Toxicology Part 2 2025 iCollege (1)

Toxicity Tests

• Definition: Evaluations that determine whether a particular substance is toxic based on various factors.

Learning Outcomes

• After this lecture, you should be able to:

  • Understand the principle of "the dose makes the poison".

  • Describe the experimental design for acute toxicity tests.

  • Compare static, static renewal, and flow-through tests regarding their design and advantages/disadvantages.

  • Define key toxicity metrics including:

    • LC50: Median lethal concentration.

    • LD50: Median lethal dose.

    • TLm: Median tolerance limit.

    • EC50: Median effective concentration.

    • Median survival time.

    • Incipient lethal level.

  • Describe tests for chronic toxicity and interpret relevant graphs.

  • Understand concepts such as criteria and standards in toxicity assessment.

  • Identify interactions between two equally toxic substances (no interaction, additive, antagonistic).

Key Concepts

"The Dose Makes the Poison"

• Assertion that the toxicity of a substance is dose-dependent.

• Quote by Emil Mrak: "There are no harmless substances, only harmless ways of using substances."

Acute Toxicity Tests

Overview

• Duration: Typically 48-96 hours.

• Main Endpoint: Traditionally lethality of test organisms.

• Test Conditions: Range of concentrations to evaluate from no effect to total lethality.

Types of Acute Toxicity Tests

• Static Non-Renewal: Same test solution throughout.

• Static Renewal: Fresh solution at intervals.

• Flow-Through: Continuous pumping of the sample.

Metrics of Toxicity

Median Lethal Concentration (LC50)

• Definition: Concentration estimated to be lethal to 50% of test organisms.

• Measurement Types:

  • Direct observation.

  • Interpolation between test concentrations.

  • Statistical analysis of mortality data.

Median Tolerance Limit (TLm)

• Definition: Concentration with 50% survival after specified exposure time.

Median Effective Concentration (EC50)

• Definition: Concentration at which 50% of organisms exhibit a specific sublethal response.

Definitions of Other Terms

• LD50: Dose causing death in 50% of the test population.

• NOEC: Highest concentration with no observed adverse effects.

• LOEC: Lowest concentration with observed adverse effects.

Chronic Toxicity Tests

• Duration: Require longer periods, ideally covering full life cycles.

• Types: Partial life cycle and early life stage tests are common.

• Focus: Assess long-term effects of toxic substances, and survival rates over extended exposure.

Metrics

• Median Survival Time: Time that half the test organisms survive a given stress.

• Incipient Lethal Level: Toxic level expected to kill 50% of organisms over an infinite time frame.

Contemporary Toxicity Assessment

• A shift towards molecular response analysis with genomics and proteomics.

• Focus on sublethal effects on growth, reproduction, and behavior rather than solely lethality.

Water Quality Criteria and Standards

Definitions

• Criteria: Scientific basis for judgment on toxicity levels.

• Standards: Established rules or measures for water quality.

Goals of Water Quality Management

• Protect organisms from both lethal and sublethal effects of toxins.

• Considerations for occasional stress on aquatic communities.

Species Variability in Toxicity Response

• Natural variability affects tolerance among species.

• Median responses from samples used for regulatory measures.

• HC5: Fifth hazard concentration affecting 5% of species.

Database for Acute Effects

• EPA Requirements: Number and types of organisms for acute tests must meet specific diversity criteria.

• Emphasis on separate data collection for marine organisms across multiple families.

Chronic Toxicity Standards

• Final chronic value calculation requires comprehensive data.

• Often uses acute-to-chronic ratio for standards when data is limited.

Two Number Criterion by EPA

• Two separate metrics to account for different tolerance to acute vs chronic exposure.

• Maximum concentration guidelines for water quality.

Interaction of Toxic Substances

• Evaluation of outcomes when two toxic substances are present simultaneously:

  • No Interaction.

  • Strictly Additive.

  • Supra-additive (greater combined effect).

  • Antagonistic effects (reduced overall toxicity).

Public Health and Toxicology

• Assessment of non-carcinogenic effects with an emphasis on threshold doses.

• EPA Definition of Adverse Effects: Any functional impairment or pathological lesions affecting overall organism performance.