	

  SEQ CHAPTER \h \r 1 United States 			Prevention, Pesticides	June 2009

Environmental Protection                 and Toxic Substances

 Agency                                             (7510P)

2-((hydroxymethyl)-amino)ethanol 

Final Work Plan

Registration Review 

June 2009

2-((hydroxymethyl)-amino)ethanol 

Registration Review Case 3070

Final Work Plan

June 2009

							Approved By:

							____________________

							Joan Harrigan-Farrelly 

							Director, Antimicrobials Division

							

Date:

____________________2-((hydroxymethyl)- amino)ethanol Registration
Review Team

Human   SEQ CHAPTER \h \r 1 Health & Environmental Effects 

William Hazel

Srinivas Gowda

Risk Management

Lance Wormell

Diane Isbell

Office of General Counsel 

Philip Ross

Introduction

This is the Environmental Protection Agency’s (EPA or “the
Agency”) Final Work Plan (FWP) for the registration review of the
formaldehyde releasing compound 2-((hydroxymethyl)- amino)ethanol
(“HMAE,” Case 3070).  The work plan includes the expected
registration review time line.  The FWP also addresses public comments
received concerning the Preliminary Work Plan (PWP) in the Summary
Document which was posted in the HMAE registration review docket
(EPA-HQ-OPP-2008-0879), and any other comments concerning initial docket
postings.  The Summary Document provided information on what EPA knows
about the pesticide and what additional risk analyses and data or
information the Agency believes are needed to make a registration review
decision.  

The Agency is implementing the new Registration Review program and will
review each registered pesticide every 15 years to determine whether it
continues to meet the Federal Insecticide, Fungicide, and Rodenticide
Act (FIFRA) standard for registration.  Changes in science, public
policy and pesticide use practices will occur over time.  The
registration review program is intended to make sure that, as the
ability to assess risk evolves and as policies and practices change, all
registered pesticides continue to meet that statutory standard.  The
public phase of registration review begins when the initial docket is
opened for each case.  Information on this program is provided at:  
HYPERLINK "http://www.epa.gov/oppsrrd1/registration_review/_" 
http://www.epa.gov/oppsrrd1/registration_review/ . 

Comments Received on the Preliminary Work Plan

In the Preliminary Work Plan, EPA solicited comments on three specific
topics: environmental justice, water body impairment and potential trade
irritants.  No comments or information were received during the public
comment period concerning these issues.

During the public comment period, EPA received one comment as described
and discussed below.  The comment received during the initial public
comment period did not affect the data needs, work plan and timeline
described in the PWP and they remain as they were presented initially in
the PWP.  Further, this document makes final the work plan for the HMAE
registration review process. 

Comment: The FIFRA Endangered Species Task Force (FESTF) submitted a
comment requesting that any technical registrant for HMAE who is not a
member of the FESTF (or a company having met its data compensation
obligations) be asked to provide a formal offer-to-pay to FESTF for
reliance on their data.  In their comment, FESTF also noted that Troy
Chemical Company and International Specialty Products are the technical
registrants for HMAE, and that Troy Chemical Company and International
Specialty Products are not FESTF members. Therefore, the technical
registrants must offer to pay FESTF to rely on FESTF submitted data or
develop substantial similar data on their own. 

Response: The Agency thanks FESTF for its comment and will consider this
information as it conducts the registration review and makes its
registration review decisions. 

Risk Assessment and Data Needs

The Agency anticipates conducting human health and ecological risk
assessments for HMAE.  Additional human health, environmental fate and
environmental hazard data are expected to be needed to complete this
registration review.  

2-((hydroxymethyl)- amino)ethanol, also known as HMAE, is an
antimicrobial formaldehyde releasing pesticide that was first registered
in April 1975.  Until recently, EPA and the registrants believed HMAE to
be chemically distinct from
hexahydro-1,3,5-tris(2-hydroxyethyl)-s-triazine (also known as
“HHT”), a cyclical antimicrobial formaldehyde releasing pesticide
containing a triazine ring.  Based on a recent review of product
chemistry data utilizing modern analytical techniques, the Agency
expects to conclude that HMAE is the same compound as
hexahydro-1,3,5-tris(2-hydroxyethyl)-s-triazine (“HHT”).  Therefore,
where possible, the Agency intends to consolidate and/or reconcile the
available information on HMAE and HHT and update the recent HHT risk
assessments completed in support of the 2008 reregistration eligibility
decision (RED).  Furthermore, in the future EPA intends to consolidate
the HMAE (Case 3070) and HHT (Case 3074) registration review cases
themselves, most likely under the name “HHT” (Case 3074). 
Reregistration eligibility decisions (RED) for HMAE and HHT were
completed in 1993 and 2008, respectively.  The HHT RED did not address
the products thought to contain HMAE.  Completed REDs are available at  
HYPERLINK "http://www.epa.gov/pesticides/reregistration/status.htm" 
http://www.epa.gov/pesticides/reregistration/status.htm 

There are four EPA-registered end-use products (EUP) addressed in Case
3070, and these products will be evaluated as part of the HMAE
registration review case.  These products are used as manufacturing
in-process preservatives and as in-can preservatives of caulks,
sealants, grouts, lattices, resin emulsions, adhesives, spackling,
ready-mixed wallboard compounds, pigment dispersions, joint cements,
cutting oils, drilling additives, and ready-mixed cements.  

