UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY
AND POLLUTION PREVENTION

September 13, 2013

Docket Number: EPA

- HQ

- OPP

- 2012

- 0083 www.regulations.gov

Errata Sheet for the mepiquat chlori de and mepiquat pentaborate Final Work Plan ( 09/12/2012 )

In the version of the mepiquat chloride and mepiquat pentaborate Final Work Plan
which was posted in the public docket, the last page was omitted from the document.
The final page has now been adde d to this version of the Final Work Plan.2 I NTRODUCTION

This is the Environm ental Protection Agency’s (EPA or the Agency ) Final Work Plan (FWP) for the registration review of mepiquat . This work plan addresses public comments received concerning the Preliminary Work Plan (PWP) , which was posted in mepiquat’s registration review docket (EPA

- HQ

- OPP

- 2012

- 0083 ). Mepiquat chloride and mepiquat pentab orate are plant growth regulators that inhibit gibberellic acid biosynthesis. They are currently registered for use on cotton with mepiquat chloride additionally registered for use on grapes. Since the mepiquat molecule is formulate d as either chloride or pentaborate salts, EPA has bridged data for the mepiquat chloride and pentaborate salts, and, throughout this document the term mepiquat refers to both active ingredients.

The Agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered pesticide every 15 years to determine whether it continues to meet the F IFRA standard for registration. Changes in science, public policy, and pesticide use practices 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 the statutory standard. The public phase of registration review begins when the initial docket is opened for each case.

Informatio n on this program is provided on the Agency’s website 1

.

The FWP begins with any update s since the PWP was issued. Next is a summary of substantive

comments received during the public comment period for the PWP concerning anticipated data

needs

, expected risk assessments, or the estimated timeline identified in the PWP

, and a summary of the Agency’s response s to th o se comments

. This section is followed by mepiquat registration review planned data needs, risk assessments expected to be conducted , and the projected registration review timeline. Lastly, there is a discussion of next steps

.

UPDATES SINCE THE PWP WAS ISSUED

There are no additional updates on mepiquat since the PWP.

SUMMARY OF COMMENTS AND AGENCY RESPONSES

During the 60

- day public comment period on the Mepiquat Preliminary Work Plan , which opened on March 28, 2012 and clo sed on May 29, 2012 , the Agency received two public

comments. Comments were submitted by FIFRA Endangered Species Task Force (FESTF) and BASF, a mepiquat technical registrant. The comments do not address the timeline described in the PWP, but they do add ress the planned ecological and human health risk assessments and data requirements. In the PWP, EPA also solicited comments on the specific topics of environmental justice, water quality concerns , and trade irritants, but no comments or information were received

on those issues.

This section does not capture every comment made on the PWP nor all of the Agency’s

responses. Summarized below are public comments that resulted in changes to the anticipated

1 http://www.epa.gov/oppsrrd1/registration_review/3 registration review data needs, risk assessments, or timeline, or are of a broader regulatory

nature. Public comments and EPA responses in their entirety are located in the docket, EPA

HQ

- OPP

- 2012

- 0083. Summarized public comments and Agency responses rel ated to the anticipated ecological risk assessment or data needs are in the Response to Comments on the Registration Review: Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments for Mepiquat Chloride and Mepiquat Pentaborate while those relevant to the anticipated human health risk assessment

or data needs are in the Mepiquat Chloride, Mepiquat Pentaborate: HED Response to Public Comments on the Preliminary Work Plan in Support of Registration Review.

Comments submitted by BASF Corporation in EPA

- HQ

- OPP

- 2012

- 0083

- 0011

.

1. Comment: “ Regarding the anticipated need for additional Avian reproduction data, the current endpoint from the test with Japanese quail, the NOAEC of 6.8 mg a.i./kg diet listed by EPA for MRID 46677001 (BASF Registration Document number 1993/10729), is derived using conservative analysis and interpretations. As additional avian reproduction data with a second upland species is unlikely to change the risk conc lusion, BASF requests continued use of the current endpoint and avoidance of additional unnecessary vertebrate testing.”

Response: The Agency concurs with the Registrant that no additional avian reproduction data are necessary

. Therefore, GLN 850.2300

- Avian Reproduction

- will not be required.

2. Comment: The analytical method for residues in sediment should not be required since the use pattern will be terrestrial, not aquatic.”

Response: The Agency concurs with the Registrant. The sediment analytical method is not required; however the method for water analysis will be required.

