Dermal In Vivo Studies
SKIN IRRITATION: Ratings corresponding to the following definitions are derived from data obtained from the test methods as described in 16 CFR 1500.41 and/or NAS Publication 1138, and categories of toxicity as described in 16 CFR 1500.3.
- Practically Non-Irritating:
- Moderately Irritating:
- Primary Skin Irritant:
- Corrosive:
. Moderately Irritating: The undiluted product causes well-defined inflammation (edema and erythema skin reaction values of 2) during the study period. Primary Irritation Index of 2-4.9.
. Primary Skin Irritant: The undiluted product causes moderate to severe inflammation (edema and erythema skin reaction values of 3 or 4) of the intact or abraded skin of rabbits during the study period. Primary Irritation Index of 5 or more.
. Corrosive: The undiluted product causes visible destruction or irreversible alterations of the tissue structure at the site of contact on intact or abraded skin of rabbits during the study period.
Acute Dermal Limit Test
- One group of 5 male and 5 female rabbits
- A single 24-hr dermal exposure to the test substance
- Animals are weighed weekly and observed for clinical signs of toxicity and death for 2 weeks after treatment
- Gross necropsy is performed on all animals that die and on all survivors at the end of the 2-week study
- No tissues are preserved; necropsy findings are recorded
- Groups of 5 male and 5 female rabbits
- A single 24-hr dermal exposure to 3 dose levels of the test substance
- Animals are weighed weekly and observed for clinical signs of toxicity and death for 2 weeks after treatment
- Necropsy is performed on all animals that die and on all survivors at the end of the 2-week study
- No tissues are preserved; necropsy findings are recorded
- The shaved intact skin of 6 rabbits is exposed to the test substance for 4 hr
- After the exposure period, the skin is graded for irritation at 1, 24, 48, and 72 hr
- Observation period may be extended for up to 21 days to evaluate the reversibility of the effects observed.
- Groups of 20 males and 20 females are treated with the test substance by dermal application at 3 dose levels for 90 days; a vehicle control group is included; a satellite toxicokinetic group of 6 males and 6 females is included for plasma drug evaluations
- Study measurements include daily clinical observations, daily irritation scores at application site, weekly body weights
- Plasma drug evaluations at approximately 4 time points on Days 1 and 28
- Hematology and serum clinical chemistry at termination
- Necropsies are performed on any animals that die or upon termination; weights are recorded for major organs
- Full histopathological examinations are conducted on the control and high-dose groups and on any unscheduled deaths
- Target organs are examined in the intermediate groups