Document ID: EPA-HQ-OPP-2007-0513-0043
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-10-29T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES,

AND TOXIC SUBSTANCES

October 23, 2008

Memorandum

SUBJECT: 	Response to Public Comments on the Triclosan Preliminary Risk 
			Assessment

FROM: 	Heather Garvie

Tim McMahon, Ph.D.

Timothy Leighton

Srinivas Gowda

Rick Petrie

Najm Shamim

Jonathan Chen

Patricia Jennings

TO:		Mark Hartman, Branch Chief

	Diane Isbell, Team Leader

	Antimicrobials Division

	 

Attached is the Agency’s Response to Comments document on the
triclosan preliminary risk assessment.  Please note that some of the
public comments have been summarized.  The document ID has been noted
next to each of the public comments so that the reader can reference the
comment in full on the triclosan public docket at   HYPERLINK
"http://www.regulations.gov"  www.regulations.gov  (docket ID #
EPA-HQ-OPP-2007-0513).  



1. Various grammatical, typographical and mathematical errors were
brought to the Agency’s attention.

Agency Response:  

These errors have been corrected.  

 From the Mass Comment Campaign Letter (EPA-HQ-OPP-2007-0513-0019):  

EPA has not established food use tolerances for triclosan and does not
plan to, even though triclosan can enter food via impregnated cutting
boards, is dispersed on crops via municipal biosolids, and
bioaccumulates in fish and other organisms.

Agency Response:  

Potential exposure via drinking water and food contact transfer from
triclosan-treated products (e.g., cutting boards) are captured in the
aggregate assessment using the National Health and Nutritional
Examination Survey (NHANES) data.  The NHANES 2003-2004 data set used to
assess the aggregate exposure of triclosan is from a random sample of
2,517 individuals that maintained the integrity of the representative
design of the survey (Calafat, et al 2007). In addition to NHANES data,
Agency also carried out the dietary risk assessment using the FDA
methodology of migration of pesticides into food through indirect
contact with: counter tops, cutting boards, ice-making equipments,
paper/paperboard, and conveyor belts. % aPADs, % cPADs for all these use
patterns did not result in any dietary risks of concern for U.S. adults
and children. The results of this methodology are consistent with the
results obtained by using NHANES data.

3.  From the Mass Comment Campaign Letter (EPA-HQ-OPP-2007-0513-0019): 

The risk assessment ignores the public health threat that triclosan

poses by promoting bacterial resistance and cross-resistance to
antibiotics.

Agency Response:

Antimicrobial resistance differs from antibiotic resistance, the latter
of which can be a concern in hospital or medical settings.  There is
currently some research attempting to demonstrate a connection between
antimicrobial resistance and antibiotic resistance in regard to
triclosan, but the linkage has not been expressly proven.   The Agency
continues to look into the issue of antimicrobial resistance and its
links to antibiotic resistance through review of current literature and
membership in the Interagency Task Force on Antimicrobial Resistance. 
The Task Force has a number of goals stated in the Public Health Action
Plan to Combat Antimicrobial Resistance (  HYPERLINK
"http://www.cdc.gov/drugresistance/actionplan/aractionplan.pdf" 
http://www.cdc.gov/drugresistance/actionplan/aractionplan.pdf ).  Though
none of the goals are associated with a specific active ingredient, many
of the activities are expected to further our understanding of the
processes involved with antimicrobial resistance, which may subsequently
further our understanding of any potential resistance from the use of
triclosan.  

The Agency will also continue to participate actively in the Interagency
Task Force on Antimicrobial Resistance described above and evaluate
information that results from that activity. Further, given the rapidly
developing scientific database for triclosan, the Agency intends to
accelerate the schedule for the registration review process for this
chemical.  Currently, the Agency intends to begin that process in 2013,
ten years earlier than originally planned.  In addition, the Agency is
aware that research is ongoing regarding triclosan.  The outcomes of
this further research may require the Agency to revisit this decision in
the future.

4. Comment:

From the Mass Comment Campaign Letter (EPA-HQ-OPP-2007-0513-0019): 

Triclosan poses unreasonable risks to wildlife, especially algae,
phytoplankton, and tadpoles. At levels currently found in waterways,
aquatic communities are already at risk.

Agency Response:

A qualitative environmental risk assessment was performed using
monitoring levels of triclosan found in waterways and toxicity values
from the tables in section I of the Ecological Hazard and Environmental
Risk Assessment Science Chapter for the Triclosan Reregistration
Eligibility Decision (RED) Document, dated September 11, 2008 to develop
risk quotients (RQs) and compare them to levels of concern (LOCs) for
triclosan.  LOCs were not exceeded for fish but were exceeded for
aquatic plants.  In addition, the Agency performed consumer
environmental modeling for triclosan.  The consumer environmental
modeling assumed that all triclosan used in the manufacture of the
antimicrobial uses is released into surface waters.  After adjustments
(see section II.B. of the Ecological Hazard and Environmental Risk
Assessment Science Chapter for the Triclosan Reregistration Eligibility
Decision (RED) Document, dated September 11, 2008), these models
concluded that estimated concentrations of triclosan in surface water do
not exceed concentrations of concern for acute risk presumptions for any
of the aquatic organisms and plants (vascular and non-vascular). 
Considering the low probability of triclosan being released into
household wastewater and surface waters from the antimicrobial uses, the
Agency also concludes that chronic aquatic risks are unlikely from
consumer uses of triclosan-treated plastic and textile items. 
Therefore, Agency can reasonably conclude that the antimicrobial uses of
triclosan (e.g., triclosan-treated plastic and textile items in
households) are unlikely to contribute significant quantities of
triclosan into household wastewater and eventually to surface water.

Environmental modeling and monitoring specific to plastic and textile
facilities, where triclosan is incorporated into these items, will be
required.  The technical registrants will be required via the DCI to
sample effluents from such facilities and receiving (surface) waters
adjacent to these facilities, determining the extent and duration of
triclosan and major degradates/metabolites (e.g., triclosan methyl).
Prior to beginning the environmental monitoring the registrants must
submit a protocol to the Agency for approval.  Depending upon the
results of this modeling and monitoring effort, the following ecological
effects data may be required (these studies are held in reserve):

Freshwater invertebrate acute study (850.1010) [Technical Grade Active
Ingredient (TGAI)];

Estuarine/marine fish acute study (850.1075) (TGAI)];

Estuarine/marine shrimp acute study (850.1035) (TGAI);

Estuarine/marine mollusk acute study (850.1025) (TGAI);

Fish early life-stage (freshwater) study (850.1400) (TGAI);

Aquatic invertebrate (freshwater) life-cycle study (850.1300) (TGAI);

Fish life-cycle study (850.1500) (TGAI);

Acute sediment toxicity to freshwater invertebrates (850.1735) (TGAI);

Acute sediment toxicity to estuarine invertebrates (850.1740) (TGAI);
and

Additional plant toxicity testing:  an additional algal toxicity test
(850.5400) with the freshwater green alga, Selenastrum capricornutum;
and studies on the rooted freshwater macrophyte, rice (Oryza sativa) –
850.4225 and 850.4250 (2 tests on seedling emergence and vegetative
vigor)

Oyster bioconcentration study – BCF (850.1710) (major
degradate/metabolite of triclosan – e.g., methyl triclosan)

Fish bioconcentration study – BCF (850.1730) (major
degradate/metabolite of triclosan – e.g., methyl triclosan)

13) Chironomid sediment toxicity test (850.1790) (major
degradate/metabolite of triclosan – e.g., methyl triclosan)

14) Aquatic food chain transfer (850.1850) (major degradate/metabolite
of triclosan – e.g., methyl triclosan)

15) Chronic sediment toxicity to freshwater and/or estuarine
invertebrates (no guideline number) (TGAI)

In addition, four studies to address bioaccumulation potential will also
be required via the DCI (850.1850; 850.1710; 850.1730; and 850.1790). 
Prior to conducting these studies, the registrants must submit protocols
to the Agency for approval.

5.  Comment:

From the Mass Comment Campaign Letter (EPA-HQ-OPP-2007-0513-0019): 

The risk assessment does not take into account triclosan exposure for

infants and young children, even though they are exposed in utero, as

demonstrated by studies that have detected triclosan in breast milk and
cord 

blood. 

Agency Response:   

An infant aggregate assessment has been added to the risk assessment. 
While NHANES data are measured exposures that represent the real world
co-occurrence of triclosan-treated products, it is necessary to use
screening-level deterministic assessments as well as to make assumptions
of potential co-occurrence of triclosan-treated products for younger
children.  USEPA (2005) Guidance on Selecting Age Groups for Monitoring
and Assessing Childhood Exposures to Environmental Contaminants, an
internally and externally scientific peer reviewed document, provides
the basis of the age group selection.  The age group of 6 to 12 months
old was selected to represent behavioral activities of children younger
than 6 years old that are exposed to triclosan-treated products. 
Characteristics of children at this age that potentially exposes
children to triclosan that would not have been captured by the 6-11 year
old age category in NHANES include nursing, increasingly likely to mouth
nonfood items (e.g., toys, combs & brushes, playground equipment), and
“development of personal dust clouds” as a characteristic relevant
to inhalation exposure.   The aggregate risks for infants 6 to 12 months
old have been estimated by combining the mean NHANES distribution with
the infant-specific bounding risks, with the exception of the inhalation
risks as they were considered negligible (MOEs in the millions and
therefore these risks do not effect the aggregate results).  See the
Revised Triclosan Residential and Occupational Risk Assessment, dated
September 8, 2008 for more information on the infant-specific exposure
pathways.  The aggregate MOE from the measured mean of the 6-11 year old
NHANES subjects combined with the bounding risks from nursing,
object-to-mouth, and hand-to-mouth indicate a long-term MOE of 390
(target MOE = 100).  The 99th percentile of the NHANES dose (when using
the 95% urine volume to estimate the 99th percentile dose) is combined
with the infant-specific bounding risks and indicates a long-term MOE of
290 (target MOE = 100). See the Triclosan Residential and Occupational
Exposure Assessment, dated September 8, 2008 for more information.

Comment:

From Ciba Specialty Chemicals and Harmet International
(EPA-HQ-OPP-2007-0513-0021):

The Agency states that the Soil Nitrification Study (MRID 472614-03) and
Soil Respiration Study (MRID 472614-04) were reviewed by the Agency and
both were classified as supplemental because EPA could not determine if
the soil used in these studies was comparable to soils found in a
typical triclosan use area in the United States.  In their joint
comments, Ciba Specialty Chemicals and Harmet explain why they believe
these studies should be classified as acceptable.

