What is environmental toxicology ? ‘ecotoxicology’ Definition: ‘study of impacts of pollutants on the structure and function of ecosystems’ manmade poisonous chemicals and their effect on the environment does not include the study of naturally occurring toxins, for example cholera toxin, or brevitoxin

Environmental toxicology is a new discipline that grew out of studies on the environmental fate and transport of pesticides in the 1940s and 1950s The discipline ‘toxicology’ is as old as medicine – many toxic plant chemicals are used as therapeutic agents in medicine. The term ‘ecotoxicology’ appeared in the literature in 1969 Field was pioneered by Rachel Carson

Environmental toxicology is highly interdisciplinary field

Rachel Carson 1907-1964 Marine Biologist from Pennsylvania MA from Johns Hopkins U. Author of ‘Silent Spring’ Received much attention, because she wrote and presented scientific facts well She was disturbed by the widespread and indiscriminate use of pesticides Many of these pesticides were known to affect wildlife e.g. kill birds She lobbied very hard to control and ban certain highly toxic chemicals Testified before congress in 1963 and called for new policies with respect to human health and the environment

Environmental toxicology is driven by legislation National Environmental Policy Act Clean Air Act Federal Environmental Pesticide Control Act Federal Water Pollution Control Act Safe Drinking Water Act Toxic Substances Control Act Resource Conservation and Recovery Act Comprehensive Environmental Response, Compensation and Liabilities Act Clean Water Act

First piece of environmental legislation was the National Environmental Policy Act 1970 Created the EPA Initially 5000 employees (1970) Budget of 1.3 B In 1995 there were >18,000 employees, budget of 7.2 B USA is divided into 10 management regions Clean Air Act Also in 1970 Required the EPA to set standards EPA in charge of controlling mobile and stationary emissions sources EPA controls hazardous pollutants Amended in 1977 to set compliance standards Amended again in 1990 to regulate acid rain and CFC emissions

Federal Environmental Pesticide Control Act 1972 amended to FIFRA – Federal Insecticide, Fungicide, and Rodendicide Act Required manufactures to provide PMNs (Pre Manufacture Notice) with toxicological information to register a pesticide Sets up system of tiered toxicity testing – mechanism, mesocosm experiment, field test Federal Water Pollution and Control Act Provided sewage treatment plant grants for many municipalities Set effluent limits based on technology standards Toxicity testing is used to set maximum allowable concentrations of toxicants in discharges and receiving waters Goal was to have all water fishable and swimable by 1983 Established goal to eliminate pollution discharges by 1985

Safe Drinking Water Act 1974 Set mandatory drinking water standards Controlled underground injection of wastes (aquifer protection) Amended in 1984 to set a schedule for establishing drinking water standards for 80 chemicals (provides notice to consumers) Toxic Substances Control Act 1976 Regulated the use of chemicals in manufacturing and production Goal was to characterize the human health and environmental impact of EVERY chemical manufactured in the USA EPA has only 90 days to review the PMN to evaluate data Because there are thousands of chemicals produced in the USA every year, QSAR models or rapid throughput assays are usually used

Resource Conservation and Recovery Act 1976 Controlled the disposal of solid waste Set new hazardous waste regulations Comprehensive Environmental Response, Compensation and Liabilities Act Also known as SUPERFUND 1980 Provided funding mechanisms to clean up abandoned waste sites Amended in 1984 to ban ‘land disposal of hazardous waste Amended in 1986 to include requirements for community emergency plans and publication of corporate Toxic Release Inventories Established the SBRP program to develop innovative approaches for cleanup and assessment of hazards

Clean Water Act 1987 sets national water quality standards Toxicological (animal) testing of ‘xenobiotics’ is federally mandated by Federal Insecticide, Fungicide, and Rodendicide Act (FIFRA) Federal Environmental Pesticide Control Act Federal Water Pollution Control Act Safe Drinking water act Toxic Substances control Act

Definition : XENOBIOTIC a chemical that is foreign to the biosphere i.e. is not produced by a natural biological or abiotic source Also called anthropogenic, man-made, synthetic, pollutant, contaminant, recalcitrant, persistent, and toxicant Distinguishes between quantity and scale – Gordon Gribble e.g. studied the natural occurrence of organohallogens (chlorbenzoates in fungi) – this is different from large scale chemical processes for the production of PCBs BTEX is an acronym for benzene, toluene, ethylbenzene, and xzylene – natural ??

Environmental toxicology depends on Lab work Effects of toxicants on biochemistry and physiology Field work Field observations of reproduction and survival in polluted vs. non-polluted sites Modeling of fate and transport of toxicants in the environment i.e. exposure and risk assessment Static models : short term modeling of ecosystems Strategic models : model of a specific aspect of a system Testable models : model makes predictions that can be tested in the field or laboratory

Purpose/function of environmental toxicology is to Identify the mode / site of action of a xenobiotic FATE and TRANSPORT / interaction of a xenobiotic with the biosphere (including specific organisms) after it is released / pollution occurs identify the effect the xenoboitic has on an ecosystems / higher level organisation e.g. loss of fertility of Alligators in Lake Apopca Introduction of xenobiotic Ecosystem effect site of action biotransformation physiology behavior community parameters biochemistry population dynamics

Parameters of xenobiotic interaction with the ecosystem Physiology, Behavior Chromosome damage Lesions, Necrosis Tumors Teratogenic effects Behavior, Mortality Community structure Diversity Energy transfer Stability Succession Chemical parameters DNA RNA Receptors Key enzymes Biochemical integrity Introduction of xenobiotic Ecosystem effect Stress proteins Metabolic indicators Acetylcholinesterase inhibition Adenyl energy charge Metallothionen production Immuno suppression enzyme induction Glutathione S Transferase Mixed Functional Oxidases Hydrolases DNA repair mechanisms Population density Productivity Mating success Fecundity Genetic alterations Competitive alterations

How do we measure these effect ? Physio-chemical characteristics: QSAR (quantitative structure activity relationship) Estimate the contribution of portions of the molecule to physio-chemical characteristics Ionic interactions Hydrophobic interactions Van der Vaals forces Hydrogen bonding

Abiotic environmental fate Partitioning Adsorption Transport/advection PCB vs. Benzene …

Biotic environmental fate The interaction of a xenobiotic at the site of action in an organism is often ‘molecular happenstance’ i.e. xenobiotic mimic compounds which are naturally found in species that they affect – hormone mimics Bioaccumulation The storage of a compound in fatty tissue of an animal Result of food chain / trophic levels Biotransformation Metabolic processes, mainly by environmental bacteria, that alter the structure and toxicity of a compound Biodegradation Breakdown of a xenobiotic to CO2 and water

Biotic mode of action (Receptors) Chemicals that interfere with biochemical receptor sites Signaling proteins in membranes Replication Protein synthesis Chemicals that damage biochemical or molecular targets DNA damage Strange breakage Chromosome abnormalities Cancer Non-genotoxic effects such as immunosuppression

Physiological and behavioral effects Standard tool for assessing toxicological effects on populations Tissue lesions Tumors Reproductive success Population success Population age structure – xenobiotics often exert a stronger effect on juveniles => a shift in age structure might indicate that a population is not doing well, because it is affected by a xenobiotic Shift in bacterial communities – contamination reduces bacterial diversity; bacterial numbers often increase because the contaminant is food for some while it is toxic for others

Community effects Ecosystem effects Species diversity Abundance Distribution Ecosystem effects Productivity Trophic level structure Stability