1. Nicole Carroll, Mikayla Fahey, Charisa Bell
Common toxins for Dogs
Nicole Carroll, Mikayla Fahey, Charisa Bell

2. Introduction
There are numerous amounts of dangerous toxins for dogs that humans consume. As dog lovers, many of these toxins are unknown to pet owners and can be encountered by dogs on a daily basis. We chose three toxins that are most common for human consumption, ranging from conditioned response to lethal doses of toxicity in dogs. Throughout this presentation we will discuss a wide range of available human foods for dogs: sugar-free gum, onions, and chocolate as common toxins for canine consumption. We will be discussing levels of toxicity, lethal dosage, methods of consumption, and Pathophysiology for each of these toxins.

3. Xylitol Toxicosis 5-Carbon sugar alcohol Extracted from Birch Wood
Found in Sugar free gum, toothpaste, mouthwash
Known conditions in canines:
Hypoglycemia 
hypophosphatemia
Limit to 5 sentences
Fig. 1
(2S,4R)-pentane-1,2,3,4,5-pentol
Hydrogen (white), oxygen (red), carbon (gray) (Pubchem, 2004)

4. Xylitol causes hypoglycemia
A dosage of .1G/KG OR HIGHER ( varies with dog)
Produces irregular increase of insulin in the pancreas and causes low blood glucose (Piscitelli et. Al, 2010)
Signs/symptoms: vomiting, weakness, ataxia, depression, and hypokalemia (low levels of potassium in blood serum) (Shell et al., 2006)
Leads to seizures and irreversible brain damage, or coma (Piscitelli et. Al)

5. Xylitol causes hyperphosphatemia
A dosage of .5 g/kg or higher (varies on the size of dog) 
causes liver failure (Piscitelli et. Al, 2010)
Signs/Symptoms: depression, vomiting, icterus (Jaundice), coagulopathy
Insulin secretes into the liver by traveling through the blood 
causes the liver failure

6. Xylitol Toxicity based on dog body mass
Size of Dogs
 Amount of toxin to induce Hypoglycemia
 Ingested piece(s) of gum
Amount of toxin to induce Hyperphosphatemia
Ingested piece(s) of gum
Small dogs- toy  breeds
(.5-10 kg)
.05 g - 1g
1/30 ≤
.25 g – 5 g
1/7≤
Medium sized dogs 
(11-26 kg)
1.1 g – 2.6 g
¾ ≤
5.5 g  -13 g
3 2/3 ≤
Large sized dogs
(27-44 kg)
2.7 g – 4.4 g
2 ¼ ≤
13.5 g – 22 g 9≤
Giant sized dogs
(45 kg+)
4.5 g or higher
3 ≤
22.5 g or higher
15≤
Table 1.1
The effective dose of Xylitol for responsive Hypoglycemia and Hyperphosphatemia with the estimated gum size consumed by each size of dog. An average piece of is 1.5 g of Xylitol

7. Xylitol PathoPhysiological effects
Hypoglycemia
Insulin increasing is causing an increased amount of potassium inside the cells and decreases sodium influx
Brain damage
Hyperphosphatemia
Elevated phosphate ions entering the blood making the intercellular membrane more permeable thus, decreases sodium influx and elevates high levels of insulin
Damages pancreas and leads to liver failure(Piscitelli et. Al, 2010) 
Organ Failure (Shell et al.,2006)

8. Discussion: xylitol to onions
It is commonly found in many sugar-free products like gum and toothpaste.  xylitol toxicity is influenced by human consumption for dogs to encounter the toxin. Xylitol is a processed extraction from Birch Wood. It is not naturally found or consumed by dogs unlike, natural toxins such as onions. 
Onions can be found commonly in gardens or in left over foods given to dogs. It can be easy for a dog owner to give their dogs onions as it is not as commonly known to be harmful. Here, we will go over the effects of onions and the amount that should be avoided.

