Contents
                                  Contents
 Questions or Comments

 Abbreviations

 Acknowledgments

 Executive Summary

 1  Introduction

 2  A General Model of Odor Detection
 8
11
13
3  Odor Detection Protocols                                                  16
   3.1  ASTM Methods E679-91 andEI432-91	  16
   3.2  Standard Method 21 SOB  	  17

4  Review of Previous Studies of MTBE                                        19
   4.1  TRC( 1993) and API (1994)	  19
   4.2  Prahetal.(1994)	20
   4.3  Young etal. (1996)	20
   4.4  Shen etal. (1997) and Shen etal. (1998)	20
   4.5  Dale etal. (1998)	21
   4.6  Stocking et al. (2000)	22
   4.7  Summary	24

5  EPA's Analysis of Stocking et al. (2000)                                      26

6  Comparison of Odor Threshold Estimators                                   29
   6.1  Subject Thresholds	29
        6.1.1  Estimators   	30
        6.1.2  Results	31
   6.2  Population Thresholds  	37
        6.2.1  Estimators   	  37
        6.2.2  Results	44
7  Conclusion
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                Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
A Individual Response Data from Stocking et al. (2000)



References
50




52

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Tables
                                     Tables

   ES.l MTBE odor threshold estimates: EPA and Stocking et al. (2000)	   9
   ES.2 Percent detecting MTBE in at least 50% of samples at various concentrations  .  10

   4.1  Summary of MTBE odor threshold studies	25

   5.1  Population threshold estimates	27
   5.2  Percent detecting at least 50% of the time at various concentrations	28

   6.1  Parameter values for the population threshold simulation	44

   A   Individual response data from Stocking et al. (2000)   	50

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              Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
                                 Figures
ES.l MTBE odor threshold estimates	   9

2.1  Dose-response curves for a hypothetical subject	  13
2.2  Dose-response curves from a hypothetical population	  14

4.1  ASTM odor threshold estimates for 57 subjects (Stocking et al., 2000)	22

5.1  EPA estimates of population thresholds Cs 0 5	28

6.1  Examples of the logistic dose-response function	31
6.2  Log-bias of estimators of C0 5   	  33
6.3  Log-variance of estimators of C0 5	  34
6.4  Mean true detection probability at estimates of C0 5	35
6.5  Variance of true detection probability at estimates of C05	36
6.6  Log-bias of estimators of C095	:	38
6.7  Log-variance of estimators of C095	  39
6.8  Mean true detection probability at estimates of C0 95   	40
6.9  Variance of true detection probability at estimates of C095  	41
6.10 Squared log-bias, log-variance, and log-MSE of estimators of C0505   	46
6.11 Squared log-bias, log-variance, and log-MSE of estimators of C010 5   	47
6.12 Squared log-bias, log-variance, and log-MSE of estimators of C01095	48

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                Questions or Comments
                                       Questions or Comments
                Questions or comments about this report may be directed to:

                                    Andrew E. Schulman, Ph.D.
                                    Office of Ground Water and Drinking Water
                                    U.S. Environmental Protection Agency
                                    1200 Pennsylvania Ave. NW, MS 4607
                                    Washington, DC 20460
                                    (202)260^197
                                    schuknan.andrew@epa.gov

                or to the Office of Ground Water and Drinking Water at (202) 260-3022.
_

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                Statistical Analysis of MTBE Odor Detection Thresholds in Drinking Water
                              Abbreviations
ASTM American Society for Testing and Materials
MSE   mean squared error
MTBE methyl tertiary butyl ether
ppb    parts per billion
ppm   parts per million
RFG   reformulated gasoline
SM    Standard Method
SMCL Secondary Maximum Contaminant Level

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Acknowledgments
                             Acknowledgments

   The following people provided helpful data or discussions about previous MTBE odor stud-
ies: Bart Koch, of the Metropolitan Water District of Southern California, for Dale et al. (1998);
Jim Prah, of the U.S. Environmental Protection Agency, for Prah et al. (1994); and Yvonne
Shen, of the Orange County Water District in Orange County, California, for Shen et al. (1997)
and Shen et al. (1998).
   The following people acted as external peer reviewers for the report: Gary Burlingame, of
the Philadelphia Water Department; Pamela Dalton, of the Monell  Chemical Senses Center;
Steve Heeringa, of the Institute for Social Research at the University of Michigan; and Pamela
Ohman, of the Department of Statistics at the University of Florida. All provided helpful
suggestions which led to an improved report.

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                 Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
                            Executive Summary
   As EPA considers establishing a Secondary Maximum Contaminant Level (SMCL) for
methyl tertiary butyl ether (MTBE), one consideration is what fraction of people can detect
MTBE in drinking water, and how reliably, at given concentrations. At least eight prior studies
have attempted to answer this question, but all of these studies have important drawbacks,
including small or biased experimental panels, flawed experimental protocols, and erroneous
statistical analysis.
   This report reexamines the data from one such study, Stocking et al. (2000). Stocking et al.
tested 57 subjects for detection of odor from MTBE in bottled water, at concentrations ranging
from 2 to  100 parts per billion (ppb). They recruited the largest panel of any MTBE study
to date; used  a panel  of consumers, rather than expert tasters; and used a statistically sound
experimental protocol (ASTM method E679-91). For these reasons, the data in Stocking et al.
(2000) provide the best available information about MTBE odor detection in drinking water.
Stocking et al. (2000) made errors in their statistical analysis, however, which caused them to
significantly overestimate some detection thresholds.
   Figure ES.l shows the results of our analysis of the data in Stocking et al. (2000).  For
any fraction of the population, Figure ES.l shows the corresponding odor detection threshold,
defined as the concentration at which that fraction of subjects can detect MTBE at least half of
the time in drinking water. The figure also shows 95% confidence intervals for the thresholds.
For example,  we estimate that 50% of subjects can detect MTBE at  least half of the time at
15 ppb, with a 95% confidence interval of 10 to 22 ppb. This estimate is consistent with those
of previous studies, which support an odor detection threshold in the range of 15 to 45 ppb.
Table ES.l compares some of our estimates to those of Stocking et al. (2000).  Table ES.2
shows similar results, in terms of the percent of subjects detecting various concentrations at
least half the time in drinking water.
   In addition to reanalyzing the data from Stocking et al., this report:

   •  Proposes a general definition of an odor detection threshold,  as the concentration at
      which a certain percent of subjects can detect the contaminant at  least a certain per-
      cent of the time. We find that 50% is a good choice for the fraction of time, because
      thresholds defined in this way are easiest to estimate.

   •  Evaluates two commonly used protocols for odor detection experiments. We find that
      ASTM protocol E679-91 is statistically sound, but that Standard Method 21 SOB should
      not be used because it does not account for the effect of guessing, and allows the prob-
      abilities of certain outcomes to depend on the subjects' knowledge of the experimental
      protocol.

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Executive Summary
a
in
00
       200

       100

        50


        20

        10
       0.5
        	 ERA'S estimate
        	95% confidence bands
          0     10     20     30    40     50     60     70     80    90     100
                                    percent of population

Figure ES.l:  MTBE odor threshold estimates:  concentrations detectable at least half of the
time in drinking water by fractions of the population.
Table ES.l:  MTBE odor threshold estimates and 95% confidence intervals (in parentheses),
from Stocking et al. (2000) and the present report (EPA).
                                        Threshold (ppb)
                         % of     Stocking
                        subjects  et al. (2000)
                                               EPA
                           5          1.6       1.3 ( 0.8,  2.3)
                          10          2.2       2.2 ( 1.4,  3.7)
                          25          6.5       5.5 ( 3.7,  8.5)
                          50        57       15   (10  ,22  )

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 10
Statistical Analysis of MTBE Odor Detection Thresholds in Drinking Water
Table ES.2: EPA estimates of percent of subjects detecting MTBE in at least 50% of samples
at various concentrations, with 95% confidence intervals (in parentheses).
MTBE
(PPb)
2
5
10
20
% detecting in at least
half of samples
9 ( 4, 14)
23 (14, 32)
39 (29, 50)
58 (47, 68)
   •  Reviews previous studies of MTBE odor thresholds and identifies problems in each
      study.

   •  Evaluates several possible threshold estimators. We find that the simple estimator speci-
      fied in ASTM method E679-91 performs well when the time fraction being estimated is
      50%.

   Considerable uncertainty remains in odor threshold estimates, beyond what is reflected in
the confidence intervals above:

   •  Stocking et al. (2000)  excluded smokers and subjects over 65 years of age from their
      experiment. Thresholds estimated from these data may therefore be too low to represent
      the general population of drinking water consumers. The study also provides insufficient
      data to allow estimation of the effects of age, disease, or stress, all of which are known
      to have important effects on odor sensitivity. Larger and more detailed  studies will be
      required to address these questions.

   •  The thresholds measure only detection of differences between plain and spiked samples,
      as opposed to recognition of particular odors or rejection of samples as undrinkable. The
      relationship between these three responses is highly variable and depends in part on a
      subject's knowledge, beliefs, and tastes.

Nevertheless the data from Stocking et al. (2000) are the best available to date for estimation
ofMTBE odor detection thresholds.

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 1  Introduction
11
                                1.  Introduction
    Methyl tertiary butyl ether (MTBE) is a fuel oxygenate and octane enhancer for gasoline.
 Small amounts of MTBE have been added to gasoline in the U.S. since 1979, to replace lead as
 an octane enhancer. Since 1992, MTBE has been used at higher concentrations in reformulated
 gasoline (RFG), to fulfill the oxygenate requirements set by Congress in the 1990 Clear Air Act
 Amendments. RFG is oxygenated gasoline, specially blended to burn cleaner than conventional
 gasoline, and required to be used year-round in cities with the worst ground-level ozone (smog).
 In 1997 about 25% of gasoline sold in the United States was reformulated gasoline containing
 MTBE (US EPA, 2000). At the same time, MTBE has been detected in drinking water wells
 in areas with leaking underground storage tanks.
    As of November 2000, EPA is proposing to establish a secondary maximum contaminant
 level (SMCL) for MTBE of 5 parts per billion (ppb) in drinking water. The Safe Drinking Wa-
 ter Act (42 U.S.C.  §§300f-j) specifies that an SMCL is a  non-enforceable standard, intended
 to maintain the aesthetic quality of drinking water. Section 1401(2) of the Act states that EPA
 may establish an SMCL for any contaminant that "may adversely affect the odor or appearance
 of such water and  ... cause a substantial number of persons ...  to discontinue its use, or ...
 may otherwise adversely affect the  public welfare."  In choosing an SMCL, EPA must there-
 fore evaluate the taste and odor properties of MTBE, in particular what fraction of people can
 reliably detect MTBE in drinking water at concentrations of interest.
    Several taste and odor studies of MTBE have been performed. We consider the results of
 these studies in Section 4. We find that all of the studies performed to date suffer from one or
 more of the following statistical flaws:

   • sample sizes that are too small (4 to 10  subjects) to  allow meaningful inferences to the
      population of drinking water consumers

   • subjects selected for high sensitivity to odor

   • unclear definitions of odor thresholds; confusion of subject and population thresholds;
      or failure to treat subject thresholds

