### UN I TED STATE S ENVIRONMENTAL PR OTE C T I ON AGENCY

WASH I NGTON, D.C. 20460



### MEMORANDUM

Date: February 6, 2014 O FFIC E OF
C HEM I CAL SA FETY AND
POLLUTION PRE VEN TION



### SUBJEC T : 

### MCPA

. Human Health Risk Assessment Seeping Document in Support of Regis t ration Review

PC Code: 03050 I

, 030502

, 030516, 030564

Decision No. : 483034

Petition No.: Not Applicab l e Risk Assessment Type: S i ngl e Ch e mical

TXR No .: Not Applicabl e
MRID No.: None



### FROM: Alexandra LaMay, Biologist DP Barcode: 0414988 Registration No. : N ot Applicable Regulatory Action: R e gistration Review Scoping

Case No .: 0017

CAS No. : 9 4 -74-6

40 CFR: § 1 80.339



### Danette Drew, Chemist**-::::;.:=::::-~ L.** **...._-- ~--c,-r-** **//**



### THRU:

TO: L inda Taylor, Tox i cologis t
Risk Assessmen t Branch II



### Health E ffects Division (7509P)



### Office of Pesticide Progr i] 

# fj.Z-t

Peter Savoia, Chemis t 

# U 0 /) 

# 0

Michae l Metzge r, Chief, 

# tv{ / ·
Risk Assessment Branch I



### H e a l th Eff e cts Division (7509P)

Office of Pesticide P rog r ams

KhueNguyen

Pest i c id e Re-eva l u ation Division (7508P)

O f fice of Pes t icide Programs

Attached is the Health E ffects Division's (H E D) human health seeping document for MCPA to
support t he registration review process

.

Page 1 of31

### Executive Summary



### The Health Effects Division (HED) has evaluated the status of the human hea l th ri sk assessment
for MCPA to determine the scope of work neces sary to support Registration Review

. The most recently completed human hea l th risk assessment was considered as part of this scoping exercise.

MCP A (2-methyl-4-chlorophenoxyacetic acid) is a selec t ive, post

- emergence system ic herbicide

used for the control of annual and perennial broadleaf weeds. MCP A is a phenoxy herbicide registered for use on alfalfa, barley, clover

, flax, oats, pasture and rangeland grass, pea s, rye, triticale, and wheat, as well as grass grown for seed, to contro l a variety of broadleaf weeds

. MCPA is also registered for use on turf, lawn s, golf courses, and rights-of-way

.

The toxicity database for MCP A (4-(chloro-2-methy l phenoxy) acetic acid) is complete and adequate for characterization of potential developmental, r ep roductive

, carcinogenetic, mutagenic, neurotoxic, and immunotoxic effects. New toxicity data [an inhalation tox i c i ty study (870

. 3465) and a developmental neurotoxicity (DNT) study (870.6300))] ha ve been received

since the l ast risk assessment. During r egist ration review of MCP A, endpoint select i on, PODs,

and UF/SFs for th e dietary and inh alatio n risk assessments may need to be re-eva l uated

, based on

new data and updated po l icies and procedures

.

The res idu e chemistry database is complete with the exception of a metabo li sm study on peas and additional residue field trial data on peas (as i dentified in the 2004 MCP A risk assessment)

. The current tolerance express i o n shou l d be updated to comply with HED's current po li cy on tolerance exp re ssio ns dur i ng regis tration review.

There are currently no Codex or Canadian maxim um residue limits (MRLs) established. There

are several MRLs being proposed by Codex. Not a ll of the proposed MRLs would be

harmonized with the current U.S. to l erances. HED is not currently involved in any joint

international review projects tha t i n volv e the active ingredient, MCP 

### A

Currently there are no acute or chronic di etary risk estimates which are of concern for MCPA

and it s metabolites. However, updated dietary exposure assessments for MCP A may be

necessary under regi st ra

t ion review if there are significant changes to the drinkin g water

estimated concentrations which will be updated by EFED, or i f there are significant changes to

th e points of departure (PoDs) o r UFs /SFs.

Pre vious residential handler and post-application exposure assessments did not result in risk

estima tes of concern for adults or childre n. An updated residential exposure and risk assessment

may be required during registration review if warranted by any significant change in exposure

assessment methodology, toxicological points of departure, or uncerta i nty factors.

Residential bystander exposures resu l ting from off-site transport (i.e., spray drift or volatilizat i on) may occur as a result of occupational applications of MCP A 

### The need for a bys tander risk assessment for MCP A will be considered during registrat ion r eview

.

Page 2 of31

### Page 3 of 31

There are no current aggregate risks estimates of concern for MCPA. During registration review, updated aggregate assessments may be conducted as required to include any significant change that might occur for toxicological P ODs, FQPA and uncertainty factors, dietary exposure estimates, residential exposure estimates, or EDWCs. A short

- term aggregate assessment should be conducted and should include residential exposures and chronic food and drinking water

.

Based on the pre vious occupational exposure assessment, most of the handler exposure risk estimates were not of concern with single layer PPE. All of the post

- application worker exposure risk estimates were not of concern on day 0. The WPS REI for MCPA is 12 hours for

t he ester form and 48 hours for the amine and sodium salt forms. A DFR study is required for MCPA at this time since some of the estimated dermal occupational post

- application MOEs are less than 4 times the LOC. An updated occupational exposure and risk a ssessment may be required during registration review if warranted by any changes to policy or points of departure.

Impurities may be formed during the manufacturing process of the phenoxy chemicals a n d may

remain in the technical product. This is a poten tial issue that will be addressed during registration review. Since the 1990s, t he manufacturing processes have been modified to reduce

concentrations of impurities in the technical products. HED will continue to monitor data on the impurities and reasse ss any potential risks as necessary.

Introduction

HED has evaluated the most recent complete human health risk assessment for MCPA to determine if sufficient data are available and if updates are needed to support registration review.

HED has also c o nsidered updates to its toxicity, exposure and usage databases, and the latest Agency science policy and risk assessment methodologies.

MCPA is a selective, post

- emergence systemic herbicide used for the control of annual and perennial broadleaf weeds. MCPA belongs to phenoxy or phenoxyacetic acid family. Phenoxy herbicides act by simulating the action of natural hormones and produce uncoordinated cell division and plant 

### growth. The mechanism of action of this herbicide is by interfering with the protein

bio

- synthesis which leads to uncontrolled cell division and growth; ultimately, killing the susceptible weeds. Products of MCPA are available in salt, ester, or amine forms. MCPA is used in mixture with many other products to achieve a wider spectrum of w eed control. MCPA can be applied in various forms (free acids, esters or salts), but it releases a single common moiety that is the pesticidally active component and serves as the basis for tolerance regulation. The active ingredients (AIs) are MCPA (PC code 030501), MCPA sodium salt (PC code 030502), MCPA dimethylamine salt (MCPA DMAS; PC code 030516), MCPA isooctyl ester (PC code 030563),

and MCPA 2

- ethylhexyl ester (MCPA 2

- EHE; PC code 030564).

Registered agricultural use sites of MCPA include: barle y, flax, grasses grown for seed, oats, pastureland, peas , rye, and wheat. The registered non

- agricultural use sites of MCPA include: nonagricultural, uncultivated areas/soils, ornamental lawns, and turf. Formulations include granulars, emulsifiable conce ntrates, and soluble concentrate/liquid s.

MCPA is also a metabolite of MCPB ( 4

- (4

- chloro

- 2

- methylphenoxy)butanoic acid ) , which is also a pesticide active ingredient. A separate scoping document will be issued for MCPB.

### Page 4 of 31

Hazard Identification/Toxicology

MCPA is a member of the dichlorophenoxy class of herbicides that function by mimicking the action of auxins, plant growth hormones.

The toxicity database for MCPA is complete and adequate for characterization of potential developmental, reproductive

, car cinogenetic, mutagenic, neurotoxic, and immunotoxic effects with the submission of new data ( inhalation study and DNT )

. The newly submitted data will need to be reviewed to support registration review, but no new toxicity data will be required.

In metabolism studies in rats

, MCPA was rapidly absorbed and eliminated mainly in the urine

and no bioaccumulation occurred. The major urinary component i s MCPA.

The kidney and liver are the major target organs following MCPA exposure. In the subchronic

inh alation toxicity study, which was submitted subsequent to the last risk assessment, portal

- of

entry effects were observed following repeat inhalation exposure. Additional toxic effects include neurotoxicity, which was observed in the acute and subchronic (ACN/SCN) neurotoxicity studies and in a rat developmental toxicity study on the dimethylamine salt of MCPA. The developmental neurotoxicity study (DNT) , which was submitted subsequent to the last risk assessment to satisfy this data requirement, did not i dentify developmental neurotoxicity. Developmental toxicity occurred in the developmental studies in rats at dose levels that produced maternal toxicity

. D evelopmental toxicity was not observed in rabbits , and

r eproductive toxicity was not observed in the rat. Qualitative susceptibility was observed in rats, as evidenced by decreased fetal body weight, altered growth, and increased litter resorptions at dose levels that produced less severe toxicity in the maternal rat (decreased maternal body weight gain)

. MCP A is classified a s not likely to be carcinogenic to humans, based on long

- term
studies in rat s and m ice, and t here are no mutagenicity concerns. MCPA is not acutely toxic by the oral, dermal, and inhalation routes of exposure, based on lethality studie s; it is not a skin irritant but shows severe eye irritation and is negative for dermal sensitization. There is no concern for immunotoxicity, and the data requirement for immunotoxicity testing has been waived (TXR No. 0056819, dated November 5, 2013).

