title: Incidence of jaw lesions and activity and gene expression of hepatic P4501A enzymes in mink (Mustela vison) exposed to dietary 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran, and 2,3,4,7,8-pentachlorodibenzofuran.
abstract: This study assessed the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 2,3,7,8 tetrachlorodibenzofuran (TCDF) on the incidence of jaw lesions and on hepatic cytochrome P4501A (CYP1A) endpoints in mink (Mustela vison). Adult female mink were assigned randomly to one of 13 dietary treatments (control and four increasing doses of TCDD, PeCDF, or TCDF) and provided spiked feed for approximately 150 d (60 d prior to breeding through weaning of offspring at 42 d post-parturition). Offspring were maintained on their respective diets for an additional 150 d. Activity of hepatic CYP1A enzymes in adult and juvenile mink exposed to TCDD, PeCDF, or TCDD was generally greater compared with controls, but changes in other CYP1A endpoints were less consistent. Histopathology of the mandible and maxilla of juvenile mink suggested a dose-related increase in the incidence of jaw lesions. The dietary effective doses (ED) for jaw lesions in 50% of the population (ED50) were estimated to be 6.6, 14, and 149 ng/kg body weight (bw)/d for TCDD, PeCDF, and TCDF, respectively. The relative potencies of PeCDF and TCDF compared with TCDD based on ED10, ED20, and ED50 values ranged from 0.5 to 1.9 and 0.04 to 0.09, respectively. These values are within an order of magnitude of the World Health Organization toxic equivalency factor (TEF(WHO)) values of 0.3 and 0.1 for PeCDF and TCDF, respectively.
authors.affiliation: Department of Animal Science, Michigan State University, East Lansing, MI, USA. bursian@msu.edu
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Bursian
authors.forename: Jeremy
authors.initials: J
authors.lastname: Moore
authors.forename: John L
authors.initials: JL
authors.lastname: Newsted
authors.forename: Jane E
authors.initials: JE
authors.lastname: Link
authors.forename: Scott D
authors.initials: SD
authors.lastname: Fitzgerald
authors.forename: Nora
authors.initials: N
authors.lastname: Bello
authors.forename: Virunya S
authors.initials: VS
authors.lastname: Bhat
authors.forename: Denise
authors.initials: D
authors.lastname: Kay
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.forename: Steve
authors.initials: S
authors.lastname: Wiseman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Budinsky
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Zwiernik
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004032:Diet; D023381:Endpoint Determination; D005260:Female; D015870:Gene Expression; D015994:Incidence; D007568:Jaw / Q000473:pathology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008907:Mink / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D036401:Toxicity Tests, Chronic
chemical_list: D001572:Benzofurans; D000072317:Polychlorinated Dibenzodioxins; D019363:Cytochrome P-450 CYP1A1; C038890:2,3,4,7,8-pentachlorodibenzofuran; C014211:2,3,7,8-tetrachlorodibenzofuran