Respiratory Sensitization Mixtures

Numerous single chemicals are known to be sensitizers. These include isocyanates, anhydrides, amines, metals and metal compounds, and plastics and their monomers. A complete list of these, as well as of biological sensitizers, was compiled by van Kampen et alJ22 Table 17.4 contains a partial list of single chemical sensitizers. 

Inhalation of sensitizing chemicals can lead to dermal sensitization, and dermal absorption of sensitizing chemicals can lead to respiratory sensitization. Airway exposure to toluene diisocyanate has been shown to induce dermal sensitization, I23l and dermal application of trimellitic anhydride has been shown to induce respiratory sensitization in test animalsJ24-26 These results are consistent with the understanding that both respiratory and dermal sensitization are associated with IgE responses. 

Respiratory sensitization is not limited to single chemical compounds. Several mixtures have been identified as sensitizers. The following are illustrative. 

Diesel exhaust particles (DEP) are composed of carbon black and adhered lipophilic and hydrophilic compounds that include approximately 18,000 different high molecular weight organic compounds, composed of aliphatic and aromatic hydrocarbons, polycyclic aromatic hydrocarbons, polycyclic 

Diphenylmethane diisocyanate Hexamethylene diisocyanate Methyl isocyanate Naphthalene diisocyanate Toluene diisocyanate 

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Table 3.4.1 Cut-off values/concentration limits of ingredients of a mixture classified as either skin sensitizers or respiratory sensitizers that would trigger classification of the mixture...

NOTE 4 If a solid or liquid respiratory sensitizer is present in the mixture as an ingredient at a concentration of > 1.0%, both an SDS and a label would generally be expected. 

Mixture Does the mixture as a whole or its ingredients have respiratory sensitization data ... 

Does the mixture contain one or more ingredients classified as a respiratory sensitizer at... 

If bridging principles do not apply, classify if any individual respiratory sensitizer in the mixture has a concentration of ... 

Chemical mixtures in cosmetics give rise to enhanced toxicity, low level toxicity, and unexpected target organ attack. Cosmetic products are composed of many lipophilic and hydrophilic chemicals. Numerous instances of strange injuries, including chemical burns and skin and respiratory sensitization from the use of cosmetic products, have been documented in which the injuries sustained could not be accounted for by a consideration of the individual chemicals involved J3°l... 

Diazomelhane (azimelhylene, diazirine [CAS 334-88-3]) Extremely irritating to eyes and respiratory tract pulmonary edema has been reported. Immediate symptoms include cough, chest pain, and respiratory distress, A potent methylating agent and respiratory sensitizer, 0.2 ppm, A2 2 ppm Yellow gas with a musty odor. Air mixtures and compressed liquids can be explosive when heated or shocked. 

Respiratory Sensitizers or Skin Sensitizers That Would Trigger Classification of the Mixture... 

OECD has also published a document on a Harmonised integrated classification system for human health and environmental hazards of chemical substances and mixtures (OECD 2001b). Chapter 2.4 addresses a harmonized system for the classification of chemicals, which cause respiratory or skin sensitization. 

Sensitization of the respiratory tract has followed chronic exposure to fumes or dust of TETA, manifested by bronchial asthma. One worker developed asthma after working with an epoxy resin-TETA formulation for 6 months in a job laminating aircraft windows. In an environmental chamber, the worker developed flulike symptoms and asthmatic breathing after simulating the job conditions for 2 hours with the resin-TETA mixture. Similar exposure to the resin alone did not produce the symptoms. 

Similarly, no respiratory effects were found in rats and mice chronically exposed by diet to 5/ 10" and 1.3 10s g/kg/day of 2,7-DCDD, respectively (NCI/NTP 1979a). In contrast, rats exposed chronically by gavage to a mixture of 1,2,3,6,7,8-HxCDD and 1,2,3,7,8,9-HxCDD at 0.18, 0.34, and 0.7 g/kg/day had a dose-related increased incidence of adenomatous hyperplastic lesions in terminal bronchioles and adjacent alveoli of both males and females no such effects were found in mice exposed chronically to 0.7 g/kg/day of that same mixture (NCI/NTP 1980). The existing information suggests that in animals, the respiratory system is not a sensitive target for CDDs toxicity via oral exposure. 

Information regarding levels of chromium(III) compounds that result in death is available only for the oral route. Systemic effects of acute- and intermediate-duration inhalation exposure to chromium(III) are limited to the respiratory system. Information on systemic effects of chronic inhalation exposure to chromium(III) is limited to a study that used a mixture of chromium(VI) and chromium(III). Studies of intermediate- and chronic duration oral exposure to chromium(III) failed to find any systemic, neurological, developmental, reproductive, or carcinogenic effects. The immunological and genotoxic effects of chromium(III) in animals have not been tested by the oral route. Information regarding effects of dermal exposure of animals to chromium(III) is limited to a study of skin ulceration after acute exposure and dermal sensitization tests. 

The mixture should be classified as a respiratory or skin sensitizer when at least one ingredient has been classified as a respiratory or skin sensitizer and is present at or above the appropriate cutoff value/concentration limit for the specific endpoint as shown in Table 3.4.1 for solid/liquid and gas respectively. 

General and specific considerations concerning labelling requirements are provided in Hazard communication Labelling (Chapter 1.4), Annex 2 contains summary tables about classification and labelling. Annex 3 contains examples of precautionary statements and pictograms which can be used where allowed by the competent authority. Table 3.4.2 below presents specific label elements for substances and mixtures that are classified as respiratory and skin sensitizers based on the criteria in this chapter. 

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