Human Health Risk 

For a detailed discussion of the anticipated human health exposure and
risk assessment needs, please refer to the
“2-((Hydroxymethyl)amino)ethanol (HHT/HMAE).  Human Health Effects
Scoping Document for the Registration Review Decision” dated December
4, 2008. 

Formaldehyde

The Office of Pesticide Programs (OPP) developed the formaldehyde
inhalation non-cancer toxicological endpoint used in the 2008
formaldehyde RED through the established reregistration process, which
includes stakeholder consultation and public comment.  However, the
result has not been subjected to an inter-agency review or external peer
review.  Because of time constraints imposed by statutory deadline, OPP
could not consider all available peer reviewed science (for example, the
intentional human dosing toxicity studies).  Thus, this value should be
considered an interim value, developed solely for the purposes of the
RED and subject to future revision and subsequent peer review and should
not be used in other contexts as EPA's opinion of the best available
science on the non-cancer effects of formaldehyde.

The Agency has formed a work group that is charged with developing a
harmonized non cancer hazard characterization document for formaldehyde.
 The Agency intends to use this non cancer information when assessing
the risks associated with the antimicrobial uses of HHT/HMAE and other
formaldehyde releasers.  In the near term, the antimicrobial uses will
also be assessed for cancer risks in the same manner as presented in the
formaldehyde RED (i.e., a range of cancer risks using the Chemical
Industry Institute of Toxicology (CIIT) model and the existing
Integrated Risk Information System [IRIS] unit risk).  Once the IRIS
update of the formaldehyde cancer unit risk is available, the Agency
will adopt that value in our risk assessments.  The formaldehyde risk
assessments are available on EPA’s Pesticide Docket at: 
www.regulations.gov.  The docket number is EPA-HQ-OPP-2008-0121.  

Toxicology Profile

	As previously stated, where appropriate, EPA intends to combine the
HMAE and HHT databases to aid in risk assessment and registration review
to develop the risk assessment and associated toxicological endpoints
for HMAE.  Therefore, the toxicological endpoints for HMAE may be
revised.

Dietary and Drinking Water Assessment

No direct food use is associated with HHT/HMAE.  However, several of the
materials preserved with this antimicrobial may be used in food
preparation, processing, or serving areas potentially resulting in
inadvertent or indirect residues in food.  Thus, EPA estimated acute and
chronic non-cancer dietary risk from exposure to HHT in the 2008 risk
assessment.  The Agency did not identify a dietary endpoint for
formaldehyde and therefore did not estimate dietary risk from exposure
to formaldehyde. The Agency plans to conduct a dietary risk assessment
(or update the HHT dietary risk assessment as necessary) as part of this
registration review case.  

Occupational and Residential Assessment

Because HHT/HMAE is currently registered for use in residential
settings, residential users (handlers) have the potential to be exposed
to HHT/HMAE and formaldehyde by using products containing HHT/HMAE.  EPA
estimated risk to residential handlers as a result of exposure to HHT
and formaldehyde in the 2008 risk assessment.  The Agency plans to
update the HHT residential risk assessment as necessary as part of this
registration review case.  

Because HMAE is currently registered for use in occupational settings,
occupational handlers have the potential to be exposed to HHT/HMAE and
formaldehyde through mixing, loading, applying a pesticide or
re-entering treated sites.  EPA estimated risk to occupational handlers
as a result of exposure to HHT and formaldehyde in the 2008 risk
assessment.  The Agency plans to update the HHT occupational risk
assessment as necessary to be used as the HHT/HMAE occupational risk
assessment for this registration review case.  

Anticipated Human Health Data Needs

The Agency anticipates that the following data will be needed to conduct
occupational and residential exposure assessments for all HMAE uses 

Anticipated HHT/HMAE Human Health Toxicity Data Needs:

90-day oral toxicity in nonrodents (GLN 870.3150)

90-day inhalation toxicity in rats (GLN 870.3465)

Developmental toxicity in nonrodents (GLN 870.3700)

2-generation reproductive toxicity study (GLN 870.3800)

Chronic studies in rodents (GLN 870.4100)

Carcinogenicity studies (rat and mouse) (GLN 870.4200)

Anticipated HHT/HMAE Occupational/Residential Exposure Data Needs

Outdoor Dermal Exposure (GLN 875.1100)

Indoor Dermal Exposure (GLN 875.1200)

Outdoor Inhalation Exposure (GLN 875.1300)

Indoor Inhalation Exposure (GLN 875.1400)

Applicator Exposure Monitoring Data Reporting for Dermal and Inhalation
Data (GLN 875.1600)

Product Use Information – Outdoor (GLN 875.1700)

Product Use Information – Indoor (GLN 875.2700)

Descriptions of Human Activity (GLN 875.2800)

Data Reporting and Calculations (GLN 875.2900)

Environmental Fate and Ecological Risk 

The Agency reviewed the environmental fate and ecological hazard
databases for HHT as part of the 2008 RED and HMAE as part of this
registration review case.  As a result of these reviews, EPA anticipates
that additional environmental fate and ecological hazard data will be
needed to complete registration review.  As stated above, where
possible, the Agency intends to rely on the 2008 risk assessments for
HHT, including any updates as necessary.

