Irritation Studies (Rabbits)
IN VIVO
Eye Irritation
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.
Primary Eye Irritation Study (Unwashed Eyes)
- 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.
Primary Eye Irritation Study (Washed Eyes)
- Same as VIV-0441 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.
Vaginal Irritation Assay
- 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 histopathologic evaluation of vagina
IN VITRO
Ocular Irritation Assays
- 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)