The acute, subchronic, and chronic toxicity profile tables for MCPA are included in Attachment 2. Toxicity endpoints, PODs, and UF/SFs were selected for oral, dermal, and inhalation exposure pathways for the Human Health Risk Assessment conducted in 200 4 (D299356 ), and

these are presented in Attachment 3. HED notes that endpoint selection was made before receipt of the inhalation study and DNT.

Conclusions: The toxicity database for MCPA is considered complete with the submission of an

inhalation st udy and a DNT. HED will need to review these new studies and may need to revisit the endpoints, PoD, and UFs/SF used for risk assessment during registration review.

Dietary Exposure

Residue Chemistry

### Page 5 of 31

The residue chemistry database is incomplete. A meta bolism study on peas and additional residue field trial data on peas remains outstanding (see Data Requirements section).

Parent MCPA is the residue of concern for tolerance enforcement and adequate analytical enforcement methods exist for plant and live stock commodities.

The chemical structure and nomenclature of MCPA is listed in Table A.1. The physicochemical properties of technical grade MCPA are listed in Table A.2.

Impurities may be formed during the manufacturing process of the phenoxy chemicals and may remain in the technical product. This is a potential issue that will be addressed during registration review. Since the 1990s, the manufacturing processes have been modified to reduce concentrations of impurities in the technical produc ts. HED will continue to monitor data on the impurities and reassess any potential risks as necessary.

The following residue chemistry data requirements were identified in the September 30, 2004 RED for MCPA. HED has updated the current status of those r equirements below as some requirements have since been fulfilled:

 860.1300 Metabolism studies on peas

There do not appear to be any data submissions reflecting the metabolism of MCPA on peas. There are adequate metabolism data for the MCPA on wheat ( grain and straw ) but peas are sufficiently different in composition than wheat that a separate metabolism study is required. This data requirement remains outstanding.

 860.1340 Residue analytical method for plants

The Residue Chemistry Chapter of the Registration Standard dated 8/31/81 noted that the PAM Vol I method is adequate for enforcement of tolerances for residues of MCPA in

livestock commodities as

- is, however the Agency had at that time recommended the method be modified with a hydrolysis step for enforcement of MCPA tolerances for plant

commodities. The current PAM Vol II methods are adequate for the enforcement of MCPA on plants and livestock commodities and no further modifications are required at

this time. The data requirement for 860.1340 r esidue analytical methods is fulfilled.

 860.1380 Storage stability data for wheat grain stored under ambient conditions for 28
days

Subsequent to the 2004 requirement, t he MCPA Task Force submitted data depicting the stability of MCPA, 2

- HMCPA and CCPA in/on wheat grain under ambient conditions to support the existing wheat processing study (MRIDs 47670701, 47670702, 47670703, 47670704, and 47670705 ). The data have been reviewed by HED ( D279942, D262444, and D227174, D. Davis, 10/12/10, MCPA. Review of Wheat Field Trials and Ambient

### Page 6 of 31

Storage Stability Data Submitted in Response to Reregistration Eligibili ty Document Data Requirements

. The storage stability data gap has been fulfilled.

 860.1480 Ruminant feeding study

Examination of EPA’s OPPIN database indicates that a ruminant feeding study has been submitted (MRID 47075201 ; Koch, D. (2007) Magnitude of the Residue of MCPA in Dairy Cow Milk, Cattle Meat and Tissues. Project Number: 49737, 214/001/10. Unpublished study prepared by ABC Laborato ries, Inc. and Genesis Midwest Laboratories. 279 p.). This study will be evaluated under MCPA registration review for acceptability and fulfillment of the feeding study requirement.

 860.1500 Four field trials reflecting a 0

- day PHI for pasture forage

Th e 2004 MCPA risk assessment determined that the number of available field trials for pasture and rangeland grass forage and hay is adequate to fulfill data requirements but

that additional data were required reflecting a 0

- day PHI for pasture grass forage

.

HED has since examined the available data and determined that the existing residue data for MCPA reflecting a 0 day PHI for rangeland grass forage is suitable to fulfill the requirement for 0 day PHI data for pasture grass forage (MRID 46331602) since th e use patterns are similar. Field trials on rangeland grass (MRID 43801301) and pasture grass (MRIDs 43782401 and 43791901) reflect two applications of MCPA at 2.0 lb are/A (4.0 lb ae/A total). Field trails were performed using both the 2

- EHE EC and DMAS SC. Samples were analyzed f

or the residues of MCPA, HMPCA, and CCPA . Rangeland grass forage was sampled at 0, 7, 21, and 30 day PHIs. Pasture grass forage was sampled at 7, 14, 21, and 30 day PHIs. Average residues in pasture grass forage are lower than av erage residue in rangeland forage at the corresponding PHIs of 7, 21, and 30 days. Average

residues (MCPA only, the residue for tolerance enforcement) in rangeland forage at a 0 day PHI were 287 ppm for the DMAS formulation and 20 5 ppm for the 2

- EHE

formul ation. The 0 day PHI results for the rangeland grass forage are sufficient to fulfill

the 860.1500 residue data requirement for “grass, forage”.

 860.1500 Pea field trial data

Although no data requirements were listed for pea field trials in the 2004 MCPA RED,

the 9/14/04 supporting chemistry document, MCPA. List A Reregistration Case 0017. Chemical No. 030501, 030502, 030516, 030564. Revised Product and Residue Chemistry Chapters for the Reregistration Eligibility Decision ( D307890 ) identified the fo llowing: “No data are available reflecting determination of the metabolites 2

- HMCPA, and CCPA. The available data indicate that residues of MCPA were <0.05 ppm in or on peas (succulent and dry) harvested 38 days after application (using ground equipment) o f

the sodium salt at 0.37

- 0.75 lb ae/A)(1

- 2x the maximum rate). Data depicting residues of MCPA, 2

- HMCPA and CCPA in or on peas (succulent and dry) harvested after application of representative EC and SC/L formulations of the dimethylamine salt and the ester are required ”.

### Page 7 of 31

U.S. field trial data for peas were subsequently submitted (MRID 47253101) and reviewed ( D346715

, 4/8/08

, T . Goodlow

, MCPA. Magnitude of Residue and S torage Stability Study on Peas) with the following conclusions: the data supplied ar e insufficient for the tolerance reassessment of peas. In order to support all uses on peas, five additional field trials including MCPA and its metabolite 2

- HMCPA are required.

Additional pea field trial data were also submitted reflecting trials in Europe (MRIDs 46837210, 46837211, 46837212, 46837213, and 46837214). That review concluded the following: The magnitude of residue studies are classified as unacceptable but upgradable due to insufficient U.S. crop field trials. The magnitude of residue s tudies can be upgraded provided the MCPB Task Force submits justification stating why the European trials are analogous to U.S. growing regions for peas (D 330176, 7/31/08, MCPB: Data Evaluation Records for Magnitude of the Residue and Storage Stability Studies for Peas Conducted in Europe ).

The data requirement for pea field trial data remains outstanding.

 860.1900 A study detailing confined accumulation in rotational crops planted following

treatment at 1.5 lb ae/A

The MCPA Task Force T hree has submitted a protocol ( No MRID, dated 12/5/ 11) for a

confined rotati onal crop study to support MCPA. HED has evaluated the protocol and

concluded that “t he choice of crops, radiolabel position, and sampling procedures are appropriate. However, the first sampling interval is much greater than the EPA and the OECD guidance recommends ” ( D305037, 2/8/12, C. Olinger

, MCPA and Salts. Confined Rotational Crop Study Protocol Review ). This study has been completed and submitted to the Agency. This study wi ll be evaluated for acceptability and fulfillment of the rotational crop study requirement.

Dietary Assessment

For risk assessment purposes, the residue of concern in livestock commodities is MCPA but in plant commodities the residues of concern include both parent MCPA and its metabolite 2

- HMCPA [(4

- chloro

- 2

- hydroxymethylphenoxy)acetic acid]. The residue considered in drinking water was MCPA (free acid).

The most recent dietary risk assessment for MCPA was performed in 2004 as part of the RED (D307891

, 9/15/04, F. Fort, Revised MCPA Acute and Chronic Dietary Exposure Assessments for the Reregistration Eligibility Decision ). Both acute and chronic dietary (food only) exposure assessments were performed using the Dietary Exposure Evaluation Model (DEEM

- F CID 

, Version 1.30) which uses food consumption data from the USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994

- 1996 and 1998. The assessments are considered very

conservative since tolerance level residues were assumed. For the a cute assessment 100% crop treated (CT) was assumed. The chronic assessment incorporated estimated % CT treated values from BEAD. Default DEEM processing factors were used.