3. Comment: “ Mepiquat chloride (and pentaborate) is of low volatility and low acute toxicity (Inhalation toxicity Category IV). Theref ore, BASF believes that a repeat inhalation exposure risk assessment can be conducted using an extrapolated inhalation value based on an oral NOAEL. With acceptable MOE’s (MOE's for mepiquat chloride and pentaborate are

estimated to be well above the level of concern), there is no need for a repeat

- dose inhalation toxicity study, and BASF plans to submit a waiver for this requirement. ”

Response: The Agency is requiring the 90

- inhalation study (GLN 870.3465) in the data call

in for mepiquat due to the pote ntial for exposure to occupational handlers via volatility or spray drift. A repeat dose inhalation toxicity study is required if there is a likelihood for significant repeated inhalation exposure to the pesticide as a gas, vapor or aerosol. To date,

no chemical specific handler data has been submitted to the Agency in support of mepiquat registrations. However, if BASF submits a formal study waiver after receipt of the DCI that provides an adequate rationale for why the study is not necessary, HED will further evaluate the need for the data requirement to support the registration review of mepiquat.

3. Comment: “ Review of all studies conducted with mepiquat chloride revealed no effects that would imply a treatment

- related suppression of the immune system. The toxicity studies

evaluated included systematic evaluation of structural immune parameters, including total4 and differential leukocyte count, examination of immune organs at necropsy, thymus and spleen weight, and/or thymus, spleen and lymph nod e histopathology. The endpoints evaluated in these studies provide valuable insight in determining the immunotoxic potential, particularly when evaluated in a weight of evidence context. Although, as stated in the OPPTS 870.7800 guideline, the endpoints de termined in standard testing may not be sufficient to predict immunotoxicity, when the knowledge that no relevant immunotoxic effects have been identified with mepiquat chloride, is taken in combination with the fact that the dose levels used in a prospect ive immunotoxicity study would in all likelihood not lead to a NOAEL that would alter the overall risk assessment, it is implied that the conduct of an immunotoxicity study is not needed.

In addition, a Retrospective Analysis conducted by CropLife America which evaluated the current toxicity endpoint database and the proposed endpoints derived from functional immunotoxicity assays (T

- cell dependent antibody response, TDAR) showed that results from immunotoxicity studies had no effect on the risk assessment s for the 78 chemicals

evaluated. Therefore, BASF believes that it is unlikely that mepiquat chloride (or pentaborate) has immunotoxic potential, and that the immunotoxicity study should be waived considering its low probability for impact on risk assessm ent. ”

Response: The Agency concurs that no relevant immunotoxic effects have been identified in the existing mepiquat toxicology studies. While data obtained from hematology, organ weights, and histopathology in the existing toxicity studies may offer s ome useful information on potential immunotoxic effects, these endpoints alone are insufficient to predict and fully characterize immunotoxicity. At this time, the guideline immunotoxicity study (OPPTS 870.7800) is not waived and is a requirement for mepi quat.5 PLANNED DATA NEEDS

The table below summarizes the planned data needs for mepiquat based on the Registration Review: Preliminary Problem Formulation for Environmental Fate and Ecological Risk, Endangered Species, and Drinking Water Assessments for Mepiquat Chloride and Mepiquat

Pentaborate

, and Mepiquat Chloride, Mepiquat Pentaborate: Human Health Risk Assessment Scoping Document in Support of Registration Review , and Response to Comments on the Registration Review: Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments for Mepiquat Chloride and Mepiquat Pentaborate ; and Mepiquat Chloride, Mepiquat Pentaborate: HED Response to Public Comments on the Preliminary Work Plan i n Support of Registration Review

. The table has been updated since the PWP to reflect public comments which resulted in changes to the data

needs

.

Planned D ata Needs for Mepiquat’s Registration Review

Guideline

Number Study Title Test Material Estimated

Timeframe

(Months from receipt of DCI)

835.4300 Aerobic aquatic metabolism TGAI 24

835.4400 Anaerobic aquatic metabolism TGAI 24

835.6100 2 Terrestrial field dissipation TGAI 24

850.4100 3 Seedling emergence ( Tier II ) TGAI 12

850.4150 4 Vegetative vigor ( Tier II ) TGAI 12

870.3465 90

- day I nhalation toxicity

- rat TGAI 24

870.7 800 Immunotoxicity TGAI 12

TGAI = tec hnical grade active ingredient;

2 See footnote 7 of 40 CFR 15 8 .1300. EPA is requiring only the environmental chemistry analytical methods and independent laboratory validation (ILV) portions of this required data requirement for sediment rather than the full field dissipation study.

3 A Tier II study is required. The DCI expecte d to be issued will provide that a Tier I plant (terrestrial and aquatic) study may be conducted in lieu of a Tier II study with the understanding that any adverse effects observed by the Tier I study would necessitate

conduct and submission of a Tier II s tudy as well.

