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A lot of science is about trying to find the best questions. Because the best questions can lead us to better answers. So, in the spirit of better questions here goes.

By loosening environmental regulations aimed at pollution prevention or remediation, the mandarins reporting to POTUS 45 have apparently made the calculation decided that some resulting uptick in pollution is justified by the jobs created thereby.

Question 1: For any given relaxation in regulations that result in an adverse biological, chemical or physical insult to the environment, what is the limit of tolerable adverse effect?

Question 2: How will the upper limit of acceptable environmental insult be determined?

Question 3: Will the upper limit of acceptable environmental insult be determined before or after the beginning of the adverse effect?

For a given situation there should be some ratio of jobs to acceptable environmental damage.

Example: By relaxing the rules on the release of coal mining waste into a river, X jobs are created and, as a result, Y households are denied potable drinking water. What is an acceptable ratio of X to Y?

Those are enough questions for now. Talk amongst yourselves.

This post has been updated. Th’ Gaussling, 6/4/16.

If you work with chemicals at the level of chemist in a production environment, chances are at some time in your career you’ll be called upon to help decide when a material is too hazardous to use in manufacture. It can be in regard to raw materials or as the final product. Your organization may have protocols or institutional policies or memories relating to certain classes of substances. Some companies, for instance, will not use diethyl ether in its processes. Others may require hydrocarbon solvents *absolutely* free of BTX. Some companies are so fastidious about worker exposure that the faintest whiff of solvent constitutes a breach. One world class company I know requires R&D chemists to include a process hazard analysis, review, and an inspection for all R&D reactions performed in the hood.  Whatever the company, most have fashioned some kind of boundary as to what is permissible to have on site and what isn’t.

Large chemical companies tend to have large EH&S departments with well established SOP’s and protocols with regard to personal protective equipment (PPE) and the measurement of occupational exposure to substances. Larger companies may have an OSHA attorney on retainer and staff members specializing in regulatory compliance.

One might suppose that smaller chemical companies may not have the depth of hazardous material experience that the larger companies have for many reasons. Smaller companies may have smaller capital equipment and a smaller staff. But smaller companies may have a greater organizational freedom which can lead to a great variety of projects. A great variety of projects often means that a great variety of materials are used on site. As such, a smaller company might very well have considerable expertise in a wide variety of chemical substances and, consequently, a wide variety of hazards.

While a smaller chemical company may have considerable expertise in handling its hazardous materials, it may be lacking in infrastructure for administrative controls and regulatory compliance. A wise CEO watches this aspect as closely as the actual operations.

Whether large or small, eventually a company has to draw the line on what hazards it will bring on site. The chemist has some very sober responsibility in this regard. Through the normal ordeal of process development, the diligent synthesis chemist will find the optimum path from raw material to product. All synthesis consists of the exploitation and management of reactivity. But there is always the “deal with the devil”. In exchange for a useful transformation, properly reactive precursors must be prepared and combined. A mishap with a 1-5 liter reaction on the bench top is messy and possibly an immediate threat to the chemist. But that same reaction in a 50 gallon or 5000 gallon pot can turn into the wrath of God if it runs away. The chemists judgment is the first layer of protection in this regard. All process chemists have to develop judgment with respect to what reagents, solvents, and conditions are feasible. Economics and safety come into play.

A runaway reaction poses several kinds of threats to people, equipment, and the viability of the company. There is the immediate thermokinetic threat stemming from the PV=nRT, meaning that energy can be dumped into PV work leading to the high speed disassembly of your equipment. A prompt release of heat and molecules kicked into the gas phase may or may not be controllable. Especially if the runaway leads to non-condensable gases. A runaway has a mechanical component in addition to the chemical action.

An runaway may cause the reactor contents to be abruptly discharged. Several questions should be answered ahead of time. Where do you want the contents to go and what are you going to do with it once it is there? Catchpots and emergency relief systems are common and resources should be invested there.

