User Guide to Thresholds and Classification - Environmental ...

198User Guide for Thresholds and ClassificationsThe evidence referred to above could be:clinical history and data from appropriate lung function tests related to exposure to the substance,confirmed by other supportive evidence, which may include:a. an in vivo immunological test (for example, the skin prick test);b. an in vitro immunological test (for example, serological analysis);c. studies that may indicate other specific hypersensitivity reactions where immunological mechanismsof action have not been proven (for example, repeated low level irritation or pharmacologicallymediated effects);d. a chemical structure related to substances known to cause respiratory hypersensitivity;data from positive bronchial challenge tests with the substance, conducted according to acceptedguidelines for determining a specific hypersensitivity reaction.Clinical history should include both medical and occupational history to determine a relationship betweenexposure to a specific substance and the development of respiratory hypersensitivity. Relevant informationincludes aggravating factors in the home and workplace, the onset and progress of the disease, and familyand medical histories of the patient in question. The medical history should also include a note of otherallergic or airway disorders from childhood, and the patient‘s smoking history.The results of positive bronchial challenge tests are considered to provide sufficient evidence forclassification on their own. It is, however, recognised that in practice many of the examinations listed abovewill already have been carried out.Animal studiesData from appropriate animal studies 3 that may be indicative of the potential of a substance to causesensitisation by inhalation in humans 4 may include:measurements of Immunoglobulin E (IgE) and other specific immunological parameters (for example, inmice); andspecific pulmonary responses in guinea pigs.13.2.4. Contact sensitisation – specific considerations (subclass 6.5B)For classification of a substance, evidence should include any or all of:a. positive data from patch testing, normally obtained in more than one dermatology clinic;3 Recognised animal models for the testing of respiratory hypersensitivity are not available. Under certain circumstances,animal testing may be used; for example, a modification of the guinea pig maximisation test for determining the relativeallergenicity of proteins. However, these tests still need further validation.4 The mechanisms by which substances induce symptoms of asthma are not yet fully known. For preventative measures,these substances are considered respiratory sensitisers. However, if on the basis of the evidence, it can bedemonstrated that these substances induce symptoms of asthma by irritation only in people with bronchialhyperreactivity, they should not be considered respiratory sensitisers.January 2012 EPA0109