### Page 8 of 31

The EFED provided the drinking water values for use in the 2004 dietary assessment using simulation models to estimate the potential concentration of MCPA in ground and surface water. Limited surface and ground water monitoring data are available for MCPA but these data are not adequate to perform a quantitative drinking water assessmen t. Conservative Tier II (PRZM

EXAMS) modeling was used to determine that estimated drinking water concentrations (EDWCs) in surface water were not likely to exceed 47.3 ppb for peak (acute) exposure and 1.9 ppb for mean (chronic) exposure. For groundwater, the SCI

- GROW model EDWC is 2.13 ppb. Drinking water estimates were derived using a pasture/rangeland application scenario. EDWC s were not incorporated directly into the DEEM models. Instead, a drinking water level of concern (DWLOC) approach was used. Und er registration review EFED will re

- examine the MCPA EDWCs using updated Tier II modeling, including the PRIZM

- GW model.

Acute dietary (food) risk estimates were not of concern for MCPA (<100% aPAD). At the 95 th


### percentile of exposure, the acute risk esti mates were 17% of the aPAD for the general U.S. population. The population subgroup with the highest estimated exposure was children 1

- 2 years

old at 36% aPAD.

Chronic dietary (food) risk estimates were not of concern (<100% aPAD). The chronic risk

esti mates were 3% of the aPAD for the general U.S. population. The population subgroup with the highest estimated exposure was children 1

- 2 years old at 9% aPAD.

The recently updated % CT estimates (7/25/13 SLUA; BEAD) resulted in significant reductions

in average %CT for most crops and modest increases for barley and green peas and would not be expected to have a significant impact on the dietary assessment.

The EDWCs were not incorporated directly into the dietary risk assessment DEEM model but were compared to calculated Drinking Water Levels of Comparison (DWLOCs). A DWLOC is a theoretical upper concentration limit for a pesticide in drinking water based on how much of the PAD remains once exposures in food have been estimated and subtrac ted. For MCPA, acute and chronic DWLOCs were calculated. Upon comparison of the chronic and acute DWLOCs with the EDWCs for MCPA, surface and groundwater concentrations were substantially less than the DWLOCs for all populations and there was no chronic or acute concern for drinking water from surface or groundwater sources. The resulting surface and ground water acute EDWCs of 47.3 ppb and 2.13 ppb were less than the calculated acute DWLOCs which rang ed from 392 ppb to 1455 ppb

. Chronic EDWCs of 1.9 ppb and 2.13 for surface and groundwater

were likewise found to be below the chronic DWLOCs and ranged from 402 to 1497 ppb

.

Conclusions: Currently there are no acute or chronic dietary risk estimates which are of concern for MCPA and its metabolites. Upda ted dietary exposure assessments for MCPA may be necessary under registration review if the toxicological P oD s or uncertainty f actors/safety factors (UFs/SFs) change, or there are significant changes in the EDWCs

.

Residential (Non

- Occupational) Exposure

### Page 9 of 31

Residential Handler Exposure

MCPA is registered for use on residential lawns, ornamental turf and trees, golf courses, and parks. There is potential for residential handler exposure. Short

- term dermal and inhalation exposure to MCPA while mixing, loading, and applying products may occur. ARIs for dermal and inhalation exposure in the previous assessment (D307892) ranged from 2.8 to 46 and are not

of concern . Since the previous assessment in 2004, the Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment has updated exposure assessment methodology for residential exposure scenarios, including methodology for adult handler exposure assessment. An updated residential handler assessm ent may be needed under registration review as a result of these revisions.

Conclusions : An updated residential handler assessment may be required under registration review if warranted by any significant change in exposure assessment methodology,

toxic ological points of departure, or uncertainty factors

.

Residential Post

- application Exposure

There is potential for residential post

- application exposure to MCPA. D ermal exposure is likely for adults and children entering treated lawns and playing golf or contacting treated plants; children may also experience incidental oral exposure during post

- application activities on

treated turf. Post

- application exposure and risks for treated lawns were previously assessed for MCPA (D 307892 ). The short

- term AR I (combined dermal and oral exposure) for toddlers playing on treated lawns ranged from 2.23

- 2.91 and are not of concern . The short

- term dermal MOEs for adults performing yard work and golfing ranged from 2,500 to 43,000 and are not of

concern . These sce narios were assessed using chemical

- specific turf transferable residue ( TTR ) data available for MCPA (MRIDs 45033101 and 44655702).

A n acute assessment was also performed for post application exposures compared to acute points of departure in the 2004 assessment . Typically, post application turf exposures are considered to

be short

- term in duration and are compared to the appropriate short

- term POD. The total acute dermal and oral MOE was 940 for toddlers playing on lawns , which is slightly less than the target MOE of 1000 . Dermal acute MOEs for adults performing yard work and golfing on treated grass ranged from 2,300 to 49,000.

Since the previous assessment, the Health Effects Division’s 2012 Standard Operating Procedures for Residenti al Pesticide Exposure Assessment has updated exposure assessment methodology for residential exposure scenarios, including adult and children exposure to treated turf and golf courses

. An updated residential handler assessment may be needed under registra tion review as a result of these revisions.

Conclusions: An updated residential post

- application assessment may be required under registration review if warranted by any significant change in exposure assessment methodology, toxicological points of depa rture, or uncertainty factors

. The TTR data requirement has been

satisfied for MCPA. There are no other data requirements for MCPA at this time.

### Page 10 of 31

Residential Bystander Exposures

Residential exposures result ing from off

- site transport ( i.e., spray drift or volatilization) may

occur as a result of agricultural applications of MCPA . The Agency is in the process of evaluating these types of exposures and may, as appropriate, develop policies and procedures to identify the need for and, subseque ntly, the way to incorporate these post

- application exposures into the Agency's risk assessments. The need for spray drift and volatilization risk assessment

for MCPA will be examined during Registration Review

.

Aggregate Risk Assessment

In accordance w ith the Food Quality Protection Act (FQPA), HED must consider and aggregate pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. The acute and chronic aggregate risk assessments for MCPA included food an d drinking water only

. Short

- term aggregate risk assessment included food and drinking water.
HED notes that estimated risks from any residues of MCPA resulting from the use of MCPB will

be addressed in the MCPA human health risk assessment.

Acute

The 2004 RED acute aggregate risk assessment addressed exposure to MCPA residues in food and water using the DWLOC approach described above. The resulting surface and ground water

acute EDWCs of 47.3 ppb and 2.13 ppb were found to be substantially less th an the calculated acute DWLOCs, ranging from 392 ppb to 1455 ppb , and are therefore not of concern.

Chronic

Chronic DWLOCs were calculated based on chronic dietary exposures to MCPA in food and

water since no chronic residential scenarios were identifi ed

. Chronic EDWCs of 1.9 ppb and

2.13 for surface and groundwater were likewise found to be below the chronic DWLOCs

, ranging from 402 to 1497 ppb , and are therefore not of concern.

Short

- term

A short

- term aggregate exposure assessment combining food, water and residential exposure was

not conducted in the 2004 RED . There was no concern for short

- term residential exposures or for the chronic food and water exposures. In the future the short

- term aggregate assessment should include residential exposures and chronic food and drinking water.

Conclusions : During registration review, updated aggregate assessments may be conducted as required to include any significant change that might occur for to xicological PODs, FQPA and uncertainty factors, dietary exposure estimates, residential exposure estimates, or EDWCs. A

short

- term aggregate assessment should be conducted and should include residential exposures and chronic food and drinking water. HED notes that estimated risks from any residues of

MCPA resulting from the use of MCPB will be addressed in the MCPA human health risk

assessment

.

### Page 11 of 31

Occupational Exposure

Occupational Handler Exposure

MCPA is registered for commercial use on lawns, ornamental turf and trees, golf courses, parks, roadsides, rights of way and agricultural use on alfalfa, barley, clover, flax, oats, pasture and rangeland grass, peas, rye, triticale, wheat and grass grown for seed . There is potential for occupational handler and post

- application exposure. Occupational handler exposure s cenarios include mixing/loading; applying by aerial, groun dboom, spreader or handheld equipment; mixing/loading /applying by handheld equipment; and flagging. These handler scenarios have been previously assessed ( D307892). The assessment noted that labels typically require single layer personal protective equip ment ( PPE ). Most of the mixer/loader MOEs exceeded the target of 100 with baseline or single layer PPE and were not of concern; the MOEs for handlers wearing single layer PPE ranged from 77 to 4,600. The MOE for mixing/loading liquids for aerial applicati on to rangeland/pastures was acceptable with the addition of a PF5 respirator to single layer PPE. The MOEs for applicators were above 100 and were not of concern. The MOEs for the mixer/loader/applicator and flagger scenarios were acceptable with single l ayer PPE.

Recommended unit exposures for occupational handler assessments have generally been derived only from the Pesticide Handlers Exposure Database (PHED). However, recently both the Outdoor Residential Exposure Task Force (ORETF) and the Agricultur al Handler Exposure Task Force (AHETF) have produced pesticide handler exposure monitoring data that the Agency is using in place of PHED ( http://www.epa.gov/pesticides/science/ handler

- exposure

- data.html ). As more reliable data become available, the Agency will continue to replace existing data. Reviewers should incorporate new exposure monitoring data, as necessary, during registration

review.

