Docket Number EPA

- HQ

- OPP

- 2010

- 1044 www.regulations.gov



## Desmedipham Final Work Plan Registration Review

December 20112 DESMEDIPHAM FINAL WORK PLAN

Introduction:

This is the Environmental Protection Agency’s ( EPA or the Agency) Final Work Plan (FWP) for the registration review of desmedipham. The F WP includes the expected registration review

timeline . The FWP also addresses public comments received concerning the Preliminary Work

Plan (PWP) i n the Summary Document , which was posted in the de s medipham registration review docket (EPA

- HQ

- OPP

- 2010

- 10 44), and any other comments concerning the initial docket postings. The Summary Document provided information on what EPA knows about this pesticide and what additional risk analyses and data or information the Agency believes are needed to make a registration review decis ion.

The Agency ’s implement ation of the registration review program req u ires review of 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, al l 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: http://www.epa.gov/oppsrrd1/registration_review/

.

Desmedipham (ethyl 3

- phenylcarbamoyloxycarbanilate) is a member of the phenylcarbamate family and is currently registered for use as a selective post

- emergence herbicide on sugar beets, red beets and spinach. Additionally, there is one desmedipham Spe cial Local Needs (SLN) registration in the state of Washington for use on Swiss chard grown for seed. Desmediph am rapidly hydrolyzes in neutral to alkaline water with complete conversion to EHPC (ethyl

- N

- (3

- hydroxyphenyl)carbamate). EHPC is a major degr a date of desmedipham and further data are needed on EHPC in support of the desmedipham registration review. Although desmedipham is a carbamate, it is not a cholinesterase inhibitor and EPA has determined that it does not have a

common mechanism of toxicit y with the N

- methyl carbamate pesticides. Also, the Agency has no information indicating desmedipham shares a common mechanism of toxicity with phenmedipham, even though it has a similar structure and mode of action in plants to phenmedipham. Desmedipham was initially registered in the United Sates in November 1974.

The Reregistration Eligibility Decision (RED) for Desmedipham was completed in March 1996

and the Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment Progress

and Risk Management Decision (TRED) for Desmedipham was completed in July 2004

.

Comments Received on the Preliminary Work Plan :

The desmedipham registration review docket was op en for a 60

- day comment period beginning

on June 29 , 2011. During this comment period, t he Agency received one submission from the technical registrant, Bayer CropScience

. The comments received did not change the planned risk assessment, data needs, or timeline described in the desmedipham PWP

. EPA also solicited

, through the PWP, comments on three specific topics: environmental justice, water body3 impairment, and trade irritants

. No comments or information were received during the comment period concerning these issues. T his document makes final the work plan for the desmedipham registration review process.

Summary of Comments and Agency Response :

A summary of the comments and the Agency’s response to comments is provided below. For a detailed description of the comments received and the Agency’s response to these comments

, please refer to the Response to Public Comments on the EFED Registration Review Problem Formulation for Desmedipham

, November 8, 2011

, available in the desmedipham registration

review docket ( EPA

- HQ

- OPP

- 2010

- 1044 ).

Bayer CropScience (BCS) Comment 1 : BCS commented that they will submit environmental fate and ecological toxicity data to fulfill the following guideline (GLN) data requirements:

**•** GLN 835.1230

– Adsorption/desorption (batch equilibrium ) (desmedipham & EHPC )

**•** GLN 835.4200

– Anaerobic soil metabolism ( desmedipham ) 1

**•** GLN 835.4300

– Aerobic aquatic metabolism ( desmedipham )

**•** GLN 850.1010

– Acute aquatic invertebrate toxicity, D aphnia magna ( EHPC )

**•** GLN 850.1035

– Acute aquatic mysid toxicity ( desmedipham )

**•** GLN 850.1735

– Whole sediment acute toxicit y invertebrates

, Chirnomous dilutus ( desmedipham )

**•** GLN 850.5400

– Aquatic plant toxicit y, algal plants (Tier II) ( EHPC )

Agency Response 1 : The Agency will review all submitted data for desmedipham and it s degradate, EHPC. These data may be useful for the re gistration review of desmedipham

. H owever, it is unclear prior to review of these data whether they will fulfill the guideline data requirements. The data require ments identified in this FWP will remai n as such until the data are

evaluated and found to be acceptable.

BCS Comment 2 : BCS provided a summary of the environmental fate data (including the test

parameters used ) to facilitate the Agency’s review of these data

.

