Experiment No. 6 Toxicity Prediction Using Protox II Mac Gilbert U. Felecio

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ENVIRONMENTAL CHEMISTRY LABORATORY MANUAL
EXPERIMENT NO. 6
Toxicity Prediction using Protox II

Mac Gilbert U. Felecio
BACKGROUND
Toxicology is the science that deals with the adverse effects of chemicals
on living system. Depending on the nature of the substance, it may elicit
different toxicities to organisms. For example, a polar compound that is soluble
in aqueous environment may have large toxicities to aquatic organisms. In
laboratories certain measurements such as lethal dosage and inhibitory
concentrations are used to assess toxicities. However, prior to these toxicity
tests, most scientist opt to predict first the possible toxicities of compounds to
acquire ideas. These softwares and online tools are useful in prediction of
toxicities. In this activity, Protox II online software will be utilized for the
prediction of toxicities of compounds. It employs the usage of quantitative
structure-activity relationships in display them as models as basis in analysis of
chemical structures and endpoints in quantitative terms.
In this virtual laboratory experiment, students will explore the Protox II

online tool to predict the toxic properties of certain compounds.
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OBJECTIVES
At the end of this activity, the students should be able to:

1. Explain the processes and kinds of toxicity;
2. Utilize and navigate the Protox II website;
3. Retrieve compounds from pubchem
4. Properly input/ draw the assigned compounds in the online tool;
5. Collect all data from the Protox II.
MATERIALS
The students need to bring the following:

None
Reagents/Materials
None
Materials
None
Equipment
Laptop and good internet connection
Student Activity Website

https://tox-new.charite.de/protox_II/index.php?site=compound_input
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Procedure
1. Click on https://tox-new.charite.de/protox_II/index.php?site=compound_input
2. Identify your assigned compounds in the table below.
3. Enter the compound into the Pubchem-Name tab. Click search.
4. Once the compound has been loaded, click the hepatoxicity, carcinogenicity,
Immunotoxicity, Mutagenicity, and Cytotoxicity in the Left Box. Once done,
click Start Tox-prediction button.
5. Collect the information needed in the Results section.
Table 1. Assigned metabolites for students
Student Number Compound 1 Compound 2 Compound 3
1 Ricinoleic acid Alternariol Tropine
2 Oleamide Orsellinic acid Cinnamic acid
3 Erucic acid Lecanoric acid Beta-truxinic acid
4 Erucamide Emodin Procaine
5 Crepenynic acid Endocrocin Benzocaine
6 Dehydromatricaria Physcion Tetracaine
acid
7 Cicutoxin Chrysiphanol Oxybuprocaine
8 Oenanthotoxin Aloe-emodin Lidocaine
9 Falcarinol Islandicin Prilocaine
10 Cichoric acid Rhein Cinchocaine
11 Malvalic acid Hypericin Articaine
12 Hydnocarpic acid Protohypericin Flecainide
13 Chaulmoogric acid Dantron Mexiletine
14 PGE2 Dithranol Procainamide
15 PGD2 Mycophenolic acid Ropivacaine
16 PGI2 Khellin Tocainide
17 PGF2 alpha visnagin Retronecine
18 Misoprostol Peucenin Senecionine
19 Gemeprost (+)-usnic acid Acetyl-intermidine
20 iloprost Griseophenone B Acetyl-lycopsamine
21 latanoprost Dehydrogriseofulvin Anaferine
22 TXB2 Griseofulvin Lobeline
23 TXA2 Patulin Lobelanine
24 LTB4 Gentisaldehyde Piperine
25 LTD4 Phyllostine Lupanine
26 LTE4 Naringenin Cystisine
27 LTC4 Lunularic acid Sparteine
28 LTA4 Resveratrol Castanospermine
29 LTA3 Averufin Nicotinic acid
30 LTA5 Aflatoxin G1 Quinolinic acid
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6. Screenshot results of each of your assigned molecules.
RESULTS AND OBSERVATIONS
Paste and label your results here.
A.) Chaulmoogric acid

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B.) Dantron
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C.) Mexiletine
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Guide Questions:
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1. Using your own words, define toxicity.

