Category Archives: Technical presentations

Highlights from ACS Webinar on Nanosafety Research

Nanoparticles are an area of increasing research interest in many fields. However, the risk data related to the safety, health and environmental impacts is still limited. How should lab researchers approach these uncertainties?

Speakers: Tilak Chandra, University of Wisconsin-Madison / Katie Kruszynski, University of Wisconsin-Madison / Markus Schaufele, Northwestern University

This ACS Webinar was moderated by Ralph Stuart and co-produced with the ACS Division of Chemical Safety and the ACS Committee on Chemical Safety.

The Committee on Chemical Safety’s list of references on nanosafety can be found on its web site.

Constructing Consequences for non-compliance

04/21 Table Read for The Art & State of Safety Journal Club

Excerpts from “Constructing Consequences for Noncompliance: The Case of Academic Laboratories” presented by Dr. Ruthanne Huising, Emlyon Business School

Full paper can be found here: https://journals.sagepub.com/doi/full/10.1177/0002716213492633

Introduction

As a profession, contemporary scientists enjoy an unusual degree of autonomy and deference. Universities are professional-bureaucracies (Mintzberg 1979). One side of the organization is collegial, collectively governed, participatory, consensual, and democratic. The other side is a Weberian, hierarchical, top-down bureaucracy with descending lines of authority and increasing specialization. These organizational structures may allow for differential interpretations of and responses to legal mandates and differential experiences of regulation and self governance. They often disadvantage regulators and administrative support staff, who occupy lower-status positions with less prestige, in their efforts to monitor, manage, and constrain laboratory hazards (Gray and Silbey 2011). What is regarded as academic freedom by the faculty and university administration looks like mismanagement, if not anarchy, to regulators[a][b].Herein lies the gravamen of the risk management problem: the challenge of balancing academic freedom and scientific autonomy with the demand for responsibility and accountability[c][d][e][f][g][h].

We…describe the efforts of one university, Eastern University, to create a system for managing laboratory health, safety, and environmental hazards and to transform established notions that =faculty have little obligation to be aware of administrative and legal procedures.[i][j][k] We describe the setting—Eastern University, an Environmental Protection Agency (EPA) inspection, and a negotiated agreement to design a system for managing laboratory hazards—and our research methods.

We describe efforts, through the design of the management system, to create prescribed consequences for noncompliant practices in laboratories. We show that in an effort to design a management system that communicates regulatory standards, seeks compliance with the requirements[l], and then attempts to respond and correct noncompliant action, Eastern University struggled to balance case-by-case discretion consistent with academic freedom and scientific creativity with the demands for consistent conformity, transparency, and accountability for safe laboratory practices.

Constructing Organizational Consequences at Eastern University: Management System as Solution?

During a routine inspection of Eastern University, a private research university in the eastern United States, federal EPA agents recorded more than three thousand violations of RCRA, CAA, CWA, and their implementing regulations. Despite the large number of discrete violations, both the EPA and the university regarded all but one as minor infractions. The university’s major failure, according to the EPA, was its lack of uniform practices across departments and laboratories on campus.[m][n][o][p] There was no clear, hierarchical organizational infrastructure for compliance with environmental laws, no clear delineation of roles and responsibilities, and, most importantly, no obvious modes of accountability for compliance….Without admitting any violation of law or any liability, the university agreed in a negotiated consent decree to settle the matter without a trial on any issues of fact or law.

At Eastern, the management system reconfigured the work of staff and researchers by moving compliance responsibility away from centralized specialists to researchers working at the laboratory bench. Scientists became responsible for ensuring that their daily research practices complied with city, state, and federal regulations. [q][r]This shift in responsibility was to be facilitated by the creation of operating manuals, inspection checklists, enhanced training, and new administrative support roles.[s][t][u][v][w][x][y][z][aa][ab][ac][ad][ae]

Research Methods: Observing the Design of an Environmental, Health, and Safety (EHS)  Management System

From 2001 through 2007, we conducted ethnographic fieldwork at Eastern University to  investigate what happens when compliance with legal regulations is pursued through a management system.

The fieldwork included observation, interviewing, and document collection. It was supplemented by data collection with standardized instruments for some observations and via several surveys of lab personnel and environmental management staff. For this article, we draw primarily from notes taken at meetings of the committee designing the system, presenting notes from the discussions concerning a catalog of consequences for poor performance required by the consent decree.

Building Responsiveness and Responsibility into an EHS-MS: Consequences for Departures from Specified Operating Procedures

The final version [of the management system manual] was agreed to only after hundreds of hours of negotiations among four basic constituencies: the academic leadership, the university attorney overseeing the consent decree, the environmental health and safety support staff located within the administration, a nonacademic hierarchy, and the lab managers and faculty within the academic hierarchy.[af][ag][ah]

These descriptions explain that each person, or role incumbent, works with a committee of faculty and staff of safety professionals that provides consultation, monitoring, and recommendations, although legal responsibility for compliance is placed entirely within the  academic hierarchy, with ultimate disciplinary responsibility in a university-wide committee.

>What will constitute noncompliance? 

Despite the adoption of the original distinctions between minor, moderate, and very serious incidents [described in a section not included in this Table Read], discussions continued about the relationship between these categories and the actual behavior of the scientists. How would the system’s categories of “acceptable” and “unacceptable” actions map onto normal lab behaviors? How much would the lives of the lab workers be constrained by overly restrictive criteria?[ai][aj][ak] As Professor Doty said, no one wanted the system to be like police surveillance. Labs are places where science students live, after all.[al][am] Once a basic list of unacceptable conditions and actions was created and communicated through safety training, the salient issue would be intentionality, as it is in much conventional legal discourse.

>Who will identify noncompliance?

Marsha (attorney for University): I think we’re going to need to be more specific, though, for university-wide committee policy. If the consequence of a particular action is termination from Eastern, then there’s policy in place for that, but what leads up to that? When do you shut down a lab?[an][ao] When do you require faculty to do inspections in departments like XYZ? A lot of people here have partial responsibility for things—the system may work well, but it’s not[ap] always clear who’s responsible. Where we need to end up is to remember this key link to the PI. In order for this to work, I think it really comes down to the PI accepting responsibility[aq], but how they deal with that locally is a very personal thing[ar][as][at][au]. I don’t think we should prescribe action, tell the PI how to keep untrained people out of [the] lab. But we need to convince the faculty of this responsibility.[av]

>How will those formally responsible in this now clearly delineated line of responsibility be informed? 

Who will tell the professor that his or her lab is dirty or noncompliant?[aw][ax][ay][az][ba][bb][bc][bd]

Informing the responsible scientist turns out to be a complex issue at the very heart of the management system design, especially in the specifications about distribution of roles and responsibilities. In the end, Eastern’s EHS-MS named a hierarchy of responsibility, as described above, from the professor, up through the university academic hierarchy, exempting the professional support staff.[be][bf]

Despite the traceable lines of reporting and responsibility on the organizational charts, consultation, advice, and support was widely dispersed so that the enactment of responsibility and holding those responsible to account were constant challenges and remain so to this day. Most importantly, perhaps, because the faculty hold the highest status and yet hold the lowest level of accessibility and accountability, the committee was vexed as to how to get their attention about different types of violations.

Marsha: …So, while you’re defining responsibilities and consequences, make sure you don’t relieve the PI of his duties. You can assign them helpers, but they need to be responsible[bg][bh][bi]. There can be a difference between who actually does everything and who is responsible[bj]. You need to make sure people are clear about that.