   • erroneous or unclear statistical analysis

   • statistically invalid experimental protocols

 Confusion  about the exact meaning of an odor threshold  is especially problematic and
 widespread.
   In addition to the "within-study" problems listed above, there are "across-study" inconsis-
tencies which make interpretation harder. Studies test different ranges of concentrations; use

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 12
Statistical Analysis of MTBE Odor Detection Thresholds in Drinking Water
different experimental protocols, with additional minor variations; and use different statistical
methods to analyze their results.
   This report has two goals.  First, we aim to resolve as many as possible of the problems
described above, by clarifying the meaning of odor detection thresholds, and by identifying
an experimental protocol and methods of statistical  analysis which allow the most reliable
statistical inferences for odor thresholds. We believe that the methods which we identify here
would make a good standard approach for defining and estimating odor thresholds. Second, we
apply these techniques to the best available MTBE odor data set, that of Stocking et al. (2000),
in order to estimate odor detection thresholds for MTBE in drinking water.
   Studies of taste or odor must distinguish between detection, recognition, and rejection of
a contaminated sample. A consumer may detect that one sample is different from another,
but not  recognize an odor or reject either  sample as undrinkable.  In this report we consider
only detection thresholds,  for two reasons. First, existing studies of MTBE consider mostly
detection, with a small amount of data on recognition and none on rejection. Second, whether
rejection follows detection depends on a subject's knowledge, beliefs, and tastes, all of which
are outside our scope.
   We begin in Section 2 by offering a precise definition of odor thresholds, based on a general
model of odor detection. In Sections 3 and 4, we review standard odor detection protocols
and existing studies of MTBE odor thresholds, in light of our definition. In Section  5  we
reanalyze the data from Stocking et al. (2000), to estimate MTBE odor thresholds. In Section 6
we compare the performance of several threshold estimators under the conditions of Stocking
et al.'s experiment. In Section 7 we present our conclusions.

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2  A General Model of Odor Detection
                        13
                2. A General Model of Odor Detection


   In this report we suppose that each person has a probability of detecting a substance of in-
terest at each concentration, and that the probability of detection increases with concentration.
"Detection" means the observation of a difference in taste or odor between a sample of plain
water (of whatever type; see below) and a sample of water plus the substance of interest.  For
convenience we refer to the substance of interest as a "contaminant."
   Figure 2.1  shows three hypothetical dose-response curves  that would satisfy our model.
Given a concentration, each curve determines the subject's probability of detecting the con-
taminant. For example, at  10 ppb, each of the hypothetical curves assigns probability 1/2 of
detection. One of the curves (sold line) yields zero probability of detection at concentrations
below about 2 ppb, and probability one of detection above about 50 ppb. The other two curves
never assign probabilities of exactly zero or one; the probabilities only approach zero or one
for very small or large concentrations (although this is not always clear from the graph). This
property is typical of statistical dose-response models.
   Our model implies that each subject has a set or range of odor thresholds, determined by
the probabilities of detection.  For example, under any of the  dose-response curves in Fig-
ure 2.1, the subject has a 50% detection threshold  of 10 ppb. The 75% detection threshold is
somewhere between about  11 and 25 ppb, depending on the dose-response model. In general,
for a number T between 0 and 1, a subject's (1007)% detection threshold, denoted CT, is
the concentration at which  the subject can detect the contaminant (1007)% of the time, or in
(1007)% of samples. We call T the time fraction of the odor threshold. A dose-response curve
is therefore a function that determines the time fraction of detections as a function of dose. As
observed above, under most statistical dose-response models there is no 0% or 100% threshold,
       _o
       1  0.5
       •S
       °-0.25
                                           10
                                       cone, (ppb)
30
100
           Figure 2.1: Possible dose-response curves for a hypothetical subject.

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 14
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
         0.75 -
         0.25
                                           10   15
                                       cone, (ppb)
                                         30
60
100
Figure 2.2: Dose-response curves and corresponding 50% detection thresholds for a hypothet-
ical population of four subjects.
only 99%, 99.9%, 99.99%,... and 1%, 0.1%, 0.01%,... thresholds.
   Consider now a population of subjects, each with his or her own odor dose-response curve.
Figure 2.2 shows the dose-responses curves and corresponding 50% detection thresholds for a
small hypothetical population. The 50% thresholds in Figure 2.2 range from 3 to 60 ppb. In
general, given a population of subjects and numbers S and T between 0 and 1, we define the
population's (S, T) odor detection threshold, denoted Cs T, as the (1005)-th percentile of the
individual subjects' (1007)% odor detection thresholds. That is, (1005)% of the subjects can
detect the contaminant (100 T)% of the time or in (1007*)% of samples, at or below Cs T. For
example in Figure 2.2, the 50% subject thresholds are 3,  10, 15, and 60, so the (50%, 50%)
population threshold is anywhere between 10 and 15. We call S the subject fraction, and T
as before is the time fraction. CST may be estimated as a sample (100S)-th percentile of
(lOOr)-percentage points of estimated dose-response curves.
   Other definitions of thresholds are of course possible. Different statistics may be  used
to summarize over the time or subject fractions; for example,  most studies summarize over
subjects by computing a geometric mean of individual thresholds. One can also summarize
first over subjects, then over time. Dale et al. (1998) take this approach by first computing
the dose response for an "average" subject, that is, by averaging dose-response curves over
subjects, and then choosing probability (time fraction) thresholds of the averaged response
curve.
   We believe that our definition of odor thresholds is the most useful one, because  it goes
directly to the true objective of the analysis: what percent of people will detect the contaminant
some given fraction of the  time. To be useful, other definitions have to be interpreted in terms
of these fractions. For example, an average subject threshold does not tell us directly how many

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2  A General Model of Odor Detection
15
people can detect the contaminant at that level; to get that information we have to interpret the
average as approximately a median. This is even more true for a geometric mean, which is a
less familiar statistic, and sometimes has to be explained as approximately a median.
    Regardless of the particular definition, however, a crucial point is that any population odor
threshold statistic summarizes the dose-response curves over both the subject and time frac-
tions. That is, a threshold must correspond at least implicitly to some percent of people de-
tecting some percent of the time.  In order to interpret the threshold, we have to know what
the fractions are. Although this point may seem obvious, many of the studies which we review
in Section 4 are difficult to interpret precisely because they fail to state or evaluate how they
summarized the dose-response, in particular over time. A typical claim is that at some con-
centration, some percent of subjects "can reliably detect" the contaminant. In some cases the
time fraction is implicit in the experimental protocol or threshold estimator, but in other cases
it cannot be determined from the information in the study.
    Our odor dose-response model does not account for several factors which are known to
influence odor detection. Covariates such as age, disease, smoking status,  and stress have all
been shown to have important effects on odor sensitivity (Schiffinan, 1992; Smith and Duncan,
1992). We do not  treat these covariates here because, with the exception  of smoking status,
no available studies of MTBE provide information about them. In the case of smoking status,
all MTBE studies which mention it exclude smokers; this approach obviates any modeling of
smoking effects, at the cost of introducing a negative bias in the threshold estimates.
    Our model also does not consider desensitization to odor through time. In serial sniffing
tests, odor sensitivity is likely to decrease for a period of minutes to hours following each sniff.
Since we are interested in drinking water, the ideal rest period between test sniffs would be the
mean time between a consumer's drinks of tap water, or on the order of one hour. In practice,
cost constraints require that tests progress faster, on the order of one minute between sniffs.
This faster testing probably reduces odor sensitivity, but most studies provide no data about
this question, so we do not consider it here.
   Finally the odor threshold is affected by the medium, that is, the type of water in which the
contaminant is presented. A contaminant may be more easily detected in distilled water, for
example, than in tap water, which typically contains chlorine and other contaminants that may
mask the odor of the contaminant of interest. For this reason any dose-response curve must be
assumed to be valid only for the stated medium. Fortunately all studies of MTBE clearly state
which medium is used, and some (Shen et al., 1997) test more than one medium.
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 16
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
                       3.  Odor Detection Protocols

   Three experimental protocols, Standard Method 2150B (APHA, 1995) and ASTM meth-
ods E1432-91 and E679-91 (ASTM, 1995a,b), specify standard methods for performing odor
detection experiments and estimating odor detection thresholds. In this section we describe
the experimental design and threshold estimators of each protocol. We argue that Standard
Method 2150B, while it has some  advantages, has statistical flaws that make it useless for
statistical modeling and estimation.  The ASTM protocols avoid these problems and should
therefore be preferred for statistical modeling.
   Samples of water plus the contaminant (substance of interest) are referred to below as
"contaminated" or "spiked." Again the language of contamination is used for convenience and
without prejudice. Samples of plain water are referred to as "uncontaminated" or "blanks."
3.1  ASTM Methods £679-91 and E1432-91

   The ASTM protocols specify that samples of the contaminant are to be presented to subjects
in increasing order, using a "forced choice triangle test." That is, for each concentration, the
subject is presented with three bottles, two blank and one spiked (or in some versions, one
blank and two spiked).  The subject is asked to sniff each of the three bottles and identify
one as different from the other two. One bottle must be selected each time, so if the subject
cannot detect a difference between the bottles, s/he is forced to guess. Thus the subject has one
chance in three of choosing the correct bottle, even if s/he cannot detect a difference. When
analyzing the results of a forced-choice test, one has to distinguish between the probability T
of detecting a difference, and the probability P of answering correctly. P is greater than T,
because a subject who cannot detect the contaminant may still guess correctly. The relationship
between the two may be shown to be
                                 P = T + (1 - T)C
                                                              (3.1)
where C is the probability of a correct guess. For a forced-choice triangle test, C = 1/3 and
so/> = (1/3) +<2/3)7\
   The two ASTM protocols specify different subject threshold estimators. ASTM method
£1432-91 defines an individual odor threshold as "the concentration for which the probability
of detection of the stimulus is 0,5" (ASTM, 1995a). Method E1432-91 proposes to estimate this
threshold by using nonlinear regression to estimate the dose-response relationship of "percent
correct above chance" (i.e.,  corrected for the 1/3 probability of a correct guess) to log-dose,
then finding the dose which yields  50% response.  This method is said to be valid only for
an experiment with multiple presentations of each concentration and a total of 20 or more

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3.2  Standard Method 21 SOB
17
presentations per subject. A population threshold is then estimated as the geometric mean of
individual thresholds, or, if desired, a (1005)% normal-theory quantile estimate of individual
thresholds. In the latter case, ASTM method E1432-91 seeks to estimate the (S, 0.5) population
threshold.
    ASTM method E679-91 uses a simpler individual threshold estimator, intended for smaller
experiments where the dose-response relationship is harder to estimate. Using this method,
each subject's threshold is estimated as the  geometric mean of the highest concentration at
which the subject gave a wrong answer and the next higher tested concentration. (If the subject
gave all right or all wrong answers, s/he is assumed to have a given a wrong answer at a next
lower concentration in the sequence, or a right answer at a next higher concentration.) As an
example, the answers at different concentrations of MTBE from subject #40 in Stocking et al.
(2000) looked like this:
cone, (ppb)
answer
2
o
3.5
o
6
+
11
o
19
+
33
+
57
+
100
+
where o represents a wrong answer, and +  a right answer.  Since this subject's last wrong
answer occurred at 11 ppb, his or her odor threshold is estimated as the geometric mean of 11
and 19, or 14. Population thresholds are then estimated as the geometric mean of the subject
thresholds. Note that this method does not explicitly take into account the effect of guessing,
and it only uses data at the highest concentrations for each subject. Even so, we will see in
Section 6 that it performs fairly well at estimating the 50% subject threshold.
3.2  Standard Method 21SOB

