Below you will find a series of questions related to the toxicology module. Please follow the instructions and provide complete answers to the questions. All answers must be given in your own words.
Question 1 (15 points): According to the lecture module on toxicology, please mention and describe 3 reasons that could account for why males and females respond differently to drugs or toxins? (Each reason will count for 5 points and should have a minimum of 2 sentences and maximum of 4 sentences.)
Question 2 (15 points): In studying the toxicity of Bisphenol-A revealed in the assigned article, information now exists that challenge classic toxicological paradigms such as ‘the dose makes the poison’. Please mention and describe 3 current challenges. (Each challenge will count for 5 points and should have a minimum of 2 sentences and maximum of 4 sentences.)
Question 3 (20 points):
Below is an example of a dose-response graph.
Here is the data generated for 6 different doses (mg/m3) for three different compounds, A, B and C. The response measured for each compound is lethality expressed in percent.
A)Please construct 3 dose-response curves on the same graph from the above data. Place doses on the x-axis and response (%) on the y-axis. (Your answer will count for 3 points.)
B)For each compound, please write the LD50, NOAEL and LOAEL values with appropriate units. (Your answers will count for 9 points.)
C)Which compound is the most toxic? Why did you select this compound? (Your answer will count for 2 points and should have a minimum of 1 sentence and maximum of 2 sentences.)
D)Which compound is the least toxic? Why did you select this compound? (Your answer will count for 2 points and should have a minimum of 1 sentence and maximum of 2 sentences.)
E)Please list 4 major assumptions that you had when you were comparing the toxicity of the compounds? (Your answer will count for 4 points.)
Why Males and Females Respond Differently to Drugs and Toxins
Question 1: Why Males and Females Respond Differently to Drugs and Toxins
Almost every person in the world uses drugs for some reasons. The drugs are always given in specified prescriptions to avoid lethal outcomes (Maffini et al, 2006). However, it has been noted that males and females respond differently to the drugs due to some reasons, the body of a female is different from that of a male from the physical appearance that enhances hormone production in endocrine system (Mennecozzi et al,2015). Differences in the body composition influences how the body responds to drugs and some of the substances and women are said to have low clearance rate that is compared to males. Thus giving similar doses to male’s leads to an outcome among the different genders Maffini et al, 2006).
According Vandenberg et al, (2009), the route of toxins and drugs is totally different in both males and females, such routes of drugs introduction include intradermal routes, intramuscular and intravenous. The route are found on the body surfaces that include gastrointestinal track and also the skin, but since the body of both males and females are different, it means the rate of absorption is totally different in both genders leading to different responses (Mennecozzi et al,2015). Based on Maffini et al, (2006)it is proved that men has high concentration of choric acid found in the bile duct while in females they have a high concentration of chenodeoxycholic acid.. These rate of differences leads to different responses to toxins and drugs that are assimilated by the body (Vandenberg et al, 2009).
According to Maffini et al, (2006), there is also a good reason in drugs and also toxins between men and female in that, there is difference in the transportation of proteins (). The transported protein are crucial in transporting into and out of the cells. A good example is what is called paclitaxel toxicity which is dependent on the variation of phenotype of CCCYP3A4/5 (Vandenberg et al, 2009). The transported protein which always depend on the sex of a given individual leads to great difference in both toxins and drug responses (Mennecozzi et al,2015).
Question 2: information that challenges the toxicological paradigm
Based on Toxicological paradigm for example, dose makes up the poison that is used for several bodies (Vandenberg et al, 2009). This bodies always do regulation of toxins and drugs in the market to reduce toxicity in our surroundings (Maffini et al, (2006).Though there is some conception that contests the paradigm, even a small amount of the dose results to substantial effect to the surrounding (Mennecozzi et al,2015). Results of minimal dosage is not seen as deadly and nonstop use interferes with endocrine system. There is also extra outcome of the body for example the ductless system that is observed regardless of introduction of toxicological paradigm (Mennecozzi et al,2015).It has been acknowledged that the business and the supports are handling problems entailing the effects of poison and drugs (Maffini et al,2006)
Challenges of Bisphenol –A
According to Maffini et al, (2006).Low dose of the BPA introduction during early stages of fetal development changes the gonads of the male reproduction unit by changing testis weight both at puberty and at adulthood stage.
When an organism such as human being is exposed to BPA in utero it leads to a negative result of increased size of the prostrate grand as well as the change in per ductal stoma and alterations It also leads to changes in granular cell function of the prostrate grand (Vandenberg et al, 2009). BPA also affects largely the female reproductive track, when low doses are induced, both first estrus and earlier vaginal opening are altered. In the ovaries of exposed prenatally there is significance increase in intra follicles (Mennecozzi et al,2015).
Question 3:
- The Dose-Response Curv
B).
|
Compound
|
LD50
|
NOAEL
|
LOAEL
|
|
A
|
20
|
10
|
15
|
|
B
|
17.5
|
5
|
10
|
|
C
|
15
|
5
|
10
|
C). substance A is the most dangerous since the LD50 is high compared to B and C
- D) Substance C is the least dangerous since the LD50 is lower than that of A and
- Statement when associating the toxicity of compounds.
According to Vandenberg et al, (2009) the postulation is that there is constantly a dose below which fails to produce a response or can be evaluated. The second thing that, once the maximum response is attained any more increase in the dosage will have no result in an increased effect (Maffini et al, 2006). It’s also assumed that toxins and drugs have strong effect and since all the drugs has expiry date their toxicity increase as more as they expire (Vandenberg et al, 2009).
References
Maffini, M. V., Rubin, B. S., Sonnenschein, C., & Soto, A. M. (2006). Endocrine disruptors and reproductive health: the case of bisphenol-A. Molecular and cellular endocrinology, 254, 179-186.
Mennecozzi, M., Landesmann, B., Palosaari, T., Harris, G., & Whelan, M. (2015). Sex differences in liver toxicity—do female and male human primary hepatocytes react differently to toxicants in vitro?. PloS one, 10(4), e0122786.
Vandenberg, L. N., Maffini, M. V., Sonnenschein, C., Rubin, B. S., & Soto, A. M. (2009). Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocrine reviews, 30(1), 75-95.
