Factors that influence toxicity

FACTORS THAT
INFLUENCE TOXICITY
Aquatic Toxicology (ZOL-656)
MSc Zoology 4th semester
Model Science College EllahAbad
1

FACTORS PERTAINING TO THE CHEMICALS
1. The factors pertaining to the chemicals are:
i. Physicochemical properties including the functional groups,
ii. Solubility in water and organic solvents,
iii. Dose/concentration,
iv. Ionic characteristics
v. Translocation and biotransformation,
vi. Their mode of action, and
vii. Interaction with other chemicals.
2

FACTORS RELATED TO THE EXPOSURES
2. The factors related to the exposures are:
i. Routes of exposure,
ii. Exposure systems,
iii. Exposure duration
3

THE EFFECTS OF PHYSICOCHEMICAL CHARACTERISTICS
OF WATER ON THE TOXICITY OF CHEMICALS
3. These factors are:
i. water temperature,
ii. dissolved oxygen,
iii. pH,
iv. salinity,
v. water hardness, and
vi. suspended and dissolved substances.
4

FACTORS PERTAINING TO THE ORGANISMS
4. The factors pertaining to the organisms are:
i. Type of species,
ii. Sex,
iii. Age,
iv. Stage of the life cycle,
v. Weight and size of individual,
vi. Health and nutritional status,
vii. Seasonal physiological state, and
viii.Acclimation of individuals.
5

ABIOTIC AND BIOTIC MODIFYING FACTORS
• The toxicity modifying factors related to the chemical, the exposure
and the surrounding medium may be considered together and termed
as abiotic modifying factors.
• The factors related to the organisms may also be termed as biotic
modifying factors.
6

FACTORS THAT INFLUENCE TOXICITY
• For the sake of convenience, this topic “FACTORS THAT
INFLUENCE TOXICITY” will be divided into following four
sections:
i. Factors pertaining to chemical,
ii. Factors pertaining to exposure,
iii. Factors pertaining to surrounding medium, and
iv. Factors pertaining to organisms.
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1. FACTORS
PERTAINING TO
CHEMICAL
8

(I) CHEMICAL COMPOSITION:
• The physico-chemical characteristics of a compound, such as
solubility, vapour pressure, ionization, functional groups, etc. are
largely governed by the chemical constitution of the compound. All
these characteristics greatly affect the toxicological properties of the
substance.
• The polar (hydrophilic) chemicals are not easily soluble in lipids.
Therefore, they cannot easily cross the membranous barriers and thus
cannot easily reach the target sites for appropriate action. However,
non-polar or lipophilic substances are highly soluble in lipids and
other organic solvents. They can readily penetrate the lipoprotein
layers of membranes, hence they readily produce their potential effects
9

(II) DOSE OR CONCENTRATION OF CHEMICAL:
• A chemical induces toxic effects on account of its interaction with
appropriate receptors. The effect is directly related to concentration of
the chemical at the target site and concentration at the target site is
often directly proportional to dose/concentration of the chemical
exposed.
• The lower doses of chemical cause less effects whereas higher doses
may cause pronounced effects. Thus, toxicity of chemical is directly
proportional to its dose/concentration.
10

(III) TRANSLOCATION OF TOXICANT:
• There are two types of toxicants:
(a) those producing local effects, and (b) those producing systemic effects.
• In case of the latter group, effective translocation is a key factor. Unless the
toxicants are readily translocated to the specific sites, they cannot produce
adverse effects. During the course of translocation, some of the toxicants
interact with certain macromolecules present in the body of organisms and
are then stored in certain relatively inactive tissues, i.e. storage depots.
• The inefficient translocation and storage of toxicants in inactive forms
reduces their toxicity, while their effective translocation to the target in
active forms enhances their toxicity.
11

(IV) BIOTRANSFORMATION OF TOXICANTS
• Certain chemicals are normally inactive. During translocation such
chemicals are biocatalytically converted into active form in the body
of organisms with the help of certain enzymes. Consequently, the
toxicity of that particular chemical is increased.
• However, in certain other cases active xenobiotics are converted to
their inactive forms during translocation and these forms are often
stored in the nontarget or relatively inactive tissues.
12

(V) CHEMICAL INTERACTIONS
• In nature often various chemicals may be present and the organisms
are not exposed to only one chemical, but to a variety of chemicals.
These chemicals interact with each other and such chemical
interactions may have great toxicological significance.
• However, in the laboratories, the organisms may be simultaneously or
consecutively exposed to two chemicals. These chemicals interact and
affect the toxicity of each other. These interactions may cause three
types of toxic effects.
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• (i) The combined effect of two chemicals may be equal to the sum of
the effect of each chemical when given alone. This type of interaction
is considered as additive.
• (ii) The combined effects of two chemicals to the organisms exposed
may be greater than the sum and this type of interaction is designated
as synergistic; for example, effects of carbon tetrachloride and ethanol
on liver; and asbestos exposure and cigarette smoking on the lungs.
• (iii) The combined effect of two chemicals to the organisms exposed
may be less than the sum and this type of interaction is termed as
antagonistic; for example, chelation of heavy metals by dimercaprol.
14

• It may thus be inferred that interaction of one chemical with another
may: (i) have no effect on their toxicity, or (ii) increase their toxicity,
or (i) decrease their toxicity
15

2. FACTORS
PERTAINING TO
EXPOSURE
16

(I) EXPOSURE ROUTES
• The toxicant gain access to the body of organisms by dermal, oral and
inhalation exposures or by intraperitoneal, intramuscular,
subcutaneous and intravenous injections. The routes of exposure
largely affect the toxicity of chemicals.
• A chemical produces more rapid and greatest effect when given by
intravenous route, because through this route the chemical directly
reaches in active form to the specific site and thus produces greatest
effects.
• The other exposure routes in descending order of toxicity are:
inhalation> intraperitoneal>subcutaneous>intramuscular>oral>topical.
17

(II) EXPOSURE DURATION
• LC50 or LD50 values of toxicants decrease with increase in duration
of exposure. The values evaluated for long-term exposures are much
less than those determined for short-term exposures.
• The exposure for short duration has less effect in comparison to long-
term exposures. This simply indicates that the toxicity of substances
increases with increase in exposure period.
18

(III) EXPOSURE SYSTEMS
• A variety of exposure systems may be used for the exposure of toxicants.
For instance, in aquatic medium, various exposure systems are used for the
exposure of toxicants to organisms, such as:
i. Static system: Where toxicant is mixed in the water and the organisms
are exposed to it in still water.
ii. Recirculatory system: Where the toxicant solution is recirculated
through certain pumps.
iii. Renewal system: Where the toxicant solution is renewed after certain
interval.
iv. Flow through system: Where the toxicant solution flows into and out of
test chamber intermittently or continuously.
19

3. FACTORS
PERTAINING TO
THE SURROUNDING
MEDIUM
20

(I) WATER TEMPERATURE
• The water temperature is expected to greatly affect the toxicity of
xenobiotics. The increased water temperature increases the solubility
of many substances, affects the chemical form of some and governs
the amounts of dissolved oxygen in water.
• Temperature change in a particular direction may increase or decrease
or cause no effect on the toxicity of chemicals, depending on the
chemical, the species, the response and the particular procedure.
21

(II) DISSOLVED OXYGEN
• Freshwater can dissolve 14.6 mg/1 level of oxygen at 0ºC, which
gradually decreases to 9.1 mg/1 with increase in temperature upto
20ºC and reaches to the level 7.5 mg/1 at 30ºC. It is, therefore, obvious
that increase in temperature decreases the dissolved oxygen content of
the water. Oxygen is essentially required for respiration by the
organisms.
• Thus, it might be expected that reduction in dissolved oxygen content
of water imposes stress on the aquatic organisms, which may greatly
increase the toxicity of a chemical in water.
22

(iii) pH
• pH may have greater effects on the toxicity of those chemicals that
ionize under the influence of pH. Usually undissociated forms of
chemicals are more toxic to organisms, because they easily penetrate
the cell membranes.
• The toxicity of ammonia is known to be greatly affected by pH of the
water. Unionized form of ammonia (NH3) is highly toxic to fish and
the toxic range is quite low (0.2-0.7 mg/1) for salmonids. In contrast,
ionized form of ammonia (NH4 + ) has very little or no toxicity.
23

(IV) SALINITY
• The greatest differences in chemical characteristics of fresh water and
seawater may be expected to enormously affect the toxicity of
chemicals.
• Generally, Euryhaline organisms are more resistant in about one third
seawater (i.e. water containing 30-40% salinity), in salinity close to
their isosmotic level.
• However, appreciable decrease in salinity of water often renders the
marine animals less tolerant. Therefore, it may be concluded that the
toxicity of xenobiotics may increase with appreciable decrease in the
salinity of the surrounding medium.
24

