UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

MEMORANDUM

Date: 1123/14 OFFICE OF CHEM IC AL SAFETY AND
POLL UTIO N PREVENTION

SUBJECT: MCPB and Sal ts

. Human Health Assessment Seeping Document i n Support of Reg i stration Review.

PC Code: 019201

Decision No

. : 483 037

Petition No. : N/A

Risk Assessment Type: N/A

TXRNo.: N/A

MRID No.: N/A DP Barcode: 0414993 Registra t ion No .: N/A Regulatory Action: Regi st ra

t i on Review

Case No .: 2365-1

CAS No.: 94-81

- 5

40 CFR: 180.318

FROM: Donna S

. Da v i s, Chemist/Risk Assessor

# ~**-----~""""-'~'-"** Alexandra LaMay,

### Biologist**ORE** A

### sso~ - 

## ?( /.

Linda Taylor, Toxicologist

### ~**4'~**

THRU:

TO: Risk Assessment Branch VI

Health Effects Division (7509P)

Michael Metzger, Chief RAB VII

Dana Vogel, Associate Director

Jess Rowland, Deputy Director

Hea lth Ef fects Division (7509P)

Khue Nguyen

Risk Management and Implementation Branch 1

Product Re-Evaluation Division (7508P)

Executive Summary

The Health Effects Division (HED) MCPB Registration R eview Team has evalua t ed the s tatu s of

the human health risk assessmen t for MCPB to determine the scope of work necessary to support Registration Review. The most recently completed human health risk assessment was considered as part of thi s scoping exercise.

Page 1 of23MCPB R eg i str ation Re v i ew Human Health Seeping Document

MC PB (4

- (4

- chloro-2-methylphenoxy)butanoic ac id ) i s a pheno xy post-emergent herbicide used

on pea and mint. The re are no residential u ses of MCPB

. A rep ea t-d ose (28- d ay) inhalati on

tox icity st ud y in rats, pea fi e ld trial da t a
, and c h e m ical-s pecific di sl od geab l e folia r residue (DFR)

data will b e required to comp lete a preliminary risk asse ss ment durin g registration review

. Additionally review of the recently submitted M C PA confined rotation al c rop s tudy

, which wi ll satisfy t he need for an MCPB confined rotational crop stu d y will need to b e com pleted during registration review.

There ar e currently no risks of concern identified for MCPB, h owever, HED will need to r ev i sit

the endpoints, points of departure, and uncertainty factors used for ri sk assessment w hen all the required toxicit y d ata h ave be en re ceiv e d and r eviewe d. The Environmental Fa te and Ef fect s
D i vision (EFED) indi ca t e d that new drinkin g water assessme n t is requir e d

. HED may have to update dietary (food and water) exposure and ri sk assessmen ts

, aggr egate risk assess men ts, a nd

occupat ion a l exposure a nd risk assessment s if significa nt chang es i n the PoDs, UFs or estimated drinking water concentrations occur. Updated assessme n ts w ill need to consider current policies

and procedures in place at the time of the preliminary risk assessment.

T h e c urren t tole r ance exp r essio n should b e updated to comply with HED ' s cur r ent policy o n toleran ce expressions during registration review. There are no international h armoniza ti on i ssues associated w i th MCPB as th ere are no Codex, Canadian or Mexican maximum residue lim its (M RLs) for MCPB.



### Introduction

HED has eva lu ate d the most recent complete hum an health risk assessment for MC PB to
determine if sufficient data are available and i f u pdates are needed to support r eg i strat i o n review.

The most rec en t human h eal th ri sk assessment was conducted in 2008 t o su p port a new use on mint (1011/08, S. L evy, D 343743). HED h as also cons idered updates to i ts tox i c it y, exposu r e and usage databa ses, and the latest Agency sc i ence policy and ri s k assessment methodologies.

While a separate scoping documen t will be i ss u ed for MCPA (4-chloro- 2- m e th y l phenoxy)acetic acid), a metabolite of MCPB

, that is a l so a pe s ti c ide act i ve in gred i ent, HED has cons idered th e

ava ilable data for M C PA t o d e termine if tho se data can address data gaps in th e MCP B databa ses for the purpose of registration review.

MC PB is a phenoxy herbicide produced as a sodium salt and an acid. It is used as a

pos tem e r gence selective weed control in pea a nd min t. The registered products are liquid/soluble

concentrate (SC) formulations and the maximum app li catio n ra te o n peas is 1 .5 lb acid

e quivalent (ae)/acre and i s 0 .5 lb ae / acre on min t. There are no re siden ti a l u ses ofMCPB.

Information o n th e chemical identify of MCPB i s included i n Attachm e nt I

.



### Hazard Identification/Toxicology

MC PB is a m e mb er of the dichlorophenoxy class of herbicides that function by mimicking the

actio n of auxin s, pl ant g r owt h h onno ne s.

P age 2 of23

### MCPB Registration Review Human Health Scoping Document

Page 3 of 23 The toxicity database for MCPB is incomplete . A 28

- day inhalation toxicity study is required

. All other toxicity data r equirements are satisfied for MCPB when supplemented with the MCPA

database . Upon receipt of the MCPB inhalation study, HED concludes that the database will be

sufficient for characterization of potential developmental, reproductive

, carcinogenetic,
mutag enic, neurotoxic, and immunotoxic effects.

