2 Morpel® Repellent 326

– Table of Contents

I. Introduction 3

II. Use and Usage Information 4

III. Scientific Assessments 5

IV. Interim Registration Review Decision 9

V. Next Steps 9

References:

This document summarizes the Environmental Protection Agency’s current position based on the following documents:

1. Registration Review

– Preliminary Ecological Risk Assessment and Endangered Species Effects Determination for Dipropyl isocinchomeronate (aka Morpel® Repellent 326, formerly MGK ® Repellent 326)

. Melanie Biscoe, Katherine Stebbins, Melissa Panger

. October 20 , 2014

.

2. Dipropyl

- isocinchomeronate (Di

- N

- propyl isocinchomeronate): Scoping and Preliminary Risk Assessment for Registration Review. Thurston G. Morton, Kelly O’Rourke, Abdallah Khasawinah

. May 19 , 2015

.

3. BEAD Chemical Profile for Registration Review: Dipropyl isocinchomeronate (PC Code 047201)

. David Brassard, Sepehr Haddad, Michelle Ranville

. April 28 , 201 4

.

4. Dipropyl Isocinchomeronate (MGK

- 326): Tier I Review of Human Incidents. Shanna Recore. April 9,

2014.

These and other supporting documents for the Morpel® Repellent 326 Registration Review case

ma y be found in the docket EPA

- HQ

- OPP

- 2014

- 0578 at http://www.regulations.gov

.3 I. INTRODUCTION

This document is the Environmental Protection Agency’s (EPA or the Agency) Interim Registration Review Decision for dipropyl isocinchomeronate (referred to within as Morpel® Repellent 326 and Morpel®; formerly MGK 326) , pursuant to 40 CFR § 155.56 and § 15 5.58. A Registration Review decision is the Agency’s determination that a pesticide meets, or does not meet, the standard for registration in the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The Agency may issue, when it deems appropriate , an interim Registration Review decision before completing a Registration Review . Among other things, the interim Registration Review decision may (1) require new risk mitigation measures; (2) impose interim risk mitigation measures; (3) identify data or information required to complete the review; and (4) include schedules for submitting the required data, conducting the new risk assessment, and completing the Registration Review

.

FIFRA, as amended by the Food Quality Protection Act (FQPA) of 1996, mandated the continuous review of existing pesticides. All pesticides distributed or sold in the United States generally must be registered by EPA, based on scientific data showing that they will not cause unreasonable risks to

human health or the environm ent when used as directed on product labeling. The Registration

Review program is intended to make sure that, as the ability to assess and reduce risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory s tandard of no unreasonable adverse effect to human health or the environment. Through the Registration Review program, the Agency periodically reevaluates pesticides to make sure that as these changes occur, products in the marketplace can be safely used. Information on this program is provided at: http://www2.epa.gov/pesticide

- reevaluation/registration

- review

- process . In 2006, the Agency implemented the Registration Re view program pursuant to FIFRA Section 3(g) and will review each registered pesticide every 15 years to determine whether it continues to meet the FIFRA standard for registration.

Morpel® Repellent 326 is a n insect repellent registered for use as a human and companion animal (dog,

cat , and horse) insect repellent. While use of Morpel® 326 on dairy cattle is mentioned in supporting documents, there are no registrations which include this use site on any technical or end use label. Morpel® is never t he sole active ingredient; it is always coformulated with other insecticides/repellents

, such as DEET, piperonyl butoxide, and pyrethrins

, to broaden the ir spectrum of repellency. Morpel®

326 is registered for use to repel flies, gnats, and other flying an d biting insects. Morpel® 326 is only registered for indoor non

- food and residential use. The Agency completed its Reregistration Eligibility

Decision document (RED) for dipropyl isocinchomeronate on March 11, 2005.

Pursuant to 40 CFR section 155.50, EPA formally initiated Registration Review for Morpel® 326 (case 2215). The following highlights significant events that have occurred during the Registration Review of Morpel® 326

.

• August 2015

– Issuance of Dipropyl iso cinchomeronate (Morpel® Repellent 326) Combined Work Plan, Summary Document, and Proposed Interim Registration Review Decision for a 60

- day public comment period.

