3.1 This test method was developed to meet the following criteria:

3.1.1 It provides positive recognition of sensory irritants of widely varying potencies.

3.1.2 It is sufficiently simple to permit the testing of large numbers of materials.

3.1.3 This test method is capable of generating concentration-response curves for purposes of compound comparison.

3.1.4 This test method has good reproducibility.

3.2 This test method can be used for a variety of divergent purposes, including the assessment of comparative irritancy of compounds or formulations and setting interim exposure levels for the workplace (1, 2).2

3.3 It has been shown that for a wide variety of chemicals and mixtures, a perfect rank order correlation exists between the decreases in respiratory rate in mice and subjective reports of sensory irritation in man (1, 3, 4, 5).

3.4 A quantitative estimate of the sensory irritancy of a wide variety of materials can be obtained from concentration-response curves developed using this method (1, 3, 4, 6, 7, 8, 9).

3.5 Although this test method is intended to measure sensory irritation of the nasal mucosa, the cornea is innervated by the same nerve. This animal model will, therefore, allow an estimate of the irritant potential of cosmetic ingredients or other household products to the eye, assuming that they can be aerosolized (10).

3.6 This test method is recommended for setting interim guidelines for exposure of humans to chemicals in the workplace, to assess acute sensory irritation resulting from inadvertent spills of household products, and to assess the comparative irritancy of formulations or materials intended for a variety of uses (see Appendix X2).

FIG. 1 Typical Tracing of Normal Mouse Respiration (Top), and of a" Moderate" Sensory Irritant Response (Bottom)

Note 1: Taken from Ref. (3).

FIG. 2 Typical Tracing of Normal Mouse Respiration (Top), a Moderate Pulmonary Irritant Response (Center), and an Extreme Pulmonary Irritant Response (Bottom)

Note 1: Taken from Ref. (8).

3.7 This test method will detect irritating effects at concentrations far below those at which pathological changes are observed (9).

Note 1: A good overview of the toxicological evaluation of irritant compounds is given in Ref (8).