Agency Response:  

The studies were determined to be supplemental due to various study
deficiencies however, no additional testing is required.  The
environmental fate chapter has been updated as follows:

“This soil nitrification study was reviewed by the Agency and
classified as supplemental due to various study deficiencies such as: 
it could not be determined if the European soil used in this study was
comparable to soils found in a typical triclosan use area in the United
States; volatiles were not collected; extractable, nonextractable and
total residues were not determined; material balances was not reported;
the pass level was not reported; the half-life were not determined; the
test material was not radiolabeled; some physico-chemical properties
were not reported; soil collection, sampling depth and storage
conditions were not reported; indications of adsorption of the test
material to the walls of the test apparatus were not reported; microbial
soil biomass was not determined; maintenance of the test conditions in
the soil were not verified; samples were not analyzed for triclosan and
the transformation of the test material was not determined; dissolved
organic carbon was not determined.  Although the soil nitrification
study contains deficiencies, the data are useful and no additional
testing is required.”

“This soil respiration study was reviewed by the Agency and classified
as supplemental due to various study deficiencies such as:  it could not
be determined if the European soil used in this study was comparable to
soils found in a typical triclosan use area in the United States;
volatiles were not collected; extractable, nonextractable and total
residues were not determined; material balances was not reported; the
pass level was not reported; the half-life were not determined; the
radiochemical purity was not reported; soil collection, sampling depth
and storage conditions were not reported; indications of adsorption of
the test material to the walls of the test apparatus were not reported;
microbial soil biomass was not determined; maintenance of the test
conditions in the soil were not verified; samples were not analyzed for
triclosan and the transformation of the test material was not
determined; dissolved organic carbon was not determined; detection
limits were not reported; dinosebacetate caused a clear inhibitory
effect on soil microbial respiration.  Although the soil respiration
study contains deficiencies, the data are useful and no additional
testing is required.”

1 The Effects of Triclosan on soil respiration (Feb 2007), OECD test
guideline 217

2 The Effects of Triclosan on soil nitrification (Feb 2007), OECD test
guideline 216

7.  Comment:

From Ciba Specialty Chemicals and Harmet International
(EPA-HQ-OPP-2007-0513-0021): 

Literature on triclosan related to POTWs and
Bioaccumulation/Bioconcentration should be updated to reflect the state
of the available literature. Additionally, recently available data may
obviate the need to conduct an anaerobic aquatic metabolism study.
Specifically, published data relevant to anaerobic metabolism may be
sufficient to remove Agency concern about this potential data gap. 
Updated literature was provided by Ciba Specialty Chemicals and Harmet
International.

Agency Response:  

The seven published studies listed above were added to the reference
list. Ciba Corporation and Har-Met International, Inc. may submit a data
waiver request with supporting rationale for Anaerobic Aquatic
Metabolism (guideline 835.4400) in response to the DCI after it has been
issued. If a data waiver request is received, the Agency will consider
it.

8. Comment:

From Ciba Specialty Chemicals and Harmet International
(EPA-HQ-OPP-2007-0513-0021):

 

In the Preliminary Ecological Hazard and Environmental Risk Assessment
the use of the term “human wastes” as a use category for triclosan
is incorrect. Human waste is not a residential or public access use for
triclosan.

Agency Response:  

The use category “human wastes” has been removed from the chapter.

9. Comment:

From Ciba Specialty Chemicals and Harmet International
(EPA-HQ-OPP-2007-0513-0021):

EPA states that “an ecological risk assessment is not typically
conducted for the types of uses registered for triclosan. However, since
triclosan has been detected in natural waters, EPA has performed a
qualitative environmental risk assessment.” The Agency continues with
the statement that “depending on the results of environmental fate
studies which may be required, additional acute and chronic non-target
organism studies may be required”. This list of possible studies
should be addressed within the context of the extensive data submitted
to EPA, namely MRIDs 420279-08 (hydrolysis), 430226-08 (Photodegradation
in water), 472614-01 (aerobic soil biotransformation), 472614-02
(aerobic aquatic biotransformation), 472614-03 (soil nitrification),
472614-04 (soil respiration), 472614-06 (ready biodegradability under
abiotic conditions in anaerobic sludge), and 472614-07 (ready
biodegradability under abiotic conditions in

activated sludge).  Ciba submitted significant environmental fate data
on triclosan which was summarized by the agency, none of which was
employed in the fate assessment. We therefore ask the agency to rely
upon the data submitted to conduct an environmental fate assessment,
should they determine one is needed. Alternatively, the agency could
cite the “accepted” pre-publication terrestrial risk assessment data
in Reiss et al (2008 accepted for publication)3 and the published
aquatic risk assessment in Capedevielle et al (2007)4.  

Agency Response:  

The Agency has considered various data for the ecological risk
assessment.  All of the MRIDs cited in this comment have been reviewed
and summarized in the revised environmental fate chapter.  All studies
were deemed supplemental with the exception of MRIDs 43022608, 47261401
and 47261402.  An explanation as to why the studies were deemed
supplemental is provided in the revised environmental fate chapter.  In
addition, a qualitative ecological assessment was conducted as well as
environmental modeling.    Also, see Agency response to comment #4.  

Comment:

From Ciba Specialty Chemicals and Harmet International
(EPA-HQ-OPP-2007-0513-0021):

The EPA, as part of the RED process for triclosan, has asked the
registrants (Har-Met and Ciba), amongst others, to assist the Agency by
providing a scientific rationale that addresses the presence of
triclosan and its transformation products in environmental compartments
such as surface waters, biosolids, soil, fish and shellfish, with
particular emphasis on quantifying the contribution from triclosan uses
regulated by the EPA. The primary concern identified appears to be the
quantification of general triclosan usage separate from the
antimicrobial pesticide registered uses that contribute to its
environmental presence. This information has already been discussed with
the Agency through confidential communications between responsible
parties. As a follow-up, additional details can be provided under a
confidential submission from each registrant. In general terms it is
recognized that approximately only 5% of the total triclosan usage in
the US goes toward EPA regulated applications. Furthermore, the majority
of these uses are as a material preservative in plastics, with minimal
potential for contribution to an environmental load. The remaining
volume is sold for uses regulated by the FDA and elsewhere throughout
the world. Therefore, the existing literature findings (triclosan
environmental concentrations) relied on by the Agency would have to be
decreased by at least 90-95%. The existing, submitted and reviewed data,
combined with the many recent publications (see list above) support our
position that the environmental risks posed by EPA regulated uses of
triclosan are insufficient to justify an extensive battery of tests. In
addition, the USGS stream sampling process, summarized in the RED, was
intentionally biased toward sites susceptible to contamination
(downstream of intense urbanization and livestock production) which
further indicates that the environmental impact of triclosan at these
locations would be minimal.

Agency Response:  

See Agency response to comment #4. 

11. Comment:

From Ciba Specialty Chemicals and Harmet International
(EPA-HQ-OPP-2007-0513-0021):

 

The Agency includes the following statement: “Note that in a search of
the available data on triclosan, the US EPA Office of Water found an
EC50 as low as 0.13 mg/L and a NOEC as low as 0.006 mg/L for the
Cladoceran Ceriodaphnia dubia”, respectively. We find this citation
incomplete and unqualified, as the full study details are not presented.
In addition, the source of the triclosan tested, its purity, and
validation of GLP Guideline procedures are not mentioned. We ask that
the full details be provided or that the “note” be removed from the
document. EPA should subject these data to the same evaluative standards
that it expects from registrants.

Agency Response:

The Office of Water citations have been peer reviewed and deemed
acceptable for regulatory purposes.  It should be noted that the Office
of Water has done an evaluation of the existing database for triclosan
environmental effects and determined that the above-mentioned study is
acceptable for use in the development of Aquatic Life Water Quality
Criteria.  OPP understands this to be a rigorous peer review process and
believes the above statement beginning with "note" should remain. 
Further, these data are acceptable for use by OPP in its regulatory
decision-making process.  The full citation is: 

Orvos D.R., D.J. Versteeg, J. Inauen, M. Capdevielle, A. Rothenstein and
V. Cunningham. 2002. Aquatic toxicity of triclosan. Environ. Toxicol.
Chem. 21(7): 1338-1349.

12.  Comment:

From Ciba Specialty Chemicals and Harmet International
(EPA-HQ-OPP-2007-0513-0021):

  

Any comments related to label statements are held in abeyance pending
resolution of our ecological/environmental concerns.

Agency Response:

  

To be eligible for reregistration, labeling changes are necessary to
implement measures outlined in Section IV of the RED document.  Specific
language to incorporate these changes is presented in Table 10 of the
RED.  Generally, conditions for the distribution and sale of products
bearing old labels/labeling will be established when the label changes
are approved.  However, specific existing stocks time frames will be
established case-by-case, depending on the number of products involved,
the number of label changes, and other factors.

13.  Comment:

From Ciba Specialty Chemicals and Harmet International
(EPA-HQ-OPP-2007-0513-0021):

 

Ciba and HM both agree that the recommended concentration of triclosan
for textile usage is typically 1% and would like the opportunity to
discuss the revision of our respective technical bulletins during the
risk mitigation phase of the RED review process. In addition, neither of
us directly supplies triclosan for HVAC usage. It is not clear from whom
this registrant purchases their TGAI nor on what efficacy data they
rely. As such, this use should be eliminated from the registration.
Also, the only paint usage of which we are aware uses a concentration of
<0.5% in a limited specialty coating.

Agency Response:

The triclosan registrants are able to decrease the concentration of
triclosan for textile usage at any time.  The assessment was conducted
using rates found on currently approved labels for textiles and paint. 
Neither the aggregate assessment nor the dermal assessment found risks
of concern associated with the textile use.  The in-can material
preservative use of triclosan in paint triggered risks of concern. 
However, the registrants have requested voluntary cancellation of the
paint use (inclusive of stains and coatings).  Once the cancellation
order is complete, this risk will be considered mitigated.  The HVAC
efficacy data has been submitted, reviewed and deemed acceptable by the
Agency.  

14.  Comment:

From Ciba Specialty Chemicals and Harmet International
(EPA-HQ-OPP-2007-0513-0021):

The agency stated that “an absorption factor of 100% was used for
inhalation exposures because there are no data available to refine this
variable”. This is an inappropriate assumption. California Department
of Pesticide Regulations (DPR) uses a default absorption value of 50%,
based on experimentally determined inhalation absorption values of many
different chemicals at environmentally relevant concentrations (Raabe,
1988; Ross et al., 2001). For triclosan, given the fact that vapor
pressure is low and particle size plays an important and significant
role in absorption potential a less

conservative assumption would be more appropriate (Casarett & Doull’s
Toxicology5).