Conclusions : An updated occupatio nal handler assessment may be required under registration review if warranted by any significant changes in e xposure assessment methodology, toxicological PODs or uncertainty factors.

Occupational Post

- application Exposure

Occupational post

- application exposure to MCPA is possible for workers entering treated fields. An assessment was previously completed for exposure to MCPA for workers entering treated

fields (D307892) ; short

- and intermediate

- term MOEs ranged from 250 to 10,000. Chemical

specific TT R data were used for the assessment. Default DFR assumptions were used as

chemical

- specific DFR data are not currently available for MCPA.

Recommended transfer coefficients for occupational post

- application assessments are derived from Agricultural Reen try Task Force (ARTF) exposure monitoring studies ( http://www.epa.gov/pesticides/science/post

- app

- exposure

- data.html ). These transfer coefficients have been updated in 2012 ba sed on a reanalysis and submission of new monitoring data. Reviewers should incorporate new exposure monitoring data, as necessary, during registration review.

### Page 12 of 31

In accordance with the updated Part 158 data requirements (2007), one or more DFR studies are required when a pesticide has residential or occupational uses that could result in postapplication dermal exposure. As part of the recent revision to the Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure Asse ssmen t , HED analyzed a number of DFR studies and selected a new default value for the fraction of the application rate available to be dislodged after a foliar application (F AR 

### ). This default value is 25%. Of the analyzed DFR studies, the maximum F AR 

### val ue seen was 89% or 3.6 times higher than the default residue transfer value. Therefore, a calculated MOE of approximately 4 times higher than the LOC (i.e., an MOE > 400 if the LOC = 100) using the default dislodg able residue value would provide an adequa te margin of safety for any potentially higher residues seen in a chemical

- specific DFR study ( Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) Studies . 6/7/2012, Exposure Science Advisory Council ). A DFR study is required for MCPA at this time since some of the estimated dermal occupational postapplication MOEs for MCPA are less than 4 times the LOC (<400).

Restricted Entry Interval (REI)

The Worker Protection Standard ( WPS ) Restricted Entry Interval (REI) for MCPA is 12 hours

for the ester form and is 48 hours for the amine and sodium salt forms.

Conclusions : A chemical

- specific DFR study is required under registration review. An updated occupational post

- application assessment may be required unde r registration review if warranted by any significant changes in exposure assessment methodology, toxicological endpoints or points of departure, or uncertainty factors.

Public Health and Pesticide Epidemiology Data

HED has evaluated the available incident data 1 

### and concludes that based on the low severity and relatively low frequency of incident cases reported for MCPA, there does not appear to be a concern at this time that would warrant further investigation

. However; due to the disproportionate amount and severity of Weed

- B

- G on Max R eady S pray (Reg No 000228

- 00424

- 000239 ) incidents the Agency will evaluate this product further during the Preliminary

R isk A ssessment.

Tolerance Assessment and International Harmonization

Established U.S. tolerances are listed under 40 CFR §180.339(a) (1) and (2) and are expressed as follows (for both plants and livestock commodities): Tolerances are established for residues of the herbicide MCPA ((4

- chloro

- 2

- methylphenoxy)acetic acid) resulting from the dir ect application of MCPA or its sodium or dimethylamine salts, or its 2

- ethylhexyl ester in or on the following food commodities.

1 MCPA (2

- methyl

- 4

- chlorophenoxyacetic acid ) : Tier I Review of Human Incidents: S. Recore . 12/3/2013.

D415 940

### Page 13 of 31

It may be noted that the current tolerance definition does not include the appropriate

measurement statement and should not include a reference to the formulation types being applied. Also the reference to “direct application” is not appropriate for livestock tolerances; currently, there are no registered direct livestock treatments of MCPA. The correct tolerance expression for both plant and livestock commodities should read as follows: Tolerances are established for residues of the herbicide MCPA ((4

- chloro

- 2

- methylphenoxy)acetic acid), including its metabolites and degradates, in or on the commodities in the table below. Comp liance with the tolerance levels is to be determined by measuring residues of MCPA ((4

- chloro

- 2

- methylphenoxy)acetic acid), both free and conjugated, determined as the acid, in or on the following commodities.

There are currently no Canadian maximum resid ue limits (MRLs) established. There are several MRLs being proposed by Codex. The U.S. tolerance and Codex MRL residue defin itions include parent MCPA only ( see Attachment 4)

.

Generally, the U.S. tolerance levels and proposed Codex MRLs are not harmonized . Codex MRLs are lower for various grains and peas but are higher for straw, fodder and grasses. Codex MRLs are lower for livestock fat, byproducts and for milk. Livestock meat levels are harmonized. Codex is also proposing limits on commodities with no U .S. tolerances such as poultry products, eggs, maize and triticale. The differences between U.S. tolerance levels and Codex MRLs may be due to differences in use pattern between the U.S. and Codex countries. In

the case of limits based on non

- detectable re sidues, or LOQ, analytical methods with different LOQs may have been used. Some differences may also be attributable to older residue definitions, i.e. U.S. tolerances for livestock commodities were originally established based on

the combined residues of MCPA and its metabolite 2

- methyl

- 4

- chlorophenol. Although that metabolite is no longer considered a residue of concern for enforcement purposes, the tolerance

levels still reflect the inclusion of that metabolite.

International or Intergovernmental Work Sharing

HED is not currently involved in any joint international review projects that involve the active ingredient, MCPA. Additionally, HED is unaware of any ongoing international assessments for

MCPA.

Cumulative

The FQPA requires the Agency to con sider the cumulative risks of chemicals sharing a common mechanism of toxicity. MCPA is a member of the alkylphenoxy herbicide class of pesticides.

This c lass also includes 2,4

- D B, 2,4

- D and 2,4

- DP. Although the various phenoxy herbicides

have similar structural components, HED has no t made a determination that they have a common

mode of toxic action. Therefore, a cumulative risk assessment has not been performed for these compounds.

Human Studies

### Page 14 of 31

There are no MCPA

- specific human studies that requir e an ethics review at this time. Previous

HED risk assessments relied in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These data, which include studies from PHED 1.1; the AHETF datab ase ; the ARTF database; and the ORETF database

, are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable ethics requirements. For certain studies, the ethics review may have included revi ew by the Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, can be found at the Agency website 2



### .

Data Deficiencies

The following data deficiencies were identified for MCPA:

Toxicolog y

 N one

Res idue Chemistry

 860.1300 Metabolism studies on peas

 860.1500 Pea field trial data

Occupational and Residential Exposure

 875.2100 Dislodgeable Foliar Residue (DFR) data

Reference s

MCPA [( 4

- chloro

- 2

- methylphenoxy)acetic acid]

. Revised Human Health Risk Assessment for the Reregistration Eligibility Decision (RED) Document. Reregistration Case No. 0017. Chemical Nos. 030501, 030502, 030516, 030564. DP Barcode D307892. September 14, 2004.

F. Fort.

MCPA: Second Revised Occupational and Residential Exposure and Risk A ssessment for the Reregistration Eligibility Decision (RED) Document. DP Barcode D305056. September 7, 2004.

T. Dole.

MCPB/MCPA: Summary of Hazard and Science Policy Council (HASPOC) Meeting of October 24, 2013: Recommendations on the Requirement of an I mmunotoxicity Study for MCPA/MCPB, a Subchronic Inhalation Toxicity Study for MCPB, and a Subchronic Dermal Toxicity Study for MCPB. TXR No. 0056819, November 5, 2013. J. Leshin.

2 http://www.epa.gov/pesticides/science/handler

- exposure

- data.html and http://www.epa.gov/opp00001/science/residential

- exposure

- sop.html

### Page 15 of 31

MCPA (2

- methyl

- 4

- chlorophenoxyacetic acid ) : Tier I Review of Human Incident s. D415 940. December 3, 2013. S. Recore

.

### Page 16 of 31

Attachment 1 . Chemical Identity and Physicochemical Properties

TABLE A.1. MCPA Nomenclature.

Compound

Common name MCPA acid

Company experimental name NA

IUPAC name 4

- chloro

- 2

- methylphenoxyacetic acid

CAS name 4

- chloro

- 2

- methylphenoxyacetic acid

CAS registry number 94

- 74

- 6 (free acid)

Molecular weight 200.6

End

- use product (EP) NA

Compound

Common name MCPA sodium salt

Company experimental name JAN018051

IUPAC name sodium (4

- chloro

- 2

- methylphenoxy)acetate

CAS name (4

- chloro

- 2

- methylphenoxy)acetic acid, sodium salt

CAS registry number 3653

- 48

- 3

Molecular weight 222.6

End

- use product (EP) 2.5 lb ae/gal SC/L (Nufarm MCPA Sodium 300 SC; 27.5% ae)

Common name MCPA dimethylamine salt

IUPAC name (4

- chloro

- 2

- methylphenoxy)acetic acid, dimethylamine salt

CAS name (4

- chloro

- 2

- methylphenoxy)acetic acid, compound with N

- methylmethanamine (1:1)

CAS registry number 2039

- 46

- 5

Molecular weight 245.7

End

- use product (EP) 4 lb ae/gal SC/L (Nufarm Rhomene® MCPA Amine Herbicide SC; 42.5% ae)

### Page 17 of 31

TABLE A.1. MCPA Nomenclature.

