Induction of respiratory hypersensitivity to diphenylmethane-4,4′-diisocyanate (MDI) in guinea pigs. Influence of route of exposure

Rattray, N.J.; Botham, Philip A.; Hext, Paul M.; Woodcock, D.R.; Fielding, I.; Dearman, Rebecca J.; Kimber, Ian

doi:10.1016/0300-483x(94)90108-2

Cited by 118 publications

(63 citation statements)

References 29 publications

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“…These studies have demonstrated that dose, route, and timing of the sensitizing dose are key determinants of sensitization and subsequent asthma. In general, relatively modest and infrequent skin-sensitizing exposure doses, such as single or two-time with 1% isocyanate, are highly effective at inducing Th2-like sensitization (11,14,16), and can be more effective than sensitization by inhalation (11,14,17). Such exposures are likely comparable to skin exposures that can occur in the workplace.…”

Section: Animal Models Of Chemical and Protein Allergen Skin Exposurementioning

confidence: 99%

Skin Exposure and Asthma: Is There a Connection?

Redlich¹

2010

Proceedings of the American Thoracic Society

100

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Numerous occupational and environmental exposures that increase asthma risk have been identified. Research and prevention have focused primarily on the respiratory tract. However, recent studies suggest that the skin may also be an important route of exposure and site of sensitization that contributes to asthma development. Factors that impair skin barrier function, such as filaggrin gene mutations or skin trauma, may facilitate allergen entry and promote Th2-like sensitization and subsequent asthma. Animal studies demonstrate that skin exposure to chemical and protein allergens is highly effective at inducing sensitization, with subsequent inhalation challenge eliciting asthmatic responses. A similar role for human skin exposure to certain sensitizing agents, such as isocyanates, is likely. Skin exposure methodologies are being developed to incorporate skin exposure assessment into epidemiology studies investigating asthma risk factors.Keywords: skin exposure; asthma; isocyanates; epidermal barrier function; sensitization Environmental and occupational asthma research and practice have focused primarily on the respiratory tract as the key route of exposure and pathogenesis. However, several lines of research support an important role for skin exposure in initiating and driving Th2-like immune responses and asthma. Human and animal studies of atopic dermatitis have identified skin epithelial barrier dysfunction, which may facilitate allergen entry, as a key factor in the development of atopic asthma and sensitization. This article highlights recent findings from a diverse literature that support the concept that skin may be an important site of exposure for certain occupational and environmental allergens.

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Section: Animal Models Of Chemical and Protein Allergen Skin Exposurementioning

confidence: 99%

Skin Exposure and Asthma: Is There a Connection?

Redlich¹

2010

Proceedings of the American Thoracic Society

100

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“…The scientific literature contains limited animal data suggesting that dermal exposure to diisocyanates may produce respiratory sensitization. 18,19,20,21 This finding has not been documented in dermally exposed workers. HP also has been described in workers exposed to isocyanates.…”

Section: Health Effectsmentioning

confidence: 86%

Health hazard evaluation report: HETA-99-0088-2753, U.S. Postal Service vehicle maintenance facility, Chicago, Illinois.

1999

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“…The challenge treatment was carried out via inhalation exposure (25.9-44.1 mg/m 3 ). A hypersensitivity reaction occurred after intradermal induction at 0.03% and above and after dermal induction at 10% and above, whereas no reactions were observed after inhalation induction and inhalation challenge treatment (Rattray et al 1994).…”

Section: Respiratory Tractmentioning

confidence: 90%

“…In a maximization test with guinea pigs and in a mouse ear swelling test, MDI was found to cause skin sensitization; in a maximization test with PMDI, however, sen-sitizing effects were not found (see documentation "4,4′-Methylene diphenyl diisocyanate (MDI) and "polymeric" MDI (PMDI)" 1997; Rattray et al 1994). Also in a local lymph node assay (LLNA) in the mouse, which was published only as an abstract, MDI had skin-sensitizing effects.…”

Section: Skinmentioning

confidence: 99%

4,4′‐Methylene diphenyl diisocyanate (MDI) [101‐68‐8] and “polymeric” MDI (PMDI) [9016‐87‐9] [MAK Value Documentation, 2008]

2015

The MAK‐Collection for Occupational Health and Safety

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The article contains sections titled: Toxic Effects and Mode of Action Mechanism of Action Toxicokinetics and Metabolism Absorption, distribution, elimination Metabolism Binding to macromolecules/biological monitoring Effects in Humans Single exposures Repeated exposure Local effects on skin and mucous membranes Allergenic effects Reproductive and developmental toxicity Genotoxicity Carcinogenicity Animal Experiments and in vitro Studies Acute toxicity Subacute, subchronic and chronic toxicity Local effects on skin and mucous membranes Allergenic effects Reproductive toxicity Genotoxicity Carcinogenicity Manifesto (MAK value, classification)

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Induction of respiratory hypersensitivity to diphenylmethane-4,4′-diisocyanate (MDI) in guinea pigs. Influence of route of exposure

Cited by 118 publications

References 29 publications

Skin Exposure and Asthma: Is There a Connection?

Skin Exposure and Asthma: Is There a Connection?

Health hazard evaluation report: HETA-99-0088-2753, U.S. Postal Service vehicle maintenance facility, Chicago, Illinois.

4,4′‐Methylene diphenyl diisocyanate (MDI) [101‐68‐8] and “polymeric” MDI (PMDI) [9016‐87‐9] [MAK Value Documentation, 2008]

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