Isocyanates measurement methodology exposure and effects Report from a workshop organised by the Swedish National Institute for Working Life and held in Brussels 26±28 April 1999 Introduction The Swedish National Institute for Working Life (NIWL) organised an international workshop with the title Isocyanates–Measurement Methodology Exposure and Effects in Brussels 26±28 April 1999. It was one of a series of workshops preceding the conference ``Worklife 2000'' January 22±25 2001 in Malmo» Sweden. Approximately 20 scientists in the Æeld from Europe and the US participated. The workshop was of an informal nature with ample time for discussion. Below a summary of the presentations is given together with some conclusions from the workshop.Isocyanates–effects and exposure Highly reactive isocyanates (R±NLCLO) are nowadays used in many workplaces. They may become airborne in gaseous or aerosolised forms. When inhaled they bind to human tissues proteins and DNA forming toxic adducts and metabolites which may cause adverse health effects. Bronchial asthma is the most frequent clinical diagnosis in isocyanate workers. Further diseases caused by these chemicals include nonobstructive bronchitis rhinitis conjunctivitis dermatitis and extrinsic allergic alveolitis. The diagnosis of isocyanate-induced disorders is based on a stepwise approach starting with a detailed occupational case history measurement of speciÆc isocyanate-IgE antibodies lung function testing follow-up during working hours and spare time and in doubtful situations occupational-type inhalative challenge with the suspected causative agent.Due to the heterogeneous pathogenic mechanisms negative immunological tests (seen in 85% of isocyanate asthma cases) and the absence of bronchial hyperreactivity to methacholine do not exclude isocyanates as causative substances. To ensure 18N J. Environ. Monit. 2000 2 This journal is # The Royal Society of Chemistry 2000 reversibility the early diagnosis of isocyanate-induced disorders is required. Since the health risk is concentrationdependent the most important preventive measure is the reduction of exposure levels. Concentrations at or below the current occupational exposure limits (OELs) (mostly 10 ppb) do not exclude effects.Therefore the development of improved routine analyses of all airborne isocyanates as well as of methods for biological monitoring is urgently required. Further where possible a health-based OEL comprising all isocyanate groups should be stipulated and workers at risk should undergo regular medical surveillance programmes. In the US health surveys of plants using isocyanates have been conducted by the US National Institute for Occupational Safety and Health (NIOSH). The construction of a new facility provided the opportunity to study the workers' health prior to and after the introduction of diisocyanate. Several tools have been used to evaluate workers' respiratory status.A health questionnaire was administered prior to and twice a year for two years after the introduction of isocyanate. Occupational and work practice questionnaires were also obtained. Lung function testing and skin testing to common allergens were performed. Blood was drawn for isocyanate speciÆc and total IgE measurements. Nasal lavage was performed on workers at the end of their work shifts. Workers are also potentially exposed to other work place antigens such as raw unÆnished wood and isocyanate Ænished wood products in places where isocyanate is used as a wood binder. Extracts from each of these materials were used to screen for potential IgEs. Preliminary data showed that speciÆc IgE to both isocyanate associated antigens and other work place antigens can be found in workers from plants using diisocyanates in their processes.Workplace asthma caused by exposure to isocyanates has shown no decrease in the UK with some 400 cases per year while the overall use of isocyanates by UK industry is increasing slowly. Levels of occupational asthma do not appear to have fallen although reporting levels may have risen through Forum increased awareness. Analysis of the summarised health data shows that incidence of asthma is not restricted to the motor vehicle industry but dangers may be as great in other isocyanate using industries such as for example spraying isocyanates into moulds to form rigid foam. In Sweden there is an intense debate about isocyanates.Special attention has been drawn to the risk entailed by the thermal degradation of polyurethane plastics and products containing polyurethanes. Some of these degradations have been unknown or overlooked. What is also new is the newly discovered generation of lowmolecular isocyanates which occur when heating up materials containing some combinations of phenyl-formaldehydeurea. Examples of workplaces where isocyanates will occur will include heating of mineral-wool in oven insulation