Compound

Common name MCPA 2

- ethylhexyl ester

IUPAC name (4

- chloro

- 2

- methylphenoxy)acetic acid, 2

- ethylhexyl ester

CAS name (4

- chloro

- 2

- methylphenoxy)acetic acid, 2

- ethylhexyl ester

CAS registry number 29450

- 45

- 1

Molecular weight 312.5

End

- use product (EP) 3.7 lb ae/gal EC (Nufarm Rhonox® MCPA Ester Herbicide EC; 44.8% ae)



### TABLE A.2. Physicochemical Properties of the Technical Grade Forms of

MCPA.

Parameter Values Reference

MCPA MCPA DMAS MCPA 2

- EHE

Melting point/range 114

- 119 °C 111 °C 260

- 265 °C DP# 307890,
F. Fort,

9/14/04 pH approximately 3 Not available 3.46 at 19.7 °C

Density (20°C)

1.18

- 1.21 g/mL 1.181 g/mL 8.9 lb/gal bulk density (1.06 g/mL specific gravity)

Water solubility (20°C)

0.03 g/100 g Rapidly dissociates to the free phenoxy acid moiety and dimethyl

ammonium ion in

water. 0.1%, w:w

Solvent solubility (20°C) 91.8 g/100 g acetone

50.2 g/100 g ethyl

ether 5.5 g/100 g

chloroform 3.3 g/100 g benzene Not available Miscible in most organic

solvents and mineral oils.

Vapor pressure (20°C) 7.7 x 10 - 6 mbar Not available 1.77 x 10 - 5 mbar

Dissociation constant, pK

a 3.07 Not available Not available

Octanol/water partition coefficient, Log(K OW ) 2.73 1.415

- 5.37

### Page 18 of 31

TABLE A.2. Physicochemical Properties of the Technical Grade Forms of

MCPA.

Parameter Values Reference

MCPA MCPA DMAS MCPA 2

- EHE

UV/visible absorption spectrum

Not available Not available Absorbance peaks

observed at 203, 228, and

279 nm for a solution of

MCPA 2

- EHE in water

with methanol co

- solvent; molar absorption

coefficient of 16784 M -

1 cm - 1 MAX 203.1 nm.

### Page 19 of 31

Attachment 2. Acute, Subchronic, and Chronic Toxicity Profile

The acute toxicity data on the MCPA, MCPA DMA, MCPA EHE, and MCPA sodium salt are

summarized in Table A

- 1 below.

Table A2

- 1 . Acute Toxicity Profile

- MCPA Technical , EHE, Amine, Sodium salt

.

Guideline

No. Study Type MRID Results Toxicity Category

870.1100 Acute oral [rat] MCPA acid 00021972 LD 50= 1 .4 g / kg III

870.1100 Acute oral [rat] MCPA EHE 00 1 56458 LD 50= 2.2 mg/kg III

870.1100 Acute oral [rat] MCPA Amine 00256980 LD 50= 1 .9 g / kg III

870.1100 Acute oral [rat] MCPA Na salt 00256979 LD 50= 3.5 g / kg III

870.1200 Acute dermal [rabbit] MCPA acid 00250090 LD 50 > 2000 mg/kg IV

870.1200 Acute dermal [ra bbi t] MCPA EHE 00156459 LD 50 > 2000 mg/kg IV

870.1200 Acute dermal [rabbit] MCPA Amine 00256980 LD 50 > 2000 mg/kg IV

870.1200 Acute dermal [ra bbi t] MCPA Na salt 00256979 LD 50 > 2000 mg/kg IV

870.1300 Acute inhalation [rat] 40053101 LC50 > 6.3 mg/L A IV

870.1300 Acute inhalation [rat] 00156460 LC50 > 3.1 mg/L A IV

870.1300 Acute inhalation [rat] 42113103 LC50 > 1.7 mg/L I II

870.1300 Acute inhalation [rat] 00 256979 LC50 > 1.7 mg/L I II

870.2400 Acute eye irritation [rabbit] 00250090 Corneal opacity and conjuctival

irritation I

870.2400 Acute eye irritation [rabbit] 00115522 No evidence of eye irritation IV

870.2400 Acute eye irritation [rabbit] 00248567 Corneal opacity I

870.2400 Acute eye irritation [rabbit] 00256979 Corneal opacity, stippling, puckering

, alopecia II

870.2500 Acute dermal irritation [rabbit] 00250090 Non

- irritating IV

870.2500 Acute dermal irritation [rabbit] 00156456 Non

- irritating IV

870.2500 Acute dermal irritation [rabbit] 00256980 Slight dermal irritation III

870.2500 Acute dermal irritation [rabbit] 00256979 Non

- irritating IV

870.2600 Skin sensitization [Guinea Pig] 43062806 Not a skin sensitizer IV

870.2600 Skin sensitization [Guinea Pig] 40352001 S kin sensitizer IV

870.2600 Skin sensitization [Guinea Pig] 40352101 Not a skin sensitizer IV

870.2600 Skin sensitization [Guinea Pig] 41613003 Not a skin sensitizer IV

A 4

- hour

### Page 20 of 31 Table A

- 2

- 2 a . Subchronic and Chronic Toxicity Profile

– MCPA acid

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

870.3100

90

- Day oral toxicity in

rats with MCPA MRID 00165471 (1985) Acceptable/guideline 0, 50, 150, or 450 ppm (equivalent to 0, 3.6, 10.9, or 32.6 mg/kg/day for males and 0, 4.0, 12.1, or 35.8 mg/kg/day for females). NOAEL = 10.9 mg/kg/day LOAEL = 32.6 mg/kg/day based on increased absolute and relative kidney weights, increased clotting time, increased creatinine levels, and presence of crystaluria (oxalate, calcium phosphate, and urate).

870.3150

90

- Day oral toxicity in dogs with MCPA MR ID 00106595 (1980) Acceptable/guideline main study

technical MCPA 0, 77

- 86, 300

- 342, or 1198

- 1370 ppm (equivalent to 0, 3.0, 12.0, or 48.0 mg/kg/d).

second study

technical MCPA 0, 7.5, 25.0, and 300.0 ppm (equivalent to 0, 0.3, 1.0, or 12.0 m g/kg/d) purified MCPA

– 300.0 ppm (equivalent to 12.0 mg/kg/d) NOAEL = 1 mg/kg/day LOAEL = 3 mg/kg/day

, based on impaired renal function, without histopathological change.

870.3200

21

- day dermal

- rabbit

with MCPA 42715001 (1992) acceptable/guideline 10, 100, or 1000 mg/kg/day Systemic toxicity NOAEL = 100 mg/kg/day LOAEL = 1000 mg/kg/day (limit dose) based on kidney findings (increase in incidence of mineralization in renal tubule) and the decrease in body weight gain Dermal toxicity

NOAEL = 10 mg/kg/day LOAEL = 100 mg/kg/day based erythema, desquamation, and diffuse acanthosis

870.3465

28

- day inhalation toxicity in rats with

MCPA 48606401 (2011) Acceptable/non

- guideline* 0, 0.05, 0.2 and 1.0 mg/L for 6 hours per day ; reduced to 0, 0.0 2 , 0. 1 and 0 .5 mg/L following 3 (females) or 4 (males) exposures due to severe toxicity

* non

- guideline status is because the MMAD for the test atmospheres especially for the mid and high dose exposures did not have a sufficient percentage of particles less than the recommended 3 microns. Since the study did not demonstrate a NOAEL for alterations in the upper respiratory tract and because of the several

responses to treatment , the issue of unacceptable particle size has added importance. LOAEC = 0.02 mg/L/day ( b oth sexes ), based on epithelial alteration in the larynx and clinical signs at portal of entry

NOAEC not established for portal of entry

effects Systemic LOAEL = 0.1 mg/L

. At the mid and high dose levels there was squamous cell metaplasia of the lary nx and in the nasal cavity, diffuse tubular degeneration of the testes, increase of oligospermia and debris in the epididymides, and follicular hypertrophy/ hyperplasia of the thyroid gland and increased absolute/relative thyroid weight, deceased

absolute and relative thymus weight in females, and decreased absolute (both sexes) and relative (females) spleen weight, alterations in RBC and WBC elements, increased prothrombin time and altered clinical chemistry parameters (glucose and urea). There were reduc tions in rearing in both sexes and lower motor activity (in females). S ystemic NOAEC level was 0.02 mg/L.