Response 2 : The Agency has revi ewed BCS’ s summary of the environmental fate data and has identified the following uncertainties:

**•** For GLN 835.4300 , a erobic a quatic m etabolism, t he pH values measured in the test

sy stems were not provided in the summary of the degradation data (Sabourin, 2003). As indicated in the Problem Formulation, at least one of the aquatic sediment systems should have a pH <6

. Therefore, if both test systems in the study have pH values ≥6, additional data will be required regardless of the study’s classification.

1 The registrant submitted data for GLN 835.4200, anaerobic soil metabolism. However, this study was not
identi fied as a data requirement in the desmedipham PWP and is not required in support of registration review

.4 **•** As indicated in the Problem Formulation, guideline

- compliant batch equilibrium studies (GLN 835.1230, adsorption/desorption) are needed for the parent desmedipham in five

acidic soils ; and the degradate EHPC in five soils of different characteristics

. Ac cordi ng

to the summary, the adsorption/ desorption study for desmedipham (Mackie et al. , 1991) uses three soils, two of which are acidic. If the study data on the acidic soils are acceptable, then data for three additional acidic soils will continue to be required. The adsorption/desorption study for EHPC (Andrew, 2003) was conducted with four soils that appear to have had different characteristics. If this study is classified acceptable, it is unlikely that an additional batch equilibrium study of a fift h soil will be required for

EHPC.

Risk Assessment and Data Needs:

The Agency will require data to conduct a comprehensive ecological risk assessment, including an endangered species assessment, for all uses of des medipham. For human health, the Agency

will require toxicity data to conduct an updated human health exposure risk assessment. Below is a summary of the issues relevant to the registration review of desmedipham.

Ecological Risk:

**•** The most recent comprehensive ecological risk assessment for desmedipham was completed in support of the RED in 1996.

**•** A crop

- specific ecological risk assessment was completed in 2007 for the use of desmedipham on red beets and spinach.

**•** EPA has not conducted a risk assessment that supports a complete endangered species determination for desmedipham. The ecological risk assessment planned during registration review will allow the Agency to determine whether use of desmedipham has

“no effe ct” 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.

**•** T he following studies are required in order to conduct a comprehensive ecological risk assessment, including an endangered spe cies assessment, for the registration review of desmedipham:

Desmedipham, Parent: Technical Grade Active Ingredient (TGAI)

o GLN 835.1230

– Adsorption/desorption (batch equilibrium of 5 acidic soils)

o GLN 835.4100

– Aerobic soil metabolism (3 soils)

o GLN 83 5.4300

– Ae robic aquatic metabolism (2 sediment s)

o GLN 835.4400

– Anae robic aquatic metabolism (2 sediment s)5 o GLN 835.6200

– Environmental chemistry analytical methods (ECM) and
independent laboratory validation (ILV) for water

o GLN 850.1010

– Acute aquatic invertebrate toxicity, Daphnia magna

o GLN 850.1025

– Acute aquatic oyster toxicity, shell deposition

o GLN 850.1035

– Acute aquatic mysid toxicity

o GLN 850.1075

– Acute aquatic fish toxicity (freshwater and marine)

o GLN 850.1735

– Whole sediment acute toxici ty invertebrates, Chirnonomus

dilutus

o GLN 850.1735

– Whole sediment acute toxicity invertebrates, Hyallella azteca

o GLN 850.1740

– Whole sediment acute toxicity, Leptocheirus plumulosus

o GLN 850.2100

– Acute avian oral toxicity, passerine

Desmedipham, Parent: Typical End

- Use Product (TEP)

o GLN 850.4150

– Terrestrial plant toxicity, vegetative vigor (Tier II) (carrots)

Desmedipham rapidly hydrolyzes in neutral to alkaline water with complete conversion to EHPC, which is a persistent major degradate of de smedipham. Exposure of aquatic and terrestrial organisms and plants to EHPC is anticipated as a result of the currently registered desmedipham uses. However, data are not available to assess toxicity of EHPC to aquatic and terrestrial organisms, and plan ts. Additionally, t he Agency has a limited understanding of how EHPC behaves in the environment and its mobility. Therefore, the following environmental fate and ecological toxicity studies for EHPC are required in support of the registration review of desmedipham:

