Age-Related Percutaneous Penetration of 2-sec-Butyl-4,6-dinitrophenol (Dinoseb) in Rats

¹⁴C]Dinoseb was applied to previously clipped back skin of33- and 82-day-old female Fischer 344 rats at a dosage rangeof 210–2680 nmol/cm². Radioactivity in the treated skin,tissues, urine, and feces was determined at 1, 6, 24, 48, 72,and 120 hr following dermal application. In vitro dermal absorptionof ¹⁴C]dinoseb was also measured in rats of the same age bystatic and flow-through methods. In vivo dermal absorption inboth young and adults appeared biphasic with 55.6 and 82.7%of the recovered dose, respectively, penetrating in 72 hr. Invitro measurements of skin absorption at 72 hr with static cellsshowed higher values in young and lower values in the adultcompared to in vivo dermal absorption values, In vitro flow-throughmeasurements at 72 hr gave lower dermal absorption values forboth young and adult rats, compared to In vivo values. Followingin vivo application, adults excreted about 70% of the totalrecovered dose in urine, 16% in feces, and retained 7% in thebody at 120 hr. HPLC analysis of urine collected at 24 hr fromadults administered ¹⁴C]dinoseb showed extensive metabolismof parent. Excretion and retention results for young were about80% of the adult values, which also was the young to adult ratioof dermal penetration. Blood had the highest concentration ofdinoseb-derived radioactivity of the tissues examined. The kidneyto blood ratio averaged 0.60 in young and 0.41 in adults, whilethe liver and carcass to blood ratio averaged 0.18 in youngand 0.11 in adult. Dermal absorption in young rats was slightlyless than that in adults, and the subsequent kinetics of retentionand excretion appeared different, In vitro dermal penetrationof dinoseb was usually lower than In vivo absorption.