A question that the wary chemist must ask is this: What if a cloud of my highly useful though reactive compound gets discharged into the air or onto the ground? Do the benefits of this reagent outweigh the downside costs? Even if a release is not the result of a thermokinetic disaster like a runaway, explosion, or fire, a simple release of some materials may be consequential enough to require the evacuation of a neighborhood. Once your materials have left the site in the form of a cloud or a liquid spill and you make the call to the fire department, you have lost control of the incident. Even if nobody gets hurt or exposed, the ensuing “regulatory compliance explosion” may knock you down.

A chemical process incident can have mechanical consequences, chemical release issues, and the matter of fire. Substances that are pyrophoric have automatic ignition problems that may be surprisingly easy to deal with, especially if they are liquid. Liquid transfer systems can be inerted easily and pyrophoric liquids can be transferred airlessly and safely. Pyrophoric solids are another matter. There  are few generalizations I can make about pyrophoric solids. Inert solids pose enough handling issues without having the added complication of air/water sensitivity. All I can say about pyrophoric solids- waste or finished product- is that you will need solids handling equipment, a big supply of LN2 and procedures for passivating hot filter cakes. Production glove boxes and Aurora filters are particularly useful. Also required is a space on the plant site where you can open up a container and let the contents burn if needed. If air gets into a container of pyrophoric solids, it’ll begin to get hot. That is when you need to have an open spot where it can smolder or ignite harmlessly and not bring the facility down. Crowded industrial parks are a bad place for such material handling.

When designing a chemical handling space, it is important to think about what happens in a fire. Flammable liquids are under the constant influence of gravity and will run to the low point on a floor. The question you must to ask beforehand is this: Where do I want the burning liquid to go? There are good choices and poor choices. Preferably a stream of burning or flammable liquid should run away from evacuation pathways and exits as well as anywhere other hazardous materials or combustibles may be contained. To some extent this is moot because indoor spaces should be covered by a fire suppression system. But outdoor spaces may be problematic in regard to crowding of a tank farm and drums and cylinders.

Burning pools of organic liquids radiate considerable energy per sq ft per sec (power in Watts). The temperature of nearby objects will rise rapidly to the flash point and the ceiling spaces will accumulate smoke and hot gas. Drums and cylinders filled with flammable liquids or gases will eventually overpressure and release their contents adding to the mayhem. The release can be in the form of a BLEVE or a flood of flammable liquid leading to a widespread pool fire.

There are resoures available to quantitate the risks of such releases. The American Institute of Chemical Engineers (AIChE) is well organized and provides much literature on the topic of chemical plant safety. In particular I am thinking of Dow’s Chemical Exposure Index Guide, 1994, 1st Edition, AIChE, ISBN 0-8169-0647-5.  This handbook takes the reader through calculations aimed at estimating the risk and likelihood of chemical releases.

Also available is Dow’s Fire & Explosion Index and Hazard Classification Guide, 1994, Seventh Edition, AIChE, ISBN 978-0-8169-0623-9.  This handbook supports the use of a quantitative risk analysis chart for the use of a risk and hazard index for generating numbers associated with process activities for cost/benefit analysis. It is well worth the addition to your library

Such flammable liquid scenarios can begin many ways.  Forklift and maintenance operations are particularly rich in opportunity for a fire. The physical location of flammable liquid storage must be well thought out. Ideally a warehouse fire should not be allowed to spread to capital equipment locations. This helps to keep workers out of harms way and contains the magnitude of the financial disaster as well.  Since most chemical plants seem to grow organically over time, unfortunate choices are usually made in regard to incident propagation.

One type of propagation incident can be ameliorated through the clever use of architecture. I am aware of one tragic incident where an explosion occurred in a processing space of a facility that had grown over the years by the addition of contiguous manufacturing and warehouse spaces. A rabbit’s warren of interconnected rooms and hallways accumulated over time. At the moment of the reactor explosion, the room and adjacent spaces were badly damaged by the blast overpressure as you’d expect. However, since the building was interconnected the overpressure propagated throughout many other distant spaces and delivered considerable structural damage to the facility. Overhead doors were bent outwards and windows and man doors blown out. Extensive damage may have been avoided by the simple expedient of providing open air walkways to separated buildings rather than enclosed hallways between adjoining areas. Of course, the benefit of this depends on the who, what, where, when, and how, but eliminating pathways for a blast wave is a cheap and easy way to start.