### Page 21 of 31 Table A

- 2

- 2 a . Subchronic and Chronic Toxicity Profile

– MCPA acid

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

870.3700a

Prenatal developmental in rats

with MCPA 42723801 (1993) acceptable/guideline 15, 60, and 120 mg/kg/day. maternal toxicity

NOAEL = 60 mg/kg/day LOAEL = 120 mg/kg/day based on decreases in body weight gain and food consumption during

treatment

developmental toxicity NOAEL = 60 mg/kg/day. LOAEL = 120 mg/kg/day based on decreased placental and fetal body weights and an increase

in the nu mber of fetuses with skeletal

retardation

870.3700b

Prenatal developmental in

rabbits with MCPA 42723802 (1993) acceptable/guideline

15, 30, and 60 mg/kg/day. maternal toxicity NOAEL = 30 mg/kg/day. LOAEL = 60 mg/kg/day based on decreases in body weight and food consumption during the treatment period

developmental toxicity NOAEL > 60 mg/kg/day (HDT) LOAEL = not a developmental toxicant

870.3800 Reproduction and fertility effects in rats

with MCPA 40041701 (1986) acceptable/guideline 0, 50, 150, or 450 ppm (equivalent to 0, 2.5, 7.5, and 22.5 mg/kg/day, respectively, for both sexes based on 1 ppm = 0.05 mg/kg/day). Parental systemic toxicity NOAEL =7.5 mg/kg/day LOAEL =22.5 mg/kg/day based on increased absolute and relative ovary w eigh ts (p<0.05;

23

- 25% greater than controls) Offspring toxicity NOAEL =7.5 mg/kg/day LOAEL =22.5 mg/kg/day based on decreased pup weight gain during lactation Reproductive toxicity NOAEL =22.5 mg/kg/day

LOAEL = no LOAEL was established.

870.4. 300

Chronic toxicity and carcinogenicity in rats

with MCPA 40634101 (1988) acceptable/guideline 0, 20, 80, or 320 ppm for 2 years (0, 1.1, 4.4, or 17.6 mg/kg/day in males and 1.4, 5.7, or 23 mg/kg/day in females) NOAEL = 4.4 mg/kg/day LOAEL= 17.6 mg/kg/day based on hepatotoxicity (increased SGPT levels in females) and nephrotoxicity (increased urea nitrogen in females) were observed. In addition,

there was an increase in the retraction and granular surface of the kidney associated with

an increase in the chronic progressive nephropathy in the males. At the doses tested, there was not a treatment

related increase in tumor incidence when compared to controls. Dosing was considered adequate.

870.4100b Chronic toxicity dogs

with MCPA 00164352 (1986) acceptable/guideline 0, 6, 30, 150 ppm (0, 0.2, 1.02, or 5.32 mg/kg/day for males and 0, 0.21, 1.02 or 5.12 mg/kg/day for females) NOAEL = 0.2 mg/kg/day LOAEL= 1.02 mg/kg/day based on hepatotoxicity (increased SGPT, SGOT, triglycerides and cholesterol le vels with histopathology changes) and nephrotoxicity

### Page 22 of 31 Table A

- 2

- 2 a . Subchronic and Chronic Toxicity Profile

– MCPA acid

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

[increased urea nitrogen, potassium, and creatinine levels with histopathology changes (increased pigmentation of the proximal tubular epithelium) in kidneys].

870.4300 Chronic toxicity and carcinogeni city in

mice with MCPA 40792301 (1988) acceptable/guideline 0, 20, 100, or 500 ppm (0, 3.2, 15.7, or 79.5 in males and 0, 3.9, 19.5, or 97.2 mg/kg/day) for 2

years. Males: NOAEL = 15.7 mg/kg/day LOAEL= 79.5 mg/kg/day based on histopathology changes in kidneys

Females: NOAEL = 3.9 mg/kg/day LOAEL= 19.5 mg/kg/day based on renal hyperplasia At the doses tested, there was not a treatment

related increase in tumor incidence when compared to controls . Dosing was considered adequate.

870.6200 a Acute oral neurotoxicity in rats

with MCPA 43562602 (1994) Acceptable/guideline 0, 200, 400, or 800 mg/kg (males) 0, 150, 300, or 600 mg/kg (females) via gavage. LOAEL = 400 mg/kg

, based primarily on gait impair ment in male rats

NOAEL = 200 mg/kg.

870.6200b

Subchronic oral neurotoxicity in rats

with MCPA 43562601 (1994) acceptable/guideline

0, 50, 500, and 2500 ppm (equivalent to 0, 3, 34, or 177 mg/kg/day for males and 0, 4, 42, or 188 mg/kg/day for femal es). NOAEL = 34 mg/kg/day LOAEL= 177 mg/kg/day based on based on decreased body weight and body weight gains, liver pathology, changes in clinical chemistry and hematological parameters, testicular atrophy, reduced values of forelimb grip strength (day 50 only) and reduced values i n the foot splay test (day 22 only) in males and reduced values of hindlimb grip strength in

females.

Gene mutation

870.5265 42840403 (1993) acceptable Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 Tested up to 5,000 μg/plate The test was negative.

870.5300

Gene mutation

– Chinese hamster ovary cells (CHO/HGPRT) 42860103 (1993) Acceptable The test was negative.

870.5915

In Vivo Mammalian Cytogenetics

- Sister Chromatid Exchange

assay 00148720 (1985) acceptable Dose: 1200 mg/kg The test was weakly positive.

870.5385

In Vivo Mammalian Cytogenetics

- Chromosomal

aberration 40027501 (1986) acceptable 0, 33, 200 or 1200 mg/kg body weight. The test was negative.

### Page 23 of 31 Table A

- 2

- 2 a . Subchronic and Chronic Toxicity Profile

– MCPA acid

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

870.5375 cytogenetic assay (human lymphocytes) 42853504 (1993) acceptable

S9

- activated doses of 1200

- 2000 ug/mL (13 hr cell harvest) that approached the solubility limit. The test was positive. The non

- activated test material was cytotoxic (>500 ug/mL

- 21 hr cell harvest), but not clastogenic.

870.7600

Der mal absorption in

rats 46327601 (2003) Acceptable/guideline 0.09 mg/cm 2 and 7.5 mg/cm 2 Over all recovery was good ranging from

90.35% to 95.46% for the low dose and 94.43% to 96.85 % for the high dose. For the low dose the majority of absorbed dose was excreted in the urine with the second highest portion in the carcass. For the high dose the absorbed test compound build up in the carcass with the highest portion at 10 hours (22.08%). At 96

hours 12.86% remained in the carcass and

12.28% was excreted in the urine. This pattern indicates saturation of excretion at the high

dose.

870.7600 Dermal penetration

in vitro

human and rat 45897010 (2002) No review located.

Table A

- 2

- 2 b . Subchronic and Chronic Toxicity Profile

– MCPA DMA

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

870.3150

90

- Day oral toxicity in dogs with MCPA

DMA 43556802 (1995) Acceptable/guideline 20, 80, and 360 ppm (equivalent in the males to 0, 0.6, 2.4 and 10.9 mg/kg/day and in the females to 0, 0.7, 2.9, and 12.8 mg/kg/day) NOAEL = 0.6 MCPA

- DMA (0.4 as MCPA acid) mg/kg/day.

LOAEL = 2.4 MCPA

- DMA (2.0 as MCPA acid) mg/kg/day, based on change s in histopathology (increases in subacute to chronic interstitial inflammation of liver), hematology, and clinical chemistry (BUN, creatinine, ALT, partial thromboplastin times)

870.3200

21

- day dermal

- rat with

MCPA DMA 43556902 (1995) acceptable/guidel ine 12, 120, or 1000 mg/kg/day Systemic toxicity NOAEL =not observed at 1000 mg/kg/day (limit dose) LOAEL = not observed at 1000 mg/kg/day (limit dose) Dermal toxicity NOAEL = 120 mg/kg/day LOAEL = 1000 mg/kg/day

870.3700a

Prenatal developmental in rats

with MCPA DMA 44954102 (1999) acceptable/guideline

0, 15, 50, or 150 mg MCPA free acid kg/day (0, 18.5, 62 and 185 mg/kg/day MCPA

- DMA) maternal toxicity NOAEL = 50 mg/kg/day LOAEL = 150 mg/kg/day based on mortality

and clinical signs (rocking, lurching, or swaying, hunched appearance, dried yellow matting/staining on the urogenital area)

developmental toxicity

### Page 24 of 31 Table A

- 2

- 2 b . Subchronic and Chronic Toxicity Profile

– MCPA DMA

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

NOAEL = 50 mg/kg/day. LOAEL = 150 mg/kg/day based on increased resorptions, decreased fetal body weight, and

external and skeletal malforma tions/variations

870.6200a

Acute oral neurotoxicity in rats

with MCPA

- DMA salt 43562702 (1994) Acceptable/guideline 0, 175, 350, or 700 MCPA

- DMA salt mg/kg (equivalent to 0, 142, 285, or 569 MCPA free

acid mg/kg) LOAEL = 175 mg/kg (equivalent to 142 MCPA Acid mg/kg) (LDT) seen in female rats based on

ataxia.

NOAEL could not be established.

870.6200b

Subchronic oral neurotoxicity in rats

with MCPA

- DMA 43562701 (1994) acceptable/guideline

0, 60, 600, or 3,000 p pm (equivalent to 0/0, 4/5, 42/48, or 208/232 MCPA

- DMA mg/kg/day [M/F]; 0/0, 3.2/4.1, 34/39, or 169/189 MCPA acid mg/kg/day). NOAEL = 34 mg/kg/day LOAEL= 169 mg/kg/day based on decreased body weight and body weight gains, liver pathology, testicular atrophy, and changes in clinical chemistry (ALT, AST, ALP, creatinine), hematological parameters and neurotoxicity (decreased forelimb grip strength).

