Introduction to Toxicology - Toxicology

Introduction to Toxicology

Toxicology

The study of the adverse effects of chemicals on living organisms and the underlying mechanisms

Like medicine, toxicology is both a science and an art. The science of toxicology is defined as the observational and data-gathering phase, whereas the art of toxicology consists of the utilization of the data to predict outcomes of exposure in human and animal population.

History of Toxicology

•          Antiquity: Ebers papyrus (1500 B.C.), Ben Chao Gong Mu (Ming dynasty)

•          Middle ages: Renaissance - Poisons and Their Antidotes (1198), arsenic-containing products

•          Age of enlightenment: Parcelsus (1493-1548) “All substances are poisons; there is none   which is not a poison. The right dose differentiates a poison from a remedy.”

•          Age of enlightenment: Orfila (1787-1853) – the first toxicologist to use autopsy material and chemical analysis systematically as legal proof of poisoning.

    Oswald Schmiedeberg (1838-1921) – the first toxicologist to train 120 students who later populated the most important laboratories of pharmacology and toxicology throughout the world.

•          Morden toxicology: 1900-

–        Development of early advances in analytic methods: heavy metals

–        Early mechanistic studies: drugs, plants

–        Introduction of new toxicants and antidotes: nitrite and thiosulfate for cyanide; DDT (1944); organophophorus compounds(1952)

–        Development of new branches

•          The Silent Spring (Rachel Carson, 1962)

“The earth’s vegetation is a part of a web of life in which there are intimate and essential relations between plants and the earth, between plants and other plants, between plants and animals. Sometimes we have no other choice but to disturb these relationships, but we should do so thoughtfully, with full awareness that what we do may have consequences remote in time and place.”

Toxicology Branch

•          According to object of study:

–        Animal Toxicology

–        Human Toxicology

–        Plant Toxicology

–        Insect Toxicology

–        Livestock Toxicology

•          According to field of study:

–        Environmental Toxicology

–        Food Toxicology

–        Occupational Toxicology

–        Clinical Toxicology

–        Forensic Toxicology

–        Analytic Toxicology

•          According to target organ of study:

–        Liver Toxicology

–        Kidney Toxicology

–        Neurotoxicology

–        Immunotoxicology

–        Productive Toxicology

–        Hemotoxicolgy

•          According to mechanism of study:

–        Cellular Toxicology

–        Molecular Toxicology

–        Membrane Toxicology

–        Biochemical Toxicology

–        Genetic Toxicology

•          According to area of study:

–        Descriptive Toxicology

–        Mechanistic Toxicology

–        Regulatory Toxicology

Main Areas of Toxicology Study

•          Descriptive Toxicology :

–        To test toxicity in experimental animals to provide important clues to a chemical’s mechanism of action.

–        To yield information that can be used to evaluate risks posed to humans and the environment.

•          Mechanistic Toxicology :

–        To identify and understand the cellular, biochemical and molecular mechanisms by which chemicals exert toxic effects on living organisms.

–        To design and produce safer alternative chemicals for therapy of poisoning and treatment of diseases.

•          Regulatory Toxicology :

–        To perform the risk assessment of a potential hazard to the human health and the ecosystem.

–        To establish standards for the amount of chemicals permitted in ambient air, industrial atmosphere, and drinking water.

Spectrum of Toxic Dose

•          Among chemicals there is a wide spectrum of doses needed to produce deleterious effects, serious injury, or death.

•          However, the measures of acute lethality such as LD₅₀ may not accurately reflect the full spectrum of toxicity associated with exposure, e.g., carcinogenic or teratogenic effects.

Spectrum of Undesired Effects (1)

•          Allergic reactions

–        Chemical allergy is an immunologically mediated adverse reaction to a chemical and is dose-related for a given individual.

–        The incidence of allergic asthma has increased substantially in recent years.

Spectrum of Undesired Effects (2)

•          Idiosyncratic reactions

–        Referring to a genetically determined abnormal reactivity to a chemical, i.g., extreme sensitive to low doses or extreme insensitive to high doses.

–        Examples of chemical idiosyncrasy include exposures to succinylcholine and methemoglobin-inducing chemicals.

Spectrum of Undesired Effects (3)

•          Immediate versus delayed toxicity

–        Most chemicals produce immediate toxic effects but not delayed effects.

–        Delayed toxicity can be seen in carcinogenic chemicals (years) and organophosphorus pesticides (weeks) such as TOCP to inhibit the neuropathy target esterase (NTE).

Spectrum of Undesired Effects (4)

•          Reversible versus irreversible toxic effects

–        The ability of exposed tissue to regenerate largely determines where the effects is reversible or irreversible.

–        Carcinogenic and teratogenic effects are usually considered irreversible toxic effects once they occur.

Spectrum of Undesired Effects (5)

•          Local versus systemic toxicity

–        Local effects occur at the site of first contact of chemicals, e.g., ingestion of caustic substances or inhalation of irritant materials.

–        Systemic effects require absorption and distribution of a toxicant from its entry point to a distant site to produce damages, some of the affected organs are referred to as the target organs of a particular chemical.

Information Resource of

Toxicology, Hazardous Chemicals, and the Environment

1. Chemical Information

Identify chemical, its synonyms, and CAS number

www.chemfinder.com

find chemical structure, chemical surrogate based on structure similarity.  Can be searched by using a chemical name, CAS Number, molecular formula, or molecular weight

toxnet.nlm.nih.gov/              (ChemID)

find which National Library of Medicine (NLM) databases contain information on the chemical.

2. Toxicology Information

http://toxnet.nlm.nih.gov/   Summarize toxicological study results, etc. 

http://toxnet.nlm.nih.gov/   search for original studies.  

http://ntp-server.niehs.nih.gov/    National Toxicology Program             

http://ehis.niehs.nih.gov/          Environmental Health Information Service www.epa.gov  Environmental Protection Agency

www.fda.gov  Food and Drug Administration    

www.osha.gov  Occupational Safety and Health Administration                              

www.atsdr.cdc.gov  Agency for Toxic Substances and Disease Registry 

www.acgih.org    American Conference of Governmental industrial Hygienist www.iarc.fr  The International Agency for Research on Cancer       

www.fao.org     Food and Agriculture Organization of the United Nations

http://www.toxicology.org/Information/siteofinterest/sites.html#Government