STATESENVIRONMENTALPROTECTION

AGENCY

OFFICEOFCHEMICALSAFETY 

AND POLLUTIONPREVENTION

PC Code: 031520,119046, and 129046 

DP Barcode: 423438 

. Date: December 10,2014

MEMORANDUM 

SUBJECT:

FROM:

REVIEWED 

BY:

THROUGH:

TO:

EFED Responses to Public Comments on the EFED Problem Formulation for the 

Environmental Fate and Ecological Risk, Endangered Species, and Drinking 

Water Assessments (DP Barcode: 416759) in Support of the Registration Review 

of Mecoprop-p (MCPP-p ). Docket ID: EP A-HQ-OPP-20 14-0361, Case 0377 

and 

Addendum to Data Gaps Identified in the Problem Formulation 

Steve Carey, Biologist 2h.A (' _..... -"' 17/t ill;'/ 

Ibrahim Abdel-Saheb, Ph~TnvYron~l Scientist 

1 

Environmental Risk Branch VI

Environmental Fate and Effects Division (7507P) 

Monica Wait, RAPL 

Environmental Risk Branch VI

Environmental Fate and Effects Division (7507P) 

cJ Mark Corbin, Branch Chief 

Environmental Risk Branch VI __ 0 . Environmental Fate and Effects Division (:; ) 

Marianne Mannix, Chemical Review Manager 

Patricia Parrott, Branch Chief 

Risk Management and Implementation Branch Ill 

Pesticide Re-Evaluation Division (7508P) 

This memorandum transmits the EFED response to comments submitted by the MCPP-p Task 

Force, San Francisco Bay Regional Water Quality Control Board, and California Central Valley 

Regional Water Quality Control Board. In addition, the memorandum is updating the data gaps 

for MCPP-p which were identified in the Problem Formulation. 

1 
2

MCPP-p Task Force Comments 

Problem Formulation for the Environmental Fate, Ecological Risk, Endangered Species, and 

Drinking Water Exposure Assessments in Support of the Registration Review of Mecoprop-p 

(MCPP-p) 

Docket ID: EPA-HQ-O PP-2014-0361-0002 

GENERAL COMMENTS 

1. Because amines and salts of MCPP-p quickly dissociate to the MCPP-p anion, as does 

the acid at physiologically, environmentally and agriculturally relevant pH conditions, all 

these forms can be considered essentially equivalent for the purposes of risk assessment. 

Quantitative application of results may require adjustment of values to reflect the 

respective molecular weights. For simplicity, all results are presented in terms of "acid 

equivalent" in quantitative risk assessments. 

2. EPA Excerpt from the Problem Formulation: “For the honeybee adult 10-day chronic 

oral study, MCPP-p is a systemic phenoxy which the plant absorbs the test material by 

the foliage or roots of the plant and is translocated throughout the whole plant to roots, 

leaves, etc.., increasing the likelihood that a pollinator would be exposed to MCPP-p 

EPA is requesting the special study to evaluate the chronic effects of MCPP-p to 

pollinators.”

Task Force Comment: Suggest minor edits for clarification: “For the honeybee adult 10-

day chronic oral study, EPA observes that MCPP-p is a systemic phenoxy which the 

plant absorbs by the foliage or roots and which is translocated throughout the whole plant 

to roots, leaves, etc.., increasing the likelihood that a pollinator would be exposed to 

MCPP-p. EPA is requesting the special study to evaluate the chronic effects of MCPP-p 

to pollinators.” 

3. EPA Excerpt from the Problem Formulation: “MCPP-p DMAS is formulated as 

granular, water-soluble concentrate liquid, water soluble concentrate dry.”

 Task Force Comment: Pressurized liquid and ready-to-use solution should be added to 

read: “MCPP-p DMAS is formulated as granular, water-soluble concentrate liquid, water 

 soluble concentrate dry, pressurized liquid (dispensed as foam) and ready-to-use 

solution.”

4. EPA Excerpt from the Problem Formulation: “MCCP-p” 

 Task Force Comment: Please correct typographical error to read “MCPP-p”. 

5. EPA Excerpt from the Problem Formulation: “Given that MCPP-p is soluble in water 

there exists the potential to dissolve in runoff and puddles on the treated field may 

contain the chemical. 
3

 Task Force Comment: Punctuation would help clarify the meaning of the sentence. Also, 

 a wording change is proposed in recognition that MCPP-p is primarily used on turf rather 

than fields: “Given that MCPP-p is soluble in water, there exists the potential to dissolve 

 in runoff and thus puddles, if present on the treated turf, may contain the chemical.” 

