6.16 List the four components of a complete risk assessment.
Solution:
6.17 The Integrated Risk Information System (IRIS), an electronic database that
identifies human health effects related to exposure to hundreds of chemicals, is available
at www.epa.gov/iris. Go to IRIS and determine (a) the weight of evidence descriptor; (b)
the reference dose (RfD); and (c) the slope factor if available for the following six
chemicals/substances: arsenic, methylmercury, ethylbenzene, methyl ethyl ketone,
naphthalene, and diesel engine exhaust.
Solution:
6.18 Why must children especially be protected from environmental contaminants? Use
the term lethal dose (LD) in your answer.
Solution:
6.19 A study of the potential of acrylonitrile to produce brain tumors in rats was
conducted by administering the carcinogen in drinking water for twenty-four months.
The results of the study for female rats are tabulated below.
Dose (mg/kg-day) Brain tumor incidence
0 1/179
0.12 1/90
0.36 2/91
1.25 4/85
3.65 6/90
10.89 23/88
(a) Determine the slope factor (SF) of the dose-response relationship (assume it’s linear).
(Don’t forget to account for the one rat that had a brain tumor even though he wasn’t
exposed to the chemical). (b) How accurate is the linear model of the data?
Solution:
(a) To account for the one rat that had a brain tumor even though it wasn’t exposed to the
Dose
incidence
Risk
0
0.006
0.000
0.12
0.011
0.006
0.36
0.022
0.016
1.25
0.047
0.041
3.65
0.067
0.061
10.89
0.261
0.256
From the plot, it is evident that the SF = 0.023 (mg/kg-day)-1
(b) The linear model of data is accurate with an R2 value of 0.98 which is close to one.
y = 0.0227x + 0.0017
R² = 0.9835
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0246810 12
Probability of Contracting a Brain
Tumor
Dose (mg/kg–day)
6.20 The EPA maintains a comprehensive site of chemical risk information, called the
Integrated Risk Information System (IRIS): http://www.epa.gov/iris/
Visit the page describing the assessment of the Reference Dose (RfD) for Chronic Oral
Exposure: http://www.epa.gov/ncea/iris/subst/0209.htm#umforal for the chemical
atrazine. Atrazine is a popular herbicide, tens of millions of pounds of atrazine are
applied to vegetation in the U.S. annually and it is a widespread drinking water
contaminant.
After reading through the brief provided by IRIS, please answer the following: (a) What
tests did the EPA/Ciba–Geigy perform in order to assess the toxicity of atrazine?
Summarize in tabular format the test subjects, time period, and overall key toxic
responses to be observed. (b) What uncertainty factor is used and how was that derived
(what are its components)? (c) What are the NOAEL and RfD for atrazine, and to which
response do these doses refer?
Solution:
a.
Test
subjects
Time
period
Toxic responses
Sprague–
Dawley rats
2 years
• Decrease body weight and weight gain,
• lower mean red cell count, hemoglobin and hematocrit,
• increase in platlet count,
• decreased triglyceride and glucose levels,
• lower absolute weight of vital organs,
• acinar hyperplasia of mammary gland,
• epithelial hyperplasia of the prostate,
• increased myeloid hyperplasia in the bone marrow of both
the femur and sternum,
• muscle and retinal degeneration, and
•
increase in coagulative centrolobular necrosis in the liver.
Groups of 5-
month old
beagle dogs
1 year
• Cardiopathy syndrome,
• cardiac toxicity,
• dilation of right and occasionally the left atriums
(manifesting as atrophy and myelosis), and
• death.
Charles
River CD
133-152
days
• Lower body weights and depressed body weight gains, and
• reduced food consumption.
Test
subjects
Time
period
Toxic responses
Charles
River rats
Dosing
period:
6-15
days
during
gestation
• Maternal toxicity,
• death,
• reduced food consumption,
• reduced weight gain,
• salivation,
• ptosis,
• swollen abdomen,
• oral/nasal discharge,
• bloody vulva, and
• delayed ossification.
Rabbit
Dosing
period:
7-19
days
during
gestation
• Maternal toxicity,
• decreased body weight gain,
• low-food efficiency,
• abnormal stool samples,
• blood on vulva,
• developmental toxicity,
• decreased total live fetuses and litter size,
• increase post–implantation loss, and
• decrease in mean fetal weight.
b. The uncertainty factor of 100 reflects 10 for interspecies extrapolation and 10 for
intraspecies–variability.
c. NOAEL is 70 ppm (3.5 mg/kg-day) and the RfD is 3.5×10-2 mg/kg-day which is based
off a 2–year rat feeding study.
