Examples of case studies associated with relevant topics are presented.
Chemical Structural Features Determine Biological Effects
underlying theory: there is a connection between a chemical structure and its interaction with biological systems. Students learn the sources of information and the different identification systems and apply this in an environmental assessment.
220.127.116.11.1 Case Study Example 1.
• Start with these compounds:
- bisphenol A
• Chemical information queries require at least three notations:
- CAS#, SMILES code, SDF. Obtain each for each chemical using Pub- Chem,24 ChemIDPlus,25 or ChemSpider26
- search toxicology information using PubChem24 compound summary and various categories of ToxNet27
• Classify each compound by hazard traits such as carcinogenicity, reproductive hazard, persistence in environment, hepatotoxicity, neurotoxicity, etc.
- give brief evidence
• Discuss the physicochemical properties that cause it to be persistent or not, bioacculmulative, and/or toxic to the environment using pBT profiler28
• Note the household products that contain the compound—Household products Database29
• In particular, note how you can move from one information source to another
18.104.22.168.2 Case Study Example 2. there is wide agreement that chemicals of great concern are those that: persist (p), bioaccumulate (B), and present toxicity (T) concerns, i.e.pbTs. only a fraction of all chemicals have been tested to determine if they are pbTs. pBT profiling is aimed at all raw materials, as an important predictive screen. students are given links to global pBT concerns including those from the us, European union, and Canada and use the public access to the pBT profiler28 and links and tutorials to ChemiDplus,25 ToxNet,27 Cactus,30 pubchem,24 and Chemspider.26
• use naphthalene as the core structure
• substitute various functional groups in the 1 and 2 positions
• see how lipophilicity changes with structural substitutions
• create a spreadsheet with chemical name, smiles code, CAs number, and sDF file
• use the name, smiles code, and CAs number to compare the environmental impact of each compound in pBT profiler (EpA)
• in ChemiD plus25 and ToxNet27 find the carcinogenicity and mutagenicity results for each compound if present in database
• use the sDF file to enter the compound (or multiple compounds) in a commercial software package such as Genego31
• compare a few chemical properties that may be involved in the difference in environmental impact, and/or carcinogenicity or mutagenicity findings in a program such as ToxTree32
• compare the “predicted” Ames test in the predictive models with the actual results in ChemiD plus25
• if there are no carcinogenicity results for any individual compound, predict the findings using real or predicted mutagenicity findings
22.214.171.124.3 Case Study Example 3.
• select two out of the three chemicals listed below and add a third chemical of your choice: butylbenzyl phthalate (BBp), diethyl hexyl phthalate (DEHp), and perfluorooctane sulfonic acid (pFOs)
• Use the CTD,33 T3DB,34 and Chemspider26 and develop a chemical-disease-gene linkage for a relevant toxicological endpoint for each chemical
• Use STITCH35 to display interactions
• For a relevant zip code, city, or county (EpA Tri,36 scorecard37) determine the most predominant environmental contaminant and using T3DB34 and CTD,33 suggest a linkage to toxicity and/or disease
126.96.36.199.4 Case Study Example 4.
• Expand case study 3 into chemical-disease pathway analyses
• Find a relevant disease pathway using tools below and form a network toxicology diagram and discuss the feasibility of the chemical disease linkage:
• KEGG pathway database: wiring diagrams of molecular interactions, reactions, and relations38
• Pathway Commons39
• Wiki Pathways40
• Pathway Maps. Life Science Research41
• Quick search for pathways using Google image: search using the chemical name, disease, and the word pathway. Important pathway images will appear and these will be linked directly to the information source.
- Draw the new pathway using yED graph editor from the yWorks Diagraming Company42
188.8.131.52.5 Typical Report for Case Studies (One Per Team if Applicable).
Introduction (explain what you are attempting to do)
Methods (explain all compound substitutions and the programs used to evaluate)
Results (show results of all compounds in table format)
Show figures of pathways if applicable
Discussion (compare results from different compounds and suggest why there are differences between compounds)