1. 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

2. 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

3. 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

4. Generalized Concepts Mechanisms of Toxicity
Oral, dermal, inhalation
Variability in biological communities
Anatomy, physiology, biochemistry
Based on genetics as well as environment

5. Definitions LD50 Threshold Limit Values, TLV
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

6. Definitions

7. 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

8. Quantification of Acute Toxcity, LD50
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.

9. Quantification of Acute Toxcity, LD50
The apex of the curve generated by this equation is LD50

10. Example Spreadsheet solution to Example 10.2 Dose (mg/kg) Death 5 4 105 4 10 9 15 14 20 16 25 11 30 35 7 40 6 45 2 50 1
Spreadsheet solution to Example 10.2

11. Solution
Excel File

12. Solution

13. 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

14. Probit Analysis

15. Probit Analysis Excel command for Probit =NORMINV(Cell/100,5,1)
See Table 10.4 p. 498

16. 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.

17. Solution

18. Solution

19. 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

20. TLA-TWA 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

21. TLV Data
American Conference of Governmental Industrial Hygienists, ACGIH
Resource for data
Gaseous and particulate airborne chemicals
Physical factors
Heat
Ultraviolet light
Ionizing radiation

22. TLV Data
Table 10.5, p. 503 abbreviated

23. TLV Data
If more than one chemical is present (common at hazardous waste sites)
Toxic effects are assumed to be additive
n = number of hazardous chemicals
Ci = concentration of chemical i

24. 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?

25. Solution

26. Solution

27. 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