Marsha: We need to convince the faculty of this responsibility….This is what we should be working on this summer. This is unfortunately the labor intensive part—we need to keep “looping back”—going to people’s offices and asking their opinions so they don’t hear things for the first time at [some committee meeting].[bk]

Marsha: We need department heads and the deans to help us with PIs in the coming months…. We need to get PIs—if we don’t get them engaged the system will fail….We will get them by pointing out all the support there is for them, but bottom line is they have to buy into taking responsibility.[bl][bm][bn][bo][bp][bq][br][bs]

In the end, the system built in three formal means to secure the faculty’s attention and acknowledgement of their responsibility for laboratory safety: (1) A registration system was implemented, in which the EHS personnel went from one faculty office to another registering the faculty and his or her lab into the system’s database. The faculty were required to sign a document attesting that they had read the list of their responsibilities and certifying that the information describing the location, hazards, and personnel in their lab was correct for entry into the database. (2) All faculty, as well as students, were required to complete safety training courses. Some are available online, some in regularly scheduled meetings, and others can be arranged for individual research groups in their own lab spaces. The required training modules vary with the hazards and procedures of the different laboratories. (3) Semiannual university inspections and periodic EPA inspections and audits were set up to provide information to faculty, as well as the university administration and staff, about the quality of compliance in the laboratories. Surveys of the faculty, students, and staff, completed during the design process and more recently, repeatedly show that familiarity with the EHS system varies widely.

Although the audit found full compliance in the form of a well-designed system, it also revealed that many of the faculty and some administrators did not have deep knowledge of it,[bt] despite the effort at participatory design.

>What action should be taken? 

Consequences vary with the severity of the incident.

It was essential to the design of the system that there be discretionary responses to minor incidents, which are inevitably a part of science.

It was assumed[bu] that regular interaction with the lab safety representative, discussions in group sessions, and regular visits by the EHS coordinator would identify these and correct them on the spot with discussion and additional direction. The feedback would be routine, semiautomatic in terms of the ongoing relationships between relatively intimate colleagues in the labs and departments. No written documents would even record the transaction unless it was an official inspection; weekly self-inspections by the safety reps were not to be fed into the data system.[bv][bw][bx][by][bz][ca][cb][cc][cd][ce] 

Consequences for moderately serious incidents include one or more of the following actions: oral or written warning(s) consistent with university human resources policies; a peer review of the event with recommendations for corrective action; a written plan by a supervisor [cf]that may include retraining, new protocols, approval from the department EHS committee, and a follow-up plan and inspection; or suspension of activities until the corrective plan is provided, or completed, as appropriate.

A list of eight possible consequence[cg][ch][ci]s accompanies the definition of a very serious incident. The list begins with peer review and a written plan, as in moderately serious incidents, but then includes new items: appearance before the university’s EHS committee or other relevant presidential committees to explain the situation, to present and get approval of a written plan to correct the situation, and to implement the plan; restriction of the involved person’s authority to purchase or use regulated chemical, biological, radioactive, or other materials/equipment; suspension or revocation of the laboratory facility’s authorization to operate; suspension of research and other funds to the laboratory/facility; closure of a lab or facility; and applicable university personnel actions, which may include a written warning, suspension, termination, or other action against the involved person(s) as appropriate.

These descriptions illustrate the sequential escalation of requirements and consequences and display, rather boldly we think, the effort of the committee to draft a legal code for enforcement of the management system’s requirements.

When the committee completed its work, Marsha, the lead attorney, went to work editing it. When it was returned to the committee, the changes, many of which were grammatical rather than substantive, nonetheless so offended the group that participation in the planning process ceased for a long while.[cj][ck][cl] The associate dean communicated to the EHS leadership that morale among the coordinators and other committee members from the laboratories was low and that their willingness to do their best was being compromised. They believed that the decisions they made collectively in the working meetings were being undermined and changed so that at subsequent meetings, documents did not read as they were drafted; they believed that crucial “subtleties, complexities and nuances to policies and proposals” were being ignored, if not actively erased. If they were to continue working together, they asked for complete minutes and officially recorded votes.

Nonetheless, it was the scientists’ and their representatives’ fear that the system would in fact become what a system is designed to be: self-observant and responsive and, thus, would eventually and automatically escalate what were momentary and minor actions into moderate, if not severe, incidents. This anxiety animated the planning committee’s discussions, feeding the desire to insert qualifications and guidelines to create officially sanctioned room for discretionary interpretation.

>Who will be responsible for taking action to correct the noncompliant incident?

Clearly, most minor incidents are to be handled in situ, when observed, through informal conversation, and the noncompliant action is supposed to be corrected by the observer’s instruction and the lab worker’s revised action. Some noncompliance is discovered through inspections that inform the PI of noncompliant incidents; a follow-up inspection confirms that the PI instructed her students to change their ways. Very few incidents actually move up the pyramid of seriousness.

A significant proportion of the chronically reported incidents are associated with the physical facilities and materials in the laboratories[cm], such as broken sashes on the hoods, eye washes not working or absent, missing signage, inadequate tagging on waste, empty first aid kits, or crowding—simply not enough benches or storage areas for the number of people and materials in the lab…Corrections are not always straightforward or easy to achieve.[cn] Tagging of waste, proper signage, and adequate first aid kits may be fixed within a few minutes by ordering new tags and signs from the EHS office and a first aid kit through the standard purchasing process. While the lab may order its own supplies, it must wait for the EHS office to respond with the tags and signs. The hood sashes and eye wash repairs depend on the university facilities office, which is notoriously behind in its work and thus appears unresponsive. In nearly every conversation about how to respond to failed inspections, discussion turned to the problems with facilities (cf. Lyneis 2012[co])…crowding is often the consequence of more research funding than actual space: the scientist hires more students and technicians than there are lab benches. This has been a chronic issue for many universities, with lab construction lagging behind the expansion of research funding over the last 20 years.

Just as the staff experienced the faculty as uninterested in the management system, the scientists experienced a “Don’t bother me” attitude in the staff, because often the ability to take corrective action does not rest entirely with the persons formally responsible for the lab.[cp][cq][cr][cs][ct] The PI depends on the extended network of roles and responsibilities across the university to sustain a compliant laboratory. This gap between agency (the ability to perform the corrective action) and accountability (being held responsible and liable for action) characterizes the scientists’ experience of what they perceive as the staff’s attitude of “Don’t bother me.” The management system is, after all, a set of documents, not a substitute for human behavior.

Discussion and Conclusion

In this article, we have used the case Eastern University to show how coordination and knowledge problems embedded in complex organizations such as academic research laboratories create intractable regulatory and governance issues and, unfortunately, sometimes lead to serious or even deadly outcomes. Overlaying bureaucratic procedures on spaces and actors lacking a sense of accountability to norms that may in real or perceived terms interfere with their productivity highlights the central challenge in any regulatory system: to balance autonomy and expertise with responsibility and accountability. Under these conditions, accountability may be, in the end, illusory.

…Rather than an automatically self-correcting system of strictly codified practices, Eastern’s EHS-MS relies on case-by-case discretion that values situational variation and accommodation. Compromises between conformity and autonomy produce a system that formally acknowledges large and legitimate spaces for discretionary interpretation while recognizing the importance of relatively consistent case criteria and high environmental, health, and safety standards. [cu][cv][cw][cx]Marsha, Eastern’s principal attorney, noted the difficulties of balancing standardized ways of working in high-autonomy settings, voicing concern about “the exceptions [that] gobble up the rule.” The logic of the common law is reproduced in the EHS-MS because, like our common law, only some cases become known and part of the formal legal record: those that are contested, litigated, and go to appeal. In this way, the formal system creates a case law of only the most unusual incidents while the routine exceptions gobble up the rule.

…safer practices and self-correcting reforms are produced by surrounding the pocket of recalcitrant actors who occupy the ground level of responsibility with layers of supportive agents who monitor, investigate, and respond to noncompliant incidents. In the end, we describe not an automatic feedback loop but a system that depends on the human relationships that constitute the system’s links.[cy][cz][da]

Group Comments

[a]Interesting set of different perspectives…

[b]The quote “They spent all this time wondering if they could, that no one thought to think about if they should” is the first thing that comes to mind when I read this sentence.