• August 2015

– Publication of Dipropyl

- isocinchomeronate (Di

- N

- propyl isocinchomeronate):

Sco ping and Preliminary Risk Assessment for Registration Review and Registration Review

– Preliminary Ecological Risk Assessment and Endangered Species Effects Determination for Dipropyl isocinchomeronate (aka Morpel® Repellent 326, formerly MGK ® Repellent 326)

.4 • October 9, 2015

– The Agency received one public comment submitted on behalf of the technical registrant, Vertellus Performance Materials, Inc. (Vertellus) , which is discussed

below. EPA also solicited comments on the specific topics of environmental justice, water quality concerns, and trade irritants, but no comments or information were

received c on cerning those issues.

• December 2015

– The Agency is now publishing the Morpel® 326 Interim Registration

R eview Decision

.

Comment received on behalf of the technical registrant, Vertellus

Comment: The comment submitted by Technology Services Group Inc., on behalf of the Morpel ® 326 technical registrant , Vertellus requested that the Agency lift restrictions placed on the regi stration of Morp el® 326 in the 2005 RED, including (1) a maximum concentration (2.5%) of active ingredient in end

- use products intended for use on humans and (2) a production and distribution cap of 20,000 pounds of active ingredient per year

. Vertellus’ justification for its request

to lift current restrictions is based on the Agency’s re

- classification of Morpel® 326 as “not likely to

be carcino gen ic to humans”.

EPA Response: The Agency agrees that based on the re

- classification of Morpel® 326 as “not likely to be carcinogenic to humans”, as documented in Dipropyl

- isocinchomeronate (Di

- N

- propyl isocinchomeronate): Scoping and Preliminary Risk Assessment for Registration Review , the aforementioned restrictions are no longer relevant. The maximum annual production and distribution cap is no longer necessary. In order to i nitiate this change, an affected registrant would need to a mend the terms and conditions of registration for the technical product

. Additionally, there is no need to
restrict the maximum concentration of active ingredient in products intended for use on humans to
2.5% given that dipropyl

- isocinchomeronat e is not expected to be carcinogenic

. However, the Agency notes that any proposed formulation changes to Morpel® Repellent 326 end

- use product s ( e.g., higher concentrations of active i ngredient) would be subject to the Pesticide Registration Improvement Ex tension Act (PRIA) application process which include s a quantitative human health

assessment

. Hence, in order to initiate changes to the r estrictions set forth in the 2005 RED, an affected registrant would need to m ake formal request s to the Agency

.

For further information about Morpel® Repellent 326 , additional documents can be found in EPA’s public docket ( EPA

- HQ

- OPP

- 2014

- 0578 ) at www.regulations.gov

.

II. USE AND USAGE INFORMATION

Morpel® Repellent 326 is an ingredient contained in insect repellent products registered for application to humans (personal use) and pets (health care products)

. Morpel® Repellent 326 is never used as the sole active ingredient; it is used to expand the repellen cy of other insecticides

. Below is a summary of the use/usage of Morpel® Repellent 326 . For more details please see BEAD Chemical Profile for Registration Review: Dipropyl isocinchomeronate (PC Code 047201) dated (April 28, 2014).

Summary of Use Morpel® Repellent 326 is formulated with a number of other insecticide active ingredients to extend the spectrum and period of repellency.

Use Sites Indoor non

- food and residential use5 Summary of Usage Annual average of 6,800 pounds/year; 4,800 for insect repel lent use on humans, 2,000 for animal

- only insect repellent uses Formulation Type(s) Aerosol, impregnated material (towelette) , pet dip Technical Registrant(s) Vertellus Specialties

, Inc. No. of Registrations 39

Restricted Use No

III. SCIENTIFIC ASSESSMENTS

A summary of the Agency’s human health and environmental fate and ecological risk assessments, Dipropyl

- isocinchomeronate (Di

- N

- propyl isocinchomeronate): Scoping and Preliminary Risk Assessment for Registration Review dated May 19, 2015 and R egistration Review

– Preliminary Ecological Risk Assessment and Endangered Species Effects Determination for Dipropyl isocinchomeronate (aka Morpel® Repellent 326, formerly

MGK ® Repellent 326) (October 20, 2015) is presented below. For the detailed risk assessments, see the Morpel® Repellent 326 Registration Review docket ( EPA

- HQ

- OPP

- 2014

- 0578 ) at www.regulations.gov

.

