Irritation Studies (Rabbits)

• Test substance is instilled into one eye of each of 6 rabbits (unwashed eyes).
• The cornea, iris, and conjunctival tissue of the treated eyes are graded for irritation effects at 1, 24, 48 and 72 hr after instillation.
• Observation period may be extended for up to 21 days to evaluate the reversibility of the effects observed.

• Same as above but with 3 additional rabbits with eyes washed at end of treatment period.
• Observation period may be extended for up to 21 days to evaluate the reversibility of the effects observed.

Ratings corresponding to the Draize Scale for scoring ocular lesions and temporal reversibility criteria as set forth in NAS Publication 1138.

• Practically Non-Irritating: The undiluted product, when instilled into the eyes of rabbits, produces no noticeable irritation or slight transient conjunctival irritation. (Average Draize score range 0.00-15.0).
• Slightly Irritating: The undiluted product, when instilled into the eyes of rabbits, produces slight to moderate conjunctival irritation, slight corneal involvement, and/or slight iritis. (Average Draize score range 15.1-25.0). The effects clear within 7 days.
• Moderately Irritating: The undiluted product, when instilled into the eyes of rabbits, produces moderate corneal involvement with or without severe iritis. (Average Draize score range 25.1-50.0). The effects clear within 21 days.
• Severely Irritating (or Corrosive): The undiluted product, when instilled into the eyes of rabbits, produces severe corneal involvement with or without severe iritis. (Average Draize score range 50.1-110.0). The effects persist for 21 days or more.

• Five groups of 5 female rabbits; control, positive control, 3 dose levels (25 animals)
• Daily vaginal administration of test substance for 10 days
• Daily clinical observations and visual scoring of genital region
• Gross necropsy and preservation of reproductive organs and bladder
• Histological evaluation of all preserved tissues
• Calculation of mean irritation score (MIS) based on histopathological evaluation of vagina

• Three dimensional human ocular tissue equivalent systems
• Chorioallantoic Membrane Vascular Assay (CAMVA)
• Bovine Corneal Opacity and Permeability Assay (BCOP)
• Keratinocyte Proliferation (turnover) Assay
• Keratinocyte/Fibroblast Viability Assay (Neutral Red or MTT)