Metabolism of aldrin to dieldrin by rat skin following topical application.
Metabolism of the pesticide aldrin to dieldrin in the rat was studied following topical and ip administration of 0.1-10 mg aldrin/kg body weight. When aldrin was applied topically to the dorsal skin at a dose of 10 mg/kg body weight, absorption was less efficient than after ip administration; lower blood levels of aldrin and dieldrin were seen and peak dieldrin levels were delayed. After ip administration of 1 or 10 mg aldrin/kg body weight, dieldrin was found at similar concentrations in the dorsal and ventral skin 7 hr later, whereas 7 hr after topical administration of 10 mg aldrin/kg, the dieldrin concentration in the skin at the dorsal site of application was four times higher than that at a ventral skin site. Similar differences in dieldrin concentrations between dorsal and ventral skin persisted throughout the 7-hr period following topical application. The results indicate that topically applied aldrin is metabolized to dieldrin in the skin during absorption, but the overall proportion of metabolism that takes place in the skin is small compared with the contribution of the liver. Dieldrin was not detected in the ventral skin remote from the application site 1 hr after topical application of aldrin, whereas a dieldrin concentration of 2.2 nmol/g was detected in the skin of the application site at this time; more than 99% of this dieldrin was probably formed locally by dermal metabolism of percutaneously absorbed aldrin. The efficiency of conversion of applied aldrin to dieldrin decreased with increasing aldrin dose in the range 0.1 to 10 mg/kg.
Graham
M J
MJ
Wolfson Unit of Clinical Pharmacology, University of Newcastle upon Tyne, UK.
Williams
F M
FM
Rawlins
M D
MD
D000287:Administration, Topical; D000452:Aldrin / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D004026:Dieldrin / Q000097:blood / Q000378:metabolism*; D005260:Female; D007274:Injections, Intraperitoneal; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption
D004026:Dieldrin; D000452:Aldrin