EPA intends to conduct the following risk assessments: environmental
fate, ecological hazard, and endangered species assessment.  

The Agency has not conducted a risk assessment that supports a complete
endangered species determination. The ecological risk assessment planned
during registration review will allow the Agency to determine whether
HMAE’s use has “no effect” or “may affect” federally listed
threatened or endangered species (listed species) or their designated
critical habitats. When an assessment concludes that a pesticide's use
“may affect" a listed species or its designated critical habitat, the
Agency will consult with the U.S. Fish and Wildlife Service and/or
National Marine Fisheries Service (the Services), as appropriate.

For a detailed discussion of the status of the environmental and
ecological risk assessments for HMAE please refer to the “Summary of
Product Chemistry, Environmental Fate, and Ecotoxicity Data for the
2-[(Hydroxymethyl)-amino]ethanol Registration Review Decision
Document” dated December 4, 2008.

Environmental Fate and Ecological Data Needs

As discussed previously, the Agency expects to conclude that HMAE is the
same compound as HHT.  Therefore, where appropriate, EPA intends to
combine the HHT and HMAE databases to aid in risk assessment and
registration review.  As a result of the 2008 RED, the Agency
anticipates issuing a data call-in (DCI) for HHT in the near future. 
The Agency anticipates that many of the HHT DCI requirements, once
satisfied, should address data needs for HMAE.  However, in an effort to
ensure that all registrants of HMAE and HHT are subject to the same data
requirements, the Agency intends to require additional data for HMAE
consistent with the data required for HHT and, if additional studies are
required for HMAE that are not currently listed in the HHT RED, the
Agency intends to require additional data for HHT consistent with the
data required for HMAE.  The requirements for additional HMAE studies
will be driven primarily by the Antimicrobials Division’s recent
development of draft guidance regarding data that may be needed on a
case-by-case basis for volatile compounds.  Although this guidance was
developed after the HHT RED, to ensure consistency across HMAE and HHT
the Agency also intends to require these studies for HHT through a
separate data call-in. 

  

HHT/HMAE Environmental Fate Data Needs

Modified activated sludge respiration inhibition (GLN 850.6800)

Activated sludge sorption isotherm (GLN 835.1110)

Ready biodegradability (GLN 835.3110)

HHT/HMAE Ecological Data Needs

Algal toxicity (Tier II) using freshwater green alga, Selenastrum
capricornutum (GLN 850.4400, GLN 850.5400)

Product Chemistry Status and Anticipated Data Needs  

All product chemistry data requirements have been fulfilled for the
active ingredients HMAE and HHT.  However, to support the nomenclature
change from HMAE to HHT, confirmatory information is expected to be
needed.  

Anticipated HHT/HMAE Product Chemistry Submission Needs

Revised Confidential Statement of Formula for the HMAE product Nuosept®
91 Preservative (EPA Reg. No. 1529-31).

Revised label to reflect the new nomenclature (HHT) for the HMAE product
Nuosept® 91 Preservative (EPA Reg. No. 1529-31).

Rationale and supporting data to demonstrate that available product
chemistry, environmental fate, and ecotoxicity data developed on HMAE
and HHT are adequate to support the proposed nomenclature change.  

Submit C-13 Nuclear Magnetic Resonance (NMR) spectroscopy data 
demonstrating that the linear azine becomes a cyclic triazine

Identify and explain any discrepancies between the available HMAE and
HHT product chemistry, environmental fate, and ecotoxicity data.  

Timeline

	EPA has created the following estimated timeline for the completion of
the HMAE registration review:

Activities	Estimated Month/Year

Phase 1: Opening the docket

Open Public Comment Period for HMAE-E Docket  	Completed

December 2008

Close Public Comment Period 	Completed

March 2009

Phase 2:  Case Development

Develop Final Work Plan (FWP)	Completed

June 2009

Issue DCI 	March 2010

Data Submission	March 2012

Open Public Comment Period for Preliminary Risk Assessments 	September
2013

Close Public Comment Period	December 2013

Phase 3: Registration Review Decision

Open Public Comment Period for Proposed Reg. Review Decision 	March 2014

Close Public Comment Period 	June 2015

Final Decision and Begin Post-Decision Follow-up	August 2015

Total (years)	7 



Next Steps

A DCI will be developed for this pesticide regarding the data needs
listed under the “Risk Assessment and Data Needs” section of this
document.  The Agency expects to issue the DCI in 2010.  Also, human
health and environmental fate and ecological hazard assessments will be
conducted for all uses.  

Docket Number: EPA-HQ-OPP-2008-0879

www.regulations.gov

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