MCPB and MCPA are chlorophenoxy herbicides that differ only in that MCPB contains two additional carbon atoms. Metabolic enzymes typically remove carbons two at a time during degradation, in a process called β

- oxidation. This results in MCPB being converted to MCPA, which explains the similarities of effects between the two compounds. In metabolism studies in

rats

, both MCPB and MCPA were rapidly absorbed and eliminated mainly in the urine; no

bioaccumulation o ccurred with either compound. For both compounds, the major urinary

metabolite i s MCPA.

The major target organs are the kidney and liver. Kidney toxicity is manifested as chronic progressive nephropathy in male rats, renal hyperplasia in male mice, and changes in clinical chemistry associated with increased pigmentation of the proximal tubular epithelium in dogs following oral exposure and as increased incidence of mineralization in the renal tubule in rabbits following dermal exposure. Liver toxicity is manifested as increased liver weights, increased liver enzymes, and alterations/necrosis of hepatocytes with slight cytoplasmic eosinophilia, single cell necrosis in rats and as hepatocellular hypertrophy in rats and dogs. The

effects are consistent ac ross time and species and do not appear to progress over time. Although absorption and distribution of chlorophenoxy herbicides and other organic acids are similar across all mammalian species evaluated, the decreased capacity of the dog to eliminate orga nic acids results in higher blood levels and a longer elimination half

- life relative to those found in the rat and other mammalian species. Consequently, effects are seen at lower dose levels in the dog than in the rat. Because of this difference, the ra t is a better predictor of the potential toxicity of MCPB and MCPA in humans than the dog, and doses and endpoints from rat studies

were used in all MCPB risk assessments.

Developmental toxicity was not observed in the rabbit but was observed in the rat at the same dose level where maternal mortality was observed following exposure to MCPB . Reproductive toxicity was not observed in the rat in the MCPA 2

- generation reproduction study

. The main effect in the reproduction study was decreased pup body weig ht gain during lactation at a dose that also caused maternal toxicity (increased ovary weight). Because neurotoxicity was observed in the acute and subchronic neurotoxicity studies with MCPA in rats, there was concern for developmental neurotoxicity

. The 10X FQPA SF for the protection of infants and children was

retained , and a developmental neurotoxicity study (DNT) was identified as a data requirement

for MCPB and MCPA. However, the Agency indicated that this data gap could be satisfied with

the DNT st udy with MCPA. A DNT on MCPA has been submitted and will be considered during registration review of MCPB

.

MCPB is classified as “ not likely to be a human carcinogen” not requiring a quant i tative cancer

risk assessment. This is based on the lack of evidence of carcinogenicity in mice and rats following exposure to MCPA , and there is no concern for mutagenicity for either compound

. There is no concern for immunotoxicity. MCPB is not acutely toxic by the oral, dermal, and

### MCPB Registration Review Human Health Scoping Document

Page 4 of 23 inhalation routes of exposur e based on lethality studies. It is a mild to moderate eye irritant but

not a dermal irritant or dermal sensitiz er

.

Acute and subchronic neurotoxicity studies in rats, which are required in accordance with new data requirements for conventional pesticid e registration (40 CFR Part 158), have been submitted on MCPA and satisfy these data requirements for MCPB. Based on current policies, a repeat dose inhalation toxicity study in rats is required due to the potential for repeated inhalation
exposure to aer osolized formulations of MCPB . The HASPOC determined that a 28

- day inhalation toxicity study is required, based on the portal

- of

- entry findings observed in the inhalation studies on MCPA and other chlorophenoxy compounds, to better estimate risk for

occup ational inhalation exposure to MCPB (TXR No. 0056819, dated 11/5/13)

.

An immunotoxicity study, which is required in accordance with new data requirements for conventional pesticide registration (40 CFR Part 158) has not been submitted for MCPB. The

HASPO C determined that the immunotoxicity study is not required for MCPB (TXR No. 0056819, dated 11/5/13).

The acute, subchronic, and chronic tox icity profile tables for MCPB and 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 8 (D343743 ), and these are presented in Attachment 3 ( Tables 3.1.1 and 3.1.2)

.

Upon receipt and review of the outstanding toxicology data and consideration of all available data, the endpoints for risk assessment and all uncertainty factors will be re

- evaluated during registration review to reflect updated data and uncertainty factor policies, and a new risk assessment done, if necessary.

Co nclusions: The toxicity data base for MCPB is considered incomplete. A repeat dose inhalation toxicity study in rats i s required. All other toxicity data requirements are satisfied for MCPB when supplemented with the MCPA database. Once th e inhalation study has b een received and reviewed and the MCPA DNT study has been reviewed and considered in light of current policies and procedures, revised endp oints, points of departure (PoDs) and uncertainty factors/safety factors may need to be considered during registration review.

Dietary Exposure

The residue chemistry database for MCPB is in complete

. The requirements for a confined rotational crop study and pea field trial data have not been satisfied; all other residue chemistry

data have been satisfied for MCPB.

