UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 1123/14 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: MCPB and Salts. Human Health Assessment Seeping Document in Support of 

Registration Review. 

PC Code: 019201 

Decision No.: 483037 

Petition No.: N/A 

Risk Assessment Type: N/A 

TXRNo.: N/A 

MRID No.: N/A 

DP Barcode: 0414993 

Registration No.: N/A 

Regulatory Action: Registration Review 

Case No.: 2365-1 

CAS No.: 94-81-5 

40 CFR: 180.318 

FROM: Donna S. Davis, 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 

Health Effects Division (7509P) 

Khue Nguyen 

Risk Management and Implementation Branch 1 

Product Re-Evaluation Division (7508P) 

Executive Summary 

The Health Effects Division (HED) MCPB Registration Review Team has evaluated the status of 

the human health risk assessment 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 this scoping exercise. 

Page 1 of23 
MCPB Registration Review Human Health Seeping Document 

MCPB (4-(4-chloro-2-methylphenoxy)butanoic acid) is a phenoxy post-emergent herbicide used 

on pea and mint. There are no residential uses of MCPB. A repeat-dose (28-day) inhalation 

toxicity study in rats, pea field trial data, and chemical-specific dislodgeable foliar residue (DFR) 

data will be required to complete a preliminary risk assessment during registration review. 

Additionally review of the recently submitted MCPA confined rotational crop study, which will 

satisfy the need for an MCPB confined rotational crop study will need to be completed during 

registration review. 

There are currently no risks of concern identified for MCPB, however, HED will need to revisit 

the endpoints, points of departure, and uncertainty factors used for risk assessment when all the 

required toxicity data have been received and reviewed. The Environmental Fate and Effects 

Division (EFED) indicated that new drinking water assessment is required. HED may have to 

update dietary (food and water) exposure and risk assessments, aggregate risk assessments, and 

occupational exposure and risk assessments if significant changes in the PoDs, UFs or estimated 

drinking water concentrations occur. Updated assessments will need to consider current policies 

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

The current tolerance expression should be updated to comply with HED's current policy on 

tolerance expressions during registration review. There are no international harmonization issues 

associated with MCPB as there are no Codex, Canadian or Mexican maximum residue limits 

(MRLs) for MCPB. 

Introduction 

HED has evaluated the most recent complete human health risk assessment for MCPB to 

determine if sufficient data are available and if updates are needed to support registration review. 

The most recent human health risk assessment was conducted in 2008 to support a new use on 

mint (1011/08, S. Levy, D343743). HED has also considered updates to its toxicity, exposure 

and usage databases, and the latest Agency science policy and risk assessment methodologies. 

While a separate scoping document will be issued for MCPA (4-chloro-2-methylphenoxy)acetic 

acid), a metabolite of MCPB, that is also a pesticide active ingredient, HED has considered the 

available data for MCPA to determine if those data can address data gaps in the MCPB databases 

for the purpose of registration review. 

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

postemergence selective weed control in pea and mint. The registered products are liquid/soluble 

concentrate (SC) formulations and the maximum application rate on peas is 1.5 lb acid 

equivalent (ae)/acre and is 0.5 lb ae/acre on mint. There are no residential uses ofMCPB. 

Information on the chemical identify of MCPB is included in Attachment I. 

Hazard Identification/Toxicology 

MCPB is a member of the dichlorophenoxy class of herbicides that function by mimicking the 

action of auxins, plant growth honnones. 

Page 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 requirements 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, 

mutagenic, 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 occurred with either compound. For both compounds, the major urinary 

metabolite is 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 across 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 organic 

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 rat 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 weight 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 study 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 quantitative 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 exposure based on lethality studies. It is a mild to moderate eye irritant but 

not a dermal irritant or dermal sensitizer.

Acute and subchronic neurotoxicity studies in rats, which are required in accordance with new 

data requirements for conventional pesticide 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 aerosolized 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 

occupational 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 

HASPOC determined that the immunotoxicity study is not required for MCPB (TXR No. 

0056819, dated 11/5/13). 

The acute, subchronic, and chronic toxicity 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 2008 

(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. 

Conclusions: The toxicity data base for MCPB is considered incomplete. A repeat dose 

inhalation toxicity study in rats is required. All other toxicity data requirements are satisfied for 

MCPB when supplemented with the MCPA database. Once the inhalation study has been 

received and reviewed and the MCPA DNT study has been reviewed and considered in light of 

current policies and procedures, revised endpoints, 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 incomplete. 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 residue 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 adequately 
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), which is the major metabolite of 

MCPB. Members of the MCPA and MCPB Task Forces indicated that a confined rotational 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 Agency (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 regions 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 revisited as part of 

registration review (personal communication from L. Liu to D. Davis, 10/28/13). Additionally, 

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 and 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 treated, 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 PoDs 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. Additionally, 

the requirement for pea field trial data will need to be satisfied for the registration review of 

MCPB.

