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Cr(VI) MOA Study Glossary

Adenoma

AKA: tumor
Benign epithelial tumor in which the cells form recognizable glandular structures or in which the cells are clearly derived from glandular epithelium (UMLS, 2015).

Apoptosis

AKA: cell death, cell suicide
A Form of cell death, also known as programmed cell death, in which a ‘suicide’ program is activated within the cell, leading to fragmentation of the DNA, shrinkage of the cytoplasm, membrane changes and cell death without lysis or damage to neighboring cells. It is a normal phenomenon, occurring frequently in a multicellular organism (NLM, 2015).

Benchmark Dose

AKA: BMD
A dose that produces a predetermined change in response rate of an adverse effect (called the benchmark response or BMR) compared to background (EPA, 2015).

Big Blue® Mice/Rodents

AKA: transgenic mice, Transgenic rodent assay
The Big Blue® Transgenic Rodent Mutation assay provides a means to measure mutations in any somatic cell or germ cells (BioReliance, 2015).

Carcinogenesis

AKA: Tumor induction
Inappropriate function of various cellular repair and adaptive mechanisms, including insufficient adaptive response to DNA damage with failure of DNA repair that leads to mutation of critical genes, inappropriate control at regulatory gene regions over expression of critical genes, failure to induce apoptosis, and failure to terminate cell proliferation (Casarett and Doull’s, 2008).

Cr(VI)

AKA: Hexavalent chromium, Cr+6, Cr(VI), hex chromium
A common oxidation state of elemental chromium.

Cr(III)

AKA: trivalent chromium, Cr+3, tri-chrome
A common oxidation state of elemental chromium

Cytogenetics

A subdiscipline of genetics which deals with the cytological and molecular analysis of the chromosomes, and location of the genes on chromosomes, and the movements of chromosomes during the cell cycle (UMLS, 2015).

Cytotoxic

AKA: Cytotoxicity
Chemicals that function through this mech- anism produce sustained cell death, often related to metabolism of

Duodenum

AKA: duodenum function, tumors, carcinogensis
The 25-30 cm long tube of the small intestine that connects the stomach to the jejunum (EPA, 2015). For the purposes of the Cr(VI) studies, the duodenum is the tissue of interest for several Cr(VI) MOA publications due to the fact that dietary absorption is high in this portion of the gastrointestinal tract.

EPA

Environmental Protection Agency

Epithelial cells

Cells that line the inner and outer surfaces of the body by forming cellular layers (epithelium) or masses; epithelial cells lining the digestive system derive from endoderm (UMLS, 2015).

Reduction Capacity

AKA: Gastric reduction, in vivo reduction, ex vivo reduction
In the context of the Cr(VI) MOA effort, reduction capacity is defined as the total mass of hexavalent chromium that can be reduced to trivalent chromium in a unit volume or mass of the defined media (EPA, 2015).

Genomics

The study of comprehensive sets of genes via high throughput methods (UMLS, 2015).

γ-H2AX immunostaining

Immunohistochemical staining for the γ-H2AX antigen as a marker of DNA damage (Thompson et al., 2015).

Hyperplasia

Abnormal multiplication of otherwise normal cells, leading to tissue enlargement (UMLS, 2015).

intestinal villi

AKA: Intestinal villus
Threadlike projections that cover the surface of the mucosa of the small intestine to increase the lumen surface area and serve as the sites of absorption of fluid and nutrients (UMLS,2015).

K-ras

AKA: Kirsten rat sarcoma viral oncogene homolog, KRAS
A protein involved primarily in regulating cell division by relaying signals from outside the cell to the cell’s nucleus. These signals instruct the cell to grow and divide or to mature and take on specialized functions (US NLM, 2015).

Micronucleus

AKA: Micronuclei, Micronuclei formation
the smaller of the two nuclei when more than one is present in a eukaryotic cell; induction is a common toxicologic indicator; a diploid nucleus involved in meiosis and sexual reproduction which does not produce RNA (UMLS, 2015).

Mode of action

AKA: MOA
Understanding how chemicals perturb normal biological function; the key steps in the toxic response after chemical interaction at the target site that is responsible for the physiological outcome or pathology of the chemical (EPA, 2015)..

Mutagenic

AKA: Mutagenic potential
The ability to induce a permanent, heritable change in the nucleotide sequence of a chromosome, usually in a single gene; commonly leads to a change in or loss of the normal function of the gene product (Lodish et al., 2000).

Nonlinear regression

A statistical process that produces a mathematical function to fit nonlinear data against an independent variable, e.g., dose rate, duration of exposure, age.

OECD 488

AKA: Transgenic Rodent Somatic and Germ Cell Gene Mutation Assays
An OECD Test Guideline which describes the appropriate parameters of an in vivo assay that detects chemicals that may indce gene mutations.

PBPK

AKA: Physiologically based pharmacokinetic modeling
A mathematical model that estimates the dose to a target tissue or organ by taking into account the rate of absorption into the body, distribution among target organs and tissues, metabolism, and excretion (EPA, 2015).

Pharmacokinetic

AKA:
The dynamic behavior of chemicals inside biological systems including the absorption, distribution, metabolism, and excretion of the analyte as a function of time (EPA, 2015).

Regenerative proliferation

AKA: cell proliferation
Increased cell production in a normal tissue or organ in response to sustained cell death and an increased demand for new cells, resulting in the rapid expansion of a cell population (UMLS, 2015).

RfD

AKA: oral reference dose, reference dose
An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human population (including sensitive target groups) that is likely to be without an appreciable risk of deleterious noncancer effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark dose, with uncertainty factors generally applied to reflect limitations of the data used. Generally used in U.S. EPA’s noncancer health assessments. Durations include acute, short-term, subchronic, and chronic (EPA, 2015).

Risk assessment

The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. Risk assessment uses clinical, epidemiological, toxicological, environmental, and any other pertinent evidence (Porta, 2014).

SIDMS

AKA: Speciated isotope dilution mass spectrometry
A quantitative method for determining elemental species based on the measurement of isotope ratio(s) in each species of a nuclide using mass spectrometry after speciated isotope dilution (EPA, 2007).

SOT

Society of Toxicology (www.toxicology.org)

TERA

Toxicology Excellence for Risk Assessment

Toxic

AKA: Toxicity
Capable of inducing short- or long-term damage to biological tissue following contact or absorption. Routes of exposure of the substance include ingestion, inhalation, or assimilation into any organism, either directly from the environment or indirectly by ingestion through food chains (EPA, 2015).

Toxicogenomics

The area of research that combines transcript, protein and metabolite profiling with conventional toxicology to investigate the interaction between genes and environmental stress in disease causation (Waters and Fostel, 2004).

Toxicokinetics

The quantitative study of the movement of an exogenous chemical from its entry into the body, through its distribution to organs and tissues via the blood circulation, and to its final disposition by way of biotransformation and excretion.

y-H2AX Immunostaining

An assay utilized to both visualize and quantify radiation-induced double strand breaks.

Transgenic rodent

AKA: transgenic mouse, transgenic rat
A rodent whose genome has been altered by the inclusion of foreign genetic material. The technique involves microinjection of foreign DNA fragments into the nucleus of a fertilized egg. The inserted gene becomes integrated into every cell and tissue of the animal (UMLS, 2015).

oral mucosa

The oral mucosa is the mucous membrane lining the inside of the mouth. The mucosa is generally a nonkeratinized stratified squamous epithelium covering muscle, bone, or glands but can show varying degree of keratinization at specific locations (UMLS, 2015).

RASS

Risk Assessment Specialty Section (Society of Toxicology)