Tag Archives: mass spectrometry

Ridding the world of chemical weapons – The role of the analytical chemist

With the centenary of the start of the First World War reminding us of the way in which poison gases have been deployed in warfare to such devastating effect, what role do chemists today have to play in eliminating the continued risk to human wellbeing posed by chemical agents?

Chemicals as a weapon of war

Source:  http://pixgood.com/world-war-1-gas.htmlChemistry has always, and probably always will, be put to the service of those who wish death and misery on other humans. From poison arrows used since prehistory to the nerve agents deployed by terrorists and renegade governments in recent times, history is littered with examples of chemicals being used for nefarious aims.

But what is it about chemical warfare agents (or CWAs) in particular that causes such revulsion? It must be something deeply ingrained, because agreements to curb use of chemicals in this way isn’t a modern phenomenon – for example,France and the Holy Roman Empire agreed in 1675 to limit the use of chemical bullets, fully two centuries before The Hague Peace Conferences of 1899 required signatories to “abstain from the use of projectiles the object of which is the diffusion of asphyxiating or deleterious gases”. Not that this did much to stop their use in the First World War – the so-called ‘chemist’s war’ – where chemicals deployed by both sides,including mustard gas and phosgene, killed more than 90,000 men and left over ten times that number permanently disabled.

The resulting public outcry led to the Geneva Protocol of 1925, but although this prohibited use of chemical agents in war, it did nothing to prevent manufacture, which continued in secret right up to the 1990s, with ever more obnoxious chemicals such as the nerve agents sarin and VX – and ways of deploying them – being devised.

Since then, all but six nations have ratified the 1997 Chemical Weapons Convention, which aims to completely eliminate the possibility of chemical weapons being used. However, the threat of chemicals being used as agents of death remains – as illustrated by the actions of Saddam Hussein’s regime in the 1980s, by Japanese terrorists in 1994 and 1995, and most recently by Syria’s Assad regime in August 2013, where sarin was used to kill thousands.

Unacceptable consequences

But going back to my question, what makes chemical agents so uniquely unacceptable to us, even though they have killed a fraction of the many millions that have been killed in war and elsewhere by so-called ‘conventional’ means?

Perhaps it is the random way that chemical weapons are used – even today, farmers on the old Western Front are occasionally hospitalised or even killed by ploughing up unexploded ordnance from the First World War. In this regard chemical agents are like landmines and nuclear bombs, with their effects persisting down the decades to those not even born at the time of the hostilities.

On the other hand, perhaps it is their capability to cause lasting misery by permanently disabling rather than by killing outright that makes them unacceptable to us? My own great-grandfather was gassed in the First World War, to die 20 years later from the damage inflicted on his lungs by chlorine.

Both of these factors come into play, I believe, but perhaps more than these, it is the instinctive feeling that directing the line of scientific enquiry to devise ever more lethal ways to kill people, as well as being profoundly unethical, is fundamentally against the spirit of science itself.

So although the burden of responsibility for killing people with chemicals lies with politicians for getting us into wars, sponsoring the development of these weapons and sanctioning their use, chemists are hardly absolved of blame. Consider for a moment how many lives would not have been pointlessly wasted if the chemists of IG Farben and arguably well-intentioned but fundamentally misguided people like Fritz Haber and Gerhard Schrader had not used their scientific expertise to develop these chemical agents in the first place.

A poisonous legacy

chemical weaponsThat’s all in the past, you might argue, and the advent of international treaties against chemical weapons means that there’s no longer any danger of history repeating itself. The world has certainly changed, that much is true, but the legacy of chemical agents remains, and takes two forms. The first is the decades-long task of decommissioning historical weapons stockpiles and associated military hardware. The second task is to prevent terrorists from using chemical agents – an ongoing task that will likely need continued vigilance.

Chemistry, and analytical instrumentation in particular, is central to these two tasks, by helping to ensure that we detect chemical agents or their precursors before they can be used to cause harm. The work we do at Markes, in developing instrumentation and expertise for these applications, is therefore essential – and a small but significant contribution to ensuring that this centenary of the start of the First World War also marks the beginning of the end of chemical agents’ toxic legacy.

Further reading

This Toxipedia article and an article in The Week magazine briefly summarise the history of chemical weapons;this scholarly book chapter published by the US Army does so in considerably more depth.

You can read a history of chemical weapons and their disarmament at the website of the OPCW (Organisation for the Prohibition of Chemical Weapons).

This open-access article in the American Journal of Public Health covers chemical warfare and the medical response during the First World War.

This BBC article from January 2014 summarises knowledge of Syria’s chemical weapons stockpile.