6. EPA Excerpt from the Problem Formulation: “low octanol/water partitioning 

coefficient” 

 Task Force Comment: Suggest revision to read “low octanol/water partition coefficient” 

7. EPA Excerpt from the Problem Formulation: “2-methyl-4-chlorophonel” 

 Task Force Comment: Please correct spelling as follows: 2-methyl-4-chlorophenol. 

8. EPA Excerpt from the Problem Formulation: “The aquatic vascular and nonvascular 

plant species were most sensitive to MCPP-p DMAS, which caused significant effects to 

at all test levels that the NOAEC could not be established; the EC05 values were used 

instead.” 

 Task Force Comment: Suggest revision to: “The aquatic vascular and nonvascular plant 

 species were most sensitive to MCPP-p DMAS, which caused significant effects at all 

 test levels such the NOAEC could not be established; the EC05 values were used 

 instead.”

9. Page 39, Appendix A – Bibliography, MRID 0789601 

 Task Force Comment: Please correct the MRID to reflect 40789601. The performing 

 laboratory is Hazleton Laboratories America, Inc.

EFED Response: Comments #1-9 will be considered and typographical errors will be corrected 

in future risk assessments.

SPECIFIC COMMENTS 

1. Problem Formulation Page 13, Table 5, Aquatic Plants, Nonvascular, Marine Diatom.

EPA Excerpt from the Problem Formulation:

Taxonomic

Group

Study

Type

Surrogate

Species

Toxicity

Value

Acute

Toxicity

Classification

Source

(Study 

classification)
4

Aquatic

Plants

Nonvascular Marine

diatom 

(Skeletonema 

costatum)

NOAEC =

<0.009 mg 

a.e./L; IC05

=

0.0008 mg

a.e./L; IC50 =

0.014

(DMAS)

-- 42633902

43657303 

(Acceptable)

Task Force Comment: We have significant comments on this endpoint because studies such as 

those listed by EPA as “Acceptable” have faced considerable questions and criticism in other 

regulatory contexts. In a 2006 submission by the MCPP-p Task Force to EPA-SRRD (MRID 

number 47008601), an overview document identified and explained the issues faced by 

multiple phenoxy compounds. The MCPP-p Task Force has recently attempted to address 

MCPP-p more specifically with the submission of a new MCPP-p Skeletonema study by the

Task Force (MRID 49355201). The concern facing the different phenoxy task forces (MCPPp, 2,4-DP-p, MCPA, MCPB and 2,4-DB) is that some of the original studies identified in this 

overview were conducted at a particular laboratory according to earlier guidelines (Subdivision 

J) and present a picture of the toxicity of phenoxies to non-target aquatic plants that is 

inconsistent with results obtained at many different contract research organizations (CRO)

using the same or more current guidelines.

Relevance of the New Study for Nonvascular Aquatic Plant Toxicity of MCPP-p:

In comparison to the 2007 RED for MCPP-p, data from the new study show the 96-Hour EC50

for the marine diatom to be 83 mg ae/L vs 0.014 mg ae/L and the NOEC to be 32 mg ae/L vs 

<0.009 mg ae/L. The MCPP-p Task Force registrants believe that the older study was flawed in 

respect to having adequate growth of the test organisms thereby skewing the results lower. 

Therefore, the new study should be referenced for these endpoints. 

Excerpt of New Study:

RESULTS

Biological Parameter

Based on Nominal Concentrations (mg MCPP-p 4

amine/L)

EC50

(95% Confidence

Limits)

NOEC

96-Hour Yield 460 (310-570) 160

96-Hour Average

Specific Growth Rate

630 (590 - 670) 160

96-Hour Area Under the

Growth Curve

550 (420 - 650) 160
5

Biological Parameter

Based on Mean Measured Concentrations (mg MCPP-p a.e./L)

EC50

(95% Confidence Limits)

NOEC

96-Hour Yield 83 (59 - 99) 32

96-Hour Average

Specific Growth Rate

110 (l10 - 120) 32

96-Hour Area Under the

Growth Curve

99 (76 -120) 32

Excerpt of MCPP-p RED:

Table 25. Summary of Aquatic Plant Toxicity Data for MCPP-p

Species Toxicity Endpoint MR1D

Vascular plant,

Lemna gibba

EC50 = 1.3 mg ae/L

NOAEC < 0.44 mg ae/L

EC05 = 0.23 mg ae/L

Frond

number

42486201

Nonvascular plant,

Skeletonema costatum

EC50 = 0.014 mg ae/L

NOAEC < 0.009 mg ae/L

EC05 = 0.0008 mg ae/L

Cell count

density

42633902

43657303

mg ae/L = milligrams of acid equivalent per liter 

With increasing emphasis and attention on potential impacts to endangered species, including 

possible indirect effects to critical habitat, there is a possibility that some of the phenoxy 

herbicides will be found to “May Affect” some endangered species based on the alga data 

generated by one CRO that, based on the weight of the evidence, appear to be outliers. Our 

concern is it appears that no number of more recent studies conducted to current guidelines will 

offset these earlier results, even if there are stark reasons to consider the initial results, 

conducted to older guidelines, highly suspect or indeed invalid for current risk assessment 

purposes.

