Bienvenidos! Welcome! Hola everyone! My name is Marlon Moraga, and I am a student in PHR 7588: Toxic Substances. For my 4 topics that I have chosen, I chose to study Captan and Folpet, Diethylene Glycol, Zinc, and Poison ivy. These 4 topics were so interesting to learn and also clinically relevant that made me want to learn more about them and hopefully it makes you want to learn about them as well!

In the Captan and Folpet blog, you’ll learn about the role that it plays as a fungicide.  Interestingly enough, it is pretty safe to use in terms of toxicity. However, once it is exposed to the eye, you are in for a nice ride of irritation! You’ll learn about the mechanism of action and how it works as a fungicide.

In the Diethylene Glycol blog, you’ll explore the many ways that one could be exposed to Diethylene glycol and why you should never ingest it! In fact, you’ll learn how easily and tempting diethylene glycol is easily consumable due to its unique attribute of taste. Did you know that a historical disaster with diethylene glycol push the establishment of the FDA?

In the Zinc blog, you’ll learn about the interesting facts on how it is an important mineral in our diet but also deadly as well when consume in high numbers. In addition, you’ll discover the variety of places that zinc can be found. Have you ever wonder what would happen if you consume too much or what happens when you do not have enough zinc in your life? Once you start reading you’ll realize how important but deadly this metal can be in our lives. Did you know that zinc went on a huge back order in many pharmacies? Later, you’ll read about how zinc was used to combat COVID-19 and its effectiveness.

Finally, you’ll learn all about poison ivy, the plant that makes us all itchy and gives us rashes. Have you ever wonder why people are allergic to these shiny 3 leaves but annoying plant and others are not? Interestingly enough, many people are not allergic to this plant, about a certain percentage of people who touches these plants are not allergic but others are! In this blog, you will get a chance to see what poison ivy looks like and its rash, as well as learn about the different medication that can be used when contact with it.

Thank you for taking your time to read my blog and hope you learned something!

 

Captan and Folpet

 

 

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What is Captan and Folpet?

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Captan and Folpet are fungicide that kills, of course, fungus. These compounds along with a third, captafol, are normally and commonly called chloroalkylthio fungicides because of the presence of side chains that contain chlorine, carbon, and sulfur. Interestingly enough, this fungicide is extensively used in agriculture and have a unique property that does not affect humans like others fungicide do. According to Elliot B. Gordon, Captan was first register in the United States on March 8, 1949, as a fruit spray. After year passed, Captan became a fungicide that was very useful and many have wanted to capitalize it for profit. It demonstrated a unique property that has a high efficaciously and low toxicity. Therefore, Folpet later came into play and was synthesized after Captan. (3)

 

 

Below is an example of a Captan and Folpet product which is found in the US and the UK. It is used to eliminate unwanted fungus that could potentially harm the crops such as fruits, vegetables, or other agriculture crops.

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How does one get exposed to Captan and Folpet?

There various ways of being exposed to Captan and Folpet, however, the most common ways of being exposed are usually through the skin or eyes, breathing in or accidentally eating the product. According to the U.S. Environmental Protection Agency, you may be exposed to very small amounts of captan and folpet in your diet from residues on foods.(2)

 

Signs and Symptoms:

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Permanent Eyes Damage        Diarrhea                 Vomitting

 

According to the EPA, Captan and Folpet can cause serious problems to the eyes. In fact, concentrated Captan or Folpet have illustrated permanent eye damages in rabbits. Therefore, from this illustration we can assume that it could lead to detrimental effect on humans as well. Additionally, Captan and Folpet is generally low in toxicity when consumed, however, consuming in high amount of Captan can cause diarrhea and possibly vomiting. (1)

 

Mechanism of Action:

Captan and Folpet quickly breaks down into a chemical compound called Tetrahydrophthalimide in the digestive system.(1) When humans consumed captan or Folpet, blood levels of tetrahydrophthalimide ultimately peaked at 10 hours after ingestion, therefore, about all the tetrahydrophthalimide was gone from the body after 96 hours interval.(2) According to a study that was conducted in a rodent, about 92 to 94% of the dose was excreted in urine and feces after 96 hours or approximately 4 days.(3)Additionally, one study illustrated low skin absorption when captan was applied to human arms.(4)

 

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Historical/Unique Exposure:

There have been no major events up to this date about Captan and Folpet. However, the discovery and production of this product has had made a national impact for the agriculture environment due to its low toxicity and high in efficaciously. Furthermore, according to an article published by Kevin. P Shea, he argued that Captan and Folpet were one of the among pesticides that caused birth-defecting deformities in 1969.(6)

