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 chloride 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 added to this version of the Final Work Plan. 

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INTRODUCTION

This is the Environmental 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 pentaborate 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 formulated 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 FIFRA 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. 

Information on this program is provided on the Agency’s website1

.

The FWP begins with any updates 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 responses to those 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 closed 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 address 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, EPAHQ-OPP-2012-0083. Summarized public comments and Agency responses related 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 conclusion, 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). Therefore, 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 callin for mepiquat due to the potential 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 total 
4

and differential leukocyte count, examination of immune organs at necropsy, thymus and 

spleen weight, and/or thymus, spleen and lymph node 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 determined 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 prospective 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 assessments 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 assessment.”

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 some 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 mepiquat.
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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 in 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 Data 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

835.61002 Terrestrial field dissipation TGAI 24

850.41003 Seedling emergence (Tier II) TGAI 12

850.41504 Vegetative vigor (Tier II) TGAI 12

870.3465 90-day Inhalation toxicity - rat TGAI 24

870.7800 Immunotoxicity TGAI 12

TGAI = technical grade active ingredient;

 2 See footnote 7 of 40 CFR 158.1300. 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 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. 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.
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RISK ASSESSMENTS FOR REGISTRATION REVIEW

During registration review, the 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 assessments 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 assessments, as well as any 

changes to the standard operating procedures or default exposure assumptions.

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

Ecological 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 effect” 

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 the toxicological points of departure or uncertainty factors, 

these should also be applied in the dietary assessment.

Occupational
7

Handlers 

(mixers, loaders, 

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 should be incorporated into the mepiquat risk assessment during 

registration review. 

Post-application Y The Agency is in the process of evaluating 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 Agency 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 assessment 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-application inhalation exposure assessment 

for mepiquat.

Other

Aggregate Y Evaluates 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 Docket

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 

Decision

2017 – April – June

Close Public Comment Period 2017 – July – Sept.

Registration Review Decision and Begin Post-Decision Follow-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.