Trends in Pulmonary Function and Prevalence of Asthma in Hexamethylene Diisocyanate Workers During a 19-Year Period

Cassidy, Laura D.; Molenaar, Donald M.; Hathaway, James A.; Feeley, T. M.; Cummings, Barbara J.; Simpson, Pippa; Li, Shun-Hwa

doi:10.1097/jom.0b013e3181f2e086

Cited by 11 publications

(14 citation statements)

References 23 publications

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“…These estimates are in agreement with observations of the absence of exposure-related respiratory symptoms in HDI-exposed workers after exposures in the 1-5 ppb range (Cassidy et al, 2010;Hathaway et al, 1999).…”

Section: Discussionsupporting

confidence: 90%

“…Due to its widespread use in automobile spray painting, there are numerous occupational studies of exposure and health effects from inhaled HDI (Cassidy et al, 2010;Hathaway et al, 1999) and from HDI-based polyisocyanates (Alexandersson et al, 1987;Tornling et al, 1990). Health effects associated with occupational exposure to HDI at air concentrations higher than the occupational exposure limits (threshold limit value ¼ 5 ppb) include nasal and lung irritation, airway hypersensitivity, and a temporary reduction in lung function.…”

Section: Introductionmentioning

confidence: 99%

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Inhalation dosimetry of hexamethylene diisocyanate vapor in the rat and human respiratory tracts

Schroeter

Kimbell²,

Asgharian

et al. 2013

Inhalation Toxicology

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Hexamethylene diisocyanate (HDI) is a reactive chemical used in the commercial production of polyurethanes. Toxic effects in rodents exposed to HDI vapor primarily occur in the nasal passages, yet some individuals exposed occupationally to concentrations exceeding current regulatory limits may experience temporary reduction in lung function and asthma-like symptoms. Knowledge of interspecies differences in respiratory tract dosimetry of inhaled HDI would improve our understanding of human health risks to this compound. HDI uptake was measured in the upper respiratory tract of anesthetized Fischer-344 rats. Nasal uptake of HDI was >90% in rats at unidirectional flow rates of 150 and 300 ml/min and a target air concentration of 200 ppb. Uptake data was used to calibrate nasal and lung dosimetry models of HDI absorption in rats and humans. Computational fluid dynamics (CFD) models of the nasal passages were used to simulate inspiratory airflow and HDI absorption. Transport of HDI through lung airways was simulated using convection-diffusion based mass transport models. HDI nasal uptake of 90% and 78% was predicted using the rat and human nasal CFD models, respectively. Total respiratory tract uptake was estimated to be 99% in rats and 97% in humans under nasal breathing. Predicted human respiratory uptake decreased to 87% under oral breathing conditions. Absorption rates of inhaled HDI in human lung airways were estimated to be higher than the rat due to lower uptake in head airways. Model predictions demonstrated significant penetration of HDI to human bronchial airways, although absorption rates were sensitive to breathing style.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Inhalation dosimetry of hexamethylene diisocyanate vapor in the rat and human respiratory tracts

Schroeter

Kimbell²,

Asgharian

et al. 2013

Inhalation Toxicology

View full text Add to dashboard Cite

show abstract

“…None of the predictive models showed any statistically significant influence of occupational exposure on the outcomes being investigated. This finding is in accordance with previous studies that did not reveal such an association [21,22]. However, the results also indicate a ''healthy hire effect'', with participants not having been exposed to low-or high-risk occupational exposure exhibiting higher risks of presenting with the outcomes than those who were exposed (albeit not statistically Overall prediction probabilities for prevalent work-related sensitisation were substantially higher than the positive predictive value (PPV) of SPT for new-onset occupational hypersensitivity, which had previously been found in apprentice bakers (33%) [23].…”

Section: Discussionsupporting

confidence: 83%

“…However, on closer inspection this is not the case. Some other prospective studies including unexposed reference groups have also indicated that the incidence of asthma and allergies in young adults who had just started their careers was often independent of occupational exposure [21,22,25]. A limitation of our study might be that even though participants were followed for ,12 years, they were still very young in SOLAR II and just at the beginning of their working lives.…”

Section: Strengths and Limitationsmentioning

confidence: 75%

Predictors of work-related sensitisation, allergic rhinitis and asthma in early work life

