Toxicology thus established itself in the late twentieth century as a classicalexamination discipline and testing science in the course of efforts of various industrial nations to regulate toxic chemicals. Research questions within this field focus on current social and political issues. The adaptation of its research agenda to external problem definitions enables toxicology to focus on a problem- and application-oriented form of knowledge-production, which incorporate the latest approaches and practices. Relevant scientific investigations of the bio-reactivity of industrially manufactured particles on the nano-scale level, and concrete statements about their health implications, have enabled toxicology to establish itself as a leading discipline. The forms and functions of toxicological knowledge production are relevant in a time when society demands consideration of its own requirements. Toxicological research promotes ends that are not only profitable, but also result in safe products and procedures. Here, the subdisciplines of particle- and inhalation toxicology in particular play a central role . The research field of particle toxicology, as a subdiscipline of toxicology, developed in the context of the study of lung disease, particularly as it occurs in the mining industry . The central organ of a particle or inhalation toxicological approach is the lung. Furthermore, mainly insoluble materials are analyzed and scientists often work with traditional toxicological methods and approaches . In the course of intensifying concern over air pollution, exhaust fumes and smog, the research field of particle toxicology gained in importance.
As a problem-oriented science, toxicology gets the chance to move in the periphery of problem-oriented but still not yet sufficiently formed cutting-edge research in the nanosciences and to profit from research funds within these fields. Nevertheless, in societal discourse, in the media and in politics, toxicologists are considered the experts with regard to the relevant questions. In our entire research area we found only two research groups, focusing on the health risks of particles in the nanometer scale, which did not characterize themselves as toxicologists. Nevertheless, these groups are methodologically, textually and technically working closely together with toxicology and in close exchange with toxicological working groups. They distinguish themselves from toxicology, arguing that they, unlike toxicology, examine entrance mechanisms by which particles enter into the body and do not focus on material effects within the organism. Furthermore, they claim to work with deeper and more realistic dosages and a minimum number of laboratory animals. Nevertheless, they produce knowledge comparable to that produced by toxicological working groups. Press coverage on the health risks of particles in the nanometer scale mainly focuses on toxicologists as the experts in this field .
Shaping disciplinary identities in toxicology: cognitive, institutional and external aspects
In our study, we found three aspects shaping the disciplinary identity of toxicology against the background of its entrance into the research field of the nanosciences and -technologies. First, science-internal factors like cognitive and institutional aspects play an important role. In our study, we understand cognitive aspects as research objects, approaches, research- and everyday-practices and resultant findings. Institutional aspects cover scientific contexts, like access to research funds and the reputation of a discipline. Under external aspects (orientation to social problems) we subsume negotiation processes in matters of definition and orientations to therapeutic approaches. We will group our results around these three aspects, and include quotations from our interviews.
Cognitive aspects: risk research as tradition and transition
The health effects of particles on the nanometer scale, discussed in science, politics, the media and by the public, are comparable to the risk concepts of toxic chemicals. Through the analysis of the toxicity of chemical substances, comparable approaches are selected and similar insights are achieved. When compared to a variety of materials, pollutants and substances being deposited into the environment, the discussed health effects of nano-scale material display their chronic toxicity. This, and its longtime research experience with particles on the micrometer and ultrafine level has enabled toxicology to establish itself as a scientific discipline in the risk analysis of particles on the nanometer scale [47
]. The analysis of the health implications of ultrafine particles in laboratory trials took place with well-defined, specially produced reference particles. The use of reference particles enabled the comparison and reproduction of particular test arrangements. Such reference particles are similar to today's industrially manufactured nanoparticles. An interview partner, who has been working for over thirty years in this field, stressed that toxicological groups already worked with nano-particles before the term 'nano' was established.