EFED Response: While the difference in results between the various studies is notable, EFED 

does not have information to explain the cause of the variation or to support that the earlier 

studies are scientifically invalid; however, for risk determination it is EFED policy to use the 

scientifically valid ecotoxicity study that provides the most conservative toxicity endpoints. For 

risk characterization, EFED considers the range of sensitivities among aquatic plants to evaluate 

whether one or all listed aquatic plants will be impacted when exposed. Also, the ECOTOX 

database or other sources of open literature will be looked at for other studies for consideration. 

2. Problem Formulation Page 15, Table 6, Mammal – Chronic, MRID 46591804

Task Force Comment: The MCPP-p Task Force does not have a copy of the DER for this 

study. A request for DERs was sent to Kaitlin Keller on June 30, 2014. 

EFED Response: The Health Effect Division (HED) reviews the 2-generation reproduction 

study with mammals. The Pesticide Re-Evaluation Division (PRD) will provide the available 

DER for the requested study to the task force. 
6

3. Problem Formulation Page 15, Table 6 and Page 29, Table 9, Terrestrial Plants 

– Vegetative Vigor, MRID 43059301

Task Force Comment: EPA indicates the study associated with MRID 43059301 is classified 

as supplemental. The MCPP-p Task Force received a letter from EPA dated March 10, 1997 

indicating the Task Force “submitted acceptable information indicating that the 100% 

acetonitrile solvent treatment did not have any adverse effects on the ten crops tested. 

Therefore, the study (MRID 43059301) is upgraded to core and fulfills the guideline 

requirement 123-1b for MCPP-p Acid.”

EFED Response: EFED will revise the study classification for MRID 43059301 from 

“supplemental” to “acceptable”. 

4. Problem Formulation Page 22, Table 7

Task Force Comment: The MCPP-p Task Force does not have copies of the DERs for 

the following studies. A request for the DERs was sent to EPA on June 30, 2014.

MRID 44110901 – Hydrolysis 

MRID 42578101 – Special Dissociation Study (DMAS) 

MRID 44147001 – Photodegradation on Soil 

MRID 44281301 – Aerobic Soil Metabolism 

MRID 42845301 – Aerobic Aquatic Metabolism 

MRID 44205701 – Leaching – Adsorption/Desorption 

MRID 42845302 – Leaching – Adsorption/Desorption 

MRID 43909701, 43909702, 43909703, 43909704, 43909705, 43943201 – Terrestrial

Field Dissipation.

EFED Response: EFED will work with the Pesticide Re-Evaluation Division (PRD) to provide 

available DERs for the requested studies to the task force. 

5. Problem Formulation Page 22, Table 7, Guideline # 201-1 and 201-2, Study 

Classification

Task Force Comment: The entry in the cells is “a” which appears to indicate there should be 

a footnote to the table. However, there is not a footnote. Please clarify. 

EFED Response: The following footnote (Member of Spray-Drift Task Force) will be 

incorporated in future assessments.

6. Problem Formulation Page 31, 32 and 33; Appendix A – Bibliography, MRID 40116101

Task Force Comment: EPA lists MRID 40116101 as the following: 

TPH Committee (1986) Response to Data Call-in on Mecoprop of March 22, 1985: [Toxicology

Data]. Unpublished compilation. 105 p.

The MCPP-p Task Force indicates MRID 40116101 has been assigned to the following studies:

Munk, R. (1986) Testing for Acute Toxicity in Fish – MCPP (Mecoprop) to the Bluegill Sunfish
7

(Lepomis macrochirus RAF). BASF Aktiengesellschaft Study Number 14F0047/83. 19 p.

Munk, R. (1986) Avian Single-Dose Oral LD50 of MCPP to the Bobwhite Quail (Colinus 

virginianus). BASF Aktiengesellschaft Study Number 11W0047/8372. 37 p.

EFED Response: The citations will be incorporated in future risk assessments.

7. Problem Formulation Page 31, Appendix A – Bibliography, MRID 42436701

Task Force Comment: There are two study numbers included in the citation for MRID 

42436701. The appropriate study number for this MRID is 119-002-03. The other study listed –

119-001-01 – was assigned MRID 42435601. 

