Percutaneous absorption of 2-nitro-p-phenylenediamine

Abstract

Synopsis Studies have been done on the absorption and metabolism of the hair colourant 2-nitro-p-phenylenediamine (2-NPPD) in rats with particular reference to skin penetration. When [(14)C]2-NPPD was given orally or injected intraperitoneally into male and female rats, excretion was rapid and mainly in the faeces (60%) and urine (35%). No radioactivity was measurable in the expired air. At 3 days after dosing, approximately 2% of the dose was retained in the body. Application of [(14)C]2-NPPD in ethanol to the clipped skin of rats gave a high skin penetration. Male rats absorbed less (11.7 mug cm(-2)) through the skin than did female rats (24.6 mug cm(-2)). Application of [(14)C]2-NPPD in a solution of a hair colourant product base to the clipped skin of rats gave a high penetration if the skin was occluded or not rinsed. Penetration was much reduced after rinsing and protection by non-occlusive patches. With these latter conditions, skin penetration in clipped rats treated with a 0.5% (w/v) solution of [(14)C]2-NPPD doubled to 6.1 mug cm(-2) when the contact time was increased from 5 to 30 minutes, increased two to three times after two and three repeated applications, increased in proportion to the applied concentration and was reduced by half when applied to unclipped skin. The metabolic pattern in urine from rats after different routes of administration showed only a trace of the parent [(14)C]2-NPPD but six other radioactive components. The identity of these components has not yet been fully resolved. Blood levels of radio-activity during 2 days after topical administration were low. Under realistic conditions of use by the consumer the calculated dose through the skin based on the experimental rat data is up to 10 mug/kg body weight per application of a semi-permanent hair colourant product containing 1% of 2-NPPD.