    Standard Method 2150B defines a subject's odor threshold as the concentration at which
odor is "just detectable" (APHA, 1995). The method states that because of variability there is
no absolute odor threshold, but it does not name a probability of detection that corresponds to
just-detectability.
    Standard Method 2150B specifies that eight contaminated samples are to be presented one
at a time to each subject, in ascending order of concentration, with two or more blanks mixed in
at random. Subjects are asked to state whether they detect any odor in each sample. A detection
threshold is then estimated for each subject as the lowest concentration at or above which the
subject made no mistakes in identifying samples with or without contaminant. (This definition
is not entirely clear however, because an accompanying graphic shows an arrow pointing to
the midpoint between the last miss and the next tested concentration.) Group thresholds are
estimated by using "appropriate statistical methods" to compute the "most probable average
threshold" from the individual thresholds; geometric means are recommended for this purpose.
    Standard Method 21 SOB has some advantages over the ASTM methods. One advantage is
that it requires fewer sniffs: only 10 sniffs for 8 contaminated samples, compared to 24 sniffs
using the triangle test. This may lead to more accurate results by reducing desensitization of
the nose over time. Another advantage is that when a subject cannot detect the contaminant, it

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 18
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
 is more natural for him or her just to say so than to be forced to guess, as in the forced-choice
 test  It is possible that a subject who is annoyed or distracted by guessing would give less
 reliable answers.
    On the other hand, Standard Method 21 SOB presents statistical difficulties which the ASTM
 methods do not. The problem is that under this method, the probabilities of the various out-
 comes may depend on the subject's knowledge of the  experimental protocol.  To see this,
 consider first the ASTM protocols, which use the forced-choice triangle test.  Under this test,
 a subject who knows the details of the experimental protocol gains no information to help him
 or her take the test. In each presentation, two bottles are plain water, and one is spiked; the
 subject may know this—in fact he or she should know it—but gains no information thereby
 about which bottle he or she should choose. Moreover, when a subject cannot detect the con-
 taminant, the probability of a correct answer is known: it's 1/3. By contrast, under Standard
 Method 21 SOB, a subject who knows the experimental protocol gains important information
 about the test: he or she learns that of, say,  10 bottles presented, 8 are contaminated and 2 are
 not. Thus when asked whether he or she detects odor in the sample, the subject knows that, 4
 times out of 5, the "right" answer is yes. This poses several problems for the modeler. First,
 when a subject cannot detect the contaminant in a spiked sample, is the probability of correctly
 answering "yes" anyway by guessing really 80%? If so, the power of discrimination of the test
 will be poor; and if not, then what is the probability? Second, when presented with a blank,
 what is the probability that a subject will identify it as contaminated? Is a subject who knows
 the protocol more likely to imagine smelting contaminant in a blank? If so, how much more
 likely? And what percent of subjects knew the protocol? (For reasons of economy, subjects
 in odor threshold studies are often lab employees or even study authors, who take such tests
 repeatedly and know the details of the experimental protocol.)
    The answers to these questions are unknown, in the absence of a separate experiment de-
 signed to measure them. Standard Method  21 SOB avoids answering  them by specifying a
 simple threshold estimator which does not require that one know the answers. Yet no statistical
justification is given for preferring this estimator,  and indeed no such justification is possi-
 ble without answering the above questions, because the statistical properties of the estimator
 depend on unknowns. Nor is it possible to propose other, model-based estimators, without
 being able to assign probabilities to right or wrong guesses. For these reasons, we believe that
 Standard Method 21 SOB should not be used for odor detection experiments.

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 4  Review of Previous Studies ofMTBE
19
               4.  Review of Previous Studies ofMTBE

    In this section we review previous studies ofMTBE odor detection thresholds in drinking
 water. Although each of the studies has some methodological problems, taken together they
 present a fairly consistent picture ofMTBE odor thresholds, which we discuss at the end of the
 section.
 4.1  TRC (1993) and API (1994)

    TRC (1993), in a report to ARCO Chemical Company, estimated odor detection and recog-
 nition thresholds for MTBE in distilled water. They tested five concentrations ranging from 106
 to 1,483 ppb, with two replicates on a panel of seven subjects. Although the authors claimed
 to use Standard Method 21 SOB, they used a forced-choice triangle test, and to estimate the
 individual detection thresholds they combined the results of that test with statements from the
 subjects about whether they could detect a difference.
    API (1994) also estimated odor thresholds for MTBE in distilled water. The authors tested
 six concentrations ranging from 23 to 740 ppb, with two replicates on a panel of seven subjects.
 This study was also carried out by TRC, and is quite similar to TRC (1993). The methodology
 of the two studies is the same, and three of the panel members were apparently the same.
    API (1994) defines the population detection threshold as trie smallest concentration  at
 which  50% of the population can detect the contaminant, but does not say how reliable the
 detection should be. That is, the authors specify a population fraction of S = 0.50, but fail  to
 identify the time fraction T. A complicated method is used to estimate the population thresh-
 old. A linear regression model  is fit with response equal to the midpoints between the tested
 log-concentrations, and predictor equal to the rank of the number of times the contaminant
 was first detected at each concentration, standardized and transformed to a normal score.  The
 intercept of the regression is claimed to be the log-detection threshold.
    Using this method, TRC (1993) and API (1994) find group odor detection thresholds of 95
 and 45 ppb, respectively, for MTBE in distilled water.
    These two studies present at least three problems. First, the sample sizes are small: each
 study used only seven subjects, and the two studies combined used a total of 11 subjects.
 Second, the higher threshold estimate  in TRC (1993) is almost certainly due to the higher
 range of concentrations tested there. The two studies shared the same methodology and even
 half of their experimental panels; the only apparent difference between them was in the ranges
 tested.  Moreover the estimated  threshold in TRC (1993) lies below the range of observation,
 implying that an extrapolation was used and casting doubt on the result. Third, the statistical
model used for the regression is theoretically unsatisfactory, because the random error occurs

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20	Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
in the predictors (sample percent correct) rather than the responses (log-concentrations). The
problem is aggravated by correlation among the predictors, which arises because they are all
estimated from the same set of subjects. As a result the regression parameter estimates are less
reliable than they could be.

4.2  Prah et al. (1994)

    Prah et al. (1994) tested 37 subjects for detection ofMTBE in distilled water, at concentra-
tions ranging from 31 ppm (parts per million, by volume) to 1000 ppm. They used an experi-
mental protocol similar to that of Standard Method 21 SOB, in which 6 contaminated samples
and 2 blanks were presented to subjects one at a time. They found an odor threshold of 180
ppb, but this number represents the concentration of MTBE in the head space (air) above the
water in the sample jar, not the concentration in water  (J. Prah, personal communication). The
corresponding concentration in water was presumably 31 ppm, which, while the lowest con-
centration tested, is 3 to 4 orders of magnitude greater than the concentrations at which subjects
have detected MTBE in other studies. Since 31 ppm was the lowest concentration tested in this
study, the results cannot plausibly shed light on detection thresholds in the range of 2 to 100
ppb.

43  Young et al. (1996)

    Young et al.  (1996) estimated taste and odor thresholds of 59 contaminants, including
MTBE, in bottled mineral water. For MTBE they used 9 female subjects between 25 and 55
years of age, selected for "above average" odor sensitivity. Young et al. (1996) used a modified
version of the HMSO odor-detection protocol (HMSO, 1982). For each subject they first iden-
tified a provisional odor threshold, by presenting spiked samples in increasing concentrations,
each paired with a blank, until the subject picked out the right sample.  They then verified the
provisional threshold by a sequence of further trials with blank-blank and spiked-blank pairs,
at the provisional and next higher thresholds. The procedure seems designed to pick out with
some certainty the lowest concentration at which a subject can detect the contaminant, but the
authors do not identify a detection probability that they associate with just-detectability, nor do
they attempt to determine the effective time fraction of their estimator.
    Young et al. (1996) find a geometric mean MTBE odor threshold of 34 ppb. Unfortunately,
the range of tested concentrations in Young et al.  cannot be determined from the paper; al-
though the authors list the dilutions they used of their  stock MTBE solution, they do not state
the concentration ofMTBE in the stock solution.

4.4  Shen et al. (1997) and Shen et al. (1998)

    Shen et al. (1997) estimated odor thresholds ofMTBE in odor-free, tap, and chlorinated
odor-free water. They used Standard Method 2150B, with 4 replicates for odor-free water and 2

-------
 4.5   Dale et al. (1998)
21
each for tap and chlorinated water. Panels for each replicate consisted of 8 to 10 "experienced"
subjects; many of the panelists took part in two or more replicates. Concentrations of 2.5 to
150 ppb were tested. At room temperature, individual detection threshold ranges were 2.5-100
in odor-free water, 2.5-150 in tap water, and 5-150 in chlorinated water. Geometric means of
subject thresholds ranged from 13.5 to 40.3 for odor-free water, 13.5 to 33.9 for tap water, and
31.3 to 43.5 for chlorinated water.  Additional tests at higher temperatures (Shen et al., 1997)
and at various temperatures and chlorine concentrations (Shen et al., 1998) gave similar results.
    As we argue in Section 3.2, because of the design of Standard Method 2150B, the meaning
of Shen et al.'s results is unclear.  Moreover both studies modified the Standard Method by
discarding all responses from a subject in a trial if the responses resulted in an "anomaly," that
is, identifying a blank as contaminated, or failing to detect odor in the highest concentration
of contaminant after identifying a lower concentration. While this practice may be defensible
as a way of improving the estimate by removing subjects who are only guessing, it illustrates
the problem of using a method such as SM 2150B, which does not account for guessing.  A
well-designed experimental protocol should not require that one throw out otherwise validly
obtained data.
4.5   Dale et al. (1998)
    Dale et al. (1998) estimated odor thresholds of MTBE in odor-free water.  They used a
panel of 4 to 7 trained sniffers, all of whom were required to be able to detect "off-flavors and
off-odors at very low concentrations." Subjects took triangle tests at 7 concentrations ranging
from 6 to 118 ppb, with 6 replicates at each concentration for each subject.
    Dale et al. (1998) used probit regression with a common slope (B. Koch, personal commu-
nication; see Section 6.2 for a description) to estimate dose-response curves for each subject.
They then summarized the curves as odor thresholds in two ways. First, they averaged the
dose-response curves over subjects, to find the dose-response for an "average" subject. Based
on this function, the average subject could detect MTBE at 20 ppb about 50% of the time, for
example. In a second, separate analysis, they found that 60% of subjects "would perceive the
MTBE" odor at 43-71 ppb (95% confidence interval), but did not say how often. That is, they
specified the subject fraction S = 0.60, but failed to state the time fraction T.
    Dale et al. (1998) used a small panel, intentionally biased toward more sensitive subjects. It
is difficult to draw inferences from such  a panel to the population of drinking water consumers.
Their estimated dose-response functions also appear to be wrong, because they modeled the
probability of odor detection as a function of untransfonned concentration, rather than log-
concentration. As a result, the averaged dose-response curve shows approximately a 45%
probability of detection at a concentration of zero.  The authors  also did not account for the
effect of guessing.  Finally their threshold estimates are hard to interpret, because they either
describe a hypothetical average subject,  or do not specify the time fraction of the threshold.