EFED Response: EFED will correct the citation for MRID 42436701 using the study number 

119-002-03 and remove study number 119-001-01. 

8. Problem Formulation Pages 75-109, Appendix D, Label use information for MCCP-p 

(PC Code 129046); MCPP- p potassium (PC Code 031503); MCPP-p (DMAS) (PC 

code 031520)

Task Force Comment: Our review and comments at this time are limited to a subset of 

registrations for which EPA’s calculation of an “A.I. Maximum Application Rate” resulted in 

what appeared to be an application rate that is much larger than the rate actually stated on the 

label. In our selected recalculations, we use the pounds per gallon of MCPP-p acid equivalent 

stated on the label as the starting point. For example, if the label declares 0.48 lb MCPP-p 

ae/gal and the rate is 2 gal/A, then the ae rate is calculated as follows: 

0.48 lb ae/gal x 2 gal/A = 0.96 lb ae/A

Using this methodology, our calculations do not agree with those of EPA and we urge the 

Agency to re-evaluate the rates in Appendix A, especially for any rates that stand out as 

unusually high. Other specific label interpretation considerations are also identified in the 

particular examples below. 

Problem Formulation Pages 87-89, EPA Reg. No. 2217-639

Task Force Comment: In multiple rows on this range of pages, EPA identifies rates of: 

2.5746325 lb/A foliar industrial 

1.28731625 lb/A broadcast industrial 

0.51200078 lb/A broadcast turf 

0.49776109 lb/A spot treatment turf 

These presumably relate to the label rates of:

2.2 gal/A foliar industrial 

1.1 gal/A broadcast industrial 

0.55 gal/A broadcast turf 

0.4375 gal/A spot treatment turf 
8

However, when the Task Force calculates the rates using the MCPP-p content of 0.96 lb 

ae/gal, we obtain values of: 

2.112 lb ae/A foliar industrial 

1.056 lb ae/A broadcast industrial 

0.528 lb ae/A broadcast turf 

0.42 lb ae/A spot treatment turf 

Nearly all of these rates are lower than those calculated by EPA.

Problem Formulation Page 98, EPA Reg. No. 2217-961

Task Force Comment: In multiple rows, EPA identifies rates of: 

0.3733847 lb/A broadcast nonagricultural 

1.71687572 lb/A spot treatment nonagricultural 

0.36486153 lb/A spot treatment turf 

0.33508883 lb/A broadcast turf 

These presumably relate to the label rates of: 

0.4875 gal/A broadcast nonagricultural 

0.49125 gal/A spot treatment nonagricultural 

0.488 gal/A spot treatment turf 

0.4875 gal/A broadcast turf 

However, when the Task Force calculates the rates using the MCPP-p content of 0.655 lb 

ae/gal, we obtain values of: 

0.319312 lb ae/A broadcast nonagricultural 

0.321768 lb ae/A spot treatment nonagricultural 

0.31964 lb ae/A spot treatment turf 

0.319312 lb ae/A broadcast turf 

The Task Force calculations all resulted in lower rates than those of EPA. Also, the labeled 

maximum annual application rate for spot treatment on nonagricultural land for this registration 

is 6 pts/A, which is equivalent to only 0.49125 lb MCPP-p ae. A rate of over 1.7 lb/A as shown 

in EPA’s table is not allowed by the label.

Problem Formulation Pages 101-102, EPA Reg. No. 228-217

Task Force Comment: Among the stated “Use Restrictions” for the entire label is: “Do not 

apply more than 4.4 gallons of product (1.5 lb MCPA)/acre per year.” Since the MCPP-p 

content for this product is 0.17 lb ae/gal, the maximum permissible MCPP-p rate under this use 

restriction is: 4.4 gal x 0.17 lb ae/gal = 0.748 lb ae/A. Even if this restriction was revised to be a 

limit per application instead of an annual limit (as a recent clarifying interpretation of the 

MCPA RED states), the MCPP-p rate for a single application would not exceed 0.748 lb ae/A. 

In multiple rows, EPA identifies rates of: 

0.00080019 lb /30 fl oz spot treatment nonagricultural 
9

0.819 lb/A broadcast nonagricultural 

17.84407666 lb/A spot treatment turf 

0.17425811 lb/A broadcast turf. 

