Subchronic (13-week) toxicity of heptachlorodibenzo-p-dioxin in male Sprague-Dawley rats.
A 13-week oral toxicity study with 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) was performed in Sprague-Dawley rats. Rats received HpCDD at five different dose levels or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at one dose level. The doses were divided into 4 daily loading doses and 6 biweekly maintenance doses. At the end of the 13-week dosing period half of the rats were scheduled for necropsy and the other half after another 13-week off-dose period. This preliminary report contains only data from male rats during the 13-week main study period. At the two highest doses of HpCDD and in the TCDD dosage group the body weight or body weight gain was reduced. Mortality was 15, 50 and 5%, respectively. Wasting syndrome was the primary cause of death, but some rats died of hemorrhage without wasting, which may be related to the dose-dependent decrease in platelet counts. Phosphoenolpyruvate carboxykinase (PEPCK), the rate limiting enzyme of gluconeogenesis, was decreased only at the two highest dose levels of HpCDD and in the TCDD group, all of which also showed mortality. Ethoxyresorufin O-deetylase (EROD) was induced dose-dependently in all treated groups. Serum total thyroxine (T4) concentrations were decreased beginning at the middle dose of HpCDD. The study demonstrates that the toxicity observed after subchronic exposure to HpCDD is very similar to that of TCDD. Most importantly, most of the effects after subchronic and acute dose exposure are identical, confirming the validity of 0.007 as the toxic equivalency factor for HpCDD.
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417.
M
M
Viluksela
B U
BU
Stahl
K K
KK
Rozman
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000633:toxicity; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014364:Tryptophan / Q000097:blood
D000072317:Polychlorinated Dibenzodioxins; D014364:Tryptophan; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D010729:Phosphoenolpyruvate Carboxykinase (GTP); C046839:1,2,3,4,6,7,8-heptachlorodibenzodioxin