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22
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
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               1.5 2  2.6 3.5 4.6  6
                    8  11  14  19 25 33  43 57  76 100132
                      MTBE (ppb)
Figure 4.1: ASTM odor threshold estimates for 57 subjects (Stocking et al., 2000). Dots are
thresholds; dashed lines are the tested concentrations.

4.6  Stocking et ai. (2000)

   Stocking et al. (2000) estimated odor thresholds of MTBE in bottled water at room tem-
perature. They used a consumer panel of 57 subjects, the largest of any MTBE study to date.
The experiment followed ASTM protocol E679-91, including the forced-choice triangle test,
with 8 concentrations, equally spaced on the log scale, from 2 to 100 ppb. Each concentration
was presented once to each subject, although subjects were allowed to repeat each presentation
once if they were unsure of their answer the first time.  Subjects were not selected from the
entire population of drinking water consumers, but rather were drawn from a list of 10,000
consumers maintained by the National Food Laboratories for taste and odor experiments. The
panel was balanced by sex and age within the range of 18 to 65 years of age.  Smokers were
excluded.  Further details about subject selection and training, container preparations, test ad-
ministration, and quality control are provided in Malcolm Pirnie (1998). The data from this
experiment are presented in Appendix A.
   Individual odor thresholds were estimated according to ASTM protocol E679-91.  Fig-
ure 4.1 shows the set of 57 threshold estimates; in accordance with the ASTM protocol, the
estimates fall between the tested  concentrations. For example, subjects who  failed to iden-
tify MTBE at 11 ppb, but correctly identified it at 19 ppb and all higher concentrations, were
assigned thresholds equal to the geometric mean of 11 and 19, or 14. Ten subjects correctly
identified MTBE at all tested concentrations, from 2 to 100 ppb; these subjects were assigned
detection thresholds of 1.5 ppb. Eight subjects failed to identify MTBE at 100 ppb (although
all identified some lower concentrations correctly), and were assigned thresholds of 132 ppb.
The geometric mean of the individual threshold estimates is 15 ppb.
   In a separate analysis, Stocking et al. (2000) used a logistic regression model

                             log (-~-p ) = a + b log C                         (4.1)

to model the fraction  P of the population correctly identifying MTBE at concentration C (in

-------
 4.6  Stocking et at. (2000)
23
 ppb). The data used to fit this model are shown on the last line of Appendix A. For example,
 at 2 ppb the sample fraction is 25/57. The slope and intercept parameters were then estimated
 as a — -0.726 and b = 0.569. (Stocking et al. did not list their parameter estimates; EPA
 used maximum likelihood (McCullagh and Nelder, 1989) to derive the estimates given here.
 These estimates give probabilities that agree fairly well with Tables 8 and 9 of Stocking et al.)
 The authors then corrected for the effect of guessing in the forced-choice test by adding 1/3 to
 the probability of detection, to approximate the probability of a correct answer. For example,
 for 25% probability of detection, take P ~  1/3 + 0.25 = 0.583 and solve (4.1) for C to find
 C = 6.5 ppb (Stocking et al. find C = 6.2).  The authors' interpretation is that 25% of subjects
 can detect MTBE at about 6 ppb.
    The logistic regression  analysis has several problems. First, the correction for guessing
 contains a simple error in the approximation of P =  1/3 + (2/3)T (equation (3.1)) by P  =
 1/3+ T. This approximation is accurate enough when T is small, but it makes a large difference
 when T =  50%.  For example using  P  «  1/3 + T, Stocking  et al. find a  threshold when
 T = 50% of about 57 ppb; using P =  1/3 + (2/3)J, the threshold is 12 ppb.
    A second problem lies  in Stocking et al.'s interpretation of the regression results.  The
 authors use the results of the fitted model to conclude that "2 Mg/L, 6 jtg/L, and 57 ftg/L ...
 represents the concentration [sic] at which 5%, 25%, and 50%, respectively, of the subjects can
 make accurate discriminations." Note that no time fraction is stated to correspond to "accurate
 discriminations." In fact, the stated percentages are a combination  of subject and time fractions,
 in such a way that neither fraction can be inferred from them. To see this, consider the following
 two possible descriptions of the study population:

   1.  At 12 ppb, 20% of the subjects have  a 10% chance of detecting MTBE, and the other
      80% have a 60% chance of detecting it. On average, the traction of detections at 12 ppb
      will be (0.20X0.10) + (0.80)(0.60) = 0.50, or 50%.

   2.  At 12 ppb, 20% of the  subjects have a 90% chance of detecting MTBE, and the other
      80% have a 40% chance of detecting it. On average, the fraction of detections at 12 ppb
      will be (0.20)(0.90) + (0.80)(0.40) = 0.50, or 50%.

 Both of these descriptions agree with Stocking et al.'s (corrected) regression results of 50%
 detections at 12 ppb, but conflict with their interpretation. In the first case, 80% of subjects
 are at least 50% likely to detect at 12 ppb;  while in the second case, only 20% are. Stated
 another way, in the first case  12 ppb is  an (80%, 50%) threshold, while in the second case it
 is a (20%, 50%) threshold.  Although this example is artificial, it shows that Stocking et al.'s
 interpretation in terms of subject fractions is not supported by their analysis.
   Another problem with model (4.1) is that the data in Appendix A do not represent 57 x 8
 independent observations, since repeated observations on a single subject are correlated. Stock-
 ing et al. (2000) apparently did not account for this correlation  in estimating a and b. The
result may be less efficient estimates and  confidence intervals that are too narrow. This may
be a reasonable compromise against the difficulty of fitting a model, but the choice needs to be
evaluated. In Section 6 we consider some models that include intra-subject correlation.

-------
24
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
   Finally, fitting a model such as (4.1), which does not account for guessing, then adjusting
for guessing post-hoc as in Stocking et al. (2000), simplifies the analysis but may not be the
best approach. A better method might be to fit a model which explicitly takes the probability
of guessing into account. We consider this possibility in Section 6.
4.7  Summary

   Table 4.1 summarizes the results of existing odor studies ofMTBE, as well as the problems
that we have identified above. All of the studies have important drawbacks; small panels and
unclear threshold definitions or properties are the most common.
   Despite the problems that we have detailed here, the results listed in Table 4.1 are fairly
consistent and support a (50%, 50%) odor detection threshold for MTBE somewhere in the
range of 15 to 45 ppb. We do not include the results of TRC (1993) and Prah et al. (1994) in
this range, since, as we argued above, the higher threshold estimates of these studies appear to
have been caused by the higher concentrations that they tested. Our reanalysis of the data from
Stocking et al. (2000), in Section 5, finds a (50%, 50%) odor detection threshold of 15 ppb,
consistent with these findings.

-------
4.7  Summary
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26
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
             5.  EPA's Analysis of Stocking et al. (2000)
   In this section we reanalyze the data from Stocking et al. (2000), in order to estimate MTBE
odor detection thresholds in drinking water. Stocking et al. (2000) contains the best available
data for estimating MTBE odor thresholds: it used the largest panel of any study to date; used
a panel of consumers rather than expert sniffers; followed the ASTM protocol, in particular the
triangle test; and tested a low enough range of concentrations, centered approximately around
the threshold estimates of other MTBE studies. The data from the study are also reproduced in
full in the paper; we reproduce them here in Appendix A.
   The data from  Stocking et al. (2000) do have some disadvantages:

   * The study panel was not selected as a random sample of drinking water consumers, as we
     assume below. Rather, subjects were chosen from a list, maintained by the National Food
     Laboratories, which conducted the experiment, of self-selected taste-and-odor study par-
     ticipants.  It is therefore difficult to know how far any analysis of this data set can be
     generalized  to the population of drinking water consumers. We know of no reason to
     expect any systematic bias due to this selection process, however.

   • Only non-smokers ages 18 to 65 were included in the study. This probably has the effect
     of biasing the results toward low thresholds.  The panel was also balanced, apparently
     deliberately, by gender and by three age groups.  It is not known to what extent these
     balances reflect the population of drinking water consumers.

   • Only one  replicate of each concentration was tested on each subject. Individual odor
     thresholds can therefore be difficult to estimate, as we see in Section 6.1. This variability
     is accounted for in our confidence intervals, however.

While keeping these reservations in  mind, we believe that the size and careful design of the
experiment make these data suitable for estimation ofMTBE odor thresholds.
   Our goal is to estimate (S, 50%) odor detection thresholds for MTBE, with S ranging from
0 to 100%. That is, we want to know at what concentration any given fraction of the population
can detect MTBE  at least half of the time. Conversely, given a concentration  of MTBE, we
want to know what fraction of people can detect it at least half of the time. Although we could
choose any time fraction to estimate, 50% seems a reasonable choice. The ASTM estimator
also tries to estimate 50% thresholds, and the results of Section 6 show that 50% thresholds are
easiest to estimate.
   In Section 6 we evaluate several estimators of population thresholds, by simulating their ef-
fectiveness under conditions similar to those of Stocking et al. (2000). When the time fraction
of the estimand is  50%, a simple estimator with small bias and variance may be obtained by

-------
5   EPA's Analysis of Stocking et al. (2000)
  27
Table 5.1: Population threshold estimates and 95% confidence intervals (in parentheses), from
Stocking et al. (2000) and the present report.
Threshold (ppb)
%of
subjects
5
10
25
50
%of
samples
50
50
50
50
Stocking

et al. (2000) EPA
1.6
2.2
6.5
57
1.3 ( 0.8, 2.3)
2.2 ( 1.4, 3.7)
5.5 ( 3.7, 8.5)
15 (10 ,22 )
computing an ASTM threshold estimate for each subject (following ASTM (1995b); see Sec-
tion 3.1 or 6.1), then computing a lognormal quantile estimate from the set of subject thresh-
olds.  Let Cj,..., Cs? be the subject threshold estimates; these are tabulated in Appendix A.
Let A and a be the sample mean and standard deviation, respectively, of log C\,..., log €57;
we find fr = 2.71 and a = 1.49. Then for any given S, the threshold estimate is
                                                                                (5.1)

where <$>"' is the inverse cumulative distribution function of the standard normal distribution.
   Figure 5.1 shows a graph of C£Q™ as a function of S, with pointwise 95% confidence
bands, obtained by bootstrap (Efron and Tibshirani, 1993). The subject threshold estimates are
also plotted for comparison. Table 5.1 lists the population threshold estimates at several values
of S,  as well as the corresponding  confidence intervals from Figure 5.1, and corresponding
estimates from Stocking et al. (2000).
   In Table 5.1, the large difference between EPA's and Stocking et al.'s 50% threshold esti-
mates is mainly due to Stocking et al.'s approximation error, described in Section 4.6. At lower
subject fractions the magnitude of that error is small, and Stocking et al.'s analysis, although
we argued that it was not the right one,  gives similar results  to ours.
   In order to estimate the fraction of people detecting a given concentration C at least 50%
of the time, one can invert (5.1) to get
                               Sc = 0((logC
(5.2)
Some results are shown in Table 5.2, with bootstrap confidence intervals. The plot of Sc as a
function of C is the same as Figure 5.1, but going from the vertical to the horizontal axis.