From the RED for Zinc Pyrithione as an in-can paint preservative, the
agency assumed that in real-use situations for commercial paint
applications, the occupational handlers will have adequate respiratory
protection by wearing either a dust/mist or organic vapor respirator as
PPE and adequate dermal protection by wearing gloves as recommended by
paint manufacturers. According to the EPA, use of gloves as PPE assumes
a 90% dermal protection factor and use of organic vapor respirator as
PPE assumes a 90% inhalation protection factor. We request that the
exposure calculations for triclosan in the

occupational handlers setting be adjusted accordingly. Additionally, the
RED for Zinc Pyrithione incorporated the use of human dermal absorption
data from its approved FDA applications as an antidandruff ingredient.
Based on this use of human data for its OTC drug use, we ask that the
human data in the OTC docket on triclosan dermal absorption also be
considered and used in the risk calculations. As such, the dermal
absorption assumption should be <20% as suggested by the EPA in the
toxicology chapter for triclosan.  Further support for not using a 100%
absorption assumption is that the approximate aerosol diameter of
airless sprayers is 20-50 µM (Berger-Preiss et al, 20056). This
produces an aerosol size distribution that is log- normal with a
bell-shaped probability curve resulting in the majority of paint
particles likely being >10 µM and thus not inhalable. Based on this
understanding of aerosol spray generation and particle size it is clear
that exposure via inhalation is minimal. In addition, the vapor pressure
of triclosan at 20°C is 1.5*10-6 torr, indicating that not only
particle size but inherent lack of volatility at ambient temperatures
(see appendix) removes any concern for an inhalation risk. Taken
together, these modifications to the exposure calculation assumptions
would result in MOE values in excess of the thresholds of 1000 for
inhalation exposure and 100 for dermal exposure for the paint related
applications. The calculation presented for the pulp and paper
industrial process needs to be clarified as the listed UE values do not
correspond to the listed CMA reference. In this case, the dermal UE
value of 0.00454 mg/lb ai and the inhalation UE of 0.000265 mg/lb ai
from the pulp and paper preservative loading study should have been
used. This correction, along with the use of the proper dermal
absorption estimate of <20% results in an acceptable MOE of 154.

Agency Response:

The generic equations presented for risk calculations were edited to
remove the “100%” inhalation absorption because the toxicological
data based for triclosan includes a route-specific inhalation toxicity
study.  The risks reported for inhalation exposure to triclosan are
based on the inhalation route-specific toxicity data, and therefore,
inhalation absorption assumptions are not used.  The inhalation concerns
for triclosan-treated paint are based on aerosol exposures, not vapor. 
Note:  EPA has inhalation concerns for aerosols up to 100 microns.

The dermal paint assessment relies on a route-specific dermal toxicity
study.  Therefore, a dermal absorption factor is not used in the risk
estimates.  

Estimated risks associated with the pulp & paper preservative loading
exposures are mitigated by the use of closed loading systems.  Product
labels will be revised to require the use of closed loading systems.

	 

15.  Comment:

From Ciba Specialty Chemicals and Harmet International
(EPA-HQ-OPP-2007-0513-0021):

The RED for Zinc Pyrithione incorporated the use of human dermal
absorption data from its approved FDA applications as an anti-dandruff
ingredient. Based on this use of human data from its OTC drug use, we
ask that the human data in the OTC docket on triclosan dermal absorption
also be considered and used in the risk calculations. As such, the
dermal absorption assumption should be at a maximum 20%, as suggested by
the EPA in the toxicology chapter for triclosan.

Agency Response:

The toxicology disciplinary chapter for Triclosan made the following
statement regarding dermal absorption: 

“A value of 50% dermal absorption for triclosan was selected on the
basis of a dermal absorption study conducted in rabbits (MRID 34335).
Since that time, additional dermal absorption data on triclosan  have
been submitted and reviewed.  In vitro dermal absorption studies using
human skin preparations and various formulations containing triclosan
(MRIDs 47261408 through 47261411) showed dermal absorption values for
triclosan ranging from 11-20% in these formulations.  A paper published
in 2000 by Moss et al.  (Food and Chemical Toxicology, Volume 38, pages
361-370) examined dermal absorption of triclosan both in vivo and in
vitro using rats as well as an in vitro human skin study. These data
supported the conclusion of dermal absorption of 21-23% in the rat
studies, and showed in vitro dermal absorption through human skin in
vitro of 6.3%.  Taken together, the available data on dermal absorption
suggest a lower value, around 20% for rat skin and possibly lower for
human skin.  Additional verification is needed.” 

The registrants cited several studies on in vivo dermal absorption of
triclosan as contained within formulations containing triclosan that
could be submitted to the Agency for review to verify whether in fact
dermal absorption in humans is significantly less than that observed in
rodent studies. The Agency informed the registrants that they could
submit these studies for review.  If these data support the conclusion
of lower dermal absorption in humans for triclosan, then the value could
be re-considered.  However, the dermal risk assessment relies on a
route-specific dermal toxicity study.  Therefore, a dermal absorption
factor is not used in the risk estimates.

16. Comment:

From Ciba Specialty Chemicals and Harmet International
(EPA-HQ-OPP-2007-0513-0021):

Section 4.9 Metabolism and Pharmacokinetics. The Stierlin, Schmid, and
Sutter (1977) metabolism study in multiple species, which predates GLP
guidelines, was assessed as Unacceptable/Nonguideline.  The agency
states that study was properly conducted and provided data regarding
excretion and plasma/blood kinetics of triclosan in monkeys, dogs, and
rats, and tissue distribution data in rats and mice, but metabolite
characterization was not a protocol component. We clarify here that the
metabolites were characterized for the dog and baboon, see MRID 79590.
These two studies were conducted in conjunction with each other. This
may result in reclassification of this study as acceptable/nonguideline
for these two species.

Agency Response:

The Agency acknowledges that MRID 79590 examined blood metabolites in
the dog and baboon.  However, it is not known if the animals used in
MRID 68161 were the same or different than those used in MRID 79590, and
several other deficiencies exist in MRID 68161.  The Agency is in
possession of other, acceptable guideline metabolism studies on
triclosan. The original classification for MRID 68161 will remain. 

17.  Comment:

From EWG summarized comments and recommendations
(EPA-HQ-OPP-2007-0513-0024):

	

Assess cumulative risks for infants drinking triclosan-contaminated
breast milk, and for all young children facing multiple exposures to
this pesticide. In the draft assessment, EPA has not evaluated the
safety of cumulative exposures to infants and young children from
contaminated breast milk and all other sources of the pesticide,
including house dust, contaminated food, plastic toys, bibs and
children’s clothing, and children’s body care products and
toothpaste. The biomonitoring studies on which the Agency relies for
cumulative exposure estimates do not include children under 6 years of
age. Triclosan poses particular risks to infants and young children, as
one study linked in utero exposures to the chemical to reduced fetal
weight and irregular skull formation during development. Other studies
link the pesticide to disruption of both the thyroid system and levels
of calcium ion in the body, which could impact growth and development
especially with respect to the brain and nervous system. 

Agency Response:

The dose reported by NHANES indicates a substantially higher dose for
the 20 to 59 year old age group compared to individuals of lesser age. 
However, it is correct that NHANES age group sampling begins with 6 year
olds.  Therefore, a separate aggregate assessment for infants has been
included in the revised risk assessment.

Comment:

From EWG summarized comments and recommendations
(EPA-HQ-OPP-2007-0513-0024):

Provide an adequate margin of safety for children. In the draft
assessment, EPA has not provided the additional margin of safety of a
factor of 10 that is required under the Food Quality Protection Act
(FQPA) for children exposed to pesticides. Although triclosan is not
approved as a food pesticide, it contaminates food and water consumed by
children and is widely used in children’s products. The Agency’s
failure to provide an additional safety margin of 10 to account for
potential neurodevelopmental effects and other impacts to which children
may be especially vulnerable violates the intent of the nation’s
pesticide law and leaves children at potential risk. 

Agency Response:

 

The Agency considered the available data for triclosan on the
developmental, reproductive, and neurotoxic effects of this chemical.
This determination is discussed in the risk assessment. The
determination from consideration of these data was that an additional
uncertainty factor to account for sensitivity of children was not needed
as there was no evidence that the effects of triclosan on developing
mammalian organisms or the young are qualitatively or quantitatively
different or more significant than those effects observed in adult
mammalian organisms. 

Comment:

From EWG summarized comments and recommendations
(EPA-HQ-OPP-2007-0513-0024):

Assess inhalation risks and other cumulative exposures to triclosan. In
the draft assessment, EPA has not evaluated risks for children and
adults who face the highest exposures and risks from triclosan,
particularly consumers who use triclosan-containing products that can be
inhaled, like powdered personal care products. EPA’s assessment
clearly shows that workers who apply triclosan-treated paint using
sprayers fall well outside standard safety margins, with a margin of
exposure of only 54. It is important that EPA assess risk from the full
range of Americans’ inhalation exposures, both residential and
occupational, since studies show that triclosan is most toxic when it is
inhaled, with harmful effects at every dose tested. Although the
biomonitoring data on which EPA relies capture a range of exposures
across the population, they do not allow for an assessment of
cumulative, high-risk inhalation exposures, and they do not encompass
the most highly exposed in the population who would face the greatest
risks. Cumulative exposure assessments that include occupational and
household exposures to triclosan are particularly critical for
commercial painters using airless spraying equipment, and pulp and paper
workers using metering pump equipment. 

Agency Response: 

Although the aggregate exposure/risk assessment using the NHANES data
provides an encompassing review of all triclosan-treated products, it
does not include exposures to children under the age of 6 years old.
Children under the age of 6 years exhibit unique activities that do not
occur at older ages. Therefore, a separate assessment for children under
6 years old has been conducted. In addition, dermal and inhalation
route-specific assessments were also conducted. 

Residential antimicrobial pesticide-registered uses of triclosan-treated
articles such as material preservative uses in mattresses, clothing,
tooth brush bristles, plastic toys, garbage bags, paper, playground
equipment, sponges, furniture, footwear, etc, will result in minimal
inhalation exposures.  Inhalation exposures are minimal because these
material preservative uses do not generate aerosols and triclosan has a
low vapor pressure (i.e., no off gassing).  The one EPA-registered
residential use of triclosan that is of concern via the inhalation route
(painting) is not aggregated with other cosmetic uses/spray deodorant
uses because it is of concern by itself.  The in-can material
preservative use of triclosan in paint has triggered risks of concern. 
However, the paint use (inclusive of stains and coatings) has been
requested to be voluntarily cancelled by the registrants.  Once the
cancellation order is complete, this risk will be considered mitigated.

20.  Comment:

From EWG summarized comments and recommendations
(EPA-HQ-OPP-2007-0513-0024):

Fully account for triclosan risks to human health. In the draft
assessment, EPA has not fully accounted for potential health risks posed
by triclosan. The Agency based its health risk calculations on a study
showing a NOAEL, or no observed adverse effect level, that is 4.6 times
higher than the NOAEL reported for a study documenting triclosan’s
ability to cause liver toxicity in mice. The Agency’s cancer risk
assessment relies on second-hand information, as EPA has stated that
Colgate has refused to provide them with its cancer study data upon
request. EPA further takes the controversial position that the liver
tumors linked to triclosan in the Colgate study are not relevant to
human health, though there is no scientific consensus on this subject.
EPA further neglects any assessment of triclosan’s potential to
disrupt the endocrine system, despite a growing body of research
indicating that the pesticide may affect thyroid and reproductive
hormone systems. 