The nature of the residue in plants is adequately understood. The resi due of concern in plants is

MCPB and its MCPA metabolite. There is no expectation of finite residues of MCPB in

livestock as a result of the currently registered uses on pea and mint ; therefore no additional

animal metabolism data for MCPB is required. The magnitude of the residue in mint is adequately understood . The nature of the residue in rotational crops is not adequa tely

### MCPB Registration Review Human Health Scoping Document

Page 5 of 23 understood. Further, the magnitude of the residue in pea is not adequately understood. An adequate enforcement method is available to enforce the existing MCPB tolerances.

The MCPB Task Force submitted a request for a waiver of the requirements for a confined rotational crop study for MCPB. HED recommended against the waiver (D340491, F. Fort, 7/30/07) but did note that this requirement could be satisfied with a confined rotational crop study with MCPA ((4

- chloro

- 2

- methylphenoxy)acetic acid) , wh ich is the major metabolite of

MCPB. Members of the MCPA and MCPB Task Forces indicated that a confined r otational crop study with MCPA was underway (Meeting 10/23/13 between the MCPA/MCPB Task Forces and EPA) and that study has been submitted to the Agen cy (personal communication from K.Nguyen to D. Davis 1/23/14)

. HED will need to review the study for acceptability as part of registration

review.

The 2005 human health risk assessment ( E. Mendez, 8/4/05), identified a need for pea field trial

data. In 2008, the MCPB Task Force submitted European magnitude of the residue data for pea (T. Goodlow, 7/31/08, D330176) . The data were not considered adequate to address field trial data requirements as insufficient information was provided to determine if the data were sufficiently representative of U.S. growing regions. The MCPB Task Force was advised that a comparison between the climate, irrigation practices, rainfall, temperature, etc. of the sites at which the trials were conducted (England and Scotland) and the U.S. growing regions for peas (regions 1, 2, 5, 11, and 12) should be provided. Further, HED indicated that additional field trials conducted in growing regions 11 and 12 may be required since the arid climate and growing practices of these regio ns are likely dissimilar from the climate and growing practices in Europe. HED is unaware of a response from the MCPB Task Force. The requirement for pea field trial data will need to be satisfied for the registration review of MCPB.

The Environmental Fate and Effects Division (EFED) has reviewed the fate data for MCPB and

has indicated that the residues of concern in drinking water should be rev isited as part of registration review (personal communication from L. Liu to D. Davis, 10/28/13). Additional ly, EFED has indicated that the drinking water assessment for MCPB may need to updated if

additional metabolites of concern are included in the risk assessment and to reflect use of all current drinking water models.

The most recent dietary exposure an d risk assessment was conducted in 2008 to support a new use on mint (D350511, S. Levy, 9/30/08). HED conducted highly conservative, health protective acute and chronic dietary risk assessments for MCPB using tolerance level residues; assumed 100% crop tr eated, and included modeled estimated drinking water concentrations. Estimated acute dietary (food and water) risks for the U.S. population and all regulated population subgroups were ≤ 5.4% of the acute population adjusted dose (aPAD). Estimated chronic dietary (food and water) risks for the U.S population and all regulated population subgroups were ≤ 22% of the chronic PAD (cPAD). For both the acute and chronic dietary risk assessments, the most highly exposed population was infants <1 year old.

HED will be required to conduct an updated dietary risk assessment if significant changes to the estimated drinking water concentrations occur as a result of revisiting the residues of concern in

### MCPB Registration Review Human Health Scoping Document

Page 6 of 23 water and/or changes to the acute and chronic PoD s or UF/SF factors for risk assessment occur as a result of new toxicity data.

Conclusions : The residue chemistry database is considered incomplete. The submitted confined rotational crop study on MCPA will need to be reviewed for registration review. Additional ly, the requirement for pea field trial data will need to be satisfied for the registration review of

MCPB.

An upd ated dietary risk assessment will be required if there is a significant change to the drinking water concentration or PoDs for risk assessmen t.

Residential (Non

- Occupational) Exposure

There are no residential uses of MCPB ; therefore, a quantitative exposure/risk assessment for direct residential applications is not necessary during registration review

. Turf transferable residue ( TTR ) data ar e not required for MCPB because there are no turf applications registered

for MCPB.

Residential Bystander Exposures

Residential exposures resulting from off

- site transport (i.e., spray drift or volatilization) may occur as a result of agricultural appl ications of MCPB . 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, subsequently, the way to incorporate these post

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

for MCPB will be examined during Registration Review

.

Conclusions: There are no registered residential uses of MCPB and, therefore, a quantitative exposure/risk assessme nt for direct residential application is not necessary during registration review. The potential for residential exposures resulting from off

- site transport (e.g., sp ray drift or volatilization) will need to be quantitatively evaluated for MCPB during the registration review process.

Aggregate Risk Assessment

In accordance with the Food Quality Protection Act (FQPA), HED must consider and aggregate pesticide exposures and risks from three major sources: food, drinking water, and direct

res idential exposures.