9. n-propyl disulphide toxin found in onions
N-prpul disuliphide is the toxin that causes dogs to get sick when the Effective dose of 30 g/kg is ingested (Berg, J.M. 2002). One onion is about 150 G.
The form of onion does not change toxicity (ie. Whether it's cooked, powder, or raw)(R.B. Cope, 2005.).  
Action: N-propyl disulphide toxin reduces the activity of the enzyme: glucose- 6-phosphate dehydrogenase in Red Blood Cell's (RBC's) of dogs (Kovalkovičová, N., et al. 2009)    
Figure 2. N-propyl disulphide molecule

10. The intermediate enzyme: Glucose-6-phosphate dehydrogenase
Glucose-6-phosphate dehydrogenase is a protective factor for RBC against oxidative reagents
Produces: glutathione reductase
Glutathione reductase is reduced by NADPH in the pentose phosphate pathway. 
This protects the RBC's cytosine residues and other proteins 

11. The intermediate enzyme: Glucose-6-phosphate dehydrogenase
The N-PROPYL DISULPHIDE TOXIN interacts with Glucose-6-phophate and stops this pathway
Glucose-6-phosphate dehydrogenase is a protective factor for RBC against oxidative reagents
Produces: glutathione reductase
Glutathione reductase is reduced by NADPH in the pentose phosphate pathway. 
This protects the RBC's cytosine residues and other proteins 

12. RBC's undergo hemolysis
Since glutathione reductase is no longer produced and reduced, it is unable to protect the red blood cells. 
The hemoglobin turns into Sulfhemoglobin. This results in a decrease in red blood cell count and the formation of heinz bodies (R.B. Cope, 2005.).   
This leads to the condition: hemolytic anemia in the dogs 
         -Treatment includes gastric decontamination, IV, and blood transfusions
         -Signs in dogs include: vomiting, difficulty breathing, and dark urine (Kovalkovičová, N., et al. 2009)
Fig 3. Red blood cells with hemolytic anemia A. H. REBA, et al  

13. Toxicity levels based on dog mass
Dog size
Toxicity amount 
Onion equivalent
kg (small) g
1/ full onions 
11-26 kg(Medium)​ g
2-5 full onions
27-44 kg (Large)​ g
full onions 
45 kg+(Giant)​
1350g +
9 full onions+
Note: it would be extremely difficult for a dog to reach this amount of onion consumed
Table 1.2 Onion toxicity amount with each dog size. One onion is equivalent to 150 grams.

14. Discussion: onions to chocolate
N-propyl-disulphide toxin that is found in onions affects the functioning of essential enzymes in dogs. However, the toxic dosage is difficult to reach, that it is very uncommon that the dog would be affected by onions. Both onions and chocolate are found in common food products. Onions are generally considered not to be lethal.
While Chocolate is a more commonly known dangerous food for dogs. Chocolate has a lower lethal dose and a lower dose response than onions.

15. Chocolate Toxicity
Chocolate toxicity is primarily caused by the Caffeine and Theobromine in Chocolate, these will be referred to as Methylxanthines throughout the presentation. 
Both compounds are methylated xanthine alkaloids of plant origin.
Chocolate toxicity is one of the most common toxicity cases seen in veterinary medicine. 

16. Methylxanthines Table 1.3 (Shell et al, 2018)
Just as for every toxin the dose is dependent on the weight of each animal but there is another component with chocolate toxicity.
 The other factor is the varying concentrations of Methylxanthines between different chocolate varieties. 
The lethal doses for the most common types of chocolate will be referenced towards the end of this presentation. 
Product
Total milligrams methylxanthines per ounce
Cacao beans
Cocoa powder, unsweetened
800
Unsweet dark chocolate
400
Semisweet chocolate
150
Milk chocolate 64
White chocolate
<1
Table 1.3
(Shell et al, 2018)

17. These two compounds are very similar.
Chemical compounds
These two compounds are very similar. 

18. Methylxantine Pathophysiological effects
Methylxanthines are rapidly absorbed  through the GI tract.
These compounds inhibit the cyclic nucleotide phosphodiesterases(PDE's) and antagonism of receptor mediated actions of adenosine 
PDE's regulate the degredation of cAMP and cGMP
These cAMP and cGMP are modulators of physiological processes, such as regulating neuronal, glandular, cardiovascular, immune mechanism, nervous system, cell growth and differentiation.
They also stimulate the catecholamine synthesis and release. 
Catecholamines are neurotransmitters such as dopamine and norepinephrine. 