870.5265

Gene Mutation

- bacterial 42624401 (1992) acceptable Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 Concentrations at 1, 4, 16, 64, or 256 μg/plate in the presence or absence of

S9

- activation. The test was negative.

870.5300

Gene mutation

– Chinese hamster ovary cells (CHO/HGPRT) 42860101 (1993) Acceptable The test was negative.

870.5375 cytogenetic assay (human lymphocytes) 42853505 (1993) acceptable Dose range: S9

- activated doses of 250, 1000, or 2000 ug/mL (13 hr cell harvest) that approached the solubility limit. The test was positive.

The non

- activa ted test material was not clastogenic.

870.5395 Micronucleus assay 42853502 (1993) acceptable 144, 288, or 576 mg/kg/day. The test was negative.

870.7600 Dermal absorption in

rats 44193901 (1996) Acceptable/guideline DMA: 0.02, 0.19, 0.97, 4.66 mg acid equivalents/cm 2 DMA: dermal penetration was 0.35%, 1.05%, 2.79%, and 5.04% (with increasing dose) of the administered dose following 10

- hr exposures and 1.01%, 3.42%, 6.02%, and 13.24%, respectively following a 24

- hour exposure

Table A

- 2

- 2 c

. Subchronic and Chronic Toxicity Profile

– MCPA EHE

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

870.3150

90

- Day oral toxicity in dogs with MCPA

- EHE 43556801 (1995) Acceptable/guideline

0, 20, 80, and 360 ppm (equivalent in the males NOAEL = 0.6 MCPA

- EHE (0.4 as MCPA acid) mg/kg/day.

LOAEL = 2.5 MCPA

- EHE (1.6as MCPA acid) mg/kg/day based on changes in clinical

### Page 25 of 31 Table A

- 2

- 2 c

. Subchronic and Chronic Toxicity Profile

– MCPA EHE

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

to 0, 0.6, 2.5 and 11.1 mg/kg/day and in the females to 0, 0.7, 2.8, and 12.7 mg/kg/day as

MCPA

- EHE) (equivalent in males to 0, 0.4, 1.6, and 7.1 m/k/d and in females to 0, 0.4, 1.8, and

8.1 m/k/d as MCPA acid) chemistry parameters (increased creatinine, urea, and alanine aminotransferase)

870.3700a

Prenatal developmental in rats

with MCPA EHE 44954101 (1999) acceptable/guideline 0, 15, 40, and 120 mg MCPA free acid kg/day (0, 23.5, 62.7, and 188.0 mg MCPA

- EHE/kg/day) maternal toxicity NOAEL = 40 mg/kg/day LOAEL = 120 mg/kg/day based on reduced and body weight gains

developmental toxicity NOAEL = 40 mg/kg/day. LOAEL = 120 mg/kg/day based on total litter resorptions, decreased fetal weight, and altered growth

870.6200a

Acute oral neurotoxicity in rats

with MCPA

- EHE 43556702 (1994) Acceptable/guideline* 0, 250, 500, or 1000 mg/kg

all clinical sings were reversible by day 14 post exposure; therefore, although the study failed to identify a NOAEL, the study is considered acceptable and the LOAEL for clinical findings is

useful for acu te reference dose consideration for

future risk assessment. LOAEL = 250 mg/kg (LDT) for male and female rats, based on FOB effects (alterations in gait and activity).

NOAEL was not identified. At higher doses (500 mg/kg for male rats and 1000 mg/kg for f

emale rats) decrease in body weight gain was observed.

870.6200b

Subchronic oral neurotoxicity in rats

with MCPA

- EHE 43556701 (1994) acceptable/guideline

0, 75, 750, or 3750 ppm (equivalent to 0/0, 5/6, 54/63, or 261/296 MCPA EHE mg/kg/day [M/F]; 0/0, 3.2/3.8, 34.6/40.4, or 167/190 MCPA Acid mg/kg/day). NOAEL = 3.2 mg/kg/day LOAEL= 34.6 mg/kg/day based on focal testicular atrophy, increased relative kidn ey weight and decreased motor activity in males

870.5265

Gene mutation

MCPA

- EHE 42870001 (1993) acceptable Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 Tested up to 5,000 μg/plate The test was negative.

870.5300

Gene mutation

– Chinese hamster ovary cells (CHO/HGPRT)

MCPA

- EHE 42860102 (1993) Acceptable The test was negative.

870.5375 cytogenetic assay (human lymphocytes)

MCPA

- EHE 42853506 (1993) Acceptable The test was negative.

870.6300 Developmental neurotoxicity in rats 48606401 (2010) Acceptable/guideline 0, 300, 900, or 1800 ppm during gestation No evidence of developmental neurotoxicity

Maternal LOAEL = 1800 ppm ( 156 mg/kg/day),

### Page 26 of 31 Table A

- 2

- 2 c

. Subchronic and Chronic Toxicity Profile

– MCPA EHE

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

MCPA

- EHE 0, 200, 600, or 1200 ppm during lactation (equivalent to 28, 83, and 156 mg/kg/day, gestation/lactation) from gestation day (GD) 6 through lactation day (LD) 21. based on decreases in body weight, body weight gain, and food consumption. Maternal NOAEL = 900 ppm ( 83 mg/kg/day).

Offspring LOAEL = 1800 ppm ( 156 mg/kg/day), based on decreases in body weight and body weight gain and an increase in pup mortality. Offspring NOAEL = 900 ppm ( 83 mg/kg/day).

870.7600 Dermal absorption in

rats
MCPA

- EHE 44193901 (1996) Acceptable/guideline EHE: 0.19 mg acid equivalents/cm 2 EHE: dermal penetration was 10.69% of administered dose following a 24

- hour exposure

### Page 27 of 31

Toxicology Data Requirements

The toxicology data requirements (40 CFR 158.340) for the food uses of MCPA are presented below. Use of the

new guideline numbers does not imply that the new (1998) guideline protocols were used.

Study Technical

Required Satisfied

870.1100 Acute Oral Toxicity

................................ ....................... 870.1200 Acute Dermal Toxicity

................................ .................. 870.1300 Acute Inhalation Toxicity

................................ .............. 870.2400 Primary Eye Irritation

................................ .................... 870.2500 Primary Dermal Irritation

................................ .............. 870.2600 Dermal Sensitization

................................ ...................... Y es

yes

yes

yes

yes

yes yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)

................................ ............... 870.3150 Oral Subchronic (nonrodent)

................................ ......... 870.3200 21

- Day Dermal

................................ .............................. 870.3250 90

- Day Dermal

................................ .............................. 870.3465 90

- Day Inhalation

................................ .......................... Y es

yes

yes

no

yes yes

yes

yes

no

yes

870.3700a Developmental Toxicity (rodent)

................................ ... 870.3700b Developmental Toxicity (nonrodent)

............................. 870.3800 Reproduction

................................ ................................ . Y es

yes

yes yes

yes

yes

870.4100a Chronic Toxicity (rodent)

................................ .............. 870.4100b Chronic Toxicity (nonrodent)

................................ ........ 870.4200a Oncogenicity (rat)

................................ .......................... 870.4200b Oncogenicity (mouse)

................................ .................... 870.4300 Chronic/Oncogenicity

................................ .................... Y es

yes

yes

yes

yes yes

yes

yes

yes

yes

870.5100 Mutagenicity

— Gene Mutation

– bacterial

.................... 870.5375 Mutagenicity

— Structural Chromosomal Aberrations

... 870.5550 Mutagenicity

— Other Genotoxic Effects

....................... Y es

yes

yes y es

yes

yes 870.6100a Acute Delayed Neurotoxicity (hen)

............................... 870.6100b 90

- Day Neurotoxicity (hen)

................................ ........... 870.6200a Acute Neurotoxicity Screening Battery (rat)

................. 870.6200b 90

- Day Neurotoxicity Screening Battery (rat)

............... 870.6300 Developmental Neurotoxicity

................................ ........ N o

no

yes

yes
CR -

- yes

yes

yes 870.7485 General Metabolism

................................ ...................... 870.7600 Dermal Penetration

................................ ........................ 870.7800 Immunotoxicity

................................ ............................. Y es CR

Y es yes

yes

- A

A HASPOC waived this requirement (TXR No. 0056819, dated 11/05/13)

### Page 28 of 31

Attachment 3. MCPA Toxicological Doses and Endpoints for Risk Assessment

Table A3. 1 Summary of Toxicological Doses and Endpoints for MCPA for Use in Dietary and Non

Occupational Human Health Risk Assessments

Exposure/

Scenario Point of

Departure Uncertainty/FQPA

Safety Factors RfD, PAD,

Level of

Concern for

Risk

Assessment Study and Toxicological Effects

Acute Dietary (General Population, including

Infants and Children) NOAEL=

50 mg/kg/day UF A = 1 0 x

UF H = 1 0 x FQPA SF= 1 x UF DB = 10x Acute RfD =

0.05 mg/kg/day

aPAD = 0.05 mg/kg/day Developmental t oxicity s tudy (rats)

MCPA DMA
Maternal toxicity LOAEL = 150 mg/kg/day (as acid equivalent) based on clinical signs of neurotoxicity.

