%0 Journal Article %J Arch Toxicol %D 2018 %T Comparative developmental toxicity of a comprehensive suite of polycyclic aromatic hydrocarbons. %A Mitra Geier %A Chlebowski, Anna C %A Truong, Lisa %A Staci M Simonich %A Kim A Anderson %A Robyn L Tanguay %K Animals %K Cytochrome P-450 CYP1A1 %K Embryo, Nonmammalian %K Larva %K Polycyclic Aromatic Hydrocarbons %K Toxicity Tests %K Zebrafish %X

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants that occur in complex mixtures. Several PAHs are known or suspected mutagens and/or carcinogens, but developmental toxicity data is lacking for PAHs, particularly their oxygenated and nitrated derivatives. Such data are necessary to understand and predict the toxicity of environmental mixtures. 123 PAHs were assessed for morphological and neurobehavioral effects for a range of concentrations between 0.1 and 50 µM, using a high throughput early-life stage zebrafish assay, including 33 parent, 22 nitrated, 17 oxygenated, 19 hydroxylated, 14 methylated, 16 heterocyclic, and 2 aminated PAHs. Additionally, each PAH was evaluated for AHR activation, by assessing CYP1A protein expression using whole animal immunohistochemistry (IHC). Responses to PAHs varied in a structurally dependent manner. High-molecular weight PAHs were significantly more developmentally toxic than the low-molecular weight PAHs, and CYP1A expression was detected in five distinct tissues, including vasculature, liver, skin, neuromasts and yolk.

%B Arch Toxicol %V 92 %P 571-586 %8 2018 Feb %G eng %N 2 %R 10.1007/s00204-017-2068-9 %0 Journal Article %J Toxicol Appl Pharmacol %D 2018 %T Systematic developmental neurotoxicity assessment of a representative PAH Superfund mixture using zebrafish. %A Mitra Geier %A D James Minick %A Truong, Lisa %A Susan C Tilton %A Pande, Paritosh %A Kim A Anderson %A JG Teeguarden %A Robyn L Tanguay %X

Superfund sites often consist of complex mixtures of polycyclic aromatic hydrocarbons (PAHs). It is widely recognized that PAHs pose risks to human and environmental health, but the risks posed by exposure to PAH mixtures are unclear. We constructed an environmentally relevant PAH mixture with the top 10 most prevalent PAHs (SM10) from a Superfund site derived from environmental passive sampling data. Using the zebrafish model, we measured body burden at 48 hours post fertilization (hpf) and evaluated the developmental and neurotoxicity of SM10 and the 10 individual constituents at 24 hours post fertilization (hpf) and 5 days post fertilization (dpf). Zebrafish embryos were exposed from 6 to 120 hpf to (1) the SM10 mixture, (2) a variety of individual PAHs: pyrene, fluoranthene, retene, benzo[a]anthracene, chrysene, naphthalene, acenaphthene, phenanthrene, fluorene, and 2-methylnaphthalene. We demonstrated that SM10 and only 3 of the individual PAHs were developmentally toxic. Subsequently, we constructed and exposed developing zebrafish to two sub-mixtures: SM3 (comprised of 3 of the developmentally toxicity PAHs) and SM7 (7 non-developmentally toxic PAHs). We found that the SM3 toxicity profile was similar to SM10, and SM7 unexpectedly elicited developmental toxicity unlike that seen with its individual components. The results demonstrated that the overall developmental toxicity in the mixtures could be explained using the general concentration addition model. To determine if exposures activated the AHR pathway, spatial expression of CYP1A was evaluated in the 10 individual PAHs and the 3 mixtures at 5 dpf. Results showed activation of AHR in the liver and vasculature for the mixtures and some individual PAHs. Embryos exposed to SM10 during development and raised in chemical-free water into adulthood exhibited decreased learning and responses to startle stimulus indicating that developmental SM10 exposures affect neurobehavior. Collectively, these results exemplify the utility of zebrafish to investigate the developmental and neurotoxicity of complex mixtures.

%B Toxicol Appl Pharmacol %8 2018 Apr 06 %G eng %R 10.1016/j.taap.2018.03.029 %0 Generic %D 2017 %T Hazard assessment of a PAH Superfund mixture in the zebrafish developmental toxicity mode %A D James Minick %A Mitra Geier %A Robyn L Tanguay %A Kim A Anderson %X
%B Pacific Northwest Chapter of the Society of Environmental Toxicology and Chemistry. 26th Annual Meeting %8 04/2017 %G eng %0 Audiovisual Material %D 2017 %T Hazard assessment of a PAH Superfund mixture in the zebrafish developmental toxicity model %A D James Minick %A Mitra Geier %A Kim A Anderson %A Robyn L Tanguay %B Society of Toxicology 56th Annual Meeting %C Baltimore %8 03/2017 %G eng %0 Generic %D 2015 %T Assessment of PAH Contribution to Superfund Site Hazard Using a Representative PAH Mixture and a Zebrafish Developmental Toxicity Model %A D James Minick %A Mitra Geier %A Robyn L Tanguay %A Kim A Anderson %B SETAC North America 36th Annual Meeting. Salt Lake City, Utah %8 11/2015 %G eng