Age-related percutaneous penetration of 2-sec-butyl-4,6-dinitrophenol (dinoseb) in rats.
[14C]Dinoseb was applied to previously clipped back skin of 33- and 82-day-old female Fischer 344 rats at a dosage range of 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 absorption of [14C]dinoseb was also measured in rats of the same age by static and flow-through methods. In vivo dermal absorption in both young and adults appeared biphasic with 55.6 and 82.7% of the recovered dose, respectively, penetrating in 72 hr. In vitro measurements of skin absorption at 72 hr with static cells showed higher values in young and lower values in the adult compared to in vivo dermal absorption values. In vitro flow-through measurements at 72 hr gave lower dermal absorption values for both young and adult rats, compared to in vivo values. Following in vivo application, adults excreted about 70% of the total recovered dose in urine, 16% in feces, and retained 7% in the body at 120 hr. HPLC analysis of urine collected at 24 hr from adults administered [14C]dinoseb showed extensive metabolism of parent. Excretion and retention results for young were about 80% of the adult values, which also was the young to adult ratio of dermal penetration. Blood had the highest concentration of dinoseb-derived radioactivity of the tissues examined. The kidney to blood ratio averaged 0.60 in young and 0.41 in adults, while the liver and carcass to blood ratio averaged 0.18 in young and 0.11 in adult. Dermal absorption in young rats was slightly less than that in adults, and the subsequent kinetics of retention and excretion appeared different. In vitro dermal penetration of dinoseb was usually lower than in vivo absorption.
Hall
L L
LL
Environmental Toxicology Division, U. S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Fisher
H L
HL
Sumler
M R
MR
Hughes
M F
MF
Shah
P V
PV
D019297:2,4-Dinitrophenol / Q000031:analogs & derivatives*; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D004140:Dinitrophenols / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D006540:Herbicides / Q000493:pharmacokinetics*; D011247:Pregnancy; D011874:Radiometry; D051381:Rats; D011916:Rats, Inbred F344; D012869:Skin Absorption; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D004140:Dinitrophenols; D006540:Herbicides; D019297:2,4-Dinitrophenol; C018527:dinoseb