Report

CE 510 Hazardous Waste Engineering Department of Civil Engineering Southern Illinois University Carbondale Instructor: Jemil Yesuf Dr. L.R. Chevalier Lecture Series 9: Quantitative Toxicology Course Goals Review the history and impact of environmental laws in the United States Understand the terminology, nomenclature, and significance of properties of hazardous wastes and hazardous materials Develop strategies to find information of nomenclature, transport and behavior, and toxicity for hazardous compounds Elucidate procedures for describing, assessing, and sampling hazardous wastes at industrial facilities and contaminated sites Predict the behavior of hazardous chemicals in surface impoundments, soils, groundwater and treatment systems Assess the toxicity and risk associated with exposure to hazardous chemicals Apply scientific principles and process designs of hazardous wastes management, remediation and treatment Generalized Concepts Classification of repeated exposure Acute Subchronic Chronic Distinction based on average life expectancy Acute (1 day) Subchronic (2 weeks-7 years) Chronic (> 7 years) Common example would be exposure to a lifetime of drinking water contaminated with trace levels of a hazardous waste Generalized Concepts Mechanisms of Toxicity Oral, dermal, inhalation Variability in biological communities Anatomy, physiology, biochemistry Based on genetics as well as environment Definitions LD50 Lethal dose to 50% of population Used to quantify acute toxcity Threshold Limit Values, TLV Used to quantify chronic exposure limits Maximum Contaminant Level, MCL Used to regulate drinking water under Safe Drinking Water Act Definitions Quantification of Acute Toxcity, LD50 Approach Divide population of animals into a number of subgroups Administer progressively higher dosages of the toxic substance to each group After toxin is administered, the number of deaths within each group are recorded over a specified period Quantification of Acute Toxcity, LD50 n x x f x i 1 n i i f x i i 1 n s2 x x f x i 1 i i n f x i 1 i Here, x is the dose and f(x) is the number of lethal responses. These values of the average and standard deviation allow us to predict the normal distribution of the population. The equation is on the next slide. Quantification of Acute Toxcity, LD50 n x x f x i 1 n i i f x i 1 i n s 2 x x f x i 1 i i n f x i 1 i 2 1 12 xs x f x e s 2 The apex of the curve generated by this equation is LD50 Example Spreadsheet solution to Example 10.2 Dose (mg/kg) Death 0 0 5 4 10 9 15 14 20 16 25 11 30 10 35 7 40 6 45 2 50 1 Solution Dose (mg/kg) Death xf(x) (x-xavg)2f(x) 0 5 10 15 20 25 30 35 40 45 50 0 4 9 14 16 11 10 7 6 2 1 0 20 90 210 320 275 300 245 240 90 50 0 1600 2025 1400 400 0 250 700 1350 800 625 25 Average 7.27 sum 167.27 831.82 sum sum xbar s2 s 23 114.375 10.695 Excel File Solution 0.04 No. of Deaths 0.035 0.03 0.025 0.02 . 0.015 0.01 0.005 0 0 10 20 30 Dose (mg/kg) 40 50 60 Probit Analysis More useful, more common method of computing LD50 and other toxicological parameters Stands for probability unit Transforms sigmoidal curves of dose-response relationships to straight lines Probits are simply deviations from the mean of a normal distribution with a standard deviation of 1 and a mean of 5. In theory, the relationships between probabilities and probit are derived from the cumulative distribution curve Probit Analysis x2 2 e dx 12 10 8 Probit 1 P 2 Y 5 6 4 2 0 0 20 40 60 Percentage (Probability) 80 100 Probit Analysis Excel command for Probit =NORMINV(Cell/100,5,1) 10 20 30 40 50 60 70 80 90 0 3.72 4.16 4.48 4.75 5.00 5.25 5.52 5.84 6.28 1 3.77 4.19 4.50 4.77 5.03 5.28 5.55 5.88 6.34 2 3.83 4.23 4.53 4.80 5.05 5.31 5.58 5.92 6.41 3 3.87 4.26 4.56 4.82 5.08 5.33 5.61 5.95 6.48 See Table 10.4 p. 498 4 3.92 4.29 4.59 4.85 5.10 5.36 5.64 5.99 6.55 5 3.96 4.33 4.61 4.87 5.13 5.39 5.67 6.04 6.64 6 4.01 4.36 4.64 4.90 5.15 5.41 5.71 6.08 6.75 7 4.05 4.39 4.67 4.92 5.18 5.44 5.74 6.13 6.88 8 4.08 4.42 4.69 4.95 5.20 5.47 5.77 6.17 7.05 9 4.12 4.45 4.72 4.97 5.23 5.50 5.81 6.23 7.33 Example An acute bioassay exposed mealworms to various concentrations of the organochlorine insecticide endosulfan. Apply a probit analysis to the following data to calculate the LD50 . A total of 20 mealworms were used to initiate each treatment. Cumulative mortality (No. Dead) is shown after 96 hr. Conc. (ppm) No. dead untreated 1 100 7 160 9 256 9 409.6 13 654.4 11 1047 15 Solution Solution Threshold Limit Value, TLV Used to measure chronic industrial exposure Chronic toxicity is difficult to quantify Less is known about long-term effects Three categories of TLV Time-weighted average, TLV-TWA Average for 8-hr work day (40-hr week) Used to determine the exposure over along periods without adverse effects (equation on next slide) Short-term exposure limit, TLV-STEL Maximum concentration for exposure for repeated periods of up to 15 minutes Ceiling, TLV-C Concentration that cannot be exceeded at any time TLA-TWA Ca Ta Cb Tb ..... Cn Tn TWA 8 Ta = time of first exposure period (hrs) Ca = contaminant concentration during the first period Tb…Tn = succeeding time periods (hrs) Cb…Cn = contaminant concentrations during the succeeding time periods TLV Data American Conference of Governmental Industrial Hygienists, ACGIH Resource for data Gaseous and particulate airborne chemicals Physical factors Heat Ultraviolet light Ionizing radiation TLV Data Table 10.5, p. 503 abbreviated Compound TLV-TWA (ppm) n-Octane Benzene Toluene PCE 300 10 100 50 TLV Data If more than one chemical is present (common at hazardous waste sites) Toxic effects are assumed to be additive n TLV TWAmix C i1 i n Ci i1 TLV TWA n = number of hazardous chemicals Ci = concentration of chemical i Example refer to example 10.4, p. 505 Determine the mixture TLV-TWA for a worker exposed to 40 ppm n-octane, 40 ppm benzene, 40 ppm toluene and 40 ppm PCE in the air of a RCRA solvent recycling operation. Are the concentrations of the chemicals exceeding the TLV-TWAmixture? Compound TLV-TWA (ppm) n-Octane Benzene Toluene PCE 300 10 100 50 Solution Solution Summary of Important Points and Concepts Toxic effects are classified based on duration of exposure, the most common exposure periods are acute, subchronic and chronic The lethal dose of 50% of the population (LD50) is the most common indicator of acute toxicity. The LD50 is used to evaluate potential toxicity during one-time exposures too high concentrations of contaminants, such as hazardous material spills. Determination of the LD50 is accomplished by dosing population sets of organisms with succeedingly higher concentrations of a toxic chemical. The sigmoidal cumulative response to the dosages given is usually transformed to probits as a basis for determining the LD50 Threshold Limit Values (TLVs) were developed for exposures to individuals in the workplace. They are a policy-related parameter based on a no-effect threshold during an 8-hour daily exposure over a working lifetime