Effect of dose on the percutaneous absorption of 2- and 4-chloronitrobenzene in rats.
The effect of dose on the dermal absorption of 2- and 4-chloronitrobenzene (2- and 4-CNB) has been investigated in rats following nonocclusive protective dermal application on an area of 4 cm2 per animal at approximately 0.0325, 0.325, and 3.25 mg/cm2 (0.65, 6.5, and 65 mg/kg, respectively). At the three-dose levels, 33-40% and 51-62% of the dose of 2- and 4-CNB, respectively, was absorbed from the skin within 72 hr. The balance of the dose was recovered in the protective device and the organic trap (i.e. that portion unavailable for dermal absorption). The absorbed radioactivity was excreted in urine (21-28% of dose, 2-CNB; 43-45%, 4-CNB) and feces (11-15%, 2-CNB; 5-12%, 4-CNB). The extent and rate of dermal absorption and urinary and fecal excretion of 2-CNB were linear over the 0.65-65 mg/kg dose range; for 4-CNB they were linear over the 0.65-6.5 mg/kg dose, and nonlinear at the 65 mg/kg dose.
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Bloomfield, NJ 07003.
A A
AA
Nomeir
P M
PM
Markham
A L
AL
Mongan
D M
DM
Silveira
M
M
Chadwick
D000279:Administration, Cutaneous; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D008297:Male; D009578:Nitrobenzenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D012869:Skin Absorption; D013223:Statistics as Topic
D009578:Nitrobenzenes; C010407:4-chloronitrobenzene; C032785:2-chloronitrobenzene