33 research outputs found
Endocrine, metabolic and apical effects of in utero and lactational exposure to non-dioxin-like 2,2 ',3,4,4 ',5,5 '-heptachlorobiphenyl (PCB 180): A postnatal follow-up study in rats
PCB 180 is a persistent and abundant non-dioxin-like PCB (NDL-PCB). We determined the developmental toxicity profile of ultrapure PCB 180 in developing offspring following in utero and lactational exposure with the focus on endocrine, metabolic and retinoid system alterations. Pregnant rats were given total doses of 0, 10, 30, 100, 300 or 1000 mg PCB 180/kg bw on gestational days 7-10 by oral gavage, and the offspring were sampled on postnatal days (PND) 7, 35 and 84. Decreased serum testosterone and triiodothyronine concentrations on PND 84, altered liver retinoid levels, increased liver weights and induced 7-pentoxyresorufin O-dealkylase (PROD) activity were the sensitive effects used for margin of exposure (MoE) calculations. Liver weights were increased together with induction of the metabolizing enzymes cytochrome P450 (CYP) 2B1, CYP3A1, and CYP1A1. Less sensitive effects included decreased serum estradiol and increased luteinizing hormone levels in females, decreased prostate and seminal vesicle weight and increased pituitary weight in males, increased cortical bone area and thickness of tibial diaphysis in females and decreased cortical bone mineral density in males. Developmental toxicity profiles were partly different in male and female offspring, males being more sensitive to increased liver weight, PROD induction and decreased thyroxine concentrations. MoE assessment indicated that the 95th percentile of current maternal PCB 180 concentrations do not exceed the estimated tolerable human lipid-based PCB 180 concentration. Although PCB 180 is much less potent than dioxin-like compounds, it shares several toxicological targets suggesting a potential for interactions
Toxicological Profile of Ultrapure 2,2 ',3,4,4 ',5,5 '-Heptachlorbiphenyl (PCB 180) in Adult Rats
Peer reviewe
Endocrine, metabolic and apical effects of in utero and lactational exposure to non-dioxin-like 2,2âČ,3,4,4âČ,5,5âČ-heptachlorobiphenyl (PCB 180):a postnatal follow-up study in rats
Abstract
PCB 180 is a persistent and abundant non-dioxin-like PCB (NDL-PCB). We determined the developmental toxicity profile of ultrapure PCB 180 in developing offspring following in utero and lactational exposure with the focus on endocrine, metabolic and retinoid system alterations. Pregnant rats were given total doses of 0, 10, 30, 100, 300 or 1000âŻmg PCB 180/kg bw on gestational days 7â10 by oral gavage, and the offspring were sampled on postnatal days (PND) 7, 35 and 84. Decreased serum testosterone and triiodothyronine concentrations on PND 84, altered liver retinoid levels, increased liver weights and induced 7-pentoxyresorufin O-dealkylase (PROD) activity were the sensitive effects used for margin of exposure (MoE) calculations. Liver weights were increased together with induction of the metabolizing enzymes cytochrome P450 (CYP) 2B1, CYP3A1, and CYP1A1. Less sensitive effects included decreased serum estradiol and increased luteinizing hormone levels in females, decreased prostate and seminal vesicle weight and increased pituitary weight in males, increased cortical bone area and thickness of tibial diaphysis in females and decreased cortical bone mineral density in males. Developmental toxicity profiles were partly different in male and female offspring, males being more sensitive to increased liver weight, PROD induction and decreased thyroxine concentrations. MoE assessment indicated that the 95th percentile of current maternal PCB 180 concentrations do not exceed the estimated tolerable human lipid-based PCB 180 concentration. Although PCB 180 is much less potent than dioxin-like compounds, it shares several toxicological targets suggesting a potential for interactions
BMD analysis of serum free T4 (A), serum free T3 (B) and serum TSH (C) in males (triangles) and females (circles).
<p>T4 and T3 were dose-dependently decreased in both genders, and TSH increased in males only. Small symbols indicate individual samples, large symbols the group mean; the vertical dotted line indicates the dose (CED) with 5% decrease or increase (CES -0.05) compared to background (a parameter). (Optimal models used for CED calculations as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104639#pone-0104639-t002" target="_blank">Table 2</a> were determined separately for females and males and are not necessarily the same shown here).</p
Significant dose-responses of PCB 180 based on total dose.
a<p>Not available.</p>b<p>Calculated as the percent difference between controls and high dose according to the fitted model.</p>c<p>Half min value added to zeros.</p>d<p>Data from Roos <i>et al.</i>, 2011.</p
Treatment groups and doses. Loading dose was administered on study days 0â5 and maintenance dose on study days 10, 17 and 24.
1<p>The target total dose of group 8 was 2000 mg/kg bw, but due to unexpected decrease in body weight (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104639#pone-0104639-g001" target="_blank">Fig. 1</a>.) the third loading dose was omitted for animal welfare reasons, and the rats received only the corn oil vehicle.</p
Densitometric analysis of Western blots for total p53 (A), p53 Ser15 (B), pChk2 Thr68 (C) and ÎłH2AX Ser139 (D) protein in livers of females.
<p>Tumor suppressor protein p53 and the DNA damage signaling markers were dose-dependently increased only in females. Each column represents mean ± SD (nâ=â5) as percent of control after adjustment to the loading control (Cdk2). Data was obtained from at least three independent analyses.</p