When is a substance just too hazardous? This is fundamentally a business or policy decision. Ultimately, it is the responsibility of the organizational leadership to draw the line on the risks that are deemed acceptable. It is the ethical responsibility of those knowledgeable and experienced with the proposed chemistries to combine information with pragmatics to provide persuasive feedback to the decision makers in charge.

There are plants that routinely manufacture nitroglycerine, phosgene, chlorine, phosphine and HCN. Workers spend their careers in these places.  Most risks can be abated by properly engineered processing and packaging. It really comes down to personal choice. Is that ammonium perchlorate plant that just offered me a job operated safely? These reactive and/or energetic materials all have properties that lead to demand for their use. Somebody is going to supply that demand. We chemists have to look inward and then act with our eyes wide open and our heads on a swivel. Myself? I wouldn’t work in a nitroglycerine factory, but I’m glad that someone does.’

[Added 6/4/16 by Th’ Gaussling] I happened to go back to this post and in doing so read a comment by “Bob”, which you can see in the comment section below. Here is a copy

“I actually believe that as a society should keep the safety rules relaxed a bit in academia. Academia, for better or worse, is our national chemical research institution”

So underpaid grad students, postdocs and staff working at  a univeristy are less human, and less deserving of safety than their for profit brethren?

That’s diabolical Mr. Gaussling. Pure evil incarnate. For whose gain do you sacrifice their lives?

I want to address this now better than I did back then. To Bob I say this: Everyone has a right to a safe workplace. Academic institutions as well as industrial operations must use best practices in regard to worker safety. This is axiomatic. Plainly I did not articulate my contention as well as I could have. I will do so now.

We have to assume that junior chemists are likely grow to be senior chemists in an organization. The role of a senior chemist in industry for example, may be quite varied through her/his career. A senior chemist who has stayed in the technical environment will almost unavoidably have been confronted with a large variety of questions in regard to circumstances and outcomes relating to hazardous materials and tricky reactions. Moreover, a senior chemist is likely to have been promoted to a level that also involves supervision, the drafting of SOPs, work instructions, MSDS documents, emergency planning, laboratory design, etc.

In my view, a senior chemist as described above has an ethical and moral responsibility to coworkers, plant operators, material handlers, and customers to oversee chemical safety. A chemist at any level has a responsibility to make known to all involved what dangerous circumstance might arise with any given chemical operation. Either in relation to the hazardous properties of substances that may be released in mishandling, or in regard to hazardous processing conditions that can lead to danger.

I’ve used the word hazard(ous) and the word danger(ous). We need some clarity on this. If you Google the words and stop with the dictionary definitions you will be left with the shallow notion that they are synonyms. If you dig deeper, say at the website of the Canadian Centre for Occupational Health and Safety (OSH), you will find a definition of “hazard” that I find particularly useful. To wit:

A hazard is any source of potential damage, harm or adverse health effects on something or someone under certain conditions at work. [italics mine]

The same fuzziness in definition exists for the word danger(ous) as well. A definition I prefer is below:

A dangerous occurrence is an unplanned and undesired occurrence (incident) which has the potential to cause injury and which may or may not cause damage to property, equipment or the environment. [italics mine]

This definition is borrowed from the University College Cork, Ireland (UCC). I believe this is a good definition and it readily sits apart from the definition of hazard above.

The key difference is that a hazard is any source of potential of damage … under certain conditions.. whereas danger is a condition brought on by an unplanned or undesired occurrence. Next, lets consider these terms in the context of chemistry.

