Systemic and myelotoxic effects of single administration of 2,3,7,8-tetrabromodibenzo-p-dioxin in rats

Abstract

Objective: Systemic and myelotoxic effects of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) were examined by the single administration of TBDD by gavage to rats.Methods: Fifteen Wistar rats of both sexes per group received 0, 10, 30, 100 or 300 μg TBDD/kg body weight. Rats surviving to the scheduled necropsy on Days 2, 7 and 36 after TBDD administration were examined for growth rate, organ weight, hematology, histopathology and adipose tissue levels of TBDD.Results: Three 300 μg/kg-dosed females died on Days 21, 23 and 27, and exhibited a marked decrease in body weight, severe thymic atrophy, decreased bone marrow hematopoiesis and hemorrhage in the subarachnoid space of brain and spinal cord. TBDD-dosed surviving rats exhibited growth retardation, decreased bone marrow hematopoiesis, decreases in red blood cell counts, hemoglobin concentrations, and hematocrit values, an increase in reticulocytes and decreases in platelet counts, white blood cell counts and eosinophils. These signs suggested TBDD myelotoxicity. Splenic extramedullary hematopoiesis was increased in both sexes given TBDD, whereas atrophy of the splenic white pulp occurred only in TBDD-dosed females. Marked decreases in body weights and the size and weight of the thymus, severe thymic atrophy and death in TBDD-dosed females suggested a wasting syndrome. The adipose tissue level of TBDD culminated on Day 7 and decreased to 20-30% of the Day 7 level on Day 36.Conclusions: The TBDD-induced effects were characterized by a wasting syndrome and myelotoxicity that appeared at the dose levels of 30 μg/kg and higher and caused death in 300 μg/kg-dosed females.

Occurrence of Two Different Types of Glutathione S-Transferase Placental Form-Positive Hepatocytes after a Single Administration of 2,3,7,8-Tetrabromodibenzo-p-dioxin in Rats

“…This finding might extend the previously reported findings 11,14,15,37) of the enhanced TBDD hepatotoxicity of female rats to higher susceptibility of female rats to the formation of GST-P-positive liver foci than males. Lucier et al 38) demonstrated using the two-stage hepatocarcinogenesis model that the number of GST-P-positive foci were greater in intact female rats receiving a single ip injection of DEN followed by repeated oral administration of TCDD at a dose equivalent to 100 ng/kg/d for 30 wk than in ovariectomized rats receiving DEN and TCDD.…”

“…The animals were quarantined and acclimated for 2 wk, and then divided by stratified randomization into 5 body weight-matched groups, each comprising 15 rats of both sexes. The conditions under which the animals were raised were described in detail previously 14,15) . The animals were cared for according to the Guide for the Care and Use of Laboratory Animals 34) .…”

“…Except for a medical case report 10) on laboratory exposure of a chemist to TBDD, there are few medical case reports and epidemiological studies or animal toxicology studies of PBDD/PBDF available for human health risk assessments. Experimental toxicology studies have revealed that TBDD caused systemic, hematological, hepatic, teratogenic and myelogenic toxicities [11][12][13][14][15] .…”

Dose- And Time-Dependent Effects of 2,3,7,8-Tetrabromodibenzo-P-Dioxin on Rat Liver

“…Single oral and intraperitoneal administrations of TBDD were reported to induce teratogenic effects in mice (Birnbaum et al, 1991) and to induce thymic atrophy, body weight loss and induction of hepatic microsomal enzymes in immature male rats (Mason et al, 1987). Yamamoto et al (2006) demonstrated that a single administration of TBDD by gavage to rats induced systemic and myelotoxic effects associated with a wasting syndrome.…”

“…The toxicity of TBDD has been reported to be less potent than that of 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) (Ivens et al, 1992 andBirnbaum et al, 1991;Yamamoto et al, 2006). TCDD is known to target the liver in humans and experimental animals (IARC, 1997;Gupta et al, 1973;Jones and Butler, 1974;Kociba et al, 1976;Plüss et al, 1988;Pohjanvirta et al, 1989).…”