Toxicological Profile of Ultrapure 2,2´,3,4,4´,5,5´-Heptachlorbiphenyl (PCB 180) in Adult Rats
| Autor: | Gerd Hamscher, Hanna M. Miettinen, Satu Sankari, Heather A. Leslie, Dieter Schrenk, Helen Håkansson, Krister Halldin, Frode Fonnum, Ulla Stenius, Leo T.M. van der Ven, Kine-Susann Dervola, Robert Roos, Maria Herlin, Inger-Lise Bogen, Kari Savolainen, Mikko A. J. Finnilä, Filip Rendel, Hellmuth Lilienthal, Lauy Al-Anati, Patrik L. Andersson, Merja Korkalainen, Jorma Toppari, Timo Hamers, Päivi Heikkinen, Juha Tuukkanen, Matti Viluksela, Annika Adamsson, Sanna Lensu, Javier Esteban |
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| Přispěvatelé: | Chemistry and Biology, Amsterdam Global Change Institute, Departments of Faculty of Veterinary Medicine, Equine and Small Animal Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Physiology Adipose tissue THYROID-HORMONE POSTNATAL EXPOSURE 010501 environmental sciences 413 Veterinary science Toxicology Pathology and Laboratory Medicine 01 natural sciences Biochemistry Rats Sprague-Dawley Follicle-stimulating hormone Hemoglobins Medicine and Health Sciences EFFECT-DIRECTED ANALYSIS 0303 health sciences education.field_of_study Multidisciplinary Behavior Animal Maintenance dose Neurochemistry Anemia Neurotransmitters Hematology Polychlorinated Biphenyls Toxicokinetics Adipose Tissue Hematocrit Liver Toxicity Blood Chemistry Medicine Environmental Pollutants Female Luteinizing hormone Research Article ARYL-HYDROCARBON RECEPTOR Neurotoxicology medicine.medical_specialty Thyroid Hormones POLYCHLORINATED-BIPHENYLS PCBS Science education Population Toxic Agents ta3111 Loading dose 03 medical and health sciences Retinoids Sex Factors Internal medicine medicine Sex Hormones DEVELOPMENTAL EXPOSURE Animals Toxic equivalency factor Molecular Biology 030304 developmental biology 0105 earth and related environmental sciences Dose-Response Relationship Drug DIBENZO-P-DIOXINS Body Weight Biology and Life Sciences IN-VITRO Kemi Luteinizing Hormone Hormones Rats DIOXIN-LIKE-PCBS Endocrinology Chemical Sciences Adrenal Cortex Exploratory Behavior SUBCHRONIC TOXICITY Follicle Stimulating Hormone DNA Damage |
| Zdroj: | PLoS ONE, 9(9). Public Library of Science PLoS ONE, Vol 9, Iss 8, p e104639 (2014) PLoS ONE Viluksela, M, Heikkinen, P, van der Ven, L T M, Rendel, F, Roos, R, Estaban, J, Korkalainen, M, Lensu, S, Miettinen, M H, Savolainen, K, Sankari, S, Lilienthal, H, Adamsson, A, Toppari, J, Herlin, M, Finnilä, M, Tuukkanen, J, Leslie, H A, Hamers, T, Hamscher, G, Al-Anati, L, Stenius, U, Dervola, K S, Bogen, I L, Fonnum, F, Andersson, P L, Schrenk, D, Halldin, K & Håkansson, H 2014, ' Toxicological Profile of Ultrapure 2,2´,3,4,4´,5,5´-Heptachlorbiphenyl (PCB 180) in Adult Rats ', PLoS ONE, vol. 9, no. 9, pp. e104639 . https://doi.org/10.1371/journal.pone.0104639 |
| ISSN: | 1932-6203 |
| Popis: | PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterization of NDL-PCBs is confounded by the presence of highly potent dioxin-like impurities. We used ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose toxicity study in young adult rats extended to cover endocrine and behavioral effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5 females were given total doses of 0, 3, 10, 30, 100, 300, 1000 or 1700 mg PCB 180/kg body weight by gavage. Dose-responses were analyzed using benchmark dose modeling based on dose and adipose tissue PCB concentrations. Body weight gain was retarded at 1700 mg/kg during loading dosing, but recovered thereafter. The most sensitive endpoint of toxicity that was used for risk characterization was altered open field behavior in females; i.e. increased activity and distance moved in the inner zone of an open field suggesting altered emotional responses to unfamiliar environment and impaired behavioral inhibition. Other dose-dependent changes included decreased serum thyroid hormones with associated histopathological changes, altered tissue retinoid levels, decreased hematocrit and hemoglobin, decreased follicle stimulating hormone and luteinizing hormone levels in males and increased expression of DNA damage markers in liver of females. Dose-dependent hypertrophy of zona fasciculata cells was observed in adrenals suggesting activation of cortex. There were gender differences in sensitivity and toxicity profiles were partly different in males and females. PCB 180 adipose tissue concentrations were clearly above the general human population levels, but close to the levels in highly exposed populations. The results demonstrate a distinct toxicological profile of PCB 180 with lack of dioxin-like properties required for assignment of WHO toxic equivalency factor. However, PCB 180 shares several toxicological targets with dioxin-like compounds emphasizing the potential for interactions. © 2014 Viluksela et al. |
| Databáze: | OpenAIRE |
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