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28
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
       200 r
             O  subject thresholds
            	 population threshold
            — 95% confidence bands
                10     20     30    40    50     60     70     80    90    100
                                   percent of subjects (S)

Figure 5.1: EPA estimates of population thresholds C505, with 95% pointwise confidence
bands. Circles are ASTM subject threshold estimates, plotted against their ranks expressed as
a percentage of 57.
Table 5.2: EPA estimates of percent of subjects detecting various concentrations at least 50%
of the time, and 95% confidence intervals (in parentheses).
                                 MTBE
                                 (ppb)   % detecting
                                    2
                                    5
                                   10
                                   20
                          9 ( 4,  14)
                        23 (14,  32)
                        39 (29,  50)
                        58 (47,  68)

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 6  Comparison of Odor Threshold Estimators
                                                                  29
           6.  Comparison of Odor Threshold Estimators

    In this section we compare the performance of several odor threshold estimators. We be-
gin in Section 6.1 with single-subject thresholds, then consider population thresholds in Sec-
tion 6.2.
    The performance of threshold estimators in an odor experiment depends on, among other
things, the experimental protocol, panel size, number of concentrations tested, and number of
replicates. In order to shed the most light on our analysis of the data in Stocking et al. (2000),
we restrict our comparison to the conditions of that study: a forced-choice triangle test of eight
contaminant concentrations, with 57 subjects and one replicate per subject per concentration.
6.1  Subject Thresholds

    Consider first an odor detection experiment on a single subject. Eight sample concentra-
tions c\,..., eg, equally-spaced on the log scale, are presented once each, in increasing order,
in a forced-choice triangle test. For any given concentration c, let
               / = the probability that the subject detects the contaminant
               p — the probability that the subject chooses the correct bottle
                     II  if the subject chooses the correct bottle,
                     0  otherwise.
                                                                (6-1)
y-
We assume that if the subject detects the contaminant (probability t), s/he chooses the correct
bottle; but if s/he fails to detect the contaminant (probability 1 - t), s/he still has probability
1/3 of choosing correctly anyway by guessing. Therefore, the relationship between t and/? is
                                  - 0(1/3) = (1/3) + (2/3)r.
                                                                (6.2)
The expected value of y (given c) is p.
   Consistent with our general model of odor detection in Section 2, we also assume that
t = g(c), for some increasing function g that maps any concentration c onto a probability /.
   The purpose of the experiment is to estimate the subject's (1007)% odor threshold, for
some number T between 0 and 1.  That is, we want the concentration CT at which the subject
can detect the contaminant (1007)% of the time or in (1007)% of samples. Cr is therefore
the solution to T = g(CT).

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30
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
6.1.1  Estimators

   We have already defined one estimator of CT in Section 3.1: the ASTM estimator, which
we denote C£STM, is the geometric mean of the highest concentration at which the subject
failed to identify the contaminant, and the next higher tested concentration. For the purposes
of this estimator we extend the sequence of concentrations C],..., eg to CQ, ..., £9, so that the
new sequence is still evenly spaced on the log scale, and we assume that the subject would have
answered incorrectly at CQ and correctly at eg. So for example, if a subject answers correctly at
all of ci,..., eg, then his or her ASTM threshold is the geometric mean of CQ and c\.
   ASTM protocol E679-91 states  that C£STM is an estimator of a subject's 50% detection
threshold. That is, it is valid only when T —  0.5. There is  no provision for modifying the
estimator for other values of T.
   Other estimators ofCT may be obtained by fitting a dose-response model
                             yj ~ Bemoulli(^y)  indep.
                             Pj = tj -I- (1 - tj)K
                              tj — h (a + b log Cj)
                                                              (6.3)
to the data (c\,yi),..., (eg, >»g), and reading concentrations from the fitted model. AT is a
number that describes the probability of guessing, and h is a function, called the link Junction,
which maps any real number onto a probability (number between 0 and 1). To be definite, let h
be the probit link, h(t) = (0» where $ is the cumulative distribution function of the standard
normal distribution.  The parameters a and b are to be estimated, say by maximum likelihood.
Given the parameter estimates a and b, we then solve T = 4>(a + b log CT) to get

                            CT = exp((<&~1(7')   a)/b).                        (6.4)

This CT is called a probit regression estimator.
   By equation (6.2), we know that the correct value of K is 1/3. So the first regression estima-
tor, which we denote cf*M1/3H', fits model (6.3) with K = 1/3 and sets c*?*Al'.
   A third approach is simply to ignore the effect of guessing altogether:  fit (6.3) with K — 0,
   A numerical modification is required for the probit regression estimators. When the data
(y\«• • •»y&) are symmetric (e.g. (1,0,1,1,1,1,0,1)), the estimate of the slope parameter b is
either zero or very small, so that CT in (6.4) is either very large or undefined. In these cases we
set CT equal to the ASTM threshold estimator. This is a significant modification to the single-
subject regression estimators, but it is less important with some of the population threshold
estimators in Section 6.2.

-------
 6.1  Subject Thresholds
31
        Figure 6.1: Two examples of the logistic dose-response function, as in (6.5).
6.1.2  Results

    In order to evaluate the threshold estimators defined above, we consider a subject whose
true, unknown odor sensitivity is defined by
                                y ~ BemoulIi(/>)   indep.
                                p = 1/3 + (2/3)f
                                                                               (6-5)
for some a and ft of our choosing, g is known as the logistic link function. For this subject, the
50% detection threshold is C0 5 = ea, and ft is proportional to the slope of the dose-response
curve at C05.  Figure 6.1 shows two examples of the logistic dose-response function. Note
that while the true dose-response function is logistic, the probit threshold estimators assume
a probit link, which has lighter tails.  In this way we build in  some misspecification of the
dose-response model.
   We suppose that the experimental log-concentrations are —3.5, -2.5,..., 2.5,3.5. This
means that if or is close to zero (and  if ft is large enough), most of the subject's  change in
response occurs in the observable range, so the dose-response should be easy to estimate. If
or is large  or small, the dose-response changes more outside the range of observation and so
should be  harder to estimate. The same is true if ft is small.  If ft is large, then the response
changes within a narrow range and may be easier to observe and estimate.
   Under the above assumptions, we can compute exact distributions of the various threshold
estimators. At  each of the 8 concentrations the subject can answer correctly or incorrectly, so
there are only 28 = 256 possible outcomes. For each possible outcome, we compute each of
the four estimators, and also the probability of the outcome under assumptions (6.5), given a
and ft. The distribution of each estimator is therefore known and can be summarized in terms
of means and variances, for example.
   The  probit estimators were computed in Matlab (The MathWorks, Inc., 1996) by  the
                                                     U.S. EPA Headquarters Library
                                                            Mail code 3201
                                                     1200 Pennsylvania Avenue NW
                                                        Washington DC 20460

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32
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
method of maximum likelihood (McCullagh and Nelder, 1989).  The likelihoods were max-
imized using the f minunc function in Matlab's Optimization Toolbox (The MathWorks, Inc.,
1999).
   Figures 6.2-6.9 show the results. Figures 6.2-6.5 are for estimators of C0 5, and Figures
6.6-6.9 are for CQ 95.
   Consider first the estimators of CQS. Figures 6.2 and 6.3 show the log-bias, defined as
.ElogCo5 — logC05, and log-variance, VarflogCpj), of the ASTM and probit estimators
of C0 5, over a range of a and ft. The performance of all four estimators depends on how
well the experiment covers the subject's range of response  (a) and on the steepness of the
response (ft).  In terms of log-bias,  the ASTM, probit-(l/3)-r, and probit-0-P estimators
perform about equally well, and all have small log-bias around a = 0, where conditions are
favorable to the experiment.  On the other hand the probit-0-r estimator underestimates the
threshold, presumably because it mistakes guessing for detection. However, Figure 6.3 shows
that any differences in log-bias are swamped by the much greater log-variance of the probit
estimators.  The probit-(l/3)-r estimator is the most variable of all, reflecting the greater
difficulty of estimating a and b in (6.3) when K £ 0.  Thus the ASTM estimator performs
best in a single-subject experiment. The probit estimators apparently suffer from having to fit
a two-parameter model to only 8 binary observations.
   An interesting question about the ASTM estimator is:  what does it  estimate?  ASTM
(1995b) claims to estimate a 50% threshold, but provides no evidence for the claim. Fig-
ure 6.4 answers this question, for both the ASTM and probit estimators of C05. The statistic
plotted in Figure 6.4 is the expected value of T, where

                                                                               (6.6)

and a, ft, and g are the subject's true parameters and (logistic) link function from^(6.5). f
is the subject's true detection probability, computed at the estimated threshold.  If f is close
to 0.5, then we are in fact estimating a 50% threshold.  Figure 6.4 shows that  on average, the
ASTM estimator does indeed estimate somewhere between  a 40% and 60%  threshold, over
a wide range of experimental conditions (a and ft). Again the probit-0-J estimator tends to
underestimate its target.  All  four estimators can  grossly over- or underestimate the target if
the subject's change in response occurs at the edge or outside of the range of experimental
concentrations (low or high a). The slope of the change in response is less crucial.
   Figure 6.5 plots the variance of f for the four estimators. The extreme variability of the
probit estimators in Figure 6.3 is not apparent on the probability scale, since T is restricted to
lie between 0 and 1. Even so the ASTM estimator is significantly less variable than the probit
estimators when a is large.
   Figures 6.6-6.9 show the  same statistics for estimators of C0 95.  The ASTM estimator is
the same as in the previous figures, since it does not depend on T. We saw above that C£STM
is a fairly good estimator of C0 5, so this estimator is of course negatively biased for C0 95.
The probit estimators are less biased, but  still mostly underestimate the threshold. All are
about equally biased: when the detection rate is 95%, the effect of guessing  is small  so the

-------
6.1  Subject Thresholds
                         33
                       ASTM
probit-(1/3)-T
     eo.  1
                     probrt-0-P
                                                 0.5
                                                                  \
                                                  -5
     0
     a
                                                                                i-
                        Figure 6.2: Log-bias of estimators of C0 5

-------
34
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
                      ASTM
       0.5
         -5
     to.   1
                    probit-0-P
                              0.5
                               -5
                                              0.5
                                         probit-(1/3)-T
                                          probrt-0-T
                                                -5
                                              0
                                              a
                     Figure 6.3: Log-variance of estimators of C0 5

-------
6.1  Subject Thresholds
                       35
                      ASTM
probit-(1/3)-T
     CO-  1
                    probit-0-P
 probit-0-T
             Figure 6.4: Mean true detection probability at estimates of C0 5
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-------
36
Statistical Analysis of MTBE Odor Detection Thresholds in Drinking Water
                      ASTM
                                          probit-(1/3)-T
                    probit-0-P
     to.  1
                                               0.5
                                                -5
                                               0.5
                                           probit-0-T
                                                                0
                                                                a
           Figure 6.5: Variance of true detection probability at estimates of CQ 5

-------
 6.2  Population Thresholds
   37
probit-0-r estimator does not suffer from ignoring it. As before, C£STM is much less variable
than any of the probit estimators, and the probit-(l/3)-r estimator is the most variable.
    In summary, the ASTM estimator performs remarkably well as an estimator of 50% subject
thresholds. It has about the same bias and much less variability than the model-based probit
estimators.  Of the probit estimators, the probit-0-P estimator, which neglects the effect of
guessing in the model but corrects for it after the fact, is best because of its smaller bias in
some cases and smaller variability than the probit-(l/3)-r estimator. The latter is extremely
variable and should not be used in experiments of this size.
    This superiority of the ASTM estimator is surprising, since it uses only part of the data
and does not explicitly take guessing into account. The probit estimators might be expected
to perform better in experiments with more data, for example with multiple subjects with an
assumed common  slope ft, or with multiple replicates per subject.  We consider the case of
more subjects in the next Section.
    For estimation  of 95% subject thresholds, no estimator performs very well. The ASTM
estimator estimates 50% thresholds, so it has significant negative bias. The probit estimators
are less biased, at the cost of much higher variability. This probably just reflects the difficulty
of estimating a 95% odor threshold from 8 binary responses. In experiments of this size one is
probably better off restricting attention to 50% thresholds.