1.24798563 lb/A spot treatment residential lawn

0.878715 lb/A broadcast residential lawn

These presumably relate to the label rates of: 

3 tsp product/30 fl oz water (for individual/small areas of weeds) spot treatment nonagricultural 

4.4 gal/A broadcast nonagricultural 

3 tsp product/2 qt water /100 sq ft (or for individual/small areas of weeds) spot treatment turf 

4.4 gal/A broadcast turf 10.5 tsp product/2 qt water (for individual/small areas of weeds) spot 

treatment residential lawn 1.5 gal/A broadcast residential lawn

However, when the Task Force calculates the rates using the MCPP-p content of 0.17 lb 

ae/gal, we obtain values of: 

0.000664 lb ae/30 fl oz (for individual/small areas of weeds) spot treatment nonagricultural 

0.748 lb ae/A broadcast nonagricultural 

0.000664 lb ae/2 qt water (for individual/small areas of weeds) spot treatment turf 

0.748 lb ae/A broadcast turf

0.0023242 lb ae/2 qt water (for individual/small areas of weeds) spot treatment residential lawns 

0.255 lb ae/A broadcast residential lawns 

The EPA calculated rate of 17.84407666 lb/A is highly inconsistent with label information and 

should not be used for risk assessment. However, we acknowledge that there are opportunities 

to improve clarity of label language.

Problem Formulation Page 106, EPA Reg. No. 228-513

Task Force Comment: The maximum label rate for spot treatment on lawns and turf is 13.5 pints 

of product per acre, which is equivalent to only 1.198 lb ae/A of MCPP-p. In contrast, EPA’s 

table identifies a rate of 60.82840701 lb/A. This rate is highly inconsistent with the label and 

should not be used for risk assessment. It is acknowledged that the label could be more clear, but 

the sense of the label is that the rates given in pints are expressed on a per acre basis and rates 

given in fluid ounces are expressed on a per 1000 square foot basis. Perhaps a point of confusion 

is that decimal points in some of the rates seem to be illegible in the EPA stamped accepted 

label.

EFED Response: EFED will work with the Biological and Economic Analysis Division 

(BEAD) of OPP to update the use summary tables at the time of risk assessment. Additionally, 

the Agency may request that registrants and/or the MCPP-p Task Force provide a use pattern 

summary table which includes this type of application information. 
10

The San Francisco Bay Regional Water Quality 

Control Board Comments 

For the MCPP registration, we support the aquatic toxicity data requests laid out in EPA’s 

Environmental Fate and Effects Division’s (EFED) Problem Formulation dated June 2, 2014. We 

urge EPA to amend the MCPP-p Registration Review Work Plan to require data to fill the data 

gaps identified by EFED, specifically: 

• Estuarine/marine invertebrate acute toxicity 

• Estuarine/marine fish acute toxicity 

• Freshwater fish early-life stage. 

In addition, we strongly encourage EPA to request data for fate and aquatic toxicity for the 

degradate 2-methyl-4-chlorophenol. As stated in the EFED Problem Formulation, information 

from the Pesticide Properties Database indicates that this degradate is more toxic to aquatic 

invertebrates and fish than the parent compound. 

We strongly encourage EPA to consider the cumulative risk of additive toxicities, both between 

MCPP-p and its degradates and also between these herbicides and other pesticides. 

California Central Valley Regional Water Quality 

Control Board Comments 

In order to prevent water quality impairments caused by MCPP-p we are requesting the

following additions to the registration review workplan: 

 Require the necessary ecological effects data for risk assessment identified in the EFED 

problem formulation:

o Estuarine/marine invertebrate acute toxicity. 

o Estuarine/marine fish acute toxicity. 

o Freshwater fish early-life stage. 

 Consider the cumulative risk of additive toxicities between MCPP-p, other phenoxy 

herbicides, and their common and toxic degradates (e.g., 2-methyl-4-chlorophenol). 

EFED Response: EFED appreciates the comments from the San Francisco Bay Regional and 

California Central Valley Regional Water Quality Control Boards (collectively CA WQCB) 

suggesting that OPP require data tested with the parent compound (estuarine/marine invertebrate 

acute toxicity, estuarine/marine fish acute toxicity, and freshwater fish early-life stage) to fill the 

data gaps needed for a complete ecological risk registration review. While no specific risk 

concern was cited by either CA WQCB other than the potential for water quality impairments; 

EFED does agree that there is a potential for exposure to freshwater and estuarine/marine 

organisms from MCPP-p use. While the aquatic studies for the parent compound were identified 

as data gaps in the problem formulation, EFED is not requiring the estuarine/marine studies 
11

given the lines of evidence indicating that exposure estimates from the Reregistration Eligibility 

Decision for the parent compound are one to two orders of magnitude below known toxicities of 

chlorophenoxy herbicides to freshwater organisms. It is assumed the estimated environmental 

exposures for MCPP-p would be at least an order of magnitude below the toxicity of the parent 

compound to estuarine/marine organisms. Also, a daphnid chronic study is available, with an 

uncertainty introduced, which can be used to calculate an ACR (Acute-to-Chronic Ratio) to 

estimate a chronic value for freshwater fish in lieu of an 850.1400 freshwater fish early-life stage 

study. Thus, requiring the aquatic studies is of low value to the ecological risk assessment 

because the potential for exposure is anticipated to be low. 