A. Human Health Risk Assessment

The human health exposu re and toxicological database is adequate for Registration Review of Morpel® 326 . The Agency does not need additional studies in order to characterize the human

health exposure, hazard and risk from Morpel® 326 . Because no additional human health or toxici ty data are needed for the Registration Review of Morpel® 326 , the Agency determined that it was appropriate to conduct a preliminary human health risk assessment for Morpel® 326 . A summary of the Agency's preliminary human health risk assessment is presented below. For detailed information

see: Dipropyl

- isocinchomeronate (Di

- N

- propyl isocinchomeronate): Scoping and Preliminary Risk Assessment for Registration Review dated May 19, 2015 in the public docket ( EPA

- HQ

- OPP

- 2014

- 0578 ) which can be

accessed at www .regulations.go v

.

1. Risk Conclusions

Hazard Characterization

The toxicological database is considered adequate for characterizing hazard and assessing risk from Morpel® Repellent 326

. The Agency does not need any additional studies for Registration Review

.

Dietary Assessment

There are no registered food uses for Morpel® Repellent 326 and it is not likely to occur in drinking

water ; therefore there is no concern for dietary risk.

Residential Assessment

Residential exposure is expected based on the registered residential uses of Morpel® 326. However, based on a conservative quantitative assessment, no risks of concern were identified.6 Occupational Assessment

Based on a screening

- level asse ssment, it was determined that there are no risks of concern associated with exposure during occupational treatment of companion animals. Occupational post application exposure is expected to be minimal because it is assumed that treated animals would be

r eturned to their residential settings after treatment.

Aggregate Assessment

Since there are no dietary risk concerns, an aggregate risk assessment for Morpel® 326 was not

neccesary

.

2. Human Health Incidents

The Office of Pesticide Programs (OPP) Incident Data System (IDS) was used to retrieve pesticide

incident data on Morpel® 326. The IDS records incidents in one of two modules: Main IDS and Aggregate IDS. Main IDS contains incidents resulting in higher seve rity outcomes and provides more detail with regard to case specifics. Aggregate IDS contains incidents resulting in less severe human incidents (minor, unknown, or no effects outcomes). In the Main IDS, from January 1, 2009 to March 5, 2014, there were no incidents involving the single chemical

, Morpel® 326

, reported in the database. There were 26 incidents reported involving more than one chemical. Twenty five of these incidents were classified as moderate severity, not life threatening and the person ret urned to his/her pre

- exposure state of health with no additional residual disability. In the Aggregate IDS, from January 1, 2009 to March 5, 2014, there were 449 reported incidents involving Morpel® 326. One hundred seventy nine incidents were classified a s unknown or no effects and 270 incidents were classified as minor severity.

The Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System for Occupational Risk

- Pestici des (SENSOR) databases were also queried. The NIOSH SENSOR

- Pesticides 1998

- 2010 data identified

73 cases involving Morpel® 326

, all involving multiple active ingredients. Of the 73 cases involving the single active ingredient, 68 cases were low in severity

, three case s w ere moderate in severity, and two cases were high severity.

Reports of adverse health effects allegedly due to a specific pesticide exposure (i.e., an "incident") are largely self

- reported and therefore, generally speaking, neither exposure to a pesticide or reported symptom (or the connection between the two) is validated or otherwise confirmed. Typically, causation cannot be determined based on incident data. For detailed information, see Dipropyl Isocinchomeronate (MGK

- 326): Tier I Review of Human Incidents dated April 9, 2014 in the public docket ( EPA

- HQ

- OPP

- 2014

- 0578 ) at www.regulations.gov

.

3. Food Tolerances

There are no existing food tolerances for Morpel® Repellent 326 because no product containing

this active ingredient is registered for any food or feed uses

.7 B. E cological Risk Assessment

Based on the limited use pattern, diffusion over a large treatment area, and the low probability of

non

- target organism exposure to Morpel ® Repellent 326, the Agency determined that it was appropriate to conduct a preliminary ecological risk assessment for Morpel® 326. A summary of the Agency's preliminary ecological risk assessment is presented below. For detailed discussions see Registrati on Review

– Preliminary Ecological Risk Assessment and Endangered Species Effects Determination for Dipropyl isocinchomeronate (aka Morpel® Repellent 326, formerly MGK® Repellent 326) , dated October 20, 2014, in the public docket (EPA

- HQ

- OPP

- 2014

- 0578) whi ch can be accessed at www.regulations.gov.

1. Environmental Fate and Exposure

Morpel® 326 remains stable under acidic conditions, and hydrolyzes in neutral and alkaline

environments. Morpel® 326 is not expected to volatize under field conditions. Based on the use pattern, significant environmental exposure (terrestrial or aquatic) is not expected.