The acute and chronic aggregate risk assessments for MCPB included food and drinking water only

. As discussed above, there were no aggregate acute or chronic risks identified in the most recent dietary assessment. An updated dietary risk assessment will only be required if there is a significant change to the drinking water concentration or PoDs for risk assessment.

There are no registered residential uses of MCPB; therefore, short

- and intermediate

- term aggregate risk assessments are not required for MCPB.

### MCPB Registration Review Human Health Scoping Document

Page 7 of 23 HED notes that estimated risks from residues of MCPA arising from the use of MCPB are

addr essed in the MCPA human health risk assessment.

Conclusions : No acute or chronic aggregate risks have been identified for MCPB. An updated dietary risk assessment will only be required during registration review if there is a significant change to the drinking water concentration or PoDs for risk assessment. Short

- and

intermediate

- term aggregate risk assessments are not required for MCPB. Estimated risks from residues of MCPA arising from the use of MCPB are addressed in the MCPA human health risk

a ssessment.

Occupational Exposure

Occupational Handler Exposure

MCPB is registered for agricultural use as an herbicide applied post

- emergence to peas and mint. The registered products are liquid / soluble concentrate (S C) formulations and the maximum application rate on peas is 1.5 lb ae/acre and is 0.5 lb ae/acre on mint.

Occupational handler exposure scenarios include mixing/loading, applying by aerial or groundboom , and flagging. Occupational handler exposures are expected to be short

- and

intermediate

- term in duration. These short

- and intermediate

- term occupational handler

exposure scenarios have been previously assessed (D319763 and D343743)

. All of the MOEs for dermal exposur e are greater than 100 when using single layer personal protective equipment (PPE) ( i.e. , baseline PPE with chemical resistant gloves). All inhalation MOEs exceed the target MOE of 100 with baseline PPE ( i.e., no respirator).

Recommended unit exposures fo r 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 Agricultural Handler Exposure Task Force (AHETF) h ave 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 re liable 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 occ upational handler assessment will be required under registration review if warranted by any significant changes in exposure assessme nt methodology, toxicological Po Ds or uncertainty factors.

Occupational Post

- application Exposure As MCPB is an herbicide used postemergence as a broadcast foliar application, o ccupational
post

- application exposure to MCPB is possible for workers entering treated fields to perform specific work activities ( e.g ., irrigation, scouting). Based on the previous assessments (D319763 and D343743), all MOEs for dermal occu pational post

- application exposure exceed the target MOE of 100 on Day 0 indicating that the post

- application risks are not of concern.

### MCPB Registration Review Human Health Scoping Document

Page 8 of 23 Recommended transfer coefficients for occupational post

- application assessments are derived from Agricultural Reentry 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 based on a reanalysis and submission of new monitoring data. Reviewers should incorporate new exposure monitoring data, as necessary, during registration review.

In accordance with the updated Part 158 data requirements (2007), one or more DFR studies are

requ ired 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 Assessme n 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 

### value s een 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 adequate m argin 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 MCPB at this time since some of the estimated dermal occupational postapplication MOEs for MCPB are less than 4 times the LOC (<400).

Restricted Entry Interval (REI)

MCPB technical material has been classified in Toxicity C ategory II for acute dermal toxicity and acute eye irritation. MCPB is classified in Acute Toxicity Category IV for primary skin irritation. Per the WPS, a 24

- hr REI is required for chemicals classified under Acute Dermal Toxicity Category II.

Conclus ion s: An updated occupational post

- application assessment will be required under registration review if warranted by any significant changes in exposure assessment methodology, toxicological endpoints or points of departure, or uncertainty factors. A chem ical

- specific DFR study is required under registration review.

Public Health and Pesticide Epidemiology Data

HED has completed its review of incident data that were reported to the Agency, the findings in

the Agricultural Health Study (AHS) as part of t he MCPB scoping process (S. Recore, 1/7/14

, D416737). Based on the low frequency and severity of incident cases reported for

, there does not appear to be a concern at this time that would warrant further investigation

. The Agency will continue to monitor the incident information and if a concern is triggered, additional analysis

will be included in the preliminary risk assessment.

### MCPB Registration Review Human Health Scoping Document

Page 9 of 23 Tolerance Assessment and International Harmonization

Tolerances are currently established under 40CFR 180.318 (a) (1) for the herbicide 4

- (2

- methyl

4

- chlorophenoxy) butyric acid in or on pea at 0.1 (N) and under 40 CFR 180.318 (a) (2) for the combined residues, free and conjugated, of the herbicide MCPB, 4

- ( 4

- chloro

- 2

- methylphenoxy)butanoic acid and its metabolite MCPA, (4

- chlroro

- 2

- methylpehnoxy)acetic acid in or on peppermint and spearmint tops at 0.20 ppm.

The current tolerance expressions are not in compliance with HED’s Interim Guidance on

To lerance E xpressions (5/27/09, S. Knizner) and should be revised during registration review.

There are no Codex, Canadian or Mexican Max imum Residue Limits (MRLs) established for MCPB in/on plant and livestock commodities ; therefore, there are no issues with resp ect to international harmonization that need to be addressed during registration review. The

International Residue Limit Status Sheet is attached to th e document as Attachment 4

.