Agency Response:  

On March 10, 1998, the Health Effects Division’s HIARC committee
examined the available carcinogenicity data for triclosan and was unable
to assign a classification to triclosan at that time since data for only
one species (rat) were submitted for evaluation of carcinogenicity. 
Since this determination, a chronic toxicity/carcinogenicity study in
the hamster (MRID 44874001) and a carcinogenicity study in the mouse
reviewed by the Food and Drug Administration were submitted and/or
obtained by the Agency.  The Agency was not able to obtain the
individual animal data records for the mouse carcinogenicity study but
was able to obtain the FDA’s review and Expert Panel reports on the
significance of the mouse study results.  On July 25, 2007, the Health
Effects Division’s Carcinogenicity Assessment Review Committee met to
discuss the additional data submitted as well as the biochemical studies
conducted with triclosan in support of a mode of action involving
peroxisome proliferation as a causative factor in the positive
tumorigenic results observed in the mouse carcinogenicity study. 

The overall weight of the evidence supports activation of peroxisome
proliferator-activated receptor alpha (PPARά) as the mode of action of
triclosan-induced hepatocarcinogenesis in mice.  Key precursor events
and the tumor response in mice were concordant with respect to both time
and dose.  The data did not support either a mutagenic mode of action or
a mode of action involving cytotoxicity followed by regenerative
proliferation as alternative modes of action.  While the proposed mode
of action for liver tumors in mice is theoretically plausible in humans,
it is quantitatively implausible and unlikely to take place in humans
based on quantitative species differences in PPARά activation and
toxicokinetic differences between the mouse and human.

 tc "V. 	SUMMARY" 

ά activation and toxicokinetics.  The quantification of risk is not
required.  

There is some evidence that triclosan disrupts thyroid hormone
homeostasis and interacts with the androgen and estrogen receptors. The
available evidence is summarized in the
5-Chloro-2-(2,4-dichlorophenoxy)phenol (Triclosan): Toxicology Chapter
for the Reregistration Eligibility Decision (RED) Document, dated August
29, 2008. The Agency is aware that research is ongoing regarding
endocrine effects of triclosan, and this further research may require
future modification to the risk assessment and the RED for triclosan. 
The EPA process of regulating pesticides allows for reevaluation at any
time if new information becomes available.

21.  Comment:

From EWG summarized comments and recommendations
(EPA-HQ-OPP-2007-0513-0024):

Fully consider triclosan risks to the environment. In the draft
assessment, EPA has not fully assessed the potential environmental risks
posed by triclosan. Though triclosan is known to have significant acute
effects on algae and other aquatic species, and is widely detected in
streams across the U.S., EPA found no studies that assessed chronic
ecotoxicological effects of the pesticide. Further, EPA’s evaluation
identifies data gaps including the lack of acceptable studies of
triclosan’s acute effects on freshwater invertebrates, marine
organisms, and selected plants. The Agency further ignores the risks
posed by triclosan that contaminates biosolids applied to agricultural
lands. EPA also neglects to assess the impact of exposure of low levels
of antimicrobial agents like triclosan on the biological wastewater
treatment systems essential to preserving the water quality of rivers
and lakes throughout the country, as well as clean water supplies for
downstream communities. 

Agency Response:  

See Agency response to comment #4.   

Comment:

From EWG summarized comments and recommendations
(EPA-HQ-OPP-2007-0513-0024):

Assess risks associated with triclosan’s transformation products. In
the draft assessment, EPA has not assessed potential health and
environmental risks posed by triclosan’s many transformation products.
In chlorinated or natural waters, triclosan can be transformed into a
number of other chemicals, including methyl triclosan, chloroform, and
even a form of dioxin. EPA’s draft risk assessment mentions some of
these chemicals, but does not evaluate associated exposures or risks for
any of them. 

Agency Response:

See Agency response to comment #4.

Comment:

From EWG summarized comments and recommendations
(EPA-HQ-OPP-2007-0513-0024):

Assess risks relating to antimicrobial resistance. In the draft
assessment, EPA has not assessed potential health risks that could
result through development of antimicrobial resistance to triclosan.
Laboratory evidence and common sense indicate that microbes can develop
resistance to the antibiotic effects of triclosan, rendering the
pesticide ineffective. 

Agency Response:

See Agency response to comment #3.

Comment:

Beyond Pesticides Comment (EPA-HQ-OPP-2007-0513-0025):

Triclosan Is Hazardous for Human Consumption in Food and Water. 

EPA is incorrect in not conducting a formal Food Quality Protection Act
(FQPA) analysis simply because there are “no food use tolerances for
triclosan.” In fact, EPA recognizes that triclosan residues pose a
potential hazard to humans through the food and water supply. The agency
has a duty to establish triclosan food tolerances and “acceptable”
water levels based on triclosan use patterns. These use patterns, as
directed by product labels, directly result in triclosan residues in the
food and water supply. The agency acknowledges that triclosan use
patterns result in exposure through food and water and therefore they
should be subject to an EPA exposure and risk assessment under a formal
FQPA analysis.  One of EPA’s registered triclosan products, EPA Reg
#2829-139 (Vinyzene dp 7000), is incorporated into cutting boards.
Researchers have found that triclosan can migrate from kitchenware info
food, including from a treated cutting board. “[E]xperiments performed
with TCS-containing kitchenware and foodstuff samples confirmed the
capability of this bactericide to migrate from treated surfaces to
food.”[2] EPA should not register any uses of triclosan that come in
contact with food before exposures are adequately assessed and a food
use tolerance set.    In stating that there are “no existing food use
tolerances for triclosan,” and that “a formal FQPA analysis is not
needed for this chemical,”(p8)[3] EPA maintains that,  “[T]he Agency
is concerned with such widespread detection of triclosan and triclosan
methyl residues because such residues may result in potential adverse
effects to humans and/or nontarget organisms, including fish, birds,
plants, algae, or other organisms.” In addition, EPA has identified
numerous outstanding data gaps. (p22)[4] The agency’s concerns have
been confirmed in recent scientific research detailing the presence of
triclosan and its residues within fish,[5] establishing an important
source of dietary exposure for the public.   Under FQPA, “a pesticide
chemical residue in or on a food shall be deemed unsafe…” 21 USC
346a(a)(1), unless EPA sets a tolerance for the chemical, or grants
exemptions from the requirement to set a tolerance. The agency, in
failing to account for exposures to contaminated fish in its dietary
risk assessment,[6] and in light of this statutory stipulation, should
deem triclosan and its residues as unsafe in food (such as fish and
shellfish, for example), given that no known tolerance has been set and
no exemption has been granted.  The presence of triclosan in surface
waters poses a dietary risk through drinking water. Triclosan is not
completely removed from treated water[7-9] and, unlike wastewater, most
surface water runoff that enters storm drains is untreated and directly
flows into creeks and rivers, which supply the drinking water for many
municipalities across the U.S. Even though the agency has noted that
this dietary exposure should be included in its aggregate risk
assessment,[3] EPA has not explicitly recognized and evaluated this
pathway and associated residues in its aggregate risk assessment. Given
the EPA's duty under FQPA, a formal FQPA analysis should be conducted to
include drinking water.  

Agency Response: 

See Agency response to comment #2. 

25.  Comment:

Beyond Pesticides Comment (EPA-HQ-OPP-2007-0513-0025):

‟ is defined under 7 USC § 136(bb) as “any unreasonable risk to man
or the environment, taking into account the economic, social and
environmental costs and benefits of the use of any pesticide.”   The
agency, however, has not evaluated or recognized that triclosan, in its
capacity as an antibacterial substance, poses real and substantial risks
to the public in its role in promoting bacterial resistance and
cross-resistance to clinically important antibiotics.   Since 2000, a
number of studies have verified the occurrence of triclosan resistance
among a variety of microorganisms. Evidence is mounting that links the
use of triclosan-containing products with the promotion of bacteria
resistant to antibiotic medications and antibacterial products.[10, 11]
Resistance effects have been shown at low, bacteriostatic and
sub-biocidal levels.[12] Triclosan resistant strains of Escherichia coli
and Salmonella enterica have already been identified.[13-15] Of major
concern is the possibility that triclosan resistance may contribute to
reduced susceptibility to clinically important antimicrobials, due to
either cross-resistance or co-resistance mechanisms. Studies examining
the mechanisms through which triclosan resistance arises have identified
gene mutations, increased target expression, and enzymatic action as
pathways leading to resistance.[11, 13, 14, 16] According to Stuart
Levy, M.D., Tufts University School of Medicine, these mechanisms lead
to a transfer of resistant genes that fosters antibiotic resistance,
some of them accounting for the observed cross-resistance with
antibiotics.[13, 17]    These studies indicate that extensive use of
triclosan provides a suitable environment for the emergence of
antimicrobial drug–resistant species, even at very low concentrations.
  EPA-regulated products, like cutting boards, counter tops, sponges,
toothbrushes, etc., expose bacteria and other microorganisms to
long-term, low levels of triclosan, which promote resistance, according
to the literature. Recent appearances of drug resistant super bugs, like
methicillin-resistant Staphylococcus aureus (MRSA),[12, 13] illustrate
the importance of conducting a full evaluation of the impacts of
triclosan residues left by triclosan-treated products.    The increasing
emergence of drug and antibacterial resistant microorganisms is a direct
threat to public health and the environment. It is therefore of the
utmost importance that the agency determines that triclosan does pose
“unreasonable risks” and reconsider its registration.  

Agency Response:  

See Agency response to comment #3.  

26.  Comment:

Beyond Pesticides Comment (EPA-HQ-OPP-2007-0513-0025):

EPA Fails to Conduct an Adequate Aggregate Risk Assessment.  The use of
biomonitoring (urine) data does not release the agency of its
responsibility to conduct its own aggregate risk assessment for
individual EPA and FDA regulated uses of triclosan. These uses, and
combination of uses, are not fully captured when using the National
Health and Nutrition Examination Survey (NHANES) to extrapolate
individual exposure to triclosan. In fact, EPA acknowledges that the
NHANES data is based on “consumer use of the various triclosan
products” and is “actual”(p9) for the population surveyed in the
survey. This does not fulfill the agency’s responsibility to assess
the potential aggregate exposure to all the registered uses. The NHANES
data also fails to take into account exposures for infants, children,
and in utero exposures, which is unacceptable given the evidence that
triclosan is in human fatty tissues. Biomonitoring data can supplement,
but does not substitute for, aggregate risk assessment in a laboratory
setting with controlled dosing. EPA acknowledges that, “Converting
spot urine concentration [from NHANES] to dose is a difficult
endeavor.”(p9) Beyond that, the agency must consider fatty tissue
residues, which has not been done. 