6.2  Population Thresholds

    Consider now the same experiment as in the previous Section, but with 57 subjects. The
same concentrations c\,..., eg are presented to each subject. Let
           t{j = /^subject / detects concentration c/)
          Pij = P(subject / chooses the correct bottle with concentration c,)
                  (1  if subject i chooses the correct bottle with concentration c,-,
                  0  otherwise.
(6.7)
Then as before, pu = (1/3) + (2/3)r0- and E(y(j) = PiJ.
   The goal of the experiment is to estimate C5 r, the concentration at which (IQQS)% of
subjects can detect the contaminant at least (1007)% of the time.
6.2.1   Estimators

   One way to estimate population thresholds is first to estimate a subject threshold for each
subject, then compute a quantile estimate from the set of subject thresholds. We consider three
estimators of this type, using different subject threshold estimators and distributional fits.  A
fourth estimator  uses an estimate of the between-subject variability, computed in the same
model as the within-subject dose-response.
   For the first estimator, we compute ASTM threshold estimates C^™	C^*™ for the
57 subjects as in  Section 6.1, then let C^5™ be an estimate of the (1005)-th percentile  of the

-------
38
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
                      ASTM
                                         probit-(1/3)-T
       0.5
         -5
                    probit-0-P
                                          probit-0-T
     CO.  1
        -5
                               -5
                      Figure 6.6: Log-bias of estimators of C0 95

-------
6.2  Population Thresholds
                                                            39
                       ASTM
     ca.  1
       0.5
         -5
       0.5
         -5
                     probit-0-P
o
a
                                   probit-(1/3)-T
                       0.5
                         -5
                                    probit-0-T
                       0.5
-5
0
a
                     Figure 6.7: Log-variance of estimators of C0 95

-------
40
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
                     ASTM
                                       probit-{1/3)-T
        -5
                   probit-0-P
     CO.  1
        -5
                                               t\J  fl
            Figure 6.8: Mean true detection probability at estimates of C0 95

-------
6.2  Population Thresholds
                         41
                       ASTM
probit-(1/3)-T
                     probit-0-P
 probit-0-T
                                                0.5
                                                  -5
     0
     a
           Figure 6.9: Variance of true detection probability at estimates of C0 95

-------
 42
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinkinz Water
 subject thresholds. Quantiles can be estimated in many ways: for example as quantiles of the
 empirical CDF, of a kernel density estimate, or of a normal distribution fitted in any of several
 ways. For data that are close to normally distributed, the differences are minor. For simplicity,
 we use a normal quantile estimator applied to the log-ASTM thresholds:
                     = exp (i
                                             in
(6.8)
 where m and s are the sample mean and standard deviation, respectively, of the log-ASTM
 thresholds.
    A problem with the ASTM thresholds is that when a subject correctly identifies the con-
 taminant at all concentrations, or fails to identify it at the highest concentration, the threshold
 estimate is arbitrarily placed just outside the range of tested concentrations. In these cases the
 threshold might be better assumed to be censored, that is, unobserved but known to be outside
 the tested range. A normal distribution can then be fit to the thresholds in a way that uses the
 censoring information. Kroll and Stedinger (1996) compared several such methods, and found
 that maximum likelihood (Cohen, 1991) works best when the goal is to estimate 10th per-
 centiles. We therefore define a second threshold estimator, C AS77M-censoredj ^ me same ^y ^
 C^ASTM-nonna^ but with m and s estimated by maximum likelihood, treating ASTM thresholds
 outside the tested range as censored,  hi cases where  fewer than three thresholds are uncen-
 sored, the likelihood estimates are either unavailable or likely to be too variable, and so instead
 We let (^ASTM-censored _ AASTM-noimal
        S, T             S,T
    A third estimator uses probit regression, as in Section 6. 1, to estimate the subject thresholds.
 Since the probit estimators were found to be highly variable with only one subject, we try to
 benefit from multiple subjects here by estimating a common slope parameter for all subjects.
 The model is
                              yij ~ Bemoulli(/ty)   indep.
                             ptj = * + (!- K)tu                               (6.9)
                              ty = wt-o-/>   ^ ££*!WW>, M m <6-8)- We denote ***** estimator £§£**"*, where the desig-
nation "fixed" stands for "fixed effects": the unknowns at and b in (6.9) are treated as fixed,
unknown constants, in contrast to the next estimator.

-------
 6.2   Population Thresholds
                                            43
    A problem with model (6.9) is that it neglects the correlation that exists between repeated
 observations on a single subjects. Also because it treats the subject effects a, as fixed numbers,
 rather than as a random sample from a population of subject effects, it does not allow inference
 to the population from which the subjects were selected. A model which avoids these problems
 is
                           (ytj\Pij) ~ Bernoulli (/>,,)   indep.
                                Ptj = 'v + 0 - ttj)K
                                                 indep.
                                                                               (6.11)
Here the subject effects a, are realizations of a random variable, which describes the distribu-
tion of subjects' sensitivities to odor. Allowing the subject effects to be random accomplishes
two goals: it induces a correlation among the responses yi\,..., yn on a single subject; and by
taking the randomness across subjects into account, it allows inference to the population from
which the subjects were drawn.
    When subjects are selected by random sampling, the population (S, T) odor threshold is
determined by the equation

       P (subject can detect concentration c in (1007)% or more of samples) = S      (6.12)

where the probability is with respect to a randomly selected subject. Under model (6.11), (6.12)
may be solved for c to give
                    CST = exp
                                        (6.13)
As before to account for guessing, we choose K — 0 in (6.11) and substitute P ~ (1/3) +
(2/3)7* for T after the fact. Given parameter estimates jia, 0%, and b, we substitute into (6.13)
to get a threshold estimate

(2/3)r)
                                                                               (6.14)
The designation "mixed" in c'max  refers to model (6.11), which is said to be a "mixed
model" because it contains both fixed effects (b) and random effects (a/) to be estimated.
    Estimation of the parameters in (6. 1 1) is nontrivial. Proposed methods include pseudo- and
quasi-likelihoods (Breslow and Clayton, 1993; Wolfinger and O'Connell, 1993) and various
kinds of simulated likelihoods (McCulloch, 1994; Geyer, 1994; Geyer and Thompson, 1992).
We use the restricted pseudo-likelihood method of Wolfinger and O'Connell (1993), mainly
because it has been implemented in a macro, GLIMMIX,  for the SAS system (SAS Institute
Inc., 1989). We used GLIMMIX to estimate the parameters of (6. 1 1) hi SAS.

-------
44
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
            Table 6.1:  Parameter values for the population threshold simulation.
M« -3
al 0.5
Up 0.3
ffft 0
0 3
2 8
1 3
0.25 1
6.2.2  Results

   In order to evaluate the population threshold estimators defined above, we consider a pop-
ulation of 57 subjects whose true, unknown odor sensitivites are defined by
                                                    indep.
                                   =g(A-(logc,--a,-))
                                a, ~ N(fj,a, aj)  indep.
                                ft ~ LNdfy, 002)  indep.
                             a, , fa indep.

where LN(^, c^2) is the lognormal distribution with mean ^ and variance aj (of ft, not of
log/3). We must choose /xa, iio, aa, and 0=.  Note that for subjects who follow (6.15), the
probit estimators are derived from models that are misspecified in two ways: they assume a
probit link and a common slope /? for all subjects.  The results of the probit estimators will
therefore include some model error.
   In the single-subject experiment in the previous section, we were able to obtain exact distri-
butions of the threshold estimators because the number of possible outcomes was small. With
57 subjects that is no longer true, so we used simulation instead to evaluate the estimators.
   For the simulation we chose values of jia , //# , cr,2. , and of shown in Table 6.1. These values
were chosen to represent a range of difficulty for the estimation. By comparison, the estimated
parameters from the Stocking et al. (2000) data, transformed to model (6.15) and scaled to the
simulated predictor range, are (j.a  = 1-27, ^ = 0.79, cr£  = 2.69, and a£ = 0.06. All of these
estimates are well within the range of values in Table 6. 1 .
   We used each combination of values of the four parameters, for a total  of 81 param-
eter combinations.   At each parameter combination we simulated 20  i.i.d. populations of
57 subjects following (6.15).  For the experimental log-concentrations, as before we chose
—3.5, —2.5, . . . , 2.5, 3.5 for each subject.  For each sample population we computed the
ASTM-normal, ASTM-censored, probit-fixed, and probit-mixed estimators of the (0. 10, 0.50),
(0.10, 0.95), and (0.50, 0.50) population thresholds.