"For us, the term 'nano' is old hat, we have always been 'nano' now for more than 10 years, although we did not use the term 'nano'." (Toxicologist I, German research center)
Toxicology established itself in the analyses of health implications of micrometer particles in the last thirty years. A close methodological and textual connection exists between research on unintentionally and combustion-produced ultrafine environmental particles and well-defined selectively produced particles on the nanometer scale. Particularly, experience from the analysis of the health impacts of particles on the micrometer scale is seen by several interview partners as a central precondition for doing research with particles on the nanometer scale, as another toxicologist from a German research center holds:
"I started with micrometer particles. 98% of my knowledge and experience is based on micrometer particles. [...] thirty years ago, I was concerned with particles, sized between 0.5 and 5 micrometers. And then the ultrafine particles came up. That was ten years ago and since then I have been doing something similar with the ultrafines." (Toxicologist III, German research center)
Besides work with particles on the micrometer scale, constitutive research on ultrafine particles supplied important insights and preconditions for working with selectively produced particles on the nanometer scale. Based on their experience with the bio-interactions of those particles, several interviewpartners are disclosing the behavior of selectively produced nano-particles.
"The industrially manufactured nano-particles are materially comparable to environmental particles. Therefore, research within these fields can well be combined. [...] Our experience with ultrafine particles is of high importance for analyzing the risks of nano-particles. Along with ultrafine particles, we began to use nano-test particles to investigate certain mechanisms." (Toxicologist II, German research center)
The transition from the 'ultrafine-' to the 'nano' scale often happens inconspicuously. Alongside research with ultrafine particles, similar experiments are repeated with selectively produced nano-particles. As a rule, however, particularly the German research groups, we analyzed, sought a clean distinction between established and new research fields.
"I don't want to give the impression that we are only working with ultrafine dust, with combustion stuff. We also work with the typical synthetic nano-particles [...] thus, we do both: We work both: on the combustion side with fly ash and environmentally relevant particles as well as with nano-technological particles. We clearly divide this into two different projects, with the appropriate nomenclatures. "(Toxicologist IV, German research center)
Most insights into the potential health effects of particles on the nano-scale level have resulted from toxicological approaches, on methods, and were achieved in toxicological research groups and laboratories. The most frequently observed health effects and bioreactive phenomena of materials on the nanometer scale are inflammatory cell reactions resulting from the deposition of such materials in the lung . The transport of nano-scale particles through the lung into the blood was also observed . In addition, the particles were found deposited in the body and to have even overcome the blood-brain barrier . In fact, nano-scale particles were found in all organs of the body . This fact was also reported by a researcher in the field of inhalation toxicology at a Swiss University:
"We found the particles distributed in the entire lung four hours after their admission. Furthermore, we found them in the blood, from where they can easily be distributed into the whole organism [...] a colleague of mine at the GSF in Munich found particles in the liver, in the kidney, in the heart and even in the brain. Epidemiological studies have shown that with accumulating concentrations of fine dust in the air, certain diseases, such as cancer, and heart, circulation and respiratory problems, are increasing." (Biologist I, Swiss university)
Furthermore, some results show that nano-scale particles are transported into the brain by olifactory nerve cells  and are involved in neurodegenerative changes . The same researcher continues:
"Nano-particles are transported along the olfactory nerves into the brain. We do not know what happens there. Besides that, there is a study showing that the histological picture of Alzheimer patients, who died at the age of 70 or 80 years, closely match a picture of the brain of accidentally killed 30 year old persons who lived in areas with a strong particle-load. "(Biologist I, Swiss, University)
A research group at the GFS – Research Center for Environment and Health (in the Helmholtz community) in Neuherberg near Munich developed a technique for quantifying the health implications of particles within the nanometer scale. It conceives of risk and a shortening of lifetime and expresses this in the number of lost life years . Thus, the risk is constructed through the 'lifetime-shortage' factor as a measurable, conceivable and concrete quantity. A researcher of this group argues:
"According to our epidemiological studies, long-term exposure with high concentrations of environmental aerosols can shorten a life span by one year. In Germany, between 4'000 and 10'000 persons per year are affected." (Toxicologist I, German research center)
In summary, we argue that, in this early phase of identity formation, toxicology strongly relies on current methods, practices and approaches. In parallel with its well-established analysis of the health effects of particles on the nanometer scale, toxicology is building for itself a new research field through its analysis of the potential impacts of nano-scale particles. Entering into this field, toxicology brings with it basic knowledge from the analysis of micrometer and ultrafine particles. In this way, the transition to a new field proceeds incrementally; this careful movement is particularly well-articulated in the quotation: "we have always been nano". This is as it were, the secured position from out of which nano-specific questions and procedures can be necessarily conceded. In the next section we will address the question of how – alongside the cognitive aspects -institutional conditions, like funding acquisition strategies and the reputation of toxicology as a science, are also shaping disciplinary identities in this research field.