Agency Response:   

The Agency has revised the risk assessment to include the use of the
NHANES survey data.  The nationally representative design of the NHANES
survey captures the co-occurrence of EPA- and FDA-registered uses.  EPA
has provided various methods of converting spot urine concentrations of
triclosan to dose to account for uncertainties in spot urine sampling. 
For example, EPA used a very conservative method in the conversion from
a urine concentration to a dose that assumes all individuals sampled
excreted the 95%tile of daily urine volume (including the 95 percentile
of daily urine excretion at the 99th percentile of the aggregate
exposure from NHANES).  Other aspects of triclosan that reduce the
likelihood of underestimating dose from spot urine samples are that the
triclosan uses such as tooth paste and hand soaps occur daily and the
urinary excretion half-life is relatively short (i.e., 11 hours) that
would capture peak co-occurring exposures at the 99th percentile. 
However, NHANES does not capture children under the age of 6 years old
that exhibit unique behavioral activities that may lead to exposures not
accounted for by the 6 year old population.  Therefore, a separate
aggregate exposure/risk assessment for infants has been added to the
assessment.

Also, see Agency response to comment #2.

27.  Comment:

Beyond Pesticides Comment (EPA-HQ-OPP-2007-0513-0025):

Risk Assessment Conclusions Are Clouded by EPA-Stated Uncertainties.  
EPA, in its unequivocal stance that triclosan exhibits no risk of
concern, accepts high degrees of uncertainty throughout its analysis,
uncertainties that establish a cloud over its conclusions. There are a
series of deficiencies and limitations noted in the document that do not
seem to affect the agency’s determination to allow the triclosan
market to grow unrestricted. The acknowledgment of serious data
deficiencies and “no risk of concern” conclusions may be taken as an
attempt to absolve the agency and its regulators from responsibility of
a future when adverse effects are linked to the widespread and growing
use of this chlorinated, bioaccumulative chemical, clearly associated
with environmental and food contamination, serious bacterial resistance
and cross-resistance with antibiotics.   Some of the uncertainty
statements that are found throughout the Preliminary Risk Assessment for
the Reregistration Eligibility Decision (RED) document include (emphasis
added): 

 Uncertainties associated with dose conversion for the aggregate
assessment for triclosan arise from using the biological monitoring data
from NHANES... "these uncertainties are balanced (and perhaps even
offset) by..." by several factors listed. ( p22) 

 "The NHANES results are believed to be representative of a range of
acute to chronic exposures to children and adults because of the
relatively short half-life of triclosan in urine (i.e., 11 hours) and
the often daily use of triclosan products such as hand soaps and
toothpaste." (p22) 

  "There are several data limitations and uncertainties associated
with the occupational handler and post application exposure
assessments…" (p30) and include: (1) Surrogate dermal and inhalation
unit exposure values, which had poor data quality and require that
confirmatory data be submitted to support the occupational scenarios.
(2) The quantities handled/treated were estimated since no standard
values were available for some [occupational] scenarios. These estimates
could be further refined from input from registrants.  

 Acute toxicity testing with estuarine and marine organisms was not
required for triclosan because end-use products are not intended for
direct application to the marine/estuarine environment or effluent
containing the active ingredient is not expected to reach this
environment. As a result, "No studies have been submitted to fulfill
these data requirements." (p35) (However, literature has found that
triclosan does indeed reach the estuarine environment via effluent and
other surface runoff. Therefore, this data gap is unacceptable.)  

 Algal toxicity tests have been "partially fulfilled." Studies on the
rooted freshwater macrophyte rice (Oryza sativa) have not been
submitted. (p37)  

 "There were no acceptable acute toxicity studies for freshwater
invertebrates or estuarine and marine organisms nor were there any
acceptable chronic toxicity studies available for aquatic organisms.
Therefore, risk to these species cannot be assessed." (p40)   

 The agency has identified that "there is a potential for triclosan
use to overlap with listed [endangered] species and that a more refined
assessment is warranted, to include direct, indirect and habitat
effects." However, "[T]his analysis has not been conducted for this
assessment. An endangered species effect determination will not be made
at this time." (p41)  

Agency Response: 

Acknowledging uncertainties and limitations in data and methodologies is
a fundamental step in characterizing a risk assessment.  Based on the
characterization of the toxicity and exposure assessment, the conclusion
is drawn that the margins of exposure (MOEs) are above the target MOE
established in the review of the toxicological data base.  Additional
characterization of the toxicological data base will be provided based
on ongoing research activities involving triclosan.  

Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2),
requires all federal agencies to consult with the National Marine
Fisheries Service (NMFS) for marine and anadromous listed species, or
the United States Fish and Wildlife Services (FWS) for listed wildlife
and freshwater organisms, if they are proposing an "action" that may
affect listed species or their designated habitat.  Each federal agency
is required under the Act to insure that any action they authorize,
fund, or carry out is not likely to jeopardize the continued existence
of a listed species or result in the destruction or adverse modification
of designated critical habitat.  To jeopardize the continued existence
of a listed species means “to engage in an action that reasonably
would be expected, directly or indirectly, to reduce appreciably the
likelihood of both the survival and recovery of a listed species in the
wild by reducing the reproduction, numbers, or distribution of the
species” (50 CFR §402.02).

To facilitate compliance with the requirements of the Endangered Species
Act subsection (a)(2) the Environmental Protection Agency, Office of
Pesticide Programs has established procedures to evaluate whether a
proposed registration action may directly or indirectly reduce
appreciably the likelihood of both the survival and recovery of a listed
species in the wild by reducing the reproduction, numbers, or
distribution of any listed species (U.S. EPA 2004).  After the
Agency’s screening-level risk assessment is performed, if any of the
Agency’s Listed Species LOC Criteria are exceeded for either direct or
indirect effects, a determination is made to identify if any listed or
candidate species may co-occur in the area of the proposed pesticide
use.  If determined that listed or candidate species may be present in
the proposed use areas, further biological assessment is undertaken. 
The extent to which listed species may be at risk then determines the
need for the development of a more comprehensive consultation package as
required by the Endangered Species Act.

For certain use categories, the Agency assumes there will be minimal
environmental exposure, and only a minimal toxicity data set is required
(Overview of the Ecological Risk Assessment Process in the Office of
Pesticide Programs U.S. Environmental Protection Agency - Endangered and
Threatened Species Effects Determinations, 1/23/04, Appendix A, Section
IIB, pg.81). Chemicals in these categories therefore do not undergo a
full screening-level risk assessment, and are considered to fall under a
no effect determination. This preliminary analysis indicates that there
is a potential for triclosan use to overlap with listed species and that
a more refined assessment is warranted, to include direct, indirect and
habitat effects.  The more refined assessment should involve clear
delineation of the action area associated with proposed use of triclosan
and best available information on the temporal and spatial co-location
of listed species with respect to the action area.  This analysis has
not been conducted for this assessment and therefore an endangered
species effect determination will not be made at this time.  The refined
endangered species assessment will be performed under the Registration
Review program (see   HYPERLINK
"http://www.epa.gov/oppsrrd1/registration_review/" 
http://www.epa.gov/oppsrrd1/registration_review/  for more information)
and will include a species by species analysis.

In addition, see Agency response to comment #4.  

28.  Comment:

Beyond Pesticides Comment (EPA-HQ-OPP-2007-0513-0025):

Triclosan Exposures and Health Risks Not Adequately Assessed.  Based on
population-based biological monitoring data, conducted by the
NHANES,[18]  the agency concluded that, “[T]he aggregate risks to
triclosan from all uses (EPA and FDA) do not trigger a risk of
concern.”(p9)[3] However, even though this study documented the
prevalence of triclosan among the U.S. population and reflects high
levels of human exposure, the agency has not sufficiently evaluated all
human exposures from products that come under its jurisdiction.  People
are exposed to triclosan mainly via dermal absorption[19] and such
exposures can result in contact dermatitis, skin irritation and
photoallergic contact dermatitis (PACD).[20-23] Residential dermal
exposures to triclosan arise due to its use on treated articles such as
mattresses, clothing, plastic toys, sponges, countertops, etc. However,
in its Occupational and Residential Exposure Assessment, the agency
fails to take into account residential exposure to treated articles such
as countertops, floors and paint that occur over the long-term
(chronic). To add to the deficiency, triclosan treated mattresses are
also not assessed separately and the agency states, “ Triclosan
treated mattresses are not assessed separately but are not of concern as
they are treated at the same concentration as the
textiles/clothing.”(p18)[24] The agency has evaluated short-term and
intermediate dermal exposures for textiles, and short-term exposure
durations for child exposure (dermal and oral) to toys.[24] Whereas it
is feasible that textiles may result in short-term to intermediate
exposures, treated mattresses should undoubtedly be assessed for
long-term (chronic) exposures, given that percutaneous absorption of
triclosan occurs,[25, 26] which can lead to skin irritation and
dermatitis, and whose long-term (chronic) effects in humans are still
uncertain.   The chemical structure of triclosan closely resembles
non-steroidal estrogens and because of this, has the ability to act as
an endocrine disruptor. It induces changes in the thyroid
hormone-mediated process of metamorphosis of the North American
bullfrog, and alters the expression profile of the thyroid hormone
receptor, even at concentrations as low as 0.15ug/L.[27-29] In fact,
studies have shown that triclosan does indeed have androgenic[28, 30]
and estrogenic activity.[30, 31] There is evidence that triclosan may
also affect the central nervous system,[32] the immune system,[1] and
renal toxicity has been observed in laboratory animals.[33]    According
to the risk assessment, EPA did not consider the endocrine disrupting
effects of triclosan because the development of an Endocrine Disruptor
Screening Program (EDSP) has not been completed.  As a consequence, it
neglects analyzing an entire category of potential adverse health
effects.  In fact, the risk assessment omits a group of studies that,
taken together, suggest that triclosan may be an endocrine disrupting
chemical, capable of interfering with multiple hormones controlling
reproduction and neurodevelopment.    There is precedent for the agency
to consider endocrine disrupting effects in a human health risk
assessment in the absence of a final EDSP.  For example, in the RED for
atrazine, the agency examined the potential endocrine disrupting effects
of atrazine on amphibians, undermining any agency claim that existing
studies of the endocrine disrupting effects cannot be considered in its
human health risk assessments. Accordingly, given the studies suggesting
that triclosan has the potential to cause endocrine disrupting effects,
EPA should have quantitatively incorporated these endpoints in its risk
assessment of triclosan.     As a lipophilic chemical, triclosan
bioaccumulates in fatty tissues. Studies have found concentrations of
triclosan in three out of five human milk samples at concentrations
ranging from 5.8ng/g to 11ng/g[34, 35]as well as in umbilical cord blood
of infants,[36] demonstrating that babies are exposed to concentrations
of triclosan in and out of the womb. These results raise concerns for
the developing fetus during vulnerable periods of development, and
elevate concerns regarding the bioaccumulative and endocrine disruptive
potential of triclosan. Another recent study has identified triclosan in
indoor dust at an average value of 702 ng/g, a level similar to what is
reported for this compound in municipal sludge.[7] This new research
adds another facet to the routes of human exposure that the agency has
not considered.  

Agency Response:

See Agency response to comments #2 and #27.

In addition, the Agency has updated the section of the risk assessment
dealing with endocrine disruption.  There is some evidence that
triclosan disrupts thyroid hormone homeostasis and interacts with the
androgen and estrogen receptors. The available evidence is summarized in
the 5-Chloro-2-(2,4-dichlorophenoxy)phenol (Triclosan): Toxicology
Chapter for the Reregistration Eligibility Decision (RED) Document,
dated August 29, 2008. The Agency is aware that research is ongoing
regarding endocrine effects of triclosan, and this further research may
require future modification to the risk assessment and the RED for
triclosan.  The EPA process of regulating pesticides allows for
reevaluation at any time if new information becomes available.

Comment:

Beyond Pesticides Comment (EPA-HQ-OPP-2007-0513-0025):

Occupational Protection is Deficient. EPA identifies severely elevated
occupational exposure risks for commercial painters and material
preservative use in paper, and then assumes full protection with
personal protection equipment. At the same time that EPA documents
severely excessive occupational hazards, it points out that “the use
of chemical resistant gloves on the label is impractical,” but in
contradiction assumes that requirements for personal protection
equipment (PPE) will be followed and virtually eliminate exposure and
risk. The agency has no evidence that PPE is practical, will be used,
and is effective.   

Agency Response:

Clarifications have been made to the risk assessment.  For occupational
uses it is OPP practice to mitigate dermal irritation by requiring the
user to wear personal protective equipment (PPE) (e.g., chemical
resistant gloves and clothing).  Mitigating with PPE is only a viable
option for pesticide-labeled products (i.e., a label is needed to inform
workers to wear PPE).  Therefore, EPA can direct workers using
pesticide-labeled products (concentrated form) at the manufacturing
setting to wear PPE to mitigate dermal irritation.  Conversely, for
in-can material preservatives there is no pesticide label that goes with
the preserved product to inform the workers that any PPE may be needed
(i.e., there is no pesticide label on a can of paint).  Thus PPE is not
a viable option to mitigate exposure to products preserved by triclosan
such as the in-can paint use.   

Dermal irritation was selected for the short-term (ST) dermal endpoint. 
The intermediate-term (IT) dermal endpoint is based on systemic effects
(i.e., not dermal irritation).   IT dermal risks for the occupational
painters have been triggered.   These IT dermal risks for the
occupational painters can not be mitigated via PPE as described above
(i.e., no label on the in-can material preservative for paint). 
However, the paint use (inclusive of stains and coatings) has been
requested to be voluntarily cancelled by the registrants.  Once the
cancellation order is complete, this risk will be considered mitigated.

30.  Comment:   

Beyond Pesticides Comment (EPA-HQ-OPP-2007-0513-0025):

Failure to Consider Chemicals with a Common Mechanism of Toxicity.   
EPA acknowledges that it did not carry out a critical cumulative risk
assessment to assess triclosan's effects in combination with other
chemicals that have a common mechanism of toxicity. This requirement in
FQPA, adopted in 1996, for which EPA issued guidance for public comment
in January 2002 (67 FR 2210-2214), has not been carried out for the
triclosan RED 12 years after taking effect. According to EPA, “AD
[Antimicrobial Division] did not perform a cumulative risk assessment as
part of this RED for triclosan because AD has not yet initiated a review
to determine if there are any other chemical substances that have a
mechanism of toxicity common with that of triclosan.” (p27)[3] We note
that the agency does not seem to take its risk assessment process and
scientific integrity very seriously when it chooses to ignore a risk
factor that could have dramatic impact on the safety of human health and
the environment.   EPA’s failure to act is especially deficient
because the antimicrobial triclocarban, which is a widely used
ingredient in soaps and deodorants, co-occurs in the environment with
triclosan[9]. These two chemicals have similar modes of action and is an
obvious candidate for common mechanism consideration. EPA must consider
the obvious and carry out its responsibility under this RED.  

Agency Response:

The Agency acknowledges that triclocarban has been detected along with
triclosan in the environment.  Although there may be some structural
similarity between triclosan and triclocarban, these chemicals belong to
two different classes (hydroxyphenylether and hydroxyphenylurea
respectively).   Further, there is not necessarily a relationship
between the mechanism of antimicrobial activity and mechanism of
toxicity in mammals. There is currently insufficient evidence to suggest
that these two chemicals share a common mechanism of toxicity with
respect to toxic effects in mammals and that a cumulative assessment
should be conducted.

31.  Comment:

Beyond Pesticides Comment (EPA-HQ-OPP-2007-0513-0025):

Triclosan Poses Unreasonable Risks to Wildlife and the Environment. The
United States Geological Survey's (USGS) study of the occurrence of
pharmaceuticals, hormones, and other organic wastewater contaminants in
water resources found that triclosan is one of the most detected
chemicals in U.S. surface waters. [37] This is because most triclosan
product uses (both EPA and FDA uses, such as antibacterial dish liquid)
are washed down the drain and contaminate waterways and water treatment
facilities.   According to the USGS study, the maximum concentration of
triclosan found was 280ng/L (with a median concentration of 40ng/L). The
environmental risk assessment conducted by EPA concluded that, based on
these observed concentrations, levels of concern were not exceeded for
fish or aquatic plants.[3]    Even though research involving
triclosan’s impact on the environment are new, some studies from the
literature have found significant declines in plant communities exposed
to triclosan. One study notes that significant reductions in algal
biomass for cyanobacteria and Chlamydomonas at 150 ng/L of
triclosan,[38]  a concentration well below the maximum concentration
observed in the USGS study. This suggests that algal communities are
being impacted at concentrations below those not considered a concern by
the agency. Another study confirmed that risks are high, particularly
for blue-green algae exposed to antibiotics, and both green and
blue-green algae exposed to triclosan.[39]  The vulnerability of algae,
which are important primary producers within the aquatic environment, to
contaminants such as triclosan poses serious consequences for aquatic
ecosystems.  Methyl triclosan, a derivative of triclosan, has been
detected in fish at concentrations in the range of other persistent
organic pollutants.[5] These levels can lead to death in fish and
increase vitellogenin production in fish eggs, which suggests estrogenic
activity.[8]Triclosan has also been detected in earthworms feeding off
the sludge from water treatment plants.[40] In tadpoles, exposure to
environmentally relevant concentrations of triclosan (at 150 ng/L)
causes changes in thyroid hormone receptor gene expression, a reduction
in body weight, increased hind limb development, and a decrease in
swimming activity.[5, 8, 27]    The agency has identified several data
gaps that are of concern, including algal toxicity tests, acute
freshwater invertebrate studies and fish early life-stage (freshwater)
studies, which have yet to be submitted by registrants.[41]    Label
hazard statements/use recommendations proposed by the agency are (1)
“This pesticide is toxic to fish and aquatic invertebrates,” and (2)
“Do not discharge effluent containing this product into lakes,
streams, ponds, estuaries, oceans, or other waters unless in accordance
with the requirements of a National Pollutant Discharge Elimination
System (NPDES) permit …”[41]   It is unclear why the agency would
recommend these label statements, while permitting the uses of products
that are recognized as having the ability to adversely impact aquatic
systems. Many of the EPA regulated uses involve the discharge of
triclosan into waterways. For example, triclosan textiles, when
laundered, create effluent that would impact waterways and water
treatment facilities. The agency has not only failed to address these
impacts in its assessment, but has not fulfilled its responsibility to
show that these uses do not pose “unreasonable adverse effects on the
environment,” as defined in 7 USC §136(bb). Wastewater treatment
plants (WWTP) are impacted by the high concentrations of triclosan in
wastewater. Triclosan, being a biocide, removes large populations of
beneficial bacteria needed for the water treatment process, placing an
economic burden on WWTPs. Triclosan adsorbs onto the sludge/sediment and
has been detected in river and estuarine sediments,[8, 42] and impacts
aquatic species in sensitive habitat regions. Sludge from WWTPs is
normally recycled and used on agricultural land, further impacting
terrestrial microbes essential for healthy ecosystems, as a result of
triclosan’s activity towards a wide spectrum of microbial species.[8]
The above-mentioned reinforces a finding that triclosan does not meet
the criteria in 7 USC § 136a(c)(5)(c). 

Agency Response:

See Agency response to comment #4.  

In response to the labeling question:

On July 23, 1993, the Office of Pesticide Programs (OPP) issued P.R.
Notice 93-10 which specified that the following revised effluent
discharge statements should appear on the labeling of pesticide products
falling within the scope of that notice: 

"Do not discharge effluent containing this product into lakes, streams,
ponds, estuaries, oceans or other waters unless in accordance with the
requirements of a National Pollutant Discharge Elimination System
(NPDES) permit and the permitting authority has been notified in writing
prior to discharge. Do not discharge effluent containing this product to
sewer systems without previously notifying the local sewage treatment
plant authority. For guidance contact your State Water Board or Regional
Office of the EPA." 

The purpose of these statements is to remind manufacturers, formulators,
and facilities which may use and discharge pesticides of their
obligations under the Clean Water Act or to local Publicly Owned
Treatment Works (POTW). OPP believes that these parties may be already
aware of their obligations via other mechanisms at the state and local
level. While OPP has specified variations of the above labeling
statements since the late 1970s, the purpose of these statements has
been to simply augment other mechanisms used by the Office of Water, the
states and local POTWs to inform pesticide producers and users of their
obligations under the CWA or local authorities. 

32.  Comment 

Beyond Pesticides Comment (EPA-HQ-OPP-2007-0513-0025):

 

Analysis Fails to Address Endangered Species.   Since the agency
acknowledges that it does not have the required data to evaluate impacts
on endangered species, it should not issue a final RED, which implies
compliance with regulatory standards. EPA states, “A preliminary
analysis indicates that there is a potential for triclosan use to
overlap with listed species and that a more refined assessment is
warranted, to include direct, indirect and habitat effects.”(p13)[3]
In a footnote, EPA states, “The Agency is making this statement
because triclosan and triclosan transformation products are being
detected in various environmental components.” The agency, similar to
other sections where it has not met its statutory responsibility, simply
concludes with the statement, “An endangered species effect
determination will not be made at this time.”(p13)  

Agency Response:

Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2),
requires all federal agencies to consult with the National Marine
Fisheries Service (NMFS) for marine and anadromous listed species, or
the United States Fish and Wildlife Services (FWS) for listed wildlife
and freshwater organisms, if they are proposing an "action" that may
affect listed species or their designated habitat.  Each federal agency
is required under the Act to insure that any action they authorize,
fund, or carry out is not likely to jeopardize the continued existence
of a listed species or result in the destruction or adverse modification
of designated critical habitat.  To jeopardize the continued existence
of a listed species means “to engage in an action that reasonably
would be expected, directly or indirectly, to reduce appreciably the
likelihood of both the survival and recovery of a listed species in the
wild by reducing the reproduction, numbers, or distribution of the
species” (50 CFR §402.02).