[c]Why are these viewed as diametrically opposed?  They can be complimentary

[d]In practice, have you found this to be the case? I find this perspective interesting, because at least in my experiences and the experiences of those I’ve interacted with, practically, they do often conflict (or, at least are *perceived* as conflicting, which really may be all that matters, culturally)

[e]In many of the issues I have explored as a grad student, I have noticed that this “freedom” often translates into no one actually being responsible for things for which someone really SHOULD be responsible. And if faculty step up to take responsibility, they are often taking on that responsibility alone.

[f]I think it’s strongly dependent on awareness (often via required training) and leadership expectations.  In instances where both were sound and established, I’ve seen these elements to be complimentary.

[g]I wonder what this training would look like. In my experience, a lot of training is disregarded as an administrative hoop to jump through every once in a while. I also think it’s wildly dependent on the culture of the university, as it exists. There is often little recourse to leverage over faculty to modify their behavior if it’s not (1) hired in, (2) positively incentivized, or (3) socially demanded by faculty peers. It seems difficult to me to try to newly instill such training requirements, with the goal of making PIs aware of their responsibility for ensuring safety. If there are no consequences (short of a major accident drawing the eye of the law), no social pressure to engage in safe behavior, and no positive incentive structure to award participation, why would faculty change their behavior? Many of them are already aware of the safety requirements—many of them just choose to prefer short term productivity and to prioritize other metrics. In an ideal world, I think I would agree with you that training at the University level would be sufficient, but I think there needs to be a much broader discussion of faculty *motivation*, not just their awareness.

[h]Agreed, the culture/environment aspects are huge in terms of how such awareness training is received.  There’s multiple incentive models, and I’d hope that legal liability isn’t the only one that would lead to proactive action.

[i]Sounds like a training deficiency if that’s the perception.

[j]What are you defining as “training”?

[k]Awareness of their obligations/requirements for both administrative (university) and regulatory elements.  This should be provided by the institution.

[l]which should include process safety

[m]This is a bit vague. Uniform practices? A one size fits all approach?

[n]This caught me out a bit as well. If all they were finding were minor infractions, do we actually have a problem here?

[o]I’m curious what these “minor infractions” were, though. What’s the scale? What’s the difference between a major and minor infraction? 3,000 opportunities for individual chemical exposures or needle pricks may be considered small when it comes to the EPA, but it seems quite substantial when it comes to individual health and safety

[p]In general, minor infractions involve things like labellng of waste containers, storage times in accumulatins areas, etc. without any physical resulting impacts. EPA writes these up and can fine for them, but infractions don’t involve physical damange

[q]Interesting…. this is what caused problems for us at Texas Tech before our accident. Individual oversight often meant no oversight…

[r]Agreed, some form of checks-and-balances should be implemented to verify elements are being completed.

[s]In my experience this is often a techniques employed by higher administration to shift the blame on frontline researchers and their supervisors.

Combine with an underfunded EHS department and this situation results in no oversight or enforcement of these requirements.

[t]But administrators are not experts as the PIs claim they are, If PI’s want freedom and recognition as experts then they do need to be held accountable but EMPOWERED by providing support mechanisms. Responsibility without empowerment is useless.

[u]My eyes immediately went to the “new admin support roles.” If you have someone who understands both the regulations and the relationships in the department, I would think that person would be more effective than someone who shows up from a different department once per year with a checklist.

[v]Agree with Anonymous. If you want the freedom, you take on the responsibility. Don’t want the responsibility, hand over the freedom.

[w]I agree that faculty should be responsible. The common arguments I hear is that faculty aren’t in the lab all the time and can’t always be responsible for what happens day to day. Sort of a cynical view that says that faculty are the idea people and others (students?) should be the implementers…

[x]I don’t think anyone expects them to be responsible for everything every single day though. I think the idea is that they should be responsible for setting the tone in their lab and having standards for the graduate researchers working in their labs – and they should be making an effort to visit their labs in order to walk around and make sure everything is operating as it should.

[y]@Jessica I agree, but if they aren’t overseeing the day-to-day elements, they need to assign that responsibility to someone and make that assignment known to the research group.  AND they need to support and empower that individual.

[z]I think I agree with Jessica here. Perhaps, someone with an eye and responsibility for safety NOT being in the lab on the day-to-day is part of the problem. maybe it *should* be a responsibility of PIs to visit their labs, to organize them, to keep up safety standards, inventory, etc. Or, perhaps it is their responsibility to hire someone to do this, specifically. Perhaps these responsibilities should be traded for teaching responsibilities, and thus institutions with high research focus can focus on hiring research teachers and managers (PIs) who are trained as such, and teachers who are actually trained as teachers.

[aa]In the 1970’s and 80’s, externally funded PIs would hire people to do this kind of stuff (often called “lab wives”) but funding for this function was shifted to additional student support

[ab]Blending what Sara and anonymous said while student support has gone up, it has also become more transactional in that it is more linked to teaching duties, while research assistantships tend to be the exception in many “research heavy universities”.

[ac]I think the responsibility of the PI should be first to open the door for safety related discussions amongst the group, and then to make the final decision on acceptable behavior if consensus is not achieved. Following that, they should bare the responsibility of any ramifications of that decision. I think they can achieve awareness of what is happening in their lab without being there every day, but they need to continuously allow the researchers to voice their concerns

[ad]I also think that PI’s might need tools to help them be accountable.  Particularly new faculty

[ae]This the unfortunate part of interdepartmental politics, how far is the new faculty wiling to speak up, when in 5 years the same older faculty members will be a part of their tenure decision.

[af]This goes to early commentary on the shifting of regulatory compliance to researchers: were any researchers involved in these discussions or were PIs/lab managers speaking for them in these discussions?

[ag]I’d hope some (if they existed at this institution) laboratory safety officers were participants.

[ah]Lab safety officers were often active participants, but often on a parallel track to the faculty level discussions. I guess which group carried more clout in the system design?

[ai]The wording of this question seems to imply that lab safety impedes on lab productivity

[aj]Building upon this, there is evidence that when safety concerns are not an issue (due to correct practices) productivity is actually better.

[ak]I don’t have evidence for this, but I think it depends on how prevalent compliance is. If everyone is being safe in their labs then I think overall productivity would go up. If some people start cutting corners then while they may get short term improvement in productivity, in the long term everybody suffers (evacuations and accident investigation halting research, bad laboratory practices accumulating, etc.)

[al]Does this imply that “students” are a class of people whose rights and responsibilities are different from other people in the laboratory?

[am]Or to put it another way – why are students living in their labs?

[an]One of the EHS professionals involved in these discussions told me “When you shut down one laboratory you have a mad faculty member; when you shut down a second, you have an environmental management system.”

[ao]Faculty do notice when their colleague’s labs are shut down…

[ap]In what way is the system “working well”? What mission is being served by the way the origional system was structured?

[aq]for compliance in their lab

[ar]This seems contradictory to earlier comments that researchers are responsible for their own compliance

[as]The government does not believe this. They believe that the president of the institution is responsible for instituional compliance. The president of the institution may or may not believe that

[at]However, since the presidents turn over much more quickly than faculty, faculty often outwait upper admin interest in this issue

[au]I hear this a lot, but then I have to wonder what the word “responsibility” means in this context. The president of my university has never been to my lab, so how would he be responsible for it?

[av]The subtext I see here is that it would be awfully expensive to have the enough staff to do this

[aw]A ‘dish best served’ by faculty peers rather than university admin staff or legal.

[ax]I don’t believe faculty will have these conversations with each other due to politics. We can have someone they respect make assessments by doing a myriad of approaches including having industry people come visit.

[ay]Or in other words, who is willing to break be the bearer of bad news?

[az]I like this. When I have discussed having issues in my own lab with others outside of my institution, so many respond with “tell the head of the department.” And I’m surprised that they don’t seem to realize that this is fraught with issues – this person’s labs are right across the hall from mine – and this person visits his lab far more often – and this person has seen my lab – he already knows what is going on and has already chosen to “not see it.” Now what?