International or Intergovernmental Work Sharing

HED is not currently invol ved in any joint international review projects that involve the active ingredient, MCPB. Additionally, HED is unaware of any ongoing international assessments for MCPB. Given the limited use pattern for this chemical and the lack of any identified new wo rk, HED has not identified any potential work sharing opportunities for MCPB.

Cumulative

The FQPA requires the Agency to consider the cumulative risks of chemicals sharing a common mechanism of toxicity. MCPB 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 cu mulative risk assessment has not been performed for these compounds.

Human Studies

There are no MCPB

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

HED risk assessments relied in part on data from studies in which adult hum an subjects were intentionally exposed to a pesticide or other chemical. These data, which include studies from PHED 1.1; the AHETF database; the Outdoor Residential Exposure Task Force (ORETF) database; the ARTF database; are (1) subject to ethics revie w 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 review by the Human Studies Review Board.

### MCPB Registration Review Human Health Scoping Document

Page 10 of 23 Descriptions of data sources, as well as guidance on their use, can be found at the Agency

website 1



### Data Requirements

Toxicity Studies Repeat dose (28

- day) inhalation study in the rat (870.3465)

Residue Chemistry Studies Pea Field Trial Data (860.1500) Confined Rotational Crop Data (860.1850)

Occupational/Residential Studies

Chemical

- specific DFR study (875.2100)

References

Table 1 : HED Memoranda Relevant to Registration Review

Author Barcode/TXR # Date Title

Jonathan

Leshin TXR No. 0056819 11/5/13 MCPB/MCPA : Summary of

Ha zard and Science Policy Council (HASPOC) Meeting of October 24,

201 3 : Recommendations on the

R equirement of an Immunotoxicity Study for MCPA/MCPB, a Subchronic Inhalation Toxicity Study for MCPB, and a Subchronic Dermal Toxicity Study for MCPB

.

Sarah J. Levy D343743 10/1/08 4

- (4

- chloro

- 2

- methylphenoxy)butanoic acid (MCPB) ; Human

- Health Risk Assessment for Proposed Section 3

New Use on Mint.

Elizabeth

Mendez D314047 8/4/05 MCPB HED Chapter of the Reregistration Eligibility Decision Document (RED)

Elizabeth

Mendez D319763 10/24/05 MCPB: Phase II Response to Error Only Comments on the HED Chapter of the Reregistration Eligibility Decision Document (RED)

1 

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

- exposure

- data.html and http://www.epa.gov/pesticides/science/post

- app

- exposure

- data.html

### MCPB Registration Review Human Health Scoping Document

Page 11 of 23 Table 1 : HED Memoranda Relevant to Registration Review

Author Barcode/TXR # Date Title

Felecia

Fort D340491 7/30/07 MCPB: Request for Waiver of Rotational Crop Study

Toiya

Goodlow D330176 7/31/08 MCPB: Data Evaluation Records for Magnitude of the Res idue and Storage Stability Studies for Peas Conducted in Europe.

Attachment s

Attachment 1. Chemical Identity Attachment 2. Toxicity Profile Tables Attachment 3. Endpoint Tables

Attachment 4

. International Residue Limits Table

### MCPB Registration Review Human Health Scoping Document

Page 12 of 23 Attachment 1. MCPB Chemical Identity

Table A1.1. MCPB Nomenclature.

Compound

Common name MCPB

IUPAC name 4

- (4

- chloro

- o

- tolyloxy)butyric acid

CAS name 4

- (4

- Chloro

- 2

- methylphenoxy)butanoic acid

CAS registry number 94

- 81

- 5

Table A1.2. Physicochemical Properties of the Technical Grade of MCPB

Parameter Value Reference

Melting point (range) 101.5

– 103.0 °C (purified technical)

D279212, H. Podall, 3/8/02 pH 5.6 (1%w/v)

Density D (20/4) = 1.33 D (20/4) = 1.26 (purified technical)

Water solubility 60.4 mg/L

Solvent solubility n

- hepane

- 0.414 g/L xylene

- 37.6 g/L methylene chloride

- 69.9 g/L

methanol

- >250 g/L

n

- octanol

- 71.6 g/L

acetone

- >250 g/L ethyl acetate

– 144 g/L

Vapor pressure 4 x10
- 7 torr
Dissociation constant, pK

a pKa = 4.6

Octanol/water partition coefficient, Log(K OW ) pH log P(o/w)

4 3.45

7 1.33

10

- 0.21

UV/visible absorption spectrum 0.881 at 229 nm

### MCPB Registration Review Human Health Scoping Document

Page 13 of 23 Attachment 2. Toxicity Profile Tables

Table A2.1 . Acute Toxicity Profile

- MCPB Technical.