Institutional aspects: acquisition and reputation
Besides the cognitive conditions, discussed in the previous section, institutional aspects are also shaping the formation of the disciplinary identities of toxicology in the context of its entrance into the research field of nanosciences and -technologies. The increasing scientific, political and economic interest in nanosciences and -technologies have opened considerable funding sources for this field. Thus, research projects for the investigation of the health implications of industrially manufactured nano-particles are usually more generously supported than similar investigations of particles originating from combustion processes. For this reason there is an interest in expanding the research breath of the nano-sciences, as a toxicologists of a German research organization holds:
"If you write the term 'nano' into your research grant applications, the probability to get funding is much higher than if you use the term 'ultrafine'."[...](toxicologist, German University)" 'Nano': this is a fashion and naturally also a proposal strategy. If I applied for research funding on ultrafine dust at the European Union, that would be old hat. It was already done in the 1970s and the 1980s. However, if I applied for funding for a project on the influence of nano-particles, then everything looks quite different." [...] (Toxicologist II, German research center) " Furthermore, it was a question of funding. In the European Union, research on ultrafine particles was promoted less after 'nano' emerged and, since then, we have also been trying to get funding for 'nano'." (Toxicologist I, German research center)
Besides funding strategies, toxicology's traditional historical role as a testing science enabled it to also enter into the new research field. The increasing growth of research and development within the nanosciences and -technologies made risk assessments inevitable. Hence, different material research institutes established research groups in toxicology as an accompanying testing science. Furthermore, they involved toxicology within their own field. As a German toxicologist argues, toxicologists were expected to analyze the potential health implications of materials on the nanometer scale, which are researched and developed within these institutes.
"Our research institute has laboratories for nano-technology, material research and chemistry that are working with nano-materials. Our task is to accompany those technological developments with toxicological research." (Toxicologist II, German research center)
In its role as an attendant testing science, several toxicologists, particularly in Germany but also in Switzerland complained of toxicology's lack of prestige. Since their research aims at discovering potential hazards, they are only able to publish their data if they have found a health effect for a substance or a product. As this is socially perceived as unfavourable, they feel themselves to be the bearers of bad news. In our interviews, we detected a certain disillusionment. In particular, toxicologists seem to lack the possibility of publishing socially favourable results such as that for a certain substance or product no danger could be proven, in renowned high-impact journals. Furthermore, some toxicologists expressed discontent with their financial situation and their lack of scientific and political appreciation. Hence, among toxicologists, particularly in the German research community the view dominates that productive disciplines enjoy a higher reputation and can publish their research results more easily and in higher-rated journals, as German toxicologists argues:
"If you work in toxicology, you only have negative results." [...](Toxicologist II, German research center) "My highest goal would be to get a safety study published in Nature. That is the problem, we can only publish negative effects. When we find positive, or rather no, effects, we cannot publish them. When we discuss that a particular substance is not toxic, this is fine for society but bad for us as scientists, since we measure research quality based on output. If a geneticist finds a new gene, a new gene product or a regulator in his laboratory, then he has a new paper. This is very simple. And the paper, if this is a basically important process, will be accepted in Science, Nature or somewhere else. This is not possible in our field. If we tested ten substances and they all turn out to be harmless, then we have just spent five years without publishing anything. As a toxicologist you hardly ever want to be in Nature or Science. Being there, you must have found a substance so toxic that you would prefer it did not exist. That is the difficulty with toxicology. But nobody recognizes that. The investors do not realize that, and neither do our clients nor society. Everybody says: Toxicology is expensive and brings nothing – from an economic perspective." (Toxicologist III, German research center)
Like ethics, toxicology assists neighboring disciplines in an accompanying and advisory way. It is basically a testing science. By turning its attention to risk, it often sees itself as being ill-reputed as a brakesman, a spoilsport, a critic or an unloved child. For toxicology, this role is unappealing. According to some interviewed German toxicologists, productive disciplines seem to undervalue the constructive aspect of toxicological knowledge production, as another German toxicologist argues:
