1. Science of Toxicology The science of toxicology (tossicologia) is based on the principle that there is a relationship between a toxic reaction (the response) and the amount of poison received (the dose). An important assumption in this relationship is that there is almost always a dose below which no response occurs or can be measured. A second assumption is that once a maximum response is reached any further increases in the dose will not result in any increased effect. An exception to this are allergic reactions which are special kinds of changes in the immune system. ED50 = effective dose for 50 % of subjects MCL = maximum containment level LD50 = lethal dose for 50 % of subjects MCLG = maximum containment level goal TD = toxic dose NOEL (NOAEL) = no observable effect level LOEL (LOAEL) = lowest observable effect level TLV = threshold limit value The knowledge gained through toxicology research with both humans and animals is used to set standards for human exposure and the amount of chemical residue that is allowed in the environment. Sometimes a very “politically controversial standard” as the research may not be conclusive or contradictory. "All substances are poisons: there is none which is not a poison. The right dose differentiates a poison and a remedy." Paracelsus (1493-1541) ecotoxicology

2. Dose - response

3. Dose response curve Dose - response

9. Liver damage Developmental toxicity Mortality Selection and knowledge of the response is important. Same dose, different responses - develop standards on the basis of the most “sensitive” response.

10. Micronutrients Cr Cu I Fe Mn Mo Se Zn Na K P Mg Ca F (Si,As,B,V Ni)

11. Dose Response Relationships for Poisons and Micronutrients Arsenic Mercury Selenium no threshold threshold 10 to 20  g/day 55  g/day 200  g/day 400 to1000  g/day optimum RDA Se = region of good health RDA = recommended daily allowance USA

12. Sources of Selenium in the human diet

13. Dose-response knowledge important in hazard identification and characterisation.

14. Arsenic in drinking water in the USA The new EPA standard goes into effect January 23, 2006. 10 ppb Old standard set by the U.S. Public Health Service in 1942 = 50 ppb Although, the average level of As measured in ground-water samples Is less than or equal to 1 ppb (  g/L), higher levels are common especially in the Western States, Midwest, and New England. The EPA estimates that 5.5% of water utilities serving more than 11 million citizens will not be able to meet the standard. How are decisions such as the As standard influenced by dose-response and other research?

26. Toxicology, dose-response studies, back-ground levels, threshold levels, and human and animal environmental standards can involve elected or appointed public officials. Research must be carefully thought out, rigorously executed, and with proper quality assurance (QA) standards. There is considerable interest ($, €) to fund research dealing with environmental (medical geology) factors that may affect human health. SUMMARY