On the shelf in the fire cabinet is a glass bottle of phosphorus oxychloride, properly sealed and segregated. As the POCl3 sits on the shelf in the cabinet, I would argue that it is only hazardous. If, however, you pick up the bottle and in walking to the fume hood drop it causing it to break and spill the contents in the open, you’ve caused a dangerous situation. It’s an imminent threat to health and safety.

Conversely, let’s say that you carried the bottle to the hood, used it, then returned it to storage without incident. In the reaction the POCl3 is consumed and in the workup the residual acid chloride is quenched by water. Congratulations! You have taken a hazardous material, used it safely, passivated the actives during workup, and eliminated at least the acute hazard relating to POCl3.

In the first situation, a hazardous material was mishandled and became dangerous. In the second situation, the hazardous material was handled properly, consumed, and residuals passivated. In this case a hazardous material was used safely and to positive effect.

Seem trivial? Well, it’s not. This difference in meaning leads to a confusion that is especially acute among the non-chemist population. But my point leads to the question of how students are taught to use hazardous materials.

I spoke of relaxing safety requirements in academia. An example of such a thing might be the use of diethyl ether. This useful solvent is banned outright in some chemical manufacturing operations across the country owing to the flammability. Even in their R&D labs. This is corporate policy handed down by those responsible for risk management, not scientists. In some industrial labs, woe is he who has an unexpected occurrence like a boil-over or a spill.

I believe that Et2O should remain in academic research labs for both the research value and for the development of valuable lab experience by students and postdocs.

You learn to handle hazardous materials by having the opportunity to handle hazardous materials.

Ether is only a simple example of what I’m trying to communicate. In order for chemists to graduate as experienced scientists with working familiarity in the properties of substances, they must have experience handling and using a large variety of substances, many of which may be substantially hazardous. And by hazardous I mean much more than just toxic. A substance may have a reactive hazard aspect that is a large part of it’s utility.  To safely handle substances that pose a reactive hazard, a chemist needs to have experience in using it. And killing it. The chemist must try to gauge the level of reactivity and modify the use of the substance to use it safely. If you’ve made or used a Grignard reagent you know what I mean. Expertise in laboratory chemistry only comes through direct experience.

Hazardous reactive materials do useful things under reasonable conditions. Non-hazardous, unreactive materials find great utility in road and bridge construction.

If we regulate out all of the risk by eliminating hazardous materials in academic chemistry, what kind of scientists and future captains of industry are we producing? What we can do is to put layers of administrative and engineering protection in the space where the hazardous transitions to the dangerous.  Academic laboratory safety is promoted by close supervision by experienced people. Limits on the amount of flammables in a lab space, proper syringe use, safe quenching of reactive residues, proper use of pressurized equipment, and a basic assessment of reactive hazards present in an experiment will go a long way to improving academic lab safety. Experienced people usually have a trail of mistakes and mishaps behind them. If we corporatize the academic research experience to a zero risk condition, we may kill the goose that lays the golden egg.

 

I have spent some time researching basic magnesium chemistry. Not anything synthetic but more safety and thermochemically related. I am not able to give a lot of particulars motivating the study, but I can say that one should consider that nitrogen over activated magnesium may not be as innocent as you think. While lithium is widely known to react with nitrogen gas to form a passivating nitride layer, the reaction of dinitrogen with magnesium is rarely encountered.

Activated magnesium residues from a Grignard or other magnesium metallation reaction may self-heat to incandescence under a nitrogen atmosphere in the right circumstances. Activated residues left isolated on the reactor wall or other features in a nitrogen blanketed reactor during an aqueous quenching procedure may self-heat to incandescence. In the presence of reactive gas-phase components like water vapor in nitrogen, activated metals can self-heat over an induction period of minutes to hours or longer.

Many metals, including magnesium and aluminum, can be rendered kinetically stable to air or humidity by the formation of a protective oxide layer. Once heated to some onset temperature by a low activation reaction, penetration of the protective layer by reactive gas composition can occur, leading to an exothermic reaction.