Guideline No. Study Type MRID Results Toxicity Category

870.1100 Acute oral [rat] 00 116340 LD 50= 1570 MG/KG III

870.1100 Acute oral [rat] 00 144801 LD 50= 4300 mg/kg III

870.1200 Acute dermal [rabbit] 00 116342 LD50 > 10000 mg/kg IV

870.1200 Acute dermal [rat] 00 144799 LD 50 > 2000 mg/kg II I

870.1300 Acute inhalation [rat] 41630001 LC50 > 1.14 mg/L III

870.2400 Acute eye irritation [rabbit] 00 116343 Moderately irritating II

870.2400 Acute eye irritation [rabbit] 00 144797 Mildly irritating III

870.2500 Acute dermal irritation [rabbit] 00 144798 Non

- irritating IV

870.2600 Skin sensitization [Guinea Pig] 00 144800 Negative IV

Table A2. 2. Subchronic and Chronic Toxicity Profile

– MCPB

Guideline No.

Study Type MRID (year)

Classification/ Doses Results

870.3100

90

- Day oral toxicity (Rat) 42883602 (1993) Acceptable/guideline 0, 100, 500, 2500 ppm (0, 6, 32, 158 mg/kg/day) NOAEL = 158 mg/kg/day LOAEL > 158 mg/kg/day

870.3150

90

- Day oral toxicity (Dog) 42883603 (1993) Acceptable/guideline 0, 12, 80, 800, 1800 ppm (0, 0.4, 2, 25, 44 mg/kg/day NOAEL = 2 mg/kg/day LOAEL = 25 mg/kg/day

, based on small prostate and clinical chemistry (elevated BUN)

870.3200

21

- Day dermal toxicity (Rabbit) See MCPA Profile Table See MCPA Profile Table

870.3465.

Inhalation tox icity (Rat) Datagap HASPOC memo (TXR No. 0056819, dated 11/5/13)

870.3700a Prenatal Developmental (Rat) 40865402 (1988) Acceptable/guideline 0, 25, 100, 225 mg/kg/day Maternal NOAEL = 25 mg/kg/day LOAEL = 100 mg/kg/day based on BW gain Developmental NOAEL = 25 mg/kg/day LOAEL = 100 mg/kg/day based on fetal BW and

ossification

870.3700b Prenatal Developmental 40865401 (1988) Acceptable/guideline Materna l NOAEL = 5 mg/kg/day LOAEL = 20 mg/kg/day based on mortality

### MCPB Registration Review Human Health Scoping Document

Page 14 of 23 Table A2. 2. Subchronic and Chronic Toxicity Profile

– MCPB

Guideline No.

Study Type MRID (year)

Classification/ Doses Results

(Rabbit) 0, 1, 5, 20 mg/kg/day Developmenta l NOAEL = 20 mg/kg/day LOAEL > 20 mg/kg/day, highest dose tested

870.3800. Reproduction See MCPA study Pro file Table See MCPA study Profile Table

870.4100 Chronic toxicity See MCPA study Profile Table See MCPA study Profile Table

870.4200 Carcinogenicity See MCPA study Profile Table See MCPA study Profile Table

870.5100 Gene Mutation: Ames assay 40564302 (1988) Acceptable/guideline 5.00, 16.7, 50, 167, 500, 1670 μg/plate No increase in mutant colonies with or without S9; cytotoxicity (

- S9) at 500 and 1670 μg/plate

.

870.5300

Gene Mutation: HGPRT 40564303 (1988) Acceptable/guideline

50, 100, 250, 500, 1000, 1500, 2000 μg/mL (±S9) Repeat at 50, 100, 250, 500, 600, 700, 800, 900,1000 μg/mL (

- S9) No t mutagenic in CHO cells at HGPRT locus

.

870.5375 Cytogenetics:

Chromosomal Aberrations in

CHO Cells 40564301 (1988) Acceptable/guideline

100, 600, 1000 μg/mL (

- S9) 75, 350, 750 μg/mL (+S9) Evidence of chromosomal aberration at cytotoxic

concentration of 750 μg/mL with S9 ). Average proliferative time lengthened by 21% at 750 μg/mL.

870.5550 Other Genotoxic

Effects: UDS

Rat primary hepatocyte

cultures 40564304 (1987) Acceptable/guideline

0.01

- 3000 μg/mL No increase in unscheduled DNA synthesis

. Cytotoxic at ≥ 3.0 μg/mL

Doses scored at 0.01, 0.03, 0.1, 0.3, 1.0 μg/mL

870.6200a Acute Neurotoxicity Study See MCPA study Profile Table See MCPA study Profile Table

870.6200b

Subchronic Neurotoxicity See MCPA study Profile Table See MCPA study Profile Table

870.6300

D evelopmental Neurotoxicity (Rat) See MCPA study Profile Table See MCPA study Profile Table

870.7485

Metabolism (rat) 44818101 (1998) Acceptable/guideline Oral: 5 mg/kg and 100 mg/kg MCPB was well absorbed (~90%), urine was major route of excretion (~87%), most excreted by 48 hr with no bioaccumulation. MCPA was major metabolite (~36%).

870.7600 Dermal Absorption

I n Vivo Dermal Penetration (Rat) 46732601 (2003)

Acceptable/guideline 0.067 mg/cm 2 or 4.0 mg/cm 2 Dermal absorption is 31.3% at 0.067 mg/cm 2

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Page 15 of 23 Table A2.3 . Subchronic and Chronic Toxicity Profile

– MCPA

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 crystal uria (oxalate, calcium phosphate, and urate).

