Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 451

Biochemical Toxicology

Spring 2010

Lecture Notes:: 23 March

© R. Paselk 2008
 
     
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Comparative Toxicology

Diagram of aniline metabolism

The preferred route of hydroxylation varies significantly, and correlates with toxicity. Thus species which produce more o-aminophenol (e.g. cats and dogs), which is more toxic, are more sensitive to aniline than those which produce more p-aminophenol (e.g. rats and hamsters). Species differences in aniline hydroxylation are compared in Table 5.9, p 139 of Timbrell 4th.

diagram of malathion metabolism

Malaoxon is a potent cholinesterase inhibitor, and thus acts as a neurotoxin for insects, while the diacid is excreted after conjugtion by mammals with little harm.

diagram of amphetamine metabolism

Variations in Absorption, Distribution, and Excretion of compounds.

Strain/genetic variations in toxicity

An important example of strain/genetic variation in toxicity is seen in the differences between so-called fast and slow acetylators as shown in Figure 5.23 (p 153) and tables 5.14 (p 152) & 5.16 (p 155) of Timbrell 4th.

Physiological Factors & Toxicology

Stress

Stress can have a variety of effects on health and on toxin metabolism. For example, cold stress and excess noise both increase the hydroxylation of aromatic compounds.

Diet

Diet can have a diverse impact on xenobiotic metabolism. Variations in enzyme expression can have particular impacts:

Both enzyme induction and inhibition can in turn have diverse and unexpected results:

Enzyme induction can often result in remarkably specific changes as a result of the new spectrum of enzyme activities.

As a result prediction of the effects of inducers requires a good deal of prior knowledge regarding the xenobiotic's metabolism as well as the enzyme induced.

Inhibitors on the other hand can display considerable specificity for tissues and effects (e.g. neurotoxicity due to neuron receptor inhibition).

Nutritional status can also effect toxin action. For example, the lack of a nutrient can have both positive and negative effects.


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Last modified 23 March 2010

© RA Paselk 2001