Percutaneous absorption of 2-nitro-p-phenylenediamine

Area of Science:

• Toxicology
• Dermatology
• Pharmacokinetics

Background:

• 2-nitro-p-phenylenediamine (2-NPPD) is a common ingredient in hair colorants.
• Understanding its absorption, metabolism, and skin penetration is crucial for consumer safety assessments.

Purpose of the Study:

• To investigate the absorption, metabolism, and skin penetration of 2-NPPD in rats.
• To assess the impact of various application conditions on 2-NPPD skin penetration.
• To estimate potential consumer exposure levels from hair colorant products.

Main Methods:

• Radiolabeled [(14)C]2-NPPD was administered orally, intraperitoneally, and topically to male and female rats.
• Skin penetration was quantified under different conditions: vehicle, occlusion, rinsing, contact time, repeated application, concentration, and skin condition (clipped vs. unclipped).
• Excretion, retention, urine metabolites, and blood radioactivity levels were analyzed.

Main Results:

• Oral and intraperitoneal administration led to rapid excretion (60% feces, 35% urine) with minimal retention (approx. 2% at 3 days).
• High skin penetration of 2-NPPD was observed, with female rats absorbing more than males. Penetration increased with occlusion, longer contact time, higher concentration, and repeated applications.
• Metabolism studies revealed six unidentified radioactive components in urine, with minimal parent compound detected. Blood radioactivity levels remained low after topical administration.

Conclusions:

• 2-NPPD is rapidly excreted and poorly retained systemically after oral or intraperitoneal administration.
• Skin penetration is a significant route of exposure, influenced by product formulation and application method.
• Estimated consumer exposure from semi-permanent hair colorants containing 1% 2-NPPD is up to 10 µg/kg body weight per application.