of binders for core making in the foundry industry and hot work in car repair shops. The polyurethane (PU) industry routinely carries out occupational hygiene measurements both in-house and at their customers' factories to assess workplace exposures during the manufacture and use of PU chemicals.A wide variety of compounds are used by the PU industry e.g. release agents blowing agents cleaning agents Ære retardants surfactants and isocyanates for routine manufacture of a vast range of products such as rigid and Øexible foams elastomers adhesives coatings paints binders etc. ICI for example has carried out occupational hygiene studies and surveys in-house and at customer premises to measure the concentration of 4,4'-diisocyanatodiphenylmethane (MDI) in the workplace during the manufacture and use of polyurethanes. Data from over a thousand personal samples have been generated. Exposure assessments have included personnel who had the potential by way of their job activities to be exposed e.g.line operatives line supervisors maintenance staff product Ænishers cleaners QA staff electricians laboratory personnel warehouse staff forklift truck drivers etc. Overall exposure to MDI is well controlled with only two values from 1327 personal samples resulting in values w0.05 mg m23 (8 h time-weight average). Adopting monitoring methods capable of detecting and quantifying all isocyanate containing species allows assessment of total isocyanate exposure as well as providing an insight to the physical form of the MDI. In summary human exposure studies indicate that isocyanate exposures during work are associated with occupational asthma. Such studies may provide insight into the relationship of diisocyanate-induced disease and speciÆc work practices and potential routes of exposure.Isocyanates–measurement methodology Collection of samples can be through use of impingers/bubblers or Ælters each involving reagents. There can be internal losses of material in both impinger inlets and on the walls of Ælter cassettes. There are also issues of the efÆciency of reactions of particles with reagents on Ælters. Impingers raise questions of particle sizes collected (for small particle sizes). Instrumental (paper tape) methods are more suitable for exposure proÆling over time than for quantiÆcation. Derivatives Each of the reagents has strengths and weaknesses. Older solutions are still in use such as Marcali ethanol nitro-reagents and 1-(2- methoxyphenyl)piperazine (2MP).On occasions several detectors are required for example a combination of electrochemical (EC) and ultraviolet (UV) detection. The reagent 1-(2- pyridyl)piperazine (2PP) is effective in separating isocyanates but still Ænds polyisocyanates difÆcult. The reagent 9- (methylaminomethyl)anthracene (MAMA) uses a detector-response ratio as a means of quantiÆcation but the ratio is not constant. Tryptamine also uses two detectors but is more constant than MAMA in Øuorescent yield. MAP [1-(9-anthrecenylmethyl)piperazine] combines the advantages of 2MP and MAMA and gives the most constant yield. Di-n-butylamine (DBA) has the fastest reaction time as high concentrations can be used.At present this is an expensive and non-routine method since it utilises liquid chromatographic-mass spectrometric determination. The Iso-Chek2 sampler is a hybrid method separating the isocyanate particles and vapour and using both MAMA and 2MP derivatization. In the UK the Health and Safety Laboratory method MDHS 25 is used which utilises the 2MP derivative with ECzUV detection. There are potential problems with MDHS 25 i.e. the reliance on the EC/UV ratio being consistent and mis-identiÆcation can occur with incorrect quantiÆcation. However good results were obtained in comparison with direct titrations of polyisocyanates. The EC/UV ratios of several industrial isocyanate samples have been investigated.Six steps in sampling and analysis each of which can have problems can be identiÆed Collection EfÆciency problems of aspiration internal losses and transmission losses are frequent. Problems are addressed through inhalable sampler Ælters and impingers. Vapour collection depends on derivatization efÆciency. Derivatization EfÆciency is affected by reagent reactivity concentration and mixing. Flexibility is recommended in sampling covering collection and derivatization given the limitations of both Ælters and impingers and taking into account the environments concerned and the duration of the sampling. Filters should be extracted in the Æeld. Use of high boiling solvents is preferred. Sample preparation The fewer things you do the better.Losses are a potential problem with liquid-liquid extraction as well as solid phase extraction. Separation Separation has been dominated by reversed-phase high performance liquid chromatography (HPLC). Several methods use a bulk product for calibration. Monomers