Toxicity is the degree at which a substance causes harm to humans or animals.
High toxicity correlates to high lethality even at low doses/concentrations while
low toxicity only causes lethal effects at high doses/concentrations.
2. What is organ toxicity? How do you assess organ toxicity?
Organ toxicity refers to the degree to which a substance causes harm or
damage to specific organs in the body. Organ toxicity can be assessed through
different means. Organ toxicity can be passed through experimental means,
such as bioassays in which the ADME of a specific toxicant can be identified.
However, a safer way to assess specific organ toxicity can be achieved with the
help of toxicity prediction softwares such as Protox II. Protox II employs the
usage of quantitative structure-activity relationships in display them as models
as basis in analysis of chemical structures and endpoints in quantitative terms.
3. Define the following terms:
a. Hepatotoxicity is the extent of a substance’s capability to cause

damage to the liver. Damage can potentially lead to liver failure
if exposed to high doses of hepatotoxin (a substance with high
hepatotoxicity).
b. Carcinogenicity is the extent of a substance’s capability to cause

specific mutations in the organism’s DNA that involves cellular
growth, which can lead to uncontrollable cell replication
(Cancer).
c. Immunotoxicity is the extent of a substance’s capability to

suppress or damage the immune system. Damage to the
immune system caused by immunotoxins can result in an
increased rate of infections, susceptibility to diseases and/or
other immune-related disorders.
d. Mutagenicity is the extent of a substance’s capability to cause

mutations or changes in an organism’s genes. This can occur
through a variety of mechanisms, such as directly damaging
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DNA itself or interfering with normal repair mechanisms

involving DNA.
e. Cytotoxicity is the extent of a substance’s capability to cause

damage or death to individual cells.
4. How do your results relate to the distinct toxicity of your

compounds?
Protox II predicts the LD50 in mg/kg of the desired compounds and classifies
it from 1-6, with 1 being the most toxic and 6 being the least toxic. It is done
according to the globally harmonized system of classification of labelling of
chemicals, or GHS.
Additionally, prediction accuracy is also calculated and displayed in Protox II.
The prediction accuracy depends on the similarity of the compound to
compounds with known LD50 values as well as the hit rates which are obtained
using a cross-validation study. The more saturated the prediction accuracy box
color, the higher the relative accuracy.
Furthermore, the Protox II toxicity model report also predicts the presence or
absence of a compound’s ability to elicit toxic effects to specific organs as well
as the probability or the confidence level of the prediction being accurate. A
probability of below 0.70 will be omitted in the results as the prediction has a
low confidence level.
As an example, a red and active prediction with a probability of 0.75 for
hepatotoxicity would mean that the compound is probably toxic to the liver
with a confidence level of 0.75 or 75%.
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5. Present the relative toxicities of your assigned compounds on

the space provided.
A.) Chaulmoogric acid

Chaulmoogric acid is classified as class 2 toxin, indicating that it is fatal when
swallowed with an LD50 of 48 mg/kg body weight. Upon checking the toxicity
model report, Chaulmoogric acid is relatively inactive at all
areas/endpoints/pathways with relatively high prediction confidence, with
hepatotoxicity being the only relatively low probability at 0.62 or 62%. Hence,
the hepatotoxicity was omitted in the prediction results.
B.) Dantron
Dantron is classified as class 6 toxin, indicating that non-toxic when swallowed

with an LD50 of 7000 mg/kg body weight. Upon checking the toxicity model
report, Dantron is relatively active in immunotoxicity, mutagenicity, as well as
being an Aryl hydrocarbon Receptor and at Mitochondrial Membrane Potential
targeting. Most areas/endpoints/pathways with relatively high prediction
confidence, with only Carcinogenicity, Immunotoxicity, and Estrogen Receptor
Alpha being omitted for having low probabilities at 0.51, 0.57, and 0.69
respectively.
C.) Mexiletine
Mexiletine is classified as class 3 toxin, indicating that it is toxic when swallowed

with an LD50 of 272 mg/kg body weight. Upon checking the toxicity model
report, Mexiletine is only relatively active in carcinogenicity, but this result is
omitted as the probability (or the confidence level) of this prediction is only
0.53. Other areas/endpoints/pathways besides carcinogenicity are all inactive
and are above the 0.70 probability threshold.

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ENVIRONMENTAL CHEMISTRY LABORATORY MANUAL

Toxicity Prediction using Protox II

In this virtual laboratory experiment, students will explore the Protox II

At the end of this activity, the students should be able to:

The students need to bring the following:

Student Activity Website

6. Screenshot results of each of your assigned molecules.

RESULTS AND OBSERVATIONS

Paste and label your results here.

A.) Chaulmoogric acid

1. Using your own words, define toxicity.

a. Hepatotoxicity is the extent of a substance’s capability to cause

b. Carcinogenicity is the extent of a substance’s capability to cause

c. Immunotoxicity is the extent of a substance’s capability to

d. Mutagenicity is the extent of a substance’s capability to cause

DNA itself or interfering with normal repair mechanisms

e. Cytotoxicity is the extent of a substance’s capability to cause

4. How do your results relate to the distinct toxicity of your

5. Present the relative toxicities of your assigned compounds on

A.) Chaulmoogric acid

Dantron is classified as class 6 toxin, indicating that non-toxic when swallowed

Mexiletine is classified as class 3 toxin, indicating that it is toxic when swallowed

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