"Toxicology is usually seen as a brakesman and spoilsport. Toxicology focuses on implications that an engineer does not necessarily see, but which could be of great importance for him. This means that there absolutely is a knowledge gain resulting from the analysis of hazardous implications. Toxicology should be a constructive element with the development of nano-technologies. Collaborations between developers and those who focus on implications are crucial. If this happens at as early a stage as possible, then this is – according to my perception – no handicap, but rather a moment of creative research, positively stimulating the whole process." (Toxicologist I, German research center)
Institutional aspects like finding acquisition strategies and toxicology's traditional role as a testing science enable its entrance into the research field of nanosciences and -technologies. Moreover, the toxicological research community expresses the desire for higher outside appreciation. Toxicology aims at constructively accompanying and creatively influencing controversial cutting edge research. Furthermore, toxicology prefers the role of the productive partner rather than the brakesman. This aim represents kind of a crucial test – at least in terms of the transitional phases for evolving disciplinary identities. While the braking and warning function belongs to its classical scope, toxicology nevertheless fears that it will not even be able to fulfil those functions. Thus the question occurs, whether these functions detract from ('spoil sport') or support toxicology's disciplinary reorientation, since it now sufficiently fulfils social requirements for safety. We will focus on this still undecided question under the title of problem-orientation in the next section. In doing so, we will also analyze the impact of toxicological participation in the therapy-oriented research of the nanosciences.
External aspects: problem orientation and negotiation processes
Besides those aspects internal to science, orientation to science-external research questions and problems also shapes the disciplinary identity of toxicology. One important example is the orientation of toxicological knowledge-production toward nanoscientific approaches to therapeutic issues in pharmacology. The aim of this research area is the development of mobile drug carrier systems based on nano-particles. Here, nano-particles are used as transport systems for therapeutic agencies. Due to its specific characteristics, a medication can be directly applied to the effected location in the body . Toxicology can adapt its insights into specific particulate and material properties and structures, developed in in-vitro and in-vivo studies, to the production of bio-inert particles with minimal health effects. Besides its function as a testing discipline, toxicology has the opportunity to adapt is knowledge to the health implications of particles on the nanometer scale range to the production of particles, for therapeutic use in pharmacology, which do not verifiably harm biological systems. We found this argument in the European as well as in the US-context.
" 'Nano' offers an enormous potential for toxicology. For example, we are able to develop bio-inert particles." [...] (Toxicologist, US-university) "A positive approach is therapy. This is, at the moment, a good idea, and one for which we have filed a project application. We will not examine any particular therapeutic aspects, but will rather aim at finding out how a nanoparticle should be designed, and what surface properties it must have in order to not cause any reaction in the organism. If I created such a particle, I could load it with a medicament or equip it with receptors such that these would then be carried into the cells. The real positive thing about this approach is that you can in the end, use it therapeutically, for example, in tumor therapy. You can attach to these cells through certain receptors, which the tumor is expriming. It will be absorbed into the cell and the agent will then be developed specifically in the tumor cells. In contrast, simplifying things, conventional chemotherapeutic agents are simply given to the organism and the tumor cells are more intensely damaged than the normal cells, as they have a higher turn-over. I would see this as a positive aspect of toxicological research." (Toxicologist IV, German research center)
Besides the therapeutic orientation, definitorial demarcations seem to be another externally induced influence on disciplinary identity shaping in toxicology. In particular, the toxicological research community does not share a uniform attitude regarding the question of when a particle can be called a 'nano-particle'. While one part of the community argues for a merely size-oriented definition, others demand an origin-oriented distinction. Through this controversy, discussions and negotiation processes are developing concerning the demarcation of the research field of the nanosciences and -technologies. Part of the toxicological research community is using a purely size-oriented approach and is including all particles within the nanometer range (with at least one dimension smaller than 100 nanometers or 10-7-10-9m) under the term 'nanoparticle', as toxicologists in Germany and in the Netherlands argued.
