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Physiologically Based Pharmacokinetic (PBPK)

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Physiologically Based Pharmacokinetic (PBPK)

Worley, Yang, and Fisher (2017), in their research, designed a model to seek clarification on the exposure of water to serum PFOA concentration as a result of PFOA manufacture. The model was specific to humans, and it includes simulations by Monte Carlo to establish the variability on sensitive model parameters. The authors hypothesize that variability in human serum PFOA concentration as a result of historical exposure to non-drinking sources (Worley, Yang, and Fisher, 2017).  The importance of the model was to help in the determination of exposure and effectiveness of mitigation mechanisms.

Cheng and NG (2017), in their student, adopt the use of a model limited to permeability in the analysis of toxic kinetics with a specific interest in masculine mice. The model focuses on cellular acceptance and buildup of PFOA through membrane facilitated transportation and passive diffusion. After a comparison of the prediction model with the experimental data, the researchers established the effectiveness of their method in predicting PFOA distribution in rats when the toxins got administered orally or intravenously. This framework got noted as useful in testing in vitro- in vivo extrapolating with a significant potential of accurately predicting PFOA toxicity in humans as well as poly and perfluorinated alkyl elements.

 ADME

Lupton, Huwe, Smith, Dearfield, & Johnston (2012), in their study, wanted to examine the accumulation of toxic PFOA in cattle after environmental exposure.  Quantification of radiocarbon got quantified for 28 days to the time of slaughter. The result indicates that PFOA was had complete absorption and excretion in the urine of the cattle within nine days after the initial exposure. The half-life of PFOA in animals got concluded to be 19.2 ± 3.3 h.  A derivative form of the toxin was also recorded in the edible meat of the cattle. The researchers found that PFOA was absorption was rapid and also it excretion was equally quick, and no significant levels of the toxins were traced in the meat leading a suggestive conclusion that edible meat from slaughter of cattle prior exposed to PFOA harbored no adequate amounts to be considered an exposure risk to humans (Lupton, Huwe, Smith, Dearfield & Johnston, 2012).

Han, Kemper & Jepson (2008) in another study examined protein binding and subcutaneous distribution in rat kidney and liver. It was noted that the liver and kidney were the primary distribution organs in rats, and the delivery has a sexual alignment. Subcutaneous levels of PFOA were found to be higher in males, while the amounts in liver cytosol were higher in female rats. Cytosol kidney space accounted for 70% of PFOA. Liver bound cytosol proteins were both 55% in the two sexes while. More PFOA were found in kidney proteins in male than in female rats (Han, Kemper & Jepson, 2008).

Genotoxicity

A study got conducted to investigate genotoxicity in PFOA by employing Utero exposure. The lung tissues had no observable microscopic alteration bit; an exposure spanning for six days caused an alteration in the cell’s gene expression (Ye at al., 2012).    Florentin, Deblonde, Diguio, Hautemaniere, & Hartemann (2011) conducted a study to analyses cytotoxicity and genotoxicity. Contrary to the popular opinion, it was found the PFOA did not induce DNA damage or oxidative stress, and therefore genotoxicity was ruled out. The results for cytotoxicity were positive (Florentin, Deblonde, Diguio, Hautemaniere & Hartemann, 2011).

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