# Toxicology --- ## What is - Study of adverse effects of - Physical - Chemical - Biological - On living organisms - On ecosystem - Improving or mitigating these effects --- ## Parcelsus > All substances are poisons, there is none which is not a poison. The right dose differentiates a poison and a remedy --- ## Dose is the poison  --- ## Toxic agents - Physical (radiation, heat) - Chemical (Arsenic) - Biological (snake venom) - Toxicity depends on dose --- ## Biological agents - NOT toxic agents, they are biological agents - Ex: viruses - If they excrete chemicals: biological toxins - Ex: tetanus (C. tetani does NOT cause the disease) --- ## Systemic versus organ toxicants  --- ## Concept of dose - Amount of substance administered over time - Absorbed/internal dose: amount at the target organ - Administered dose: amount externally administered --- ## Exposure - Concentration of the substance in - Environmental media - Duration and frequency of events - During which the body was in contact with the media - Exposure = Quantity of the substance in Environment --- ## Importance of Dose-response - Causal inference: "biological gradient" - Threshold effect: lowest dose at which effect occurs - Slope: Rate at which injury builds --- ## Dose-response curve  --- ## Comparable dose-response curves: interpret  --- ## Question https://docs.google.com/document/d/1GgA8TUvWEw29AZCzlzdraYqFx6MLmsJ9dOn-y9jxO4A/edit?usp=sharing --- ## NOAEL and LOAEL  --- ## NOAEL > HIGHEST dose at/up to which there is NOT an observed toxic effect --- ## LOAEL > LOWEST dose at which an observed toxic effect observed --- ## Types of toxicity - Acute: Occurs within seconds/minutes/hours/days within exposure - Examples: - Bhopal Gas disaster, Methyl isocyanate - Carbon monoxide poisoning in people in locked in cars with heaters on --- ## Subchronic toxicity - Occurs over weeks or months > Doctor worked in laboratory and reported with chronic anaemia: we found that she was exposed to benzene --- ## Chronic toxicity - Months to years of exposure - Long term continual exposure damage builds up - Example: Inorganic arsenic toxicity with skin disease - Development of lung fibrosis or mesothelioma among those who work with Asbestos - Occupational cancers --- ## Carcinogenicity - Two stage process - **Initiation**: normal cells undergo irreversible changes - **Promotion**: initiated cells --> cancerous --- ## Developmental toxicity - Toxic effects to the **embryo OR foetus** - **Teratogenicity**: Irreversible conditions that leave permanent birth defects in live offspring --- ## Genetic toxicity - Due to damage to DNA/altered genetic expression - Single Nucleotide Polymorphism: change in one nucleotide in the gene sequence - SNP should be more than 1% - Mutation: change in the gene sequence but rare, less than 1% - Can lead to loss of function or alered functions, or associated with diseases - Epigenetic changes: Environment change gene sequences post birth, polyA tails, others --- ## Hazard identification - 1 - Some animal testing, - Increasingly alternative forms - See [https://www.nlm.nih.gov/enviro/altbib.html](https://www.nlm.nih.gov/enviro/altbib.html) - Machine learning approaches --- ## Hazard identification - 2 - Clinical investigations - Epidemiological studies - Postmarketing surveillance on drugs --- ## Environmental Health Risk Assessment (EHRA)  --- ## Summary - Parcelsus? - Exposure? - Dose? - Dose-response curve? - We will study EHRA next episode