870.3150

90

- Day oral toxic ity in dogs with MCPA MRID 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 mg/kg/d ay ) 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.

870.3150

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 M CPA acid) mg/kg/day

, based on changes in histopathology (increases in a subacute to chronic interstitial inflammation of liver), hematology, and clinical chemistry (BUN, creatinine, ALT, partial thromboplastin times)

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 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) 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 chemistry parameters (increased creatinine, urea, and alanine a minotransferase)

870.3200

21

- day dermal

- rat with

MCPA DMA 43556902 (1995) acceptable/guideline 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

870.3200

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

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Page 16 of 23 Table A2.3 . Subchronic and Chronic Toxicity Profile

– MCPA

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

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

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/k g/day. LOAEL = 120 mg/kg/day based on decreased placental and fetal body weights and an increase

in the number of fetuses with skeletal

retardation

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

mattin g/staining on the urogenital area)

developmental toxicity 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

870.3700a

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

870.3700b

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

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Page 17 of 23 Table A2.3 . Subchronic and Chronic Toxicity Profile

– MCPA

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

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 de creased 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 ur ea nitrogen in females). 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 incre ase 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 levels with histopathology changes) and nephrotoxicity [increased urea nitrogen, potassium, and

creatinine lev els with histopathology changes (increased pigmentation of the proximal tubular epithelium) in kidneys].

870.4300 Chronic toxicity and carcinogenicity 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.

870.6200b

Subchronic oral neurotoxicity in rats

with MCPA 43562601 (1994) acceptable/guideline

0, 50, 500, and 2500 ppm (equ ivalent to 0, 3, 34, 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

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Page 18 of 23 Table A2.3 . Subchronic and Chronic Toxicity Profile

– MCPA

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

or 177 mg/kg/day for males and 0, 4, 42, or 188 mg/kg/day for females). and hematological parameters, testicular atrophy, reduced values of forelimb grip strength (day 50 only) and reduced values in the foot splay test (day 22 only) in males and reduced values of hindlimb grip strength in

females.

870.6200b

Subchronic oral neurotoxicity in rats

with MCPA

- DMA 43562701 (1994) acceptable/guideline

0, 60, 600, or 3,000 ppm (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 m g/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).

870.6200b

Sub chronic 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 kidney weight and decreased motor activity in males

Gene mutation

870.5265

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

870.5265

Gene Mutation

- bacterial

MCPA

- DMA 42624401 (1992) Acceptable /guideline 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.

870.5265

Gene mutation

MCPA

- EHE 42870001 (1993) Acceptable /guideline 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

- acid 42860103 (1993) Acceptable /guideline 800 μg/mL (

- S9) or 1000 μg/mL (+S9)

. The test was negative for induction of forward gene mutation in Chinese hamster ovary cell HGPRT assays up to cytotoxic doses of 800 μg/mL (

- S9) or 1000 μg/mL (+S9)

.

870.5300

Gene mutation

– Chinese hamster ovary cells (CHO/HGPRT)

MCPA

- DMA 42860101 (1993) Acceptable /guideline 2500 μg/mL ±S9

. The test was negative for induction of forward gene mutation up to cytotoxic doses of 2500 μg/mL ±S9

.

870.5300 42860102 (1993) The test was negative.

### MCPB Registration Review Human Health Scoping Document

Page 19 of 23 Table A2.3 . Subchronic and Chronic Toxicity Profile

– MCPA

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

Gene mutation

– Chinese hamster ovary cells (CHO/HGPRT)

MCPA

- EHE Acceptable /guideline Doses up to limit of solubility in culture medium (200 μg/mL ±S9)

870.5915

In Vivo Mammalian Cytogenetics

- Sister Chromatid Exchange

assay

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

870.5385

In Vivo Mammalian Cytogenetics

- Chromosomal

aberration

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

870.5375 cytogenetic assay (human lymphocytes)

MCPA 42853504 (1993) Acceptable /guideline

S9

- activated doses of 1200

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

chromosome aberrations at +S9 doses of 1200

- 2000 μg/mL (13 hour harvest); approaching solubility limit . The no n

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

- 21 hr cell harvest), but not clastogenic.

870.5375 cytogenetic assay (human lymphocytes)

MCPA

- DMA 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

- activated test material was not clastogenic.

870.5375 cytogenetic assay (human lymphocytes)

MCPA

- EH E 42853506 (1993) Acceptable /guideline

20

- 160 μg/mL (

- S9)

40

- 320 μg/mL (+S9) The test was negative for inducing structural chromosome aberrations in pooled human lymphocytes at 20

- 160 μg/mL (

- S9) or 40

- 320 μg/mL (+S9)

. Significant increase in structural aberrations at highest (+S9) dose; suggestive evidence of clastogenicity in presence of S9 activation and type of induced aberrations were consistent with positive findings from MCPA acid and DMS salt assays.