Desmedipham Degradate, EHPC

o GLN 835.1230

– Adsorption/desorption (batch equilibrium in five soils)

o GLN 850.1010

– Acute aquatic invertebrate toxicity, Daphnia magna

o GLN 850.1025

– Acute aquatic oyster toxicity, shell deposition

o GLN 850.103 5

– Acute aquatic mysid toxicity

o GLN 850.1075

– Acute aquatic fish toxicity (freshwater and marine)

o GLN 850.1300

– Aquatic invertebrate life

- cycle, Daphnid

o GLN 850.1350

– Aquatic invertebrate life

- cycle, mysid

o GLN 850.1400

– Fish early life stage toxicit y (freshwater and saltwater)

o GLN 850.4100

– Terrestrial plant toxicity, seedling emergence (Tier II)

o GLN 850.4150

– Terrestr ial plant toxicity, vegetative v igor (Tier II)

o GLN 850.4400

– Aquatic plant toxicity, vascular plants (Tier II)

o GLN 850.5400

– Aquat ic plant toxicity, algal plants (Tier II)

**•** Please refer to the document s EFED Registration Review Problem Formulation for Desmedipham

, June 27, 2011, and the Response to Public Comments on the EFED Registration Review Problem Formulation for Desmedipham , N ovember 8, 2011

, i n the6 desmedip ham registration review docket for a detailed discussion of the risk assessment and

data needs.

Human Health Risk:

**•** A human health aggregate risk assessment for desmedipham was conducted , that did not include worker exposure, in support of the Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment Progress and Risk Management Decision (TRED) for Desmedipham , which was completed in 2004

.

**•** Updated dietary (food and drinki ng water) and an occupational (handler and post

application) exposure assessments were conducted in 2007 for the use of desmedipham on red beets and spinach.

**•** T he following data are required for use in reevaluating and updating the human health toxicity p rofile for the registration review of desmedipham:

o GLN 870.6200

– Acute and subchronic neurotoxicity

o GLN 870.7800

– Immunotoxicity

**•** An updated dietary (food and drinking water) risk assessment may be required during registration review to incorporate current models and methodologies for estimating residues in food and drinking water, as well as to incorporate any possible revisions to the points of departure or uncertainty factors. If a revised dietary assessment is needed, it should include updated cons umption information.

**•** Since there are currently no residential uses and no anticipated residential exposures from desmedipham use, residential handler and post

- application exposure assessments are not anticipated as being needed during registration review at this time.

**•** U pdat ed occupational handler and post

- application exposure assessments will be needed during registration review to incorporate updated/current guidelines, models, standard operating procedures, and new toxicological endpoints (if they are established) for all scenarios, formulations and use sites. In addition, at the time of the registration review risk assessment, if exposure data and methodologies for estimating exposure have changed or if updated incident data indicate risk issues that need to be addressed, these issues will be incorporated in to a new assessment.

**•** The desmedipham tolerance expression in 40 CFR §180.353 will be reviewed during registration review to ensure that it appropriately covers the metabolites and degradates of desmedipham, that it specifies the residues to be measured for each commodity, and that the tolerance expression reflects current EPA policy.

**•** There are no established or proposed international Codex, Canadian, or Mexican Maximum Residue Limits (MRLs) for desmedipham. Should MRLs be established,7 desmedipham tolerances will be considered for possible harmonization with international

MRLs

.

**•** Please refer to the document Desmedipham

. Revised: Registration Review Scoping Document for Human Health Assessments

, June 21, 2011, in th e desmedipham registration review docket for a detailed discussion of the risk assessment and data needs.

Endocrine Disruptor Screening Program:

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposur e to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assess ments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its desmedipham reregistration decision

, EPA reviewed these data and selected the most sensitive endp oints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), desmedipham is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed th e EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrato r may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Ti er 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and

establish a dose

- response relationship between the dose and the E, A, or T effect.

Under FFDC A section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingred ients. De smedipham is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data

call

- ins, requiring the submission of EDSP screening assays for desmedipham. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit the website: http://www.epa.gov/endo/

.8 Timeline:

EPA has created the following estimated timeline for the completion of the desmedipham registration review.

Registration Review for Desmedipham

– Projected Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and Public Comment Period 2011

– June

Close Public Comment 2011

– August Case Development

Final Work Plan 2011

– Dec ember

Issue DCI 2012

– July

– Sept.

Data Submission 2014

– July

– Sept. Open Public Comment Period for Draft Risk Assessments 2016

– Jan.

– March

Close Public Comment Period 2016

– April

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

Decision 2016

– July

– Sept.

Close Public Comment Period for Proposed Registration Review

Decision 2016

– Oct.

– Dec.

