Toxicodynamics
[1] A biological target, also known as the site of action, can be binding proteins, ion channels, DNA, or a variety of other receptors.
endocrine disrupting chemicals (EDCs) and carcinogens are examples of classes of toxicants that can act as QSARs.
The process of toxicodynamics can be useful for application in environmental risk assessment by implementing toxicokinetic-toxicodynamic (TKTD) models.
TKTD models include phenomenas such as time-varying exposure, carry-over toxicity, organism recovery time, effects of mixtures, and extrapolation to untested chemicals and species.
[1] EDCs are generally considered to be toxicants that either mimic or block the transcriptional activation normally caused by natural steroid hormones.
[3] In wildlife, exposure to EDCs can result in altered fertility, reduced viability of offspring, impaired hormone secretion or activity and modified reproductive anatomy.
[5] Endocrine disruption as a mode of action for xenobiotics was brought into awareness by Our Stolen Future by Theo Colborn.
[1] Although production of DDT has been banned in the Western world, this chemical is extremely persistent and is still commonly found in the environment along with its metabolite DDE.
[1] DDE is an antiandrogen, which means it alters the expression of specific androgen-regulated genes, and is an androgen receptor (AR)-mediated mechanism.
[7] A purely anthropogenic substance, PCBs are no longer in production in the United States due to the adverse health effects associated with exposure, but they are highly persistent and are still widespread in the environment.
[8] The binding of the complex to these elements causes a rearrangement of the chromatin and transcription of the gene, resulting in production of a specific protein.
The effects of carcinogens are most often related to human exposures but mammals are not the only species that can be affected by cancer-causing toxicants.
[10] Neoplasms occurring in epithelial tissue such as the liver, gastrointestinal tract, and the pancreas have been linked to various environmental toxicants.
The biotransformation process can activate the PAH compound and transform it into a diol epoxide,[citation needed] which is a very reactive intermediate.
[citation needed] The binding of diol epoxides and DNA base pairs blocks polymerase replication activity.
[citation needed] Due to these processes, PAH compounds are thought to play a role in the initiation and early promotion stage of carcinogenesis.
This type of carcinogenesis does not change the sequence of DNA; instead it alters the expression or repression of certain genes by a wide variety of cellular processes.
[10] It has been proposed that modification of gene expression from nongenotoxic carcinogens can occur by oxidative stress, peroxisome proliferation, suppression of apoptosis, alteration of intercellular communication, and modulation of metabolizing enzymes.
[13] Due to its widespread industrial use and release into the environment, carbon tetrachloride has been found in drinking water and therefore, has become a concern for aquatic organisms.
Experimental cancer studies have shown that carbon tetrachloride may cause benign and malignant liver tumors to rainbow trout.
[13][14] carbon tetrachloride works as a nongenotoxic carcinogen by formulating free radicals which induce oxidative stress.
[15] Toxicodynamics can be used in combination with toxicokinetics in environmental risk assessment to determine the potential effects of releasing a toxicant into the environment.
Both toxicokinetics and toxicodynamics have now been described, and using these definitions models were formed, where the internal concentration (TK) and damage (TD) are simulated in response to exposure.
A review of the assumptions and hypotheses of each was previously published in the creation of a general unified threshold model of survival (GUTS).