19. Signs and symptoms by mg/kg
>20mg/kg: mild signs of agitation and G.I. distress
(e.g. vomiting, Diarrhea, abdominal pain)
>40mg/kg:  moderate signs of cardiotoxicosis can be seen 
(e.g. tachycardia, hypertension)
>60mg/kg: Severe signs of neurotoxicosis can be seen 
( e.g. tremors, seizures)
mg/kg: LD50 for dogs
Death

20. Toxicity Levels based on dog mass
Milk Chocolate
( mg/gram of methylxanthines)
Weight
Mild Reaction
Moderate to Severe
2.27 kg
21.26 gm
42.53 gm
4.5 kg
85.05 gm
9.1 kg gm
13.6 kg gm gm
18.2 kg gm
22.7 kg gm gm
27.3 kg gm
31.8 kg gm gm
36.4 kg gm
Table 1.4
Toxicity Levels based on dog mass

21. Toxicity Based on Dog Mass Continued
Semi-Sweet Chocolate
(5.29mg/gram of methylxanthines)
Weight
Mild Reaction
Moderate to Severe 
2.27 kg
8.51 gm
14.04 gm
4.5 kg
17.01 gm
34.02 gm
9.1 kg
68.04 gm
13.6 kg
53.87 gm gm
18.2 kg
59.35 gm gm
22.7 kg
70.88 gm gm
27.3 kg gm gm
31.8 kg gm
36.4 kg gm gm
Table 1.5
Toxicity Based on Dog Mass Continued

22. Toxicity Based on Dog mass continued
Baking Chocolate 
(15.87 mg/gram of methylxanthines)
Weight
Mild Reaction
Moderate to Severe
2.27 kg
2.84 gm
5.67 gm
4.5 kg
11.34 gm
9.1 kg
22.68 gm
13.6 kg
17.01 gm
34.05 gm
18.2 kg
45.36 gm
22.7 kg
28.35 gm
56.70 gm
27.3 kg
68.04 gm
31.8 kg
39.69 gm
79.38 gm
36.4 kg
90.72 gm
Table 1.6
Toxicity Based on Dog mass continued 

23. Conclusion * Click to add text *
Fig. 7: Each Toxin response based on dog size. *Reference Table 1.4*
Fig. 8: Lethal dosage for each of the foods consumed. Onions do not appear because LD50 is too high. *Reference Table 1.4*
Conclusion

24. Discussion
This presentation examines the effects of Xylitol, Onions and Chocolate. Based on our results, chocolate is the most toxic due to commonality and small dosage. Secondly, xylitol has a small dose and commonly occurs due to its usage in multiple household products. Lastly, Onions have the highest dosage and is found in more food products than household products. 
Figure 7 shows that it takes the smallest dose for chocolate to activate a response in any size of dog. While sugar free gum: xylitol is moderately small, in comparison to Onions which is the largest dose for responsive effects. 
Figure 8 shows the effective dose of each toxin. The table shows the milk chocolate has an LD50 at an average of G/Kg. Xylitol's LD50 is G/Kg which is lower than chocolates LD50. Onions did not show any lethal dosage in research. this is not to say that Hemolytic anemia cannot lead to death, but that the onions have such a high dosage that death most likely has not been solely occurred due to Onion toxicity. 

25. Summary and Conclusions
Conclusively, the toxins discussed in this presentation effect all dog's health, negatively. Chocolate is more toxic at lower concentrations, but Xylitol is more lethal due to the lower LD50. If a dog consumes any these toxins, it is the responsibility of the owner to take into consideration the amount consumed, and the dog should be taken to the vet if needed.  If you are unsure of the severity you can always call a local veterinarian to discuss the possibilities. 

26. citations 
Berg J.M., Tymoczko J.L., Stryer L. Biochemistry. 5th edition. New York: W H Freeman; Section 20.5, Glucose 6-Phosphate Dehydrogenase Plays a Key Role in Protection Against Reactive Oxygen Species
Bender, A. T Cyclic Nucleotide Phosphodiesterases: Molecular Regulation to Clinical Use. Pharmacological Reviews, 58(3), doi: /pr
Cope RB. Allium species poisoning in dogs and cats. Vet Med. 2005:562–566.
Kovalkovičová, N., Sutiaková, I., Pistl, J., & Sutiak, V Some food toxic for pets. Interdisciplinary toxicology: 2(3),
Piscitelli, Christopher m, et al. Xylitol Toxicity in Dogs. Compendium, 2010, pp. e1– e3., doi: 484/filePV0210_piscitelli_CE.pdf.
Rebar, A. H., Lewis, H. B., Denicola, D. B., Halliwell, W. H., & Boon, G. D Red Cell Fragmentation in the Dog: An Editorial Review. Veterinary Pathology, 18(4), 415–426. 
Shell, Linda G. Medical Associate: Xylitol Toxicosis. VIN, Medical Associate , 2 Feb. 2006,
Shell, Linda G Methylxanthine toxicosis. VIN, Medical Associate ,  
Nicole's- blue text