In addition, exposure estimates and toxicity of the degradates have not been included in past 

assessments for MCPP-p. If exposure and/or toxicity of the degradates are significant, then the 

risks to potentially exposed organisms could be underestimated. A review of the Pesticide 

Properties Database (http://sitem.herts.ac.uk/aeru/ppdb/en/Reports/876.htm) indicates the aquatic 

toxicity data for the degradate 2-methyl-4-chlorophenol on bluegill sunfish, daphnia magna, and 

lemma gibba are available and should be submitted to the Agency for a formal in-house review 

to determine whether the data is acceptable for use in the risk assessment. Upon further 

investigation, these studies with the degradate were in the ECOTOX database. The studies with 

the bluegill sunfish and daphnia magna will be pulled by EFED and reviewed for consideration. 

However, the study with the lemna gibba is from an unknown source, and any additional 

information on the source/content of that lemna gibba study would be helpful. The citations for 

the bluegill sunfish and daphnia magna are as follows: 

ECOTOX Reference 

Number: 5590

Author(s): Buccafusco,R.J., S.J. Ells, and G.A. LeBlanc

Publication Year: 1981

Title: Acute Toxicity of Priority Pollutants to Bluegill (Lepomis macrochirus)

Source: Bull. Environ. Contam. Toxicol.26(4): 446-452

ECOTOX Reference 

Number: 5184

Author(s): LeBlanc,G.A.

Publication Year: 1980

Title: Acute Toxicity of Priority Pollutants to Water Flea (Daphnia magna)

Source: Bull. Environ. Contam. Toxicol.24(5): 684-691

EPA appreciates the need to address cumulative risk from mixtures of pesticides both within and 

across modes of action. EPA, FWS, and NMFS collectively engaged the National Academy of 

Sciences (NAS) on the issue of mixtures as part of the broader approach to conduct ESA 

compliant pesticide risk assessments. As noted by the NAS report, the ability to quantitatively 

assess risk from mixtures (tank mixes, formulated product, and environmental) is perhaps the 

most daunting challenge facing EPA and the Services. EPA currently considers cumulative 

mixture toxicity where data are available on combined effects from one or more compounds. 

EPA acknowledges that mixtures represent a consideration that may influence the toxicity of the 
12

active ingredient; however, there are many uncertainties and limitations to quantitatively 

assessing the impact of mixtures on the overall risk picture. As the NAS noted, there are 

significant challenges to incorporation of mixtures analyses into the risk assessment process 

including the lack of a generic peer-reviewed method to assess the risks from mixtures, 

uncertainty on the temporal aspects of exposure to mixture constituents (e.g. each constituent 

behaves differently once in the environment), lack of knowledge about mechanism of action in 

non-targets, and uncertainty on the portability of observed interactions across taxa. EPA and the 

Services have made the issue of developing an approach for assessing mixtures toxicity a priority 

for future risk assessments. 
13

Addendum to Data Gaps Identified in the Problem Formulation

The Problem Formulation requested three studies to evaluate the potential for MCPP-p to 

adversely affect pollinators: a honeybee adult acute oral toxicity study (following OECD 213), a 

honeybee adult 10-day chronic oral (special study), and a honeybee larval repeated dose study 

(special study renamed as honeybee larval chronic oral toxicity study). However, EFED policy 

on pollinator protection has recently been updated1

. Thus, justifications are provided below for 

the following Tier I bee studies: 

 Acute oral toxicity to adult honey bees 

 Acute oral toxicity to larval honey bees 

 Chronic oral toxicity to adult honey bees 

 Chronic oral toxicity to larval honey bees 

While the larval acute oral toxicity study (following OECD 237) was not specified in the MCPPp Problem Formulation, the release of the new pollinator guidance requires that this study should 

be conducted to support the MCPP-p risk assessment. Note that it is possible to conduct the 

larval chronic oral study in such a way as to derive both an LD50 (acute endpoint of interest) and 

a NOAEC (chronic endpoint of interest) from a single study. If the chronic larval toxicity study 

is conducted in such a way that it derives both an LD50 and NOAEC, then a separate acute larval 

toxicity study is not needed. For pollinator studies without finalized OECD guidelines, protocols 

should be submitted for EPA review and comment prior to study initiation. 