 

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Resources:

1. Amendment to the 1999 Captan Reregistration Eligibility Decision (RED); U.S. Environmental Protection Agency, Office of Chemical Safety and Pollution Prevention, U.S. Government Printing Office: Washington, DC, 2004
2. Berthet, A.; Bouchard, M.; Danuser, B. Toxicokinetics of Captan and Folpet Biomarkers in Orally Exposed Volunteers. J. Appl. Toxicol. 2011, 32, 194–201.
3. Pesticide Residues in Food-1995. Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment (JMPR): Captan; Food and Agriculture Organization of the United Nations and World Health Organization Core Assessment Group: Geneva, Switzerland, 1995.
4. Berthet, A.; Bouchard, M.; Vernez, D. Toxicokinetics of Captan and Folpet Biomarkers in Dermally Exposed Volunteers. J. Appl. Toxicol. 2011, 32, 202–209.
5. Gordon, E. B. (2009, December 16). Captan and Folpet. Retrieved from https://www.sciencedirect.com/science/article/pii/B9780123743671000902
6. Captan and Folpet. (n.d.). Retrieved from https://www.tandfonline.com/doi/abs/10.1080/00139157.1972.9932990?journalCode=venv20

 

Introduction:

 

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Background:

What is Diethylene Glycol?

 

Diethylene Glycol? What does it look like?

• • Diethylene glycol (DEG) is a sweet-tasting, colorless, nonodoriferous, hygroscopic liquid

 

Image source can be found here

 

Where is Diethylene Glycol found?

• Occupations or Materials 
  • Local or international automotive and cigarettes industry.
  • Diethylene Glycol manufactures:
    • Diethylene Glycol can be used as main component in antifreeze or braking fluid
    • Diethylene Glycol can be used and found in the making of cigarettes.

 

    Image source can be found here                       Image source can be found here

 

 

• Mechanism of Action:(1)
  • DEG or Diethylene Glycol is metabolized in the liver via the same NAD-dependent pathway as ethanol.
  • DEG is later oxidized to 2-hydroxyethoxyacetaldehyde by NAD-dependent alcohol dehydrogenase
  • DEG is later metabolized even further to 2-hydroxyethoxyacetic acid (HEAA) by aldehyde dehydrogenase.
    • Demonstrations  of how DEG is metabolized and later excreted through the renal passage.

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• • • Diethylene glycol is rapidly absorbed and distributed to the kidneys, brain, liver, spleen, and adipose tissue. The kidneys receive most of the DEG.(2)
• Purpose: (3)
  • Even though Diethylene seem to be toxic, it serves a big purpose in the automotive industry by producing anti-freeze. Therefore, most cars would overheat or freeze without the use of anti-freeze.

 

• Toxicokinectics:

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• • Absorption:(4)
    • Diethylene glycol is absorbed rapidly in the gastrointestinal tract; transcutaneous absorption is minimal through intact skin. No report of respiratory absorption is described.
  • Distribution:(4)
    • Diethylene glycol is distributed widely throughout the most perfused organs such as kidneys, brain, liver, spleen, and adipose tissue.
  • Metabolism:(4)
    • Diethylene glycol is metabolized in the liver and later it is oxidized to 2-hydroxyetoxyacetaldehyde by alcohol dehydrogenase and then to 2-hydroxyethoxyacetic acid by aldehyde dehydrogenase.
  • Excretion: 
    • Diethylene glycol is excreted through the kidneys and later its out of the body by urination. Diethylene glycol can severely cause renal failure.
• Toxicity 
  • Signs & Symptoms, Deficiency

 

   Abdominal Pain                 Kidney failing                     Confusion

 

• Target Organs for Diethylene Glycol: Brain, GI tract, Renal, and systemic impacts

 

• Historical Exposure:(1)
  •  The first mass poisoning was the sulfanilamide-Massengil disaster in the United States in 1937. DEG was used as a solvent in the elixir of sulfanilamide, an antibiotic
  • It was a substitute solvent for a good deal of pharmaceutical medicine because it was cheap.
  • Recent articles illustrated that this catastrophe led to the passage of the 1948 Federal Food, Drug and Cosmetic Act, which requires drug manufacturers to demonstrate safety of the product prior to marketing.

 

• Fun Facts: 
  • Diethylene Glycol was added into wine back in the centuries to have a sweeter taste. Little did they know, diethylene glycol is extremely toxic. Down below there is a video illustrating this interesting fact.

