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5TOXICOLOGY(c cht hc)A waste is considered hazardous if it exhibits any of four characteristics reactivity, corrosivity, ignitability, or toxicity. Of these, the potential for toxicity, both to humans and to other biota (ecotoxicity), has caused the greatest public concern and has prompted massive regulatory initiatives in hazardous waste management. It follows that the management of hazardous waste has as its fundamental objective the protection of human and ecological health by reducing the risk, if not the toxicity, of the substances in hazardous wastes to acceptable levels. An understanding of toxicology is therefore needed to determine whether the management of hazardous waste or the remediation of contaminated sites meets this objective.Chapter 4 covered the fate and transport of substances from their release into the environment up to their contact with receptor. This chapter addresses the toxic effects caused by hazardous substances on gaining access to the human body and other living organisms. Toxic effects can range from mild allergic reactions to death. Indeed, the constituents of some hazardous waste can kill humans outright as evidenced by graphic accounts. Some constituents can cause death in insidious ways such as cancer.What is toxicology?What is the single most important thing for an engineer to know about toxicology?

What is the key limitation of applying toxicology?5-1 EXPOSUREOverview of Fate of Substances

Absorption

Absorption mechanisms

Diffusion

Specialized absorption

Absorption via the ingestion route

Absorption via the inhalation route

Absorption via the dermal contact route

Effect of exposure route on toxic response

Distribution and Storage

Biotransformation and Elimination

Pharmacokinetics

Exposure Period5-2 TOXIC EFFECTSConcept of Structural Affinity

Mechanism of Toxic Action and the Manifestations of Toxic Effects

Classification of Toxic Actions and Effects

Classification by end point

Classification by target organ

Classification by immediate versus delayed effects

Classification by irreversible versus reversible effects

Classification by local versus systemic effects

5-3 DOSE-RESPONSE RELATIONSHIPSNature of Dose-Response RelationshipsDose-Effect Relationship

Toxicological Data Human Populations

Type of epidemiological studies

Limitations of epidemiological studies

Toxicological Data Experimental Animals

Interpretation of findings

Limited number of animals

Selection of surrogate species

Other tests

Adequacy of Data

5-4 NONCARCINOGENS

Concept of Threshold

No Observed Adverse Effect Level (NOAEL)

Acceptable Daily Intakes and Reference Doses

Toxicological Databases

Calculation Procedure for Assessment of Noncarcinogenic Risk5-5 CARCINOGENS*Initiation of Cancer

Promotion of Cancer

Progression of Cancer

Role of Carcinogenic Chemicals

Genotoxic carcinogens

Nongenotoxic carcinogens

Complete carcinogens

Other Carcinogens

Affinity

Classes of Carcinogens

Testing for Carcinogenicity

Limited size of test groups

Relevance of tumors

Other tests

Dose-Response Relationship for Carcinogens

Low-Dose Extrapolation Models

Tolerance distribution models

Mechanistic models

Extrapolation error

Toxicological databases for carcinogens

Mixed exposure to carcinogens

Background and Lifestyle Carcinogenesis

Background carcinogenesis

Lifestyle and occupational carcinogenesis

Safe levels of carcinogenic chemicals in hazardous wastes

5-6 ECOTOXICOLOGY*Evaluation of Toxic EffectsToxic End PointBioassay

Short-Term Toxicity Tests

Long-Term Toxicity Tests

Biomarkers

Aquatic Toxicity of Trace Metals

Example of Aquatic Toxicity of Copper to Fish

Aquatic Toxicity of Hydrocarbons

Aquatic Toxicity of Pesticides

Water Quality Criteria

Terrestrial Toxicology

Feral Plants and Mammals

Avian Toxicology

DISCUSSION TOPICS AND PROBLEMS

REFERENCES