Corrosive Chemicals and TER Testing
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Questions and Answers

What is the mean TER value threshold for a substance to be considered non-corrosive to skin?

  • 3 kΩ
  • 10 kΩ
  • 5 kΩ (correct)
  • 1 kΩ
  • Which condition indicates that a substance may be corrosive to skin?

  • No visible damage on skin disc
  • Mean TER value of ≥5 kΩ
  • Mean TER value of ≤5 kΩ with visible damage (correct)
  • Dye content below positive control level
  • What does the dye-binding step help determine during skin permeability testing?

  • If the chemical is volatile
  • Whether the increase in permeability is due to physical destruction (correct)
  • The exact concentration of the test substance
  • If the substance is acidic
  • In which scenario is a substance confirmed as non-corrosive?

    <p>Mean TER ≥5 kΩ and the skin disc shows no damage</p> Signup and view all the answers

    What happens when corrosive chemicals reduce the TER below a threshold?

    <p>The substance shows high permeability due to stratum corneum destruction</p> Signup and view all the answers

    What is one of the primary mechanisms through which UVB radiation contributes to skin cancer development?

    <p>Inhibition of the p53 pathways</p> Signup and view all the answers

    Which condition can arise from excessive NET formation during infection-related inflammation?

    <p>Tissue and organ damage</p> Signup and view all the answers

    How do ROS generated by UVA radiation affect cellular components?

    <p>They interact with lipids and proteins to form DNA adducts.</p> Signup and view all the answers

    Basal cell carcinoma primarily arises from which type of skin cell?

    <p>Keratinocytes of hair follicles and sebaceous glands</p> Signup and view all the answers

    What role does autophagy play in cellular health?

    <p>It helps maintain cellular energy homeostasis.</p> Signup and view all the answers

    Which of the following is NOT a mechanism linked to skin cancer development?

    <p>Decreased cell proliferation</p> Signup and view all the answers

    What is one consequence of oxidative stress in skin cells?

    <p>Induction of apoptotic pathways</p> Signup and view all the answers

    Which statement accurately describes squamous cell carcinoma (SCC)?

    <p>It develops from precursory lesions like actinic keratoses.</p> Signup and view all the answers

    What does the OECD guideline No. 497 focus on?

    <p>Hazard identification and characterization</p> Signup and view all the answers

    What is required for the DA3 to provide a final prediction?

    <p>Two concordant results from studies</p> Signup and view all the answers

    How many DAs are included in the OECD guideline No. 497?

    <p>Three</p> Signup and view all the answers

    What distinguishes skin sensitizers from nonsensitizers according to the guideline?

    <p>They can be separated by weighted multiple information</p> Signup and view all the answers

    What approaches integrate computational methods with experimental tests?

    <p>In silico and in vitro methods</p> Signup and view all the answers

    Which of the following is NOT mentioned as part of the assessment of sensitization potential?

    <p>Psychological evaluations</p> Signup and view all the answers

    What does the acronym DA stand for in the context of the OECD guideline?

    <p>Defined Assessment</p> Signup and view all the answers

    Which of the following describes the role of expert judgment in hazard assessment according to the guideline?

    <p>It is not used when two concordant results are obtained</p> Signup and view all the answers

    What skin condition is characterized by a leathery appearance and irregular pigmentation due to chronic exposure to UV radiation?

    <p>Photo-aging</p> Signup and view all the answers

    What biochemical process is primarily activated by UV radiation, leading to skin damage?

    <p>MAPK pathway activation</p> Signup and view all the answers

    Which of the following is NOT a characteristic of skin aging linked to UV radiation?

    <p>Increased hydration</p> Signup and view all the answers

    What is the consequence of inflammation triggered by UV radiation?

    <p>Degradation of collagen and elastin</p> Signup and view all the answers

    What kind of skin change involves a deposition of abnormal, degraded elastin fibers?

    <p>Solar elastosis</p> Signup and view all the answers

    Which cytokines are released as a result of UV radiation activating the inflammatory response?

    <p>IL-1β, TNF-α, IL-6</p> Signup and view all the answers

    What visible skin change can result from chronic UV exposure that results in increased visibility of small blood vessels?