Kellberger¹,

Peters-Weist²,

Heinrich³

et al. 2014

European Respiratory Journal

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Although work-related asthma and allergies are a huge burden for society, investigation of occupational exposures in early work life using an unexposed reference group is rare. Thus, the present analyses aimed to assess the potential impact of occupational exposure and other risk factors on the prevalence of work-related sensitisation and incidence of allergic rhinitis/asthma using a population-based approach and taking into account an unexposed reference group.In SOLAR (Study on Occupational Allergy Risks) II, German participants of ISAAC (International Study of Asthma and Allergies in Childhood) phase II were followed from childhood (9-11 years) until early adulthood (19-24 years). Data on 1570 participants were available to fit predictive models.Occupational exposure was not statistically significantly associated with disease prevalence/incidence. Sensitisation in childhood, parental asthma, environmental tobacco smoke exposure during puberty, sex and study location were statistically significant predictors of outcome.Our results indicate that occupational exposure is of little relevance for work-related sensitisation prevalence and allergic rhinitis/asthma incidence in early work life, while other risk factors can be used to improve career guidance for adolescents. Further research on the role of a potential healthy hire effect and the impact of longer exposure duration is needed. @ERSpublications Occupational exposure not predictive of work-related sensitisation, allergic rhinitis and asthma in early work life

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“…Analysis of worker populations exposed to controlled atmospheres of MDI below 5 ppb (Gee and Morgan, 1985;Musk et al, 1982;Pham et al, 1988), 10 ppb TDI (Musk et al, 1982), or to 3 ppb HDI (Hathaway et al, 1999;Cassidy et al, 2010) did not identify any increase in the incidence of work-related respiratory symptoms. In contrast, exposure of workers to concentrations of MDI of 5 ppb or more was associated with a more frequent occurrence of work-related asthma (Tarlo et al, 1997).…”

Section: Diisocyanatesmentioning

confidence: 95%

Thresholds in chemical respiratory sensitisation

et al. 2015

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There is a continuing interest in determining whether it is possible to identify thresholds for chemical allergy. Here allergic sensitisation of the respiratory tract by chemicals is considered in this context. This is an important occupational health problem, being associated with rhinitis and asthma, and in addition provides toxicologists and risk assessors with a number of challenges. In common with all forms of allergic disease chemical respiratory allergy develops in two phases. In the first (induction) phase exposure to a chemical allergen (by an appropriate route of exposure) causes immunological priming and sensitisation of the respiratory tract. The second (elicitation) phase is triggered if a sensitised subject is exposed subsequently to the same chemical allergen via inhalation. A secondary immune response will be provoked in the respiratory tract resulting in inflammation and the signs and symptoms of a respiratory hypersensitivity reaction. In this article attention has focused on the identification of threshold values during the acquisition of sensitisation. Current mechanistic understanding of allergy is such that it can be assumed that the development of sensitisation (and also the elicitation of an allergic reaction) is a threshold phenomenon; there will be levels of exposure below which sensitisation will not be acquired. That is, all immune responses, including allergic sensitisation, have threshold requirement for the availability of antigen/allergen, below which a response will fail to develop. The issue addressed here is whether there are methods available or clinical/epidemiological data that permit the identification of such thresholds. This document reviews briefly relevant human studies of occupational asthma, and experimental models that have been developed (or are being developed) for the identification and characterisation of chemical respiratory allergens. The main conclusion drawn is that although there is evidence that the acquisition of sensitisation to chemical respiratory allergens is a dose-related phenomenon, and that thresholds exist, it is frequently difficult to define accurate numerical values for threshold exposure levels. Nevertheless, based on occupational exposure data it may sometimes be possible to derive levels of exposure in the workplace, which are safe. An additional observation is the lack currently of suitable experimental methods for both routine hazard characterisation and the measurement of thresholds, and that such methods are still some way off. Given the current trajectory of toxicology, and the move towards the use of non-animal in vitro and/or in silico) methods, there is a need to consider the development of alternative approaches for the identification and characterisation of respiratory sensitisation hazards, and for risk assessment.

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Trends in Pulmonary Function and Prevalence of Asthma in Hexamethylene Diisocyanate Workers During a 19-Year Period

Abstract: This study provides support for the current American Conference of Governmental Industrial Hygienists threshold limit value time-weighted average of 5 ppb.

Cited by 11 publications

References 23 publications

Inhalation dosimetry of hexamethylene diisocyanate vapor in the rat and human respiratory tracts

Inhalation dosimetry of hexamethylene diisocyanate vapor in the rat and human respiratory tracts

Predictors of work-related sensitisation, allergic rhinitis and asthma in early work life

Thresholds in chemical respiratory sensitisation

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