Developing a framework for assessing chemical respiratory sensitization: A workshop report

North, Colin M.; Ezendam, Janine; Hotchkiss, Jon A.; Maier, Curtis C.; Aoyama, Kohji; Enoch, Steven J.; Goetz, Amber K.; Graham, Cynthia; Kimber, Ian; Karjalainen, Antti; Pauluhn, Jürgen; Roggen, Erwin L.; Selgrade, MaryJane K.; Tarlo, Susan M.; Chen, Connie L.

doi:10.1016/j.yrtph.2016.06.006

Cited by 50 publications

(22 citation statements)

References 75 publications

(14 reference statements)

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“…Specific IgE antibodies to diisocyanates linked to human albumin have been identified in up to 55% of patients with OA related to diisocyanates [54,55] and have been reported to be very specific for the diagnosis, although having relatively low sensitivity [56]. This suggests an IgE-associated allergic mechanism, at least for a large subset of those with OA from diisocyanates [57]. Support for an IgE-mediated response is also provided by anecdotal case reports of anaphylaxis related to diisocyanates.…”

Section: Case Study #2: Isocyanate-induced Asthmamentioning

confidence: 99%

Opportunities and obstacles in translating evidence to policy in occupational asthma

Tarlo

Delclos

Henneberger

et al. 2018

Annals of Epidemiology

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Purpose Occupational asthma (OA), a common respiratory disorder in Western countries, is caused by exposures at the workplace. It is part of a broader definition of work-related asthma (WRA) that also includes pre-existing asthma aggravated by substances present in the workplace environment, and it is potentially preventable. The purpose of this paper is to illustrate preventive measures for occupational asthma by case studies. Methods In three case studies we discuss preventive measures that have been associated with reductions in incidence of occupational asthma from natural rubber latex and from diisocyanates as supported by published literature. We also discuss challenges in relation to asthma from cleaning products in healthcare work. Results and conclusions Several preventive measures have been associated with reduction in incidence of occupational asthma from natural rubber latex and from diisocyanates, and may provide lessons for prevention of other causes of occupational asthma. Cleaning products remain an unresolved problem at present with respect to asthma risks but potential measures include the use of safer products and safer applications such as avoidance of spray products, use of occupational hygiene methods such as improving local ventilation, and when appropriate, the use of personal protective devices.

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Section: Case Study #2: Isocyanate-induced Asthmamentioning

confidence: 99%

Opportunities and obstacles in translating evidence to policy in occupational asthma

Tarlo

Delclos

Henneberger

et al. 2018

Annals of Epidemiology

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“…3 Efforts to outline a framework for assessment of potential respiratory-sensitizing chemicals are underway. 4 Currently, however, there are no standardized, validated, and regulatory-accepted models for detecting these chemicals or discriminating them from skin sensitizers, potentially due to remaining gaps within the literature as to the exact mechanistic steps leading to respiratory allergy. 5 Another important issue in the development of predictive test methods is the route of exposure in the sensitization phase.…”

Section: Introductionmentioning

confidence: 99%

An Adverse Outcome Pathway for Sensitization of the Respiratory Tract by Low-Molecular-Weight Chemicals: Building Evidence to Support the Utility ofIn VitroandIn SilicoMethods in a Regulatory Context

Sullivan

Enoch

Ezendam

et al. 2017

Applied In Vitro Toxicology

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Sensitization of the respiratory tract is an important occupational health challenge, and understanding the mechanistic basis of this effect is necessary to support the development of toxicological tools to detect chemicals that may cause it. Here we use the adverse outcome pathway (AOP) framework to organize information that may better inform our understanding of sensitization of the respiratory tract, building on a previously published skin sensitization AOP, relying on literature evidence linked to low-molecular-weight organic chemicals and excluding other known respiratory sensitizers acting via different molecular initiating events. The established key events (KEs) are as follows: (1) covalent binding of chemicals to proteins, (2) activation of cellular danger signals (inflammatory cytokines and chemokines and cytoprotective gene pathways), (3) dendritic cell activation and migration, (4) activation, proliferation, and polarization of T cells, and (5) sensitization of the respiratory tract. These events mirror the skin sensitization AOP but with specific differences. For example, there is some evidence that respiratory sensitizers bind preferentially to lysine moieties, whereas skin sensitizers bind to both cysteine and lysine. Furthermore, exposure to respiratory sensitizers seems to result in cell behavior for KEs 2 and 3, as well as the effector T cell response, in general skewing toward cytokine secretions predominantly associated with T helper 2 (Th2) response. Knowledge gaps include the lack of understanding of which KE(s) drive the Th2 polarization. The construction of this AOP may provide insight into predictive tests that would in combination support the discrimination of respiratory-sensitizing from non-and skin-sensitizing chemicals, a clear regulatory need.

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“…New LMW agents are occasionally identified as causal agents of sensitiser-induced occupational asthma 4. The respiratory sensitisation potency of these agents is seldom identified in animal or in vitro tests before their industrial usage, resulting in the fact that new sensitisers are often first described in clinical case reports 5. Specific inhalation challenge is the most definitive method of identifying these agents 6…”

Section: Introductionmentioning

confidence: 99%

3-(Bromomethyl)-2-chloro-4-(methylsulfonyl)- benzoic acid: a new cause of sensitiser induced occupational asthma, rhinitis and urticaria

et al. 2017

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Developing a framework for assessing chemical respiratory sensitization: A workshop report

Cited by 50 publications

References 75 publications

Opportunities and obstacles in translating evidence to policy in occupational asthma

Opportunities and obstacles in translating evidence to policy in occupational asthma

An Adverse Outcome Pathway for Sensitization of the Respiratory Tract by Low-Molecular-Weight Chemicals: Building Evidence to Support the Utility ofIn VitroandIn SilicoMethods in a Regulatory Context

3-(Bromomethyl)-2-chloro-4-(methylsulfonyl)- benzoic acid: a new cause of sensitiser induced occupational asthma, rhinitis and urticaria

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