[ba]Building upon more that “head of department” does not actually mean higher in the hierarchy of authority. These people are still colleagues at the same level of authority most of the time.

[bb]I remember hearing during the research process for the NAS report on Academic Lab Safety, that Stanford Chem had an established structure for true peer inspections of other faculty spaces and in some instances risk assessment of new research efforts.  From what I recall that was successful and implemented as that was the expectation.  So maybe it just needs to be the expectation, rather than optional.  Another alternative is you staff the administrative side with folks that have research experience, then the message may be better received.

[bc]I really like that idea – that faculty would be engaged in the risk assessment of new research efforts. You are right that it would have to be established as a norm at the university – not as optional work – or work that goes to a committee that virtually no one is on.

[bd]The biosafety world is run by a faculty involved oversight committee for grant proposals, for historical funding reasons. My experience is faculty are very reluctant to approach this process critically as peer review, but it does put biosafety issues on the agenda of the PI writing the grant

[be]Interesting that this group is left out.  As an EHS employee I see an opportunity to be the consistency and impartiality across departments.  Also can disseminate best practices that are implemented in some labs

[bf]Absolutely, and serve as a valuable mechanism for knowledge transfer.

[bg]Yes, delegate task responsibility but not ultimate liability.

[bh]Yes, we have a form we have for the delegation of tasks to the Lab Safety Coordinator (LSC). Ultimate responsibility at PI level, but allow them to delegate tasks using this form.

[bi]That is great that its formally documented!

[bj]Lawyers believe this. Safety professionals not so much.

[bk]Should this responsibility be part of the on boarding process for new laboratory workers in general? I would note that “Eastern U” has had problem with grad student and postdoc misbehavior in the lab, including criminal acts against lab mates. These are handled by police rather than EHS, but EHS is often involved in assessing the degree of the problem.

[bl]Herein lies one of the problems with the unorganized academic hierarchy where PI’s fall into. While systems that improve safety should always attempt to be non-punitive, at the end of the day the repeat offenders still have the freedom to not comply. 

This can become problematic if that particular faculty member has a more influential role and position in their department.

[bm]I agree with you that in this case study faculty may have the freedom not to comply until the situation escalates. It is not the case that this is always true. Some universities have the authority to shut down labs. There may be a mad faculty member, but it is a powerful statement to the rest of the faculty to get their acts together.

[bn]The thing about this, thought, is that shutting down a lab is very nearly the “nuclear” option. I would imagine it would be incredibly problematic to determine who deserves to have their lab shut down and who doesn’t. And what has to occur before the lab is allowed to reopen.

[bo]The other problem this presents is the impact of a lab closure on “innocent” grad students in the lab and colloborators with the lab, both on campus and externally. These factors can make for a very confusing conversation with PIs, chairs and deans, which I’ve had more than once

[bp]In my experience, the only time admin and safety committees have even considered lab shutdown is when there’s outright defiance of the expectations and no effort made to resolve identified safety and compliance issues.  I’m not sure I’d considered those criteria as being a ‘nuclear’ option, seems more like enforced accountability IMHO.

[bq]I feel like what you just described is what I meant by “nuclear” option. Their doesn’t seem to be anything between “innocuous notice” and “lab shutdown.”

[br]Agree on the point as well about graduate students being the ones who actually “pay” in  a lab shutdown. If a faculty member is tenured, then they are getting their paycheck and not losing their job while their lab is shutdown. However, it directly harms the graduate students in no uncertain terms.

[bs]@Jessica Then it sounds like the institution lacks some form of progressive discipline/resolution structure if there’s only one of two options.  Sadly some of that (progressive discipline structure) needs to be created with the involvement of HR to ensure labor laws and bargaining unit contracts aren’t violated.  But there absolutely needs to be a spectrum of progression of options before lab shutdown is all thats left.  And yes, I agree that the graduate student(s) bear a disproportionate penalty at times in the event of a lab shutdown.

[bt]Is this after having the faculty sign on to the program through the registration process?

[bu]I would say “hoped” here rather than “assumed”

[bv]Why no documentation of the informal interactions/feedback?  Or was it optional?  From a regulators perspective, if it isn’t documented it never happened.

[bw]Good point.  The accountability system could take the informality into account but if a lab racks up a bunch of minor, informal infractions it is probably indicative of culture.

[bx]I also worry that not having it documented could lead to the ability for the feedback to be “forgotten” or denied as to having happened in the future if a larger infraction occurs.

[by]This is something that was discussed as problematic in the paper. If it is undocumented, no one knows just how many warnings an individual has had. It is also one of the problems with solely relying on researchers watching out for each other. You don’t know how many times a convo was had and weather the issue was fixed OR the person just got tired of correctly their colleague.

[bz]We are trying a pilot program using this approach. A EH&S building sweep to build a relationships with labs and let them know we don’t just visit to document non-compliance. We are not sure what we’ll document, since these are friendly visits.

[ca]Have you read Rosso’s paper about the SPYDR program they do at BMS? I thought it was a very interesting approach that could be adapted to the academic environment.

[cb]https://drive.google.com/file/d/1oCu1q6xqc12PpArTaDQ3lmlIvk-zpFbk/view?usp=sharing

[cc]Thank you Jessica!

[cd]What I particularly like about the feel of this approach is that they are having management intentionally visit labs in order to ASK THE RESEARCHERS what they feel like the problems are. This speaks to me because, as a graduate student, I was frustrated with EHS inspections in which they were focused on their checklist and minor infractions that didn’t matter while they walked right past really problematic things that were not on the checklist – and I would’ve much rather been encouraged to discuss those issues!

[ce]@Jessica Great point about inspectors being too ‘tunnel visioned’ on their compliance checklist and not able to be truly receptive to bigger issues, whether observed or vocalized during (collaborative) discussion with the research group members.

[cf]Is this a supervisor of the lab or to the lab?

[cg]There was a PhD dissertation at “Eastern U” that described how this was negotiated and the impact of those negotiations on the design of the computerized database that was used to implement the system. It’s a fascinating story to read.

[ch]Are you able to quickly find a link to share here?

[ci]That would be great to see!

[cj]This seems very strange to me. Was any additional information provided about the substantive changes that were made that could’ve potentially justified this type of response?

[ck]In working with the EPA, an agreement we were working on was almost scuttled by too many commas in a key sentence. It took 6 months to resolve it because sets of lawyers were convinced that those commas changed the meeting entirely. I couldn’t see the difference myself

[cl]The way through this was for the “clients” (techmical people from the school and the EPA) to get together without the lawyers in the room and come to a mutual understanding and then tell the lawyers to knock it off

[cm]Hardly fair to hold PIs accountable but give the university a pass on providing a safe work place.  Although since this is outside the “academic freedom” morass it should be easier to address

[cn]Or are expensive and inappropriate for the PI to do.

[co]I have some of the same problems with facilities

[cp]I am disappointed that this is not a bigger part of this paper. Faculty are often characterized as “not caring” when I think the situation is much more complex than that. As a graduate student trying to get problems fixed, I can certainly attest to how difficult this is – even to know who to go to, who is supposed to be paying for it, who is supposed to be doing the work – and while I am chasing all of that, I am not getting my research done. It can be atrocious to try to get responsiveness within the system – and I can see why it would be viewed as pointless to chase by researchers at least at some institutions.

[cq]As an EHS staff member I can see a cultural rift between the groups.  Comes down to good leadership at the top which is in short supply.  Faculty and staff all work for the same university…

[cr]@Jessica I agree that getting resolution on infrastructure issues as a graduate student can be a huge time sink and at times even ineffective.  That’s where having an ally/collaborator from the professional staff or EHS groups can be invaluable. They often know the structure and can help guide said efforts.

[cs]I would be interested in what percentage of the faculty had this attitude. In my experience, it represents about 20% of an institutional faculty population; 20% of the faculty are proactive in seeking EHS help; and the remaining 60% are willing to go with the departmental flow with regards to safety culture.