6.21 Visit the page describing the assessment of the Reference Dose (RfD) for Chronic
Oral Exposure: http://www.epa.gov/ncea/iris/subst/0209.htm#umforal for the chemical
atrazine. Atrazine is a popular herbicide, tens of millions of pounds of atrazine are
applied to vegetation in the U.S. annually and is a widespread drinking water
contaminant. (a) What are the NOAEL and RfD for atrazine, and to which response do
these doses refer? (b) Assume the following additional toxicity data points: LOAEL – 5
mg/kg/day (affects 5% of population); LD50 – 15 mg/kg/day; Other data points – 22
mg/kg/day (affects 75% of population), 30 mg/kg/day (affects 95% of population). Draw
a dose-response curve for these data. (c) What is the approximate slope of the curve? (d)
Now consider applying atrazine to your lawn and assume that there are babies in the
household that like to eat grass. What is the maximum amount of grass that a baby can
eat safely in a day? Assume the following conditions: baby weight ~10kg, residual
atrazine concentration on grass from one application is ~0.01% (where 1% = 10,000
ppmm). (e) Given these results from part (d), does spraying your lawn with atrazine
present any serious risk in this case? Use the “Hazard Quotient” to make this
determination.
Solution:
c. Adding a trendline to the % effect of response vs. the concentration of atrazine plot,
and setting the intercept to zero, the approximate slope of the curve is 3.2 % effect of
response/mg/kg/day.
d. As given in the problem: 1% = 10,000 ppmm which, as covered in chapter 2, is equal
to 100 mg atrazine/kg grass. From part a, the NOAEL is 3.5 mg/kg-day. Using unit
conversions and the weight of an average baby given in the problem as 10kg; the amount
of grass a baby can eat per day can be calculated as shown:
3.5 𝑚𝑔
𝑘𝑔−𝑑𝑎𝑦×10 𝑘𝑔×1 𝑘𝑔 𝑔𝑟𝑎𝑠𝑠
100 𝑚𝑔 𝑎𝑡𝑟𝑎𝑧𝑖𝑛𝑒×1000𝑔
1 𝑘𝑔 =𝟑𝟓𝟎 𝒈𝒓𝒂𝒎𝒔 𝒐𝒇 𝒈𝒓𝒂𝒔𝒔
e. The hazard quotient can be calculated using equation 6.6:
__average daily dose
HQ RfD
=
Use the reference dose found from part a and your results from part d as well.
𝐻𝑄 =
350 𝑚𝑔 𝑔𝑟𝑎𝑠𝑠
𝑑𝑎𝑦 ×1
10 𝑘𝑔
3.5 ∗10−2 𝑚𝑔
𝑘𝑔−𝑑𝑎𝑦 =1000
Spraying your lawn with atrazine presents a serious risk to babies who eat grass since the
hazard quotient is much greater than 1.
y = 3.2283x
R² = 0.9677
0
20
40
60
80
100
120
0 5 10 15 20 25 30 35
% effect of response
Concentration of atrazine (mg/kg/day)
Does Response Curve of Atrazine
6.22 The sigmoid curve used in a dose-response analysis (and many other engineering
applications) has the form:
xLD
e
xresponse
−
+
=
50
1
1
)(
, where x is the dose in mg/kg/day
(a) Show mathematically that the inflection point of the dose-response curve occurs
when x = LD50. What does this mean in practical terms? (b) Using the
information provided in Question 6.21, provide the dose-response equation for
atrazine. What is the dose necessary to produce a lethal response in 90% of the
test population?
Solution:
6.23 Consider a pharmaceutical product with two dose-response curves, one that shows
the effective dose (ED) and the second that shows the lethal dose (LD). Assume that
LD50 = 2 ×ED50 and is equal to 28.27 mg/kg/day. This pharmaceutical company makes
money from selling each course of this drug (D dollars per effective dose) but must pay
damages for each death that it causes (1,000D dollars per lethal dose). (a) Putting aside
questions of ethics and market acceptability, what should the company set as its
recommended dose in order to maximize profits? Show all your work. Hint: You will
need to utilize the equation in problem 6.22.
Solution:
6.24 Visit the following EPA Office of Pesticides webpage that provides information on
the state of the U.S. federal scientific debate on atrazine:
http://www.epa.gov/oppsrrd1/reregistration/atrazine/atrazine_update.htm
Write a one-page memo from the perspective of the strategy team at Syngenta, one of the
main global manufacturers of atrazine, giving a summary of the EPA activities, findings,
and rulings. From a strategy perspective, what overall recommendations would you give,
knowing what you do about how the EPA is considering atrazine?
Solution:
Students’ answers may vary.
6.25 Assume an adult female who weighs 50 kg drinks 2 L of water every day and the
absorption factor for the chemical of concern is 75 percent (so 25 percent of the chemical
is excreted). The concentration of the chemical in the drinking water is 55 ppb.
Determine the dose in mg/kg–day.
Solution:
6.26 (a) Determine the dose (in mg/kg–day) for a bioaccumulative chemical with BCF =
103 that is found in water at a concentration of 0.1 mg/L. Calculate your dose for a 50 kg
adult female who drinks 2 L lake water per day and consumes 30 g fish per day that is
caught from the lake. (b) What percent of the total dose is from exposure to the water,
and what percent is from exposure to the fish?
Solution: