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Emissions Transport and Fate Concentrations Exposure Dose Dose-response Relationship Health Risk Schematic overview of a Health Risk Assessment.

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Presentation on theme: "Emissions Transport and Fate Concentrations Exposure Dose Dose-response Relationship Health Risk Schematic overview of a Health Risk Assessment."— Presentation transcript:

1 Emissions Transport and Fate Concentrations Exposure Dose Dose-response Relationship Health Risk Schematic overview of a Health Risk Assessment

2 GLOSSARY OF TOXICOLOGY CONCEPS Acute Exposure: Exposure:14 days or less Chronic Exposure- Exposure to a chemical for 365 days or more Short-Term Exposure Limit (STEL): The maximum concentration to which workers can be exposed for up to 15 min continually. No more than four excursions are allowed per day, and there must be at least 60 min between exposure periods. The daily TLV-TWA may not be exceeded. Threshold Limit Value (TLV)-A concentration of a substance to which most workers can be exposed without adverse effect. Time-Weighted Average (TWA)-An allowable exposure concentration averaged over a normal workday or 40-hour workweek.

3 Lethal Concentration(LO) (LCLO) The lowest concentration of a chemical in air which has been reported to have caused death in humans or animals. Lethal Concentration(50) (LC50) A calculated concentration of a chemical in air to which exposure for a specific length of time is expected to cause death in 50% of a defined experimental animal population. Lethal Dose(LO) (LDLO) The lowest dose of a chemical introduced by a route other than inhalation that is expected to have caused death in humans or animals. Lethal Dose(50) (LD50) The dose of a chemical which has been calculated to cause death in 50% of a defined experimental animal population.

4 Toxic Dose (TD50) A calculated dose of a chemical, introduced by a route other than inhalation, which is expected to cause a specific toxic effect in 50% of a defined experimental animal population

5 No-Observed-Adverse-Effect Level (NOAEL) The dose of chemical at which there were no statistically or biologically significant increases in frequency or severity of adverse effects seen between the exposed population and its appropriate control. Reference Dose (RfD) An estimate of the daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious effects during a lifetime. The RfD is operationally derived from the NOAEL (from animal and human studies) by a consistent application of uncertainty factors Lowest-Observed-Adverse-Effect Level (LOAEL) The lowest dose of chemical in a study, or group of studies, that produces statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control.

6 Hazard ratio (Hazard ratio = intake/reference dose) Expresses non-carcinogenic effects as a quotient of an exposure intake rate (daily dose) and a reference dose (e.g. NOAEL) related to the selected exposure pathways and a (fixed) chronic exposure duration of approximately seven years Ecosystems (Natural Environment). Predicted Environmental Concentration (PEC) Predicted No Effect Concentration (PNEC). Concentration below which unacceptable effects on organisms will most likely not occur PNEC is calculated by dividing the lowest short term L(E)C50 or long term NOEC value by an appropriate assessment factor.

7 Dose-response functions for carcinogenic and non-carcinogenic pollutants

8 Possible forms of exposure-response functions

9 Dose-response and exposure-response function Involves the characterisation of the relationship between the dose administered or received and the incidence or severity of an adverse effect in the exposed population or ecosystem Aspects to be considered: The metabolism of a chemical at different doses Its persistence over time An estimate of the similarities in disposition of a chemical between humans and animals.

10 Mutagen A substance that causes mutations. A mutation is a change in the genetic material in a body cell. Mutations can lead to birth defects, miscarriages, or cancer. Neurotoxicity The occurrence of adverse effects on the nervous system following exposure to chemical. Carcinogen A chemical capable of inducing cancer. Embryotoxicity and Fetotoxicity Any toxic effect as a result of prenatal exposure to a chemical including malformations and variations, altered growth, and in utero death.

11 Fate and exposure Cause-effect chain for ecosystem and human health

12 EXPOSURE ASSESSMENT Is the estimation of the concentration/doses to which human populations or environmental compartments are or may be exposed. Characteristics to be taken into account: Magnitude of actual and/or potential receptor exposures to environmental contaminants. Frequency and duration of these exposures Nature and size of the populations potentially at risk Pathways by which the risk group may be exposed

13 Human health Dose-response The risk of carcinogenic pollutants is estimated with a factor of potential cancer. The risk of non-carcinogenic pollutants is characterised by a reference dose. These values for non-carcinogenic endpoints are called: Oral Reference Doses (RfDs) Inhalation Reference Concentrations (RfCs) by the USEPA, ( U.S. Environmental Protection Agency ) Acceptable Daily Intakes (ADIs) by the FDA ( Food and Drug Administration) Oral and inhalation Minimal Risk Levels (MRLs) by ATSDR.(Agency for Toxic Substances and Disease Registry )

14 Cancerigen Risk = Dose (mg/kg d) * FP (mg/kg/d) -1

15 Framework of Environmental Risk Assessment

16 DOSE-RESPONSE ASSESSMENT Toxicological studies: QSPRs (Quantitative structure-Property Relationships) The goal is to use information about chemical structure to deduce physical-chemical properties, environmental partitioning and reactions tendencies, and even uptake and effects on biota QSARS: Quantitative structure activity relationship In vitro assays Animal assays (rat, mouse, rabbit) Epidemiological information

17 How to get dates for exposure assessment? Environmental monitoring Biological Monitoring (blood, urine, hair, nails, or breast milk) Ecological Monitoring (grass, soils, fish or shellfish) Fate and exposure models

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19 Multimedia models

20 Comparison of the toxicological approach by bioassays/ animal tests and the epidemiological approach using empirical studies to determine damage factors for human health impacts

21 Framework for the assessment of uncertainty and variability

22 Crystal Ball screenshot

23 Monte Carlo Simulation LCI results for heavy metals

24 Monte Carlo Simulation LCI results for cadmium

25 Sensitivity analysis result for PCDD/Fs

26 Report 3. Look information about the follow toxicological properties: Referenci Dose(RfD) in water, food  Referency Concentracion (RfC)  NOAEL  DL 50  STEL  TLV  Cancinogenic Potency (inhalacion, ingestion)  For PCDD/Fs, PCBs y PAHs look for the toxicity factors equivalents (FEQ) to calculate the (TEQ).  Health effects IRIS: epa.gov/region09/waste/sfund/prg/index.htm TERA (Toxicology Excellence for Risk Assessment)


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