[ct]” Faculty and staff all work for the same university…” and work on the same mission, although in very different ways. 

Another challenge is that many faculty don’t have a lot of identification with their host institution and often perceinve they need to change their schools in order to improve their lab’s resources or their personal standing in the hierachy

[cu]And if we don’t have experts in actual scientific application looking at the problems or identifying problems then the system is broken. A lab can look “clean and safe” but be filled with hazards due to processes. I believe a two tier audit system needs to be in place: First tier compliance Second tier: Safety in lab processes

[cv]YES! I have often been frustrated when having discussions in the “safety sphere” on these issues. By coming at it from the “processes” perspective, the compliance rules make a lot more sense.

[cw]Reliance on point-in-time inspections can be misleading.  My group (EHS) does this for all labs across campus.  It is a good start- ensures the lab space is basically safe.  But what is missed is what happens when people work in the lab (processes).  In a past life, different industry, I worked with a group to develop best practices for oil spill response.  If response organizations subscribed to the practices they had guidelines on how to implement response strategies.  Not super prescriptive, but set some good guardrails.  Might be useful here?

[cx]Experts in process safety are often soaked up by larger industries with much more predictable processes. The common sense questions they ask (what chemicals do you use?, who will be doing the work?) are met with blank stares in academia

[cy]I think this is a profound observation which leads to the success or failure of this kind of approach.

[cz]…this is also foreshadowing for some of her other papers on this case study :).

[da]Spooky!

Anaphylaxis Induced by Peptide Coupling Agents

On WEDNESDAY, March 24 the CHAS Art and State of Safety Journal Club discussed the paper “Anaphylaxis induced by peptide coupling agents: Lessons learned from repeated exposure to HATU, HBTU, and HCTU.” 1st author Kate McKnelly led this discussion on this paper.The full paper can be found at this link: https://pubs.acs.org/doi/10.1021/acs.joc.9b03280. Comments on the table read are found below.

INTRODUCTION After working for years with peptide coupling agents HATU, HBTU, and HCTU[a][b],[c][d] a twenty-seven-year old female researcher (K.J.M.) developed life-threatening anaphylaxis. She began working with the aforementioned peptide coupling agents in May 2015. During the next few years, she worked heavily with these uronium peptide coupling agents. In March 2016, she began developing allergy symptoms of sneezing, coughing, and a runny nose. During the next couple of years, her symptoms progressed[e] to the point of anaphylaxis. These coupling agents are especially insidious because a severe allergy developed slowly over the course of three and a half years of exposure to the point of a life-threatening incident.

About one and a half years after beginning to work with these coupling agents, she noticed she had allergy symptoms when she weighed out coupling agents and Fmoc-protected amino acids for use in solid-phase peptide synthesis. In July[f][g] 2018, she began suspecting she was becoming allergic to coupling agents because she experienced sneezing and a runny nose immediately after spilling HCTU onto her glove. It was not until September 2018 that she experienced her first brush with allergy-induced anaphylaxis. She was at the weekly research group meeting in a seminar room down the corridor from the laboratory, and she began wheezing slightly. The wheezing was fleeting and went away after the group meeting when she left the building. A couple of weeks later, she started wheezing as she drove two labmates home. This time, the wheezing was louder—her labmates could also hear it—so she took the antihistamine diphenhydramine (generic Benadryl) to stop the reaction. Within 20 min, she could no longer hear wheezing.

Finally, in late October 2018, the researcher sat down at her desk in the lab and almost immediately began coughing, sneezing, feeling tightness in her throat, and subsequently wheezing. She attempted to remove herself from whatever she was exposed to in the lab and moved down the hallway to an office outside the lab. Once there, she continued reacting, and the wheezing progressed until she could hear a rattling wheezing sound when breathing through her nose. She immediately left the lab to obtain diphenhydramine. As[h] she exited the building, her symptoms stopped progressing. An hour after taking diphenhydramine, the wheezing subsided completely. In hindsight,[i][j][k] she should have called 911 for emergency medical help, because a throat-closing anaphylactic reaction can occur quickly, sometimes so quickly that there is barely enough time to avoid fatality.

How did this happen? How could this have been prevented?[l][m][n][o][p][q][r] We have been tackling these questions since the incident occurred. We provide this case study as a cautionary note about the potential hazards from chemical exposure that can develop over time and sneak up on a researcher. We first sought to determine what caused this anaphylactic reaction to occur. We then adjusted how peptide coupling agents were handled in the lab to minimize exposure and attempt to prevent other researchers from becoming sensitized as well. In sharing our experience here, we hope to contribute to the widespread implementation of standard operating procedures for peptide coupling agents and protect others who work with them.

LITERATURE SEARCH

We first scoured the literature for information on sensitization by peptide coupling agents HATU, HBTU, and HCTU and Fmoc-protected amino acids. Information regarding sensitization varied among chemical supplier material safety data sheets (MSDSs). HATU is reported to cause skin, eye, and respiratory irritation and is denoted by an exclamation mark hazard symbol. HBTU is reported to cause respiratory sensitization. HCTU is not reported to have known toxic effects. [s][t][u][v][w][x][y]We found only nine published cases of sensitization by the uronium coupling agents HATU and HBTU and none by HCTU or by Fmoc-protected amino acids. The first reported case implicating uronium coupling agents as chemical sensitizers came in 2003. Yung et al. described a researcher at a university that first developed eye irritation, a runny nose, and coughing (rhinitis) after weighing HBTU. Her symptoms progressed over the course of 2 weeks, developing into chest tightness, a cough, and skin rashes (urticaria) and culminating in sore, red itchy eyes, coughing, sneezing, and urticaria within 1 h of being in the laboratory. The researcher was tested with skin prick tests for allergies to HATU, HBTU, and HCTU because all chemicals were present in the lab. She tested positive for sensitivity to HATU and HBTU but negative for HCTU and various Fmoc-protected amino acids[z][aa]. Because the researcher did not exhibit sensitivity to HCTU, the authors suggested that this uronium coupling agent may be a safer alternative for widespread use. Other publications report that HCTU is nontoxic and nonirritating.

The other published instances of chemical sensitization to uronium coupling agents have involved HBTU exclusively. In 2003, another researcher, this time in a pharmaceutical plant, developed occupational rhinitis and bronchial asthma from HBTU and TBTU, which is identical to HBTU except for the counterion. The allergies were confirmed by positive skin prick and nasal challenge tests. In 2005, Bousquet et al. reported a chemistry researcher who developed allergic rhinitis and dermatitis on the hands and fingers which then progressed over the course of a year to include his face, upper back, neck, elbows, and ankles. The authors confirmed the researchers’ sensitivity to HBTU through patch testing and found he was not allergic to dimethylformamide, dichloromethane, acetonitrile, triisopropylsilane, HATU, or BOP. From 2006 to 2010, six more instances of chemical sensitization from HBTU were reported with similar respiratory and skin reactions. One example, in 2006, involved a university researcher developing an anaphylactic response to HBTU over the course of three years, similar to the case reported in this paper. All of these examples were published in allergy and other medical journals, which are not generally read by researchers who use peptide coupling agents.[ab][ac][ad][ae][af][ag]

EXPERIMENTAL CONFIRMATION

We suspected that peptide coupling agents caused K.J.M.’s allergic reactions. An allergist and clinical immunologist (W.S.) tested the researcher for allergies to a panel of over 60 allergens by skin prick tests to determine if common environmental allergens accounted for her anaphylaxis. She was only slightly allergic to two environmental allergens, but not so allergic that they would cause anaphylaxis. Skin prick tests were then performed to determine if she was allergic to HATU, HBTU, HCTU, DCC, Fmoc-leucine–OH, Fmoc-phenylalanine–OH, and Fmoc-asparagine(Trt)–OH. The researcher worked with most of the canonical amino acids in their Fmoc-protected forms, so three were chosen as representative amino acids. DCC was included as a control because it is a notorious sensitizer that the researcher had never previously worked with.