2. Risk Conclusions

Aquatic Organisms

The Agency estimated potential exposure and acute risk to aquatic organisms. The Agency

conservative ly estimate d exposure, and re sulting acute risk quotients (R Qs) are far below the Agency's level of concern. While chronic RQs were not estimated, given the large margin of safety observed for acute effects, the Agency believes it unlikely that chronic risks would approach concern levels. Similarly , risk to aquatic plants is presumed to be below the level of concern based on Morpel® 326’s low toxicity and low potential to enter aquatic environments.

Terrestrial O rganisms

Based on the registered use patterns of Morpel® 326, exposure to terrestrial organisms is not expected. Even if a non

- target organism were to inadvertently come into contact with Morpel® 326

, the exposure levels would be expected to be low. Give n Morpel® 326’s low toxicity profile, effects

to non

- target organisms would not be expected to exceed the Agency’s levels of concern even if exposure to terrestrial organisms occurred.

Pollinator studies have not been required for Morpel® 326 . However, with the June 2014 Guidance for Assessing Pesticide Risks to Bees now in place, EPA has begun to require these data where applicable. Consistent with existing guidance 40 CFR, Part 158, Subpart G § 158.630, po llinator data are required for pes ticide active ingredients with terrestrial, forestry and residential outdoor uses. Based upon the typical use pattern for Morpel® 326 (personal repellent spray or towelettes) and the lack of a complete terrestrial exposure pathway, EPA is not requir ing pol linator data at this time.

3. Ecological Incidents

There are no reported ecological incidents involving Morpel® 326. A review of all available

information in the following databases was completed in April 2014 , covering the time period from

1994 to 2014 : Ecological Incident Information System 8 (EllS), OPP Aggregate Incident Reports8 database, and Avian Monitoring Information System (AIMS ) . For additional discussion of the reported ecological incidents, see Registration Review

– Preliminary Ecological Risk Assessment and Endangered Species Effects Determination for Dipropyl isocinchomeronate (aka Morpel® Repellent 326, formerly MGK® Repellent 326)

.

C. Endangered Species Assessment

Because of Morpel® 326’s low use diffused over a large treatment area and the low probability of

non

- target organism exposure to Morpel® 326 , the Agency concludes that effects on the environment are not reasonably expected to occur from the registered use of Morpel® 326

. The refore, the EPA is making a "no effects" determination under the Endangered Species Act (ESA) for all listed species and a finding that no adverse modification of designated critical habitat for such species is expected from the registered use of Morpel® 3 26

.

D. Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, includ ing 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, o rgan weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproduct ive effects in different taxonomic groups. As part of its most recent registration decision for Morpel® Repellent 326, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard

databa se. However, as required by FFDCA section 408(p), Morpel® Repellent 326 is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the 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 Administrator 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 estr ogen, 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 Tier 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 ef fect.

Under FFDCA 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 iner t ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 1 and includes some pesticides

1 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.9 scheduled for Registration Review and chemicals found in water. For further information on the status of the EDSP, the po licies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 2

IV. INTERIM REGISTRATION REVIEW DECISION

In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this I nterim Registration Review D ecision. Except for the EDSP component of the Morpel® Repellent 326 Registration Review case, the Agency has made the following interim decision : (1) no additional

data , including pollinator data, are required at this time; and (2) no changes to the affected registrations or their labeling are needed at this time. EPA has not identified any risks of concern to

human health. Currently registered uses of Morpel® Repellent 326 are not expected to result in

adverse effects to listed or non

- listed species or their critical habitat s

. As such, EPA is making a “no

effect” determination under the ESA for all listed species and no adverse modification of designated

critical habitat for such species is expected for all currently registered uses of Morpel® Repellent

326

. In this Interim Registration Review Decision, EPA is making no human health or

environmental safety findings associated with the EDSP screening of Morpel® Repellent 326. Before completing this Registration Review, the Agency will make an EDSP FFDCA section 408(p)

determination.

Additionally, with the issuance of this Interim Registration Review Decision

, the EPA finds that the maximum annual production and distribution quantity and the maximum concentration of 2.5% active ingredient set forth in the 2005 RED are no longer necessary. In order to effectuate any

c hange to Morpel 326 registrations, the registrant i s required to submit a formal request to the Agency

.

V. NEXT STEPS

I n accordance with 40 CFR Sections 155.5 7 and 155.58

, EPA will make a final Registration Review

decision for Morpel® 326 after an EDSP FFDCA section 408(p) determination has been made.

2 http://www2.epa.gov/endocrin e

- disruption/endocrine

- disruptor

- screening

- program

- edsp

- 21st

- century