-------
6.2  Population Thresholds
45
    Figures 6.10—6.12 show the results of the simulation, in terms of squared log-bias, log-
variance, and log-mean squared error (MSE) of estimates of the (50%, 50%), (10%, 50%), and
(10%, 95%) thresholds. The simulation yields a large number of results, with 4 estimators of
each of the 3 estimands at each of 81 parameter combinations.  In order to make the results
easier to digest, we summarized them first by averaging over the tested values of aa and erg.
Both cra and a* turned out to have only a small effect on bias and variance, at least within the
range of values that we tested.
    Figures 6.10—6.12 lead to three conclusions.  First, thresholds with 5 and T close to 1/2
are easiest to estimate. In the case of T this agrees with the results of the previous section.
Even with 57 subjects, it is difficult to estimate 95% subject thresholds from only 8 binary
observations on each subject.
    Second, no matter which threshold is being estimated, the results depend heavily on the
experimental conditions. They depend especially on ^, the mean slope of the dose-response
curves. All four estimators perform best when fig is large, and badly when //.» is close to zero.
Geometrically, when ^ is small the dose-response curve is relatively flat, so the inverse calcu-
lation used to compute the threshold is sensitive to misspecification of the curve. Algebraically,
in (6.14) this happens because b is small in the denominator.
    Third, the ASTM-normal estimator has small variance in all cases, and this makes it a good
choice for thresholds with T close to 0.5, where it also has small bias.  When  T  =  0.95,
no estimator performs uniformly best; the probit-fixed estimator is usually best but can also
perform quite badly, for example when /^ = I and na = 3.
    The ASTM-censored estimator performs generally about the same as the ASTM-normal.
Its bias is smaller in some cases and larger in others; variance is generally low but rises in
some difficult cases. Although perhaps theoretically more satisfactory, the ASTM-censored
estimator yields no clear advantage to compensate for its extra computational complexity.
    The probit-mixed estimator performs the worst of the four, with generally higher bias and
variance man the ASTM 'and probit-fixed estimators. However, this estimator may still be
useful because it can provide confidence intervals that take into account both inter- and intra-
subject variability and intra-subject correlation. By contrast, the ASTM estimators come with
no subject-specific confidence intervals at all. One can form a confidence interval for the popu-
lation quantile estimate, but this approach neglects intra-subject variability. For the probit-fixed
estimator, the probit regression provides  confidence intervals for subject thresholds, which
must then be combined across subjects, taking into account the normal quantile estimate. This
approach also neglects intra-subject correlation. However, we have not evaluated the accuracy
of confidence intervals from any of the threshold estimators.
    In the case  of Stocking et al. (2000), the estimated parameters,  scaled to the simulated
predictor range, are /la  = 1.27 and /l^ = 0.79.  Figure 6.10 shows that each of the three
estimators may perform either well or badly when ^ is between 0.3 and 1 and (iu is between
0 and 3. The ASTM-normal estimator is probably best in this case, since it at least has small
variability throughout that range.
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-------
 46
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
                                     (S.T) = (50%,50%)
20
15,
5,
°«
0.3 3 -
0.3 0
0.3 -3
1 2
1





A




T
I







9




f
I

>





.,




i
T

>





....
'.'.•


i
4

•



4
• v ; •
T- - - •"• • -
•....•....
V'V
•• . ••





v
. . .1





••4
. . i



I








9.
>




T

i






.•. .
>



i


••••?



«


.»
...*

    7N AC  PF PM      AN  AC  PF  PM
                         Bias2
                                               Var
                                                              AN AC  PF
                                                                  MSE
Figure 6.10: Squared log-bias, log-variance, and log-MSB of the ASTM-normal (AN), ASTM-
censored (AC), probit-fixed (PF), and probit-mixed (PM) estimators of CQ s 0 5. Responses are
averaged over the simulated values of aa and a*. Where circles are missing, the response is off
the scale of the graph.

-------
6.2  Population Thresholds
                                    47
                                     (S.T)
                      AN  AC  PF
                         Bias2
AN  AC  PF
     Var
AN  AC PF
    MSE
Figure 6.11: Squared log-bias, log-variance, and log-MSB of the ASTM-normal (AN), ASTM-
censored (AC), probit-fixed (PF), and probit-mixed (PM) estimators of C0, 05. Responses are
averaged over the simulated values of aa and c^. Where circles are missing, the response is off
the scale of the graph.

-------
 48
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
                                     (S,T) =
         20,
1",
0.3 3 -
0.3 0
0.3 -3
1 3
1
1 -
3
3
3

"\
*\
3 -
0
-3
(
I •
T ••'•'
f
i
v
•\

>
ft
1 1
T
.• . •-'
» |

	 	 i —


?..
(fc.
.T.
T

<
.1


<
A
V.
•
i

-T 	
>
T

>. . . •
• - -
	 T"

i

£. . .
— r

%
t.;

-
— v


f
T
— r
4
•f ' '
t
' 1
-
-
»
1 i
t
;.}
1 'f

T — r


T.
. .T.
— \
f\f


1

,
- D
                                          AN  AC  PF
                                                                   MSE
                         Bias
Figure 6.12: Squared log-bias, log-variance, and log-MSE of the ASTM-normal (AN), ASTM-
censored (AC), probit-fixed (PF), and probit-mixed (PM) estimators of C0 j 0 95. Responses are
averaged over the simulated values of au and Og. Where circles are missing, the response is off
the scale of the graph.

-------
7   Conclusion
49
                                7.  Conclusion
    Our analysis leads to the following conclusions.

   1. Odor detection thresholds should be defined as the concentrations at which a certain
      percent of people can detect the contaminant a certain percent of the time. Both the time
      and subject fractions must be specified in order for a threshold to be interpretable.

   2. In experiments with small amounts of data on each subject (e.g. 8 presentations and no
      replicates), the simple threshold estimator specified in ASTM method E679-91 performs
      at least as well as, and often better than, more complicated estimators based on proba-
      bility regression. With this small amount of data, thresholds with a time-fraction of 50%
      are easiest to estimate.

   3. On average,  the ASTM E679-91 threshold  estimator estimates a  subject's 40%-60%
      detection threshold, over a wide range of experimental conditions.

   4. Each of the previous odor threshold studies of MTBE has one or more methodological
      problems. The data from Stocking et al. (2000), however, are sound and represent the
      largest and best-designed study of MTBE odor thresholds to date.

   5. For design of an odor detection experiment in a way  that facilitates statistical  anal-
      ysis,  ASTM  method E679-91  is preferable to Standard Method 2150B. The ASTM
      method, because it uses a forced-choice test, allows guessing to be treated statistically
      in a straightforward manner. Under the Standard Method, statistical analysis is  diffi-
      cult because the probabilities of guesses are unknown and may depend on the subject's
      knowledge of the experimental protocol.

   6. Based on a reanalysis of the data from Stocking et al. (2000), 50% of people can detect
      MTBE at least 50% of the time in drinking water at a concentration of 15 ppb, or between
      10 and 22 ppb with 95% confidence. At 5 ppb, about 23% of subjects can detect MTBE
      at least half the time in drinking water, or between 14% and 32% of subjects with 95%
      confidence.

   Significant uncertainties remain in our threshold estimates. The estimates may be too low,
because smokers and older subjects were excluded from Stocking et  al.'s experiment.  Also
the relationship between detecting odor on the one hand, and rejecting a sample of water as
undrinkable on the other, is complex and outside the scope of this study.

-------
50
Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
 Appendix A.  Individual Response Data from Stocking et al.

                                  (2000)

   The following table of individual subject responses is reproduced from Stocking et al.
(2000), Table 7. Correct and incorrect responses are indicated by + and o, respectively.  The
rightmost column lists the threshold estimates computed according to ASTM method E679-91,
described in Section 3.1.  The bottom row shows the total number of correct responses.
                          MTBE Concentration (ppb)
                                        ASTM
Subject
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24

2
+
O
O
o
+
o
o
+
o
o
+
o
+
+
o
o
+
o
+
+
+
+
+
+

3.5 6 11 19 33 57
o + + + + +
O O + + + +
+ O O O O +
O O O O O +
o + o + + o
o + + + + +
+ + o + + +
+ o + + + +
o + o + + +
o o o o o o
o + + + + +
o o o + o +
+ + + + + +
+ + + + + +
+ + o + + +
o + o o o +
o + + + + +
o + + + + +
+ ++ + + +
o + + o + o
+ + + + + +
+ + + + + +
+ 00 + + +
+ ++ + + +
continued on next page
100 threshold
+ 4.6
+ 8.1
+ 43.2
+ 43.2
+ 75.6
+ 4.6
+ 14.1
+ 8.1
+ 14.1
+ 75.6
+ 4.6
o 132.3
+ 1.5
+ 1.5
+ 14.1
o 132.3
+ 4.6
+ 4.6
+ 1.5
o 132.3
+ 1.5
+ 1.5
+ 14.1
+ 1.5


-------
A  Individual Response Data from Stocking et al. (2000)
51

MTBE Concentration (ppb)
Subject
2
3.5
6
11 19 33 57
100
ASTM
threshold
continued from previous page
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
Total
correct
o
o
4
O
O
o
4
4
4
O
O
O
4
4
4
O
4
O
O
O
o
+
o
o
o
o
o
4
4
4
O
O
o

25
4
4
O
o
4
4
O
4
4
O
O
O
4
O
4
O
+
4
O
4
'4
4
4
4
O
O
0
4
4
O
o
o
o

28
4
4
O
4
O
+
O
4
4
O
o
o
4
4
O
+
+
0
o
4
4
4
O
O
o
+
o
4
4
O
4
O
4

35
4 O 4 4
4 O 4 4
O 4 O O
4444
O 4 4 4
O 4 4 4
4 O O 4
4 O O O
0404
O O O 4
4 O 4 4
4 O 4 4
4444
4444
O 4 4 4
O 4 4 4
4444
4444
O O O 4
O 4 O 4
O 4 4 4
4 4 O 4
0 O 4 4
4 O 4 4
4 O 4 4
4444
4444
4444
4444
O O 4 4
4444
O O 4 4
4 O 4 O

34 38 44 51
4
4
4
O
4
4
O
4
4
O
O
4
4
4
4
4
4
4
4
4
4
4
O
4
4
+
+
+
4
+
4
4
4

49
24.7
24.7
75.6
132.3
14.1
14.1
132.3
75.6
43.2
132.3
132.3
24.7
1.5
4.6
14.1
14.1
1.5
8.1
43.2
43.2
14.1
43.2
132.3
24.7
24.7
4.6
8.1
1.5
1.5
24.7
4.6
24.7
75.6


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 52	Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
                                  References
APHA (1995), "Threshold odor test" Method 2150B, in Standard Methods for the Exam-
   ination of Water and Wastewater (19th ed.), Washington, D.C.: American Public Health
   Association.
API (1994), "Odor threshold studies performed with gasoline and gasoline combined with
   MTBE, ETBE and TAME," API Publication 4592, American Petroleum Institute, Washing-
   ton, D.C.
ASTM (1995a), "Standard practice for defining and calculating individual and group sensory
   thresholds from forced-choice data sets of intermediate size," Method E1432-91, in 1995 An-
   nual Book of ASTM Standards, volume 15.07, West Conshohocken, Pa.: American Society
   of Testing and Materials.
ASTM (1995b), "Standard practice for determination of odor and taste thresholds by a forced-
   choice ascending concentration series method of limits," Method E679-91, in 1995 Annual
   Book of ASTM Standards, volume 15.07, West Conshohocken, Pa.: American Society of
   Testing and Materials.
Breslow, N. E. and Clayton, D. G. (1993), "Approximate inference in generalized linear mixed
   models" Journal of the American Statistical Association, 88,9-25.
Cohen, A. C. (1991), Truncated and Censored Samples: Theory and Applications, New York:
   Marcel Dekker.
Dale, M. S., Moyian, M.  S., Koch, B., and Davis, M. K. (1998), "MTBE: Taste-and-odor
   threshold determinations using the flavor profile method," in Proceedings 1997 Water Qual-
   ity Technology Conference, Denver, Colorado, November 9-13, 1997,  American Water
   Works Association.
Efron, B. and Tibshirani,  R. (1993), An Introduction to the Bootstrap,  London: Chapman
   &HaU.
Geyer, C. J. (1994), "Estimating normalizing constants and reweighting mixtures in Markov
   chain Monte Carlo," Technical Report 568, School of Statistics, University of Minnesota.
Geyer, C. J. and Thompson, E. A. (1992), "Constrained Monte Carlo maximum likelihood for
   dependent data," Journal of the Royal Statistical Society (ser. B), 54, 657-699.
HMSO (1982), "Methods  for the examination of water and associated materials, odour and
   taste in raw and potable waters," Standing Committee of Analysts, HMSO, London.
Kroll, C. N. and Stedinger, J. R. (1996), "Estimation of moments and quantiles using censored
   data," Water Resources Research, 32,1005-1012.

