Quantitative structure-activity relationships for predicting skin and respiratory sensitization

Rodford, Rosemary; Patlewicz, Grace; Walker, John D.; Payne, Martin

doi:10.1897/01-438

Cited by 29 publications

(22 citation statements)

References 27 publications

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“…Dissemination of information should be reinforced. To identify risk from low-molecular-weight agents, research on the relationship between the structure of these agents and their activity, on molecular interactions between chemical sensitizers and human airway proteins, and on the ability to detect and localize chemical adducts in human lung tissue should be improved (417)(418)(419)(420)(421)(422)(423)(424)(425).…”

Section: Prevention and Surveillancementioning

confidence: 99%

Occupational Asthma

Mapp

Boschetto

Maestrelli

et al. 2005

Am J Respir Crit Care Med

285

213

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Substantial epidemiologic and clinical evidence indicates that agents inhaled at work can induce asthma. In industrialized countries, occupational factors have been implicated in 9 to 15% of all cases of adult asthma. Work-related asthma includes (1) immunologic occupational asthma (OA), characterized by a latency period before the onset of symptoms; (2) nonimmunologic OA, which occurs after single or multiple exposures to high concentrations of irritant materials; (3) work-aggravated asthma, which is preexisting or concurrent asthma exacerbated by workplace exposures; and (4) variant syndromes. Assessment of the work environment has improved, making it possible to measure concentrations of several high- and low-molecular-weight agents in the workplace. The identification of host factors, polymorphisms, and candidate genes associated with OA is in progress and may improve our understanding of mechanisms involved in OA. A reliable diagnosis of OA should be confirmed by objective testing early after its onset. Removal of the worker from exposure to the causal agent and treatment with inhaled glucocorticoids lead to a better outcome. Finally, strategies for preventing OA should be implemented and their cost-effectiveness examined.

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Section: Prevention and Surveillancementioning

confidence: 99%

Occupational Asthma

Mapp

Boschetto

Maestrelli

et al. 2005

Am J Respir Crit Care Med

285

213

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“…For recent reviews on skin‐sensitization QSAR models, the reader is directed to Rodford et al (21) and Smith Pease et al (16). The QSAR model applied in this work was developed by Estrada et al in 2003 (13), relating topological sub‐structural molecular descriptors (TOPS‐MODE) to experimental data derived from the local lymph node assay (LLNA).…”

mentioning

confidence: 99%

Ranking of hair dye substances according to predicted sensitization potency: quantitative structure–activity relationships

et al. 2004

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Allergic contact dermatitis following the use of hair dyes is well known. Many chemicals are used in hair dyes and it is unlikely that all cases of hair dye allergy can be diagnosed by means of patch testing with p-phenylenediamine (PPD). The objectives of this study are to identify all hair dye substances registered in Europe and to provide their tonnage data. The sensitization potential of each substance was then estimated by using a quantitative structure-activity relationship (QSAR) model and the substances were ranked according to their predicted potency. A cluster analysis was performed in order to help select a number of chemically diverse hair dye substances that could be used in subsequent clinical work. Various information sources, including the Inventory of Cosmetics Ingredients, new regulations on cosmetics, data on total use and ChemId (the Chemical Search Input website provided by the National Library of Medicine), were used in order to identify the names and structures of the hair dyes. A QSAR model, developed with the help of experimental local lymph node assay data and topological sub-structural molecular descriptors (TOPS-MODE), was used in order to predict the likely sensitization potential. Predictions for sensitization potential were made for the 229 substances that could be identified by means of a chemical structure, the majority of these hair dyes (75%) being predicted to be strong/moderate sensitizers. Only 22% were predicted to be weak sensitizers and 3% were predicted to be extremely weak or non-sensitizing. Eight of the most widely used hair dye substances were predicted to be strong/moderate sensitizers, including PPD - which is the most commonly used hair dye allergy marker in patch testing. A cluster analysis by using TOPS-MODE descriptors as inputs helped us group the hair dye substances according to their chemical similarity. This would facilitate the selection of potential substances for clinical patch testing. A patch-test series with potent, frequently used, substances representing various chemical clusters is suggested. This may prove useful in diagnosing PPD-negative patients with symptoms of hair dye allergy and would provide some clinical validation of the QSAR predictions.

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“…For such reasons, chemicals identified as contact sensitizers are often suspected of posing a potential for respiratory sensitization. On the other hand, contact sensitization and respiratory sensitization are different hypersensitivity phenomena caused by differing immunological mechanisms (Enoch et al, 2009; Kimber and Dearman, 2005; Rodford et al, 2003). Respiratory and contact sensitizers induce different cytokine profiles, provoke responses by different T-cell populations, and most respiratory sensitizers (but not contact sensitizers) induce specific immunoglobulin E (IgE) (De Jong et al, 2009; Kimber et al, 2010; Toebak et al, 2006; Vandebriel and van Loveren, 2010).…”

Section: Respiratory Sensitization Versus Respiratory Irritationmentioning

confidence: 99%

“…An extensive literature documents its utility for contact sensitizers, but there is only limited experience for respiratory sensitizers and irritants (Gerberick et al, 2008; Patlewicz et al, 2007; Rodford et al, 2003). Because of their high NPV, SAR analyses seem able to effectively exclude from further testing LMW chemicals that are not respiratory sensitizers.…”

Section: In Silico Analysesmentioning

confidence: 99%

Methyl methacrylate and respiratory sensitization: A Critical review

Borak¹,

Fields²,

Andrews³

et al. 2011

Critical Reviews in Toxicology

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Methyl methacrylate (MMA) is a respiratory irritant and dermal sensitizer that has been associated with occupational asthma in a small number of case reports. Those reports have raised concern that it might be a respiratory sensitizer. To better understand that possibility, we reviewed the in silico, in chemico, in vitro, and in vivo toxicology literature, and also epidemiologic and occupational medicine reports related to the respiratory effects of MMA. Numerous in silico and in chemico studies indicate that MMA is unlikely to be a respiratory sensitizer. The few in vitro studies suggest that MMA has generally weak effects. In vivo studies have documented contact skin sensitization, nonspecific cytotoxicity, and weakly positive responses on local lymph node assay; guinea pig and mouse inhalation sensitization tests have not been performed. Cohort and cross-sectional worker studies reported irritation of eyes, nose, and upper respiratory tract associated with short-term peaks exposures, but little evidence for respiratory sensitization or asthma. Nineteen case reports described asthma, laryngitis, or hypersensitivity pneumonitis in MMA-exposed workers; however, exposures were either not well described or involved mixtures containing more reactive respiratory sensitizers and irritants.The weight of evidence, both experimental and observational, argues that MMA is not a respiratory sensitizer.

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Quantitative structure-activity relationships for predicting skin and respiratory sensitization

Cited by 29 publications

References 27 publications

Occupational Asthma

Occupational Asthma

Ranking of hair dye substances according to predicted sensitization potency: quantitative structure–activity relationships

Methyl methacrylate and respiratory sensitization: A Critical review

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