870.5395

M icronucleus assay

CD

- 1 mice bone

marrow cells

MCPA

- acid 42853501 (1993) 96, 192, 384mg/kg/day, 24, 48, 72 hours Unacceptable/guideline (no need to repeat; see MRID 42853502) No indication of cytotoxicity on target organs or signs of toxicity

870.5395

Mic ronucleus assay

CD

- 1 mice bone

marrow cells 42853503 (1993) Unacceptable/guideline (no need to repeat; see MRID 42853502 on acid) 450, 900, 1800 mg/kg/day No cytotoxicity at any dose level; in preliminary test, no mortality at 3200 mg/kg/day (♀)/2000 mg/kg/day (♂)

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Page 20 of 23 Table A2.3 . Subchronic and Chronic Toxicity Profile

– MCPA

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

MCPA

- EHE

870.5395 Micronucleus assay

MCPA

- DMA 42853502 (1993) Acceptable /guideline 144, 288, or 576 mg/kg/day. The test was negative (MTD was 576 mg/kg/day)

.

### MCPB Registration Review Human Health Scoping Document

Page 21 of 23 Attachment 3 . MCPB Endpoints and Doses for Risk Assessment

Table A3.1. Summary of Toxicological Doses and Endpoints for MCPB for Use in Dietary Human 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 females

13

- 49 years old ) NOAEL = 2 00

mg/kg /day UF A = 10x

UF H = 10x

UF DB = 10x

FQPA SF = 1x Acute RfD = 0.2

mg/kg/day

aPAD = 0.2 mg/kg/day Acute neurotoxicity (MCPA

, rat ). LOAEL = 400 mg/kg/day based on gait impairment in

males.

Chronic Dietary (all populations) NOAEL = 4.4

mg/kg/day UF A = 10x

UF H = 10x

UF DB = 10x

FQPA SF = 1x Chronic RfD = 0.0 044

mg/kg/day

cPAD = 0.0 044 mg/kg/day Chronic toxicity (MCPA , rat ). LOAEL = 17.6 mg/kg/day based

on liver and kidney toxicity.

Cancer (oral ) 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). UF DB = incomplete database. FQPA SF = FQPA Safety Factor. PAD = population

- adjusted dose (a = acute, c = chronic). RfD = reference dose.

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

Assessments.

Exposure
Scenario Point of

Departure Uncertainty/

FQPA Safety

Factors RfD, PAD, Level of

Concern for Risk

Assessment Study and Toxicological

Effects

Dermal Short

- (1

- 30 days) and

Intermediate

- (1

- 6 months)

Term NOAEL = 25

mg/kg/day UF A = 10x

UF H = 10x Occupational LOC for

MOE = 100 21

- Day dermal toxicity (MCPA

, rabbit ). NOAEL = 100 mg/kg/day, LOAEL = 1000 mg/kg/day based on kidney toxicity and decreased body weight gain. Dermal absorption

of MCPB is 4x that of MCPA. Dermal Long

Term (>6 months) NOAEL = 4.4

mg/kg/day UF A = 10x

UF H = 10x

Dermal

absorption

factor = 31% Occupational LOC for

MOE = 100 Chronic toxicity (MCPA , rat ). LOAEL = 17.6 mg/kg/day based on liver and kidney toxicity.

Inhalation Short

- (1

- 30 days) and

Intermediate

- (1

- 6 months) Term NOAEL = 5

mg/kg/day UF A = 10x

UF H = 10x

UF DB = 10x

Inhalation

absorption rate

= 100% Occupational LOC for

MOE = 100 Developmental toxicity (MCPB

, rabbit ). LOAEL = 20 mg/kg/day based on maternal mortality.

### MCPB Registration Review Human Health Scoping Document

Page 22 of 23 Table A3.2. Summary of Toxicological Doses and Endpoints for MCPB for Use in Occupational Human Risk

Assessments.

Exposure

Scenario Point of

Departure Uncertainty/

FQPA Safety

Factors RfD, PAD, Level of

Concern for Risk

Assessment Study and Toxicological

Effects

Inhalation Long

Term (>6 months) NOAEL = 4.4

mg/kg/day UF A = 10x

UF H = 10x

UF DB = 10x

Inhalation

absorption rate

= 100% Occupational LOC for

MOE = 100 Chronic toxicity (MCPA, rat). LOAEL = 17.6 mg/kg/day based on liver and kidney toxicity.

Cancer (oral ) 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). UF DB = incomplete database. MOE = margin of exposure. LOC = level of concern.

### MCPB Registration Review Human Health Scoping Document

Page 23 of 23 Attachment 4

. MCPB International Residue Limits Table

Table A4. Summary of US and International Tolerances and Maximum Residue Limits for

MCPB Residue Definition : US Canada Mexico 1 Codex
40 CFR § 180.318

Plant: MCPB (4

- (4

- chloro

- 2

- methylphenoxy)butanoic acid) and MCPA ((4

- chloro

- 2

- methylphenoxy)acetic acid)

Livestock: None None None

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

US Canada Mexico 1 Codex

Pea* 0.1

Peppermint, tops 0.20 Spearmint, tops 0.20

*Pea tolerance for residues of MCPB. Recommended update to tolerance expression from 2005

RED to ROC of MCPB and MCPA has not been made. Completed: M. Negussie; 12/02 /2013

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.