2. Lesson 18: Environmental Inpact
Thursday, March 31, 2016

3. Understandings
High-level waste (HLW) is waste that gives off large amounts of ionizing radiation for a long time.
Low-level waste (LLW) is waste that gives off small amounts of ionizing radiation for a short time.
Antibiotic resistance occurs when microorganisms become resistant to antibacterials.

4. Applications
Description of the environmental impact of medical nuclear waste disposal.
Discussion of environmental issues related to left-over solvents.
Explanation of the dangers of antibiotic waste, from improper drug disposal and animal waste, and the development of antibiotic resistance.
Discussion of the basics of Green Chemistry (sustainable chemistry) processes.
Explanation of how Green Chemistry was used to develop the precursor for Tamiflu (oseltamivir).

5. Environmental Impact
The synthesis of many medications have environmental impact
You need to be able to describe these impacts and talk about green Chemistry

6. Solvents
Solvents are traditionally volatile organic substances which are toxic to all living organisms. They affect the nervous and respiratory systems and many, particularly chlorinated solvents such as dichloromethane, affect the liver and kidneys. Many also contribute to photochemical smog by forming secondary pollutants and also some are greenhouse gases and/or contribute towards ozone depletion. Some may also pollute ground water.

7. Solvent Waste
Most drugs are complex molecules, so their synthesis and extraction involves multiple steps.
In many parts of this process, organic solvents are used. These may be toxic and are often left over at the end of the synthesis, leading to problems of disposal. It is estimated that up to 80% of the mass of reactants that does not end up in the pharmaceutical product is due to solvents, including water. Disposal of solvents often involves incineration, which can release toxins into the environment. Overall, solvents are by far the biggest contributor to the emissions of the pharmaceutical industry.

8. Assessments of Solvents
Solvents are assessed in the following ways:
toxicity to workers – whether the solvent is carcinogenic (cancer causing) or associated with other health issues
safety of the process – whether the solvent is highly flammable, explosive, or can cause toxic by-products
harm to the environment – whether the solvent will contaminate soil and ground water, cause ozone depletion, or contribute to greenhouse gas formation when released or burned.

9. Solvents

10. Going Green
One of the principles of Green Chemistry is the use of safer solvents and to avoid the use of auxiliaries where possible. Water is clearly the safest solvent for the environment, and supercritical carbon dioxide (CO2 under pressure) can also be used in some processes.
Another principle of Green Chemistry is to prevent waste. Case-studied examples include the production of the arthritis drug Celebrex by Pfizer, where scenarios with and without solvent recycling were rigorously compared.

11. Solvent Waste

12. Nuclear Waste
We previously discussed the many uses of radioisotopes in medicine
Numerous radioisotopes are used or produced in various medical processes and these have half-lives that vary enormously – 131I, used to treat thyroid cancer, has a half-life of just 8 days; 60Co, used to treat other forms of cancer, has a half-life of 5.3 years.

13. Low vs. High Level Decay
Low-level waste has a low activity (not many radioactive nuclei decay each second to produce ionising radiation) and usually contains isotopes with short half-lives (ionizing radiation is given off for a shorter period of time).
High-level waste has a high activity (many radioactive nuclei decay each second to produce ionizing radiation) and usually contains isotopes with longer half-lives (ionizing radiation is given off for a long time).

14. Three Methods Of Disposal
Dilute and disperse
Delay and decay
Confine and contain

15. Low Level Waste
This includes items that have been contaminated with radioactive material or have been exposed to radioactivity. Examples are gloves and other protective clothing, tools, syringes and excreta from patients treated with radioisotopes.
Low-level waste may be stored on site until it has decayed to such an extent that it can be disposed of as ordinary waste (e.g. in landfill sites or released into the sewage system) or shipped to a central site for more specialized disposal.
Some low-level waste is incinerated, which reduces its volume considerably and distributes the radioisotopes over a wide area – ‘dilute and disperse’. The ash from incineration is assessed for activity and disposed of appropriately.
Low-level waste with higher activity is often just buried underground (‘near-surface’ disposal) – for example, in individual concrete canisters or in concrete-lined vaults. Low-level waste may need to be contained underground for up to 500 years depending on its activity and half-life.

16. High Level Waste
This includes spent fuel rods and other materials from nuclear reactors. High-level waste will remain hazardous to humans and other living things for thousands of years.
High-level liquid waste can be converted to glass (vitrification) to make storage easier. High-level waste is first kept in storage pools (cooling ponds) under water, usually for a minimum of nine months, but sometimes spent fuel rods are stored in this way for decades. After sufficient cooling, fuel rods may be transferred to dry storage casks – these have very thick walls and are made of steel and concrete. The dry casks are then stored in concrete bunkers.
Permanent storage of high-level radioactive waste is a major problem and various solutions have been suggested – such as burying the waste deep underground in stable geological areas. Over thousands of years, however, it is di cult to predict what processes could occur to cause release of the radioactive material. Many people argue that there is no suitable solution for the disposal of high-level waste.

17. Supercritical Carbon Dioxide
Radioactive ash may be contained using supercritical CO2

18. Lesson 19: Antibiotic Waste
Friday, April 1, 2016

19. Antibiotic Resistance
Hospitals often face a particular problem in dealing with antibiotic- resistant bacteria.
So-called superbugs are bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) that carry several resistant genes, and cause infections that are extremely difficult to treat.
Extensive use of broad- spectrum antibiotics, that is those that are used against a wide range of bacteria, has also enabled infections such as Clostridium difficile to thrive.