To facilitate compliance with the requirements of the Endangered Species
Act subsection (a)(2) the Environmental Protection Agency, Office of
Pesticide Programs has established procedures to evaluate whether a
proposed registration action may directly or indirectly reduce
appreciably the likelihood of both the survival and recovery of a listed
species in the wild by reducing the reproduction, numbers, or
distribution of any listed species (U.S. EPA 2004).  After the
Agency’s screening-level risk assessment is performed, if any of the
Agency’s Listed Species LOC Criteria are exceeded for either direct or
indirect effects, a determination is made to identify if any listed or
candidate species may co-occur in the area of the proposed pesticide
use.  If determined that listed or candidate species may be present in
the proposed use areas, further biological assessment is undertaken. 
The extent to which listed species may be at risk then determines the
need for the development of a more comprehensive consultation package as
required by the Endangered Species Act.

For certain use categories, the Agency assumes there will be minimal
environmental exposure, and only a minimal toxicity data set is required
(Overview of the Ecological Risk Assessment Process in the Office of
Pesticide Programs U.S. Environmental Protection Agency - Endangered and
Threatened Species Effects Determinations, 1/23/04, Appendix A, Section
IIB, pg.81). Chemicals in these categories therefore do not undergo a
full screening-level risk assessment, and are considered to fall under a
no effect determination. This preliminary analysis indicates that there
is a potential for triclosan use to overlap with listed species and that
a more refined assessment is warranted, to include direct, indirect and
habitat effects.  The more refined assessment should involve clear
delineation of the action area associated with proposed use of triclosan
and best available information on the temporal and spatial co-location
of listed species with respect to the action area.  This analysis has
not been conducted for this assessment and therefore an endangered
species effect determination will not be made at this time.  The refined
endangered species assessment will be performed under the Registration
Review program (see   HYPERLINK
"http://www.epa.gov/oppsrrd1/registration_review/" 
http://www.epa.gov/oppsrrd1/registration_review/  for more information)
and will include a species-by-species analysis.

33.  Comment:

Beyond Pesticides Comment (EPA-HQ-OPP-2007-0513-0025):

EPA Fails to Evaluate Major Degradates.  Triclosan in water, when
exposed to sunlight, degrades and forms toxic compounds, like
2,8-dichlorodibenzo-p-dioxin (DCDD), dichlorophenols and other similar
compounds, [7, 8, 43-45] which are known to be carcinogenic and
persistent. Other major degradates, as identified by the agency, include
methyl triclosan, which has been shown to bioaccumulate in aquatic
organisms and possibly in human beings, as well as 2,4-dichlorophenol
(DCP), which is listed by the European Union as a potential endocrine
disruptor,[46] and an EPA priority pollutant.[47] Triclosan has also
been found to interact with free chlorine, normally occurring in tap
water, to form chloroform.[48] The agency has failed to conduct risk
assessments for these major degradates and transformation products,
which pose substantial hazards beyond those associated with the active
ingredient itself.[7] 

Agency Response: 

The 2,8 dichlorodibenzo-p-dioxin congener has no dioxin-like activity
and does not bind to the Ah receptor.  It is also not accurate to assume
that dioxin congeners, dichlorophenols, or other contaminants in the
environment are the sole result of any degradation of triclosan.  

There is some evidence that triclosan disrupts thyroid hormone
homeostasis and interacts with the androgen and estrogen receptors. The
available evidence is summarized in the
5-Chloro-2-(2,4-dichlorophenoxy)phenol (Triclosan): Toxicology Chapter
for the Reregistration Eligibility Decision (RED) Document, dated August
29, 2008. The Agency is aware that research is ongoing regarding
endocrine effects of triclosan, and this further research may require
future modification to the risk assessment and the RED for triclosan. 
The EPA process of regulating pesticides allows for reevaluation at any
time if new information becomes available.

In addition, see Agency response to comment #4 regarding degradates.  

34.  Comment:

Beyond Pesticides Comment (EPA-HQ-OPP-2007-0513-0025):

 

EPA Fails to Evaluate Triclosan Efficacy and Necessity.  40 CFR
158.640(1) states that efficacy data is waived unless “the pesticide
product bears a claim to control pest microorganisms that pose a threat
to human health and whose presence cannot be observed by the user
including but not limited to, microorganisms infectious to man in any
area of the inanimate environment..,” however, the agency’s
documents do not indicate the submission of such data. Low
concentrations of triclosan in products such as sponges, cutting boards,
etc. only serve to increase bacterial resistance, as cited above, and,
in turn, threaten human health. In the absence of efficacy data, it is
unclear whether these products indeed serve the purpose they are
intended for, or whether they serve to exacerbate the problem. With
proper hygiene and sanitation, triclosan treated products become
redundant.    

Agency Response:

Triclosan treated article products are bacteriostatic in nature, meaning
that they prevent growth, and are not registered to “kill” specific
organisms of public health concern.  If this were the case, efficacy
data would be submitted and reviewed by the Agency.  Prior to 1982, data
was collected for products with claims not related to public health.  At
that time it was determined that sufficient efficacy data for
bacteriostatic claims had been gathered.  A registrant is still required
to conduct efficacy data and keep it on file, however it is currently
not reviewed by the Agency.  Should new information be received that
would warrant the re-examination of these claims, the Agency has the
right to ask for such data under 40CFR 161.640(a)(1).

35.  Comment:

Beyond Pesticides Comment (EPA-HQ-OPP-2007-0513-0025):

‟ and contain triclosan as the active ingredient (e.g. Ajax
Antibacterial, Dawn Antibacterial). Upon closer examination, labels
state “Fights germs on hands when used as a hand soap.” The human
and environmental impacts that arise from the product's primary use for
dishes have not been accounted for by either agency. The fact that the
manufacturer on the label refers only to its antimicrobial effects on
hands does not release EPA of the responsibility to evaluate the
exposure and health and environmental impacts associated with its
primary use on dishes. Certainly, EPA should be concerned about the use
pattern of a product such as this on inanimate objects and the
possibility of short and long-term dermal and oral exposures to the
active ingredient, which is a known and registered pesticide.    Another
issue is the reality that many triclosan treated products are exempt
from registration because of claims to only protect the product in which
it is incorporated. According to the EPA, the Code of Federal
Regulations allows an exemption for:  “An article or a substance
treated with or containing a pesticide to protect the article or
substance itself (for example, paint treated with a pesticide to protect
the paint coating, or wood products treated to protect the wood against
insects or fungus infestation), if the pesticide is registered for such
use.”[49]   Products such as hairbrushes, hair accessories, and
sporting equipment, including helmets, etc., have been identified as
containing triclosan but have eluded EPA review for incidental human
health effects in the RED. EPA has failed to assess whether human
exposures, especially dermal exposures, occur as a result of the use of
such products. The RED falls short in not assessing a large number of
products on the market to which humans are exposed, with product
packaging advertising triclosan components that offer “antimicrobial
product protection.” While the manufacturer claims product protection,
these products‟ use patterns create human and environmental exposures.

Agency Response: 

As indicated in the comment above, there are a wide variety of
triclosan-treated products.  The NHANES data provides for measured
exposures to the general population for the wide range of
triclosan-treated products used by consumers (both EPA and FDA regulated
products).  The potential for dermal irritation to occur from incidental
dermal exposures from products treated at low concentrations of
triclosan are expected to be minimal.  For example, the localized dermal
irritation effects tested at the concentrated product (i.e., 99 percent
triclosan) occurs at levels lower than the NOAEL of 100 ug/cm2 and EPA
applied a 10x uncertainty factor for risk assessment purposes.  Plastic
articles are treated at a use dilution of 0.5 percent triclosan.  Only a
fraction of triclosan in impregnated articles would be available on the
surface.  Furthermore, only a fraction of the triclosan on the surface
would be transferred to a localized skin area for irritation to occur. 
For illustrative purposes, the film thickness of a fluid on the hands is
1.75 mg/cm2, which was extracted from the document entitled, “A
Laboratory Method to Determine the Retention of Liquids on the Surface
of Hands” (Cinalli, 1992).  The film thickness is based on a machinist
immersing both hands in metalworking fluid and then partially cleaning
hands with a rag.  Clearly this is an exaggerated estimate of exposure
compared to dermal contact of triclosan-impregnated articles.  This type
of a screening-level approach indicates that 1.75 mg/cm2 x 1000 ug/mg
unit conversion x 0.005 triclosan application rate is 8.75 ug/cm2.  This
conservative estimate does not indicate a dermal irritation concern.
Additional residue transfer assumptions for impregnated articles up to 2
percent could be determined for similar screening-level assessments but
are not warranted based on the above discussions. Dermal irritation is
concentration dependant.  Given the exaggerated screening-level
assessments illustrated above, refinements to more accurately assess
dermal irritation would require additional studies in animals at the
dilute concentration to which consumers are exposed (e.g., 0.5 to 2
percent).

36.  Comment:

Beyond Pesticides Comment (EPA-HQ-OPP-2007-0513-0025):

Incident Reporting Has Been Undermined by EPA.   This document cannot be
independently evaluated without a comment about the “no reported
incidents for triclosan” comment in the RED, which grows out of a long
history of the agency undermining the effective collection of data that
could and should inform regulatory action. As the agency knows, the
Pesticide Incident Monitoring System (PIMS) was shut down by EPA, thus
limiting the agency’s access to data from trained sites associated
with outreach and data collection efforts.  The Centers for Disease
Control Poison Control Centers, while important, picks up the most
egregious poisonings, usually those caused by accidental ingestion. The
FIFRA 6(a)2 “incident” data that EPA collects from pesticide
manufacturers has been emasculated by the agency’s own guidelines and
lack of enforcement, and is deficient by not requiring manufacturers to
report all communication with the public on adverse effects of its
products. EPA itself, in its OPP Report on Incident Information,
characterizes the 6(a)2 data as “low to uneven levels of detail, lack
of fully automated system difficulty of working with data (need to
review hard copies instead of electronic searches).” While it is
admittedly challenging to manage an effective database, the agency has
not made it a priority and effectively undermined its value, making its
“no reported incidents” less than meaningful.   

Agency Response:

The following databases are included in the Agency incident data search:

OPP Incident Data System (IDS) - The Incident Data System of The Office
of Pesticide Programs (OPP) of the Environmental Protection Agency (EPA)
contains reports of incidents from various sources, including
registrants, other federal and state health and environmental agencies
and individual consumers, submitted to OPP since 1992.  Reports
submitted to the Incident Data System represent anecdotal reports or
allegations only, unless otherwise stated.  Typically no conclusions can
be drawn implicating the pesticide as a cause of any of the reported
health effects.  Nevertheless, sometimes with enough cases and/or enough
documentation risk mitigation measures may be suggested.

Poison Control Centers - as the result of a data purchase by EPA, OPP
received Poison Control Center data covering the years 1993 through 2003
for all pesticides.  Most of the national Poison Control Centers (PCCs)
participate in a national data collection system, the Toxic Exposure
Surveillance System, which obtains data from about 65-70 centers at
hospitals and universities.  PCCs provide telephone consultation for
individuals and health care providers on suspected poisonings involving
drugs, household products, pesticides, etc.

California Department of Pesticide Regulation - California has collected
uniform data on suspected pesticide poisonings since 1982.  Physicians
are required, by statute, to report to their local health officer all
occurrences of illness suspected of being related to exposure to
pesticides.  The majority of the incidents involve workers.  Information
on exposure (worker activity), type of illness (systemic, eye, skin,
eye/skin and respiratory), likelihood of a causal relationship, and
number of days off work and in the hospital are provided.

