DOUBLE-LABELED 36C1 180£ STUDY SHOWS PERCHLORATE IS NOT

METABOLIZED IN VIVO

e 18
During the peer review meeting, reference was made to a double-labeled perchlorate 6C1 04-)
study by Anbar et al. (1959) that was cited in the draft RID document (page 3-3). The
incomplete description of the study has led to the general concern that CI04- may be metabolized
as far as cr before elimination in the urine. However, the contention of Anbar and coauthors is
that Cl04- is not metabolized in vivo. The authors' comments regarding the results oftheir study
are given below.

Amounts ofCr and CI03- in the urine constitute "an upper limit for the metabolization of
perchlorate ions, namely less than 1/1000 ofthe excreted perchlorate." Therefore, the maximum
amount of perchlorate that could have been metabolized was less than 0.1% of the injected
radio labeled species.

Alternative reasons for detection of a small amount of chloride (Cn and chlorate (CIOn were
listed.

• The small amount of other chlorine species may have been due to contamination of the
K36C1 1804- with less than 0.1 % K36Cr.

• Some perchlorate may have absorbed on the silver chloride precipitant used to measure
chloride concentration.

Therefore, the authors assumed there was "practically no reduction of perchlorate ions in vivo"
(Anbar et al., 1959).

Attachment 1
 ANALYSIS OF COLD PERCHLORATE IN RAT THYROID BY ION

CHROMATOGRAPHY: CIOJ - AND cr DO NOT INTERFERE WITH CI04- ANALYSJS

Our laboratory has measured serum and thyroid perchlorate levels in the rat and found that
perchlorate is concentrated in thyroid tissue. In fact, the thyroid to serum (T:S) ratios were as
high as 30: 1 in the male rat after exposure to CI04' in drinking water. Rats subjected to acute
CI0 4' exposures also showed T:B ratios greater than one. Table 1 shows the T:B ratios in adult
male rats at various times after administration of 0.01 , 1.0 and 3.0 mg CI04"!kg body weight
(BW).

. . t ra f Ion lD aut
Table 1. ThIyrol'd :serum ra f lOS a ft er CIO4..Ivad mIDIS d I rna e r ats
Time 0.01 me/~ 1.0 mWk~ 3.0 m~/k~
I (hours) thyroid serum T:S thyroid serum T:S thyroid serum T:S
0.08 0.3 0.028 10.7 20.26 1.21 16.7 23.28 3.12 7.5
0.25 0.3 0.023 13.0 22.21 1.12 19.8 31 3.31 9.4
0.5 0.36 0.025 14.4 20.99 1.29 16.3 29.78 3.16 9.4
1 0.25 0.024 lOA 22.01 0.98 22.5 34.57 3.17 10.9
2 0.26 0.022 11.8 24.2 0.78 31.0 33.22 2.95 11.3
6 0.26 0.018 14.4 14.76 0.4 36.9 17.85 0.91 19.6
9 0.09 ND 9.26 0.23 40.3 12.66 1.03 12.3
24 0.01 ND 5.56 0.21 26.5 10.76 0.54 19.9
ND - indicates samples that were below analytical detection

These thyroid samples were obtained from rats exposed to CI0 4' either through drinking water or
via tail vein injection. Tissues were then homogenized with water and filtered. The prepared
thyroid tissue samples were analyzed for CI04' using ion chromatography (IC) and a modified
version of EPA Method 314, using a lOa mM NaOH mobile phase and an AS-II column. This
method utilizes both size and charge density to separate anions on an ion exchange column.
Some ions, such as perchIOl:ate, are tightly bound to the exchange medium in the column and
therefore remain in the column for longer periods oftime. Other anions, such as CIO)', cr, F'
and r. move quickly through the column. Thus, it is possible to distinguish between similar
anions based on their retention times with confidence.

To rule out the possibility of interference by the potential metabolites of CI04", the IC method
was tested against standards spiked with chlorate and perchlorate, as well as thyroid samples
obtained from rats dosed with CI0 4'. Th}TOids were taken from two CI04' exposed rats. One
thyroid served as perchlorate-only control and the second thyroid sample was spiked with CIO)".
The resulting chromatograms are shown below (Figures 1 through 3).

Attachment 2
 I
chlorate
void
4.00

3.00

~ :::lLL~,----,perc~=-
o 2,0 4.0 6.0 8.0 10.0
minutes

Figure 1. Water standard spiked with perchlorate and chlorate standards. The void peak
appears immediately after the dip in the baseline due the water from the injected sample.
Perchlorate is well separated from chlorate by approximately six minutes.

20.0
void
15.0
10.0
CIJ

::l..

5.0 perchlorate

,
-5.0

0 2.0 4.0 6.0 8.0 10.0

minutes

Figure 2. Typical chromatogram obtained from a thyroid of a rat exposed to perchlorate.

The perchlorate peak appears at approximately eight minutes and is well separated from
the initial void volume.

 chlorate
1201

,
I
100 (
80 1
(fJ
:::l
60 i void II
40 ! IIi perchlorate
20 J .; 1'·
'I .;\;
o ! t.~_,¥,~ ... w '
./­

o 2.0 4.0 6.0 8.0 10.0

minutes

Figure 3. Chromatogram of a rat thyroid exposed to perchlorate in vivo and spiked with a
chlorate standard after removal from the carcass. The chlorate peak appears shortly after
the void peak and is well separated from the perchlorate peak.

In previous studies, this laboratory explored the relative affinity of several potential interfering
anions for the ion exchange column, including CIO}- and cr (Clewell, 1999). The method was
identical to that used for the samples above, except that the concentration of the mobile phase
was lowered slightly from 100 mM to 35 mM NaOH in order to better separate the earlier peaks.
These studies showed that cr had even less affinity for the AS-II column than CIO:;. Thus,
chloride could not be interfering with the CI0 4- measurements.

 f ppm a!! Hamw.J'ds

.
14.0"f
1:.0+

iO.of

8.0~

5.0 75 10.0 12.5 15J} 17.5

miUll16

Figure 4. Chromatogram of water spiked with various anions, including chlorate and
chloride. Chlorate has a higher affinity for the exchange column than chloride and
therefore has a larger retention time. Perchlorate has a higher retention time than both
potential metabolites and did not elute from the column within the 20 minutes.

It is apparent from the chromatograms shown above that the IC method is able to distinguish
CI04- from Cl03" and cr without difficulty, The measured peaks in samples from CI04­
exposures correspond well with the retention time ofthe Cl04- standards. The perchlorate peak
is well separated from interferences in the control thyroid samples and does not show any
overlap with the peaks from the CI03- and cr standards.

 PERCHLORATE ACCUMULATION IN TISSUES WITH NIS

CI04- was consistently found to be concentrated in NIS-containing tissues. Intra-laboratory

studies collected tissues known to express NIS after dosing Sprague-Dawley rats with CI04' via
drinking water and tv including, gastrointestinal (Gl) contents, skin and milk from the lactating
mammary gland. Tables I and 2 present data collected from the lactation drinking water CI04­
studies (Yu et 01., 2000b) used for development of the lactation model (Clewell et 01., 200la).
Female rats were exposed to CI04' in drinking water from gestation day (GO) 2 to postnatal day
(PND) 5 or 10. The tissue:serum ratios are consistently greater than one, suggesting active
transfer into these tissues.

Table 1. Perchlorate in maternal tissues on PND 5

Dose Group Serum Thyroid Skin GI contents
(mg/kg-day) (1l2/mL) (llwmL) (llwmL») (1l2lmL)
mean SD mean SD mean SD mean SD
0.01 0.057 0.006 0.7 0.09 NO ND ND ND
0.1 0.31 0.03 4.69 0.49 0.4 0.04 0.3 0.03
I 0.5 0.04 14.29 1.76 2.52 0.28 1.21 0.15
10 4.72 0.48 61.22 6.61 7.02 0.80 5.45 0.49

Table 2. Perchlorate in maternal tissues on PND 10

I Dose Group Serum Milk Thyroid
(m2/kg-day) (ug/mL) (J.lg/mL) (ug/mL)
mean SD mean SD mean SD
0.01 0.225 0.055 0.354 0.04 1.13 0.15
0.1 0.358 0.135 0.766 0.119 4.45 0,52
1 0.643 0.139 1.565 0.313 22.29 1.52
10 3.548 0.838 6.869 1.97 43.86 4.15

Active uptake of perchlorate by NIS-containing tissues was also evident in acute iv studies
performed on male rats. Male rats given an iv dose 0£0.01 mglkg CI04' were sacrificed one and
two hours post-dosing and several of the tissues with NIS were analyzed for CI04' levels.
Measured serum, skin, stomach contents and thyroid CI04 ' concentrations are shown in Table 3
(Yu et 01., 2000a).

Attachment 3
 .
T a hie 3 . Perchiorate'ID ma e rat a fter 01 m2 CIO 4
-/k(£! IV
. d ose
Time

Skin Stomach Contents Thyroid Serum

(hour 8
(Ilg/g) (Ilg/g) 8 (Jlg/g) b (Jlglg) 8
s)
mean SD mean SD mean SD mean SD
0.25 3.20 0.29 0.07 0.01
1 0.22 0.02 8.21 0.86 3.50 0.34 0.16 om
2 0.24 0.02 1.13 0.11 0.13 0.01
8 Mean ± SD, n = 6
b Mean ± SD, n = 5 to 6

Tissues lacking NIS did not show the same accumulation ofCl04- as those tissues are known to
contain the symporter. Tissue:serum ratios measured in muscle, fat and liver were less than one
at all time points (Yu et at., 2000a; Merrill et al., 2001 b). The fact that CI04- is consistently
sequestered only in tissues with NIS suggests that the symporter, and not another anion channel,
is responsible for its uptake.

2
 UP-REGULATION OF THYROID PERCHLORATE WITH INCREASED NlS
EXPRESSION

Up-regulation of the iodide transfer into the thyroid via NIS is accomplished through an intricate
feedback system, wherein decreased thyroid hormone levels in the serum signal the
hypothalamus-pituitary-thyroid axis to produce thyroid stimulating hormone (TSH). This
production ofTSH causes an increase in the number and activity ofNlS, resulting in increased
transfer of iodide across the basolateraI membrane into the thyroid follicle. In the PBPK models,
this increased transfer of iodide across the thyroid basolateral membrane is represented by an
increase in the follicular Vmax (VmaxcTi). In rats exposed to CI04' in drinking water for two
weeks, increased uptake of iodide and C104- was seen in the up-regulated thyroids. In fact, as the
thyroid goes from a na"ive to a TSH-induced up-regulated state, the follicular Vmax for C104 ­
(VmaxcTp) increases proportionately with that of iodide. This strongly suggests that NIS, not
another channel, is likely the main transporter of perchlorate.

An intra-laboratory study was performed, in which Sprague-Dawley rats were exposed to C10 4­
in drinking water at doses of 0.01, 0.1,1.0,3.0,10.0 and 30.0 mg CI04"/kg-day for 14 days. On
day 14, rats were challenged with an iv dose of 0.033 mglkg 125 r (with carrier). TSH levels were
increased in all groups receiving C10 4- within 24 hours and remained significantly higher than
controls through day 14. However, a slight decrease was seen between days 5 and 14 (Yu et aI.,
2000a). On day 14, no measurable inhibition ofthyroid 125r uptake was seen in the 0.01 through
10.0 mglkg-day dose groups. Only the 30.0 mg/kg-day dose group showed slight inhibition after
2 weeks ofC10 4- exposure. Thus, it can be concluded that thyroid was fully compensated (up­
regulated) within the two exposure weeks for all but the highest dose group. We can assume that
the increase in the iodide follicular Vmax [VmaxTFi(upregulated)] exactly compensates for the C104­
induced inhibition (represented in the model as an increase in the apparent follicular Km for
iodide (KmTFi). Equation I demonstrates that the overall uptake ofan up-regulated thyroid is
equal to that of a na"ive thyroid:

VmaxTF; xCVI'S; V maxTF;(upregulatedj xCVI'S; Equation 1

KmTF; + CVI'S; ,
CVTS; + KmTF; (1+
C V IIKmTF
'Spj)
p

where:
RupTF i '" Rate of active uptake of 125r into the thyroid follicle (ng/hour)
VmaxTFi = maximum capacity of 125r at the thyroid follicle (ie. NIS sites) (nglhour)
KmTFi. = Michaelis-Menten (M-M) affinity constant for 125r at NIS (ngIL)
CVTSi = blood 125 r concentration in thyroid stroma (nglL)
KmTFp == (~-M) affinity constant for CI04- (competitive inhibitor) at NIS (ngIL)
CVTSi,p = 12~r or C10 4- concentration in thyroid stroma (ngIL).

By rearranging Equation 1, we find that the value for the up-regulated follicular Vmax can be
calculated by the following:

Attachment 4
 V maxTFi(naivt) X(CVTS j + KmTF{l + CJ7Sj{mTFJ)
VmaxTF =-------'-------------'­ Equation 2
I (upr<1{l'Ja"'d) CVTS + KmTF, J

Since the iodide concentration in the thyroid stroma (CVTS j) is negligible in comparison to
KmTFj, it can be removed from the equation.

_' (CVTS p / ) Equation 3

V max TFj (upregulated) - V max TFi(naive) X 1+ / KmTFp

If CI04- is truly a competitive inhibitor, NIS would be responsible for transporting both anions
into the follicle. Thus, one would expect a simultaneous increase in the follicular Vmaxs for
both anions. The change in the VmaxTp should then be proportional to that ofVmaxTj, resulting
in the up-regulated value [VmaxTFp(upregulated)] shown below.

V maxTF- .
V max T.'F = I( upregulated)
x V max T.'F E ' 4
quatlOn
P(upregulated) V maxTF- . P(naive)
I (nQlve)

Figure I shows measured thyroid iodide uptake after 14 days of exposure to 0.01, O. t, 1.0, 3.0,
10.0 and 30.0 mg CI04Ag-day versus simulations from the previous model (naYve VmaxTFi)
and using Equation 3 for up-regulation ofVmaxTF j •

 100 :r--------------,

0.01 mglkgld 0.01 mglkwd --="'"'' ... 0

O.Omglkgld .~""'T"

~-~fi'l

J.O mglkgld =.J

3.0 mglkgld
.5
.:... 1.0
= 10.0 mglkgld

iv IlS). 30.0 mglkgld

0.1 0.1 "." ..'. ···?"·"'·r·~ _. ._._ _.,_ .

325.0 325.6 326.2 326.8 327.4 328.0 325.0 325.6 326.2 326.8 327.4 3280

Time (bours) Time (bours)

A B

Figure 1. (A) Previous model over-prediction l~, uptake inhibition in male rat thyroids
after 14 days of CI04- exposure in drinking water at 0, 0.01, 0.1, 1.0,3.0, 10.0 and 30.0
mglkg-day, followed by a 33 mglkg l2Sr iv with carrier. (B) Same prediction using
Equation 3 to predict up-regulated VmaxTFj • Solid lines and bars represent model
prediction and mean ± SD of measured data, respectively.

Figure 2A shows the predictions of thyroid CI04- concentrations from the previous model based
on values from a narve thyroid (Merrill et aZ., 200lb). The model is able to simulate the data at
the 1.0 mglkg-day dose and below through day 14, and up to 10.0 mg/kg-day through day 1. The
model was unable to reproduce the increased ClOt' uptake on day 5 and 14 in the 3.0, 10.0 and
30.0 mg!kg-day dose groups. Figure 2B shows model simulations of the same data using
Equation 4 to calculate the up-regulated VmaxTF p• The model slightly over-predicts thyroid
CI04- concentrations at 3.0 mg/kg-day dose and higher. However, the simulations are within the
standard deviations of the day 14 data.

 r,-'-"'''--'''' . _ ........._-_ -_ ····_·1

~!~ (\ (\ (\!~ /\ (\ f\ I~ (\ A0\ Qt\!

30.0 mglkgld
10'

V\ v(\V\~(w(\~r\~!\v(\ w' ~r\v/w\v(\ ~ n

10'
10.0 mglkwd
IO'J. i~(\\{,\~.(\~n~r\~(\.~(\~/~~r. ~(\vr\t\V\~
.'(1,\1/\ v\ ~/\~r\V\ V\ V(\ ~/\ ~f\ ~(\ ~(\ V\\r\\~
~ I 3.0 mg'kgld
~ 1
! ~i \Ii \/ \1 \1 \1 \f \'1 \1 \1 \1 \{ \i ~"i.
'1 ~ ~ \ \ v ~

{./\N\f\A(V\(V\/VVV'V\1
i:1h~~:::~~¥¥~(~.(.~¥:.J ! t"i . V I \ I \

10 (f\j ~~\~~'IiYf~~~r:\:r'fi\'r~/\ff1 10" Ii

1.0 mglkgld
•. /\(\/'VVV/y\/VVY\/V\I
l.°j'rfWlV\~V
i ~It!
0.1 . . . . _ r·.. ·· ·.,.-·
O.oI mglkgld
..· _ · T · - · . . l .. -~J
"l/~VVVVVVVWV~
0.1 .i. -----"·T--·--····--· ·-,-·----·---····-····t··--··-···· --_... J

0.0 67.2 J34A 201.6 268.8 336.0 0.0 67.2 134.4 201.6 268.8 336.0

Time (houl's) Time (hours)

A B

Figure 2. (A) Simulations using VmaxTFp established from acute data fail to predict

thyroid CI04- concentrations at drinking water doses greater than 1.0 mg/kg-day. (B)

Simulations fit data across doses using Equation 4 for up-regulated VmaxTFpo Model

predicted (lines) and measured means ± SD (bars) show thyroid CI04-concentrations

during ingestion of 0.01, 0.1,1.0,3.0,10.0 and 30.0 mg/kg-d CI04- in drinking water for 14

days.

In conclusion, the changes in follicular Vmax needed to simulate the increased CI04- and r
concentrations in the up-regulated rat thyroid were found to be proportional to one another. This
proportional change in maximum capacities of both anions suggests that the increased TSH up­
regulates the transfer of both iodide and CI04 - into the thyroid. Further evidence ofTSH­
induced up-regulation of thyroid CI04- uptake is seen in the work of Chow et al. (I969) and
Lewitus et af. (1962). Chow, Lewitus and their coauthors dosed rats with TSH and followed this
dose with CI04-. Both reported increased thyroid CI04- uptake in the groups dosed with TSH
compared the control groups. Together, these studies provide compelling evidence that NIS is
the major transport route for CI0 4- in the thyroid.

 RADIOLABELEDPERCHLORATESTUDYSUGGESTSPERCHLORATEIS

TRANSLOCATED INTO THYROID STROMA, FOLLICLE AND LUMEN

Chow and Woodbury (1970) measured 36C104- uptake in the thyroids of rats and guinea pigs
after ip administration of the radiolabeled ion. Some ofthe animals were used to study time
course of 36CI04- in the thyroid, while others were used to examine histological changes in the
thyroid and changes in electrochemical potential in the presence of 36Cl04-.

The authors examined the 36Cl04- time course data and observed that there were two apparent
phases in the uptake of%Cl04- into the thyroid, the first being a rapid transport (tw = 2 min) and
the second being a slower transport (tl(2 = 33 min). The authors suggest that the first phase
represents the rapid transport into the interstitial and cellular compartments. The second phase
represents the rapid transport and slow equilibration of 36Cl04- in the luminal fluid. The data,
along with the histological measurements of the stroma, cell, and lumen, were used to calculate
the relative 36C104- concentrations ofthe compartments. This process was repeated for Cr.
Chloride did not show the same accumulation in the thyroid seen with perchlorate. The values
obtained for the relative compartment concentrations of the two anions are given below for two
of the measured doses (Chow and Woodbury, 1970).

Table 1. Relative Concentrations of Perchlorate and Chloride in the Thyroid

Compartments from Chow and Woodbury (1970).
KJ6C104 Cell:Stroma Lumen:Stroma Lumen:CeU
(mmol/~)
jt:JCI04- jC>cr ·l('CI04- JC>cr JOCI04- jOcr
0.005 6.15 0.14 147 0.95 24.0 6.8
0.01 2.2 0.13 48 1.0 21.6 7.7

From the time course behavior and measured potentials in the cellular compartments, the authors
conclude, ,,36 CI04" is concentrated in the lumen of the thyroid by a two-step process. Firstly,
36C104- is actively transported across the basal cell membrane from the stromal fluid into the
cellular fluid. In the cellular fluid, 36C104- then passes across the apical cell membrane into the
lumen and it is further concentrated during this process" (Chow and Woodbury, 1970).

Attachment 5
 KINETIC BEHAVIOR OF PERCHLORATE IN RAT THYROID SUGGESTS
THREE-COMPARTMENT MODEL STRUCTURE

A three compartmental thyroid, consistent with the physiological structure (i.e., stroma, follicle
and lumen) is required to capture the kinetic behavior of thyroid Cl04' (Figure I). This was also
found to be true by Chow and Woodbury (I 970). They found that the uptake curve for CI04­
showed two distinct phases, corresponding to a rapid transfer into the stroma and follicle and
slower transfer into the lumen (see Attachment 7). Intra-laboratory data show similar results in
the clearance of Cl04' in the thyroid of the male rat after iv dose of radiolabeled perchlorate. The
Cl04' appears to be cleared from the thyroid in two phases. The first shows quick elimination
from the follicle; the second is slower, suggesting slow release from a deep compartment (the
thyroid lumen).

The models were originally described with two compartments, the stroma and cell. However,
the hvo-compartment structure failed to simulate the behavior ofCl04'. The model could not
simulate the 2 phases, thus resulting in a model that could either fit the first two data points or
the last, but could not capture the kinetic behavior of the time course data. CI04- was taken up
and released from the follicle too quickly in the model (Figure I). With a three-compartment
model of the thyroid, it was possible to simulate the entire time course with one set of
parameters. The kinetic behavior is well described assuming the rapid transfer between the
stroma and follicle, and a slower release from the lumen.

22.0 - , - - - - - - - - - - - - - - - - - - - - - ,

,-, 17.6
~
e
'-'
:E Three·compartment
o 13.2

~
.5
~ 8.8
o
fj....

I
<l>
0.. 44

TWO'CClDlpartmenl
0.0
0.0 9.8 19,6 29.4 39.2 49.0

Time (hours)
Figure 1. Thyroid 36CI04' concentration in the male rat after iv administration of 3.3
mglkg with a two-compartment (bottom) and three-compartment (top) thyroid. Solid lines
±
and bars represent the model simulation and mean SD of the measured data.

Attachment 6
 ELECTROGENICITY STUDIES OFFER MORE THAN ONE EXPLANATION FOR

REPORTED RESULTS

The sodium-iodide symporter is a protein located on the basolateral membrane of thyroid

follicular cells. NIS transports iodide into the thyroid follicle against a concentration gradient by
way of an energy dependent co-transport mechanism (Na+/K+·ATPase). NIS transports two
sodiums (Na) for every one iodide (l) and is driven by an inwardly directed Na-I- gradient. This
2:1 Na+tr ratio has been established by several investigators (Kosugi et al., 1996; Eskandari et
al., 1997; Riedel et al., 2000).

Recent studies on NIS electrogenicity have shown that a bathing medium containing r causes an
inward current in an oocyte with NIS. When 500 JlM CI04' was added to the bathing medium,
the inward current disappeared (Eskandari et al., 1997). Two possible reasons were given for the
disappearance of the current.

1) Perchlorate blocks r transport, but may not be transferred into the thyroid cell.
2) Perchlorate competes with r and is transported by NTS at a 1:1 ratio with Na+.

Although several authors (Riedel 2001 a, b) have stated their preference for the first explanation,
that CI04' is not translocated into the cell, they all have also concluded that CI04' transport by
NIS at 1: I stochiometric ratio with Na+ is also a viable explanation (see also Nilsson, 1999;
Dohan et al., 2000). Such a stochiometry would abolish the iodide-driven inward current but
maintain the competitive inhibition of iodide uptake. These studies offer a compelling argument
for the relationship of structure activity to the effectiveness of the thyroid uptake inhibitor. They
also open the field to further research, in order to more clearly define the mechanism of these
iodide uptake inhibitors. However, these studies do not attempt to quantitatively measure CI04'
in the thyroid, and they do not offer concrete evidence disproving the translocation of CI04'
across the follicular membrane. When these electrogenicity studies are taken in context with the
many other studies in literature (Wolff, 1998; Chow and Woodbury, 1970; Hildebrandt and
Halmi, 1981; etc.) and recent experiments (Yu et al., 2000a, b), the weight of evidence suggests
that perchlorate is a truly competitive inhibitor. Thus, the mode of action, which serves as the
foundation for the kinetic models, was based upon the entire body of available information.

Attachment 7
 CALCULATION OF MAXIMUM THYROID PERCHLORATE CONCENTRATION

ASSUMING ALL MEASURED PERCHLORATE IS BOUND TO NIS IN THE

THYROID MEMBRANE

One suggested mechanism by the authors of several articles (Eskandari et al., 1997; Riedel
2001a, b; Nilsson, 1999; Dohan et al., 2000) and by members of the Peer Review Panel, involves
the binding but not translocation ofCl04' at the follicular membrane of the thyroid by NIS. In
other words, the CI0 4' anion is able to compete with iodide for binding sites on the NIS.
However, when bound to CI04' the NIS is not able to cross the follicular membrane. Thus, the
CI04" measured in the thyroid would have to be bound to the symporter in the membrane of the
cell and not within the cell itself.

If true, this theory would require that all measured CI04" molecules be bound to NTS in order to
be found within the cellular membrane at the time of analysis. Thus, each perchlorate molecule
would correspond to one inhibited symporter. This line of thought has two direct consequences.

• The relationship of iodide inhibition and perchlorate concentration should be linear.

• The CI04' thyroid concentration that results in 100% inhibition should also be the maximum
possible thyroid concentration.

In order to check the feasibility of this proposed mode of action, the measured Cl04"
concentrations were plotted against the corresponding inhibitions in the thyroids of adult male
rats given an tv dose of 0.01, 0.1, 1.0 and 3.0 mg Cl0 4"!kg BW (Yu et al., 2000a). Figures 1 and
2 show the relationship ofCI04' concentration to % inhibition in the rat thyroid. The non­
linearity of this relationship is evident in both sets of measured values.

1 Attachment 8
 .e 100 --­
:a0
>-<
80
:s
...
0
>-Q) 60·
...c~
'­f-<
0
....0..
"" Y = 3.l377x
;::;:J 40 2
0 R =0.8584
:B
.D
...c
20 •
.s
t?­ O
0 10 20 30 40
Perchlorate Concentration (mg/kg thyroid)

Figure 1. Plot of perchlorate concentration versus percent inhibition of iodide uptake in the
thyroid at two hours post-dosing.

.e
:a0
.....
:s
...
0
100

80 ­
-l

>-
...c 60
II
.\1
f-<~
,-E y =2.7769x
0 0..
;:: ;:J 40 . 2
0 R =0.7724
-.;::::
.....
.....
.D
...c 20
•
.s
:f?­
0 o­
0 10 20 30 40

Perchlorate Concentration (mg/kg thyroid)

.Figure 2. Plot of perchlorate concentration versus percent inhibition of iodide uptake in the
thyroid at nine hours post-dosing.

In spite of the apparent non-linear dose-response curves, a straight line was fit to the measured
data points and an equation was generated from the relationship ofthe thyroid CI04'

2
concentration to the inhibition of iodide uptake. Again, if the above hypothesis is correct, the
amount ofCI04- in the thyroid follicle should correspond to the number of unavailable NIS
binding sites. Thus, at 100% inhibition, the thyroid CI04 ' concentration should reach its
maximum concentration. Setting y = 100 in the equations from Figure 1 and 2 yields maximum
CI04- concentrations in the male rat thyroid of 31.9 and 36.0 mg CI04'/kg tissue, respectively.

In order to test the accuracy of the calculated maximum thyroid CI04' concentration,
measurements were needed in the thyroid of a non-upregulated rat after in vivo CI0 4' exposure.
These data were not available above a dose 01'3.0 mg/kg BW within this laboratory. However,
Chow and Woodbury (1970) measured the thyroid CI04' concentration in the male rat after an iv
dose of 14 mg Cl04·!k.g BW and found Cl04' concentrations o£170 mglkg-thyroid at this dose.

Neither of the criterion for this proposed mode of action are satisfied when tested against data.
The non-linearity of the dose-response curve suggests that the thyroid CI04' concentration is not
directly related to the iodide inhibition. In the lower doses, there is apparently more CI04' in the
thyroid than can be accounted for by occupied NIS. The calculated maximum CI04'
concentration also underestimates the ability of the thyroid to accumulate CI04·. The fact that
100% occupancy of the NIS cannot account for the mass of CI04' measured in the thyroid
indicates that the CI04' ion must also be located in other areas of the thyroid, not exclusively in
the membrane NIS. Thus, there must be translocation of the Cl04' anion in the thyroid cells.

RECENT DEVELOPMENT IN GESTATION MODEL: IMPROVED DESCRIPTION OF

IODIDE UPTAKE IN THE PLACENTA

The PBPK models presented in the EPA document represent the progress in model development
as of June 200 I. However, since the submittal deadline, new data were made available,
including measurements of perchlorate-induced inhibition of uptake in the placenta as well as
several fetal tissues. The new data sets facilitated changes in the gestation and lactation models.
Active uptake of iodide and CI04- by N IS inhibition of placental iodide transfer by CI04- was
added to the gestation model. The presence ofNIS in the placenta is supported by literature, as
is the ability of CI0 4- to reduce iodide levels in the fetus (Versloot et al., 1997). Due to time
limitations and the lack of data, placental iodide and CIO£ transfer were reasonably described as
first order clearance processes in the first version of the model (Clewell et al., 200 Ib). However,
further investigation allowed a more thorough model description of placental inhibition, which is
vital when determining the ability of the fetal thyroid to obtain the iodide necessary for hormone
synthesis.

This report will present the current fits ofthe model to the new data. A manuscript with the
complete description of the gestation model is currently in preparation. The updated dosimetrics
have been provided to the EPA and the external peer review panel in a previous consultative
letter (Merrill et al., 2002). These changes resulted in significantly different values for fetal
inhibition. However, they did not affect the values for the serum perchlorate concentrations used
by the U.S. EPA for species/life stage extrapolation (USEPA, 2002). Therefore, these changes
are provided, not to change the risk assessment, but to inform the peer review panel of further
progress and to address their concern as to the description of the placenta.

New Experiments

Timed-pregnant Sprague-Dawley dams were given a tail vein injection of 1.0 mg CI04-lkg BW
on GD 20. Two hours post-dosing with CI04-, dams were given a tracer dose (average dose ==
1.87 ng/kg BW) of 12Sr on GD 20. Dams (n=6) were sacrificed at 0.5, 1,2,4, 8, 12 and 24 hours
post_1 2Sr dosing. Maternal and fetal serum, skin and GJ tract, as weB as maternal thyroid, G1
content, placenta and mammary gland tissue were collected and analyzed for 12Sr with a gamma
counter. Fetal serum was pooled by litter due to small sample volume. Fetal skin and Gr tract
were analyzed individual1y. Inhibition kinetics were examined in this same manner. However,
tv.'o hours prior to the administration of 125r (average dose = 1.&7 ng/kg BW), dams from the
inhibition group were dosed with 1.0 mglkg BW CI04- via tail vein injection and euthanization
was performed at 0.5, 1,2,4,8, 12 and 24 hours post_1 31 r

Modifications to Model Structure

Active uptake was simulated in the placenta using MicheaHs-Menten kinetics as described for
the other NIS compartments in the previous consultative letter (Clewell et aI., 2001b) and the
EPA risk assessment document. Inhibition was added to the description of the placenta, maternal
and fetal GJ contents and skin in the manner described for the thyroid.

Attachment 9
Figure 1 shows the new model schematic. Table 1 contains the revised perchlorate and iodide
parameters. The only change from that of Clewell et al. (200Ib) is the active uptake in the
placenta compartment. Figure 2 shows the fit of the model to inhibition data in the maternal and
fetal tissues. Table 3 shows the model prediction of inhibition of total fetal iodide measured by
Sztanyik and Turai (1988). The model is able to adequately describe inhibition kinetics in the
maternal and fetal rat and is able to predict inhibition of iodide transfer to the fetus with these
modifications to the original structure.

Pregnant Dam Fetus

Ivc.J> bound ClO.. Ktransl
\ Plasma ~t
t----~f~9-.: QC CA..> QC CA..>
RUes
pDose

Urine

QSK

--i Slowly
Perll1s;'d
I
+-os

Ktrans2

Figure 1. Scbematic ofPBPK model for pregnant dam (left) and fetus (right).

2
 T a ble 1 Ch emlcaI S eCllc
0 °fi P arameters
Parameters Perchlorate Iodide
lPartition Coefficients (unitless) Dam Fetus Dam Fetus
lowly Perfused 1Plasma PS 0.31 0.31 0.21 0.21
Rapidlv Perfused 1 Plasma PR 0.56 0.56 0040 0040
FatJ Plasma PF 0.05 --- 0.05 -­
Kidneyl Plasma PK 0.99 0.99
1.09 1.09
iver/Plasma PL 0.56 0.56
0.44 0.44
Gastric Tissue/Gastric Blood PG 0.50 1.80
1.00 1.00
Gastric Juice/Gastric Tissue PGJ 1.30 2.30
2.00 2.00
kin Tissue/Skin Blood PSk
l.l5 1.15
0.70 0.70
f'hyroid TissuelThyroid Blood PTF
0.15/2.25" 0.15/2.26"
0.15 0.15
l1lvroid Lumenfrhvroid Tissue PTL
7.0 7.0
7.0 7.0
iRed Blood Cells/Plasma PRBC 0.73 0.73
1.00 1.00
~lacentaJ plasma PPI 0.56 --- 0040 --­
vlammarv/Plasma PM 0.66 --- 0.66 -­
\fax Capacity, Vmaxc (nlUhour/k~)
L8x I03 0- 2.25xl 0 3 4.0x10 o-5.0xI0
4 4
Irhyroid Follicle VmaxcTF
4 4b 6.0
hvroid Colloid VmaxcTL 1.0xl0 1.0x10 ­ 6.0xlO' xIO IT>­

kin VmaxcSk 6.0x1O s 4.0x1Os 6.0xl ()4 3.0xlcf

}utVmaxcG 8.0x10 5 LOxl0 5 LOxl06 2.Ox10 6
4
Mammary VrnaxcM 2.2x10 -- 5.0xI04 --­
!Placenta VmaxcP 6.0x10
4
--- 5.5x10
4
--­
iAffinity Constants, Km (neIL)
hyroid Follicle KmTF
LOx I05 I.OxIO' 4.0xllf 4.0xIlf
Thyroid Colloid KmTL
1.0xlO~ I.Ox10 8 I.OxI09 I.Ox10 9
~kjnKrnSk 1.0xlO s I.Ox10 5 6
4.0xllf
4.0x10
5 5 6
GutKmG I.OxlO LOx 10 4.0x10 4.0xIO°
MammarvKmM LOx 10 5
--- 4.0xI0
6
-­
Placenta KmP 1.0x10
5
-- 4.0x10
6
-­
Ilermeability Area Cross Products, (Ubour-kl?:)
3astric Blood to Gastric Tissue PAGe 1.00 1.00
0.80 0.10
}astric Tissue to Gastric Juice PAGJc 1.00 1.00
0.60 0.30
6.0xI0""1 6.0x I0""/
LOxIO"" LOx I0""
frhyroid Stroma to Follicle PATFc 1.4x 10'4 L4xlO·4b

rrhyroid Follicle to Colloid PATLe 0.01 O.Olb

LOx I0"" 1.0xIO-4
\Skin Blood to Skin Tissue PASkc 1.00 1.00
0.10 0.02
Mammary Blood to Mammary Tissue PAMe 0.04 -- 0.01 -­
Placenta Blood to Placenta Tissue PAPc 0.1 --- 0.005 --­
!Plasma to Red Blood Cells PARBCc 1.00 1.00 1.00 1.00
!clearance Values, (L/hour-k2)
lurinary excretion ClUc 0.07 --- f 0.03 --­
h'ransfer from Placenta to Fetus CITrans 1c 0.065 0.06
Irransfer from Fetus to Placenta CITrans2c 0.12 i 0.12
Bindinl!: Constants
IAssociation to Binding Sites VmaxcB 4.0x10
3

4
l.5xl0
3
--­ --­
IAffinity for Binding Sites KmB LOx 10 1.5x 10" --­ -­
/Dissociation from Plasma Binding Sites ClUnbc 0.034 0.01 --­ --­
Notes: a IndIcates values for up-regulated thyrOId, Scaled from adult value
•• b

3
 4.0 2.0

3.2 ~ 1.6
~ bll
5
5 a
...'"
i:: 2
OJ
u
2.4 en 1.2
'"
0: ~
.5 I J;J..
OJ J! .5
-0 1.6 0.8
'5
0
Without Perchlorate "
"'"
'5
Without Perchlorate

~
'0 0
'0 .... "
~ 0.8
'"

.......~
', ~
~
0.4 ,

0.0
f With Perchlorate
J 0.0 -l .
F With Perchlorate
J
478.0 483.4 488.8 494.2 499.6 505.0 478.0 483.4 488.8 494.2 499.6 505.0

Time (hours) Time (hours)

A B
10 7.0

::3' 5.6
C.
.5
.5
""en 4.2

~
>t­
.S

.5 4 ..g 2.8

'ii
9
o
'5
'"
p:: 1.4

o
478.0 483.4 488.8 494.2 499.6 505.0 483.4 488.8 494.2 499.6 505.0

Time (hours)
c Time (hours) D

n
Figure 2. Radioiodide (l2S concentration with and without 1.0 mglkg administration in

(A) placenta, and fetal (ll) serum, (C) GI contents and (D) skin. Solid lines represent model

predictions. Bars represent the mean ±SD of the data. Maternal GI contents and skin

were not significantly different between control and inhibited animals in the data or model

simulations.

Table 2. Model Predicted Inhibition oflodide Uptake in Total Fetus Versus Data of
Sztanyik and Turai (1988)
KCI04 Dose Time of CI04- dose Model Predicted Measured %
(mg) (after 131 r dose) % Inbibition in Inhibition in Fetus
(min) Fetus (% Control)
(% Control)
6.0 20 13% 8.1-15.1 (12)
3.0 60 18% 14.2-19.8 (17)
3.0 120 20% 24.2-34.6 (30)

 COMPARISON OF PERCHLORATE-SPECIFIC PARAMETERS IN PBPK MODELS

ACROSS LIFE STAGES

The perchlorate chemical specific parameters are nearly identical for the rat models across life
stages, with the exception of the maximum uptake (Vmaxc) ofCI04- into the gastricjuice/OI
contents and the permeability area cross product (PA) in the thyroid follicle. Due the available
data, the value VmaxcGp represents the saturable uptake in the gastric (stomach) juice of the male
rat and human and the entire gastro-intestinal (01) contents in the pregnant and lactating rats.
Therefore, the values of these parameters cannot be directly compared between the male and
developmental models.

The PA value for CI04- uptake in the thyroid follicle is somewhat higher in the pregnant rat than
the male rat. This difference is supported by the CI0 4- time course data in both male and
pregnant rats and by the fact that greater loss of radioiodide is also seen in during pregnancy in
the rat in historical studies (Versloot et al., 1997). This loss is represented in the models by an
increased value for PA at the follicular membrane (PATc), allowing the ion to move out of the
cells more quickly.

Attachment lO
 e erehi orate Parameters A cross L·ti
T a hie 1 Comparlson 0 fR at Mo diP I e Staecs

Perchlorate Parameters Male Rat Pre~nancy Lactation

Dam Fetus.LQl.:l.m Neonate
Partition Coefficients (unitless)
Slowly Perfused I Plasma PS 0.31 0.31 0.31 0.31 0.31
Rapidly Perfused I Plasma PR 0.56 0.56 0.56 0.56 0.56
Fat! Plasma PF 0.05 0.05 --- 0.05 0.05
Kidneyl Plasma PK 0.99 0.99 0.99 0.99 0.99
LiverlPlasma PL 0.56 0.56 0.56 0.56 0.56
Gastric Tissue/Gastric Blood PG 0.70 0.50 1.80 1.80 3.20
Gastric Juice/Gastric Tissue PGJ 1.70 1.30 2.30 2.30 5.60
~in Tissue/Skin Blood PSk 1.15 1.15 1.15 1.15 1.15
Thyroid TissuelThyroid Blood PT 0.13 0.13 0.13 0.13 0.13
Thyroid LumenIThyroid Tissue PDT 7.00 7.0 7.0 7.0 7.0
Red Blood CellslPlasma 0.80 0.73 0.73 0.73 0.73
Maximum Capacities (ng/hour/k~ BW)
Thyroid Follicle Vmaxc T 2.2E+03 1.8E+03 0- 2.25e3 1.5E+03 I.5E+03
Thyroid Colloid Vmaxc DT 1.0£+04 I.OE+04 1.0E+04 I.OE+04 1.OE+04
Skin Vmaxc S 6.2£+05 6.0E+05 4.0E+05 8.0E+05 8.0E+05
Gut Vmaxc G 2.0E+05 8.0E+05 I.OE+05 1.0E+06 I.OE+06
Affinity Constants (ng/L)
!Thyroid Follicle Km T 1.8E+05 1.0E+05 1.0E+05 I.OE+05 1.OE-+{)5
Thyroid Colloid Km DT 1.0E+08 1.0E+08 1.0E+08 1.0E+08 1.0E+08
Skin Km S 2.0E+05 1.0E+05 1.0E+05 1.0E+05 1.0E+05
Gut Km G 2.0E+05 1.0E+05 1.OE+05 1.OE+05 1.0E+05
Permeability Area Cross Products (Llhourlk~ BW)
Gastric Blood to Gastric Tissue PAGc 1.00 1.00 1.00 1.00 1.00
Gastric Tissue to Gastric Juice PAGJc 0.80 1.00 1.00 1.00 1.00
Thyroid Blood to Thyroid Tissue PATc 4.0E-05 1.4E-04 1.4E-04 4.0E-05 I.OE-03
Thyroid Tissue to Thyroid Lumen PADTc 0.01 om 0.01 0.01 I.OE-03
Skin Blood to Skin Tissue PASkc 0.80 1.00 1.00 0.50 1.00
Plasma to Red Blood Cells PARBCc 1.00 1.00 1.00 1.00 1.00
Clearance Values (L/bourlkg BW)
Urinary excretion CLUc 0.07 0.07 --- 0.07 0.0075
Transfer from Placenta to Fetus --- 0.065 --- -­
fransfer from Fetus to Placenta --- 0.120 -- -­
Serum Binding Constant~
Vmaxc Bp (ng/hour/kg BW) 3.5E+03 5.0E+03 1.5E+03 9.0E+03 2.0E+03
Km Bp (oglL) 1.1E+04 1.0E+04 1.5E+04 1.0E+04 1.0E+04
Kunbc p (Llhourikg BW) 0.028 0.034 0.034 0.034 0.01

 REFERENCES

Anbar, M., S. Guttmann, and Z. Lewitus. (1959), The mode of action of perchlorate ions on the
iodine uptake of the thyroid gland. IntJ.Appl.Radiat.Isot., 7:87~96.

Chow, S.Y., L.R. Chang, and M.S. Yen. (1969). A comparison between the uptakes of
radioactive perchlorate and iodide by rat and guinea~pig thyroid glands. J.Endocrinol., 45: 1-8.

Chow, S.Y. and D.M. Woodbury. (1970). Kinetics ofdistribution of radioactive perchlorate in
rat and guinea~pig thyroid glands. J.Endocrino!.,47:207-218.

Clewell, RA. (1999). The development of an alternative technique for the trace level analysis of
perchlorate in aqueous matrices [thesis]. Dayton, OH, Wright State University.

Clewell, RA., E.M. Merrill, K.O. Yu, D.A. Mahle, T.R. Sterner, J.W. Fisher, and J.M. Gearhart.
(200 I a). Physiologically~based pharmacokinetic model for the kinetics of perchlorate-induced
inhibition of iodide in the lactating and neonatal rat. AFRL-HE-WP~CL~0007.

Clewell, R.A, E.A. Merrill, K.O. Yu, DA. Mahle, T.R. Sterner, P.J. Robinson, and J.M.
Gearhart. (2001 b). Physiologically-based pharmacokinetic model for the kinetics of perchlorate­
induced inhibition of iodide in the pregnant rat and fetus. AFRL-HE-WP-CL-200 1-0006.

Dohan 0, A. De la Vieja, and N. Carrasco. (2000). Molecular study of the sodium-iodide

symporter (NIS): A new field in thyroidology. Trends EndocrinoI.Metab,. 11:99-105.

Eskandari, S., D.O. Loa, G. Dai, O. Levy, E.M. Wright, and N. Carrasco. (1997). Thyroid Na+/I­
symporter. Mechanism, stoichiometry, and specificity. J.BioI.Chem.,272:27230-27238.

Gluzman, B.E., and H. Niepomniszcze. (1983). Kinetics of the iodide trapping mechanism in
normal and pathological human thyroid slices. Acta Endocrino!., 103,34-39.

Hildebrandt, J.D. and N.S. HalmL (1981). "Intrathyroidally generated iodide: The role of
transport in its utilization." Endocrinology. 108(3):842-849.

Kosugi, S., N. Sasaki, N. Hai, H. Sugawa, N. Aoki, C. Shigemasa,; T. Mori, A. Yoshida. (1996).
Establishment and characterization of a Chinese hamster ovary cell line, CHO-4J, stably
expressing a number of Na+lI- symporters. Biochem.Biophys.Res.Commun.227(1):94-101.

Lewitus, Z., S. Guttmann, and M. Anbar. (1962). Effect of thyroid-stimulating hormone (TSH)
on the accumulation of perchlorate and fluoroborate ions in the thyroid glands ofrats.
Endocrinology 70:295-297.

Merri1l, E.A., R.A. CleweJl, and J.M. Gearhart. (2002). Additional information regarding the
comparison ofPBPK-derived internal dosimetrics for perchlorate-induced inhibition ofthyroid
iodide uptake and sensitivity analysis for the male rat model. AFRL-HE-WP-CL-2002-0004.

Attachment II
Merrill E.A., R.A. Clewell, T.R. Sterner, and J.M. Gearhart. (2001 a). PBPK model for
perchlorate-induced inhibition of radioiodide uptake in humans. AFRL-HE-WP-CL~0008.

Merrill E.A., R.A. Clewell, J.M. Gearhart, P.T. Robinson, T.R. Sterner, K.O. Yu, L. Narayanan,
and 1.W. Fisher. (200 Ib). PBPK model for perchlorate-induced inhibition in the male rat.
AFRL-HE-WP-CL-0005.

Nilsson, M. (1999). Molecular and cellular mechanisms of transepithelial iodide transport in the
thyroid. BioFactors. 10:277-285.

Riedel, C., O. Dohan, A. De la Vieja, C.S. Ginter, and N. Carrasco. (200Ia). Journey of the
iodide transporter NIS: from its molecular identification to its clinical role in cancer. Trends
Biochem.Sci. 26:490-496.

Riedel, C., O. Levy, and N. Carrasco. (200 Ib). Post-transcriptional regulation of the
sodium/iodide symporter by thyrotropin. J Biol.Chem., 276:21458-21463.

Sztanyik, L.B., and I. Turai. (1988). Modification of radioiodine incorporation into the fetuses
and newborn rats by thyroid blocking agents. Acta Physiol.Hung. 72(3-4):343-354.

USEPA. 2002. Perchlorate environmental contamination: Toxicological review and draft risk
characterization. (External Review Draft). Available: www.http://cfpub.epa.gov/ncea.

Versloot, P.M., Schroder-Van Der Elst, J.P., Van Der Heide, D., and Boogerd, L. (1997). Effects
of marginal iodine deficiency during pregnancy: iodide uptake by the maternal and fetal thyroid.
AmJ.Physiol., 273 (6 pt. I), EI121-EI126.

Wolff, J. (1998). Perchlorate and the thyroid gland. Pharmacolog.Rev., 50, p. 89-105.

Yu, K.O., L. Narayanan, RJ. Godfrey, P.N. Todd, C.D. Goodyear, T.R. Sterner, T.A. Bausman,
S.M. Young, D.R. Mattie, and J.W. Fisher. (2000a). Effects of perchlorate on thyroidal uptake of
iodide with corresponding hormonal changes. AFRL-HE-WP-TR-2000-0076.

Yu, K.O, D.A. Mahle, L. Narayanan, RJ. Godfrey, G.W. Butler, P.N. Todd, M.A. Parish, J.D.
McCafferty, T.A. Ligman, C.D. Goodyear, T.R. Sterner, T.A. Bausman, D.R. Mattie, and J.W.
Fisher. (2000b). Tissue distribution and inhibition of iodide uptake in the thyroid by perchlorate
with corresponding hormonal changes in pregnant and lactating rats (drinking water study).
AFRL-HE-WP-CL-0038.

 t-'ercnlorate - tsacKgrouna

(from Slide 2)

• 1 chlorine + 4 oxygen atoms

• Potassium or ammonium perchlorate is an oxidizer used

in:
- Some Missiles, rockets, munitions (DoD/NASA)

- Fireworks, explosives, road flares, matches, dyes, paint, air bags

• Also found in:

- Some fertilizers, natural minerals, degradation of household bleach
products, water disinfection products
• A salt...Highly soluble in water...Used in past to treat
overactive thyroids...But can inhibit normal thyroid
function at certain levels...Pregnant women/fetuses
especially sensitive
 Perchlorate - Background
Acquisition, Technology and Logistics

• 1 chlorine + 4 oxygen atoms

• Potassium or ammonium perchlorate is an oxidizer used

in:
- Missiles, rockets, munitions (DoD/NASA)

- Fireworks, explosives, road flares, matches, dyes, paint, air bags

• Also found in:

- Some fertilizers, natural minerals, degradation of household bleach
products, water disinfection products
• A salt...Highly soluble in water...Used in past to treat
overactive thyroids...But can inhibit normal thyroid
function at certain levels...Pregnant women/fetuses
especially sensitive
2
 ORA Background
~ Toxicology

• Perchlorate has been linked with interferences with iodide

uptake into the thyroid gland
• Perchlorate has not been shown to be a carcinogen.
II There is much disagreement within the scientific community

of perchlorate's true affects on human health

~ Regulatory

• At present there is no national standard

• EPA is proposing new strict drinking waters standards likely
in the 1-4 ppb range
• ~taF!dards are expected to be finalized in 2003
 Perchlorate State-of-the-Science Symposium (PS3 2003)

Omaha, Nebraska

September 29 - October 1 2003

What is PS 3 About?

The Perchlorate State-of-the-Science Symposium (PS3 2003) will

provide a review of fundamental science issues related to the potential
health risks from low-level exposure to perchlorate. Researchers who
performed the most important recent scientific studies will present their
work. Leading scientific experts will evaluate these studies and, taking
into account their strengths and weaknesses, develop consensus reports
on the state-of-the-science as of 2003. These summary documents will be
submitted for publication in a peer-reviewed journal, and will be provided
to the National Academy of Science for consideration at their upcoming
review of perchlorate. These documents can also be relied upon to serve
as the sound, scientific foundation for site-specific decision-making
regarding perchlorate pending the conclusion of the National Academy
review in 2004 and subsequent revisions to various government risk
assessments.

What Is Perchlorate, and Why Does It Matter?

Perchlorate is the anion salt comprising the active ingredient in

ammonium perchlorate, the major ingredient in solid rocket motors,
fireworks, and automotive airbag inflators. It is a trace constituent of
certain fertilizers and is found naturally at scattered locations. Potassium
perchlorate has been used for pharmaceutical purposes for over 50 years.

Perchlorate can now be detected at levels as low as 4 parts per billion

(Ppb) in water. Since the recent improvement in analytical capabilities, it
has been detected at low levels (typically below 20 ppb) in ground and
surface waters, including drinking water supplies, across more than two
dozen states.

Media reports allege that low-level perchlorate exposure may cause a

host of thyroid disorders. Federal and State regulatory agencies have
issued draft risk assessments concluding that low-level exposure poses
potential health risks. Because of the lack of scientific consensus on
human health risks, these documents have proven to be highly
controversial.

-1­
What is the Regulatory Environment for Perchlorate?

Regulatory uncertainty persists because perchlorate is not a regulated

hazard waste, hazardous substance or drinking water contaminant.
Despite this, certain USEPA regional offices and some State regulatory
agencies have been issuing sampling and cleanup directives based on
USEPA guidance documents dated 1992,1995, and 1999 which establish
4-18 parts per billion (Ppb) as a "provisional" range for remediation. In
January 2003, USEPA's guidance went further, recommending that
regulators "carefully consider the lower end of the provisional range."

Some federal agencies and other stakeholders have significant

concerns about this "provisional" range for remediation. The 4-18 ppb
range is based on a single clinical study of 12 Graves' disease patients
that was published in 1952. (Graves' disease is a hyperthyroid condition
in which the thyroid gland produces too much thyroid hormone.) Eight of
the 12 patients were administered gram doses of perchlorate for the
express purpose of shutting down their production of thyroid hormones.
"Gram" doses are over 100,000 times greater than current environmental
exposures.

USEPA issued its first external review draft risk assessment for
perchlorate in 1998. This document proposed a hea1th~based level
equivalent to 32 ppb in drinking water. A USEPA external peer review
panel met in 1999 to review the draft risk assessment, and concluded that
the agency had erred in ways that significantly overstated the likely
human health risk. The panel recommended additional research that it
believed would provide a strong scientific basis for raising the health­
based level substantially above 32 ppb.

DoD and the Perchlorate Study Group spent millions of dollars to

develop the new and better scientific information about perchlorate
recommended by the 1999 peer review panel. Most of these new studies
were specifically approved by USEPA. DoD and the Perchlorate Study
Group marshaled the resources to perform this research in concurrence
with USEPA requirements, and in some cases relinquished management
control to the Agency. In addition, several epidemiological studies were
performed in various populations, including workers exposed to the
equivalent of more than 15,000 ppb perchlorate for several years and
children naturally exposed to over 100 ppb since birth. No adverse effects
have been detected in any of these studies.

·2·

...... --_._---­
 Another study performed was a clinical trial in human volunteers
designed to determine the threshold for iodide uptake inhibition. Iodine
uptake inhibition is a mundane, reversible and inconsequential biomarker
that can be triggered by a host of natural phenomena including diet and
sleep patterns. Identifying the threshold below which perchlorate
exposure failed to trigger this biomarker enabled researchers to estimate
a no-effect level below which subsequent adverse effects were biologically
infeasible, even for sensitive subpopulations.

USEPA's response was to label this biomarker a "key event" that could
potentially lead to an adverse effect, then revise its risk assessment as if
this "key event" were adverse rather than mundane. l The clinical trial
showed that the threshold for iodide uptake inhibition was approximately
200 ppb in drinking water. Thus, by proposing a health-based level of 1
ppb, USEPA seeks to establish a standard that many scientists believe is
more than two orders of magnitude below the no-effect level, and at least
five orders of magnitude below any detectable adverse effect.

Who Should Attend?

This symposium is being held for scientists, consultants, regulatory

agency officials and others interested in learning about the state-of-the
science on perchlorate. It provides a unique opportunity for all
stakeholders to learn first-hand about the most salient recent scholarly
research directly from the authors of the research themselves rather than
having to rely on a secondary, derivative interpretation by someone else.
Participants will also have a rare opportunity to interact with
distinguished, independent experts in various fields specifically relevant
to evaluating the scientific merits of recent research.

What Will the Symposium Cover?

PS3 2003 will summarize the state-of-the-science of perchlorate as of

1998, and then address the most hotly debated scientific questions about
perchlorate:

I "The key event is defined as an empirically observable precursor step that is a

necessary element of the mode of action or is a marker for such an element." See USEPA
2002, "Perchlorate Environmental Contamination: Toxicological Review and Risk
Characterization; EPA External Review Draft, page 7-4.

·3­
 • Do rat brain morphometry studies and behavior studies show
evidence of a neurodevelopmental hazard in humans?
• How should PB-PK modeling be used to estimate human health
risk?
• What are the relative scientific merits of human and animal data
for estimating risk, taking into account differences in information
quality?
• What kinds of effects on the thyroidal system are genuinely
"adverse" effects? In what way and for what subpopulations are
they "adverse"?

Special luncheon and dinner presentations also will be delivered on

additional scientific topics:

• Sources of perchlorate in the environment

• Comparing environmental exposure to perchlorate and dietary
exposure to nitrates
• The scope, scale and causes of iodine deficiency in the United
States.

·4·

.. -•...... ------­
groundwater is in Massachusetts, near but outside and not associated with Camp Edwards at the
Massachusetts Military Reservation (MMR). Further, perchlorate contamination potentially
related to the use of fireworks has been found following water supply well sampling and testing
in several other locations around the state as well as in surface water at Tewksbury,
Massachusetts (Ebbert, 2004). The DEP is conducting a fireworks residue field test at the
University of Massachusetts Dartmouth Campus to be monitored with eight groundwater­
monitoring wells. Pre-display analytical results show perchlorate concentrations of non-detect to
36 ppb. The site has hosted displays for about ten years (Lelunert, 2004). The amount of
perchlorate available for groundwater contamination from fireworks depends upon how many
displays, the types of fireworks involved, amount of misfires, and the length of time period over
which displays were done in a single area. Misfires may contribute significant perchlorate to the
envirorunentalloading as well and their frequency although low, does vary. More testing for
perchlorate in groundwater at fireworks display locations in other states needs to be done.

4.4.8. Pyrotechnics - Safety or Hazard Flares

Perchlorate is one of the primary components found in percentage amounts in emergency and
signal flares. This application of pyrotechnics produces colored light as a signal. In safety or
hazard flares, strontium nitrate is combined in a mixture with an oxidizer and a chlorine source
(potassium perchlorate), along with various fuels. The available chlorine from the perchlorate
and the strontium combine to color the emitted light, bright red (Conkling, 1990). The
manufacturing sites of flares are known to have precipitated perchlorate releases into ground
water in California and releases are also possible in other locations where similar facilities are or
were situated. One study has been perfonned to attempt to measure the amount of perchlorate
that may be released from road safety flares under various conditions. These tests indicate that
the residue from fully burned flares may still contain a small amount of perchlorate and that
partially burned flares leached significant concentrations of perchlorate when placed in contact
with water (Silva, 2003). These results underscore the need for more study on the use of flares
and any potential envirorunental impacts from their use. Additionally, flares containing
perchlorate are also used in some cloud seeding operations.

4.4.9 Pyrotechnics - Matches

In some cases, pyrotechnics are utilized to produce heat. An example of this would be the safety
match. A safety match uses a blend of potassium chlorate and sulfur with a fuel and binder
(Conkling, 1990). Potassium perchlorate was/is used in the production common stick matches. If
an envirorunental concern existed associated with matches, it would likely be at the production
facilities. See Section 4.4.11 Uncertain Nautral and Man-Made Potential Sources of Perchlorate
regarding matches and clandestine methamphetamine lab waste.

4.4.10. Medical/Pharmaceutical

Historically, in medical practice, potassium perchlorate has been used in the treatment of thyroid
disorders to suppress the over production ofhonnones due to an overactive thyroid gland. The
thyroid produces honnones that act as regulators for certain functions and is necessary for nonnal
growth and development, especially during gestation and childhood. Iodine, acquired through the
diet, is an essential element for the production of these thyroid-produced honnones. Perchlorate
?-22
can readily substitute for the iodide chemically so that it can block the uptake of iodine by the
thyroid gland resulting in a reduction of these honnones with subsequent detrimental
physiological effects (Soldin et aI, 2001).

Currently, potassium perchlorate has been employed in medical procedures in three different
ways. First, it is used in the treatment of induced hypothyroidism or thyrotoxicosis resulting from
the primary treatment of tachyarrhythmia or ischemic heart disease by the iodine-containing drug
amiodarone. Second, potassium perchlorate is also used to limit the uptake of sodium
pertechnetate in the thyroid when the pertechnetate is administered in the course of brain and
blood pool imaging and placenta localization. Third, as a diagnostic agent, potassium perchlorate
has been used in the treatment of certain thyroid disorders. These include the inability of the
thyroid to nonnally assimilate iodine, Pendred's syndrome, thyrotoxicity due to radioactive
iodine exposure, and Hashimoto's thyroiditis. The potassium fonn of perchlorate appears to be
used exclusively for medicinal purposes over other salts of perchlorate probably due to lessened
physiological impacts of the potassium over other possible cations (CA DTSC, 2004).

The likelihood of medical perchlorate source release to the environment would appear to be
slight given that storage occurs in structures, amounts stored for medical purposes are small and
are in containers, and hospitals have waste disposal programs. Small spills or inappropriate
disposal may have occurred previously, but there is nothing to indicate this has necessarily
happened. More research into quantities and current/past disposal practices is needed.

4.4.11 Uncertain Natural and Man-Made Potential Sources of Perchlorate

The problem when investigating an emerging environmental contaminant is that new infonnation
continues to come to light, whether that be regarding past management practices, current uses,
locations of use, or newly suspected but uncertain sources. In the case of the latter, there is a
small but apparently growing list of suspected perchlorate sources. Confinnation and verification
testing has not necessarily been done in all cases and research in these areas is ongoing. A short
list of these sources would include lightning, cloud seeding operations, clandestine
methamphetamine lab wastes, and certain anti-corrosion cathodic protections systems. Whether
perchlorate is produced as a consequence of lightning striking a chlorinated water supply, as well
as the exact mechanism for this is being researched. Cloud seeding operations have used
potassium perchlorate as a component of some oftheir flare designs to produce nuclei for water
drop fonnation leading to precipitation. Whether this fonnulation is still in use is unknown
(Western Kansas Weather Modification Program). There is also the possibility that in some
clandestine methamphetamine labs, in the process to obtain red phosphorus from matches
containing perchlorate, a waste stream containing concentrated perchlorates as a byproduct may
be produced.

Evidence of perchlorate being produced (71 to 77!!glL) by at least one cathodic protection system
used to protect an elevated steel storage tank holding a municipal chlorinated water supply in
Levelland, Texas (Jackson et aI, Texas Tech University). Details of this particular occurrence as
well as experimental confinnation were presented in an article in the Journal of the American
Water Works Association (Jackson et aI, 2004). Results and conclusions from the study in the
AWWA article were: chloride and hypochlorite (OCr)/hypochlorous acid (HOCl) ions were
present due to the chloramination disinfection process, the anodes consisted of high-silicon cast­
?-23
Health and Environmental
Impacts
• Thyroid inhibitor (preferential uptake of
Perchlorate over iodide).
• Possible carcinogen according to EPA, not
directly but via hormonal disruption.
• Possible impacts in child development have
not been determined.
• Impacts to sensitive ecological receptors
such as amphibians are being researched.

Federal Facilities Program Meeting August 6, 200 I

and modeling predict a Colorado River perchlorate concentration of approximately
2 ppb may be achievable by the end of 2005.

5.3 Department of Defense Perchlorate Investment

The Department of Defense has played a leadership role in investing in perchlorate

science and technology. Over the last decade, DoD has invested a total of
approximately $59 million on perchlorate research. A majority of this expenditure
has occurred since 1997 when analytical detection capabilities allowed for the low
parts per billion level detection of perchlorate. The DoD investment of
approximately $8.5 million on human health and ecotoxicity studies has
contributed significantly to the development of the scientific understanding of
perchlorate needed by EPA and state regulators before perchlorate can be
regulated under environmental statutes. The Department's approximate $40
million treatment technology investment has improved the fundamental
understanding of the chemical, physical, and biological processes related to
perchlorate reduction across a wide range of hydrogeochemical conditions. In
addition, the Department has invested approximately $8 million in initiatives
designed to make military munitions items safer to handle and more
environmentally benign.

In continuance of DoD's leadership role in perchlorate science and technology,

DoD is funding a perchlorate isotopes forensics project being conducted by the
USGS, DOE's Oak Ridge National Laboratory (ORNL), and other investigators.
Using advanced analytical techniques that are capable of differentiating between
oxygen isotopes in man-made and natural perchlorate, it may be possible to assess
perchlorate detections and assign clean-up responsibilities.

To maximize the usefulness of the Department's perchlorate investment, DoD will

adopt an integrated investment strategy that will simultaneously consider
analytical detection, health effects, treatment technologies, and ecological effects.
Such an integrated approach will ensure that as the risks associated with
perchlorate exposure at environmentally-relevant concentrations are accurately
characterized and as regulatory actions on perchlorate are initiated, appropriate
risk management strategies and promising technologies will be available to both
public and private sector entities.

5.3.1 Human Health and Ecotoxicity

DoD has invested approximately $8 million in human health and ecotoxicity

studies to further the scientific understanding of the potential human health and
environmental effects associated with low-level exposure to perchlorate. Most of
these initiatives were conducted in full cooperation with EPA under the auspices
71
of the Interagency Perchlorate Steering Committee (IPSC), predecessor to the
rWG. 87 Research areas include:

Developmental and neurobehavioral studies

The development of state-of-the-art physiologically based pharmacokinetic
(PBPK) models
The effect of perchlorate on iodine-deficient laboratory animal populations
Whether borderline iodine deficient diets increase the susceptibility to
perchlorate-induced hypothyroidism
Perchlorate toxicity in metabolically-induced animals
Biotransport of perchlorate in soils
Lettuce uptake studies and
The effects of perchlorate on avian species, reptiles, amphibians and fish.

5.3.2 Remediation Technology

Early DoD investment in perchlorate science and technology can be linked to the
increased demand for, and decreased availability of, OB/OD facilities with the
capacity to treat large rocket motors. The demand for such OB/OD facilities
resulted from international arms control treaties and agreements that targeted the
destruction of strategic missile systems. At the same time that strategic missile
systems were being removed for demilitarization in compliance with international
agreements, however, domestic environmental regulations that sought to limit
OB/OD due to air quality concerns and the closure of military bases under BRAC
restricted the use and availability ofOB/OD facilities.

To comply with both international arms agreements and domestic regulations, the
Air Force began investigating the use ofbioremediation technologies to treat
perchlorate-containing propellant production waste streams in 1990. The
technologies that were identified and developed as a result of this initial
investment have served as the basis for subsequent investigations into the
biotreatment of perchlorate-contaminated water supplies.

SERDP is DoD's corporate environmental technology research and development

program. 88 SERDP, in full partnership with EPA and other organizations,
identifies, develops, and transitions environmental technologies that relate directly
to accomplishment of defense missions.

87 Department ofDefense Report to Congress: Department ofDefense Activities in the Interagency

Perchlorate Steering Committee. August 25 2004,
https://www.denix.osd.mil/denixiPublic/Library/Water/Perchlorate/Correspondence/IPSCReporttoCongres
s-25Aug04.pdf
88 Information on SERDP research projects andfunding opportunities can be obtained at
http://www.serdp.org/.
72
APPENDIX A - Charge to the National Academies' National Research
Council Committee to Assess the Health Implications of Perchlorate Ingestion

Perchlorate has been the focus of several recent government and scientific studies,
including an EPA draft risk assessment. These studies have raised concerns among
a number of Federal agencies regarding how to best characterize the potential risk
posed by chemicals that disrupt the function of the thyroid gland. There has been
agreement among the Agencies to forward a set of scientific questions associated
with our ability to understand the health implications of perchlorate exposure to
the National Academies' National Research Council for immediate and
accelerated review.

A crosscutting issue is verification that the key studies underlying the health
assessment are of the quality, reliability and relevance that are required to draw
conclusions about the health implications of exposure to low levels of perchlorate
in drinking water among sensitive subpopulations.

For each of the questions posed below, a response may be best represented by
either a point estimate or a range. Where specific numbers are lacking in the
scientific literature, please use best scientific judgment to determine what range is
scientifically defensible.

1. What is the current state-of-the-science or understanding regarding the

potential adverse effects due to disruption of thyroid function in humans and
other animals at various stages of life?
Multiple researchers have proposed a model that frames potential adverse
neurodevelopmental and neoplastic effects of perchlorate to be a
consequence of the perturbation of thyroid hormone regulation after
disruption of iodide uptake by the gland. Does the state-of-the-science
support this basic model?
./ What is your level of confidence in such a model?

Using best scientific judgment, at what level does the chronic inhibition of
iodide lead to adverse, not just adaptive, health effects in humans,
especially sensitive subpopulations? Please indicate your level of
confidence in each of these determinations.
./ Consider how the iodine-rich diet in the United States might
influence the degree to which adverse effects might be expected in
sensitive subpopulations.

2. Using best scientific judgment, what is the level where changes in thyroid
honnones can lead to adverse, not just adaptive, health effects in humans,

76
 especially sensitive subpopulations? Please indicate your level of confidence
in these determinations.

3. Evaluate the key animal studies available for understanding and assessing the
implications of perchlorate ingestion. Endpoints of concern should include
brain morphometry, behavioral changes, thyroid hormone changes, and thyroid
histopathology.
What is your level of confidence in extrapolating what the adverse changes
documented in animals that have ingested perchlorate may mean for
adverse effects in humans, especially sensitive subpopulations?
Specifically address the validity of models that extrapolate from studies of
brain morphometry in rats to adverse effects in human population,
especially sensitive subpopulations.

4. Based on your evaluation of the available animal and human studies, suggest
"uncertainty factors" that would provide an approximation of a safe lifetime
exposure for humans, especially sensitive subpopulations.

5. Would adverse effect other than those associated with iodide uptake inhibition
be expected as a result of ingesting low levels of perchlorate on a daily basis?

6. Based on the responses to the above questions:

Are the EPA findings consistent with the panel's findings?
Did EPA properly evaluate and consistently critique all the relevant
literature that supports, or fails to support, the conclusions in its risk
assessment? Did EPA choose the best available scientific studies for use in
supporting a health risk assessment?
If your review finds that any other key studies are appropriate but not
properly considered by EPA, please provide advice regarding how EPA
should use this information and modify their assessment.
Is there an alternative percent iodide uptake inhibition that would serve to
protect individuals at various life stages and thyroid status? EPA used the
lower limit on a 5 percent response for iodide uptake inhibition as a
surrogate for a No-Observed-Adverse-Effect-Level to be protective of
various life stages and thyroid status.
Is the EPA's use of the uncertainty factors consistent with your findings
when applied to the animal data and in human clinical or epidemiological
studies?

77

 INFORMATION PAPER

DAIM-ED
2 July 2003

SUB.IECT: Potential Perchlorate Contamination Emanating From Army Installations

PROBLEM:

The environmental community has targeted perchlorate, a chemical constituent used

extensively in rockets, missiles and military munitions, as a hazardous contaminant.

Perchlorate is not a regulated contaminant but the environmental regulatory and activist

community is insisting that the DoD and the Army address the 'contaminant' by

performing sampling and cleanup actions.

BACKGROUND:

• The DoD and NASA are the largest users of perchlorate. As ammonium perchlorate
(AP), it is used as the prime-oxidizing agent in the nation's missiles and rockets. AP
and potassium perchlorate (KP) are also used extensively in pyrotechnic formulations
for munitions items, such as simulators, obscurants, flares, fuzes, etc.
• Perchlorate has known health effects when ingested. Perchlorate competes with, and
inhibits iodine uptake in the thyroid. Iodine is essential for normal hormonal and
developmental processes. Of special concern are populations with underdeveloped
thyroids such as infants, fetuses, and people with compromised thyroid systems.
Pregnant and lactating mothers are also of concern because of their ability to pass
perchlorate to infants and fetuses during pregnancy and lactation. At issue is the level
at which perchlorate shows adverse health effects.
• Perchlorate salts have been shown to be extremely soluble and mobile in water and
pass quickly to groundwater where it remains in a stable form and can persist for
decades. Perchlorate releases have been reported in at least 29 states and are most
often associated with perchlorate manufacturing plants and military installations.
Large-scale production of perchlorate began in the 1940's, with widespread DoD use
beginning in the 1950's. Perchlorate has been found and is suspected at many Army
installations. Perchlorate releases at Army facilities are suspected to come from past
operations involving replacement pf perchlorate in rockets and missiles,
demilitarization of perchlorate containing items, from unburned perchlorate found in
'low-order' munitions, and from the use of simulators and pyrotechnics during training
operations.
• Perchlorate is currently unregulated. The EPA has drafted a perchlorate health risk
assessment that is under review by the National Academy of Sciences. The finalized
risk assessment report will lead to the development of a health-based standard that
will be used for the basis of cleanup actions. Some states and EPA regions have
issued health advisories in advance of these final standards.
• Despite the lack of a regulatory standard many environmental regulators and
community groups are insisting that assessments and cleanup of perchlorate
contamination begin now. Arguments for immediate cleanup actions are based on
perchlorate does not appear to pose an immediate threat to nearby animals. their food
chain. or sensitive ecosystems.

IV. ENDANGERMENT DETERMINATION

Actual or threatened releases of perchlorate from this Site present an ilIUJlinent

and substantial endangerment to public health, or welfare, or the en vironment.

V. PROPOSED ACTION

This removal action seeks to address the perchlorate contamination in

groundwater extracted at the Site. The removal action objectives are to remove
perchlorate contamination from extracted groundwater at the Site to prevent exposure to
drinking water users and further impacts to groundwater or surface waters.

A. Proposed Actions

The proposed removal aclion consists of the following activities:

Treatment of all groundwater that reaches the Site-specific perchlorate action

level of 14 jJ.gfL using ion exchange technology.

Preparation of a contingency plan for initiation of wellhead treatment or provision

of an alternative water supply in instances where percWorate concentrations are
approaching and may exceed the Site-specific action level of 14 jJ.gfL in a
domestic water supply well.

1. Treatment of Perchlorate-Impacted Groundwater

Perchlorate-impacted groundwater that is extracted at the Site will be treated with

ion exchange technology when concentrations reach 14 jJ.gIL. Ion exchange is a
reversible physical-chemical reaction wherein an ion from solution is exchanged for a
similarly charged ion attached to an immobile solid. During ion exchange, the
perchlorate in groundwater, which is a negativelycharged ion, is exchanged with an ion
provided in resin, typically chloride. The perchlorate then binds to the resin, leaving the
treated water uncontaminated.

The resins used for ion exchange for perchlorate treatment resemble small beads~
and typically consist of resins made from synthetic. inorganic, or natural polymeric
materials that contain ionic functional groups to which exchangeable ions are attached.
When the resin reaches an eqUilibrium concentration where no additional percWorate can
be extracted from the water, the resin is regenerated or disposed of.

An ion exchange system was installed at the MTS in April 2005 and has been
operating since that time. The system has consistently removed perchlorate to
concentrations below the detection limit of 2 jJ.gIL.
 Soldiers On Point for the Nation... On Point for the Environment
J
llij'!!

'N~~~~~~~~~~~~~~
What is Perchlorate?
IillhJ

• Perchlorate (CI04-) is both a naturally occurring and synthetic

anion that forms salts with ammonium, potassium, magnesium
and sodium.
• Perchlorate has known health effects when ingested:
- Inhibits normal hormonal and development processes by inhibiting the
uptake of iodine in the thyroid. Infants, fetuses, pregnant mothers and other
'sensitive' sub-populations are suspected to be particularly vulnerable.
• Perchlorate is persistent in the environment:
- Extremely soluble, stable, and mobile in water and can persist for many
decades in groundwater and surface water.
• The DoD is the largest user of perchlorate salts:
- As ammonium perchlorate (AP), it is the prime oxidizer in most solid
missile and rocket fuels.
- As potassium perchlorate (KP) and AP it is used in many pyrotechnic
formulations for simulators, obscurants, initiators, fuzes, etc.
- Production of AP and KP began in the 1940's with widespread DoD use
since the 1950's.

Malcolm Garg/DAIM-EDT. 703-601-1513 malcom.garg@hqda.army.mil 2 of 7 10/19/2003

 SUPERFUND AND FEDERAL FACILITY SITES WHERE ACTION HAS BEEN

TAKEN TO ADDRESS PERCHLORATE CONTAMINATION

ALABAMA

Redstone Army Arsenal- Huntsville, AL fNPL)

Established in 1941, Redstone Anny Arsenal is an active U.S. Anny facility occupying about
38,300 acres in Madison County, Alabama. Between 1942 and 1945, the Anny produced
conventional and chemical munitions for World War II, including perchlorate-based colored
smoke munitions. Subsequently, the Thiokol Chemical Corporation and the Rohm and Haas
Company began operations at Redstone in 1949 in support of the Anny, Navy, Air Force and
NASA aerospace programs. The Raytheon Company began solid propellant research and
development operations in the fonner Rohm and Haas area in 1974. The manufacture of solid
propellants at Redstone ceased in 1996 when Thiokol ceased operations at this National
Priorities List facility.

The maximum concentration of perchlorate detected to date in shallow groundwater is 19,000

ppb. A chlorinated solvent and perchlorate plume has migrated beyond the east boundary of the
facility; however, residents in the adjacent subdivisions utilize a public water supply and are not
at risk from the contamination. In 2000, EPA, the Alabama Department of Environmental
Management (ADEM) and Redstone agreed to shut down a groundwater treatment system for
chlorinated solvents that was inadvertently discharging untreated perchlorate to the Tennessee
River. Perchlorate has also been detected in soils beneath storage pads and in surface water
along Redstone's eastern boundary. Redstone plans to complete environmental media
characterization for perchlorate at the higher priority sites in Fiscal Year (FY) 2004 and conduct
perchlorate treatability studies in FY2004 - FY2005 in support of remedy selection.

CALIFORNIA

Aerojet General Corp. Superfund Site - Rancho Cordova, CA fNPL)

The Aerojet Superfund site is a 5,900 acre rocket manufacturing site fifteen miles east of
Sacramento, California. Soils and groundwater at the site are contaminated with volatile organic
compounds such as trichloroethylene (TCE) and rocket propulsion components including
perchlorate. In the early 1990's, detection of part-per-million levels of perchlorate in a drinking
water supply aquifer led EPA's Superfund team to request the country's first evaluation of
perchlorate's toxicity. The first large-scale perchlorate treatment process in the U.S. was
developed and implemented at the Aerojet site in 1998. This biological system treats more than
seven million gallons of contaminated groundwater each day and reduces blended perchlorate
concentrations from 2,500 ppb to less than 4 ppb. In the July, 2001 Record of Decision (ROD)
for the Aerojet site, EP A set an enforceable site-specific cleanup standard for perchlorate at
4 ppb l . EPA's August, 2002 Unilateral Administrative Orderrequires Aerojet General to design,
build and operate a groundwater extraction and treatment system to contain and clean up
groundwater contamination in the western portion of the Aerojet site. The order also requires
Aerojet to provide replacement water for wells lost due to contamination.

Edwards AFR, CA (NPL)

Edwards AFB is a 301,000 acre military base located in the Antelope Valley region in Southern
California. Edwards AFB was placed on the National Priorities List (NPL) in 1990 and entered
into a Federal Facility Agreement (FFA) with the U.S. EPA, the California Department of Toxic
Substances Control (DTSC) and the California Regional Water Quality Board (RWQCB) in
1992. Perchlorate contamination at Edwards AFB resulted from years of solid-fuel propellant
development and rocket testing. This solid propellant testing created several groundwater
plumes on Edwards AFB in Operable Units (OUs) 4, 5,6, 9 and 10. The maximum
concentration of perchlorate detected at Edwards AFB was 160,000 ppb in OU 5. An ion
exchange treatability study has been implemented at Site 285 in OU5. This treatability study
was initiated in May 2003 and is expected to run for two years with the hope that this study will
not only demonstrate the technology's effectiveness, but also achieve cleanup to levels safe to
human health and the environment. Since May 2003, 2.6 million gallons of groundwater have
been treated and 7lbs of perchlorate have been removed. This OU is currently in the Remedial
InvestigationlFeasibility Study phase with a Record of Decision (ROD) scheduled for 2008. The
Air Force is responsible for all costs associated with the investigation and cleanup of the
perchlorate.

Olin Flare Facility - Morgan Hill. CA

Perchlorate contamination over nearly four miles was first discovered by the Santa Clara Valley
Water District, but had not been confirmed as a single plume until January 2003. The source has
been traced to a flare manufacturing facility that had used perchlorate as one of the ingredients.
The Water District has a major outreach effort that has received extensive press and community
response. An extensive well testing program is underway for approximately 1,200 residential
wells in the area, one public water supply system well has been closed, and bottled water is being
supplied to nearly 400 households by the potentially responsible party (PRP), Olin, and the Santa
Clara Valley Water District. The Regional Water Quality Control board is overseeing cleanup
efforts by Olin Corporation.

Rialto-Colton Area. CA
In the Rialto-Colton area in San Bernadino, California, perchlorate has been detected in 20 water
supply wells at concentrations above the California action level of 4 ppb. The loss of these wells

I ROD was signed prior to the January, 2003 OSWER Error! Mllin Document Only.Slalus ofEPA 's Inlerim

Assessmenl Guidance for Perchlorale Memo that reaffirmed the Error! Main Document Only.provisional clean-up
level or action level range of 4-1 g ppb which was recommended in the 1999 ORO Interim Assessmenl Guidance for
Perch/orale.
 PERCHLORATE ISSUES
. ;~~t~i~~~~T

Perchlorate Cleanup

• The is no legal driver to do anything

• There is no standard Federal or state

• Scientific opinion says somewhere

between 1ppb and 200ppb is fully

protective of human health

• Permission must be received before

any action taken
5

Michael J. Oette I SFIM-AEC-TSO I (41014311-1828 (OSH 584) I mlchael.dette@us.army.mll 50128 111032R FEB2004
 PERCHLORATE ISSUES

-
i) . ~ ~~i~~~~~:~

Potential Sensitive

Subpopulations

Unborn children of women who are:

• Iodine deficient.
• Have subclinical hypothyroid
conditions (pregnancy rarely occurs
in frank hypothyroid mothers).
• Have normal iodide but low levels of
T3 and T4 due to increased
metabolism.
1

Michael J. Delle I SFIM-AEC·TSO 1(41014311-1828 (DSN 584)1 mlchael.delle@us.anny.mll 10128 111032R FEB2004
 PERCHLORATE ISSUES

. _;d;~~~ ?:/;~ ;~ \~~'~:;:~~?~:::~~I~ji:~ ;if3~<:i-:-~ ~'

Properties in Humans

• Moves through the body quickly

- Leaves the body with a half life of 5-8 hours

- Does not bioaccumulate

- Is not metabolized

• No adverse health effects from short-term

exposure
• Adverse health effects occur only if
exposure is chronic and concentration is
sufficiently high
- Thyroid effects at > 1mg/kg-day in rats
2

MIchael J. Dette' SFIM-AEC·TSO I (4101 43e·1626 (DSN 534)' mlchael.deltllQus.army.m11 2 of 28 111032R FEB2004
 HA
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of day,
• Nitrate herefo
..
mechanis direct
,
•
cODlparlsons Iy relevant
• Nitrate is found
especially green, Ie

these foods are consid

 vs.
E
•
e In ou ~

contri
• A single omDlo
10 to 1000 ~ ntial as

perchlorate at DWEL.

• lUI from the tota e hundreds

or thousands of time h1rthrough

ingestion ofperchlorat L&&~ng water.

 EPA

TERA2002 TERA2002
Ppossible

Study

Species human

LOAEL

(mg/kg-day) 0.01 I 4ft I

_15 I 0.02

~
TotalUF 300 10

RID (mg/kg-day) 0.00003 ,.,002 0.002

Confidence I Medium I Med/High

~ High
High

DWEL I 0.001 mg/L I 0.667 mg/L 0.067 mg/L I 0.067mg/L

 Legend: BRAC : : Base Realignment and Closure SW Cone = Surface Water Contamination

N (in BRAC Column) : : Site is not a BRAC Facility 5011 Contam = Soil Contamination

Y (in BRAC Column) : : Site is a BRAC Facility ppb = parts per billion

NPL =National Priorities List =

Y (in Soil Contam Column) Perchlorate has been detected in soil

N (In NPL Column) = Site is not on the NPL _:::: denotes EPA is not aware that perchlorate has been

=
F (in NPL Column) Site is on the Final NPL detected in that particular medium at that specific facility

=
OW Cone Drinking Water Concentration [ ] : : Data was obtained from DOD response to inquiries from Sens. Boxer &

GW Cone = Groundwater Concentration Feinstein

McGregor Naval Weapons Industrial Reserve Plant

~~
(NWIRP) ] McGregor N N 05/1998
Red River Army Depot] Texarkana y N - 7 417 160 11/1999
- -- -

345 - DOD

Camp Bullis 3 .5 - 424 - TCEQ

~~
TX I San Antonio N N 08/2001

3
UT Hill AFB Ogden N F [Y] 70 0511998

WA Carno Bonneville Vancouver Y N - 250 - - - - 2001

Y
880 (soil)

2500

Alliant Tech; Naval Ordnance, Allegheny Ballistics (SUbsoil)

wv Laboratory 2 Rocket Center N I F I - I 34900 I 400 1190 (sed) I 1999

()~weR~.~~1~<I_)f'~'£;I:USt'· -." _t:;i:c0~ «;;;%~~ ; ~. ~ . i.:' .~:; . ': ': . <-'\' '/ '.-" ~~&;,/":

t
• ' -,t

i;i~~:aoa~·~ J.~I ~i F=
~ IJet Propulsion Labora~!YJNASA) . _

CA Lawrence Natl Lab, DOE Experimental Site 300 (DOE)

CA ISanta Susana Field Lab, Rocketdyne Division (DOE)

--------:7
=
Sangamo Electric Dump/Crab Orchard National Wildlife

- --

tt~
IL IRefuge (USF&W - 001) Carterville 1200 I 0412000

NM ILos Alamos National Laboratory DOE Los Alamos

.---"
N 3 220

NM ISandia National Labs (DOE) A1bu uer ue N - - I - I

I Y

TX IPantex Plant (USDOE) Amarillo F - 340

'PRLV#i'TE#JJ!I'ES~' If';. ',,",

--------- ' " .'i"~ ,,~. "

2
AR IAerojet (Formerly Atlantic Research Corp.) lEast Camden 1 1 N I - I 640000 I 12500 1 y I
LAZ. IAerodyne Corp. - - lIempel...--=--------1 N I - I 18 - I - I I

Page 3
legend: =
BRAC Base Realignment and Closure SW Cone = Surface Water Contamination
N (in BRAC Column) = Site is not a BRAC Facility Soil Contam = Soil Contamination
=
Y (In BRAC Column) Site is a BRAC Facility ppb = parts per billion
NPL = National Priorities list Y (In Soli Contam Column) = Perchlorate has been detected in soil
=
N (in NPL Column) Site is not on the NPl - = denotes EPA is not aware that perchlorate has been
=
F (in NPL Column) Site is on the Final NPl detected in that particular medium at that specific facility
=
DW Cone Drinking water Concentration []= Data was obtained from DOD response to inquiries from Sens. Boxer &
=
GW Cone Groundwater Concentration Feinstein

Apache Powder Co. Benson F

Unidynamics/Phoenix Goodyear AirpOrt Goodyear F

---~
--------- 30

2 ~.---'
- - ­
Universal Propulsion Co., Inc.
White Tanks
Aerojet General Corp. - Rancho Cordova 2
Phoenix

Rancho Cord.
.----_..---­
N
N
F
-
260
- I -
640000
H
Alpha Explosives lincoln '- ~ ------- N - 67000
Casmalia Resources Casmalia F I - 58

ul.--_..
City of Rialto (B.F. Goodrich Aerspace & Defense + othe

~-~.----
CA PRPs) Rialto
CA ,bockheed Propulsion_(;.omp.arl}'jFormer) 2 _. - Redlands
-----
CA Olin Safety Flare Morgan Hill
CA San Fernando Valley Glendale .- - - .
.------- N
F
15
-
167
13
CA San Gabriel Valley .---~ F 159 2180
CA StrinQfellow Glen Avon ~ F - ~2000
CA UTC San Jose ~ N - 180000
CA Whittaker Bermite S. Clarita, Saugus .------- N 47
CA Whittaker Ordnance Hollister ~ N 810 I 810
IA Hills Iowa Perchlorate Site Hills . .---------- N 52 91
IA Unknown Ewart ~ N 29
. - f--.-­
IA Unknown Napier ~ N 11
Tri-Gounty Airport (Former Herington Army Airfield)
KS (FUDS) I
NN - 9
MO ICI Explosives USA Inc. Joplin _---·1 N - 107000
NE Nebraska Ordnance Plant 4 N I F - 24
NE Unknown lewiston ~--- I N - 5
NE Unknown Mead ~I N 24

Page 4
 EXECUTIVE SUMMARY

2 Perchlorate is one of several emerging contaminants that have generated a great deal of attention
3 in the past few years. It is highly soluble and mobile in water, and has contaminated human food
4 supplies as well as public drinking water. Perchlorate is a human health concern because it can
5 interfere with iodine uptake by the thyroid gland and result in decreased thyroid hormone
6 production.
7
8 Perchlorate contamination appears to be widespread. Recent studies have found perchlorate in
9 every media. Perchlorate is both naturally 0 ccurring and man-made. Naturally occurring
10 sources of perchlorate include Chilean nitrate -bearing caliches commonly exported for fertilizer,
II and man-made sources include fireworks, flares, and rocket propellant.
12
13 This document discusses methods that can b e used to reduce the concentration of perchlorate in
14 water and soil. It includes known techniques that can be chatracterized as physical processes, in -
15 situ biological processes, and ex -situ biological processes. Site evaluation and remedy selection
16 considerations are discussed, and potential stakeholder concerns are addressed. Case studies are
17 presented, and an extensive listing of references is given for additional research.

111
1 OVERVIEW OF REMEDIATION TECHNOLOGIES FOR PERCHLORATE

2 CONTAMINATION IN WATER AND SOIL

3 1. INTRODUCTION AND SCOPE

4 Perchlorate is both a naturally-occurring and man-made anion consisting of one chlorine atom
5 bonded to four oxygen atoms (C10 4} Highly soluble and mobile in water, perchlorate is
6 generally also very stable in the dissolved state. Most of the attention focused on perchlorate
7 contamination has concerned groundwater and surface -water. However, perchlorate can also
8 contaminate soil and vegetation and has entered the human and enviro nmental food chains. The
9 potential for perchlorate contamination in drinking water and food supplies is a human -health
10 concern because it can interfere with iodide uptake by the thyroid gland and, through this mode
11 of action, result in decreased thyroid h onnone production.
12
13 Perchlorate is an emerging contaminant that has garnered a great deal of attention over the past
14 decade. Emerging contaminants are a concern because these chemicals have demonstrated
15 toxicity, are found to be accumulating in the envir onment, or are being detected in humans or
16 other living organisms, and may have some newly -identified potential to cause adverse effects on
17 public health or the environment.
18
19 Perchlorate contamination is widespread. Two random studies found perchlorate at detectable
20 concentrations in every person tested. A multi -state study at Texas Tech University found
21 perchlorate in the breast milk of 20 women. (Assocated Press, Feb 24, 2005). Another study
22 conducted by the Division of Laboratory Sciences, National Cente r for Environmental Health,
23 CDC, included a random subsample consisting of 2,820 study participants (males and females)
24 aged 6 years and older and perchlorate was found in every person tested. (Blount et al." 2006)
25
26 Public awareness and concern regarding perchlorate have increased as a result from several
27 factors including:
28
29 • Perchlorate is an emerging contaminant with associated health uncertainties and
30 subsequent fear of the unknown.
31
32 • Initial environmental detections of perchlorate releases were associat ed with solid rocket
33 propellant which is a particularly sensational linkage.
34
35 • Drinking water supplies of a large number of Americans have been affected by
36 perchlorate releases.
37
38 • More recent studies have reported perchlorate contamination in the human foodc hain.
39
40 • Perchlorate has the potential to impact a sensitive sector of the general population (i.e.,
41 pregnant women including fetal development and young children).
42
43 • The building database of evidence that perchlorate contamination is widespread.
 ITRC--Overview 0/ Remediation Technologies/or Perchlorate
Contamination in Groundwater and Drinking Water May 2007

Aeojet Case Study

2 Aerojet Site Background

3 In the early 1950's Aerojet-General Corporation (Aerojet) came to eastern Sacramento County to
4 establish a site to develop, manufacture and test rocket propulsion systems. The site chosen
5 consisted of over 12,500 acres offormerly dredged land in a remote area approximately 16 miles
6 east of downtown Sacramento (See Figure 1). The gold -dredging activities by the Natomas
7 Company left the site in a condition that at the time was considered unsuitable for most types of
8 development '.
9
10
11
12
13
14
15
16

rl
ITRC·-Overview 0/ Remediation Technologies/or Perchlorate
Contamination in Groundwater and Drinking Water May 2007

tN

\_····_·--1 1-5
) I

\ .Y\ .,.....
\

\I

\\
~ ')
" \ - - - _ .__.j

Figure 1 . Aerojet-General
Corporation Facility LocaUon
 lTRC--Overview ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

1 The dredging removed soils and rock up to 100 feet below ground surface over a majority of the
2 Aerojet Site leaving large cobble piles in near parallel rows with little soil or vegetation. The
3 cobble piles are separated by fine -grained slickens ponds that represent the settling area of the
4 wash water from the dredging. Buffalo Creek represents the primary drainage feature across the
5 site, draining approximately 40% of the site. A majority of the property has no discernable
6 drainage and rainfall infi ltrates within the cobble piles 2. Buffalo Creek, together with Alder
7 Creek along the northern edge of the Aerojet site, direct stonnwater runoff to the American River
8 (See Figure 2).

Acrojel Case Stlld~' - Figllr~ 2

9
10
1I
12 Groundwater is found at less than 10 feet below ground surface at th e eastern edge of the
13 Aerojet site. Traveling west across the site the depth to groundwater increases to over 100 feet
14 by the time the western edge of the Aerojet site is reached. With the large amount of infiltration
15 on the Aerojet property and the occ urrence of bedrock at shallow depths to the east, groundwater
16 flow is radial at the site. At the east side of Aerojet there is flow to the north and south. The
17 flows gradually shift westerly so that at the west side at the Aerojet site the flow is to the west­
18 southwest.
19
20 The groundwater in the vicinity of the Aerojet site is of excellent quality and used extensively for
21 domestic, commercial, and industrial use. The groundwater has low concentrations of dissolved
22 salts and metals. The fresh groundwater extends to 600-900 feet below ground surface

r1
 ITRC--Overview ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

1 surrounding Aerojet in Pliocene to Pleistocene sediments. Below that there is a layer of

2 brackish water in Cretaceous marine sediments 2.
3
4 The land surrounding the Aerojet site was initially open space or was us ed for agricultural or
5 industrial purposes. Aerojet also leased adjacent properties for buffer purposes and for waste
6 treatment and disposal. Over time, property to the west and north of the Aerojet site was put to
7 residential use. In addition, 4000 acres of the initial 12,500 acres was leased by the McDonnell­
8 Douglas Corporation (MDC) to conduct rocket propulsion systems (See Figure 2). The MDC
9 area is known as the Inactive Rancho Cordova Test Site (IRCTS).

10

11 Aerojet conducted three general types of ind ustrial activities: solid rocket manufacturing and

12 testing; liquid rocket manufacturing and testing: and chemical manufacturing. The solid rocket

13 manufacturing activities consisted of development and manufacture of solid rocket propellant

14 (primarily ammonium perchlorate), which is loaded into rocket motor casings. Solid rocket

15 propellant was formulated, mixed, cast and cured. Solid rocket testing took place in isolated

16 areas where the solid rocket motor was strapped down. The rocket motor was fired to test

17 propellant and motor performance. As this document concerns the chemical perchlorate, liquid

18 rocket manufacturing and testing and chemical manufacturing will not be discussed further

19 except to point out that the pollutants released by those processes (i.e., n-nitrosodimethyamine,

20 hydrazine, PROWL®) commingled with the pollutants produced from the solid rocket

21 development in many instances. These commingled pollutants require the development of

22 multiple treatment technologies to cleanup the pollutants.

23

24 Solid rocket manufacturing and testing was done for the United States Military Services and

25 Space Agencies. Solid rocket products developed and manufactured by Aerojet consisted

26 primarily of jet-assisted take-off motors; tactical rockets such as Falcon, Hawk, Harpoon,

27 Sidewinder, Maverick, Bullpup, Genie, Sparrow, AMRAAM, Tartar and Navy Standard Missle;

28 ballistic missiles Minuteman I, II and III, Polaris, Midgetman, Peacekeeper, and space boosters;

29 and sounding rockets 3 .

30 Sources ofPerchlorate in Soil and Groundwater

31 During the solid rocket motor manufacturing processes large amounts of solvents, primarily
32 trichloroethylene (TCE), and copious amounts of water were used to ensure cleanliness of
33 casings and tooling to minimize explosion and fire hazard. Washdown of the manufacturing
34 facilities transferred ammonium perchlorate, and solvents to unlined ponds and low areas
35 surrounding the facilities. The water and pollutants migrated readily through the dredged
36 materials to impact soils and groundwater.
37
38 There are times when rocket propellant must be removed from the rocket motor casing. To do so
39 the rocket motor was taken to the hog out facility where the propellant is removed using a water
40 knife in order to avoid explosion hazards. The water containing ammonium perchlorate in both
41 solid and dissolved forms was discharged to unlined and lined ponds. Leakage from the ponds
42 and overflow from the hog out facility created the largest source of perchlorate in groundwater at
43 the Aerojet site with concentrations reaching over 100 mg/L. Two hog out facilities were used,
44 one by Aerojet on the 8,500 acre property and one by McDonnell-Douglas on the IRCTS.

rA
 ITRC--Overview ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

1
2 Perchlorate is also found at areas where waste ammonium perchlorate rocket propellant was
3 taken to be destroyed by burning and detonation. Waste propellant was stockpiled on pads in the
4 open bum/open detonation area on -site and off-site at Area 41 (Cavitt Ranch). Leaching from
5 the stockpiled areas and incomplete destruction of the waste materials led to rainf all moving the
6 perchlorate into the soil and groundwater at those two areas.
7
8 Another source of perchlorate in soils and groundwater is the Aerojet solid waste disposal sites.
9 Four landfills were established to receive waste construction materials, asbest os, and general
10 office waste. Groundwater downgradient from the landfills was found to contain perchlorate up
11 to 26 ~g!L. During characterization of the landfill waste materials, low concentrations of
12 perchlorate up to 1 mglkg were found throughout the waste materials. It is believed that the
13 perchlorate in the landfill came from disposal of the cardboard boxes that were used to ship
14 perchlorate to Aerojet.
15
16 There is also a source of perchlorate in groundwater on the IRCTS not associated with solid
17 rocket testing and manufacturing. A now defunct company, Kinnetech, tested down hole
18 explosives for use in the oil industry at the Alpha/IOC -1 complex on the lRCTS, which was not
19 used for testing solid rocket motors. Explosives containing perchlorate were pia ced below the
20 water table and detonated and the results analyzed.
21
22 Two areas where it might be expected to find perchlorate in soils and groundwater is the solid
23 rocket testing area and Magazine Area, where perchlorate and other explosive materials is st ored.
24 However, the Stage I Remedial Investigation conducted in the early 1990's and subsequent
25 groundwater monitoring has not found an indication that perchlorate is in the soils or
26 groundwater beneath the solid rocket testing area or the Magazine Area. At the solid rocket test
27 area it is believed that the ignition of the small rocket motors completely consumed the
28 perchlorate, the residual perchlorate was of such small quantities that it could not be measured,
29 or the residual perchlorate was carried away by the wind to be deposited downwind. At the
30 Magazine Area it is not surprising that perchlorate has not been found in the soils. Being
31 explosive, perchlorate is handled and stored very carefully. Containerized perchlorate is stored
32 in bunkers in the Magazine Area waiting processing into solid rocket propellant. Opening of the
33 containers does not occur until the containers are in the processing area.

34 Groundwater Contamination

35 The practices described above caused pollution of the groundwater with perc hlorate and solvents
36 at many locations on the Aerojet and IRCTS sites. In 1979, the California Central Valley
37 Regional Water Quality Control Board (Regional Water Board) issued Cleanup and Abatement
38 Orders to Aerojet due to the disposal practices and the finding of TCE in off-site private water
39 supply wells. At the time, perchlorate was not believed to be a contaminant of concern at the
40 concentrations being detected (around 1000 ~gIL), but was used as an indicator of waste and
41 waste migration.
42
43 The investigation into the sources of contamination and groundwater pollution led to Aerojet
44 being placed on the Superfund list in 1982 and the development by Aerojet of interim

r ..
 ITRC--Overview of Remediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

I groundwater extraction and treatment systems (GETs). The GETs were designed to minimize
2 the flux ofVOCs off site. The GETs were installed from 1982 -1985 in Sectors A, B, D, E and F
3 on the Aerojet property (see Figure 2). The GET systems utilized air stripping to remove VOCs
4 and solar ponds to remove NDMA, where needed. The treated water from GETs D, E and F was
5 recharged back to the groundwater via groundwater recharge wells downgradient from the
6 extraction system. Those GETs also intercepted perchlorate and the perchlorate was recharged
7 back to the groundwater, as the perchlorate was no t removed by the treatment systems. Thus, the
8 plume of perchlorate was allowed to continue its migration off -site. The recharge water
9 contained up to 8 000 !J.glL perchlorate at GETs E and F.
10
11 In December 1995, USEPA confinned its provisional reference dos e of perchlorate, which when
12 translated into a drinking water value, produced a range of 4 to 18 !J.glL. Monitoring of
13 groundwater conducted at the property boundary by Aerojet at the time showed concentrations of
14 perchlorate at up to 8000 !J.glL at the prope tty boundary. The Practical Quanitation Level (PQL)
15 was 400 J.1g1L. Aerojet was requested by the Regional Water Board to collect samples from
16 downgradient water supply wells and analyze the samples for perchlorate. All samples came
17 back with no reportable concentrations of perchlorate. However, when pressed, Aerojet stated
18 that several water supply wells had detectable concentrations of perchlorate estimated to be in
19 the 100-200 !J.gll range. Aerojet was issued a Cleanup and Abatement Order in October 199 6
20 requiring the development and application of treatment technologies to remove perchlorate from
21 the GETs effluent. Aerojet's development of the fluidized bed reactor in response to this Order
22 is discussed below in the perchlorate treatment section.
23
24 The initial detections of perchlorate led to the closing of two public water supply wells. Through
25 efforts by the Regional Water Boards contract laboratory, and soon after the California
26 Department of Toxic Substances Control's Hazardous Materials Laboratory the PQL for
27 perchlorate was initially lowered to 32 J.1g1L and then to 4 !J.glL in the first part of 1997. The
28 lowered PQL revealed that an additional seven additional water supply wells had detections of
29 perchlorate greater than 4 J.1g1L. Wells were turned off, new wells and pipelines were
30 constructed to bring water supplies to the areas where wells were closed. See Figure 3 depicting
31 the perchlorate plume.
32
 ITRC--Overview ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

Acrojct Case Stud)' - Fi~lIr(.· 3

I
2
3
4 Subsequently, Aerojet was directed to develop a remedial investigation and feasibility study
5 (RVFS) for the plume of pollutants, including perchlorate, which had migrated past their
6 property boundary to the west where the impacted water supply wells are located. The area is
7 designated the Western Groundwater Operable Unit (WGOU). See Figure 4. Aerojet completed
8 the RI/FS for the WGOU in 2000, with USEPA issuing a Record of Decision in 2001. The
9 remedy specified in the Record of Decision included groundwater pump and treat at the leading
10 edge of the plume and the property boundary, and long term and short term alternate water
II supply plans to replace water supplies that are taken out of service in the future due to the
12 pollution. Cleanup values specified include perchlorate at 4 Jlg/I, the lower end of the risk range
13 at the time of the Record of Decis ion. Aerojet is in the process of implementation of the remedy
14 and conducting treatability studies to look at alternate ways of addressing the perchlorate
15 pollution in-situ and ex-situ, as discussed further below. At the same time, McDonnell-Douglas
16 and Aerojet were required to address the off-site migration of perchlorate emanating from the
17 IRCTS.
18

r'l
 /TRC--Overview ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

Aerojet Case StUdy - figure 4

..

tN

2 Treatment of Extracted GroW1dwater

3 Initial Studies on Perchlorate Reduction

4 In December 1995, under request by the Regional Water Board, Aerojet provided in fonnation on
5 results of bench-scale and pilot studies perfonned to detennine methods to treat wastewater
6 containing perchlorate. Aerojet had been studying the removal of perchlorate from wastewater
7 generated from its hog out facility and for application to their GET facilities. Aerojet worked
8 with EARTH TECH, Inc. to evaluate the feasibility of treating perchlorate -impacted
9 groundwater at the Aerojet site. In their initial evaluation, EARTH TECH detennined that
10 biological and chemical reduction were iden tified as potentially viable treatment process based
l i o n those processes ability to treat similar oxygen containing compounds such as nitrate.
12
13 EARTH TECH performed laboratory treatability studies on both biological and chemical
14 reduction of perchlorate. Biological reduction was evaluated for both carbon/fluidized bed
15 reactor (FBR) developed by Envirex, Inc. and a standard fixed film (FF) using plastic media
16 support. Water from the effluent of GET F was amended with an organic substrate, ethanol or
17 acetate, and nutrients (nitrogen and phosphorous) prior to being fed into the FBR and FF
18 treatment systems. The feed source to supply the biological mass was the return activated sludge
19 from the City of Grand Rapids Wastewater Treatment Plant. Flow rates of370 ml/min and 98
20 miVmin were TW1 through the FBR and FF treatment systems, respectively. Ethanol was chosen

rQ
 ITRC--Overview ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

1 as the carbon source due the potential cost -effectiveness compared to the use of acetate. Influent
2 concentrations of perchlorate were 7000 to 9000 IlgiL4 .
3
4 The results of the treatability studies showed that both the FBR and FF systems were capable of
5 reducing perchlorate. The data showed that perchlorate reduction occurred under anaerobic
6 conditions and slightly lowered the pH from 7.6 to 6.8. Under optium operating conditions the
7 loading rates of perchlorate to the treatment systems were 0.11 grams perchlorate/liter/day for the
8 FF system and 0.7 grams perchlorate/liter/day for the FBR system using the same ethanol feed
9 concentration of 17.5 mglL. The testing also showed that the FBR system appeared to be more
10 resilient and recovered more quickly from system upsets than did the FF system 4.
II
12 In addition to biological reduction, jar tests were used to detennine the viability of chemical
13 reduction of perchlorate. The reducing agents sodium sulfite, sodium bisulfite and sodium
14 thiosulfate were added at concentrations from 10 to 1,000 grams per liter. The conclusions from
15 the test were that even at the highest dosages of reducing agents, chemical reduction was
16 ineffective in reducing perchlorate under nonnal conditions 4.

17 Pilot -Testing Biological Reduction

18 In 1996, based on the results of the laboratory -testing showing that there was a potential effective
19 treatment for the removal of perchlorate, the Region al Water Board directed Aerojet to perfonn
20 an on-site pilot-study. Aerojet initially developed an on -site demonstration of the GAC/FBR at
21 the GET F facility. An Envirex GAC/FBR capable of handling 30 gpm was supplied with water
22 from the air stripper at GET F. The reactor was 20 inches in diameter and 15 feet tall. The
23 carbon source for the testing was ethanol and nitrogen and phosphorous were also added to
24 assure sufficient nutrients were available for bacteria growth. A dual media filter was added to
25 the pilot system to handle the waste biosolids and a frac tank to handle the backwash water from
26 the filters. Return activated sludge from the Sacramento Regional Wastewater Treatment
27 Facility was added to the FBR as the source of bacteria 5.
28
29 Aerojet supplied the results of the pilot testing in February 1997. Those results showed that the
30 GAC/FBR pilot system achieved good removal of perchlorate with effiuent concentrations of
31 perchlorate below the PQL at the time of 400 Jlg/L at a hydraulic loading rate of 15 gpm and
32 influent concentrations of 6000 to 8500 Jlg/L perchlorate (50 pounds of perchlorate per day per
33 1,000 cubic feet of bed volume). Ethanol feed rates were high initially at 80 mglL and gradually
34 reduced until there was no residual ethanol or detectable concentrations of perchlorate. Besides
35 occasional problems with equipment such as level sensors and the ethanol feed system, several
36 conditions arose that required adjustments to the system. At one point during steady state
37 conditions there was rapid fluidized bed growth associated with the buildup of biological
38 material. This caused carryover of the granular activated carbon into the fluidized bed recycle
39 system and plugging of the recycle line. This problem was rectified by controlling the fluidized
40 bed height by periodically recirculating a portion of the top of the bed through a pump that
41 sheared off the biomass from the granular carbon, allowing the carbon to settle to the bottom and
42 the lighter biomass to wash from the system. Later it w as found that the bed height control pump
43 tended to grind the carbon into fine particles that allowed the carbon to be washed away with the
44 biomass. Granular activated carbon was periodically added to the system to rectify this problem.
45 A different bed height control system would be necessary on the full-scale system 6 •

ro
 ITRC--Ollerview ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

1
2 The pilot study showed that factors effecting perfonnance of the FBR treatment system included:
3
4 • Sufficient ethanol is required to accomplish the reduction of perchlorate. During the
5 study it was detennined that approximately 3.6 parts of ethanol are required for each part
6 of perchlorate.
7
8 • Dissolved oxygen concentrations affect perchlorate removal. When concentrations of
9 dissolved oxygen exceeded 0.1 to 0.2 mg/l the removal of perchlorate diminished.
10
11 • An important factor in the removal of perchlorate is the organic loading rate. High
12 organic loading rates caused a rapid fluidized bed growth that resulted in bed height
13 control problems. This could be potentially overcome with a modified bed height control
14 system.

15 Implementation of an FBR System at GET ElF

16 Based on the positive results of the bench -scale and pilot studies Aerojet was directed in 1996 to
17 develop an Engineering Evaluation/Cost Analysis (EE/CA) for adding perchlorate treatment t 0
18 the GET E and GET F facilities. Aerojet initially proposed a treatment system at GET F that was
19 later modified to a single treatment system that combined GET E and GET F (GET ElF). The
20 GET F system would be sized to handle 1500 gallons per minute of co mbined flow utilized
21 FBRs with GAC as the support media for removal of perchlorate, ultraviolet light with hydrogen
22 peroxide to remove NDMA and most of the VOCs and air stripping to remove the remainder of
23 the VOCs. The treated water would continue to be recharged to the groundwater to maintain the
24 hydraulic barrier to help control contaminant plume migration.
25
26 The initial proposed full-scale treatment system for perchlorate at GET ElF consisted of an FBR
27 system to remove perchlorate at concentrations of 7 to 10 mg/L, followed by filtration for
28 removal of waste biomass and disinfection for pathogen removal prior to recharge into
29 groundwater. Disinfection was designed to remove pathogens associated with the activated
30 sludge used to provide the bacteria for biological reduction. Phosphorous and nitrogen would be
31 added, as groundwater source does not generally contain sufficient concentrations of these
32 nutrients for maintenance of a viable biomass. As the treated water would be sent to the
33 UV/peroxide treatment system for removal of NDMA and VOCs, the water leaving the FBRs
34 would pass through a filter screening system to remove of residual waste biomass. The filter
35 system consists of continuous backwash sand filters, backwashed with final effluent from the
36 FBR, system with the backwash discharged to a holding tank to settle out the biomass, which is
37 then trucked to the sanitary sewer. The effluent from the filtering process would then be
38 disinfected using a UV disinfection process to remove E. coli that were found to be present
39 during the initial startup phases of the pilot study. To eliminate the need for the disinfection
40 system, Aerojet used biomass from a wastewater system at a jam manufacturer to provide the
41 initial biomass for the system. See Figure 5 for a schematic of the treatment system. Table 1 has
42 the full-scale basis of design for GET F, later expanded to include GET E, estimated capital
43 costs, and estimated annual operation and maintenance costs 7.
44

r '0
 ITRC--Overview ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

fl~~---,

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2
3 During the design process EARTH TECH evaluat ed whether or not the use of silica sand media
4 in place of GAC was preferred, whether methanol should be used as the organic substrate instead
5 of denatured ethanol, and whether or not to place the air stripping process behind the perchlorate
6 FBRs. Through short-tenn pilot studies it was determined that GAC would be used as the media
7 to support bio-growth as it appeared to provide a faster startup, better perfonnance and quicker
8 recovery under process upset conditions, and appeared to provide a lower perchlorate

r 11
 ITRC--Overview 0/ Remediation Technologies/or Perchlorate
Contamination in Groundwater and Drinking Water May 2007

1 concentration in the effluent. These differences were believed to be due to the GAC had a
2 rougher surface and could support a greater biomass concentration. The pilot studies also
3 showed that methanol-fed FBRs were slower to startup and did not prov ide as good of
4 perfonnance as the ethanol-fed FBRs, and therefore ethanol was maintained as the organic
5 substrate. It was decided to place the air strippers behind the FBRs so that there would be a
6 lower dissolved oxygen concentration entering the FBRs, t hereby reducing the ethanol and
7 nutrient needs. In addition, switching the order of treatment processes would reduce the biomass
8 production and subsequent disposal costs and potentially allow for increased flow rates through
9 the FBRs that would accommodate future increased flows to the plant 8.
10
II During 1997 and 1998, Aerojet designed and built the GET ElF treatment system. The design
12 was modified to include GET E and the hydraulic capacity increased to 3,600 gpm, with four
13 Envirogen FBRs each able to proces s 900 gpm. Sufficient space and infrastructure was provided
14 to allow the GET ElF treatment system to be expanded to 7,200 gpm if needed. Each of the
15 FBRs is 14 feet in diameter and 21 feet tall and filled with 40,000 pounds of GAC. The recycle
16 rate is 900 gpm with a forward flow rate of 900 gpm, giving a total flow rate through each FBR
17 of 1,800 gpm. The FBRs are operated in an upflow mode, fluidizing the GAC and providing a
18 large surface area for attachment of the biomass. Final effluent from the pi ant would be passed
19 through bag filters to remove any residual solids prior to recharge to groundwater. The plant
20 commenced operation in December 1998 processin? only the flow from the GET F extraction
21 wells and utilizing only two FBRs, FBRI and FBR2 .
22
23 During early operation of the GET ElF facility, Aerojet had difficulty in controlling the bed
24 height on FBRI. Both FBRI and FBR2 were both seeded with the same initial biomass and
25 approximately the same volume. The only difference was that FBRI received most of the
26 biosolids that had settled to the bottom of the seed tank. Even with the difficulty in controlling
27 bed height, non-detectable concentrations of perchlorate were in the effluent from the FBRs
28 (PQL of 4 j.1g/L). Aerojet had the biomass of the two reactors studied and the conclusion was
29 that a population of filamentous bacteria, thiotrhrix ramose, a sulfur bacteria, had developed
30 primarily in the bottom of the FBR where the reduced sulfur from the bioreactor recycle was
31 mixing with dissolved oxygen from the influent groundwater. The bed height limiters at the top
32 of the FBRs were not able to shear the filamentous bacteria from the GAC. The growth of the
33 bed height increased uncontrolled 9 .
34
35 Aerojet commissioned Harding Lawson Associates and Enviroge n to develop and implement
36 possible control strategies for the bed height. Two control strategies were developed and tested.
37 The first was to minimize influent dissolved oxygen concentrations, as most filamentous bacteria
38 grow under aerobic conditions and use dissolved oxygen as an electron receptor. The second
39 was to minimize the reduced sulfur concentration as it combines with the dissolved oxygen in the
40 bottom of the reactors creating an environment that favors filamentous bacteria. The studies
41 showed that reducing the dissolved oxygen concentration lowered the filamentous bacteria
42 growth and the resulting bed height. The studies also showed that the concentrations of
43 filamentous bacteria were much greater in FBRl than FBR2. Based on that informatio n Aerojet
44 killed the bacteria population in FBRl and reseeded it using biomass from FBR2. At the same
45 time seeding FBRs 3 and 4 to allow the flow from the GET E extraction wells to be added to the
46 treatment facility. The results of this modification wer e that the bed height in all four FBRs rose

r 1'1
 /TRC--Overview ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

I to approximately 12-14.5 and stabilized negating the need to make changes in attempt to reduce
2 dissolved oxygen or reduced sulfur 9.
3
4 Over subsequent years, the GET ElF facility was modified to remove the nutrien t addition
5 system as it was shown that there were sufficient concentrations of micronutrients to achieve
6 sufficient biomass growth. In addition, with the issuance of the Record of Decision for the
7 Western Groundwater Operable Unit and subsequent enforceme nt documents, GET ElF was
8 modified to allow the discharge of the effluent to surface waters under an NPDES permit that
9 would allow the water to be taken out downstream of the discharge for reuse within the
10 groundwater basin.
II
12 The remedy under the Record of Decision increased the flow that would be treated at the GET
13 ElF facility. Aerojet performed a pilot test on one FBR that showed that each FBR could process
14 up to 1500 gpm and still meet the effluent limitation of 4 I!g/L. Some piping and additional
15 VOC and NDMA treatment capacity changes were made to bring the rated capacity of the GET
16 ElF plant to 6000 gpm. Also, a clarifier was added to enhance settling of biomass in the
17 backwash tank and reduce the concentrations of suspended solids in order to meet effluent
18 limitations contained in the NPDES permit. To date, the GET ElF facility is in substantial
19 compliance with the effluent limitation of 4 Jlg/L.
20
21 Capitol costs and operating costs for the GET ElF facility are found on Table 1.

22 Ion Exchange Treatment of Perchlorate at GET Systems

23 More recently, Aerojet has also employed ion exchange resin treatment systems at several GET
24 facilities for the removal of perchlorate from extracted groundwater. Ion exchange systems have
25 been constructed on-site at GET B and GET D, and off-site at GET H, GET J, and GET K. At
26 GET B and GET D perchlorate concentrations in the influent were relatively low at 150 - 250
27 Jlg/L. Flow at the facilities is currently 1500 gpm at GET Band 1000 gpm at GET D. Given the
28 relatively low concentrations and low flow rates at these two GETs, and the evaluation in
29 forthcoming operable unit feasibility studies of the GETs, Aerojet determined that it was more
30 cost-effective to use ion exchange instead of the FBR technology which has a relative ly high
31 capital cost. The off-site GET systems had much lower concentrations of perchlorate but higher
32 flows than GETs Band D. Not only did the reduced capital cost for ion exchange come into the
33 decision on the off-site GETs, but the operation and main tenance costs (primarily replacing spent
34 resin) was comparative to the FBR technology. In addition, the off -site treatment systems are
35 located in communities adjacent to residences and commercial facilities, making the FBRs less
36 attractive given the need to store ethanol and the potential for the generation of nuisance odors.
37
38 At its ion exchange facilities Aerojet has used has used the following IX resins to treat
39 perchlorate-impacted water:
40
41 • USFilterA-284
42 • US-Filter K-9708
43 • Rohm & Haas A-530E
44 • Rohm & Haas PWA-2

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 ITRC--Overview ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

1
2 Each resin has different perchlorate adsorption capacities with A -284 having the lowest and
3 PWA-2 has the highest capacities. Aerojet has found that fine «S micron) particulate matter in
4 the influent water could cause ion exchange plugging problem s. Depending on the extent of this
S problem, Aerojet selects the ion exchange media based on time for breakthrough of perchlorate.
6 For example, if Aerojet was experiencing plugging quickly, Aerojet would A -284 because the
7 perchlorate adsorption capacity is low, resulting in the shortest run time before breakthrough. If
8 the PWA-2 was utilized at a system with high fine particulate matter, a portion of the PWA -2
9 would be wasted as the resin would need to be changed due to clogging instead of due to resin
10 saturation with perchlorate. Aerojet tries to match the run time to the estimated time that
11 clogging would occur. The clogging can be a problem even with bag filters on the influent. This
12 is particularly true with the ion exchange units at GET B.
13
14 The other concern with ion exchange is disposal of the spent resin. Since Aerojet is a Superfund
15 site, Aerojet must dispose of its material at CERCLA -approved facilities. Due to future liability
16 concerns associated with the leachability of perchlorate, Aeroj e t has decided to either dispose all
17 perchlorate impacted waste material in a Class I landfill or incinerate the waste. Aerojet prefers
18 to incinerate the waste; however, there are limited options. There is a limited number of
19 incineration facilities that are CERCLA-approved. Two such facilities are the Systech
20 Environmental's cement kiln facility in Fredonia, Kansas and Clean Harbor's Aragonite facility
21 in Utah lO •

22 Biodegradation ofPerchlorate in Groundwater

23 Starting in 1998 Aerojet has conducted several treatability studies looking at in situ
24 bioremediation of perchlorate in groundwater using various extraction and electron donor
2S delivery schemes and electron donors. Usually these treatability studies attempted to address the
26 biodegradation of TCE at the same time since in nearly all cases where there is perchlorate in the
27 groundwater there is also TCE.
28
29 The first treatability study conducted by Aerojet took place in late 1998. This first study was a
30 laboratory study designed to (1) assess whether or not the indigenous microorganisms could be
31 stimulated to anaerobically biodegrade perchlorate to chloride and water, and (2) evaluate
32 whether perchlorate and TCE could jointly be biodegraded. The study showed that the
33 indigenous microorganisms could rapidly biodegrade perchlorate in microcosms amended with a
34 variety of carbon substrates/electron donors including ethanol, molasses and liquefied food
3S waste. No lag or acclimation period was observed before on -set of the degradation activity with
36 calculated half-lives of 1.2 to 1.8 days. The second part of the study demonstrated that molasses
37 and liquefied food waste could biodegrade perchlorate to less than the Action Level (at the time
38 18 IlglL). However, TCE was not degraded as well as perchlorate. The best results for TCE
39 occurred with the addition of food waste and bioaugmentation with the natural dehalogenating
40 microbial inoculum referred to as KB _Ill .
41
42 In February 2000 Aerojet and used the positive results of the laboratory study to propose a field
43 demonstration pilot test of in situ bioremediation of perchlorate and TCE in groundwater. The
44 objectives of the pilot study were to (I) confrrm the performance of enhanced in situ
45 bioremediation of perchlorate-impacted groundwater on a field scale through elec tron donor

r IA
 ITRC--Overvif?W ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

1 addition, (2) evaluate TCE dechlorination through electron donor, (3) evaluate TCE
2 dechlorination through bioaugmentation with KB -I, (3) identify and optimize design and
3 operational factors that influence the perfonnance of field -scale bioremediation systems, and (4)
4 assess the ability and costs for full-scale use of the system. The pilot test took place at Area 20
5 where groundwater is 30 to 40 feet below ground surface and contains approximately 15 mg/L
6 perchlorate and 2 mg/L TCE. The pilot te st consisted of a closed loop system where
7 groundwater was extracted, amended with electron donors and KB -1 and recharged 65 feet
8 upgradient back to the same aquifer via a second well. See Figure 6 for the system layout and
9 cross-section 12.
10
AcroJct ('ase Study - I'igurr (,

JRCTS J)i1ot Stud~' l.a~·out

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II
12 The pilot test at Area last for 280 days from mid-July 2000 until mid-April 2001. The extraction
13 well operated at 5 gpm during the test. The initial electron donor was calcium magnesium
14 acetate (CMA), which was followed by sodium acetate and subsequently sodium la ctate. CMA
15 acetate was used due to its relative cost, availability and accepted use as a commercial product
16 and sodium acetate was used when CMA was not available. Initial concentrations of CMA
17 and/or sodium acetate were 50 mg/L on a time weighed average in four pulses per day.
18 Concentrations of acetate in the extraction well were non -detect showing that the acetate was
19 being consumed over the 65 -foot distance. Acetate was being effective in reducing perchlorate

r I~
 ITRC--Overview ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

1 but not effective on reducing TCE, so at day 64 the there was a switch to sodium lactate as the
2 electron donor 13.
3
4 Initial ORP and dissolved oxygen concentrations were 153 to 162 mV and 4.0 to 4.8 mglL,
5 respectively. During the acetate addition phase the ORP dropped to around -50 mV with
6 significant perchlorate reduction (13 mg/L to 0.43 mg/L in the first 15 feet during the first 7 days
7 of the test, and to 0.004 mg/L 35 feet away from the extraction well by day 63). The switch to
8 sodium lactate caused the ORP to be reduced to -100 mY. Similar reductions in perchlorate
9 occurred, however the dechlorination of TCE was slow with TCE dechlorination half -life within
10 the treatment area of up to 335 days. Therefore, bioaugmentation with KB -1 was initiated on
11 day 157. Positive results were immediate and the concentrations of TCE were reduced to less
12 than 5 Ilg/L within 35 days, resulting in an estimated half-life of 6 days 13 h.
13
14 Nitrate concentrations declined during the test from 5.5 mg/L to less than I mg/L. Sulfate
15 concentrations, initially around 11 mg/l remained stable during the acetate portion of the pilot
16 test indicating the perchlorate bioremediation can occur without stimulating sulfate reduction.
17 Sulfate reduction was not wanted as it would increase the demand for electron donor, develop
18 more strongly reducing redox potential that could result in mobilization of metals, and sulfide
19 reduction causes the production of sulfides that would cause the water to have an unpleasant
20 odor. The addition of lactate promoted sulfate reduction as shown by t he concentrations of
21 sulfate dropping to less than 0.5 mg/L. Other changes in groundwater quality that occurred
22 during the test were the increase in concentrations of dissolved iron and manganese above their
23 respective secondary drinking water standards 0000 Ilg/L and 50 Ilg/L 13.
24
25 The conclusions of the test were that adding acetate or lactate could readily biodegrade
26 perchlorate in situ to less than 4 Ilg/L without a significant acclimation period. Acetate was
27 preferred since it did not promote strongly r educing or anaerobic conditions, did not stimulate
28 sulfate reduction, and had little impact on secondary drinking water parameters. In addition, TCE
29 could be dechlorinated in situ through the addition oflactate and KB -I, however, not without the
30 mobilization of iron and manganese h. One system maintenance issue of concern was the
31 clogging by biomass of the well screen and delivery lines. Initial swabbing and redevelopment
32 of the well screen and reducing the frequency of electron donor helped control the microbial
33 biofouling.
34
35 Aerojet followed on the success of the Area 20 with several more in -situ pilot tests on the
36 Aerojet main site and the IRCTS. Those projects were designed to look at different well
37 configurations to create biological reduction zones in the aquifer, look at a variety of electron
38 donors, and evaluate mechanisms to reduce the impacts on secondary water quality parameters.
39 A summary of those projects is as follows:
40
41 • Pilot Test ofIn Situ Bioremediation to Treat Perchlorate in GET D Recha rge Water. In
42 2001 Aerojet conducted a test on a recharge well well in the GET D, whose effluent
43 contained perchlorate at concentrations near 200 Ilg/L. The goal was to add an electron
44 donor to the effluent prior to recharging the water into the aquifer and establish a
45 biological reduction zone in which the perchorate would be reduced. If successful,
46 Aerojet would not need to construct an aboveground treatment facility to remove

r II:
 ITRC--Overview ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

1 perchlorate at GET D. The test utilized acetate and ethanol as the electro n donor and it
2 was shown that in situ biodegradation of perchlorate occurred within 25 -75 feet of the
3 recharge wells. Perchlorate was reduced to less than 4 IlgIL and the half -life was
4 estimated at 4-5 hours. Iron and manganese were mobilized, but sulfate reduction did not
5 occur. The study did not last long enough to determine if/when the iron/manganese
6 concentrations were reduced to concentrations that were not a concern. Biofouling of the
7 recharge well was controlled with chlorine dioxide addition that prevented growth of the
8 biomass within, or immediately adjacent to the well. See Figure 7 for a layout of the
9 system 14.
10
Ael'ojet Case Study· Figure 7
CET [) PHol Study LU~'()ut

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11
12 • Pilot Test for lnsitu Bioremediation ofPerchlorate and Trichloroethene in Groundwater
13 Using and Active Biobarrier. Also during 2001, the United States Department of
14 Defense Strategic Environmental Research and Development Program (SERDP) and
15 Aerojet conducted a pilot test at the Area 20 site discussed above. The goal of the project
16 was to demonstrate that an active biobarrier approa ch would work for plume migration
17 control and treat perchlorate and TCE. The pilot system used two extraction wells 400
18 feet apart with a recharge well in the middle, all aligned perpendicular to the direction of
19 groundwater flow. In this manner, ground water would be captured across the plume and
20 bioremediation cell established also across the plume. See Figure 8. Groundwater was
21 extracted at 10 gpm from each extraction well, amended with ethanol and recharged

r 1'7
 ITRC-·Overview 0/ Remediation Technologies/or Perchlorate
Contamination in Groundwater and Drinking Water May 2007

1 through the recharge well. Chlorine dioxi de was used to control biofouling. The results
2 of the 72-day pilot test showed that perchlorate degradation was initiated without a
3 significant acclimation period with concentrations decreasing from greater than 8,000
4 ~glL to less than 4 ~glL within 35 feet of the recharge well resulting in estimated half­
5 lives wereO.5 to 1.8 days. TeE dechlorination also occurred with concentrations falling to
6 less than 5 /lg/L within 35 feet of the well. However, complete dechlorination of TCE to
7 ethene only occurred in the portion of the test area that had been previously augmented
8 with KB-I during the Area 20 pilot test described above. Outside that portion of the test
9 area, dechlorination stalled at 1,2 -dichloroethene J5. See Figure 8.
10
Ae"ojc{ Case Study - Fi~ure 8

Area 20 Blobarrie.. IliJot Study Lalyout

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11
12 • Phase II Pilot Test of In Situ Bioremediation to Treat Perchlorate in GET D Recharge
13 Water. This pilot test was conducted by Aerojet in 2002 in an attempt to ascertain
14 whether perchlorate concentrations in the recharge water' could be reduced from 225 ~glL
15 to less than 4 ~g/L without inducing concurrent manganese reduction and causing
16 dissolved manganese concentrations to exceed the secondary drinking water standard of
17 50 /lg/L. The pilot test confirmed that electron donor optimization can reduce and
18 potentially mitigated mobilization 0 f manganese. However, it was concluded that it
19 would be difficult to complete prevent manganese oxide dissolution during perchlorate
20 bioremediation with large projects 16.
21

rIo
 ITRC--Overview ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

1 • Pilot Test ofIn Situ Bioremediation ofPerchlorate and Trichloroethene in Groundwa ter,
2 IReTS. This pilot project conducted by Aerojet and The Boeing Company on the IRCTS
3 was very similar to the active biobarrier test described above. Extraction and recharge
4 well configuration was the same, however, there was approximately 500 feet bet ween the
5 extraction wells and the recharge wells. Ethanol was used as the substrate and KB -1 was
6 added to promote the dechlorination of TCE. The active portion of the test has been
7 completed and the results confirmed the results of the previous pilot tes ts with effective
8 remediation of perchlorate and TCE. Mobilization of manganese did occur within the
9 biologically active cell. Currently monitoring is on -going to determine if the dissolved
10 manganese concentrations return to background downgradient from the pilot test area 17.
11
12 • Small-Scale Radial Pilot Test Downgradient of the Former GET F Sprayfield. In 2004
13 Aerojet conducted a pilot test to determine if a biologically active zone could be created
14 in situ by injecting a slow -release electron donor (olea te) through a recharge/extraction
15 well. Potassium oleate in water was injected at 50 gpm for one day to create a
16 biologically active zone around the well. Following injection, the system was allowed to
17 acclimate for 4 weeks. It was believed that the pota ssium oleate would react with the
18 exchangeable calcium and magnesium of the clay minerals in the aquifer and precipitate
19 calcium and magnesium oleates, thereby reducing the mobility of the oleate.
20 Groundwater was then extracted at the well at 4 gpm pullin g the perchlorate at
21 concentrations up to 6,700 f.LglL in the aquifer through the biologically active zone.
22 During the acclimation phase the ORP dropped to -200 mV in the remediation zone.
23 Extracted groundwater contained less than 4 J.lglL during the first nine days of extraction
24 but then steadily increased to 500 J.lg/L by the 19 lh day. The conclusions of the study
25 were that there were a number of 0rerational features and uncertainties that would limit
26 the applicability of the technology 1 . See Figure 9.
27 [Figure 9 did not come through on any of the emails]
28
29 • In-Situ Bioremediation of Perchlorate Using Horizontal Flow Treatment Wells. This
30 project is being performed as part of a grant awarded by he Environmental Security
31 Technology Certification Program (ESTC P). This project is similar to the other pilot
32 projects already conducted except that the process uses two wells to extract and recharge
33 creating a biologically active zone perpendicular to the flow of groundwater between the
34 two wells. The system is des igned to create a biologically active zone perpendicular to
35 the flow of groundwater between the two wells. This project is currently on -going
36 (January 2006). See Figure 10.
37

r 10
 ITRC--Overview ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

Aerojet Case Study. Figure 10

.
Horizontal Well Pilot Stud". Lnout
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1
2
3 • In-Situ Bioremedation of Groundwater at GET B. The pilot test conducted at GET B was
4 designed to detennine if adding electron donor upgradient of the GET 8 extraction wells
5 would cause perchlorate to be degraded prior to the extraction wells and negate the need
6 for installation of aboveground treatment at the GET B system. Corn s yrup was the
7 electron donor of choice. Over 172,140 pounds of com syrup were applied over the 270 -
8 day test. Due to mechanical problems and the reduced ability to pump the com syrup
9 during cold weather the dosing was not equally distributed to each rech arge well.
10 Reductions in perchlorate from approximately 170 Jlg/L to 75 Jlg/L were noticed in
11 monitor wells closest to the recharge wells. However, the reductions were not consistent
12 throughout the aquifers 19, See Figure 11 for a layout of the system.
13
 ITRC--Overview 0/ Remediation Technologies/or Perchlorate

Contamination in Groundwater and Drinking Water

May 2007

Aerojer Case Study - Figure 11

(;£1' B In-Situ Pilot Study LIl)'out

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3 • Pilot Test: Perchlorate Source Site Bioremediation at the Former Propellant Hog Out
4 Facility (Sites 50F and 51F). Aerojet commenced a pilot test at the former .,propellant
5 hog out facility to determine the feasibility of biodegrading perchlorate in both the 30­
6 foot vadose zone and shallow groundwater containing up to. A radial biobarrier was to
7 be constructed, as described above for the small-scale project on the IRCTS, at the
8 downgradient edge of the hogout facility using potassium oleate. The well would then be
9 pumped to contain water flowing beneath the hog out facility and then recharged via the
10 former impoundments flushing the perchlorate from the soils to the groundwater. The
II perchlorate would then be pulled to the extraction well through the bi ologically active
12 zone and the perchlorate degraded. It turned out that there was not an indigeneous
13 population of perchlorate degrading bacteria beneath the hog out facility. It is believed
14 that the high concentrations of ammonia in the ammonium -perchlorate propellant killed
15 off the bacteria. The system has been modified to operate in batch mode with
16 groundwater extracted at 1 gpm into a tank where bacteria and carbon source are added.
17 Once the perchlorate is degraded it is discharged to the former pond for infiltration. Due
18 to lack of attachment areas in the tank, the biomass is not large and perchlorate
19 degradation is relatively slow. Aerojet is currently (as of January 2007) evaluating

,... "II
 ITRC--Overvie'>11 ofRemediation Technologies for Perchlorate

Contamination in Groundwater and Drinking Water

May 2007

I modifications that will allow the pilot test to be operated on a continuous basis rather
2 than batch mode 20. See Figure 12.

Acrojet Case Study - j;igurc 12

Hog Out J)ilot Study layout

s_

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AW'''OI
o

3
4 • Pilot Test: In-Situ Remediation of Perchlorate and TeE Using A Dual Permeable
5 Reactive Barrier (Area 40, Sites 36B and 37B). In December 2006 Aerojet constructed
6 two permeable reactive barriers (PRBs) in parallel downgradient from Sites 36B and 37B
7 in Area 40 and perpendicular to the direction of groundwater flow. Area 40 is one of the
8 few areas where bedrock is a relatively shallow depth below the ground surface (less than
9 30 feet). The firs t PRB utilizes zero-valent iron to stimulate the reduction of TeE. The
10 downgradient PRB has molasses injected and circulated through the barrier using a series
It of injection and extraction wells. Initial concentrations of TCE and perchlorate
l2 upgradient of the PRBs exceeded 30,000 Ilg/L and 23,000 Ilg/L, respectively. Samples
13 collected in the first month following installation showed that perchlorate decreased by
14 an order of magnitude through the each of the PRBs. TCE reduction through the first
IS PRB was three orders of magnitude.

r'''l''l
 ITRC--Overview ofRemediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

Biodegradation ofPerchlorate in Soils

2 While Aerojet was investigating, evaluating and implementing treatment methods for removing
3 perchlorate from extracted groundwater, Aerojet was also evaluating methods for removing
4 perchlorate from soil, particularly by biodegradation that was shown to be viable in water
5 treatment. One piece of property that was impacted by perchlorate that was of particular concern
6 in that Aerojet did not own it, was Area 41, or Cavitt Ranch. This property wa s remote from the
7 Aerojet site and used for disposal and destruction of spent solvents and solid rocket propellant.
8 Soils at Cavitt Ranch were no more than 3 feet thick overlying fractured bedrock. TCE and
9 perchlorate were present in both soils and groun dwater at high concentrations. Isolated areas of
10 metals above remedial goals were also found in spots where laboratory wastes were taken for
II destruction.
12
13 Aerojet' s first attempt at potential remediation strategies for remediation of perchlorate in soils at
14 Cavitt Ranch occurred in late 1997 when they commissioned Dr. Robert Borch to look at the
15 potential for heap leaching of soils to remove the perchlorate. Dr. Borch conducted column
16 studies to detennine the leachability of perchlorate from the soils. Hi s studies showed that
17 leaching of perchlorate was very efficient even when the infiltration proceeded more slowly than
18 anticipated. The heap leaching process produced a brine that would still require treatment or
19 another disposal alternative 21 .
20
21 In early 1999 Aerojet contracted with Geosyntec Consultants to perfonn bench -scale
22 biotreatability tests on perchlorate -impacted soils from Cavitt Ranch. The tests included both
23 composting and anaerobic slurry treatment of the soils. In the composting study, the soils were
24 bulked with manure, alfalfa, and sawdust with moisture added to make the piles approximately
25 50% moisture. A second treatment added liquid food waste to the bulking mixture. The bench ­
26 scale composting of soils found that 30 mg/kg of perchlorat e in soil was reduced to <2 mglkg
27 within several weeks, producing rapid perchlorate half -lives of 3 to 4 days. Use of the liquid
28 food waste did not appear to change the outcome as the native soils had sufficient bacteria of the
29 appropriate kind to provide for perchlorate reduction. The anaerobic slurry was made using
30 saturated soils and a variety of electron donors - ethanol, manure, food waste, vinegar and
31 molasses. Perchlorate biodegradation in the anaerobic slurry occurred after an acclimation
32 period of up to 40 days, after which it proceeded rapidly, regardless of which electron donor was
33 used, even at initial concentrations of up to 10,000 mg/L perchlorate 22.
34
35 Following the successful bench-scale testing described above Aerojet proposed a pilot test that
36 looked at composting perchlorate-impacted soils at Cavitt Ranch. Two soil compost piles were
37 constructed, one on bare ground with suction lysimeters placed to evaluate potential leaching of
38 perchlorate during the composting trial, and one on plastic liner with a simple leachate collection
39 system. Two to three cubic yards of perchlorate -impacted soils were used for each pile. Initial
40 perchlorate concentrations were 200 to 500 mg/kg. Soils were amended in such a manner that the
41 piles consisted of approximately 35% soil, 25% manure, 20% sawdust or wood chips, and 20%
42 alfalfa. Clean water was added to maintain a moisture content of 35 to 45% by volume.
43 Temperature and moisture conditions were monitored within the piles. Perchlorate destruction
44 was rapid as the concentrations of perchlorate during the 30 day test were reduced to <0.1 mglkg
45 in internal soil samples and 2 mg/kg in surface samples 23.
46

,.. ."
 ITRC--Overview of Remediation Technologies for Perchlorate
Contamination in Groundwater and Drinking Water May 2007

1 The successful application of bioremediation of perchlorate in compost piles led Aerojet to

2 conduct treatability studies at sites 56B and 49B at Cavitt Ranch whereby manure was applied to
3 the surface over perchlorate -impacted soils. If this approach were successful it would save cost
4 and time over constructing and monitoring compost piles. In October 1999 manure was applied
5 at 3-4 inches (49B) and 12 inches (56B) at the two test plots. Water was applied to the test plots
6 to maintain sufficient moisture to promote biodegradation. During the first month, surface
7 concentrations of 1100, 4600, and 1500 mglkg had been reduced to 15, 12, and 7.9 mglkg,
8 respectively, at the 56B test plot and surface concentrations of 2000, 1800, and 470 mglkg were
9 reduced to 172, 98, and 1.2 mglkg, respectively, at the 49B test plot. The lower layers below the
10 upper one to two inches did not appear to be affected within the fust month and remained dry as
11 no rainfall occurred during the first month 24.
12
13 To accelerate the degradation of perchlorate at the deeper depths Aeroj et aerating the soils in a
14 section of each of the test plots to a depth of 4-5 inches using a tine aerator. During the next
15 seven weeks significant rainfall occurred saturating he entire soil profile and weather bedrock
16 with manure leachate. No differences were seen at between the tilled untilled sections. At the
17 56B test plot where soils are thinner only low levels of perchlorate (maximum 16 mglkg)
18 remained after 18 weeks that originally had up to 4600 mglkg. At test plot 49B with the thinner
19 manure layer and deeper soil layer, concentrations had decreased from 2000 mglkg to 62 mglkg
20 in the upper 2-inches and from 560 to 180 mglkg in the deeper soils. It was estimated that during
21 the end of the rainy season the test plots will dry out and the perchlorate will be wicked to the
22 upward by capillary action (observed at other locations). The perchlorate will then be in the
23 biologically active soil/manure layer where perchlorate degradation would occur until the soil
24 became dry. Aerojet concluded that simply applying a layer of manure would be effective in
25 remediating the perchlorate in the shallow soils at Cavitt Ranch. The study concluded that a
26 thicker manure layer overlay is best as it provides a higher organic loading rate and increased
27 water content for release to the underlying soil 25.
28
29 Aerojet expanded the field application at Cavitt Ranch in April and May 2001. At 10 areas with
30 high levels of perchlorate (50 to 11,000 mg/kg) high -level areas, soil was excavated, amended
31 with cow manure and calcium magnesium acetate, placed back in the excavation and cove red
32 with a 6-12 inch layer of composted cow manure. An additional 65 bare areas (due to burning
33 during rocket propellant destruction) with low concentrations of perchlorate were treated by a
34 simple overlay of composted manure. One year later, the soil wa s resamp1ed and the average
35 perchlorate concentration at the monitoring locations had declined from 452 mglkg to 1.4
36 mglkg26.
•
• ExploSl
• Matches
• Batteries
• Automobile Air B

• De 'IlIIJl

solutil
• Non-vola
• Kinetically s te negligible
at room temp)
• Minimal sorption f
 NVI TAL
~

BE~~~~

• o groun
• HigH sorption
Mobili
• Inert - ve
conditions
• Ifreleased at hi~
have density driven
DNAPL)
• Result ==> Big PIUDles that don't go away!

 ..WHERE
~
.Y?
• Per,
Toxico "lIl

NCEA-1­
16, 2002.

- Many questions .alidity ofthe

science and their c

- Establishes a propose

mg/kg-day (UF==300).
 ne
~
• Total
~
• Human'
inhibition
- lUI is fully re
- lUI is several ste.L •

effect, therefore a la
built in
•

c
•
~ ~

~ ~
c ~

""'""' .
(D
0
~ 00
~ 00
UJ (D
0 (D
0
~

(D
 tors
.
cau

str d diet

• Nitrat 'lIIIl
,herefor
tnechanis direct
•
COtnparlsons ly relev

• Nitrate is found
especially green, Ie - these
foods are considered
 rate
•
IS , I
• A sin
10 to 1~
perchlorate
• lUI form the t
hundreds or thou
through ingestion 0
water.
 .WHERE

• Regia
-RfDo­ ~

- Residentia
- Industrial Soi
- Tap Water (caine

• Region 3 RBCs, 04­

- Nothing
 ..WHERE

- Indoor
- Industrial 130 mg/
~
- Industrial Soi mg/kg
- Tap Water = 3.7
 ·.WHERE

• Per,
Toxico ..

NCEA-1­
16, 2002.

- Many questions alidity of

conclusions.
- Establishes a propose, ceo dose of 0.00003
mg/kg-day (UF==300).
B. Larry Glidewell (AFMCjPAO)

Human Health and Toxicology

General Comments

Although the Department of Defense (DOD) contributed data used by EPA in the risk
assessment, DOD does not support all of the conclusions as stated in the document, nor
does DOD support EPA's proposed revised RfD value. However, we do believe this
harmonized assessment based perchlorate's inhibition of iodine uptake as the mode of
action represents a first for a major EPA chemical risk characterization. In addition, we
believe that the careful evaluation and use of available dosimetry modeling, both to
perform cross-species dosimetry in lieu of defaults, as well as to evaluate the potential
for age-dependent sensitivity differences, is a strong point of the EPA risk
characterization.

Risk Assessment/Characterization

Use and Analysis of Epidemiological Studies

EPA's perchlorate risk characterization puts too much weight on the results of certain
animal studies. This data selectivity creates a biased or fatally flawed perchlorate risk
characterization. While human studies data, including epidemiological, occupational,
and clinical information were presented and discussed in Chapter 4, giving the
perception that the data were factored into EPA's decision, the data in the studies were
not used to derive the draft perchlorate reference dose (RfD). In addition, it is apparent
that the agency has provided an unbalanced consideration of available epidemiological
studies. The Agency dismissed several well-conducted, published studies that were
negative while giVing great credence to one unpublished graduate study that was
positive. The fact that two studies have demonstrated that workers exposed to very
high concentrations of perchlorate do not display alterations of thyroid function is an
important piece of information for evaluating the risks from perchlorate exposure. In
the graduate study the odds ratios for perchlorate exposure as a presumptive positive
for congenital hypothyroidism were in the opposite direction compared to increasing
exposure. Therefore, the odds ratios for the high exposure group were likely due to
chance.

Uncertainty Factors

An overall increase in the uncertainty factor from 100 to 300 is unwarranted and
excessive. The agency has chosen to increase the uncertainty factor that it applies to
derive the RID despite the completion and analysis of numerous additional studies.
These studies were recommended by the first Peer Review panel in 1999 specifically to
reduce the degree of uncertainty, and EPA participated in the development of the study
protocols. Areas of contention include the use of:
 • An uncertainty factor of 10 for a LOAEL;
• An uncertainty factor of 3 for duration;
• An uncertainty factor of 3 for database insufficiency; and
• Uncertainty factors for cancer risk and immunotoxidty that appear
inconsistent with the biochemical mechanism of the mode of action.

Detailed discussion of the misapplication of uncertainty factors is included in DOD's

public comments submitted to the Docket.
C. Marni Bekkedal (Naval Health Research Center, Toxicology Detachment)

Weight-of-the-Evidence and Point-of-Departure

Implementation of a weight-of-the-evidence approach for the selection of a point-of­

departure is potentially more subjective than the traditional approach of carrying out
separate calculations on each candidate critical study or endpoint.

The Agency selected a point-of-departure in the rat of 0.01 mg/ kg-day. The basis for
this determination is provided by multiple analyses over many studies and endpoints.
Analyses include conventional Significance testing, benchmark analysis, Bayesian
statistical analysis, ANOVA and profile analysis. These endpoints reflect exposures for
periods ranging from a few weeks to a large fraction of a lifetime, over life-stages
varying from gestation to adulthood. The validity of an attempt to characterize all of
these results with a single point of departure must be questioned.

There is no evidence to support the belief that immunotoxicity could be a more

sensitive critical effect than the developmental endpoints used as the basis for this
assessment.

LOAELs and NOAELs

The difficulty of implementing EPA's weight-of-the-evidence approach is illustrated by

the rationale given by the agency for calling the 0.01 mg/ kg-day point of departure a
LOAEL based on four classes of endpoints:

• Profile analysis of brain morphometry effects in neonatal rats;

• Increased motor activity in neonatal rats;
• Thyroid histopathology; and
• Thyroid hormone changes in a number of studies.

Only two of these classes of endpoints, brain morphometry and hormone analyses,
actually demonstrated effects at the cited 0.01 mg/kg-day point-of-departure. Both of
these classes of endpoints are highly inconsistent, suggesting a problem in identifying
0.01 mg/kg-day as a LOAEL or NOAEL.

EPA's policy on changes in brain morphometry is that, in the absence of data that
would prove otherwise, changes in the size of a particular brain region are considered
adverse. However, in the absence of a consistent dose-response or data that would
support the assertion that the observed responses could be the result of compensatory
mechanisms, there is no conclusive evidence that demonstrates that the changes in
brain region size were exposure-related. Given the uncertainty associated with the
small sample size, considering these changes a LOAEL may not be justified. The ability
of humans to more easily maintain blood thyroid hormone levels is important with
regard to the developmental toxicity of perchlorate, where decreases in thyroid
hormone in fetal and neonatal rats are believed to influence brain development and
perhaps induce changes in brain morphometry.

The other basis for describing the 0.01 mg/kg-day point of departure as a LOAEL is the
results of hormonal analyses in several studies indicating changes in T4, T3 and/ or ISH
at doses as low as 0.01 mg/kg-day. However, these changes are not consistent and, as
with the brain morphometry data, should be considered an equivocal LOAEL/NOAEL,
justifying an uncertainty factor of at most 3.
D. Mike Garrison (HQ AFCEF/CCR-D)

Endpoints Used to Derive Ecological Screening Benchmarks

The primary concern over the eco-risk component of the EPA Perchlorate Document
centers on the choice of endpoints used to derive the screening benchmarks. In
deriving an ecological screening benchmark, a well-known requirement for endpoint
selection is that it is based on an ecologically relevant effect such as survival,
reproduction or growth. Within the eco-risk arena, effects that are not dearly related to
the survival, growth and reproduction of an organism are frequently argued as being
irrelevant and unsuitable for benchmark derivation. In the current document,
ecological screening benchmarks for perchlorate appear to be based on endpoints with
no known or implicated ecological relevance. For example, the apparent alteration in
thyroid function, which serves as the basis for the herbivore dietary screening
benchmark, has not been shown to result in any ecologically relevant effects. In fact,
data suggest that at levels where thyroid effects occur, there are no effects on
development, growth or reproduction. Similarly, the use of "redness and swelling" as
an ecologically relevant endpoint for the chronic aquatic assay is unjustified. At the
very least, the effects of perchlorate chosen as endpoints for screening benchmark
derivation should be adequately supported. In the current draft document, support of
the choice of benchmarks is inadequate. If convincing justification cannot be made for
current benchmark values, it is suggested that the screening benchmarks be revised
using endpOints with known ecological relevance.

Interspecies Variability

Chemicals which inhibit thyroid hormone synthesis would not result in the dramatic
changes in blood T4 and T3levels in humans that have been reported in the rat. Doses
that result in alterations in blood thyroid hormone levels in rats (and consequently
produce the developmental effects observed in the brain of rats) would not be expected
to produce similar disruption in humans due to the presence of TBG, which is also
present in the developing human fetus and neonate.

Comparing rat and rabbit developmental studies show evidence for the magnitude of
rat sensitivity to the inhibition of iodine uptake by perchlorate. However, in the rabbit
developmental toxicity study (Argus, 1998c) there were no statistically significant
differences in the levels of T3 or TSH in dams that received up to 100 mg/kg-day from
gestation day (GD) 6 to GD28, when compared with the controls. The EPA paid little
attention to the dissimilar results between rats and rabbits in the perchlorate document.
E. Dave Mattie (AFRI/HEST)

Transport of Perchlorate into Thyroid Cells

AFRljHEST would like to point out evidence in support ofuptake ofperchlorate into the
thyroid:

• In the AFRL studies by Yu et al (2000 a,b which are IV and drinking water
studies) when NIS is upregulated in rats, thyroid perchlorate concentration also
increased, as well as iodide. Cold perchlorate was measured in the thyroid of
rats in these studies using ion chromatography (a modification of the EPA
Method 314). This method is selective for perchlorate. We checked for chlorate
and chloride in the thyroid and confirmed we were looking at perchlorate and
not metabolites. Perchlorate is concentrated in thyroid, we saw thyroid to serum
ratios between 10 and 30 in the male rat in drinking water studies at doses from
0.1 and 10 mg/kg-day.
• In fact, the PBPK models can predict these upregulated levels quantitatively
when the model assumed that NIS upregulation maintained the iodide uptake in
the presence of perchlorate competitive inhibition.

On Analytical Issues

• The matrix is an issue with the HPLC method for perchlorate. The sensitivity is
reduced in blood, urine, milk and rat tissues but you can still separate the
perchlorate peak without any interference because of the sample preparation we
have developed for biological matrices.
• In the 90-day perchlorate study by Springborn Labs a Hamilton Thome IVOS 10
semen analyzer (Hamilton Thorne Research, Beverly, MA) was used for the
sperm count, concentration, and motility assessments.

On the Use of Human Data

• We have heard a lot about the inconsistencies in the animal data especially
because of soy products in the diet. This further supports the use of human data.
There are concerns about the use of the Greer study. However, the Crump study
in Chile looked at the critical effect - T3, T4 in children and TSH in newborns. A
reference dose could be developed from the Crump data that would be similar to
the RID for the Greer study showing that both the human clinical and
epidemiological studies are mutually supportive. We recently received the blood
and urine samples from the Crump study. In initial analyses just completed we
can detect perchlorate in the blood and urine. Blood levels are approximately
what the PBPK model predicted.
• Furthermore a follow-on study will start shortly looking at pregnant women in
the same three cities in Chile. Perchlorate will also be measured in blood, urine
and also milk. I feel you don't need to wait for this study to use the Crump study
 now for the development of an RfD - the results will serve as further validation
of the use of human data.

Ouestions for the Panel

• Is the Greer study compromised by scientific limitations such that it can't be used
for risk assessment?
• Is it reasonable to conclude that the rat data is a more reliable basis for human
health risk assessment for perchlorate?
• Is there any reason that a dose below the NOEL for iodine uptake inhibition
would cause any risk?
• And finally we would ask that you provide definitive comments and clear
conclusions back to EPA to help resolve controversial scientific issues rather than
simply identifying the issue.
contamination. The Institute is conducting these studies to evaluate the spatial
distribution of perchlorate exposure in various aquatic and riparian organisms.
Preliminary results of these studies appear in later paragraphs below.

Ecotoxicology studies include the Frog Embryo Teratogenesis Assay: Xenopus (FETAX)
and a phytoremediation study to examine uptake, distribution, and degradation in
experimental systems with rooted cuttings of woody plants, including willow, Eastern
Cottonwood and eucalyptus. Researchers are also perfonning laboratory analyses of
perchlorate levels in different tissues (including the thyroid gland) of organisms collected
from the study. The thyroid gland is a primary target organ of perchlorate in higher
animals. These studies are intended to evaluate perchlorate exposure levels that are
associated with a known or potential ecological impact.

Finally, investigators are planning ecological modeling and risk assessment studies to
predict long-tenn exposures and impacts in aquatic and terrestrial food chains.

Preliminary Ecological Results

TIEHH is currently conducting biological sampling within the study area. Preliminary
results suggest that perchlorate is taken up by aquatic organisms. Fish tissue samples
collected from the Lake Waco and Lake Belton Watersheds contained perchlorate at
concentrations ranging from non-detectable (ND) to 1,230 nanograms/gram (ng/g) wet
weight. Laboratory studies on the uptake and distribution of perchlorate in catfish
demonstrated uptake of perchlorate in fish tissues, with preferential distribution into the
heads versus fillets. The uptake of perchlorate by fish is highly variable, with only one
largemouth bass out of 16 yielding detectable concentrations at one collection site.
Additional studies by TIEHH on plants, amphibians, and small mammals are ongoing.
Preliminary results from body burden studies indicate that perchlorate is not detectable in
the fish tissue collected from Station Creek or Little Bosque River. TIEHH's laboratory
is presently processing fish liver samples for analysis collected in September 2001. The
Texas Tech Institute utilized an electroshocking boat for further fish collection from the
open water in Lakes Belton and Waco in late January and early February 2002.
Investigators will complete perchlorate analysis on frog samples collected from Lake
Waco and NWIRP McGregor after breeding enough tadpoles to perform the analysis.
The Institute collected and analyzed Elm and smartweed samples for perchlorate. Plant
samples had detectable concentrations of perchlorate in all cases where perchlorate was
found in the sediment pore water. Researchers detected no perchlorate in plant samples
where the bulk water contained perchlorate but the sediment pore water did not.

Early small mammal collection attempts only resulted in the collection of 3 least shrews
(Cryptotis parva). Further small mammal and avian trapping took place in January 2002,
and succeeded in capturing several deer mice, cotton rats, house mice, and harvest mice
using live traps and snap traps. Avian species collected were northern cardinal,
mockingbird, eastern phoebe, Lincoln sparrow, song sparrow, and white~crowned
sparrow. Birds were collected using a mist net. Analysis of these specimens was not
complete at the time of this report preparation.

7
 o.,.rt1rNIIt of DrfvIU
Perchlorate
~:;;;~~~o~"~kJ;$roup
•
Doll iHommi!t@dlo
proucring th@publk, our
mi1itary troop I, andtht
@nvironmtnl. This Is one in a
~~Iiu of fact shifts that have
b~~n pr.par~ to provide the
public wit h in/ormation about
DoD's tlfolfS on Ptrdllotalt.
- MEDICINAL: Perchlorate wa~ once u~ed to treat
Fact Sheets
facts About Perchlorate
Military Uses of Perchlorate
Health Effects of Perchlotate
DuO Elforts on Perchlorate
TOllicol09Y
Epidetniol09Y
Facts About Perchlorate
What is perchlorate?
Perchlorate i~ both a man-made and naturally
occurring compound. In ~olid form, it i~ a type
of ~alt. Perchlordte dissolves easily and move~
quickly in groundwater and surface water. Once
dl~~olved In water it remains in water for a very
longtime.
What are the uses of
perch lorate?
thyroid disorders in people with athyroid
condition called Graves'Disease. Perchlorate Is
still u~ed today under limited conditions to test
for thyroid hormone production.
COMMERCIAL: Perchlorate is used in the
production of expl~ives and fireworks.
Additional uses include the production
of matches, dyes, electroplating, rubber
manufacturing. paInt production,
and certain chemical fertilizer~. It i~ an
important part of safety devices that
we use everyday such as road flares and
airbags.
NATIONAL DEFENSE: Perchlorate has been used
by the Department of Defen~e (DoD) and the
space program since the 1940's. It is an efficient
oxidizer ilnd a major component in solid fuel
used in rockets and missiles. It has been used
by all fcur military branches at a variety of
faCilities including: ammunition plants, research
laboratories. depots, proving grounds. testing
facHitles, rocket maintenance facilities. and
training ba~es. The primary reason it has been so
Widely used is because It has proven to be the
safest. most stable material for our service men
and women to handle due to Its high Igl\ition
temperature. Perchlorate
releases at DoD sites have
occurred due to prior
removal, recovery, and
the disposal practices of
" .--
~, .... '-. -.~
. .'
propellant from missile~ and exp'o~ives. fuJilY.
DoD pilau',· "tria "mulling p..o....dm·'·,. .
10 pn'II~11f ....J<'IISt'S ofp"rCMrJ/,rlft: ht/o du:
l'U "iroll rlll·llt.
How can' be exposed to
perchlorate?
People can be exp~ed to perchlorate by
drinking water that contain~ perchlorate. The
Food and Drug Administration Is currently
evaluating possible exposure related to
COl\5umption of vegetables that have been
irrigated with water that contains perchlorate.
'N'NW c!sanJda.gov/-cms/cJo4sl.Irv.h:mi
People who live near areas where perchlorate
has been used, tested, produced, or disposed of
may be exp~ed to low levelS in their drinking
water. The DoD will sample for perchlorate at
its sites if there are both a reasonable baSis
to suspect the presence of perchlorate and
a way for people to come into contact with
water that contains potentially harmful levels
of perchlorate. EPA. other federal agencies,
states, water suppliers. and industry are actively
dddre~sing this issue by testing for perchlorate
ir. drinking water and surface water. If you
believe that you may have perchlorate in your
drinking water, please contact your local/state
health department or water utility for additional
Information.
 000 will take mea1ur~
to ensure that people'1
health will be protected
if thel' d,lnkingwater
contains harmfulle'4els
of perthlorate that
originated from DoD 11te1.
for more detailed Information:The DoD his perchlorate Information at the following website:
www,denjx.osd mjl/denixtPu bileAibrarvJWater/Perchlorate/per<hIDrate.hl ml. The U.S. EPA draft r/slt
auessment on perchlorate can be viewed at www.epa.govlncea. The U.s. EM perchlorate web site can
be viewed at www.epa.gov/safewalerlccJ/eercblorate/Perchlorate.html. Other useful websltesdiscussing
heallh effects of perchlorate can be found at www.counciiOnWaterQuality.org and www,thyroid.oC9.
(an exposure to perchlorate
affect my health?
A large amount of information is available on
the health effects of perchlorate. Health studies
using data from patients who were given
perchlorate to treat thyroid conditiOns indicate
that high doses, thousands of times higher than
what has been found in drinking water. can
affect metabolism. growth, and development
of the body. The potential health impacts
of exposure to low levels in drinking water
continue to be studied to determine a definite
safe level.
How do you test for
perchlorate?
Before 1997. laboratory-testing methods
could not measure low levels of perchlOiate
in water supplies. DoD was instrumental In
the development of a new. more effective
technique in 1997, which has helped identify
additional sources of perchlorate. At present,
drinking water can be tested fOi perchlorate
through EPA's Unregulated Contaminant
Monitoring
Program. The
U.s. Geological
Survey and others
are monitoring
(or perchlorate
in surface water.
U.s. EPA, 000,
and other agencies are continuing to work on
improving methods to test for perchlorate.
What are the laws rE!gulating
perchlorate?
Currently, there are no feder,,1 drinking water
standards for perchlorate. DoD and other
federal agencies are cooperating with U.s, E.PA
as it establishes a regulatory level of perchlorate
to protect health. Once established. DoD will
comply with regulatory requirements. In the
meantime, DoD I/)ill hIke IIIMH<I'I'.' 10 1'/1.'111'1'
,hill pt·opl":. iJMlrI, ,,'illb, pr/JI,'(ut1 ~f tim I'
driukillg II'INa ('(JIIlllill! I,"rlliftd lel"·[. of
p,'n·blo/',It,. ,b.11 oJ';gilltlll·tlfrolJl DoD .ii,..,.
On January 22. 2003. the U.s. EPA reaffirmed
its 1999 gUidetine5 of an interim level for
perchlorate in water. The National Academy
of Sciences 'NlII review ,wal!able research
results and studies which will help the u.s. EPA
establish a regulatory level.
U.S, EPA may establish adnnking water
standard called a III/I.\"imltlli COI/IIlI/limlill
/1",.,/ (.'Hen after completion of the National
Ac,idemy of Sciences review The MCl is a
maximum amount of perchlorate the U.s.
EPA will allow in drinking water to ensure the
protection of human health.
California EPA established a Public Health Goal
(PHG) for perchlor.)te in drinking water in March
2004. The California Department of Health
SerVices has determined that perchlorate
concentrations lower than the public health
goal are con~idered to be protective of all
people. including children and pregnant
women. Other states. such as Texas and
Massachusetts. h-lve either proposed a drinking
water level or have begun the process.
USING THE BEST AVAILABLE S<IENCE: A panel of
leading scien tific experts met in October 2003
to review the fundamental science issues
regarding perchlorate and pOSSible health
effects The results
of this meeting
can be viewed at
's',,,,·w.perchlorate
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Perchlorate
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Health Effects of Perchlorate

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PERCHLORATE SALTS: Perchlorate salts are commonly
found as ammonium, potassium, and sodium
perchlorate. Just like table salt, they dissolve
easily in water and will remain in the water for
along lime. Regardless of the original source of
PERCHLORATE FACTS
Perchlorate is easily absorbed into our
bloodstreams after ingestion but leaves
the body very qUIckly. Perchlorate, at levels
far higher than what has been found in
perchlorate salt, once dissolved all perchlorate in
drinkIng water, slows down the uptake of
water will have the same effects.
Iodide Into the thyroid
MEDICINAL USE Of PERCHLORATE: Perchlorate Infants and small children may be more
has been used for more than 50 years as a sensitive to perchlorate tha n adults. EPA
medicine for people with hyperthyroidism Is focusing on those most sensitive in its
(too much thyroid activity) and other thyroid ongoing evaluation.
gland disorders. Doses given to patients are Perchlorate does not cause cancer at
tens of thousands of times higher than the the low levels that are currently being
amount of perchlorate in any drinking water measured in drinking water.
supplies. Perchlorate continues to be prescribed
in Europe and elsewhere for the treatment of Perchlorate does not cause Graves' Disease.
certain thyroid conditions. However, It has been Perchlorate does not cause changes in
replaced in the U.S. with newer medications, thyroid hormones at the levels that are
partly because it takes such high and frequent currently being measured In drinkIng water.
doses to have any effect.

body. At prolonged and high doses, perchlorate

RISK ASSESSMENT OF PERCHLORATE: The United
can slow the uptake of Iodide into the thyrOid
States Environmental Protection Agency (EPA)
and affect how the thyroid functions. In adults,
has conducted J comprehensive risk assessment
the thyroid helps to regulate metabolism; in
for perchlorate to determine asafe exposure
children, the thyroid also plays a role in proper
level for people, including those most senSitive
development. A comprehensive review Df all the
to perchlorate. Offici031 conclUSions have yet
existing health studies is currently underway.
to be drawn from the EPA's most recent draft
/lsk assessment, and the National Academy
The National Academy of SCiences is currently
of Sciences is reviewing the data used in the
evaluating the eXisting health studies and EPA's
assessment.
recent risk assessment on Perchlorate. /1/ t!uo
1If"(/lili1l1t!, (),,[) po/il)' i, 10 1"ln' 1IIt',l.'lfI't''< 10
HEALTH UFECTSOF PERCHLORATE: At present, there
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IS a large amount ct Information available on
Fact Sheets FO/fl h'll'lfllid Inlds u/jw',h/or",,' tlJIlI
the he.llth effects from exposure to perchlorate;
facts About Perchlorate 'origi,JtIINlji'(JIII D"V ",·ril,ilie!.
however, some questions still remain. Health
Military Uses of Perchlorate
studies uSing data from patients who were
Health E/feels of Perchlorate given perchlorate to treat thyroid conditions
DoD E/folts on Perchlo,ate Indicate that extremery high doses can affect
Toxicology metabolism, grolVth. and development of the
Epidemiology
 A panel of leading scientific experts met in
October 2003 to review available perchlorate
health studies and basic sCience issues
regarding perchlorate and possible health
effects. The results of this meeting can be
viewed at ·/!I.'.!'.".p<,lch'cr.lt<'SYff,POS!o.lf"
• CRUMP, ET AL.: CHILEAN STUDY Of PREGNANT
WOMEN: In Chile, an epidemiological study
was performed on pregnant women who
drank water which contained naturally
occurring perchlorate, at levels at teast 10
limes higher than what we've detected in Our
drir:king water. Tht'fe were no health eifects
observed.

• GREER, ET Al. CLINICAL STUDY: A clinical study

Examples of Available Human
using human volunteers was performed to
Health Studies
determine whether levels of perchlorate
• USE AS AMEDICATION: There is a great deal
Similar to the low levels that are currer,tly
of information about the health effects of
being found in the groundwater are safe for
perchlorate since It has been used for treating
people. This study was performed in the same
thyrOid disorders for more than SO years.
way pharmaceuticdl companies reView soon-
The prescribed doses were thousands of
to-be-approved medicines. At the low levels
times higher than what has been detected
used in the study. no health effects were
in drinking water sources. It is still used
observed.•
today under limited conditions to test for
thyroid hormone production. Interestingly,
despite perchlorate being so persistent in
the environment, it remains In the body for
only ashort time. The use of perchlorate as a
medicine is very inefficient because the effect
is only short term

For more detailed information: The DoD has perthlorate information at the following website:
www.denix.0sd,miIJdl!nix/Publir/librarYIWall"rlPerchlorate/perchlorate.h1001. The US. EPA draft risk
assessment on perchlorate can be viewed at www.epa.go\l/ncea. The Us. EPA perthlorate web slte can
be viewed at wW~lafewalerfc(l/oerchlorateIDer(hlorate.h!ml, Other useful websites discussing
health effects of perchlorate tan be found at: www.CQuociIOnWaterOualitx,org and wNw.thyroid.org.