3. factors affecting toxicity

7/21/2019 3. Factors Affecting Toxicity

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Toxicant, toxin, and poison are often used interchangeablyin the literature; however, they are different.


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Toxicologists primary goal: to establish a quantitative

relationship between toxic exposure and degree ofeffect.

Dose-response curve.

Toxicant concentration in the exposure medium.

Assumption: direct relationship of ambient toxicantsconcentration to the dose accummulated by theorganism.

However, extraneous factors may significantly affect therelationship.

By varying the bioavailability of a toxicant.

By altering its metabolism.

Once absorbed, how toxic a xenobiotic will be?


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Biotic factors (on the host).

Abiotic factors (environmental).

Intrinsic toxicity. Dose.

Exposure conditions.


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Taxonomic group.

Variation among species.

Variation within species.

Age/body size.

Gender.

Nutrition.


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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.


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Variation within species: Individuals may vary greatly in their sensitivity to a

toxicant.

Some very sensitive, others resistant.

Example: aspirin some are hypersensitive, but noindication of adverse effects in most people atcommon levels used.

Sensitivity to toxic chemicals can be equated

with taxonomic relationship. Reasonable extrapolation may be made within

species, genera, and families.


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Significant influence on toxic response.

Calibration of drug dosage to age or weight.

Life stages:

Animal larvae are more sensitive; eggs are more resistant (eggmembrane protection).

Babies & small children are more sensitive (immune system lessdeveloped).

Elderly people are more sensitive (immune system lessefficient).

Small animals are more sensitive Larger surface area : volume ratio.

Fast chemical uptake per unit weight, higher ventilatory andmetabolic rates.


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Gender

Differences in sex hormones (androgen andestrogen) 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.


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Biotic factors (on the host).

Abiotic factors (environmental).

Intrinsic toxicity. Dose.

Exposure conditions.


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Temperature pH and alkalinity

Salinity

Hardness

Chemical mixtures

Dissolved organic carbon


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Ectothermic metabolism increases approximatelytwofold for every 10C change in temperature.

Changes in metabolism may affect chemical toxicity.

Reflected by changes in respiratory rate, chemical

absorption, detoxification, 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.


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A negative effect of elevated temperature: increaseof oxygen usage.

Thermal death may be the result of tissue anoxia.

Thus, the toxicity of chemicals that increase metabolicdemand or inhibits oxygen uptake and utilization may be

enhanced at higher temperatures.

In water exacerbated by lower oxygen solubilityhigher temperatures.

The solubility of many toxic chemicals may increaseat elevated temperatures.

Temperature changes are likely to have effects onenzyme activity (or inhibition thereof).


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pH affects chemical toxicity in a variety of ways.

Hydrogen ions in aquatic environment.

pH


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The vulnerability to acid input may begreatly affected by the buffering capacity ofthe water.

This buffering capacity is referred to asalkalinity.

Mainly a function of CO32-, HCO3-, OH-content.

Also phosphates, borates, silicates, some organics.


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Optimal salinity may vary from species to species.

Outside its optimal salinity, organisms may be moresusceptible to toxic stress.

Metals such as Cd, Cu, Ag, and Zn, the effect of

salinity on their bioavailability is related to theirchemical speciation.

Example: The most bioavailable form of cadmium is thefree cadmium ion (Cd2+), which predominates infreshwater.

In increasingly saline media, cadmium forms chloridecomplexes such as CdCl+and CdCl2which are lessavailable and, therefore, less toxic.


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Water hardness principal components: Ca2+and Mg2+.

Hardness alone has no effect on the speciation of othercations such as metals.

It is usually correlated with pH and alkalinity.

There is evidence that hardness affects the toxicity oforganic surfactants.

But data are variable and often confounded by pH differences.

The correlation among hardness, alkalinity, and pHoften makes it difficult to differentiate the effects.

Some studies showed that, at a fixed combination ofpH and alkalinity, increasing water hardness isassociated with a reduction in metal toxicity.


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Organisms are usually exposed to chemical mixtures.

Numerous toxic chemicals may interact to produce jointtoxicity.

Chemicals with similar toxic action show additive toxicitywhen 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].


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Isobologram showing theoretical relationship between the toxicaction(s) of two toxicants in a mixture. Axes show the relative

contribution of toxicants A and B to the mixture.


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Explanation of the isobologram figure.


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Natural DOC is found in a variety of forms andconcentrations in the aquatic environment.

Different study results:

Amelioration of metal toxicity through the formation ofmetal-organic complexes at the expense of the morebioavailable free metal ion.

Metal bioavailability may actually be increased through theformation of organic complexes.

Different organic ligands may be differentiallybioavailable by virtue of the relative strength of theorganic bonds.

3. factors affecting toxicity

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