Performing a “kill reaction” or a quench of a reactive metal at the bench or at scale is always problematic and requires the skill and close attention of the process chemists and operators. I guess what I’d like to pass on is that nitrogen is not an innocent spectator in the presence of finely divided, activated magnesium. Humid nitrogen can support a combustion reaction to produce nitrided magnesium once preheated to an onset temperature.

If you mean to kill any reactive residues, it is important to apply the quenching agent in such a manner that the heat generated can be readily absorbed in the quenching medium itself. A good example of a quenching agent is water. Often a reactive must be killed slowly due to gas generation or some particular. Adding a quenching agent to a solution or slurry by slow feed or titration may be your best bet. If you have another vessel available, a feed to a chilled quenching agent will also work.  Dribs and drabs of water on a neat reactive material will lead to hotspots that may be incendive.

Th’ Gaussling has been dabbling in the strange land of cheminformatics lately. I’m trying to develop some productivity tools in on various platforms to make chemical information more accessible to fellow staff members.

One particularly useful tool is the InChI, or International Chemical Identifier. The InChI is a character string that is derived from a chemical structure. This string can be hashed (irreversibly) into a shorter string of alphabetic characters called the InChIKey. Using ChemSketch, one can draw a structure and generate an InChI string and an InChIKey string. What you’ve done here is to jump the gap from chemical structure to a searchable character string. These InChIKeys can be planted into documents such as Excel spreadsheets, Word files, and Access databases. A search for the InChI character string can find all of the documents in a folder containing the string or to a record in a database containing it.

Granted, this can be done in other ways. A chemical name can be searched as can a CASRN. Names are subject to syntactical variation and could complicate the search. If you have generated a new structure that is not listed in CAS and the nomenclature is complex, then an InChIKey identifier can serve as an unambiguous term for subsequent searches.

If you hate using the Java based drawing module in SciFinder, an InChI string or SMILES string can be used instead. Just open the structure drawing module and look in the upper left hand corner of the window. There will be a screwy looking button to select for pasting in an InChI or SMILES string. This will cause the Java module to draw the structure for you. It’s pretty handy.

2/23/14

Five months past treatment for throat cancer I will set aside The Squamous Chronicles and instead post The Adenocarcinoma Chronicles. Having won the advanced prostate cancer lottery as well, my current adventures involve treatment below the beltline.  Here are my impressions of the experience to date.

Physicians, or more specifically in this context, oncologists, are ethically constrained to apply agreed upon treatments for the indications presented by the patient. I have gotten no “off-label” kind of advice up to now. In my case, my PSA was 39 and the biopsy readings from the pathologist were assigned Gleason 9. Well, sonofabitch. That was a fine kettle of fish. Looks like my watchful waiting was long in the waiting and too light in the watchfulness.

The standard treatment regimen in my case is hormone ablation and radiation. For hormone ablation I have had Degarelix and Lupron. For radiation I have begun IMRT (Intensity Modulated Radiation Therapy) with a dose of 76 Gy to the targeted tissue mass. I asked about scatter dose to the testes just because of the obvious proximity. The Rad Onc looked it up and said it was 1 Gy. I then pointed out that I’ve had a goodly bit of radiation in the last year and was there anyone who keeps a running total on the cumulative dose? As expected, the answer was “no” followed quickly by the standard rationale that the disease was far more dangerous than the radiation. I’d say the same thing I suppose.

Things that my docs are reluctant to offer are opinions on how this whole disease plays out. There seem to be several elements to this reticence. First, predicting the future is difficult, especially with a stochastic phenomenon like cancer radiotherapy. Second, there are good reasons for the doc to not focus on gloomy topics like life expectancy, especially if the survival stats are not the best. Most people at some point spontaneously think of cancer as a death sentence. At present I view it as a chronic condition that will play out stepwise in terms of a convergent treatment and remission series that eventually ends with refractory and widespread disease. Seems pretty obvious. It is the time-scale that I am uncertain of.

I am writing about this because my treatment regimen seems relatively ordinary to this point given the status of the condition. Perhaps there are some fellows who have yet to climb on this train who are uncertain of where it goes. This is my journey and I’ll pass along my notes.

