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  xs 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
i1
i
n
Ci

i1 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