VOCs in the news

As part of our regular sweep of news items in the analytical sciences, we often come across instances where volatile organic compounds (VOCs) are the focus of attention. We thought it might be useful and interesting to bring these together in a regular round-up – so here’s the first!

VOCs used to profile bacteria

VOCs emitted by cultures of ten strains of the diarrhoea-causing bacterium Clostridium difficile have been profiled using a custom-built headspace–TOF MS setup. Paul Monk and colleagues at the University of Leicester, UK, identified 69 VOCs and used them to distinguish between the strains – methanol, p-cresol, dimethylamine, ethylene sulfide, dimethyl sulfide and methyl thioacetate were most of value. The authors say that their method “may have utility as a rapid means of identifying C. difficile infection”.

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The case for phthalates as endocrine disruptors strengthens

The case for phthalates being endocrine disruptors has been further bolstered by research carried out by John Meeker and Kelly Ferguson at the University of Michigan, Ann Arbor, USA. They used HPLC–MS–MS to assess urinary levels of 13 phthalate metabolites – primarily oxygenated and singly-hydrolysed derivatives of phthalate esters. Significant reductions of testosterone were found in both men and women of different ages. Notably, substantial increases in metabolites of bis(2-ethylhexyl) phthalate (dioctyl phthalate) in 6–12-year-old boys were associated with a 29% drop in testosterone.

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Apple tightens regulations on hazardous solvents

Benzene and n-hexane have been banned from use as cleaning agents and degreasers in the final assembly process at 22 of Apple’s iPhone and iPad production plants. Their new Regulated Substances Specification additionally stipulates that “All cleaning agents and degreasers used at final assembly process facilities for the manufacturing of Apple products shall be tested for benzene, n-hexane and chlorinated organic solvent content at a certified lab prior to use in production”, and that permitted levels in the breathing zone of workers must be <100 mg/m3 (28 ppm) for n-hexane, and <0.32 mg/m3 (0.1 ppm) for benzene.

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US National Academy of Sciences concludes that formaldehyde causes cancer

The long-running debate in the US over whether formaldehyde is carcinogenic took moved forward in August with the publication of a report by the US National Academy of Sciences (NAS), where they conclude that the answer is “yes it is”.

This follows their critical 2011 review of the US EPA’s draft assessment of formaldehyde. Although the EPA document said that the evidence is “sufficient to conclude a causal association” between formaldehyde exposure and a variety of cancers, the NAS review said that there were “recurring methodologic problems” in this study.

The new document from NAS is their own independent assessment of the literature through to November 2013. Here they conclude that there is “sufficient evidence of carcinogenicity” in humans for nasopharyngeal cancer, sinonasal cancer and myeloid leukemia, and “convincing relevant information” that formaldehyde induces mechanistic events associated with the development of cancer.

These and other aspects lead the committee to conclude that “formaldehyde should be listed in the RoC [Report on Carcinogens] as “known to be a human carcinogen”.”.

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Is carbon tetrachloride still being emitted despite global ban?

Studies carried out by a team led by Qing Liang at the NASA Goddard Space Flight Center, Maryland, USA, have suggested that the observed slow decline of the ozone-depleting carbon tetrachloride (tetrachloromethane) can only be explained if it is still being emitted (see also this press release). This stands in contrast to the near-zero emissions estimate based on production and feedstock usage, a result of the regulations initiated by the 1987 Montreal Protocol.
Liang’s research, which is based on computer modelling of the concentration gradient between the northern and southern hemispheres, estimates that current unknown emissions are still about 30% of pre-treaty peak emissions. He says “it is now apparent there are either unidentified industrial leakages, large emissions from contaminated sites, or unknown CCl4 sources”.

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Plant volatiles – An area that keeps on growing

From time to time, I scour the scientific literature for interesting examples of where people have used thermal desorption in scientific research – which is great for highlighting some of the latest trends in how people are harnessing the power of modern analytical technology.

As an organic chemist (and former Publishing Editor of the journal Natural Product Reports), plant volatiles particularly interest me, and I’m always keen to see what’s been happening in this small but rapidly growing field. So here’s my choice of the most interesting papers from the last few years where our TD equipment has helped researchers to study plant volatiles.

David Barden

Insects know the best time for ripe pickings

Brown moth on a leafIt’s been known for some time that volatiles released by plants are used by insects to home in on their favourite food plants – see for example this BBC article on how the attractiveness of flowers to moths is affected by pollution. Now it’s also been shown that they can use this information to switch between different food sources according to the time of year.

Work by Adriana Najar-Rodriguez and colleagues at the Institute of Agricultural Sciences, Zurich, Switzerland, found that the Oriental fruit moth could tell when both peach and pear trees were in season, on the basis of the changing blends of volatiles emitted over the course of the year.