As hypothesized, the researcher had severe positive allergic reactions to uronium peptide coupling agents but only mild responses to Fmoc-protected amino acids. The coupling agents HATU, HBTU, and HCTU all caused the formation of large hives, comparable in size to those formed by the histamine positive control. DCC did not cause any reaction, which is not surprising as the researcher was never previously exposed to DCC. Fmoc-leucine–OH, Fmoc-phenylalanine–OH, and Fmoc-asparagine(Trt)–OH all elicited minor reactions and produced hives much smaller in size than the histamine positive control. The lack of a strong reaction to the Fmoc-protected amino acids is not surprising, as they are not known chemical sensitizers.

ANALYSIS

This paper serves as the first reported case of chemical sensitization resulting in anaphylaxis from three common uronium coupling agents: HATU, HBTU, and HCTU. The sensitized researcher (K.J.M.) can no longer work in her research lab. She cannot go into the building where the lab exists; the hallways, rooms, and common spaces all cause her to react, first with a runny nose and throat tightness and then with wheezing.[ah][ai][aj][ak][al][am] Her allergic response is so severe that she risks anaphylaxis whenever exposed to these coupling agents, and she now must carry an epinephrine autoinjector (generic EpiPen) as a safety precaution whenever she is near researchers actively working with peptide coupling agents. She has become sensitive to colleagues who have been in her research laboratory and must be careful to ask them to change their clothes and in some cases wash or cover their hair to prevent her exposure to the pervasive coupling agents. These events prompted the research group as a whole to re-evaluate how the group handles peptide coupling agents and to change their standard operating procedures to prevent group members from becoming sensitized to coupling agents.

Chemical sensitization causes an immune response in the form of reactions as mild as seasonal allergy symptoms, like rhinitis, and as severe as dermatitis and anaphylaxis. Many[an][ao][ap][aq][ar] chemical sensitizers are chemicals that can modify human proteins. All reactive compounds that can modify proteins should be treated as potential sensitizers unless they are known with certainty to be safe. In spite of this hazard, most researchers do not treat compounds that can react with proteins with proper precautions. Peptide coupling agents are prime examples.

Peptide coupling agents induce the formation of an amide bond from the reaction of a carboxylic acid group with an amine group. The coupling agents react with the carboxylic acid and activate it for subsequent attack by a nucleophilic amine. After the amine reacts with the activated carboxylic acid, an amide bond forms. Human proteins display multiple carboxylic acid groups (e.g., glutamic acid and aspartic acid) and amine-containing groups (e.g., lysine) in the form of amino acid residues at protein surfaces. The reactivity of coupling agents toward amino acid residues primes them to cause sensitization by modifying proteins in the human body.

The carbodiimide coupling agent DCC (dicyclohexylcarbodiimide) is a notorious chemical sensitizer with a long history of causing sensitization. DCC was first reported as a peptide coupling agent by Sheehan and Hess in 1955. It quickly grew in popularity due to the ease with which it induced the formation of peptide bonds. Soon after its introduction, a publication reported that DCC caused three cases of allergy-induced skin rashes (contact dermatitis) in 1959. Zschunke and Folesky subsequently reported seven cases of DCC-induced contact dermatitis in a pharmaceutical plant in 1975. In 1979, two independent cases of DCC sensitivities were published in the journal Contact Dermatitis. In one case, a lab worker developed a blistering eruption rash on his hands and forearms, and in the second case, a research chemist developed a rash over nearly his entire body that persisted for five days before he was hospitalized. Since 1979, 11 more cases were reported of DCC causing similar skin contact allergic reactions. In one of these cases, the researcher also developed sensitivity to diisopropylcarbodiimide (DIC) and suffered a vesiculopapular rash on his cheeks and the backs of his hands from both DCC and DIC. The authors of each of these reported cases confirmed sensitization with skin patch tests.

The many reports of DCC sensitization lead to toxicology testing to confirm the hazard it poses to human health. DCC and DIC were nominated for testing by the National Toxicology Program in 1993. Hayes et al. then tested DCC and DIC on the skin of mice for their potential as sensitizers and in 1998 reported sensitization at concentrations as low as 0.006% (w/v) for DCC and 0.3% (w/v) for DIC. Another report in 2002 confirmed DCC and DIC as sensitizers to mice when examining the mechanism of DCC- and DIC-induced chemical sensitization. In 2011,[as][at][au] Surh et al. further characterized DCC and DIC for toxicity and carcinogenicity and determined that both DCC and DIC caused skin sensitivity in rats and mice, but only DCC exhibited carcinogenicity. The detrimental health effects of the peptide coupling agents DCC and DIC are worrisome for anyone who handles them.

HATU, HBTU, and HCTU were developed between the late 1970s and the early 2000s and are now widely used as coupling agents in peptide synthesis. Despite being implicated as sensitizers in at least ten reported cases, including the current one, they have not been rigorously tested for their immunogenic and toxicological properties.

LABORATORY ACTION PLAN

In response to the sensitization of K.J.M., we developed standard operating procedures to handle HATU, HBTU, and HCTU more safely. We found guidelines for handling sensitizers, which recommended never opening sensitizers outside of a fume hood and minimizing exposure if handling them outside of a fume hood. Our lab dedicated a portion of a fume hood to weighing out coupling agents and amino acids and placed a balance in the hood[av].[aw][ax][ay] A waste container was placed in this fume hood as a receptacle for weighing paper and other materials contaminated by coupling agents or Fmoc-protected amino acids. Coupling agents and amino acids are transferred into sealable containers before removal to individual researchers’ fume hoods. As with other standard operating procedures for handling hazardous chemicals, personal protective equipment (PPE) in the form of a lab coat, eye protection, and disposable gloves [az][ba][bb][bc][bd]should be worn at all times when handling coupling agents. We anticipate that these procedures will reduce the risk of other researchers becoming sensitized in the future.[be][bf][bg][bh][bi][bj][bk][bl][bm][bn][bo]

Any research lab that performs peptide synthesis should take extra precautions to avoid exposing researchers to coupling agents. The Supporting Information provides a standard operating procedure to handle peptide coupling agents more safely in the research laboratory by minimizing exposure[bp].

CONCLUSION

Peptide coupling agents, regardless of whether they are carbodiimide reagents, uronium reagents, phosphonium reagents, etc., all perform the same chemical function of facilitating amide bond formation and therefore can all covalently modify human proteins. If a chemical can modify human proteins, it is a prime candidate as an immune sensitizer, even if it is not a known sensitizer. We hope that our laboratory’s experience of the hazards of HATU, HBTU, and HCTU will serve as a cautionary note to those working with any peptide coupling agents.

[a]I see that PF6- is frequently the counter ion. Was this tested as an allergen?

[b]In second paragraph of the literature search part they mention a researcher who became sensitized to both HBRU and TBTU, which has a different counter ions, so while it sounds like the counter ion wasn’t tested for specifically, it doesn’t seem to be the culprit here. This makes sense since the counter ions do not partake in the coupling reaction and only has a slight influence on coupling efficiency

[c]What is the best practices to handle these coupling agents? Tilak

[d]This is discussed towards the end – also if you are interested in the protocol they shared, that is in the SI if you follow the link to the paper.

[e]Why it is important to pay special attention to unusual symptoms.

[f]and report symptoms

[g]Reporting symptoms early is also important for legal (i.e. Workers Comp) reasons

[h]Another scenario I have seen a lab worker suffer was a techinician in a electron microscopy lab. She accidently brushed her hand against a container of an epoxy they used to set up samples for the microscope and didn’t think anything of it. The next day when she can to work, her fingers started itching and keep getting worse for a week. She eventually had to leave that job.

The difference from this report is that it was a single exposure that led to the sensitization rather than repeated exposure over time.

[i]Why it is important to keep an eye on our colleagues as well and ask questions. As wild as this sounds, it is so easy for us to dismiss our own symptoms as minor even if we would be incredibly concerned about those same symptoms if we observed them in another person!

