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1.
Toxicol Sci ; 110(1): 107-16, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19420013

ABSTRACT

Polybrominated diphenyl ethers (PBDEs) are widespread persistent and bioaccumulative environmental contaminants. Recent scientific attention has focused on the developmental toxicity of PBDE commercial mixtures following perinatal exposure of rodents; however, these studies do not necessarily predict toxicity to highly exposed top predators, such as mink (Mustela vison). Here we assessed the effects of environmentally relevant doses (0, 0.1, 0.5, and 2.5 ppm [wt/wt] in feed) of a technical pentabrominated diphenyl ether mixture, DE-71, on reproductive performance of mink and on development of offspring exposed perinatally and post-weaning until 33 weeks. A dietary concentration that causes no effects on reproduction in rodents, 2.5-ppm DE-71, resulted in complete reproductive failure in these mink, while whelping rates were not affected at all lower does. Developmental effects in offspring were evident in 33-week-old juveniles, which were more sensitive to effects than their respective dams. Juvenile thyroid hormone homeostasis was also much more sensitive compared to rodents, and at 0.5-ppm DE-71, total triiodothyronine (T3) was significantly decreased in all males and females, even despite a compensatory increase of total thyroxine (T4) in females. T4-outer-ring deiodinase activity, mainly contributed by type II deiodinase, was not affected at any dose for any life stage, but thyroid follicular epithelium cell height was elevated in the 0.5-ppm-treated juveniles (p = 0.057). Ethoxyresorufin O-deethylase activity was significantly induced in all offspring at 33 weeks, most likely as a consequence of polybrominated dioxin, furan, or biphenyl impurities in DE-71. Biomonitoring of wild mink in the Great Lakes region indicated that most populations had lower concentrations than what are expected to affect thyroid hormone homeostasis, but margins of safety are small and mink around Hamilton Harbour exceeded the no observed adverse effect level for T3 disruption.


Subject(s)
Flame Retardants/toxicity , Halogenated Diphenyl Ethers/toxicity , Mink/physiology , Reproduction/drug effects , Teratogens/toxicity , Animals , Animals, Domestic , Animals, Newborn , Animals, Wild , Cytochrome P-450 CYP1A1/blood , Eating/drug effects , Female , Great Lakes Region , Liver/drug effects , Liver/enzymology , Liver/metabolism , Male , Organ Size/drug effects , Pregnancy , Risk Assessment , Survival Analysis , Thyroid Diseases/chemically induced , Thyroid Diseases/pathology , Thyroid Hormones/blood
2.
Environ Toxicol Chem ; 26(5): 988-97, 2007 May.
Article in English | MEDLINE | ID: mdl-17521147

ABSTRACT

Polybrominated diphenyl ethers (PBDEs) are persistent, bioaccumulative, organohalogen compounds that are increasing exponentially in the Great Lakes (Canada/USA) biota. The present study was undertaken to examine the immunological effects of a commercial PBDE mixture in ranch mink (Mustela vison). Twenty-week-old mink (n = 10 mink/group) were exposed to 0, 1, 5, or 10 ppm of DE-71 through their diet for eight weeks. The phytohemagglutinin-induced cutaneous reaction, and antibodies specific to keyhole limpet hemocyanin conjugated to dinitrophenol were measured. Liver microsomal ethoxyresorufin-O-deethylase (EROD) activity also was measured. Organs were weighed and spleens were examined histologically. No differences were found in the PHA-induced skin response in exposed mink; mink in the two highest treatments exhibited significant increases in antibody production over control mink. Systemic toxicity was apparent; significant body weight reductions were found in mink exposed to 5 and 10 ppm of DE-71. Exposed mink had significantly larger relative spleen, adrenal, and liver masses than control mink. Spleens of mink exposed to 10 ppm of DE-71 had significantly increased germinal center development and incidence of B-cell hyperplasia. The activity of EROD was induced in all treated mink relative to controls and was positively associated with the liver somatic index. Hematocrit in mink from the two highest exposure groups was significantly lower than control mink. Percentage neutrophils increased and percentage lymphocytes decreased significantly in mink from the higher two dosage groups. Our findings have direct relevance to wild mink in the Great Lakes ecosystem, because mink are top predators of the aquatic food web, providing evidence for the vulnerability of this species to the effects of environmental PBDE mixtures.