Acute Dietary (Females 13

- 49 years of age) NOAEL =

40 mg/kg/day UF A = 1 0 x

UF H = 1 0 x FQPA SF= 1 x UF DB = 10x Acute RfD =

0.04 mg/kg/day

aPAD = 0.04 mg/kg/day Developmental toxicity study ( rats )

MCPA

- 2

- EHE

LOAEL = 120 mg/kg/day (as acid equivalent) based on total litter resorptions.

Chronic Dietary (All Populations) NOAEL=

4.4 mg/kg/day UF A = 1 0 x

UF H = 1 0 x FQPA SF= 1 x UF DB = 10x Chronic RfD

= 0044 mg/kg/day

cPAD =

0.0044 mg/kg/day Chronic toxicity / carcinogenicity study

( rats )

MCPA acid
LOAEL = 17.6 mg/kg/day based on hepatotoxicity and nephrotoxicity at 17.6 mg/kg/day.

Incidental Oral

Short

- and

Intermediate

Term NOAEL=

4.4 mg/kg/day UF A = 1 0 x

UF H = 1 0 x FQPA SF= 1 x UF DB = 10x Residential

LOC for

MOE = 1000 Subchronic neurotoxicity and chronic

toxicity studies in rats based on neurotoxicity, renal, and testicular

toxicities. a

Dermal ( Short

- and

Intermediate

Term ) Dermal

NOAEL=

100 mg/kg/day UF A = 1 0 x

UF H = 1 0 x FQPA SF= 1 x UF DB = 10x Residential

LOC for

MOE = 1000 21

- day dermal toxicity study (rabbits)

LOAEL = 1000 mg/kg/day based on nephrotoxicity and the decrease in body weight gain.

Dermal (Long

Term ) NOAEL=

4.4 mg/kg/day UF A = 1 0 x

UF H = 1 0 x FQPA SF= 1 x UF DB = 10x Dermal absorption

factor = 7 % Residential

LOC for

MOE = 1000 Chronic toxicity /carcinogenicity study

( rats )
LOAEL = 17.6 mg/kg/day based on hepatotoxicity and nephrotoxicity at 17.6 mg/kg/day.

Inhalation ( All

durations ) NOAEL=

4.4 mg/kg/day UF A = 1 0 x

UF H = 1 0 x FQPA SF= 1 x UF DB = 10x

Inhalation absorption factor =

100% Residential

LOC for

MOE = 1000 Chronic toxicity /carcinogenicity study

( rats ) LOAEL = 17.6 mg/kg/day based on hepatotoxicity and nephrotoxicity at 17.6 mg/kg/day.

Cancer (oral, dermal, inhalation) Classification: Not likely to be carcinogenic to humans

### Page 29 of 31

Point of Departure (PoD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential v ariation in sensitivity among members of the human population (intraspecies). UF L = use of a LOAEL to extrapolate a NOAEL. FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of expo sure, LOC = level of concern, NA = Not Applicable

* NOTE: The Special FQPA Safety Factor recommended by the HIARC assumes that the exposure databases (dietary food, drinking water, and residential) are complete and that the risk assessment for each poten tial exposure scenario includes all metabolites and/or degradates of concern and does not underestimate the potential risk for infants and children.

a = The HIARC selected the dose of 4.4 mg/kg/day for short and intermediate term incidental oral exposure risk assessments based on the similarity of toxicity seen in the subchronic neurotoxicity studies in rats with the acid, DMA and EHE forms, as well as the toxicity seen following chronic exposure in rats with the acid.

Table A3 .2 Summary of Toxicological Doses and Endpoints for MCPA for Use in Occupational Human

Health Risk Assessments

Exposure/

Scenario Point of

Departure Uncertainty

Factors Level of Concern

for Risk

Assessment Study and Toxicological Effects

Dermal ( Short

and

Intermediate

Term) Dermal

NOAEL=

100 mg/kg/day UF A = 1 0 x

UF H = 1 0 x Occupational LOC

for MOE = 100 21

- day dermal toxicity study (rabbits)

LOAEL = 1000 mg/kg/day based on nephrotoxicity and the decrease in body weight gain.

Dermal (Long

Term NOAEL=

4.4 mg/kg/day UF A =10x

UF H =10x

Dermal absorption

factor = 7 % Occupational LOC

for MOE = 100 Chronic toxicity /carcinogenicity study

( rats ) LOAEL = 17.6 mg/kg/day based on hepatotoxicity and nephrotoxicity at 17.6 mg/kg/day.

Inhalation (All Durations) NOAEL=

4.4 mg/kg/day UF A =10x

UF H =10x

Inhalation absorption

factor = 100% Occupational LOC

for MOE = 100 Chronic toxicity /carcinogenicity study

( rats ) LOAEL = 17.6 mg/kg/day based on hepatotoxicity and nephrotoxicity at 17.6 mg/kg/day. Cancer (oral, dermal, inhalation) Classification : Classification: Not likely to be carcinogenic to humans

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). MOE = margin of exposure. LOC = level of concern. N/A = not applicable.

### Page 30 of 31

Attachment 4. International Residue Limits

MCPA (PC030501 ; 11/7/13) Summary of U S and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 1 

### Codex 2, 3

40 CFR 180.

Plant: (a) General . (1) MCPA ((4

- chloro

- 2

- methylphenoxy)acetic acid), both free and conjugated, resulting from the direct application of MCPA or its sodium or dimethylamine salts, or its 2

- ethylhexyl ester None MCPA



### Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 1 

### Codex 2, 3

Alfalfa, forage 0.5 Alfalfa, hay 2.0 Barley, grain 1.0 0.2 Barley, hay 40 Barley, straw 25 50 barley straw and fodder, dry Clover, forage 0.5 Clover, hay 2.0
Flax, seed 0.1 0.01 (*) Grain, aspirated fractions 3.0 Grass, forage 300 Grass, hay 20 500 hay or fodder (dry) of grasses Lespedeza, forage 0.5 Lespedeza, hay 2.0 Oat, forage 20 Oat, grain 1.0 0.2 Oat, hay 115
Oat, straw 25 50 oat straw and fodder, dry Pea, dry 0.1 0.01 (*) Pea, field, hay 0.1
Pea, succulent 0.1
Pea, field, vines 0.1 Rye, forage 20 Rye, grain 1.0 0.2 Rye, straw 25 50 rye straw and fodder, dry Trefoil, forage 0.5 Trefoil, hay 2.0 Vetch, forage 0.5 Vetch, hay 2.0 Wheat, forage 20 Wheat, grain 1.0 0.2 Wheat, hay 115
Wheat, straw 25 50 wheat straw and fodder, dry

40 CFR 180.

Livestock: (2) MCPA ((4

- chloro

- 2

- methylphenoxy)acetic acid) resulting from the direct application of MCPA or its sodium or dimethylamine salts, or its 2

- ethylhexyl

ester MCPA

The residue is not fat soluble.



### Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 1 

### Codex 2, 3

### Page 31 of 31

Summary of U S and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 1 

### Codex 2, 3

Cattle, fat 0.1 0.2 mammalian fats (except milk fats) 5

Cattle, meat 0.1 0.1 meat (from mammals other than marine mammals) Cattle, meat byproducts 0.1 3 edible offal (mammalian)
Goat, fat 0.1 0.2 mammalian fats (except milk fats) 5

Goat, meat 0.1 0.1 meat (from mammals other than marine mammals) Goat, meat byproducts 0.1 3 edible offal (mammalian) Hog, fat 0.1 0.2 mammalian fats (except milk fats) 5

Hog, meat 0.1 0.1 meat (from mammals other than marine mammals) Hog, meat byproducts 0.1 3 edible offal (mammalian)
Horse, fat 0.1 0.2 mammalian fats (except milk fats) 5

Horse, meat 0.1 0.1 meat (from mammals other than marine mammals) Horse, meat byproducts 0.1 3 edible offal (mammalian)

Milk 0.1 0.04 Sheep, fat 0.1 0.2 mammalian fats (except milk fats) 5

Sheep, meat 0.1 0.1 meat (from mammals other than marine mammals) Sheep, meat byproducts 0.1 3 edible offal (mammalian) MRLs with NO US Equivalent
Eggs 0.05 (*)

Maize 0.01 (*) Maize fodder (dry) 0.3 4
Poultry, fats 0.05 (*) Poultry, meat 0.05 (*) Poultry, edible offal of 0.05 (*)

Triticale 0.2 Triticale straw and fodder, dry 50 Completed: M. Negussie; 11/14/13

1 Mexico adopts U

. S

. tolerances and/or Codex MRLs for its export purposes.

2 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MR Ls indicated as proposed have not been finalized by the CCPR and the CAC.

3 All tolerances are proposed

4 Annex I to JMPR 2012 includes “straw”. Codex code AS 0645 only refers to “fodder”. Clarification from the secretariat may be needed.

5 Annex I to JMP R 2012 indicates only Mammalian fats. Codex code MF 0100 excludes milk fats. Clarification from the secretariat may be needed.