[j]A lab tech reported to me a situation in which she and a colleague were transferring insect samples between killing jars which contained 70% ethanol in the open lab. After about half an hour, she noticed that her partner was getting goofy. She then realized that they were both getting drunk from breathing the ethanol that was evaporating as they did the transfers. It’s not likely that she would have noticed this without seeing that her partner was being affected.

[k]Really good point. Also, would she have noticed her own symptoms if she had been working alone? Could’ve just interpreted this as tiredness.

[l]Would a system where researchers can report any symptoms as soon as they occur would have prevented it from getting worse?

[m]I suppose it depends on whether or not people use the system, how easy it is to use, who they are reporting to – as well as how seriously the person themselves takes their own symptoms.

[n]There are many places the someone can be exposed to allergens and the pattern they describe in the paper is more evident in retrospect than as it occurs. Animal care workers have prospective monitoring for allergies to the mice, etc. they work with, but that doesn’t prevent many from having to retire from this profession due to allergies acquired over time

[o]When I was working at the USDA, I learned of multiple people who developed allergies to moth scales over time due to a protocol in regular use that essentially required them to gently suck moths into the tip of a tube in order to move them. Gross to think about now (I never did this), but it was standard practice for a long time and many still do it this way.

[p]I have seen similar techniques outside of the chemistry lab setting. I haven’t had any lab person defend mouth-pipetting of chemicals to me since about 2005; perhaps it is a past practice, at least in academia? I’d like to think so.

[q]I knew people doing this when I was working there up through 2016!

[r]I’ve never actually seen anyone mouth pipette chemicals, so I believe the campaign against that has been a bit more effective.

[s]So “looking up the SDS” provided no information in this case.

[t]GHS SDSs should include information about sensitization, but I suspect that a chemical supplier wouldn’t add that content to a SDS based on “anecdotal evidence”. I suspect that there would need to be a published peer review study before the information was added to a SDS.

[u]Well – that is my point. We are here working on the cutting edge, but official documentation like SDSs will be necessarily behind. I cringe every time a grad student tells me “well I just looked up the SDSs and carried on” w/o having talked to ANYONE ELSE about their projects.

[v]Toxicology studies will always lag behind the introduction of new reagents. Maybe it would help to have a recognition of what classes of chemicals could be potent sensitizers and apply the precautionary principle to those.  Here’s an example: “First, a chemical with dermal sensitization potential has to be able to penetrate into the skin—meaning it must have a low molecular weight, usually less than one kilodalton—and induce or elicit an immune response by being chemically reactive and electrophilic with skin proteins.”  (from: https://synergist.aiha.org/201911-dermal-sensitizers)  I understand that the above is broad, but it’s a start.  Peptide coupling agents certainly fit the bill.

[w]It is interesting that in most cases there was little allergic reaction to HCTU, but much more severe reactions to HATU and HBTU. I wonder if once one is sensitized to the latter there is an allergic reaction to HCTU? This was the case in this study.

[x]It is also so hard to know how many people experienced these symptoms and did not connect them to exposure to these agents – so they have effectively gone unreported.

[y]I think form a chemical standpoint that would make sense. HCTU is essentially HBTU with an added chlorine, so it’s not a stretch to believe that the immune system recognizes both of these reagents in the same manner

[z]Anyone doing work with coupling reactions for peptide. peptide-mimics ought to have training on sensitizers since most of these are amines which cause sensitization

[aa]Who determines this? When I sent this article to our chemical safety specialists, they were surprised to see it! As were the members of the 1 lab I know in our building that works with these.

[ab]Another frustration with “the literature.” Safety information about chemicals doesn’t seem to have a home – it is scattered throughout so many different places that it can be easily missed by the people who need to know the information. Case in point: This case study was published in the Journal of Organic Chemistry!

[ac]These should have been posted in C&EN. That was often done during that time period as a way to alert the general chemical community. Part of the other problem is that many biochemists don’t read ACS publications.

[ad]https://cen.acs.org/safety/lab-safety/Peptide-coupling-agents-cause-severe/98/web/2020/01

[ae]It took until 202 for this to come out in C&EN?

[af]2020

[ag]While it made the rounds at the time, there are plenty of undergrads and grads working in labs who aren’t reading C&EN. C&EN is a pretty specialized resource. When I was working in a molecular genetics lab, I hadn’t even heard of C&EN.

[ah]Is there that much of the sensitizer floating around the building? Why weren’t they working with this in the hood???

[ai]Hoods are not black holes. For example, when it comes to powders they can disrupt use of the material because of the air movement in the work area

[aj]We have seen similar reports in other settings. Usually anecdotal and not as clearly documented as this. Review the literature on “multiple chemical sensitivities”. I frequently have trouble with these reports as the claims seem very wild. However, we know that sub-picomol levels of agents such as we are discussing here can induce an allergic Rx in hyper-sensitive people.

[ak]Taysir shared a comment below on why these are difficult to work with in hoods.

[al]Agree with Ralph.  The appropriate engineering control for working with or weighing powders are enclosures with HEPA filtration design for that purpose, not fume hoods.

[am]Like Neal, I remember the emergence of the idea of Multiple Chemical Sensitivies and how much this confused the EHS world. There was a weird mix of science and pseudo-science that we were required to react to in addressing situations both in the lab and outside it

[an]A question this paragraph raises for me as a trainer is whether I should call attention to the chemical properties of the material the way this article does or whether I should alert people to the symptoms that they should be alert to as warning signs. The OSHA lab standard suggests training peiople on “signs and symptoms” rather than focusing on chemcials

[ao]Would it be better to do both? If one knows the symptoms but not the agent, then there could a wide range of things that could lead to these symptoms, even some not in the lab. It seems like there really needs to be causality established.

[ap]I would also think that this would be considered when discussing the design of experiments and lab protocols. You don’t want to wait until someone is having symptoms to do something about it.

[aq]I feel like the safety aspects of the research carried out in the lab doesn’t get discussed enough , even in group meetings. It’s only after something terrible has happened. I’m wondering how this culture can be affected.

[ar]Monica – that is a fundamental point of the increased interest among grad students in safety. As they move on to their careers they will become the safety leaders.

[as]1955 to 2011 – it is pretty wild to see how long it can take for a regularly used chemical to be recognized for the harm it can cause. This is important to keep in mind as we work on the cutting edge of scientific experimentation!

[at]Part of the problem, again, may be in the communication forums used during that time. I wonder if some of the more common social media will make this easier now…

[au]I may not be following the correct social media, I don’t see a lot of lab procedure information there. Where would one look for these stories?

[av]The measures taken are pretty basic – and involve things that are now available in virtually ALL labs. This is another important consideration.

[aw]Is there a process for decontaminating the balance and hoods in place? Can the agents be deactivated by other chemicals?

[ax]I believe bleach will not work with these chemicals, may be cleaning by ethanol is the best solution

[ay]We generally use methanol followed by water

[az]Since some of the agents are known to cause respiratory distress, would a face mask or any type of respiratory protection help?

[ba]We have been using N95 masks when working with these reagents. I don’t have any data to support this practice though

[bb]This will need fit tested

[bc]Yup, DEHS at my institution provides that testing

[bd]I suspect that the allergeric reactions could be triggered by skin exposure and other environmental contamination as much as respiratory exposure. The NP95 masks will help by avoiding cross contamination from your hands to your face, which may be helpful

[be]As a result of this paper, I convinced my group to buy a new balance to keep in the hood for weighing out HCTU and to follow the suggested protocol. The issue we ran into is that due to the hood flood it takes a very long time for the balance to tare. Since our peptide synthesizer is cartridge based we have to weigh the coupling reagent individually for each amino acid. As a result, it now takes days instead of hours to finish weighing all the amino acids. Many researchers in our lab have instead elected to wear N95 masks when weighing the coupling reagent instead of using the hood balance

[bf]That is interesting. We didn’t have any hoods in my lab with balances in them, but I have used them in other labs and had no issues with them taring. I’m wondering now what made the difference.