Subject(s)
B-Lymphocytes/drug effects , Environmental Pollutants/toxicity , Germinal Center/drug effects , Microsomes, Liver/drug effects , Phenyl Ethers/toxicity , Polybrominated Biphenyls/toxicity , Polychlorinated Biphenyls/toxicity , Spleen/drug effects , Animals , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Canada , Dose-Response Relationship, Drug , Environmental Pollutants/immunology , Environmental Pollutants/metabolism , Food Contamination , Germinal Center/immunology , Germinal Center/metabolism , Great Lakes Region , Halogenated Diphenyl Ethers , Microsomes, Liver/enzymology , Mink , Phenyl Ethers/immunology , Phenyl Ethers/metabolism , Polybrominated Biphenyls/immunology , Polybrominated Biphenyls/metabolism , Polychlorinated Biphenyls/immunology , Polychlorinated Biphenyls/metabolism , Spleen/metabolism , United States
3.
Environ Res ; 101(1): 53-67, 2006 May.
Article in English | MEDLINE | ID: mdl-16499904

ABSTRACT

A study was conducted to determine whether changes in thyroid and vitamin A dynamics were induced in ranch mink exposed to environmentally relevant concentrations of polyhalogenated aromatic hydrocarbons. Adult female mink were fed diets that contained 0% (control), 10%, 20%, or 30% wild carp (Cyprinus carpio) collected from the Saginaw River, Michigan, USA. Total polychlorinated biphenyls concentrations were 0.03, 0.83, 1.05, and 1.69 mg/kg feed, respectively; the 2,3,7,8-tetrachlorodibenzo-p-diozin toxic equivalents were 3.4, 27.9, 47.6, and 73.2 ng/kg, respectively. Diets were fed 3 weeks prior to breeding and throughout gestation and lactation. When the kits were weaned at 6 weeks of age, they were continued on their respective diets until 27 weeks of age. Plasma thyroid hormone concentrations, thyroid gland activity and structure, and vitamin A dynamics were assessed in young mink at 6 and 27 weeks of age. Plasma total T4 and free T4 in 6-week-old female and male kits fed the 10% carp diet were significantly higher than those of controls, while kits fed the 20% and 30% carp diet had nonsignificant decreases relative to the control mink. Plasma total T3 concentrations in 27-week-old juvenile males fed the 30% carp diet were significantly lower than those in individuals fed the 10% carp diet. No overt thyroid toxicity was apparent as thyroid weight, activity, and structure in kits and juveniles of both sexes were similar among diet groups. Plasma retinol and total ester concentrations in both kits and juveniles were reduced in mink fed the 30% carp diet relative to controls. The ratio of retinol to retinyl palmitate in livers of juveniles fed the 30% carp diet was two times higher than that in control mink. Significant reductions in kidney retinol and fatty acyl retinyl esters were observed in kits and juveniles fed the 30% carp diet relative to control values.


Subject(s)
Benzofurans/toxicity , Mink/metabolism , Polychlorinated Biphenyls/toxicity , Polychlorinated Dibenzodioxins/analogs & derivatives , Vitamin A/analysis , Animals , Benzofurans/analysis , Carps , Dibenzofurans, Polychlorinated , Diet , Environmental Monitoring , Female , Kidney/metabolism , Liver/metabolism , Male , Maternal-Fetal Exchange , Michigan , Polychlorinated Biphenyls/analysis , Polychlorinated Dibenzodioxins/analysis , Polychlorinated Dibenzodioxins/toxicity , Pregnancy , Rivers , Thyroid Gland/anatomy & histology , Thyroid Gland/drug effects , Thyroxine/blood , Triiodothyronine/blood , Vitamin A/blood , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity
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