 

• References:

1. Diethylene Glycol Poisoning · California Poison Control System (CPCS). 20 Sept. 2018, calpoison.org/news/diethylene-glycol-poisoning.
2. Marraffa, J.M. “Diethylene Glycol.” Encyclopedia of Toxicology (Third Edition), Academic Press, 14 Apr. 2014, www.sciencedirect.com/science/article/pii/B9780123864543004905.
3. Sebastian, Manu. “Renal Toxicity.” Handbook of Toxicology of Chemical Warfare Agents, Academic Press, 22 Apr. 2009, www.sciencedirect.com/science/article/pii/B9780123744845000389.
4. Devoti, E., Marta, E., Belotti, E., Bregoli, L., Liut, F., Maiorca, P., Mazzucotelli, V., & Cancarini, G. (2015). Diethylene Glycol Poisoning From Transcutaneous Absorption. American Journal of Kidney Diseases, 65(4), 603–606. https://doi.org/10.1053/j.ajkd.2014.07.032

 

 

Introduction:

 

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Background:

 

 

Where is Zinc found?

• Food
  • Meat, shellfish, legumes, seeds, nuts, dairy, eggs, whole grains

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• Water
  • Can be found in rusty pipes where water travels towards the house

 

• Occupations
  • Local or international careers such as zinc mining, welding, etc.
  • Zinc manufactures:
    • Zinc can be used to make supplements by pharmaceutical companies
    • Zinc can be manufactured as a source of power in batteries
    •                Image source can be found here

 

• Mechanism of Action:(4)
  • Zinc has three primary biological roles: Catalytic, Structural, and Regulatory
  • Zinc promotes resistance to epithelial apoptosis through cell protection
    • In HL-60 cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A20 mRNA, which, via TRAF pathway
    • Image source is found here
    •  zinc restores mucosal barrier integrity and enterocyte brush-border enzyme activity, it promotes the production of antibodies and circulating lymphocytes against intestinal pathogens
• Structural: (5)
  • Plays a role in DNA recognition, RNA packaging, transcriptional activation, regulation of apoptosis, protein folding and assembly, and lipid binding.

 

• Toxicokinectics:
  • 

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• • Absorption:
    • First it is absorbed in the GI-Tract by the small intestine and later excreted in feces.
  • Distribution:
    • 
    • This image will illustrate the distribution of Zinc within the body
  • Metabolism:
    • Zinc is an essential component of a large number (>300) of enzymes participating in the synthesis and degradation of carbohydrates, lipids, proteins, and nucleic acids as well as in the metabolism of other micronutrients.(6)
  • Excretion: 
    • Zinc is absorbed predominantly in the duodenum and proximal jejunum, and excreted mainly in the feces. There are no body stores of zinc and so daily intake of zinc is needed to maintain adequate body levels.(7)
• Toxicity 
  • Signs & Symptoms, Deficiency
    • 
      • Image source is found here
    • Target Organs for Zinc excess: brain, respiratory tract, GI tract, prostate, and systemic impacts
    • Target Organs for Zinc deficiency: brain, thymus, skin, reproductive system
• Historical Exposure:
  • No historical exposure
  • Recently has been out of stock in many pharmacy due to COVID-19.
  • Recent articles illustrated that Zinc could increase the immune system to combat COVID-19
  • According to the World Health Organization, in total, 1.4% (0.8 million) of deaths worldwide were attributable to zinc deficiency: 1.4% in males and 1.5% in females(8)
• References:

 

1. Pappas, S. (2015, January 21). Facts About Zinc. Retrieved from https://www.livescience.com/29378-zinc.html
2. Plum, Laura M et al. “The essential toxin: impact of zinc on human health.” International journal of environmental research and public health vol. 7,4 (2010): 1342-65. doi:10.3390/ijerph7041342
3. “Office of Dietary Supplements – Zinc.” NIH Office of Dietary Supplements, U.S. Department of Health and Human Services, ods.od.nih.gov/factsheets/Zinc-HealthProfessional/.
4. Zinc. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01593
5. “Zinc Metabolism.” Zinc Metabolism – an Overview | ScienceDirect Topics, www.sciencedirect.com/topics/medicine-and-dentistry/zinc-metabolism.
6. (n.d.). Retrieved from http://www.fao.org/3/y2809e/y2809e0m.htm#bm22.1
7. Willacy, H. (2019, April 26). Zinc Deficiency, Excess and Supplementation. Zinc problems. Retrieved from https://patient.info/doctor/zinc-deficiency-excess-and-supplementation-pro
8. Chapter 4. (2010, November 2). Retrieved from https://www.who.int/whr/2002/chapter4/en/index3.html#:~:text=In total, 1.4% (0.8,loss of healthy life years.

 

Introduction:

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Background:

What is Poison Ivy?