4 A Tier II study is required. The DCI expected to be issued will provide that a Tier I plant (terrestrial and aquatic) study may be conducted in lieu of a Tier II study with the understanding that any adverse effects observed by the Tier I study would necessitate conduct and submission of a Tier II study as well.6 RISK ASSESSMENTS FOR REGISTRATION REVIEW

During registration review, t he Agency will conduct a comprehensive ecological risk assessment, including an endangered species assessment, for all uses of mepiquat

. For human health, EPA

will conduct revised dietary, residential

, and occupational risk assessment s during registration

review

. If toxicological endpoints or points of departure are revised based on the data that are required for registration review

, they will be considered in the new assessment s
, as well as any changes to the standard operating p rocedures or default exposure assumpti ons

.

The table below summarizes the planned registration review risk assessments based on the EFED

Problem Formulation and HED Scoping Document ; the planned assessments have not changed

from what was included in the PWP

.

Planned Risk Assessments for Mepiquat’s Registration Review

Type of Risk

Assessment Conduct ? Notes

Eco logical and Environmental Fate Comprehensive ecological (species to be

assessed include

terrestrial and aquatic organisms ), including endangered species Y The Agency has not conducted a risk assessment that supports a complete endangered species determination for mepiquat. The ecological risk assessment planned during registration review will allow the Agency to determine whether mepiquat’s use has “no effe ct” or “may affect” federally listed threatened or endangered species (listed species) or their designated critical habitats.

Incidents Y The Agency will incorporate any updated ecological incident data into the mepiquat risk assessment during registration review.

Human Health Dietary

Food Y The Agency anticipates updating the dietary assessment to include any revised PODs or uncertainty factors. Drinking water Y EFED will be performing a revised drinking water assessment under registration review. Drinking water EECs provided by EFED should be incorporated directly into the dietary exposure analysis. If after evaluation of more recently submitted toxicity studies there are

revisions to th e toxicological points of departure or uncertainty factors, these should also be applied in the dietary assessment. Occupational7 Handlers (m ixer s, loader s, applicators ) Y No chemical specific handler data were submitted in support of mepiquat registrations; therefore, handler dermal and inhalation exposure assessments were performed based on surrogate data from the Pesticide Handler’s Exposure Database (PHED, August 1998). However, pesticide handler exposure monitoring data has been updated by the Occupational Pesticide Handler Unit Exposure (OPHED) Surrogate Reference Table (June 21, 2011, http:/ /www.epa.gov/pesticides/science/handler

- exposure

- data.html )

which includes ORETF and AHETF data. As more reliable data become available (such as that from the AHETF and ORETF) the Agency will continue to replace existing data. Any updated exposure

data sh ould be incorporated into the mepiquat risk assessment during registration review.

Post

- application Y The Agency is in the process of e valuating the SAP report ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ) and may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the way to incorporate post

- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Age ncy may revisit the need for a quantitative post

- application inhalation exposure assessment for mepiquat.

Residential

Handlers Y There are currently no registered residential uses, however, the Agency anticipates evaluating the need for a bystander asses sment for mepiquat based on potential for exposure via volatility or spray drift.

Post

- application Y The Agency is in the process of evaluating the SAP report ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html )

as well as available post

- application inhalation exposure data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to incorporate residential post

- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative residential post

- applica tion inhalation exposure assessment

for mepiquat

. Other Aggregate Y E valuates the combined risk from dietary and residential exposures.

Cumulative Y If, in the future, the Agency determines that new information on mepiquat is available that could potentially impact a cumulative risk assessment and result in a risk of concern, the Agency will revisit the

need for a cumulative risk assessment

. Tolerances Y The tolerance expression in 40 CFR §180.384 will be reviewed during registration review to ensure that it appropriately covers the metabolites and degradates of mepiquat and that it specifies the residues to be measured in each commodity.

Incidents Y The Agency will incorporate any updated human incident data into the mepiquat risk assessment during registration review.8 TIMELINE

EPA has created the following estimated timeline for the completion of mepiquat’s registration

review

. The projected timeline has not changed since the PWP.

Registration Review for Mepiquat

– Projected Registration Review Timeline

Activities Estimated Date Opening the D ocket Open Docket and Public Comment Period 2012

– March

Close Public Comment 2012

– May Case Development

Final Work Plan 2012

– September

Issue DCI 2013

– April

– June

Data Submission 2015

– April

– June Open Public Comment Period for Draft Risk Assessments 2016

– Oct.

– Dec.

Close Public Comment Period 2017

– Jan.

– March Registration Review Decision Open Public Comment Period for Proposed Registration Review

D ecision 2017

– April

– June

Close Public C omment P eriod 2017

– July

– Sept. Registration Review D ecision and Begin P ost

- D ecision F ollow

- up 2018 Total ( years ) 6

NEXT STEPS

As noted previously, the Agency plans to require several environmental fate, ecological effects,

and human health studies for mepiquat through a data call

- in, expected to be issued in April

– June 2013.