can be used for calibration in other methods. Isocratic elution has advantages simple stable and unvarying baseline. Gradient elution is more powerful and faster but may have an adverse effect on the baseline. In the MAP method pH gradient elution is used. It is also powerful selective and gives a stable baseline. Forum IdentiÆcation Retention time is important for monomers while for oligomers selective detectors are needed multi-dimensional detectors or two detectors.For identiÆcation of MAP a UV/Øuorescence ratio is used. For safe and complete identiÆcation mass spectrometry is needed. QuantiÆcation There can be direct calibration curves for monomers while for oligomers it is a matter of bulk calibration or monomer calibration. Thermal degradation of PUR For thermal degradation a method based on the derivatization of aromatic and aliphatic isocyanates using di-nbutylamine (DBA) followed by the derivatization of aromatic and aliphatic amines with ethylchloroformate has been used. The DBA-method has been demonstrated for isocyanate-adducts -monomers and thermal degradation products of PUR for example when welding buses. Fast reaction rates between isocyanates and DBA were observed and the method was found to be robust with no inØuence of interfering compounds.For a 0.01 mol 121 DBA concentration the reaction rate was very fast and it was not possible to study the time dependence of the reactions. The removal of the reagent during the work-up procedure greatly facilitates the subsequent chromatographic determination and allows the use of DBA at high concentrations. Quality assurance of isocyanate measurements National standardisation has been diverse. For example the Swedish National Institute for Working Life in 1997 recommended the DBA method. The UK Health and Safety Executive recommends 2MP (which meets the performance requirements of EN 482) and Marcali.NIOSH has three methods 2MP tryptamine and the nitro reagent method. Internationally the ISO standardisation committee ISO/TC146 has 5 methods under consideration 2MP; and four new work items; DBA Iso-Chek2 MAP and Guide on selection of procedures. In 1991 the European Commission decided that certiÆed reference materials 19N J. Environ. Monit. 2000 2 Forum in the form of 2MP derivatives should be prepared for isocyanates. The speciÆed certiÆcation studies have been undertaken and CertiÆed Reference Materials (CRMs) have been prepared and can be obtained from the Community Bureau of Reference (BCR). There are independent proÆciency testing schemes like the UK WASP (Workplace Analysis Scheme for ProÆciency).Conclusions recommendations and needs for future research . Isocyanates result in more reported cases of occupational asthma and similar respiratory disorders than any other group of chemicals. Industrial uses of isocyanates include manufacture of polyurethane foam surface coatings adhesives and textiles and occupational exposure can occur particularly in processes involving heating and spraying isocyanates. . Most countries have adopted occupational limit values based on monomeric isocyanates. However polyisocyanates (diisocyanate polymers or prepolymer adducts with polyamines) and low molecular weight isocyanates (such as methylisocyanate) are also used or can occur industrially. Toxicological evidence suggests that they should also be included in setting appropriate harmonised limit values.. Methods exist for the determination of airborne isocyanates. These are mostly complicated expensive and require a high degree of technical competence. There is a need for simpler more cost-effective methods. This would facilitate monitoring by Small and Medium Sized Enterprises (SMEs). . There is a need for the further development of sampling and analytical methods for isocyanates particularly airborne but also for dermal exposure and biological monitoring. Where possible such methods should be simple and cost 20N J. Environ. Monit. 2000 2 effective and distinguish between vapour and particulate isocyanates. . Sampling and analysis methods should be supported by validation (such as according to EN 482) quality control quality assurance and certiÆed reference materials.. The relative toxicity and metabolism associated with health effects of different isocyanate species should be further investigated in particular connection with setting limit values and improving biological monitoring. The parent compounds and metabolites may be genotoxic or carcinogenic in addition to having allergenic potential. The metabolism of aromatic and aliphatic isocyanates has not been studied in detail. There is also a lack of epidemiological studies on isocyanate workers. Therefore it is strongly recommended that such investigations are carried out. .Cases of occupational asthma have been observed where no measurable isocyanates in air were identiÆed implying a deÆciency in the sampling and analytical methods used and/or an incorrect limit value and/or exposure via routes other than inhalation. For this reason air measurements should be seen as part of an occupational hygiene assessment that might also include estimates of surface contamination skin absorption and/or biological monitoring and health surveillance. . In cases where isocyanate exposure cannot be prevented by substitution or minimised by engineering controls and is controlled by the use of personal protective equipment particular attention should be paid to the correct selection maintenance and use of such personal protective equipment.. There is debate about the current levels of exposure using available technologies and methods. All too often measurements are infrequent governed by the requirements of law. Occupational hygienists should be encouraged to do more assessment. . There is a discussion of prevention as opposed to monitoring. There is an opportunity to address this issue for politicians. What is wanted is control of the environment rather than the requirement to dress up workers in special clothing. Regular monitoring can reduce the incidence of exposure accompanied by health surveillance. . There are difÆculties in predicting particular problems in individual workplaces. There is a need for improved education and communication.. International practice is already affected by requirements of environmental legislation such as requirements of the US Environmental Protection Agency as it affects the workplace; there can be obligations to report when particular materials are in use. Additional information A full report from the workshop will be published by the Swedish National Institute for Working Life in Work Life 2000 Yearbook 2 2000 (Ed. R. Ennals) Springer London. Conclusions and recommendations from the workshop will be reported at the conference ``Worklife 2000'' January 22±25 2001 in Malmo» Sweden. For information see http://www.niwl.se/ wl2000/. Information on ISO standardisation can be obtained from the convenor of ISO TC146/SC2/WG4 Richard H Brown at the address given below.Jan-Olof Levin Roger Lindahl Anders O » stin National Institute for Working Life Department of Chemistry Umea Sweden Richard H. Brown Health and Safety Laboratory ShefÆeld UK Richard Ennals Kingston University Kingston Business School Kingston upon Thames UK Book Review Metabolic Pathways of Agrochemicals Edited by T. Roberts and D. Hutson Royal Society of Chemistry. 1999. £225. ISBN 0-85404-499-X. Over the last 20 years or so there has been an ever increasing regulatory demand for information concerning the degradation of pesticides in the environment yet in that time there has not been an extensive review or text that summarises metabolic pathways in soil plants and animals as well as chemical degradation.This void is now Ælled with this book which is Part 2 of a two part series. Part 2 covers Insecticides and Fungicides whilst Part 1 covered Herbicides and has already been published. This book is comprehensive in the range of categories of compounds covered which are Insecticides Insect Growth Modulators Insect Pheromones Insecticide Synergists Nematicides Rodenticides Fungicides and Plant Activators. In total these categories cover a total of 294 compounds. Consequently the book is large and the question could be asked should it have been broken down even further separating out Fungicides and Plant Activators for instance. However the book is well organised being divided into compound categories and the compounds within each category are listed alphabetically thus making it easy Book Review Environmental Impact of Power Generation Edited by R.E. Hester and R. M. Harrison Royal Society of Chemistry 1999 £25/$45. ISBN 0-85404-250-4 Modern society demands increasing energy consumption to maintain current lifestyles. The growth in energy use from the start of the industrial revolution and to the middle of the 20th Century was accompanied by signiÆcant environmental impact. Notable was the deteriorating air quality culminating in episodes such as the London smog of 1952. The public outcry resulted in legislation that provided a framework for addressing the problems. Along with the legal developments came recognition of the beneÆts of cleaner energy sources such as gas and electricity made even more attractive by cost differentials.to locate compound speciÆc information. There is a useful broad overview given at the beginning of each compound category and the information provided on individual compounds is well structured. Basic information on Uses Mode of Action and Physical Chemical Data is given initially followed by Metabolic Pathways and completed by references. The focus of the book is obviously Metabolic Pathways and this section is sub-divided into Chemical Degradation Degradation in Soils Metabolism in Plants and Ænally Metabolism in