Slide 1ToxicologyFields of ToxicologyRegulating agenciesEPA TermsSuperfundLove Canal AgreementSites in Erie CountySites in Niagara CountyTerminologyToxic EffectsSpectrum of toxic doseApproximate Acute LD50Toxicity Rating ChartExposureToxic responseAdverse EffectsFrequency of target organ involvement in systemic toxicityInteractions of multiple chemicalsReversible versus IrreversibleToxicity Influencing FactorsToleranceDose ResponseDose ResponseSlide 25ED50Dose Response CurveComparison of Dose ResponsesSlide 29Slide 30Characterization of RiskDescriptive animal toxicity testsGeneral Principles of ToxicologyDavid Shubert Ph.D. 125 Sherman Annex [email protected] •Definition – subdivision of pharmacology which studies the adverse effects of substances on living organisms.–Paracelsus (1493-1541) “All substances are poisons; there is none which is not a poison. The right does differentiates a poison and a remedy.”Fields of Toxicology•Subdisciplines – –Descriptive toxicology – toxicity testing, utilizing experimental animals–Mechanistic toxicology- identifying and understanding the mechanisms –Regulatory toxicology – utilizing data from descriptive and mechanistic toxicologists to assess the risk–Forensic toxicology – concerned with the medicolegal aspects of the harmful effects–Clinical toxicology – involved with treating patients poisoned–Environmental toxicology & Ecotoxicology – adverse effects of chemicals on nonhuman organismsRegulating agencies•FDA – Federal Drug Administration–FDCA - Federal Food, Drug, and Cosmetic Act •EPA ––FIFRA - Federal Insecticide, Fungicide, and Rodenticide Act–TSCA - Toxic Substances Control Act –RCRA - Resource Conservation and Recovery Act–CERCLA – (Superfund) Comprehensive Environmental Response, Compensation, and Liability Act – 1980•OSHA- Occupational Safety and Health AdministrationEPA Terms•NPL - National Priorities List (NPL) •RCRA - RCRA Corrective Action differs from Superfund in that Corrective Action sites generally have viable operators and on-going operations.•Brownfields are abandoned, idled, or under-used industrial and commercial facilities at which expansion or redevelopment is complicated by real or perceived environmental contamination.Superfund•The 1978 discovery of toxic chemicals beneath the suburban infrastructure of Love Canal, in Niagara Falls, New York first illuminated the consequences of environmental neglect. For decades, many American businesses had disposed of hazardous waste improperly, contaminating tens of thousands of sites nationally, including nearly 250 within Region 2 alone. Accidents, spills, and leaks of hazardous materials resulted in land, water, and air that pose immediate and potential threats to public and environmental health.Citizen reaction to these localized threats led Congress to establish the Superfund Program in 1980, an initiative designed to locate, investigate, and clean up the most hazardous sites nationwide. Superfund is officially called CERCLA, or the Comprehensive Environmental Response, Compensation, and Liability Act. The EPA administers the Superfund Program in cooperation with individual states and tribal governments.•The national EPA office that oversees management of the program is the Office of Superfund Remediation and Technology Innovation (OSRTI). The sites dealt with under Superfund are listed on the NPL, or National Priorities List. Superfund constitutes a crucial environmental and economic precedent within American legislative history.Love Canal AgreementSites in Erie County•Erie County Brant Wide Beach Development NPL •Erie County Buffalo Buffalo Brownfields •Erie County Buffalo Buffalo Color RCRA •Erie County Cheektowaga Pfohl Brothers Landfill NPL Erie County Development Downtown Inc. Buffalo Development Downtown Inc. Buffalo NY Brownfields Erie County Lackawanna Lackawanna Brownfields Erie County Lackawanna Tecumseh Redevelopment, Inc. RCRASites in Niagara County•Niagara County Burt Akzo Nobel Polymer Chemicals LLC RCRA Niagara County East of Griffin Park in Niagara Falls Hooker 102nd Street NPL Niagara County Middleport F M C Corp. dublin Road Landfill RCRA Niagara County Model City C W M Chemical Services Llc RCRA Niagara County Niagara County Brownfields Nigara County Niagara Falls Frontier Chemical Waste Process, Inc. - Royal Avenue Facility RCRA Niagara County Niagara Falls Niagara Falls Brownfields Niagara County Niagara Falls 914th Airlift Wing - AFRC RCRA Niagara County Niagara Falls Cecos International Incorporated RCRA Niagara County Niagara Falls Dupont Necco Park NPL Niagara County Niagara Falls Durez Corporation RCRA Niagara County Niagara Falls Forest Glen Mobile Home Subdivision NPL Niagara County Niagara Falls Love Canal NPL Niagara County Niagara Falls Occidental Chemical Corporation - Buffalo Avenue RCRA Niagara County Niagara Falls Olin Corporation RCRA Niagara County Niagara River Hooker Chemical/ S-area NPL Niagara County Niagara Falls Hooker - Hyde Park NPL Niagra County Pendelton Frontier Chemical Waste Process, Inc. - Pendleton Site RCRA Niagara County Wheatfield Niagara County Refuse NPL Niagara County Wheatfield Textron Realty Operations Incorporated RCRATerminology•Xenobiotic- is a term used to describe foreign substances taken into the body. The word is taken from the Greek xeno, meaning "foreigner". •Toxicology is dependent on –Level (Dose)–Duration (Time)–FrequencyToxic Effects •Variable–Nature of the toxicant – three forms if mercury, elemental, inorganic, organic–Potency – how much?–Target Organ (Distribution and/or Receptors)– what does it affect in the body?–Mechanism of action - what protein/ receptor/channel etc. does it affect?Spectrum of toxic dose•Acute toxicity – effects seen shortly after exposure–(LD50) – •Delayed toxicity – the effects are not seen immediately following exposure•Chronic toxicity – the result of long- term exposure to a toxic substanceApproximate Acute LD50 Agent LD50 (mg/kg) Ethyl alcohol 10,000 Sodium chloride 4,000 Ferrous sulfate 1,500 Morphine sulfate 900 Phenobarbital sodium 150 Picrotoxin 5 Strychnine sulfate 2 Nicotine 1 d-Tubocurarine 0.5 Hemicholinium-3 0.2 Tetrodotoxin 0.10 Dioxin (TCDD) (manmade)