Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 451

Biochemical Toxicology

Spring 2010

Lecture Notes:: 1 April

© R. Paselk 2008
 
     
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Toxic Responses, cont.

Teratogenesis, cont.

Teratogenesis is highly complex, but one should expect that it should be easy to disturb such a complex and highly coordinated process as development, and that the timing of the disturbance should be important. (Timbrell 4th, Figures 6.22, p 239 and 6.23, p 240)

Manifestations of teratogenesis include:

Dose-Response: Clearly seems to be a "no effect" level for most if not all teratogens for the first three manifestations; little evidence for concentration on functional disorders. There is a clear need to hit a minimal number of cells to manifest an effect, and the number of cells effected shows a clear dose/response effect.

Mechanisms of teratogenesis include:

Mutagenesis

Mutagenesis effects show up in offspring for multicellular organisms (as opposed to bacteria).

Mutation - define as a heritable change in cell genotype.

Tissue Lesions

Tissue sensitivities vary as do exposures.

Concentrations of toxins will generally be highest at point of exposure. Thus skin, GI tract and lungs often suffer disproportionate damage.

Similarly, liver will receive high concentrations due to being the portal of entry from the GI tract.

Kidney experiences high concentrations due to concentrating mechanisms:

Damage within organs depends on anatomy and physiology.

Examples:


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© RA Paselk 2001