[bg]Probably due to our hoods being ancient to be honest. I am not happy about this solution, but I understand why people go for it

[bh]generally it is difficult to weigh powders inside the chemical fume hood due to air flow, however, crystalline material is ok

[bi]Housekeeping is very important to handle such chemicals in the lab

[bj]It also takes some time and practice to get used to working with powders and crystalline materials that I don’t think most students really get until they are working in a research lab. Working a hood does add to the complexity of this.

[bk]The lab I worked in in the 80’s had ventilation weighing station for working with silca and asbestos dusts. It takes a very careful ventilation design for sensitive balances to be able to operate in a wind current. We also had a special table which was very heavy to provide a steady surface for the balance.

[bl]A weighing enclosure will also work for this purpose

[bm]I agree with Jessica about the practice/ or hands-on on weighing

[bn]We just use a three side piece of acrylic around the scale and have no problems. As an alternative, you could teach people in the lab to weigh out chemicals using analytical subtractive techniques. This is the fastest method by far. (weigh out your vial, add some chemical to the vial in the hood, put the lid on and weigh again, add solvent to desired concentration)

[bo]Was working only with solutions considered? I.e., upon receipt of a new bottle of coupling agent, dissolve it in a solvent to a known concentration, then for each use, volumetrically measure what’s needed and then dilute? Wet methods are excellent for controlling exposures to dusts/particulate. Look at construction sites during large-scale demo…you usually see a big hose running to minimize dust.

[bp]We use a synthesizer often. All chemicals are weighed out and diluted in the hood. The sealed bottles are then transferred to the synthesizer. A tube is then use to carry any escaping vapors back to the fume hood.

ACS Webinar: Community Protection Strategies in the Covid Era

Thursday, August 13, 2020 at 2-3pm ET

Speakers: Robin Izzo, Princeton University and ACS CHAS; Frankie Wood-Black, Sophic Pursuits
Moderator: Ralph Stuart, Keene State College and ACS CCS

Register for Free! at https://www.acs.org/content/acs/en/acs-webinars.html

What You Will Learn

  • Advantages and challenges of using personal protective equipment for community protection 
  • Best practices in physical distancing and peer coaching in the teaching and research settings 
  • Ventilation considerations in managing COVID concerns

Time for Questions and Answers will be included.

Co-produced with: ACS Division of Chemical Health and Safety ACS Committee on Chemical Safety

Fall 2020 CHAS at a Glance

The Fall 2020 ACS National Meeting will be held virtually. This page provides an overview of the CHAS activities associated with this meeting. You can download a printable version of the page here. Details about our technical program can be found at the ACS national meeting web site. You can also Visit the ACS Safety and Green Chemistry Booth near the exhibit hall entrance.

Our Divisional Executive Committee business meeting will be held 10 AM to noon Pacific time on Sunday, August 16. Contact us at membership@dchas.org for connection details and the agenda book.

SAFETY CULTURE IN THE MEDIA, September 2020 CHAS Chat

Thursday, September 10, 03:00 PM Eastern Time

Presenter: Ralph Stuart, CHAS Membership Chair.

Abstract: While safety culture in the laboratory setting is well described in several resources (for example, the National Academies publications Prudent Practices and Safe Science), its use in the larger culture is less clear. This paper will report on how mass media across the globe discuss safety culture, both as a management approach and at the practical level. The information provided will be based on about 9 months worth of review of mainstream media stories that mention “safety culture”.

July 9 CHAS Chat: Virtual Chemistry Teaching Labs

On July 9, 2020, Sammye Sigmann of Appalachian State University led a CHAS Chat discussion of resources for teaching chemistry labs in virtual or blended formats. The next CHAS chat on teaching labs under Covid conditions is scheduled for July 23 from 3 to 4 PM Central Daylight Time and will be on Back in the Lab Again – Managing In-Person Teaching Labs in the era of Social Distancing led by Frankie Wood-Black.

The powerpoint file Sammye used to lead the July 9 discussion is available to download. Answers to some of the questions asked in the chat session are available below. The video Sammye showed that provides an Introduction to the Laboratory Space is available on Youtube.

You can download the video we recorded of the session here. A rough transcript of the discussion is available to CHAS members to review; contact Ralph Stuart, the CHAS membership chair, at membership@dchas.org for more information about accessing this.

Q&A from the chat

From  Neal Langerman : Sammye – in the pre-pandemic world, what out of pocket expenses did a student incur for a semester of lab? How does this compare w/ the $40 fee?

While we dropped this platform due to changing our textbook, in the past we had used Hayden McNeil’s Sapling to deliver quizzes to students in lab. If I am remembering correctly, it was ~$25 per semester.  This company is good about allowing students a year to use their paid subscription in case they drop the course. They are doing this with the simulations as well.

We have not asked, but is some institutions, they may cover the costs.  I know that some places are covering the cost of kits.

From  Aliana Lungu : Anyone can share resources for intro Organic Chemistry Labs (techniques, etc.)? Thank you!

There should be some in the spreadsheet at the first link on slide 13 of the ppt.

From  Connie Fox : We’ve discussed virtual labs – what about managing in-person teaching labs with associated limitations of distancing and cleaning between sections?

I did mention that we are reducing density by half in our labs – even though technically, we are low density due to fire code at 50 sq ft per student.  Low density on top of high ventilation should actually make labs some of the lower risk spaces. Additionally:

  • Each student will be provided with a disposable mask for each f2f lab week that they put in the trash at the end of lab. Logic being that if their cloth mask is unknowingly contaminated, it will not be immediately washed.  To me, masks are different than their clothes that might be unknowingly contaminated because they are breathing through them.
  • We are reducing movement and shared equipment where possible. We also will put out one balance for 3 students to keep congestion in the balance room down. There will be more reagent bottles to use.  Possibly we will go to gloves on all experiments. We are fortunate to have tabletop ventilation which will help with congestion at the fume hoods.
  • No partner experiments.
  • I am not exactly sure about cleaning between sections.  It may be that the students themselves help with this. I am thinking 70% EtOH in spray bottles.

From  Jennifer Gile : Sammye, thank you for the video, that’s an excellent idea.  Our department is doing videos on using the balance, pouring acids, etc. We’re hoping this helps when students come face to face. 

The more I think about using videos as prelab assignments, the better I like it!

From  Jennifer Gile : My department asked two questions for this webinar:

How can we make socially distanced labs flow better? 

I think that some of the idea in the question on managing in person labs speak to this question.

How can we make virtual labs more authentic? 

I like the idea of combining delivery methods – Maybe student watch a video of a person titrating and then go to the simulation software.  If you are able to do synchronous delivery during a set lab time the instructor could actually do the titration while the students watch.  That way they could ask questions.

We did touch on this a bit when there was discussion about course delivery requiring more work for students.  I think that is just how it is going to have to be.

ACS Webinar: Meaningful and Concise Safety Summaries for ACS Publications

Now available at:
https://www.acs.org/content/acs/en/acs-webinars/professional-development/safety-summary.html

Safe research is good research. Scientists have an ethical obligation to disseminate safety concerns to downstream users of their research. As the premier journals for disseminating chemical research, ACS Publications has enacted a new requirement specifying that authors address safety concerns in work submitted for publication in all American Chemical Society Journals.

Our speakers:

Sammye Sigmann, Appalachian State University
Leah McEwen, Cornell University
Sara Tenney, ACS Publications

Join Samuella Sigmann of Appalachian State University and the ACS Division of Chemical Heatlh & Safety, Leah McEwen of Cornell University and the ACS Division of Chemical Information, and Sara Tenney of ACS Publications as they discuss the new chapter “Communicating Safety Information” from the 2020 ACS Guide to Scholarly Communication. During this webinar, you will discover how to develop meaningful and concise safety summaries for manuscripts based on risk assessment.