Using Markes’ UNITY-ULTRA automated thermal desorption system with GC–MS analysis, they found that a set of five aldehydes – hexanal, (E)-hex-2-enal, heptanal, benzaldehyde and octanal – were present in the volatile blends at the stages when the peach and pear trees were most attractive to the moths. The authors suggest that this information should be used when designing chemical attractants for female fruit moths.

Birds use volatile emissions to find lunch

In a fascinating piece of research, carried out by a team led by Luisa Amo at the Netherlands Institute of Ecology, Wageningen, Great Tits were found to be more attracted to caterpillar-infested apple trees than uninfested trees, even when they could not see the larvae or the leaf damage caused by them.

Great titThis is an example of a ‘tritrophic’ system – that is, one involving three levels of the food chain, and in essence an extension of the plant–herbivore system described above.Such systems are well-studied,* but this one is remarkable because it involves caterpillars being predated by birds, not other insects.

Despite this fundamental difference, the system studied appears to operate in the same way as normal – namely, the apple trees release a distinct set of volatiles when the leaves are attacked by the caterpillars, and these volatiles are used by the birds to locate the trees where a meal can be found.

To help confirm that the birds were using volatile cues, the authors enclosed tree branches with a polymer bag, and flushed the collected vapours onto sorbent tubes, with analysis by Markes’ UNITY thermal desorber and GC–MS. This analysis showed that the infested trees emitted more alpha-farnesene and dodecanal than uninfested trees, but less 1,2,4-trimethylbenzene, oct-1-en-3-ol, methoxy phenyl oxime, non-1-ene and and octan-3-ol.

The authors say that their findings are in line with previous studies on the use of smell by birds to detect prey, and indeed indicate that it may be more important than previously thought. They add that this area of research is exciting because birds eat far more caterpillars than other insects – so the potential benefits for pest control obtainable by breeding plants with enhanced volatile emissions may be correspondingly greater.

* The insect predators don’t always eat their prey straight away. Many studies of tritrophic systems look at parasitic wasps, which inject their eggs into living caterpillars. These caterpillars eventually suffer a grisly death by being eaten alive by the wasp larvae. See this BBC article for a rare example of research into this area being picked up by the mainstream media.

Volatiles help plants distinguish relatives from strangers

Research led by Richard Karban at the University of California, Davis, USA, has shed light on how plants might communicate with each other, by identifying specific compounds that correlate with the ability of neighbouring plants to repel insect herbivores.

SagebrushIn the study, which also involved scientists from Japan and Finland, portable dynamic headspace equipment was used to sample volatiles emitted from branches of 59 sagebrush plants in Sagehen Natural Reserve, California, USA. Volatiles were collected onto sorbent tubes from Markes and then analysed with Markes’ TD-100 automated thermal desorber, in conjunction with GC–MS.

They found that although volatile profiles differed greatly, individual profiles were generally dominated by either alpha-thujone or camphor, and that just two additional compounds (beta-thujone and cis-salvene) were sufficient to classify these two ‘chemotypes’ of sagebrush. Importantly, a separate experiment involving analysis of compounds from seed-raised plants showed that the chemotypes were highly heritable, 80% of ‘children’ having the same chemotype as their ‘mother’.

They then investigated the effectiveness of plant communication by collecting headspace from one plant and incubating it with another plant for 24 hours, before exposing the plant to the open air and so to insect herbivores. They found that the transferred volatiles were more effective at deterring herbivory in the recipient when the plants were the same chemotype. The authors suggest that this knowledge, together with the fact of chemotype heritability, suggests that plant volatiles could help plants to distinguish ‘relatives’ from ‘strangers’, so increasing the value of the information encoded by plant volatiles.

For more on this research, see this article on the phys.org website.

Raised CO2 makes Brussels sprout plants less attractive to aphids

Another piece of research by Adriana Najar-Rodriguez and colleagues at the Institute of Agricultural Sciences, Zurich, Switzerland, shows for the first time that plant adaptations to rising carbon dioxide (CO2) levels reduce the colonisation of plants by herbivorous insects.

In the work, Brussels sprout plants were reared inside climate-controlled chambers, and headspace volatiles collected passively over 6 hours onto Radiello sorbent samplers. The sorbent cartridges were then desorbed using Markes’ UNITY-ULTRA, with analysis by GC–MS.

They found that 10 weeks’ exposure to doubled CO2 resulted in a number of changes to the volatile profile – namely the appearance of (Z)-hex-3-enyl acetate, dodecane and tridecane, the disappearance of decanal and undecanal, and statistically significant reductions in 10 terpenoids, as well as a 50% fall in dimethyl disulfide.

At the same time, they used wind-tunnel choice experiments to investigate the preferences of winged cabbage aphids for the different plants, and found that the colonisation of plants reared under doubled CO2 was 26% lower than regular plants.

