Dataset Information

Multidimensional in vivo hazard assessment using zebrafish.

ABSTRACT: There are tens of thousands of man-made chemicals in the environment; the inherent safety of most of these chemicals is not known. Relevant biological platforms and new computational tools are needed to prioritize testing of chemicals with limited human health hazard information. We describe an experimental design for high-throughput characterization of multidimensional in vivo effects with the power to evaluate trends relating to commonly cited chemical predictors. We evaluated all 1060 unique U.S. EPA ToxCast phase 1 and 2 compounds using the embryonic zebrafish and found that 487 induced significant adverse biological responses. The utilization of 18 simultaneously measured endpoints means that the entire system serves as a robust biological sensor for chemical hazard. The experimental design enabled us to describe global patterns of variation across tested compounds, evaluate the concordance of the available in vitro and in vivo phase 1 data with this study, highlight specific mechanisms/value-added/novel biology related to notochord development, and demonstrate that the developmental zebrafish detects adverse responses that would be missed by less comprehensive testing strategies.

SUBMITTER: Truong L

PROVIDER: S-EPMC3871932 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multidimensional in vivo hazard assessment using zebrafish.

Truong Lisa L Reif David M DM St Mary Lindsey L Geier Mitra C MC Truong Hao D HD Tanguay Robert L RL

Toxicological sciences : an official journal of the Society of Toxicology 20131017 1

There are tens of thousands of man-made chemicals in the environment; the inherent safety of most of these chemicals is not known. Relevant biological platforms and new computational tools are needed to prioritize testing of chemicals with limited human health hazard information. We describe an experimental design for high-throughput characterization of multidimensional in vivo effects with the power to evaluate trends relating to commonly cited chemical predictors. We evaluated all 1060 unique ...[more]

PMID: 24136191

Similar Datasets

Project description:Currently, assessment of the potential immunotoxicity of a given agent involves a tiered approach for hazard identification and mechanistic studies, including observational studies, evaluation of immune function, and measurement of susceptibility to infectious and neoplastic diseases. These studies generally use costly low-throughput mammalian models. Zebrafish, however, offer an excellent alternative due to their rapid development, ease of maintenance, and homology to mammalian immune system function and development. Larval zebrafish also are a convenient model to study the innate immune system with no interference from the adaptive immune system. In this study, a respiratory burst assay (RBA) was utilized to measure reactive oxygen species (ROS) production after developmental xenobiotic exposure. Embryos were exposed to non-teratogenic doses of chemicals and at 96 h post-fertilization, the ability to produce ROS was measured. Using the RBA, 12 compounds with varying immune-suppressive properties were screened. Seven compounds neither suppressed nor enhanced the respiratory burst; five reproducibly suppressed global ROS production, but with varying potencies: benzo[a]pyrene, 17β-estradiol, lead acetate, methoxychlor, and phenanthrene. These five compounds have all previously been reported as immunosuppressive in mammalian innate immunity assays. To evaluate whether the suppression of ROS by these compounds was a result of decreased immune cell numbers, flow cytometry with transgenic zebrafish larvae was used to count the numbers of neutrophils and macrophages after chemical exposure. With this assay, benzo[a]pyrene was found to be the only chemical that induced a change in the number of immune cells by increasing macrophage but not neutrophil numbers. Taken together, this work demonstrates the utility of zebrafish larvae as a vertebrate model for identifying compounds that impact innate immune function at non-teratogenic levels and validates measuring ROS production and phagocyte numbers as metrics for monitoring how xenobiotic exposure alters the innate immune system.

Project description:IntroductionArtificial turf or synthetic grass releases hazardous substances such as heavy metals, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs).ObjectiveThe current study aimed to evaluate the concentration levels of hazardous substances that are emitted from artificial turf as a result of sunlight effect; and to assess the expected exposure risks to such emitted substances during various activities.The current study aimed to evaluate the concentration levels of hazardous substances that are emitted from artificial turf as a result of the effect of sunlight. And to assess the expected risks of exposure to these substances emitted during the various activities.Study designVOCs emitted from artificial turf samples were monitored and collected in the ambient air of three football fields, the ambient air around a piece of new artificial turf that has not yet been used on playing fields, but has been exposed to sunlight within one year and in the indoor air around a piece of new artificial turf. Which has not yet been used on the playgrounds and was placed at room temperature and away from sunlight.ResultsThe current study shows that average afternoon morning VOCs levels were 277, 333, 405 and 509 mg/m3 in winter, autumn, spring and summer, respectively. The most predominant PAHs compounds present in the samples were compounds with 3-rings and 4-rings.The average daily intake (ADI) for three exposure routes (ingestion, inhalation, and dermal contact) was calculated for different age categories (3-6, 7-15, 16-18, 19-22, 23-55, and 56-70 year). Non-Carcinogenic exposure risk as hazard quotient (HQ) and hazard index (HI) were detected.ConclusionAll HI values were <1, indicating that there is no potential adverse health effects occur as a result of a chemical exposure. Total carcinogenic risk (R) values for the different age categories were higher than 1E-04 for three football artificial grass fields, which indicated a high cancer risk development probability. HI and R probability increased in the age group of 7-15 year > 3-6 years.

Dataset Information

Multidimensional in vivo hazard assessment using zebrafish.

Publications

Multidimensional in vivo hazard assessment using zebrafish.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets