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ENVIRONMENTAL PROTECTION AGENCY
Environmental Protection Agency
RIN ID: RIN 2040-ZA02
EPA ID: [EPA-HQ-OW-2008-0068; FRL-8727-6]
NOTICE: NOTICES
ACTION: Drinking Water:
DOCUMENT ACTION: Notice.
SUBJECT CATEGORY: Drinking Water: Preliminary Regulatory Determination on Perchlorate
DATES: Comments must be received on or before November 10, 2008.
DOCUMENT SUMMARY: This action presents EPA's preliminary regulatory
determination for perchlorate in accordance with the Safe Drinking
Water Act (SDWA). The Agency has determined that a national primary
drinking water regulation (NPDWR) for perchlorate would not present ``a
meaningful opportunity for health risk reduction for persons served by
public water systems.'' The SDWA requires EPA to make determinations
every five years of whether to regulate at least five contaminants on
the Contaminant Candidate List (CCL). EPA included perchlorate on the
first and second CCLs that were published in the Federal Register on
March 2, 1998 and February 24, 2005. Most recently, EPA presented final
regulatory determinations regarding 11 contaminants on the second CCL
in a notice published in the Federal Register on July 30, 2008. In
today's action, EPA presents supporting rationale and requests public comment on its
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preliminary regulatory determination for perchlorate. EPA will make a
final regulatory determination for perchlorate after considering
comments and information provided in the 30day comment period
following this notice. EPA plans to publish a health advisory for
perchlorate at the time the Agency publishes its final regulatory
determination to provide State and local public health officials with
technical information that they may use in addressing local
contamination.
SUMMARY: Preliminary Regulatory Determination on Perchlorate,
SUPPLEMENTAL INFORMATION
I. General InformationA. Does This Action Impose Any Requirements on My Public Water System?
Today's action seeks public comment on EPA's preliminary
determination that a national primary drinking water regulation is not
necessary for perchlorate, and thus imposes no requirements on public
water systems. After review and consideration of public comment, EPA will issue a final regulatory determination.
B. What Should I Consider as I Prepare My Comments for EPA?
You may find the following suggestions helpful for preparing your comments:
1. Explain your views as clearly as possible.
2. Describe any assumptions that you used.
3. Provide any technical information and/or data you used that support your views.
4. If you estimate potential burden or costs, explain how you arrived at your estimate.
5. Provide specific examples to illustrate your concerns.
6. Offer alternatives.
7. Make sure to submit your comments by the comment period deadline.
8. To ensure proper receipt by EPA, identify the appropriate docket identification number in the subject line on the first page of your response. It would also be helpful if you provided the name, date, and Federal Register citation related to your comments.
II. Purpose, Background and Summary of This Action
This section briefly summarizes the purpose of this action, the statutory requirements, previous activities related to the Contaminant Candidate List and regulatory determinations, and the approach used and outcome of this preliminary regulatory determination.
A. What is the Purpose of This Action?
The purpose of today's action is to present EPA's preliminary regulatory determination on perchlorate, the process and the rationale used to make this determination, a brief summary of the supporting documentation, and a request for public comment.
B. Background on the CCL and Regulatory Determinations
1. Statutory Requirements for CCL and Regulatory Determinations.
The specific statutory requirements for the Contaminant Candidate List
(CCL) and regulatory determinations can be found in section 1412(b)(1)
of the Safe Drinking Water Act (SDWA). The CCL is a list of
contaminants that are not subject to any proposed or promulgated
national primary drinking water regulations (NPDWRs), are known or
anticipated to occur in public water systems (PWSs), and may require
regulation under the SDWA. The 1996 SDWA Amendments also direct EPA to
determine, every five years, whether to regulate at least five
contaminants from the CCL. The SDWA requires EPA to publish a Maximum
Contaminant Level Goal\1\ (MCLG) and promulgate an NPDWR \2\ for a contaminant if the Administrator determines that:
\1\ The MCLG is the ``maximum level of a contaminant in drinking
water at which no known off anticipated adverse effect on the health
of persons would occur, and which allows an adequate margin of
safety. Maximum contaminant level goals are nonenforceable heath goals'' (CFR 141.2).
\2\ An NPDWR is a legally enforceable standard that applies to
public water systems. An NPDWR sets a legal limit (called a maximum
contaminant level or MCL) or specifies a certain treatment technique
(TT) for public water systems for a specific contaminant or group of contaminants.
(a) The contaminant may have an adverse effect on the health of persons;
(b) The contaminant is known to occur or there is a substantial
likelihood that the contaminant will occur in public water systems with a frequency and at levels of public health concern; and
(c) In the sole judgment of the Administrator, regulation of such
contaminant presents a meaningful opportunity for health risk reduction for persons served by public water systems.
While carrying out the process to make a determination, the law requires EPA to take into consideration the effect contaminants have on subgroups that comprise a meaningful portion of the general population (such as infants, children, pregnant women, the elderly, individuals with a history of serious illness or other subpopulations) that are identifiable as being at greater risk of adverse health effects than the general population.
If EPA makes a final determination that a national primary drinking
water regulation is needed, the Agency has 24 months to publish a
proposed MCLG and NPDWR. After the proposal, the Agency has 18 months
to publish and promulgate a final MCLG and NPDWR (SDWA section 1412(b) (1) (E)).\3\
\3\ The statute authorizes a nine month extension of this promulgation date.
EPA published preliminary regulatory determinations for nine CCL 1
contaminants on June 3, 2002, (67 FR 38222 (USEPA, 2002a)), and final
regulatory determinations on July 18, 2003 (68 FR 42898 (USEPA,
2003a)). EPA published preliminary regulatory determinations for eleven
CCL 2 contaminants on May 1, 2007, (72 FR 24016 (USEPA, 2007)) and
finalized these regulatory determinations on July 30, 2008 (73 FR 44251
(USEPA, 2008c)). As part of its May 1, 2007, FR notice of preliminary
regulatory determinations for 11 contaminants, EPA also presented information on several contaminants
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from the second CCL for which the Agency was not yet making a
preliminary regulatory determination, including perchlorate.
Specifically, EPA indicated that additional information was needed to
more fully characterize perchlorate exposure and determine whether it
is appropriate to regulate perchlorate in drinking water (i.e., whether
setting a national primary drinking water standard would provide a
meaningful opportunity to reduce risk for people served by public water
systems). The May 1, 2007, FR notice describes how the Agency was
considering additional information including FDA food data and CDC
human exposure data to determine whether to regulate perchlorate. (See
the May 1, 2007, FR notice at 24038 for a discussion regarding the
information that EPA had on perchlorate as well as the additional
information that was needed before the Agency could make a preliminary regulatory determination for perchlorate).
C. What Comments and Information Did EPA Receive Regarding Perchlorate in Response to the May 1, FR Notice?
Eight commenters on the Regulatory Determinations 2 Preliminary FR notice addressed perchlorate. EPA received comments that supported and comments that opposed regulating perchlorate. One of the commenters who encouraged regulation stated that perchlorate is known to occur in public water supplies in a number of States and ``while occurrence data does [sic] not suggest that perchlorate occurs at levels of public health concern in the vast majority of public drinking water supplies, and the population at risk appears to be small, that group does include a sensitive subpopulation (pregnant women and developing fetuses) of significant concern.'' Another commenter wrote ``the contamination of water supplies by perchlorate is ongoing'' and ``perchlorate that has entered the soil and contaminated aquifers will likely lead to additional impacted sites.'' A commenter wrote that ``a number of States are moving to regulate perchlorate and a patchwork of different regulations will confuse the public and the regulated water community.''
The commenters opposed to regulating perchlorate also cited the available information to support their recommendation. One commenter wrote that ``the extensive scientific record indicates that establishing a drinking water standard for perchlorate would not yield a meaningful opportunity to reduce risk to human health.'' Another commenter stated that perchlorate ``does not appear, at this stage, to be a nationwide problem.''
Several commenters also addressed EPA's assessment that additional investigation is necessary to ascertain total human exposure before a preliminary regulatory determination could be made. Commenters wrote that the principal study on which EPA's Reference Dose (RfD) is based already accounts for background sources of perchlorate and therefore EPA should not adjust the RfD to account for other nondrinkingwater exposures.
EPA has considered the perchlorate comments submitted in connection
with the May 1, 2007, notice in the development of today's action. EPA
will consider these and any further comments submitted in response to
this notice before preparing a final regulatory determination for perchlorate.
D. What is EPA's Preliminary Regulatory Determination on Perchlorate and What Happens Next?
EPA is making a preliminary regulatory determination in this notice that a national primary drinking water rule is not necessary for perchlorate because a national primary drinking water regulation would not provide a meaningful opportunity to reduce health risk. EPA will make a final regulatory determination for perchlorate after considering comments and information provided in the 30day comment period following this notice. One of the analyses that EPA considered for this preliminary determination is a physiologicallybased pharmacokinetic (PBPK) model that predicts radioactive iodide uptake (RAIU) inhibition in the thyroid for various subpopulations and drinking water concentrations. The model, which is described in section IV.B.5, has already been published in peerreviewed articles (Clewell et al., 2007 and Merrill et al., 2005), but EPA subjected the model to intensive internal review prior to considering it for this regulatory determination and made several adjustments as a result. EPA believes it is appropriate to have these adjustments peerreviewed. While the application of the model to nonadult subpopulations was part of the previously peerreviewed articles, EPA will also ask the peer reviewers to comment on this issue to help EPA ensure that the model is appropriate for use in assessing health outcomes associated with perchlorate exposure for these populations. EPA intends to complete this review before publishing its final determination and will consider any comments from the reviewers. Additionally, EPA plans to publish a health advisory for perchlorate at the time the Agency publishes its final regulatory determination to provide State and local public health officials with information that they may use in addressing local contamination.
Additionally, at the same time that EPA publishes a health advisory
for perchlorate, the Agency will withdraw its existing January 2006
guidance regarding perchlorate and potential cleanup levels under the
National Oil and Hazardous Substances Contingency Plan (National
Contingency Plan, NCP) and will replace it with revised guidance. (See
memorandum dated January 26, 2006, from Susan Parker Bodine to EPA
Regional Administrators (US EPA, 2006).) Specifically, the January 2006
guidance, in part, addresses the use of preliminary remediation goals
(PRGs) for perchlorate contaminated water at National Priority List
(NPL) sites. The January 2006 guidance recommends a PRG of 24.5 ppb,
assuming that all exposure comes from ground water at the site. The
recommended PRG is based on the assumption that all exposure comes from
ground water, because at the time the January 2006 guidance was issued
there was insufficient information available on the levels of
perchlorate in food to calculate a national relative source
contribution (RSC). In the absence of such national data on the levels
of perchlorate found in foods, the approach outlined in the January 2006 guidance was considered by the Agency to be the most
scientifically defensible. In addition, because the recommended PRG
generally is the starting point for determining appropriate site
specific cleanup levels, the guidance also indicates that the cleanup
level at any site should be evaluated on a casebycase basis, and
modified accordingly, based on sitespecific information, including
exposure to nonwater sources, such as foods. EPA now has sufficient
data to calculate a national RSC and has used this RSC to calculate a
health reference level (HRL) for drinking water as part of the basis
for today's preliminary determination. When EPA issues the final
regulatory determination for perchlorate, the final HRL will be the
basis for the health advisory value in the health advisory document the
Agency expects to issue at that time. Thereafter, it may be appropriate
to use the health advisory value as a ``to be considered'' (TBC) value
in developing potential cleanup levels for perchlorate at Superfund
sites. In addition, some State regulations may be applicable or relevant and appropriate requirements (ARARs)
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when establishing cleanup levels for perchlorate at Superfund sites.
III. What Scientific Data and Analyses Did EPA Evaluate in Making a Preliminary Regulatory Determination for Perchlorate?
This section summarizes the health effects, occurrence, and population exposure evaluation information EPA used to support the preliminary regulatory determination for perchlorate. EPA's conclusions with respect to these data are discussed in Section IV.
A. Evaluation of Precursor and Adverse Health Effects
Section 1412(b)(1)(A)(i) of the SDWA requires EPA to determine
whether a candidate contaminant may have an adverse effect on public
health. EPA described the overall process the Agency used to evaluate
health effects information in the May 1, 2007, Federal Register Notice
(72 FR 24016 (USEPA, 2007)). This section presents specific information
about the potential for precursor and adverse health effects from
perchlorate, including a discussion of an extensive report completed by
the National Academy of Sciences (NAS) on the issue and other research published after that report.
1. NAS Review of Perchlorate Health Implications and EPA's Reference Dose
In 2003, the National Research Council (NRC) of the NAS was asked to assess the current state of the science regarding potential adverse effects of disruption of thyroid function by perchlorate in humans and laboratory animals at various stages of life and, based on this review, to determine whether EPA's findings in its 2002 draft risk assessment were consistent with the current scientific evidence.
In January 2005, the NRC published ``Health Implications of Perchlorate Ingestion,'' a review of the state of the science regarding potential adverse health effects of perchlorate exposure and modeof action for perchlorate toxicity (NRC, 2005).
Perchlorate can interfere with the normal functioning of the thyroid gland by competitively inhibiting the transport of iodide into the thyroid. Iodide is an important component of two thyroid hormones, T4 and T3, and the transfer of iodide from the blood into the thyroid is an essential step in the synthesis of these two hormones. Iodide transport into the thyroid is mediated by a protein molecule known as the sodium (Na+)iodide (I) symporter (NIS). NIS molecules bind iodide with very high affinity, but they also bind other ions that have a similar shape and electric charge, such as perchlorate. The binding of these other ions to the NIS inhibits iodide transport into the thyroid, which can result in intrathyroidal iodide deficiency and consequently decreased synthesis of T4 and T3. There is compensation for lowlevels of iodide deficiency, however, such that the body maintains blood serum concentrations of thyroid hormones within narrow limits through feedback control mechanisms. The compensation for decreased thyroid hormone is accomplished by increased secretion of the thyroid stimulating hormone (TSH) from the pituitary gland triggered by the reduced hormone levels, which has among its effects the increased production of T4 and T3 (USEPA, 2005b). The thyroid's ability to compensate in this way is limited, though, such that sufficiently high levels of perchlorate exposure result in a reduction of T4 and T3 blood levels (after thyroid iodine stores are depleted). Sustained changes in thyroid hormone and TSH secretion can result in thyroid hypertrophy and hyperplasia (i.e., abnormal growth or enlargement of the thyroid) (USEPA, 2005b).
Children born with congenital hypothyroidism may suffer from mild cognitive deficits despite hormone remediation (Rovet, 2002; Zoeller and Rovet, 2004), and subclinical hypothyroidism and reductions in T4 (i.e., hypothyroxinemia) in pregnant women have been associated with neurodevelopmental delays and IQ deficits in their children (Pop et al., 1999, 2003; Haddow et al., 1999; Kooistra et al., 2006; Morreale de Escobar, 2000, 2004). Animal studies support these observations, and recent findings indicate that neurodevelopmental deficits are evident under conditions of hypothyroxinemia and occur in the absence of growth retardation (Auso et al., 2004; Gilbert and Sui, 2008; Sharlin et al., 2008; Goldey et al., 1995).
Results from studies of the effects of perchlorate exposure on hormone levels have been mixed. One recent study did not identify any effects of perchlorate on blood serum hormones (Amitai et al., 2007), while another study (Blount et al., 2006b) did identify such effects. The results of the Blount study are discussed further in Section III.A.2.
The data from epidemiological studies of the general population
provide some information on possible effects of perchlorate exposure.
Based upon analysis of the data available at the time NRC (2005)
acknowledged that ecologic epidemiological data alone are not
sufficient to demonstrate whether or not an association is causal, and
that these studies can provide evidence bearing on possible
associations. Noting the limitations of specific studies, the NRC (2005; chapter 3) committee concluded that the available
epidemiological evidence is not consistent with a causal association
between perchlorate and congenital hypothyroidism, changes in thyroid
function in normal birthweight, fullterm newborns, or hypothyroidism
or other thyroid disorders in adults. The committee considered the
evidence to be inadequate to determine whether or not there is a causal
association between perchlorate exposure and adverse neurodevelopmental
outcomes in children. The committee noted that no studies have
investigated the relationship between perchlorate exposure and adverse
outcomes among especially vulnerable groups, such as the offspring of
mothers who had low dietary iodide intake, or lowbirthweight or preterm infants (US EPA, 2005b).
The NRC recommended data from the Greer et al. (2002) human
clinical study as the basis for deriving a reference dose (RfD) for
perchlorate (NRC, 2005). Greer et al., (2002) report the results of a
study that measured thyroid iodide uptake, hormone levels, and urinary
iodide excretion in a group of 37 healthy adults who were administered
perchlorate doses orally over a period of 14 days. Dose levels ranged
from 7 to 500 [mu]g/kg/day in the different experimental groups. The
investigators found that the 24hour inhibition of iodide intake ranged
from 1.8 percent in the lowest dose group to 67.1 percent in the
highest dose group. However, no significant differences were seen in
measured blood serum thyroid hormone levels (T3, T4, total and free) in
any dose group. The statistical no observed effect level (NOEL) for the
perchlorateinduced inhibition of thyroid iodide uptake was determined
to be 7 [mu]g/kg/day, corresponding to an iodide uptake inhibition of
1.8 percent. Although the NRC committee concluded that hypothyroidism
is the first adverse effect in the continuum of effects of perchlorate
exposure, NRC recommended that ``the most healthprotective and
scientifically valid approach'' was to base the perchlorate RfD on the
inhibition of iodide uptake by the thyroid (NRC, 2005). NRC concluded
that iodide uptake inhibition, although not adverse, is the most
appropriate precursor event in the continuum of possible effects of
perchlorate exposure and would precede any adverse health effects of perchlorate exposure. The lowest dose
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(7 [mu]g/kg/day) administered in the Greer et al., (2002) study was
considered a NOEL (rather than a noobservedadverseeffect level or
NOAEL) because iodide uptake inhibition is not an adverse effect, but a
biochemical precursor. The NRC further determined that, ``the very
small decrease (1.8 percent) in thyroid radioiodide uptake in the
lowest dose group was well within the variation of repeated
measurements in normal subjects.'' A summary of the data considered and
the NRC deliberations can be found in the NRC report (2005).
The NRC recommended that EPA apply an intraspecies uncertainty factor of 10 to the NOEL to account for differences in sensitivity between the healthy adults in the Greer et al., (2002) study and the most sensitive population, fetuses of pregnant women who might have hypothyroidism or iodide deficiency. Because the fetus depends on an adequate supply of maternal thyroid hormone for its central nervous system development during the first trimester of pregnancy, iodide uptake inhibition from lowlevel perchlorate exposure has been identified as a concern in connection with increasing the risk of neurodevelopmental impairment in fetuses of highrisk mothers (NRC, 2005). The NRC (2005) viewed the uncertainty factor of 10 as conservative and protective of health given that the point of departure (the NOEL) is based on a nonadverse effect (iodide uptake inhibition), which precedes the adverse effect in a continuum of possible effects of perchlorate exposure. The NRC panel concluded that no additional uncertainty factor was needed for the use of a lessthanchronic study, for deficiencies in the database, or for interspecies variability. EPA's Integrated Risk Information System (IRIS) adopted the NRC's recommendations resulting in an RfD of 0.7 [mu]g/kg/day, derived by applying a tenfold total uncertainty factor to the NOEL of 7 [mu]g/kg/ day (USEPA, 2005b).
The NRC emphasized that its recommendation ``differs from the traditional approach to deriving the RfD.'' The NRC recommended ``using a nonadverse effect rather than an adverse effect as the point of departure for the perchlorate risk asessement. Using a nonadverse effect that is upstream of the adverse effect is a more conservative, healthprotective approach to the perchlorate risk assessment.'' The NRC also noted that the purpose of the 10fold uncertainty factor is to protect sensitive subpopulations in the face of uncertainty regarding their relative sensitivity to perchlorate exposure. The NRC recognized that additional information on these relative sensitivities could be used to reduce this uncertainty factor in the future (NRC, 2005).\4\ \4\ ``There can be variability in responses among humans. The intraspecies uncertainty factor accounts for that variability and is intended to protect populations more sensitive than the population tested. In the absence of data on the range of sensitivity among humans, a default uncertainty factor of 10 is typically applied. The factor could be set at 1 if data indicate that sensitive populations do not vary substantially from those tested.'' (NRC 2005, p 173) 2. Biomonitoring Studies
After the NRC report was released, several papers were published that investigated whether biomonitoring data associated with the National Health and Nutrition Examination Survey (NHANES) could be used to discern if there was a relationship between perchlorate levels in the body and thyroid function. These papers also help to evaluate populations that might be considered to be more sensitive to perchlorate exposure.
Blount et al., (2006b) published a study examining the relationship
between urinary levels of perchlorate and blood serum levels of TSH and
total T4 in 2,299 men and women (ages 12 years and older) who
participated in CDC's 20012002 NHANES.\5\ Blount et al., (2006b)
evaluated perchlorate along with a number of covariates known or likely
to be associated with T4 or TSH levels to assess the relationship
between perchlorate and these hormones, and the influence of other
factors on this relationship. These covariates included gender, age,
race/ethnicity, body mass index, serum albumin, serum cotinine (a
marker of nicotine exposure), estimated total caloric intake, pregnancy
status, postmenopausal status, premenarche status, serum Creactive
protein, hours fasting before sample collection, urinary thiocyanate,
urinary nitrate, and use of selected medications. The study found that
perchlorate was a statistically significant predictor of thyroid hormones in women, but not in men.
\5\ While CDC researchers measured urinary perchlorate
concentration for 2,820 NHANES participants, TSH and total T4 serum
levels were only available for 2,299 of these participants.
After finding evidence of gender differences, the researchers
focused on further analyzing the NHANES data for the 1,111 women
participants. They divided these 1,111 women into two categories,
higheriodide and loweriodide urinary content, using a cut point of
100 [mu]g/L of urinary iodide based on the median level the World
Health Organization (WHO) considers indicative of sufficient iodide
intake \6\ for a population. Hypothyroid women were excluded from the
analysis. According to the study's authors, about 36 percent of women
living in the United States have urinary iodide levels less than 100
[mu]g/L (Caldwell et al., 2005). For women with urinary iodide levels
less than 100 [mu]g/L, the study found that urinary perchlorate is
associated with a decrease in (a negative predictor for) T4 levels and
an increase in (a positive predictor for) TSH levels. For women with
urinary iodide levels greater than or equal to 100 [mu]g/L, the
researchers found that perchlorate is a significant positive predictor
of TSH, but not a predictor of T4. The researchers state that
perchlorate could be a surrogate for another unrecognized determinant of thyroid function.
\6\ WHO notes that the prevalence of goiter begins to increase
in populations with a median urinary iodide level below 100 [mu]g/L (WHO, 1994).
Also, the study reports that while large doses of perchlorate are known to decrease thyroid function, this is the first time an association of decreased thyroid function has been observed at these low levels of perchlorate exposure. The clinical significance of the variations in T4/TSH levels, which were generally within normal limits, has not been determined. The researchers noted several limitations of the study (e.g., assumption that urinary perchlorate correlates with perchlorate levels in the stroma and tissue and measurement of total T4 rather than free T4) and recommended that these findings be affirmed in at least one more large study focusing on women with low urine iodide levels. It is also not known whether the association between perchlorate and thyroid hormone levels is causal or mediated by some other correlate of both, although the relationship between urine perchlorate and total TSH and T4 levels persisted after statistical adjustments for some additional covariates known to predict thyroid hormone levels (e.g., total kilocalorie intake, estrogen use, and serum Creactive protein levels). A planned followup study will include additional measures of thyroid health and function (e.g., TPO antibodies, free T4). An additional paper by Blount et al., (2006c), discussed further in Section III. C. 2. a., found that almost all participants in the NHANES survey, including the participants in this group, had urinary levels of perchlorate corresponding to estimated dose levels that are below the RfD of 0.7 [mu]g/kg/day.
The Blount study suggested that perchlorate could be a surrogate for another unrecognized determinant of
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thyroid function. There are other chemicals, including nitrate and
thiocyanate, which can affect thyroid function. Steinmaus et al.,
(2007) further analyzed the data from NHANES 20012002 to assess the
impact of smoking, cotinine and thiocyanate on the relationship between
urinary perchlorate and blood serum T4 and TSH. Thiocyanate is a
metabolite of cyanide found in tobacco smoke and is naturally occurring
in some foods, including cabbage, broccoli, and cassava. Increased
serum thiocyanate levels are associated with increasing levels of
smoking. Thiocyanate affects the thyroid by the same mechanism as
perchlorate (competitive inhibition of iodide uptake). Steinmaus et al.
analyzed the data to determine whether smoking status (smoker or
nonsmoker), serum thiocyanate, or serum cotinine were better predictors
of T4 and TSH changes than perchlorate, or if the effects reflected the combined effects of perchlorate and thiocyanate
Of female subjects 12 years of age and older in NHANES 20012002, 1,203 subjects had data on blood serum T4, serum TSH, urinary perchlorate, iodine and creatinine. Subjects with extreme T4 or TSH (3 individuals) or with a reported history of thyroid disease (91) were excluded from further analyses. Of the remaining women, 385 (35 percent) had urinary iodine levels below 100 [mu]g/l. Steinmaus, et al. evaluated serum cotinine as an indicator of nicotine exposure, with levels greater than 10 ng/ml classified as high and levels less than 0.015 ng/ml classified as low.
The authors found no association between either perchlorate or T4 and smoking, cotinine or thiocyanate in men or in women with urinary iodine levels greater than 100 [mu]g/l. In addition, they found no association between cotinine and T4 or TSH in women with iodine levels lower than 100 [mu]g/l. However, in women with urinary iodine levels lower than 100 [mu]g/l, an association between urinary perchlorate and decreased serum T4 was stronger in smokers than in nonsmokers, and stronger in those with high urinary thiocyanate levels than in those with low urinary thiocyanate levels. Although noting that their findings need to be confirmed with further research, the authors concluded that for these lowiodine women the results suggest that at commonlyoccurring perchlorate exposure levels, thiocyanate in tobacco smoke and perchlorate interact in affecting thyroid function, and that agents other than tobacco smoke might cause similar interactions (Steimaus et al., 2007).
EPA also evaluated whether health information is available
regarding children, pregnant women and lactating mothers. The NRC
report discussed a number of epidemiological studies that looked at
thyroid hormone levels in infants. A more recent study by Amitai et
al., (2007) assessed T4 values in newborns in Israel whose mothers
resided in areas where drinking water contained perchlorate at ``very
high'' (340 [mu]g/L), ``high'' (12.94 [mu]g/L), or ``low'' (<3 [mu]g/L)
perchlorate concentrations. The mean (
3. Physiologicallybased Pharmacokinetic (PBPK) Models
PBPK models represent an important class of dosimetry models that can be used to predict internal doses to target organs, as well as some effects of those doses (e.g., radioactive iodide uptake inhibition in the thyroid). To predict internal dose level, PBPK models use physiological, biochemical, and physicochemical data to construct mathematical representations of processes associated with the absorption, distribution, metabolism, and elimination of compounds. With the appropriate data, these models can be used to extrapolate across and within species and for different exposure scenarios, and to address various sources of uncertainty in health assessments, including uncertainty regarding the relative sensitivities of various subpopulations.
Clewell et al., (2007) developed multicompartment PBPK models describing the absorption and distribution of perchlorate for the pregnant woman and fetus, the lactating woman and neonate, and the young child. This work built upon Merrill et al.'s, (2005) model for the average adult. Related research that served as the basis for the more recent PBPK modeling efforts was discussed by the NRC in their January 2005 report on perchlorate.
The models estimated the levels of perchlorate absorbed through the gastrointestinal tract and its subsequent distribution within the body. Clewell et al., (2007) provided estimates of internal dose and resulting iodide uptake inhibition across all life stages, and for pregnant and lactating women. The paper reported iodide uptake inhibition levels for external doses of 1, 10, 100, and 1000 [mu]g/kg/ day. Results at the lower two doses indicated that the highest perchlorate blood concentrations in response to an external dose would occur in the fetus, followed by the lactating woman and the neonate. Predicted blood levels for all three groups (i.e., fetus, lactating women and neonates) were four to fivefold higher than for non pregnant adults. Smaller relative differences were predicted at external doses of 100 and 1000 [mu]g/kg/day. The authors attributed this change to saturation of uptake mechanisms. The model predicted minimal effect of perchlorate on iodide uptake inhibition in all groups at the 1 [mu]g/kg/day external dose (about one and one half times the RfD), estimating 1.1 percent inhibition or less across all groups. Inhibition was predicted to be 10 percent or less in all groups at an external dose of 10 [mu]g/kg/day (about 14 times the RfD).
The results of the model extrapolations were evaluated against data
developed in two epidemiologic studies performed in Chile, one studying
school children (Tellez et al., 2005) and another following women
through pregnancy and lactation (Gibbs et al., 2004). The model
predicted average blood serum concentrations of perchlorate in the
women from the Gibbs et al., (2004) study which were nearly identical
to their measured perchlorate blood serum concentrations. The blood
serum perchlorate concentrations predicted from the Tellez et al.,
(2005) study were within the range of the measured concentrations, and
the concentrations of perchlorate in breast milk predicted from the model were within two standard deviations of the measured
concentrations. The authors concluded that the model predictions were
consistent with empirical results and that the predicted extent of
iodide inhibition in the most sensitive population (the fetus) is not significant at EPA's RfD of 0.7 [mu]g/kgday.
The NRC recommended that inhibition of iodide uptake by the
thyroid, which is a precursor event and not an adverse effect, should
be used as the basis for the perchlorate risk assessment (NRC, 2005).
Consistent with this recommendation, iodide uptake inhibition was used
by EPA as the critical effect in determining the reference dose (RfD)
for perchlorate. Therefore, PBPK models of perchlorate and radioiodide, which were developed
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to describe thyroidal radioactive iodide uptake (RAIU) inhibition by
perchlorate for the average adult (Merrill et al., 2005), pregnant
woman and fetus, lactating woman and neonate, and the young child
(Clewell et al., 2007) were evaluated by EPA based on their ability to
provide additional information surrounding this critical effect for
potentially sensitive subgroups and reduce some of the uncertainty regarding the relative sensitivities of these subgroups.
EPA evaluated the PBPK model code provided by the model authors and found minor errors in mathematical equations and computer code, as well as some inconsistencies between model code files. EPA made several changes to the code in order to harmonize the models and more adequately reflect the biology (see USEPA, 2008b) for more information.
Model parameters describing urinary excretion of perchlorate and iodide were determined to be particularly important in the prediction of RAIU inhibition in all subgroups; therefore, a range of biologically plausible values available in the peerreviewed literature was evaluated in depth using the PBPK models. Exposure rates were also determined to be critical for the estimation of RAIU inhibition by the models and were also further evaluated.
Overall, detailed examination of Clewell et al., (2007) and Merrill et al., (2005) confirmed that the model structures were appropriate for predicting percent inhibition of RAIU by perchlorate in most lifestages. Unfortunately, the lack of biological information during early fetal development limits the applicability of the PBPK modeling of the fetus to a late gestational timeframe (i.e., near full term pregnancy, ~GW 40), so EPA did not make use of model predictions regarding early fetal RAIU inhibition. Although quantitative outputs of EPA's revised PBPK models differ somewhat from the published values, the EPA evaluation confirmed that, with modifications (as described in USEPA, 2008b), the Clewell et al., (2007) and Merrill et al., (2005) models provide an appropriate basis for calculating the lifestage differences in the degree of thyroidal RAIU inhibition at a given level of perchlorate exposure. The results of EPA's model application are discussed in Section IV.B.5.
B. Evaluation of Perchlorate Occurrence in Drinking Water
The primary source of drinking water occurrence data used to support this preliminary regulatory determination is the data provided by public water systems in accordance with the first Unregulated Contaminant Monitoring Regulation (UCMR 1). The Agency also evaluated supplemental sources of occurrence information.
1. The Unregulated Contaminant Monitoring Regulation. In 1999, EPA developed the UCMR program in coordination with the CCL and the National Drinking Water Contaminant Occurrence Database (NCOD) to provide national occurrence information on unregulated contaminants (September 17, 1999, 64 FR 50556 (USEPA, 1999b); March 2, 2000, 65 FR 11372 (USEPA, 2000b); and January 11, 2001, 66 FR 2273 (USEPA, 2001b)).
EPA designed the UCMR 1 data collection with three parts (or
tiers). Occurrence data for perchlorate are from the first tier of UCMR
(also known as UCMR 1 List 1 Assessment Monitoring). EPA required all
large \7\ PWSs, plus a statistically representative national sample of
800 small \8\ PWSs, to conduct Assessment Monitoring.\9\ Approximately
onethird of the participating small systems were scheduled to monitor
for these contaminants during each calendar year from 2001 through
2003. Large systems could conduct one year of monitoring anytime during
the 20012003 UCMR 1 period. EPA specified a quarterly monitoring
schedule for 1,896 surface water systems and a twiceayear, sixmonth
interval monitoring schedule for 1,969 ground water systems. The
objective of the UCMR 1 sampling approach for small systems was to
collect contaminant occurrence data from a statistically selected,
nationally representative sample of small systems. The small system
sample was stratified and populationweighted, and included some other
sampling adjustments, such as including at least 2 systems from each
State. With contaminant monitoring data from all large PWSs and a
statistical, nationally representative sample of small PWSs, the UCMR 1
List 1 Assessment Monitoring program provides a contaminant occurrence data set suitable for national drinking water estimates.
\7\ Systems serving more than 10,000 people.
\8\ Systems serving 10,000 people or fewer.
\9\ Large and small systems that purchase 100 percent of their
water supply were not required to participate in the UCMR 1 Assessment Monitoring or the UCMR 1 Screening Survey.
EPA collected and analyzed drinking water occurrence data for
perchlorate from 3,865 PWSs between 2001 and 2005 under the UCMR 1. EPA
found that 160 (approximately 4.1 percent) of the 3,865 PWSs that
sampled and reported had at least 1 analytical detection of perchlorate
(in at least 1 sampling point) at levels greater than or equal to the
method reporting limit (MRL) of 4 [mu]g/L. These 160 systems are
located in 26 States and 2 territories. Of these 160 PWSs, 8 are small
systems (serving 10,000 or fewer people) and 152 are large systems
(serving more than 10,000 people). These 160 systems reported 637
detections of perchlorate at levels greater than or equal to 4 [mu]g/L,
which is approximately 11.3 percent of the 5,629 samples collected by
these 160 systems and approximately 1.9 percent of the 34,331 samples
collected by all 3,865 systems. The maximum reported concentration of
perchlorate was 420 [mu]g/L, from a single surface water sample from a
PWS in Puerto Rico. The average concentration of perchlorate for those
samples with positive detections for perchlorate was 9.85 [mu]g/L and
the median concentration was 6.40 [mu]g/L. A summary of the perchlorate occurrence statistics in UCMR 1 is shown in Table 1.
\10\ Table 1 shows perchlorate detection sat levels greater than and equal to the MRL of 4 [mu]g/L.
Table 1UCMR 1 Occurrence of Perchlorate at Concentrations >= 4 [mu]g/L \10\
Sampling Sampling
System size Number of Samples w/ points points w/ Sampled Systems w/
samples detects tested detects systems detects
Small Systems..................... 3,295 15 1,454 8 797 8
Large Systems..................... 31,036 622 13,533 379 3,068 152 ¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤
Total Systems................. 34,331 637 14,987 387 3,865 160 Notes:
[[Page 60270]]
1. For both large and small systems, at 3,865 systems with data, there were 34,331 samples taken at 14,987
(entry) points resulting in 637 (1.86%) sample detects representing 387 (2.58%) of the entry/sample points in 160 (4.14%) of the systems.
2. For 3,068 large systems with data, there were 31,036 samples taken at 13,533 entry points resulting in 622
(2.00%) detections representing 379 (2.80%) entry/sample points in 152 (4.95%) of the systems.
3. For 797 small systems with data, there were 3,295 samples taken at 1,454 entry points, resulting in a total
of 15 (0.455%) detections representing 8 (0.55%) entry/sample points at 8 (1%) of the systems.
Table 2 presents EPA's estimates of the population served by water
systems for which the highest reported perchlorate concentration was
greater than various threshold concentrations ranging from 4 [mu]g/L
(MRL) to 25 [mu]g/L. The fourth column of Table 2 presents a high end
estimate of the population served drinking water above a threshold.
This column presents the total population served by systems in which at
least one sample was found to contain perchlorate above the threshold
concentration. EPA considers this a high end estimate because it is
based upon the assumption that the entire system population is served
water from the entry point that had the highest reported perchlorate
concentration. In fact, many water systems have multiple entry points
into which treated water is pumped for distribution to their consumers.
For the systems with multiple entry points, it is unlikely that the
entire service population receives water from the one entry point with
the highest single concentration. Therefore, EPA included a less
conservative estimate of the population served water above a threshold
in the fifth column in Table 2. EPA developed this estimate by assuming
the population was equally distributed among all entry points. For
example, if a system with 10 entry points serving 200,000 people had a
sample from a single entry point with a concentration at or above a
given threshold, EPA assumed that the entry point served onetenth of
the system population, and added 20,000 people to the total when
estimating the population in the last column of Table 2. This approach
may provide either an overestimate or an underestimate of the
population served by the affected entry point. In contrast, in the
example above, EPA added the entire system population of 200,000 to the
more conservative population served estimate in column 4, which is likely an overestimate.
Table 2UCMR 1 Occurrence and Population Estimates for Perchlorate Above Various Thresholds
Population
estimate
Population for entry
served by or sample
PWS entry or sample PWSs with points
PWSs with at least 1 points with at least 1 at least 1 having at
Thresholds \a\ detection > threshold of detection > threshold of detection > least 1
interest interest \b\ threshold detection >
of threshold
interest of
\c\ interest
\d\
4 [mu]g/L..................... 4.01%..................... 2.48%..................... \e\ 16.6 M 5.1 M
(155 of 3,865)............ (371 of 14,987)...........
5 [mu]g/L..................... 3.16%..................... 1.88%..................... 14.6 M 4.0 M
(122 of 3,865)............ (281 of 14,987)...........
7 [mu]g/L..................... 2.12%..................... 1.14%..................... 7.2 M 2.2 M
(82 of 3,865)............. (171 of 14,987)...........
10 [mu]g/L.................... 1.35%..................... 0.65%..................... 5.0 M 1.5 M
(52 of 3,865)............. (97 of 14,987)............
12 [mu]g/L.................... 1.09%..................... 0.42%..................... 3.6 M 1.2 M
(42 of 3,865)............. (63 of 14,984)............
15 [mu]g/L.................... 0.80%..................... 0.29%..................... 2.0 M 0.9 M
(31 of 3,865)............. (44 of 14,987)............
17 [mu]g/L.................... 0.70%..................... 0.24%..................... 1.9 M 0.8 M
(27 of 3,865)............. (36 of 14,987)............
20 [mu]g/L.................... 0.49%..................... 0.16%..................... 1.5 M 0.7 M
(19 of 3,865)............. (24 of 14,987)............
25 [mu]g/L.................... 0.36%..................... 0.12%..................... 1.0 M 0.4 M
(14 of 3,865)............. (18 of 14,987)............ Footnotes:
\a\ All occurrence measures in this table were conducted on a basis reflecting values greater than the listed thresholds.
\b\ The entry/samplepointlevel population served estimate is based on the system entry/sample points that had
at least 1 analytical detection for perchlorate greater than the threshold of interest. The UCMR 1 small
system survey was designed to be representative of the nation's small systems, not necessarily to be representative of small system entry points.
\c\ The systemlevel population served estimate is based on the systems that had at least 1 analytical detection for perchlorate greater than the threshold of interest.
\d\ Because the population served by each entry/sample point is not known, EPA assumed that the total population
served by a particular system is equally distributed across all entry/sample points. To derive the entry/
sample pointlevel population estimate, EPA summed the population values for the entry/sample points that had
at least 1 analytical detection greater than the threshold of interest.
\e\ This value does not include the population associated with 5 systems serving 200,000 people that measured perchlorate at 4 [mu]g/L in at least one sample.
2. Supplemental Occurrence Data. The Agency also evaluated drinking
water monitoring data for perchlorate in California and Massachusetts.
EPA considers these State data to be supplemental for purposes of this regulatory determination, because they are not nationally
representative. EPA believes these State's monitoring results are
generally consistent with the results collected by EPA under UCMR 1. The California Department of Public Health
[[Page 60271]]
(CDPH) last updated its perchlorate monitoring results on July 10, 2008
(CDPH, 2008). The Massachusetts's Department of Environmental
Protection (MA DEP) last updated its draft report on The Occurrence and
Sources of Perchlorate in Massachusetts in April, 2006 (MA DEP, 2005).
C. Evaluation of Perchlorate Exposure From Sources Other Than Drinking Water
An important element of EPA's regulatory determination process is to consider the contaminant exposure that individuals are likely to receive from sources other than drinking water. An individual's total exposure to a contaminant is more relevant to his or her risk for adverse health effects than is exposure to the contaminant from drinking water alone.
Because there are significant sources of perchlorate exposure other than through the drinking water route, EPA determined that data on exposure to perchlorate from these sources is critical to the evaluation of whether or not there is a meaningful opportunity for health risk reduction through a national primary drinking water rule for perchlorate. Dietary studies pose a particular challenge because there is great variety in the American diet and many foods must be analyzed to enable a comprehensive dietary exposure estimate. However, EPA believes that two recent studies provide a sound basis for evaluating total perchlorate exposure. These are the Food and Drug Administration (FDA) Total Diet Study and an analysis of NHANES/UCMR data conducted by EPA and CDC.
FDA's Total Diet Study (TDS) combines nationwide sampling and analysis of hundreds of food items along with national surveys of food intake to develop comprehensive dietary exposure estimates for a variety of demographic groups in the U.S. CDC's NHANES data base measured perchlorate in the urine of a representative sample of Americans. EPA and CDC used data from the NHANES data base and UCMR monitoring to estimate perchlorate exposure from food and water together, and food alone, for different subpopulations. This section of the notice provides details on the results of these studies. Because the sources of exposure encompassed by each of these studies overlap, EPA has considered them both in making a regulatory determination in an effort to provide the most comprehensive basis for the preliminary determination.
In this section, EPA also provides a brief review of other dietary and biomonitoring studies that, while not directly incorporated into our determination, tend to reinforce the results of the primary exposure studies.
1. Food Studies. The FDA, the United States Department of Agriculture (USDA), and other researchers have studied perchlorate in foods. The most recent and most comprehensive information available on the occurrence of perchlorate in the diet has been published by FDA. This section describes two perchlorate studies released by FDA.the Total Diet Study and FDA's Exploratory Survey Data on Perchlorate in Food.
a. FDA Total Diet Study, 2005 and 2006. Since 1961, FDA has periodically conducted a broadbased food monitoring study known as the Total Diet Study (TDS). The purpose of the TDS is to measure substances in foods representative of the total diet of the U.S. population, and to make estimates of the average dietary intake of those substances for selected agegender groups. A detailed history of the TDS can be found at the following Web site: http://www.cfsan.fda.gov/~comm/tdstoc.html.
Murray et al., (2008) briefly describe the design of the current TDS. Dietary intakes of perchlorate were estimated by combining analytical results from the TDS with food consumption estimates developed specifically for estimating dietary exposure from TDS results. While the perchlorate data for TDS foods were collected in 20052006, the food consumption data in the current TDS food list is based on results (Egan et al., 2007) from the USDA's 199496, 1998 Continuing Survey of Food Intakes by Individuals (9498 CSFII), which includes data for all age groups collected in 199496, and for children from birth through age 9 collected in 1998. Although over 6,000 different foods and beverages were included in the food consumption surveys, these foods and beverages were collapsed into a set of 285 representative foods and beverages by aggregating the foods according to the similarity of their primary ingredients and then selecting the specific food consumed in greatest quantity from each group as the representative TDS food for that group. The consumption amounts of all the foods in a group were aggregated and assigned to the representative food for that group. It is these 285 representative foods and beverages that are on the current TDS food list. This approach to estimating dietary intakes assumes that the analytical profiles (e.g., perchlorate concentrations) of the representative foods are similar to those of the larger group of foods from the original consumption survey to which they correspond. This approach provides a reasonable estimate of total dietary exposure to the analytes from all foods in the diet, not from the representative TDS foods alone. The sampled TDS foods are purchased at retail from grocery stores and fastfood restaurants. The foods are prepared tableready prior to analyses, using distilled water when water is called for in the recipe. The analytical method developed and used by FDA to measure perchlorate in food samples has a nominal limit of detection (LOD) of 1.00 ppb and a limit of quantitation (LOQ) of 3.00 ppb (Krynitsky et al., 2006).
Murray et al., (2008) reports that FDA included perchlorate as an analyte in TDS baby foods in 2005 and in all other TDS foods in 2006. Iodine was analyzed in all TDS foods from five market baskets surveyed in late 2003 through 2004. Using these data collectively, FDA developed estimates of average dietary perchlorate and iodine intake for 14 age gender groups. To account for uncertainties associated with samples with no detectable concentrations of perchlorate or iodine (nondetects or NDs), FDA calculated a lowerbound and upperbound for each estimate of average dietary exposure, assuming that NDs equal to zero and the LOD, respectively. Specifically, FDA multiplied these upper and lower bound concentrations by the average daily consumption amount of the representative food for the given subpopulation group to provide a range of average intakes for each TDS food.
Table 3 summarizes the FDA estimated upper and lowerbound average
dietary perchlorate intakes (from food) for 14 agegender groups on a
per kilogram of body weight per day basis to enable direct comparison
to the perchlorate RfD. Murray et al., (2008) reports that average body
weights for each population group were based on selfreported body weights from respondents in the 9498 CSFII.
[[Page 60272]]
Table 3Lower and UpperBound (ND = 0 and LOD) Perchlorate Intakes From FDA's TDS Results for 20052006
Average perchlorate intake
from food ([mu]g/kg/day) Population group
Lowerbound Upperbound
Infants611 mo........................ 0.26 0.29
Children2 yr.......................... 0.35 0.39
Children6 yr.......................... 0.25 0.28
Children10 yr......................... 0.17 0.20
Teenage Girls1416 yr................. 0.09 0.11
Teenage Boys1416 yr.................. 0.12 0.14
Women2530 yr......................... 0.09 0.11
Men2530 yr........................... 0.08 0.11
Women4045 yr......................... 0.09 0.11
Men4045 yr........................... 0.09 0.11
Women6065 yr......................... 0.09 0.10
Men6065 yr........................... 0.09 0.11
Women70+ yr........................... 0.09 0.11
Men70+ yr............................. 0.11 0.12
Based on their analysis of TDS data, FDA reports that detectable
levels of perchlorate were found in at least one sample in 74 percent
(211 of 286) of TDS foods (Murray et al., 2008). The average estimated
perchlorate intakes for the 14 agegender groups range from 0.08 to
0.39 [mu]g/kg/day, compared with the RfD of 0.7 [mu]g/kg/day. Though
not shown here, Murray et al., (2008) reports that average estimated
iodine intakes for the 14 agegender groups range from 138 to 353
[mu]g/person/day, and for all groups exceed the relevant U.S. dietary
reference values used for assessing the nutritional status of populations.\11\
\11\ Murray et al., (2008) compared estimated average iodine
intakes with U.S. Dietary Reference Intakes for iodine (NAS, 2000).
The reference values cited by Murray et al., (2008) are as follows:
130 [mu]g/person/day for infants, 65 [mu]g/person/day for children
18 years, 73 [mu]g/person/day for children 913 years, and 95 [mu]g/person/day for the remainder of population.
The results of the TDS dietary intake assessment provide an estimate of the average dietary perchlorate intakes by specific age gender groups in the U.S. However, Murray et al. note that the current TDS design ``does not allow for estimates of intakes at the extremes (i.e., upper or lower percentiles of food consumption) or for population subgroups within the 14 age/sex groups that may have specific nutritional needs (e.g., the subgroups of pregnant and lactating women within the groups of women of child bearing age).'' Nevertheless, Murray et al. stated that: ``These TDS results increase substantially the available data for characterizing dietary exposure to perchlorate and provide a useful basis for beginning to evaluate overall perchlorate and iodine estimated dietary intakes in the U.S. population.''
b. FDA Exploratory Survey Data on Perchlorate in Food, 20032005.
Prior to including perchlorate in the TDS, FDA conducted exploratory
surveys from October 2003 to September 2005 to determine the occurrence
of perchlorate in a variety of foods. In May 2007, FDA provided an
estimate of perchlorate exposure from these surveys (http://
www.cfsan.fda.gov/~dms/clo4ee.html). Using the data from these
exploratory studies and food and beverage consumption values from
USDA's 9498 CSFII, FDA estimated mean perchlorate exposures of 0.053
[mu]g/kg/day for all ages (2+ years), 0.17 [mu]g/kg/day for children
(25 years), and 0.037 [mu]g/kg/day for females (1545 years). There
are uncertainties associated with the preliminary exposure assessment
because the 27 foods and beverages selected represent only about 32 to
42 percent of the total diet depending on the population group.
Additionally, the overall goal of the sampling plan was to gather
initial information on occurrence of perchlorate in foods from various
locations with a high likelihood of perchlorate contamination. With the
preceding caveats in mind, the results of these exploratory studies are
generally consistent with the more complete results of the 20052006
TDS. For the purpose of developing a national estimate of dietary
perchlorate exposure, the results of FDA's exploratory studies are superseded by the results of the TDS.
c. Other Published Food Studies.
Since publication of EPA's May 2007 notice, Pearce et al., (2007) published an analysis of perchlorate concentrations in 17 brands of prepared ready to eat and concentrated liquid infant formula. Perchlorate concentrations in the 17 samples ranged from 0.22 to 4.1 [mu]g/L, with a median concentration of 1.5 [mu]g/L. The researchers did not estimate the dose infants would consume at the concentrations observed in the study. FDA also included sampling and analysis of infant formula in their 2008 TDS analysis, discussed above.
Studies, such as those published by Kirk et al., (2003, 2005) and Sanchez et al., (2005a, 2005b) have examined perchlorate in milk and produce. These studies and others were summarized in EPA's May 2007 notice describing the status of EPA's evaluation of perchlorate (72 FR 24016 (USEPA, 2007)).
2. Biomonitoring Studies. Researchers have also begun to investigate perchlorate occurrence in humans by analyzing for perchlorate in urine and breast milk. For example, CDC has included perchlorate in its National Biomonitoring Program, which develops methods to measure environmental chemicals in humans. With this information, the CDC can obtain data on levels and trends of exposure to environmental chemicals in the U.S. population.
a. Urinary Biomonitoring. In the largest study of its kind, Blount
et al., (2006c) measured perchlorate in urine samples collected from a
nationally representative sample of 2,820 U.S. residents as part of the
20012002 NHANES. Blount et al., (2006c) detected perchlorate at
concentrations greater than 0.05 [mu]g/L in all 2,820 urine samples
tested, with a median concentration of 3.6 [mu]g/L and a 95th
percentile of 14 [mu]g/L. Women of reproductive age (1544 years) had a median urinary perchlorate
[[Page 60273]]
concentration of 2.9 [mu]g/L and a 95th percentile of 13 [mu]g/L. The
demographic with the highest concentration of urinary perchlorate was
children (611 years), who had a median urinary perchlorate
concentration of 5.2 [mu]g/L. Blount et al., (2006c) estimated a total
daily perchlorate dose for the NHANES participants aged 20 and older
(for whom a creatinine correction method was available) and found a
median dose of 0.066 [mu]g/kg/day (about one tenth of the RfD) and a
95th percentile dose of 0.234 [mu]g/kg/day (about one third of the
RfD). Eleven adults (0.7 percent) had estimated perchlorate exposure
greater than perchlorate's RfD of 0.7 [mu]g/kg/day (the highest
calculated exposure was 3.78 [mu]g/kg/day). Because of daily
variability in diet and perchlorate exposure, and the short residence
time of perchlorate in the body, these single sample measurements may
overestimate longterm average exposure for individuals at the upper
end of the distribution and may underestimate the longterm average
exposure for individuals at the lower end of the distribution. Blount
et al. did not estimate daily perchlorate dose for children and
adolescents due to the limited validation of estimation methods for these age groups at that time (Blount et al., 2006c).
In a recent unpublished, but peer reviewed, study, EPA and CDC investigators merged the data sets from NHANES and UCMR 1 to identify the NHANES participants from counties which had a perchlorate detection during the UCMR survey (USEPA, 2008a). The
FOR FURTHER INFORMATION CONTACT Eric Burneson, Office of Ground Water
and Drinking Water, Standards and Risk Management Division, at (202)
5645250 or email burneson.eric@epa.gov. For general information
contact the EPA Safe Drinking Water Hotline at (800) 4264791 or e
mail: hotlinesdwa@epa.gov. Abbreviations and Acronyms
a. i.active ingredient
>greater than
>=greater than or equal to
[mu]microgram, onemillionth of a gram
[mu]g/gmicrograms per gram
[mu]g/kgmicrograms per kilogram
[mu]g/Lmicrograms per liter
ATSDRAgency for Toxic Substances and Disease Registry
AWWARFAmerican Water Works Association Research Foundation
BMDbench mark dose
BMDLbench mark dose level
BWbody weight for an adult, assumed to be 70 kilograms (kg) CASRNChemical Abstract Services Registry Number
CBIconfidential business information
ChEcholinesterase
CCLContaminant Candidate List
CCL 1EPA's First Contaminant Candidate List
CCL 2EPA's Second Contaminant Candidate List
CDCCenters for Disease Control and Prevention
CDPHCalifornia Department of Public Health
CFRCode of Federal Regulations
CMRChemical Monitoring Reform
CWScommunity water system
DWdry weight
DWELdrinking water equivalent level
DWIdrinking water intake
EPAUnited States Environmental Protection Agency
EPCRAEmergency Planning and Community RighttoKnow Act
FDAUnited States Food and Drug Administration
FQPAFood Quality Protection Act
FRFederal Register
FWfresh weight
ggram
g/daygrams per day
HRLhealth reference level
IOCinorganic compound
IRISIntegrated Risk Information System
kgkilogram
Lliter
LD
LOAELlowestobservedadverseeffect level
MA DEPMassachusetts Department of Environmental Protection
MCLmaximum contaminant level
MCLGmaximum contaminant level goal
mgmilligram, onethousandth of a gram
mg/kgmilligrams per kilogram body weight
mg/kg/daymilligrams per kilogram body weight per day
mg/Lmilligrams per liter
mg/m\3\milligrams per cubic meter
MRLminimum or method reporting limit (depending on the study or survey cited)
Nnumber of samples
NASNational Academy of Sciences
NCEHNational Center for Environmental Health (CDC)
NCFAPNational Center for Food and Agricultural Policy
NCINational Cancer Institute
NCWSnoncommunity water system
NDnot detected (or nondetect)
NDWACNational Drinking Water Advisory Council
NHANESNational Health and Nutrition Examination Survey (CDC) NISsodium iodide symporter
NOELnoobservedeffectlevel
NPDWRnational primary drinking water regulation
NPSNational Pesticide Survey
NQnot quantifiable (or nonquantifiable)
NRCNational Research Council
NTPNational Toxicology Program
OAoxanilic acid
OWOffice of Water
OPPOffice of Pesticide Programs
PBPKphysiologically based pharmacokinetic
PCRpolymerase chain reaction
PGWDBpesticides in ground water data base
PWSpublic water system
RAIUradioactive iodide uptake
REDReregistration Eligibility Decision
RfCreference concentration
RfDreference dose
RSCrelative source contribution
SABScience Advisory Board
SDWASafe Drinking Water Act
[[Page 60264]]
SOCsynthetic organic compound
SVOCsemivolatile organic compound
T3triiodothyronine
T4thyroxine
TDSTotal Diet Study (FDA)
TRIToxics Release Inventory
TSHthyroid stimulating hormone
TTtreatment technique
UCMR 1First Unregulated Contaminant Monitoring Regulation
UFuncertainty factor
USUnited States of America
USDAUnited States Department of Agriculture
USGSUnited States Geological Survey
USTunderground storage tanks
VOCvolatile organic compound
WHOWorld Health Organization
Supplementary Information:
I. General Information
A. Does This Action Impose Any Requirements on My Public Water System?
B. What Should I Consider as I Prepare My Comments for EPA? II. Purpose, Background and Summary of This Action
A. What is the Purpose of This Action?
B. Background on the CCL and Regulatory Determinations
C. What Comments and Information Did EPA Receive Regarding Perchlorate in Response to the May 1, FR Notice?
D. What is EPA's Preliminary Determination on Perchlorate and What Happens Next?
III. What Scientific Data and Analyses Did EPA Evaluate in Making a Preliminary Regulatory Determination for Perchlorate?
A. Evaluation of Adverse Health Effects
B. Evaluation of Perchlorate Occurrence in Drinking Water
C. Evaluation of Perchlorate Exposure from Sources Other Than Drinking Water
IV. Preliminary Regulatory Determination on Perchlorate
A. May Perchlorate Have an Adverse Effect on the Health of Persons?
B. Is Perchlorate Known to Occur or is There a Substantial Likelihood That Perchlorate Occurs at a Frequency and Level of Public Health Concern in Public Water Systems?
C. Is There a Meaningful Opportunity for the Reduction of Health
Risks From Perchlorate for Persons Served by Public Water Systems? V. EPA's Next Steps
VI. References
Common CFR Searches
14 CFR Part 39 40 CFR Part 52 14 CFR Part 71 33 CFR Part 165 50 CFR Part 679 47 CFR Part 73 26 CFR Part 1 40 CFR Part 180 33 CFR Part 117 50 CFR Part 17 44 CFR Part 67 50 CFR Part 648 14 CFR Part 97 40 CFR Part 63 33 CFR Part 100 50 CFR Part 622 50 CFR Part 660 44 CFR Part 65 26 CFR Part 301 39 CFR Part 111 40 CFR Part 300 6 CFR Part 5 40 CFR Part 271 47 CFR Part 64 40 CFR Parts 52 and 81 50 CFR Part 665 10 CFR Part 50 44 CFR Part 64 49 CFR Part 571 39 CFR Part 3020