The need for higher Tier semi-field and full field pollinator studies for MCPP-p will be 

determined after review of these Tier I studies. 

Data Justifications 

Guideline Number: Special Study

Study Title: Adult Honey Bee Acute Oral Toxicity

Rationale for Requiring the Data

This study is needed for the assessment to evaluate risks to honey bees if the registered uses of MCPP-p

will result in adverse effects to honey bees or other insect pollinators. Registered non-agricultural use 

sites of MCPP-p include: nonagricultural areas, uncultivated areas/soils (i.e., roadsides and rights-ofway), ornamental lawns and turf (i.e. golf courses, cemeteries, parks, sports fields, turfgrass, lawns, and 

other grass areas), and sod farms. Therefore, MCPP-p residues may result in exposure to foraging bees. 

Residues can in turn be brought back to bee colonies where in-hive bees including young adult and 

developing brood (i.e., eggs, larvae and pupae) may be exposed. Therefore, exposure at all bee life 

stages would be expected and may extend for chronic exposures.

 

1

(Guidance for Assessing Pesticide Risks to Bees, 06.23.2014; signed by Donald Brady, Director, EFED; 

http://www2.epa.gov/sites/production/files/2014-

06/documents/pollinator_risk_assessment_guidance_06_19_14.pdf)
14

Guideline Number: Special Study

Study Title: Adult Honey Bee Acute Oral Toxicity

Rationale for Requiring the Data

Since the Problem Formulation for MCPP-p was signed, the Agency finalized its framework to assess risk 

to pollinators (USEPA, 2014). EPA now requires this study for all use sites where potential exposure to 

pollinators may occur. Registrants may request a waiver of the study if use practices significantly restrict 

exposure of the pesticide to bees.

Although EPA has not developed a guideline for this study, the acute (single dose) adult toxicity study 

following OECD TG213 provides acute oral toxicity data on adult bees and may be used to satisfy the 

requirement for acute oral toxicity to adult bees. At this time, EFED is asking that a protocol for the 

study be submitted beforehand to increase the likelihood of an acceptable study submission.

Practical Utility of the Data

How will the data be used and how could the data impact the Agency’s future decision-making? 

The acute toxicity study with young adult bees provides median lethal dose (LD50) value for honey bees 

(A. mellifera) based on acute oral exposure. These data are used in conjunction with acute contact LD50

data obtained through OCSPP 850.3020 to estimate the acute toxicity of technical grade active 

ingredient (TGAI) to individual young adult honey bees. The studies also provide slopes for the doseresponse curves that can in turn be used for estimating the likelihood of individual effects and sublethal 

effects observed in the study will be used to further characterize effects observed following a single 

exposure to the technical grade material. Data obtained from this study will be used in estimating acute 

risk to individual adult bees. Risk estimates based on these data will be considered along with other lines 

of evidence to determine whether higher-tier studies are needed at the whole colony level.

These data are needed for the registration review risk assessment and for future endangered species 

assessments. The data would allow the Agency better characterize the potential for risk to insects 

(including beneficial pollinators) from the use of MCPP-p. These data will help the Agency determine 

whether any mitigations are needed. If the registration review and any future endangered species risk 

assessments are performed without these data, the Agency would have to assume that MCPP-p "may 

affect" insects, including bees and beneficial pollinators, directly (and endangered species from other 

taxa indirectly), and uses of MCPP-p might need to be restricted in areas where pollinators could be 

exposed. 

Guideline Number: Special Study

Study Title: Adult Honey Bee Chronic Oral Toxicity

Rationale for Requiring the Data

This study is needed for the assessment to evaluate risks to honey bees if the registered uses of MCPP-p

will result in adverse effects to honey bees or other insect pollinators. Registered non-agricultural use 

sites of MCPP-p include: nonagricultural areas, uncultivated areas/soils (i.e., roadsides and rights-ofway), ornamental lawns and turf (i.e. golf courses, cemeteries, parks, sports fields, turfgrass, lawns, and 

other grass areas), and sod farms. Therefore, MCPP-p residues may result in exposure to foraging bees. 

Residues can in turn be brought back to bee colonies where in-hive bees including young adult and 
15

Guideline Number: Special Study

Study Title: Adult Honey Bee Chronic Oral Toxicity

Rationale for Requiring the Data

developing brood (i.e., eggs, larvae and pupae) may be exposed. Therefore, exposure at all bee life 

stages would be expected and may extend for chronic exposures.