Registration Review Decision and Begin Post

- Decision Follow

- up 2017 Total (years) 6

Next Steps:

The Agency will require multiple environmental fate/ ecological effects and human health studies through a data call

- in, which is expected to be issued in mid

- 2012. This new information will be

used to conduct risk assessments for de s medipham uses.9 S UMMARY OF DATA GAPS

- Desmedipham

The table below summarizes all data needs for desmedipham identified in t he “ Ecological

Risk ” and “ Human Health Risk ” sections of this Final Work Plan document ; the EFED Registration Review Problem Formulation for Desmedipham

, June 27, 2011 ; the Response

to Pu blic Comments on the EFED Registration Review Problem Formulation for Desmedipham , November 8, 2011; and the Desmedipham

. Revised: Registration Review Scoping Document for Human Health Assessments

, June 21, 2011

.

2 See footnote 7 of 40 CFR 158.1300. On ly the environmental chemistry analytical method and associated independent laboratory validation portion of GDLN 835.6200, aquatic field dissipation, are required.

3 Study must be conducted as static

- renewal or flow

- through because the parent desmedipham is unstable.

4 Study must be conducted as flow

- through because the parent desmedipham is unstable.

5 St udy must be conducted as static

- renewal because the parent desmedipham is unstable.

6 The DCI will require that a study protocol be submitted for review and approval by the Agency prior to initiation of this study.

7 A Tier II study is required. The DCI will provide that a Tier I plant study may be conducted in lieu of a Tier II study wit h the understanding that any adverse effects observed by the Tier I study will necessitate conduct and

submission of a Tier II study as well. Table 1. Data Needs for Desmedipham Registration Review

Guideline

Number Data Requirement Test

Material Study

Duration

835.1230 Adsorption/Desorption (batch equilibrium in 5 soils) TGAI 12

835.1230 Adsorption/Desorption (batch equilibrium in 5 soils)

– EHPC EHPC 12

835.4100 Aerobic Soil Metabolism (3 soils) TGAI 24

835.4300 Aero bic Aquatic Metabolism (2 sediments ) TGAI 24

835.4400 Anaer obic Aquatic Metabolism (2 sediments) TGAI 24

835.6200 Environmental Chemistry Methods (ECM) and Independent Laboratory Validation (ILV) for Water 2 TGAI 12

850.1010 Acute Toxicity Freshwater Invertebrates ( Daphnia magna ) TGAI 24

850.1010 Acute Toxicity Freshwater Invertebrates ( Daphnia magna )

– EHPC 3 EHPC 24

850.1025 Acute Aquatic Oyster Toxicity, shell deposition 4 TGAI 12

850.1025 Acute Aquatic Oyster Toxicity, shell deposition

– EHPC EHPC 12

850.1035 Acute Aquatic Mysid Toxicity 4 TGAI 12

850.1035 Acute Aquatic Mysid Toxicity

– EHPC EHPC 12

850.1075 Acute Aquatic Fish Toxicity (freshwater & saltwater) 4 TGAI 12

850.1075 Acute Aquatic Fish Toxicity (freshwater & saltwater)

– EHPC EHPC 12

850.1300 Aquatic Invertebrate Life Cycle (Daphnid)

– EHPC EHPC 12

850.1350 Aquatic Invertebrate Life Cycle (Mysid, saltwater)

– EHPC EHPC 12

850.1400 Fish Early Life Stage Toxicity (freshwater & saltwater)

– EHPC EHPC 12

850.1735 Whole Sediment Acute Toxicity Invertebrates, Chirnonomus dilutus 5 TGAI 12

850.1735 Whole Sediment Acute Toxicity Invertebrates, Hyallella azteca 5 TGAI 12

850.1740 Whole Sediment Acute Toxicity, Leptocheirus plumulosus TGAI 12

850.2100 Acute Avian Oral Toxicity (passerine species) 6 TGAI 12

850.4100 Terrestrial Plant Toxicity , Seedling Emergence (Tier II)

– EHPC 7 EHPC 12

850.4150 Terrestrial Plant Toxicity, Vegetative Vigor, on carrots (Tier II) 7 TEP 12

850.4150 Terrestrial Plant Toxici ty, Vegetative Vigor (Tier II)

– EHPC 7 EHPC 12

850.4400 Aquatic Plant Toxic ity, Vascular Plants (Tier II)

– EHPC 7 EHPC 1210 Table 1. Data Needs for Desmedipham Registration Review

Guideline

Number Data Requirement Test

Material Study

Duration

850.5400 Aquatic Plant To xicity, Algal Plants (Tier II)

– EHPC 7 EHPC 12

870.6200 Acute and Sub

- chronic Neurotoxicity TGAI 24

870.7800 Immunotoxicity TGAI 12