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References
53
Malcolm Pirnie (1998), 'Technical memorandum: Taste and odor properties of methyl tertiary-
  butyl ether and implications for setting a secondary maximum contaminant level," unpub-
  lished.
McCullagh, P. and Nelder, J. A. (1989), Generalized Linear Models (2nd ed.), London: Chap-
  man & Hall.
McCulloch, C. E. (1994), ""Maximum likelihood estimation of variance components for binary
  fate? Journal of the American Statistical Association, 89, 330-335.
Prah, J. S., Goldstein, F. M., Devlin, R., Otto, D., Ashley, D., House, S., Cohen, K. L., and
  Gerrity, T.  (1994), "Sensory, symptomatic, inflammatory, and ocular responses to and the
  metabolism of methyl tertiary-butyl ether in a controlled human exposure experiment," In-
  halation Toxicology, 6, 521-538.
SAS Institute Inc. (1989), SAS/STAT User's Guide. Version 6 (4th ed.), Cary, NC: SAS Institute
  Inc.
Schiffinan, S. (1992), "Olfaction in aging and medical disorders," in Science ofOlfaction, eds.
  M. J. Serby and K. L. Chobor, 500-525, New York: Springer-Verlag.
Shen, Y. F., Bergen, M., Yoo, L. J., and Fitzsimmons, S. R. (1998), "Effect of residual chlorine
  on the threshold odor concentrations of MTBE in drinking water," in Proceedings  1997
  Water Quality  Technology Conference, Denver, Colorado, November 9-13,1997, American
  Water Works Association.
Shen, Y. F., Yoo, L. J., Fitzsimmons, S. R., and Yamamoto, M. K. (1997), "Threshold odor
  concentrations of MTBE and other fuel oxygenates," in Proceedings of the 1996 American
  Chemical Society Meeting, San Francisco, American Chemical Society.
Smith, D. V. and Duncan, H. J. (1992), "Primary olfactory disorders: Anosmia, hyposmia, and
  dysosmia," in Science ofOlfaction, eds. M. J. Serby and K. L. Chobor, 439-466, New York:
  Springer-Verlag.
Stocking, A. J., Suffet, I. H., McGuire, M. J., and Kavanaugh, M. C. (2000), "Implications of a
  MTBE consumer threshold odor study for drinking water standard setting," Malcolm Pirnie,
  Inc., Oakland, Calif., draft of June 12,2000.
The MathWorks,  Inc. (1996), Using MATLAB, Natick, Mass.: The MathWorks, Inc.
The MathWorks,  Inc. (1999), Optimization  Toolbox User's Guide, Natick, Mass.: The Math-
  Works, Inc.
TRC (1993), "Final report to ARCO Chemical Company on the odor and taste threshold studies
  performed with methyl-tertiary-butyl ether (MTBE) and ethyl-tertiary-butyl ether (ETBE),"
  TRC Project No. 13442-M31, TRC Environmental Corporation, Windsor, Conn.
US EPA (2000), "MTBE in fuels," http://www.epa.gov/mtbe/gas.htm.
Wolfinger, R. and O'Connell, M. (1993), "Generalized linear mixed  models:  A  pseudo-
  likelihood approach," Journal of Statistical Computation and Simulation, 48, 233-243.

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54	Statistical Analysis ofMTBE Odor Detection Thresholds in Drinking Water
Young, W. E, Hoith, H., Crane, R., Ogden, T., and Amott, M. (1996), "Taste and odour thresh-
  old concentrations of potential potable water contaminants," Water Research, 30,331-340.

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                       Federal Register /Vol. 66, No.  145 /Friday, July 27, 2001 /Notices
                                                                   39163
   Summary: EPA expressed a lack of
 objections to the proposal.
   EBP No. F-USN-D11030-VA Marine
 Corps Heritage Center (MCHC)
 Complex, Construction and Operation at
 Marine Corps Base (MCB) Quantico, VA.
   Summary: EPA supports the proposed
 action and has determined that the FEUS
 adequately addresses the environmental
 concerns related to the preferred
 alternative.
   ERP No. F-USN-K35041-CA Naval
 Station (NAVSTA) San Diego
 Replacement Pier and Dredging
 Improvements, Construction, Dredging
 and Dredged Material Disposal, San
 Diego Naval Complex, San Diego, CA.
   Summary: No formal comment letter
 was sent to the preparing agency.
   ERP No. FA-NRC-A00164-00
 GENERIC—License Renewal of Nuclear
 Plants, Arkansas Nuclear One, Unit 1,
 COE Section 10 and 404 Permits, Pope
 County, AR (NUREG-1437).
   Summary: No formal comment letter
 was sent to the preparing agency.
  Dated: July 24.2001.
 Joseph C. Montgomery,
 Director. NEPA Compliance Division. Office
 of Federal Activities.
 [FR Doc. 01-18828 Filed 7-26-01; 8:45 am]
 BILLING CODE 65&MO-P
 ENVIRONMENTAL PROTECTION
 AGENCY
 [FRL-701$-«]

 Science Advisory Board; Notification
 of a Public Advisory Committee

 SUMMARY: Pursuant to the Federal
 Advisory Committee Act, Public Law
 92—463, notice is hereby given that the
 Arsenic Benefits Review Panel of the
 EPA Science Advisory Board (SAB) will
 conduct a public teleconference meeting
 Tuesday August 14, 2001 from 10a.m.-
 12 noon Eastern Time.
  The conference call meeting will be
 coordinated through a conference call
 connection in room 6013 Ariel Rios
 North (6th Floor), U.S. Environmental
 Protection Agency, 1200 Pennsylvania
 Avenue N.W., Washington, DC. The
 public is strongly encouraged to attend
 the meeting through a telephonic link,
 but may attend physically if
 arrangements are made in advance with
 the SAB staff. In both cases,
 arrangements should be made with the
 SAB staff by noon the Wednesday
 before the meeting. Staff may not be able
 to accommodate die presence of people
 who appear in person without advance
 notice. Additional instructions about
how to participate in the conference call
can be obtained by calling Ms. Rhonda
 Fortson, Management Assistant, at (202)
 564—4563, and via e-mail at:
 fortson.rhonda@epa.gov.
   Purpose of the Meetings: The
 Subcommittee is preparing a report on
 the Arsenic Benefits assessment as
 announced in the Federal Register
 Notice on July 2. 2001, 66 FR 34924-
 34928. The purpose of the call is to
 allow the Subcommittee to complete its
 work on this issue.
   Availability of the written materials in
 advance of the conference call meetings:
 The draft report will become available
 to the public shortly before the meeting
 and it will be made available to the
 public on request by Email before the
 meeting. For email copies, please
 contact Mr. Thomas Miller, Designated
 Federal Officer, at miUer.tom@epa.gov.
   For Further Information—Any
 member of the public wishing further
 information concerning the conference
 call meeting or wishing to submit brief
 oral comments must contact Mr.
 Thomas Miller, Designated Federal
 Officer, Science Advisory Board
 (1400A), U.S. Environmental Protection
 Agency, Ariel Rios Building, 1200
 Pennsylvania Avenue, NW, Washington,
 DC 20460; telephone (202} 564-4558;
 FAX (202) 501-0582; or via e-mail at
 miller.tom@epa.gov. Requests for oral
 comments must be in writing (e-mail,
 fax or mail) and received by Mr. Miller
 no later than noon Eastern Time one
 week prior to the meeting.
Providing Oral or Written Comments at
SAB Meetings
  It is the policy of the Science
Advisory Board to accept written public
comments of any length, and to
accommodate oral public comments
whenever possible. The Science
Advisory Board expects that public
statements presented at its meetings will
not be repetitive of previously
submitted oral or written statements.
Oral Comments: For teleconference
meetings, opportunities for oral
comment will usually be limited to no
more than three minutes per speaker
and no more than fifteen minutes total.
Deadlines for getting on the public
speaker list for a meeting are given
above. Speakers should both e-mail
their comments to the DFO in MSWord
and WordPerfect formats (suitable for
IBM-PC/Windows 95/98) and provide 5
paper copies of their comments and
presentation slides for distribution to
the reviewers and public at the meeting.
Written Comments: Although the SAB
accepts written comments until the date
of the meeting (unless otherwise stated),
because this is a conference call
meeting, any comments to be mailed to
the Subcommittee in advance of the
  meeting should be received in the SAB
  Staff Office by noon at least a week
  before the meeting. E-mailed comments
  will be accepted until the day before the
  meeting, although earlier submission is
  encouraged; these should be sent in
  both MSWord and WordPerfect
  comments (suitable for IBM-PC/
  Windows 95/98).
    Meeting Access—Individuals
  requiring special accommodation at this
  meeting, including wheelchair access to
  the conference room, should contact Mr.
  Miller at least five business days prior
  to the meeting so that appropriate
  arrangements can be made.
    Dated: July 23, 2001.
  Donald G. Barnes,
  Staff Director, Science Advisory Board.
  [FR Doc. 01-18822 Filed 7-26-01; 8:45 am]
  BILLING CODE KtO-SQ-P
  ENVIRONMENTAL PROTECTION
  AGENCY
  [OPP-50875A; FRL-6791-5]

  Amendment/Extension of an
  Experimental Use Permit

  AGENCY: Environmental Protection
  Agency (EPA).
  ACTION: Notice.

  SUMMARY: EPA has granted an
  experimental use permit (EUP) to the
  following pesticide applicant. An EUP
  permits use of a pesticide for
  experimental or research purposes only
  in accordance with the limitations in
  the permit.
  FOR FURTHER INFORMATION CONTACT: By
  mail: Mike Mendelsohn, Biopesticides
  and Pollution Prevention Division
  (7511C), Office of Pesticide Programs,
  Environmental Protection Agency, 1200
  Pennsylvania Ave., NW., Washington,
  DC 20460. Office location, telephone
  number, and e-mail address: 1921
  Jefferson Davis Hwy., Rm. 910W13,
  Crystal Mall #2, Arlington, VA; (703)
  308-8715; e-mail address:
  mendelsohn.mike@epa.gov.
  SUPPLEMENTARY INFORMATION:

  I. General Information

  A. Does this Action Apply to Me?
   This action is directed to the public
  in general. Although this action may be
  of particular interest to those persons
  who conduct or sponsor research on
  pesticides, the Agency has not
  attempted to describe all the specific
  entities that may be affected by this
  action. If you have any questions
  regarding the  information in this action,
  consult the designated contact person
  listed for the individual EUP.

U S. EPA Headquarters Library
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