Update 3/13/14

Now 14 treatments into radiation. With the help of medical textbooks ordered from Amazon, I have slowly been learning more about the disease and the treatment. During my weekly consult with the Rad-Onc I asked the question- “What was the T number from the pathologists notes?” He replied it was T3c N1.  The N1 means there is a node involved so it’s Stage 4 cancer. No one actually came out and said this to me so I had to ask. It is one thing to suspect it and another to hear it. Hard to say if this knowledge is in some way empowering.

The fouling of public waters in West Virginia by 4-methylcyclohexanemethanol (MCHM) is regrettable and my heart goes out to all of the families whose lives have been and are disrupted by the spill. In my judgment the descriptions of the substance found in Wikipedia and ChemSpider seem very evenhanded given what is known presently about the toxicology of the substance. The SymBioSys LASSO numbers found in ChemSpider are reassuring in the sense that the structure of MCHM does not line up well with the receptors in the list. The low scores are suggestive of substrate mismatch with these receptors based on calculation. That is a good thing. So is the relatively high flash point of 80 °C.

There are several uses of this substance. At the large scale its use has been patented as a frothing agent for coal beneficiation (US 4915825). That patent is now expired. It is useful for separating coal particles from inorganic mineral particles. Other uses include the preparation of ester derivatives to produce plasticizers either as a stand alone ester or, as a listing in SciFinder shows, a hydrophobic co-monomer.

From what I have heard in the media, the secondary containment failed, allowing material to discharge into the nearby river. This is easy to figure out. A visual inspection by plant EH&S should have noticed failure of the secondary containment during periodic inspection and flagged it for repairs. The US Chemical Safety Board is investigating and will eventually publish a finding.

It seems to me that the people of WV must be willing to publically demonstrate en mass if anything is to change there. The lack of regulatory oversight on facilities like this is not surprising. It is exactly as intended by the power brokers of the state.

Ran into an interesting recommendation on fighting a lithium fire in Joshi, D.K., et al, Organic Process Research & Development, 2005, 9, 997-1002.

In addition to the usual admonitions on the handling of a reactive metal like Li, they warned that water, sand, carbon dioxide, dry chemical, or halon should not be used. Rather, they suggest dry graphite or lithium chloride instead.  This seems quite reasonable to me, having reacted both silica and CO2 with magnesium powder in chemical demonstrations in a previous life. If Mg will reduce SiO2 and CO2, then hot/burning lithium ought to be reactive as well.

A similar recommendation is given in Furr, A.K. CRC Handbook of Laboratory Safety, 5th Edition, p. 299, ISBN 0-8493-2523-4.

Lots of semi-batch process development and safety work going on in my lab. We use our reaction calorimeter for a variety of studies now. Naturally we want to know about energy accumulation with a given feed rate or any unforeseen induction or initiation problems in a reaction. We can also home in on recommendations for safe feed rates of reactants into a reaction mass.

What I am beginning to learn from the RC1 work is that running a reaction at low temperature is frequently done for sketchy reasons. Unless there are selectivity or side product issues, you really have to question why the reaction is specified to be run at low temperature. I think some of it comes from habit gained in grad school.  Low temperature may introduce dangerous situations with abrupt initiation by accumulation of unreacted reagents. Or it may lead to overly long feed time with the associated costs of added plant time and labor.

There are reagent incompatibilities like nBuLi in THF above – 15 C or so. But you’ll find that MeTHF is a bit more tolerant of temperature than is THF.

The precise temperature management capabilities (Tr) of an RC1 including the ability to lock on a temperature or precision ramping gives insight on solubility questions or on freezing points. The instrument also provides heat capacity data for engineering calculations. it is a very useful apparatus.

Any questions?

This video was produced at Pultroon Studios in Smoldering Forest, Colorado.

The subject had received 15.7 mCi of 18F-glucose 6 hours prior to filming. His current whereabouts are unknown.

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