The authors also found that the rate at which carbon dioxide or water entered or left the leaf through the stomata (‘stomatal conductance’) was significantly reduced, and suggest that this, together with possible changes in leaf enzyme activity, could explain the reduction in volatile emissions. They then suggest that this in turn (perhaps in concert with additional cues such as changes in plant size) reduces the attractiveness of the plants to the aphids.

Dr David BardenWhatever the underlying mechanism, the authors say that this is one of the very few cases where changes in atmospheric CO2 have been shown to influence herbivory. They also point out that the changes in volatile emissions could have important ecological implications – such as the ability to attract predators of the herbivores (as I’ve described in Luisa Amo’s research above).

David Barden received his Ph.D. in Organic Chemistry from Cambridge University in 2004, and during his time as an editor at the RSC wrote news pieces for Chemistry World on various scientific topics. He is now Technical Copywriter at Markes International, where he draws on the expertise of his colleagues to explain how new thermal desorption and mass spectrometry technologies can be applied to analyse volatile organic compounds in a wide variety of situations.

Up close and personal – The chemicals used in personal care products


Recent research published in Occupational & Environmental Medicine carried out by Swedish scientists has again highlighted the exposure of hairdressers to potentially hazardous chemicals, this time of carcinogenic and sensitising toluidines in hair dyes and hair-waving (‘perming’) products.

This is just the latest in a long line of news stories about chemicals in personal care products – including methylisothiazolinone in suncream, triclosan in antibacterial products, and phthalates in nail polish,

The latest research, led by Gabriella Johansson at Skåne University Hospital in Lund, Sweden, has been picked up by a number of outlets, including Reuters, ChemicalWatch, SpectroscopyNOW, Medical Xpress, Nature World News and MedicalResearch.com. What the researchers found was that m-toluidine was present above the limit of detection in the blood of >97% of a cohort of hairdressers, personal dye users and controls (a total of 387 people), with the figure for  o-toluidine being ~50%. The chemicals were detected indirectly by GC–MS analysis of their adducts with haemoglobin, which is a good way of assessing average exposure because of haemoglobin’s relatively long lifetime.

This of course isn’t the first time that chemicals originating from hair dyes have raised alarm bells – p-phenylenediamine gained attention in late 2011 following a death from a suspected allergic reaction. The issue this time is that toluidines, unlike p-phenylenediamine, were banned from cosmetics in the EU in the late 1970s (as stipulated on page 18 of the original 1976 EU directive), so it is a surprise to find them in the blood at all.

Two facts uncovered in Johansson’s study seem to suggest that these haircare products are the source of the toluidines. Firstly, they found that o-toluidine concentrations increased with the number of hair-waving treatments, and that m-toluidine increased with the number of hair-dyeing treatments. Secondly, and more tellingly perhaps, they analysed a commerical (multi-component) hair-waving product and found both o-toluidine (up to 0.23 ng/g) and m-toluidine (0.15 ng/g).

However, the matter is not as clear-cut as it might seem, because, as the authors say “We evaluated the exposure … [for] hairdressers, consumers and controls, and found no overall significant difference.” Likewise, research last year led by Marie Thi Dao Tran at Copenhagen University Hospital found that “the prevalence and the severity of fragrance-related symptoms [of chemical intolerance] were similar in hairdressers and the general population”.

Such research points to a complex picture, with possibly multiple routes of exposure subject to factors not accounted for in the current study. Clearly, there is a need to devote more attention to where the compounds are coming from, as the authors themselves suggest: “A study measuring both exposure to aromatic amines and product analysis … would strengthen the conclusions about hairdressers’ exposure to carcinogenic aromatic amines, and is encouraged”.

Indeed, such analysis should really go hand-in-hand in this sort of study, and is essential in order to draw any meaningful conclusions from the work. Analysing all the haircare products used by several hundred people is not going to be a small task, but perhaps is illustrative of the amount of effort that needs to be made to link cause and effect in such a complex area.

The good news is that this sort of analysis – once a highly labour-intensive endeavour – is becoming increasingly quick and straightforward, because of advances in sample preparation and automation. Advanced analytical techniques like GC×GC–TOF MS are also playing their part, by making it possible to get reliable, quantitative information out of such highly complex samples – as we’ve illustrated ourselves in Application Note 522 for the case of allergens in cosmetics.

David Barden received his Ph.D. in Organic Chemistry from Cambridge University in 2004, and during his time as an editor at the RSC wrote news pieces for Chemistry World on various scientific topics. He is now Technical Copywriter at Markes International, where he draws on the expertise of his colleagues to explain how new thermal desorption and mass spectrometry technologies can be applied to analyse volatile organic compounds in a wide variety of situations.