20. Antibiotic Resistance
Antibiotic resistance arises by genetic mutation in bacteria and would normally account for a very small proportion of the bacterial population. But increased exposure to the antibiotic dramatically increases the number of resistant organisms, as it effectively kills off the competition.

21. Antibiotic Usage
Antibiotics are not just used for humans. In fact, they are used for
therapeutic use in aquaculture and household pets
growth promotion and prophylactic use in animal livestock
pest control in agriculture
sanitizers in toiletries and household cleaning products
sterilization and culture selection in research and industry.
All these other uses have led to increase antibiotic resistance

22. Antibiotics in Animals
The use of antibiotics in animal feeds is worth particular note. The drugs are given to lower the incidence of disease in the stock as a precautionary measure, in other words administered to healthy animals. The antibiotics pass through animal waste into the soil and water and so enter the human food chain, where they increase exposure of bacteria to the antibiotic.

23. Improper Drug Disposal
Another source of antibiotics in the environment is through improper drug disposal. Expired, unused antibiotics are frequently discarded by households and by the medical profession, and this can result in contamination of surface, ground, and drinking water supplies. Studies have also shown that in some countries, ef uent from pharmaceutical production plants can be contaminated with antibiotics.

24. Antibiotic Resistance
Full documentary if you want to not sleep tonight:

25. Lesson 18: Green Pharmaceutical Chemistry Manufacturing

26. Green Chemistry
Green chemistry (or sustainable chemistry) is an approach to chemical research and chemical industrial processes that seeks to minimize the production of hazardous substances and their release into the environment.

27. 12 Principals of Green Chemistry
Prevention – it is better to prevent waste than to treat or clean up waste after it has been created.
Atom economy – synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product.
Less hazardous chemical syntheses – wherever practicable, synthetic methods should be designed to use and generate substances that possess little or no toxicity to human health and the environment.
Designing safer chemicals – chemical products should be designed to affect their desired function, while minimizing their toxicity.

28. Safer solvents and auxiliaries – the use of auxiliary substances (solvents, separation agents etc.) should be made unnecessary wherever possible and innocuous when used.
Design for energy efficiency – the energy requirements of chemical processes should be recognized for their environmental and economic impacts and should be minimized. If possible, synthetic methods should be conducted at ambient temperature and pressure.
Use of renewable feedstocks – a raw material or feedstock should be renewable, rather than depleting, whenever technically and economically practicable.
Reduce derivatives – unnecessary derivatization (use of blocking groups, protection/ deprotection, temporary modification of physical/ chemical processes) should be minimized or avoided if possible because such steps require additional reagents and can generate waste.
Catalysis – catalytic reagents (as selective as possible) are superior to stoichiometric reagents.

29. Design for degradation – chemical products should be designed so that at the end of their function they break down into innocuous degradation products and do not persist in the environment.
Real-time analysis for pollution prevention – analytical methodologies need to be further developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances.
Inherently safer chemistry for accident prevention – substances, and the form of a substance used in a chemical process, should be chosen to minimise the potential for chemical accidents including releases, explosions and fires.
(Green Chemistry:Theory and Practice by Paul Anastas & John Warner (1998) Figure 4.1 from p. 30. By permission of Oxford University Press

30. Green Chemistry - Video

31. Best Synthetic Routes use readily available and safe materials
have the minimum number of steps
convert as much of the starting materials as possible into the required
product at each step – good atom economy and good yield
use as little solvent as possible
use as little energy as possible.

32. Atom Economy
Atom economy can be used as a measure of how efficient a particular reaction is in terms of converting as much of the starting materials as possible into useful products.

34. Green Chemistry – Tamiflu
Oseltamivir (Tamiflu) is an antiviral that may lessen the spread of the u virus within the body by preventing the release of new viral particles from their host cells. The drug has attracted particular attention as it is the only orally administered antiviral that may be effective in cases of H5N1 (avian u) infection.
The key precursor for the synthesis of Tamiflu is shikimic acid, or its salt shikimate

36. Shikimate
This compound is found in low concentrations in many plants, but the Chinese star anise, Illicium verum, which grows in Vietnam and South-West China, has been a favored source. Shikimate is found in the star-shaped fruit of the tree, and can be extracted in a lengthy chemical process. But the low yields from this process are blamed for the worldwide shortage of Tamiflu in 2005, and again during the flu pandemic of 2009 when many governments stock-piled the drug.

38. Alternate Sources – Green Chem
Some of the promising developments in this eld, which are all applications of Green Chemistry, include the following.
The production of shikimate from fermentation reactions of genetically engineered bacteria. This process has been developed by the pharmaceutical company Roche.
The harvesting of shikimate from the needles of several varieties of pine trees. Even though yields are quite low, the needles represent a plentiful resource.
The extraction of shikimate from suspension cultures of the Indian sweetgum tree. This is an inexpensive natural source and does not involve genetic manipulation.

39. Other Examples of Green Chemistry
The production of the drug Viagra by Pfizer uses a modified reaction route that produces just a quarter of the waste of the original process. It reduces the amount of solvent and avoids the use of toxic and hazardous reagents.
The synthesis of the anti-inflammatory drug ibuprofen has been altered from a six-step to a three-step reaction route. This has increased the atom economy of the process from 40% to 77% and reduced the energy demand.
Synthesis of the analgesic drug Lyrica was modified to use a natural reagent of an enzyme with water as a solvent to reduce the use of non-renewable organic materials. This has eliminated the emissions of more than 3 million tones of CO2 compared with the original process.