"Nano particles are particles which are at least in one dimension smaller than 100 nanometers. Through this, also nano tubes and plane particles are also incorporated. With the ultrafine, all three dimensions must be smaller than 100 nanometers. Therefore, we are classically ultrafine and to that extent also nano. Because ultrafine is always nano as well." (Toxicologist I, German research center)
This enables the researchers involved to call their research on ultrafine particles 'nanoscience', and to partake of the rich funding opportunities in this field (see also section 4.2).
Toxicologists who plead for an origin-oriented distinction, argue that randomly emerging particles on the nanometer scale, usually resulting from combustion processes, should be called 'ultrafine-' or 'ambient air particles'. Furthermore, such particles usually consist of complex material mixtures. Only industrially manufactured, materially clearly defined particles within this size-range ought to be called 'nano particles'. We found this argument as well in the European than in the US context.
"Concerning nomenclature at the very least the basic need for a distinction between clearly defined, engineered nanosized particles and those accidentally released into the environment, should be met [...] Defining complex material mixtures, I'd rather use the general term 'ultrafine particles'. For engineered materials, I would use the term nano-material. The term 'nano-material' implies technical design and intentional manufacture. The size range of particular ultrafine particles only coincidentally lies in the nanometer scale. Therefore, I would use terms like 'combustion particle' or 'environmentally relevant particle' for particles unintentionally released into the environment, and definitely not the term 'nanoparticle'." (Toxicologist II, German research center)
As a compromise between the two positions, other members of the toxicological research community suggest the use of the term 'nano-scale particle' for both kinds of particles. This still size-oriented concept permits research in the field of ultrafine particles to be included under the term 'nano', and it allows such research to profit from the considerable research funds available to the nanosciences. At the same time, this definition is seen as allowing the desired demarcation for public-risk discourse.
"Therefore, I'd suggest the term 'nano-scale particle' as a comprehensive definition for environmental particles within the nanometer scale. "(Toxicologist, US-university)
The openness of the term 'nano', and the vague boundaries of the nanosciences and -technologies leave considerable space for toxicology to form its own disciplinary identity. Research fields, like the analysis of the health risks of ultrafine particles, can be subsumed under the 'nano-sciences'. The definitions used so far are set less for scientific than for political reasons, such as funding acquisition strategies and carreer interests. Hence, it is feared that a merely size-oriented definition could transfer public concerns over the health effects of ultrafine particles onto the entire area of the nano-sciences. This would, according to some, provoke public resistance to the nanosciences as such. Therefore, there is an interest in narrowing the research field of the nanosciences. Yet such demarcations also decide, whether another, quite relevant discipline (here: Toxicology) should obtain access to what is distinguished as a key technological field, and so also to the considerable research funds available to that field. In the negative case, toxicology would remain a less spectacular side-field with more modest funds. Therefore, the term 'nano' is not only rewriting a research field, with its specific questions and methods, but it also acts as a funding acquisition strategy and a reputation boost for individual researchers and groups. The entry of toxicology into the nano-sciences is enabled not only by its long research tradition in the analysis of the health implications of environmental and combustion particles on the micro- and nanometer scale, but as much by its taking advantage of an ambiguity by definition and vague demarcations of the research field of nanosciences and -technologies
Besides the social negotiation of definitioned demarcations, orientation to social issues also plays a substantial role in shaping disciplinary identities in toxicology. By participating in the development of therapeutics, like medical transmitter systems, toxicology sees a chance to leave behind its cognitively less attractive status as a purely evaluative field, and to develop from a classical testing science into a productive discipline. The entrance into the research field of the nanosciences and -technologies is seen as an opportunity for toxicology to transform its disciplinary identity and its mode of knowledge production. Whether such a transformation is actually taking place, and is introducing a new disciplinary identity, and whether toxicology will establish itself as a productive nanoscience, will be discussed in the final section.