National Pesticide Telecommunications Network (NPTN) - NPTN is a
toll-free information service supported by OPP.  A ranking of the top
200 active ingredients for which telephone calls were received during
calendar years 1984-1991, inclusive, has been prepared.  The total
number of calls was tabulated for the categories of human incidents,
animal incidents, calls for information, and others.; and

Incidents and Epidemiological Studies Published in Scientific Literature

Reported incidents do not reflect all health concerns associated with
chemical exposure.  Therefore, the Agency relies on the risk assessment
to evaluate potential risks of concern.  In addition, federal law
requires registrants of pesticides to inform EPA about harmful effects
of their products. These effects include, for example, unexpected levels
of toxicity observed in test animals or incidents such as death or
hospitalization of a person. Information reportable under this provision
includes not only new information derived from scientific studies, but
also reports of incidents of harmful effects resulting from the use of
pesticide products. Thus, the requirement provides an important check on
the correctness of the original decision to register a pesticide. 

The Agency uses risk assessments to characterize the nature and
magnitude of health risks to humans (e.g., residents, workers,
recreational visitors) and ecological receptors (e.g., birds, fish,
wildlife) from chemical contaminants and other stressors, that may be
present in the environment.  Risk managers use this information to help
them decide how to protect humans and the environment from stressors or
contaminants. 

37.  Comment:

Various public comments were received stating personal opinions on the
preliminary risk assessment and reregistration of triclosan.

 

Agency Response:

The Agency acknowledges these submissions.  The Agency is strongly
committed to involving stakeholders and the public in its development of
pesticide reregistration decisions.

Comment:  

McKenna Long & Aldridge comment regarding use of triclosan as a
materials preservative in conveyer belts (EPA-HQ-OPP-2007-0513-0027):

Agency Response:  

The Agency will contact McKenna Long & Aldridge regarding this
submission.

Comment:

From the Tri-TAC Comment Letter on the ecological risk assessment,
cumulative risk and environmental fate (EPA-HQ-OPP-2007-0513-0029): 

TriTAC believes that all quantities of triclosan in the environment
should be attributed to antimicrobial uses.  Uses of triclosan that are
regulated by the Food and Drug Administration, such as toothpaste and
antimicrobial hand soap, are antimicrobial in nature and contribute to
the concentrations found in the environment that cause water quality
impacts and impacts to biota.  If FDA-regulated uses are found to
contribute a significant portion of environmental concentrations, EPA
should work with the FDA to incorporate mitigation measures for impacts
irrespective of source.

Agency Response:

The nationally representative design of the NHANES survey captures the
co-occurrence of EPA-registered and FDA-regulated uses.  

Comment:

From the Tri-TAC Comment Letter on the ecological risk assessment,
cumulative risk and environmental fate (EPA-HQ-OPP-2007-0513-0029):

TriTAC contends that the ecological hazard and environmental risk
assessment chapter identifies several data gaps and indicates additional
studies may be required.  The chapter neglects the issue of endocrine
disruption in aquatic organisms in aquatic organisms, which have been
documented by others and show that triclosan may have thyroidal,
oestrogenic and androgenic effects[1,2].  Because triclosan is typically
found in receiving waters at trace concentrations, endocrine disruption
and chronic effects to aquatic biota may be more probable than acute
effects and should therefore be incorporated in this risk assessment. 
Furthermore, because some species may be harmed at early stages in their
development, early life development studies should be required for
freshwater, marine, and estuarine organisms.

Agency Response:

The Agency has updated the section of the risk assessment dealing with
endocrine disruption.  Also, see Agency response to comment #4 and the
second paragraph of the Agency response to comment #33.

41. Comment:

From the Tri-TAC Comment Letter on the ecological risk assessment,
cumulative risk and environmental fate (EPA-HQ-OPP-2007-0513-0029):

The subchapter, “Estuarine and Marine Organisms, Acute”, states that
no acute toxicity for estuarine and marine organisms is required because
“effluent containing the active ingredient” is not expected to reach
this environment.  However, the Environmental Fate chapter shows that
triclosan is indeed expected in effluent.  In light of this, acute
toxicity for estuarine and marine organisms should be required.

Agency Response:

The Agency has revised the ecological hazard and environmental risk
assessment science chapter for the Triclosan Reregistration Eligibility
Decision (RED) Document.  See Agency response to comment #4.

42. Comment:

From the Tri-TAC Comment Letter on the ecological risk assessment,
cumulative risk and environmental fate (EPA-HQ-OPP-2007-0513-0029):

The ecological hazard and environmental risk assessment chapter notes
that hazard labels will be required on products with registered uses of
triclosan.  We are concerned that other uses of triclosan not covered by
this re-registration, such as antimicrobial hand soap and toothpaste,
will continue to go unlabeled.  All uses of triclosan that have a direct
route to the sanitary sewer should require these hazard labels.

Agency Response:

Please see the Agency response to comment #31.  In addition, the Agency
does not have regulatory authority over FDA-regulated products.  

43. Comment:

From the Tri-TAC Comment Letter on the ecological risk assessment,
cumulative risk and environmental fate (EPA-HQ-OPP-2007-0513-0029):

Because POTWs treat wastewater from multiple sources with a variety of
chemicals, it is important to understand the cumulative risk of
triclosan in combination with other chemicals that may behave similarly.
 The EPA should require the registrant to provide information about the
common mechanism of toxicity with other chemicals and set forth a
schedule for completing an aggregate exposure assessment and cumulative
risk assessment.  POTWs’ biological processes, their ability to comply
with permits and whole effluent toxicity tests, and the aquatic
environments into which they discharge may be impacted by cumulative
toxicity from triclosan in combination with other agents.

Agency Response:

The Agency has completed an aggregate exposure assessment using the
NHANES data.  

Risks summarized in the RED document are those that result only from the
use of triclosan.  The Food Quality Protection Act (FQPA) requires that,
when considering whether to establish, modify, or revoke a tolerance,
the Agency consider “available information” concerning the
cumulative effects of a particular pesticide’s residues and “other
substances that have a common mechanism of toxicity.”  Unlike other
pesticides for which EPA has followed a cumulative risk approach based
on a common mechanism of toxicity, EPA has not made a common mechanism
of toxicity finding as to triclosan.  The Agency acknowledges that
triclocarban has been detected along with triclosan in the environment. 
Although there may be some structural similarity between triclosan and
triclocarban, these chemicals belong to two different classes
(hydroxyphenylether and hydroxyphenylurea respectively).   Further,
there is not necessarily a relationship between the mechanism of
antimicrobial activity and mechanism of toxicity in mammals. As defined
in the Office of Pesticide Programs’ 2002 document “Guidance on
Cumulative Risk Assessment of Pesticide Chemicals that Have a Common
Mechanism of Toxicity,” available at:   HYPERLINK
"http://www.epa.gov/pesticides/trac/science/cumulative_guidance.pdf_" 
http://www.epa.gov/pesticides/trac/science/cumulative_guidance.pdf ,
common mechanism of toxicity refers to “two or more pesticide
chemicals or other substances that cause a common toxic effect by the
same, or essentially the same, sequence of major biochemical
events…”  There is currently insufficient evidence characterizing
major biochemical events between triclosan and triclocarban to suggest
that these two chemicals share a common mechanism of toxicity. 

44. Comment:

From the Tri-TAC Comment Letter on the ecological risk assessment,
cumulative risk and environmental fate (EPA-HQ-OPP-2007-0513-0029):

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)The Environmental Fate Science Chapter provides many citations
regarding pass-through of triclosan to receiving waters, as well as
partitioning to biosolids.  However, it does not include information
regarding triclosan’s impacts to biological processes at wastewater
treatment plants or the impact in the beneficial reuse of biosolids. 
This section should include this information as well as an assessment of
triclosan’s ability to compromise POTW compliance with water quality
permit requirements.

Agency Response:

The Agency has revised the environmental fate science chapter for the
Triclosan RED Document.  Also, see Agency response to comment #4.

45. Comment:

From the Tri-TAC Comment Letter on the ecological risk assessment,
cumulative risk and environmental fate (EPA-HQ-OPP-2007-0513-0029):

In the Environmental Fate Science Chapter, aqueous photolysis studies
indicate that triclosan degrades quickly when exposed to light. 
However, continual discharge of triclosan into the environment presents
a problem of “pseudo-persistence”.  For example, while degradation
may occur, triclosan remains “pseudo-persistent” because it is
constantly being introduced into receiving waters via POTW effluent. 
This section should address the continual presence of triclosan in the
environment and point to the Ecological Hazard and Environmental Risk
Assessment chapter for studies on population and generational impacts
related to this continual exposure.  If these studies are not available,
they should be required of the registrant.

Agency Response:

The Agency has revised the environmental fate science chapter for the
Triclosan RED Document.  Also, see Agency response to comment #4.

46. Comment:

From the Tri-TAC Comment Letter on the ecological risk assessment,
cumulative risk and environmental fate (EPA-HQ-OPP-2007-0513-0029):

Degradation and transformation products are noted in the environmental
fate science chapter, including methyl triclosan and 2,4-dichlorophenol.
 However, environmental and ecological hazards and risk assessments are
not presented for these transformation products in this chapter of
elsewhere.  An assessment of these compounds in terms of impacts to
wastewater treatment plants’ biological processes, the potential for
these transformation products to pass through to the aquatic
environment, and their impacts to aquatic life should be incorporated. 
In addition, an assessment of how these transformation products impact
the beneficial reuse of biosolids is necessary.

Agency Response:

The Agency has revised the environmental fate science chapter for the
Triclosan RED Document.  Also, see Agency response to comment #4.

47. Comment:

From the Tri-TAC Comment Letter on the ecological risk assessment,
cumulative risk and environmental fate (EPA-HQ-OPP-2007-0513-0029):

This chapter notes that an endangered species assessment has not been
conducted and a determination will not be made at this time.  California
has numerous listed species, including invertebrates, amphibians, fish
and water fowl that may be impacted by the constant introduction of
triclosan into receiving waters.  We therefore support an additional
endangered species assessment; if this assessment indicates threatened
and endangered species may be harmed, we ask that the EPA require
mitigation measures of the registrant.

Agency Response:

The Agency has revised the ecological hazard and environmental risk
assessment science chapters for the Triclosan RED Document.  Also, see
Agency response to comment #32 and comment #4.

 The Agency is making this statement because triclosan and triclosan
transformation products are being detected in various environmental
components (see Revised Environmental Fate Science Chapter for the
Triclosan Reregistration Eligibility Decision (RED) Document, dated
September 11, 2008).

 The Agency is making this statement because triclosan and triclosan
transformation products are being detected in various environmental
components (see Revised Environmental Fate Science Chapter for the
Triclosan Reregistration Eligibility Decision (RED) Document, dated
September 11, 2008).

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