    <p>Telangiectasia</p> Signup and view all the answers

    What role do matrix metalloproteinases (MMPs) play in photoaging?

    <p>Degrades extracellular matrix proteins</p> Signup and view all the answers

    What is the primary function of thymidine kinase in the context of the assays mentioned?

    <p>It allows cells to proliferate in the presence of trifluorothymidine.</p> Signup and view all the answers

    What characteristic do mutant cells exhibit in the presence of trifluorothymidine during the assays?

    <p>They can form colonies.</p> Signup and view all the answers

    Which of the following statements correctly describes the transition from TK+/- to TK-/- cells?

    <p>It results from a mutation affecting thymidine kinase activity.</p> Signup and view all the answers

    Which cell line is used for the mouse lymphoma assay (MLA)?

    <p>L5178Y TK+/-3.7.2C cells</p> Signup and view all the answers

    What type of cells are TK6 TK+/- cells in the assays described?

    <p>Heterozygous cell lines</p> Signup and view all the answers

    In the presence of trifluorothymidine, what happens to the un-mutated TK+/- cells?

    <p>They stop proliferating and do not form colonies.</p> Signup and view all the answers

    What is the role of trifluorothymidine in the assays?

    <p>It inhibits cell division.</p> Signup and view all the answers

    Which assay uses L5178Y TK+/-3.7.2C cells to test for mutations?

    <p>Mouse lymphoma assay (MLA)</p> Signup and view all the answers

    Study Notes

    Corrosive Chemicals and Skin Testing

    • TER (Trans Epidermal Resistance) below 5 kΩ indicates corrosiveness in skin testing.
    • Non-corrosive substances have a mean TER value ≥ 5 kΩ.
    • Positive confirmation of corrosiveness involves dye penetration through rat skin post-exposure to chemicals.
    • A mean TER ≤ 5 kΩ with no visible skin damage and low disc dye content suggests non-corrosive materials.

    Skin Cancer Development Mechanisms

    • Key mechanisms include:
      • Inhibition of p53 pathways, which regulate the cell cycle and prevent cancer formation.
      • Increased DNA damage through various forms of radiation such as UVA.
      • Genetic mutations contributing to abnormal cell growth.
      • Oxidative stress leading to cellular damage.
      • Immunosuppression making skin cells vulnerable to cancer.
      • Induction of apoptotic pathways, resulting in programmed cell death.

    Non-Melanoma Skin Cancer (NMSCs)

    • Squamous cell carcinoma originates from basal keratinocytes in actinic keratoses.
    • Basal cell carcinoma arises from basal keratinocytes of the epidermis and hair follicles.
    • Both types can penetrate the dermis and degrade extracellular matrix.

    Effects of UV Radiation on Skin Aging

    • Chronic UV exposure leads to:
      • Leathery and rough skin texture.
      • Irregular pigmentation and persistent hyperpigmentation.
      • Wrinkles and elastosis, a condition where skin loses elasticity.
      • Telangiectasia, characterized by spider veins.
      • Solar elastosis caused by deposition of abnormal elastin and collagen breakdown.

    Inflammation and Photoaging Mechanisms

    • UV radiation triggers inflammation which generates reactive oxygen species (ROS).
    • ROS cause degradation of collagen and elastin, key proteins for skin structure.
    • Activation of MAPK pathway leads to the release of inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6).
    • AP-1 and NF-kB pathways stimulate matrix metalloproteinases (MMPs) causing damage to the extracellular matrix.

    Future Perspectives in Toxicity Testing

    • OECD guideline No. 497 adopted in 2021 promotes hazard identification for skin sensitization.
    • Defined approaches (DAs) emphasize predictions via multiple data sources, including physicochemical properties and in vitro methods.
    • Gene mutation assays use specific thymidine kinase heterozygous cell lines (e.g., L5178Y TK+/-3.7.2C for MLA and TK6 TK+/- for TK6 assay) to assess mutagenic potential.
    • The presence of resistant mutant cells in assays indicates successful mutagenesis in response to test substances.

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    Description

    This quiz focuses on the impact of corrosive chemicals on the transepithelial electrical resistance (TER) of the skin. Participants will learn about the criteria for classifying a test substance as non-corrosive based on mean TER values. Understand the parameters and implications of TER in toxicology assessments.

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