that, at a xed combination of
pH and alkalinity, increasing water hardness is
associated with a reduction in metal toxicity.

Organisms are usually exposed to chemical mixtures.
Numerous toxic chemicals may interact to produce joint
toxicity.
Chemicals with similar toxic action show additive toxicity
when acting in concert.
Some chemical mixtures may not act in an additive fashion,
when different chemical classes are involved.
Categories of joint toxic action according to Knemann
(1981):
antagonism
no addition (independent action)
partial addition
concentration addition (simple additive toxicity)
supra addition [potentiation of the toxic action(s) of one or more of the
components of the mixture].
Isobologram showing theoretical relationship between the toxic
action(s) of two toxicants in a mixture. Axes show the relative
contribution of toxicants A and B to the mixture.
Explanation of the isobologram figure.
Natural DOC is found in a variety of forms and
concentrations in the aquatic environment.
Different study results:
Amelioration of metal toxicity through the formation of
metal-organic complexes at the expense of the more
bioavailable free metal ion.
Metal bioavailability may actually be increased through the
formation of organic complexes.
Different organic ligands may be differentially
bioavailable by virtue of the relative strength of the
organic bonds.