An updated dietary risk assessment will be required if there is a significant change to the 

drinking water concentration or PoDs for risk assessment.

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 are 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 applications 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 Agency'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 assessment for direct residential application is not necessary during registration 

review. The potential for residential exposures resulting from off-site transport (e.g., spray 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 

residential 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 

addressed 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 

assessment. 

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 (SC) 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 exposure 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 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 Agricultural 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 occupational handler assessment will be required under registration 

review if warranted by any significant changes in exposure assessment methodology, 

toxicological PoDs or uncertainty factors.

Occupational Post-application Exposure

As MCPB is an herbicide used postemergence as a broadcast foliar application, occupational 

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 occupational 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 

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 Assessment, 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 (FAR). This default value is 25%. Of the analyzed DFR 

studies, the maximum FAR value 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 dislodgable residue value would provide an 

adequate 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 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 Category 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. 

Conclusions: 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 chemical-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 the 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-methyl4-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 

Tolerance Expressions (5/27/09, S. Knizner) and should be revised during registration review. 

There are no Codex, Canadian or Mexican Maximum Residue Limits (MRLs) established for 

MCPB in/on plant and livestock commodities; therefore, there are no issues with respect to 

international harmonization that need to be addressed during registration review. The 

International Residue Limit Status Sheet is attached to the document as Attachment 4.

International or Intergovernmental Work Sharing

HED is not currently involved 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 work, 

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 class also includes 2,4-DB, 2,4-D and 2,4-DP. Although the various phenoxy herbicides 

have similar structural components, HED has not 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

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 human 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 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 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 

website1

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 

Hazard and Science Policy Council 

(HASPOC) Meeting of October 24,

2013: Recommendations on the 

Requirement 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 Residue and 

Storage Stability Studies for Peas 

Conducted in Europe. 

Attachments

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 x10-7torr

Dissociation constant, pKa pKa = 4.6

Octanol/water partition coefficient,

Log(KOW)

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] 00116340 LD50=1570 MG/KG III

870.1100 Acute oral [rat] 00144801 LD50=4300 mg/kg III

870.1200 Acute dermal [rabbit] 00116342 LD50 > 10000 mg/kg IV

870.1200 Acute dermal [rat] 00144799 LD50 > 2000 mg/kg III

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

870.2400 Acute eye irritation [rabbit] 00116343 Moderately irritating II

870.2400 Acute eye irritation [rabbit] 00144797 Mildly irritating III

870.2500 Acute dermal irritation [rabbit] 00144798 Non-irritating IV

870.2600 Skin sensitization [Guinea Pig] 00144800 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 toxicity (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

Maternal 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 Developmental NOAEL = 20 mg/kg/day

LOAEL > 20 mg/kg/day, highest dose tested

870.3800. Reproduction See MCPA study Profile 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)

Not 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 

Developmental 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

In Vivo Dermal Penetration 

(Rat)

46732601 (2003)

Acceptable/guideline

0.067 mg/cm2 or 4.0 mg/cm2

Dermal absorption is 31.3% at 0.067 mg/cm2
MCPB Registration Review Human Health Scoping Document

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 toxicity 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/day) 

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 MCPADMA

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 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 aminotransferase) 

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
MCPB Registration Review Human Health Scoping Document

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/kg/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 

matting/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 malformations/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
MCPB Registration Review Human Health Scoping Document

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 weights (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). 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 levels with 

histopathology changes) and nephrotoxicity 

[increased urea nitrogen, potassium, and 

creatinine levels 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 (equivalent 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 
MCPB Registration Review Human Health Scoping Document

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 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).

870.6200b

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 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 non-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-EHE

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

Micronucleus 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

Micronucleus 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 (♂)
MCPB Registration Review Human Health Scoping Document

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 = 200 

mg/kg/day

UFA = 10x

UFH = 10x

UFDB = 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

UFA = 10x

UFH = 10x

UFDB = 10x

FQPA SF = 1x

Chronic RfD = 0.0044

mg/kg/day

cPAD = 0.0044

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. UFA = extrapolation from animal to human (interspecies). UFH = 

potential variation in sensitivity among members of the human population (intraspecies). UFDB= 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

UFA = 10x

UFH = 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 LongTerm

(>6 months)

NOAEL = 4.4 

mg/kg/day

UFA = 10x

UFH = 10x

Dermalabsorption 

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

UFA = 10x

UFH = 10x

UFDB = 10x

Inhalationabsorption 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 LongTerm (>6 months)NOAEL = 4.4 

mg/kg/day

UFA = 10x

UFH = 10x

UFDB = 10x

Inhalationabsorption 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. UFA = extrapolation from animal to human (interspecies). UFH = 

potential variation in sensitivity among members of the human population (intraspecies). UFDB= 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 Mexico1 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 Mexico1 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.