(V) WATER HARDNESS
• The total hardness of water has little effect on the toxicity of most of
the chemicals except for metals. The toxicity of ammonia, phenols,
surfactants and pesticides has been reported to be affected the least by
the hardness of water. LAS, a surfactant, has been reported to be 1.5
times as toxic to bluegills in hard water as in soft water.
25

(VI) SUSPENDED AND DISSOLVED MATTER
• Natural water often contains suspended and dissolved matter including
organic ligands and chelators. They may partly detoxify some of the
xenobiotic chemicals as a result of sorption or binding. The metals are
chief examples that may be detoxified by this mechanism.
• The toxicity of metals is often greatly decreased by the suspended and
dissolved matters present in water because of sorption and binding
while other xenobiotics are much less affected.
26

4. FACTORS
PERTAINING TO
ORGANISMS
27

(I) TEST SPECIES
• The toxicity of xenobiotics greatly varies with variation in test
organisms, as the tolerance to chemicals differs in different groups of
organisms. Among the organisms of same group, the toxicity of
chemical varies with variation in species of the organisms. Even in
different individuals of same species, the toxicity of chemicals varies
because of variation in susceptibility owing to certain genetic factors.
Thus, certain individuals of a species may be susceptible to a chemical
whereas the other may be resistant to the same chemical.
• The toxicity of a chemical may vary among various fish species. Spear
and Pierce (1979) reported that salmonids and minnows are about 15
times more susceptible to copper than that of sunfish.
28

(II) SEX
• The toxicity of chemicals differs with respect to sexes, because the
males and females differ in their responses due to hormonal and
metabolic differences. Males in some species biotransform compounds
more rapidly than females, although this is not true for all species.
• For instance, aldrin (an organochlorine pesticide) is much more toxic
to male rats than to female rats.
29

(III) AGE
• Generally, the young animals are more susceptible to xenobiotics. For
a majority of chemicals, the young are 1.5 to 10 times more
susceptible than the adults. The main reasons for the susceptibility of
young ones may be less resistance and lack of biotransformation
enzyme systems.
• It has already been reported that the newly born individuals do not
posses the enzyme systems catalyzing the biotransformation reactions.
These enzyme systems develop gradually, reach at peak at a certain
stage, thereafter tend to decline.
30

(IV) LIFE-STAGE
• The toxicity of chemicals varies with different stages of the life-cycle.
Generally, the early life-stages or immature stages are more
susceptible to toxicant exposures than the late stages or mature
individuals. The fries and fingerlings of fishes are most sensitive
stages. Omkar (1980-81, unpublished data) has also found juveniles of
freshwater prawns to be more susceptible to pesticide exposures than
those of adult individuals.
• In certain organisms or a group of organisms, a particular stage of the
life-cycle may be particularly susceptible to toxicants and exposure of
toxicants at this stage appreciably affects the results. For instance, the
time of molting is particularly susceptible in case of aquatic
arthropods.
31

(V) SIZE
• The toxicity of chemicals is also affected by the size of the organisms.
Often larger sized individuals are more resistant to toxicants and this
has been found true in case of certain fishes.
• Hearth and Sprague (1978) reported that copper tolerance to rainbow
trout gradually increases with increase in size of the fish.
32

(VI) HEALTH AND NUTRITION
• The toxicity of chemicals to organisms is affected by the health and
nutritional status of organisms. Generally, the healthy individuals are
more tolerant to toxicants than diseased ones. The diseased and
parasitized individuals have been reported to be more sensitive to
various toxicants than the normal ones.
• For example, unhealthy fishes have been reported to be more
susceptible to sodium chloride and an organophosphate pesticide,
guthion. The toxicity of chemicals is also affected by the nutritional
status of the organisms.
33

(V) ACCLIMATION
• The animals acclimated to sub lethal levels of a toxicant may become
more tolerant or more weakened, depending upon the mode of action
of toxicant and the types of detoxifying mechanism of the animals.
• For instance, acclimation of trout to sub lethal (0.22 mg/1) level of
arsenic for three weeks, increased the threshold of LC50 by a factor of
1.5. While acclimation to one-third of the lethal level of cyanide to
fish rendered them to become more sensitive by a factor of one-third
in the first week. The tolerance improved to the original level by the
end of three weeks.
34

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