Animals. The degradation pathway schematics are excellent although sometimes the plant and animal schemes are combined sometimes plant and soil and sometimes they are separate.However this does not detract from their value. The sources of information for the book were varied and included the open literature (in some cases back as far as 1967) Pesticide Manual IUPAC and ACS Meetings PSD Evaluations along with some information from companies. A notable exception is data available from the USA via EPA and it is not clear whether or not this was deliberately omitted. In certain cases no or little information is given under some headings (e.g. tebuconazole metabolism Modern technology in homes and businesses places even greater demands for electricity from conventional or alternative sources.This type of historical development is part of the discussion in Chapter 1 of this book the 11th in a series aimed at providing a concise yet authoritative review of contemporary environmental issues. Nine expert authors have written seven chapters that range from reviews of traditional air pollution from combustion sources through nuclear energy issues to modern concerns over electric and magnetic Æelds. Environmental management system perspectives legal pressures techniques to identify the best practicable environmental option and some aspects of energy efÆciency are also covered. It is Forum in plants and animals) and data may have been available from company submissions to the EPA (provided the compound was registered in the USA).Furthermore the data available may well have been more extensive than that published in this book. Also a little extra quantitative data on metabolites would have beneÆted the reader signiÆcantly. It would also have been useful to have included details of the compound manufacturers. In conclusion the book is a must for every one with an interest in insecticide and fungicide metabolism and degradation. The authors must be complimented on undertaking such a mammoth task and as a result the reader has been rewarded with an excellent reference book. As mentioned before there is an argument that the book should have been separated into two but in my opinion due to the similarities in part structures of compounds I think that for the time being it is better that it remains as one book.However this may change as more data becomes available thus increasing the size of the book. Terry Clark Zeneca Agrochemicals UK clear that the breadth of coverage is considerable and many of the authors are to be congratulated on producing such wide ranging yet concise reviews. However the balance and some content are surprising. There is much repetition of traditional historical air pollution detail that is readily found in many air pollution texts yet global warming has relatively little mention by comparison particularly in terms of its impact; yet environmental impact is the title of the book. While a chapter entitled `energy efÆciency and conservation' suggests ways to address global warming its focus on economic instruments offers little practical advice on technical solutions or on how to change human behaviour to address the problem.Resource depletion is another omission 21N J. Environ. Monit. 2000 2 Forum from the environmental impact of power generation while renewable sources and their own impact receive scant attention. A UK focus is acknowledged in the book and hence avoids the international debates about inordinate US energy consumption. However international incidents such as Chernobyl and Three Mile Island inevitably raise public concern and are very brieØy mentioned. Transport is touched upon in Chapter 2 and in terms of environmental impact and energy use it is undoubtedly an important issue. However it sits uneasily with the title of the book and the reader will not 22N J. Environ. Monit. 2000 2 Ænd the section in the index under transport but only under road transport. Another idiosyncrasy of the index is illustrated by reference to the Integrated Pollution and Prevention Control Directive (sic). Help with the abbreviations and acronyms that appear throughout the book would also assist the reader yet only one chapter has a glossary. This fact together with some repetition across chapters suggests a lack of coherency. The independent writing of each author does not appear to have been brought together by strong editorial input. The reader may also be confused by some lack of clarity in expression of the air quality bandings compared with the values cited in government publications. The book aims to contribute to the public understanding of science in this important area while simultaneously claiming that it will be essential reading for students and practitioners in environmental science and engineering. Unfortunately it seems unlikely to meet the needs of these readerships. R. S. Barrat Open University UK