Since the Problem Formulation for MCPP-p was signed, the Agency finalized its framework to assess risk 

to pollinators (USEPA, 2014). EPA now requires this study for all use sites where potential exposure to 

pollinators may occur. Registrants may request a waiver of the study if use practices significantly restrict 

exposure of the pesticide to bees.

Although EPA has not developed a guideline for this study and OECD has yet to finalize test guidance for 

chronic studies, efforts are currently underway to develop standardized guidelines for assessing effects 

from chronic (10-day) exposures to adult bees in the laboratory. At this time, EFED is asking that a 

protocol for the study be submitted beforehand to increase the likelihood of an acceptable study 

submission.

Practical Utility of the Data

How will the data be used and how could the data impact the Agency’s future decision-making? 

The 10-day toxicity study with young adult bees provides no-observed adverse effect level (NOAEL) and 

lowest-observed adverse effect level (LOAEL) for assessing potential chronic effects. Data obtained from 

this study will be used in estimating chronic risk to individual adult bees. Risk estimates based on these 

data will be considered along with other lines of evidence to determine whether higher-tier studies are 

needed at the whole colony level.

These data are needed for the registration review risk assessment and for future endangered species 

assessments. The data would allow the Agency better characterize the potential for risk to insects 

(including beneficial pollinators) from the use of MCPP-p. These data will help the Agency determine 

whether any mitigations are needed. If the registration review and any future endangered species risk 

assessments are performed without these data, the Agency would have to assume that MCPP-p "may 

affect" insects, including bees and beneficial pollinators, directly (and endangered species from other 

taxa indirectly), and uses of MCPP-p might need to be restricted in areas where pollinators could be 

exposed. 

Guideline Number: Non-Guideline

Study Title: Larval Honey Bee Acute and Chronic Oral Toxicity

Rationale for Requiring the Data

This study is needed for the assessment to evaluate risks to honey bees if the registered uses of MCPP-p

will result in adverse effects to honey bees or other insect pollinators. Registered non-agricultural use 

sites of MCPP-p include: nonagricultural areas, uncultivated areas/soils, soils (i.e., roadsides and rightsof-way), ornamental lawns and turf (i.e. golf courses, cemeteries, parks, sports fields, turfgrass, lawns, 

and other grass areas), and sod farms. Therefore, MCPP-p residues may result in exposure to foraging 

bees. Residues can in turn be brought back to bee colonies where in-hive bees including young adult and 

developing brood (i.e., eggs, larvae and pupae) may be exposed. Therefore, exposure at all bee life 

stages would be expected and may extend for chronic exposures. 
16

Guideline Number: Non-Guideline

Study Title: Larval Honey Bee Acute and Chronic Oral Toxicity

Rationale for Requiring the Data

Since the Problem Formulation for MCPP-p was signed, the Agency finalized its framework to assess risk 

to pollinators (USEPA, 2014). EPA now requires this study for all use sites where potential exposure to 

pollinators may occur. Registrants may request a waiver of the study if use practices significantly restrict 

exposure of the pesticide to bees.

Although EPA has not developed a guideline for this study, the 21-day larval toxicity study currently 

under development by OECD provides both acute and chronic oral toxicity data on developing bee brood 

and (when this guidance is finalized) may be used to satisfy the requirement for both acute and chronic 

oral toxicity to honey bee larvae. Registrant may submit a separate acute (single dose) larval toxicity 

study following OECD TG237 as well as the 21-day repeat dose chronic toxicity study. 

Practical Utility of the Data

How will the data be used and how could the data impact the Agency’s future decision-making? 

The 21-day larval toxicity study under development by OECD provides both acute and chronic toxicity data 

on developing bee brood and will yield a median lethal dose (LD50) for assessing acute toxicity during the 

early part of the study as well as a 21-day no-observed adverse effect level (NOAEL) and lowest-observed 

adverse effect level (LOAEL) for assessing chronic effects. Effects on survival and development (adult bee 

emergence) from repeat exposures to the active ingredient will be used in estimating chronic risk to 

individual brood. Risk estimates based on these data will be considered along with other lines of evidence 

to determine whether higher-tier studies are needed at the whole colony level.

These data are needed for the registration review risk assessment and for future endangered species 

assessments. The data would allow the Agency better characterize the potential for risk to insects 

(including beneficial pollinators) from the use of MCPP-p. These data will help the Agency determine 

whether any mitigations are needed. If the registration review and any future endangered species risk 

assessments are performed without these data, the Agency would have to assume that MCPP-p "may 

affect" insects, including bees and beneficial pollinators, directly (and endangered species from other taxa 

indirectly), and uses of MCPP-p might need to be restricted in areas where pollinators could be exposed.