Percutaneous absorption and tissue distribution of [3H]diacetoxyscirpenol (anguidine) in rats and mice.
Acute toxicity, absorption, excretion, and tissue distribution of topically administered diacetoxyscirpenol (DAS, anguidine) were studied in Fischer rats and CD-1 mice. Mortality (75%) was observed in rats treated with a single dose of 2.625 mg of DAS to 1.44 cm2 of skin, whereas the proportionate (0.75 mg to 0.42 cm2 of skin) and even higher doses were not lethal to mice. Histopathological lesions induced in the rat were similar to those observed by administration through other routes, mainly involving lymphohematopoietic tissues and the gastrointestinal tract. Although lesions in internal organs were less severe, the skin of the mouse was more severely damaged at the application site than that of the rat. During the 90-min period after topical application of a single dose of [3H]DAS, the rat absorbed and retained more [3H]DAS and excreted less radioactivity through urine and feces than the mouse. By 24 hr after treatment, the rat had absorbed, excreted, and retained about twice as much [3H]DAS as had the mouse (p < 0.05 or < 0.005). At 7 days posttreatment, the rat had absorbed more than four times the amount of [3H]DAS than had the mouse (13.1 vs 57.5%; p < 0.005). However, tissues of the mouse retained a higher proportion of administered radioactivity (4.1%) than those of the rat (1.0%; p < 0.05). Total excretion of radiolabel by the rat was approximately sixfold higher than that of the mouse (56 to 9%; p < 0.005). The ratio of excretion in urine to that in feces in the rat was about 2 to 1 (37 to 18%) and in the mouse was about 3.5 to 1 (7 to 2%). Significant differences in the time course of tissue distribution of [3H]DAS in the rat and mouse were found when data were expressed as the percentage of absorbed dose present in tissues or as specific radioactivity (dpm) per gram tissue. These results demonstrated a significant interspecies difference in acute percutaneous toxicity of DAS and different patterns of absorption, excretion, and tissue distribution of topically administered [3H]DAS in rats and mice.
Division of Toxicology, Whitaker College of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139, USA.
J S
JS
Wang
W F
WF
Busby
G N
GN
Wogan
D000042:Absorption; D000287:Administration, Topical; D000818:Animals; D005269:Femur / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009183:Mycotoxins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D009928:Organ Specificity / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013950:Thymus Gland / Q000187:drug effects; D014255:Trichothecenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D014781:Viscera / Q000187:drug effects
D009183:Mycotoxins; D014255:Trichothecenes; C001809:diacetoxyscirpenol