### 4-CP A Human Health Risk Assessment DP No. D419 1 51



### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON

, D.C. 20460



### MEMORANDUM

Date: 07/17/2014 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### SUBJECT: 4-Chlorophenoxyacetic acid. Human Heal th Risk Assessment in Support of Registration Review.

PC Code: 01940 I Decision No. : 489496 Petition N o.: NA 

### DP Barcode: 0419151 Registration No.: NA 

### Regulatory Action: Registration Review Case No.: NA 

### Risk Assessment Type: Sing l e Chemical TXRNo

. : NA 

### CAS No.: 122-88-3 

### MRIDNo.: NA 40 

### CFR: 180.202



### FROM: Ideli z Negron-Encarnacion, Ph.D., Risk

# Assesso**'** '

# ~**~** Ana Rivera-Lupiaiiez I Seyed Tadayon, Chemists 

## j c..J2

_ . _ 

# J Ronnie J. 

### Bever, 

### Jr., Ph.D., Toxicolog i st · 

# 'I**~** 

## 't1 Risk Assessment Branch (RAB) VN II Health Effects Division (HED; 7509 P



### THROUGH: William Irwin, Ph.D., DABT,**Toxi~o** 

### MichaelS. Metzger, Branch Chief RAB V/VII (HED; 7509P)



### TO: Miguel A. 

### Zavala, Chemical Review Manager Patricia Parrott, Branch Chief Risk Management and Impl ementation Branch III Pesticide Re-evaluation Di vision (7508P)

Page 1 of32

### 4-CPA Human Health Risk A ss essment 

### DPNo. 04 1 915 1

1.0 E xecutive Summary

.. . .. . .. ... . . ...... . ... . .. . ... . . . . . ... .. .. . ... . ...... . .... . .. .. . . .... . . ... . .. ...... . . .. .... ...... .. . ... .. 3 2.0 HED Recommendations

. .. .. .. ... . ..... .. . ... .. .. ...... . . ... . ..... ... .. . .. . ..... . . ....... .. .. ... . ... .. ..... . ... .. .. ... .. . 4 2.1 Data Deficiencies

.. . .. ... . ..... .. . . ............ .... .. .. ......... .. ... .. ............. .. ...... . .. ....... .. . . . .. ... . .. ... ... . ..... 4 

### 2.2 Tolerance C onsiderations and International Harmonization

............... . ..................... 4 2.3 Label Recommendations

........ . . .. .. .. ....... . . ... . .. ......... . . . . .... . . ....... . .. .. .. . ........ . . . . . ... . .. . ....... . .... 4 3.0 Introduction

. .. . .......... . . . ........... . ...... . .............. .. ............. .. ............................ . .... . ................ 4 

### 3. 1 C hemical Identity

.... . .. .. .. . ......... . .... . .. . ... .. .... . . . .. .. ... . . . ..•.

.. . .. ... .. . . .... . . ... .. . .... . . . . . . . . .. ...... ..... ... 4 3.2 Physical/ C hemical C haracteristics

.. .. .. . .. ........ . . . . . . . ........... ..... .... . ... . . .. .. . . . . .. .... . .. . ... ... . . ... .. 5 3.3 Pesticide Us e Pattern

.... . .............................. . .. . . . ........ .. ... . .............. . . . ............. .. .. . ............. 5 

### 3.4 Ant i cipated Exposur e Pathways

.... . .... . ...... .. .. .. .. .. . .. .......... . ... .. ...... ...... .. .. ....... . .. ... .. . ....... . 5 3

. 5 C onsideration of Environmental Ju s tice

. .. ...... .... ....... . ... ..... .. .... ..... . . . . .. . . ........ .. .. ...... ... .. 6 4.0 Hazard Characterization and Dose-Response Assessment ............•..

. .............. . ........... 6 4. 1 Summary of Toxicological Effects

.. ....... . .. .. . .. ........... . .. .. ........... . . . .... . ... . .. . ....... . ..... . ....... . . 6 

### 4.2 Safety F actor for Infants and C hildren (FQPA Safety Factor) .....•.............

. ........ . ...... 8 4.2.1 C ompleteness of the Toxicology Database

......... . .............. . ........... . ..•

. ... . .... . .. . .... . .. .. ....... 8 4.2.2 E vidence of Neurotoxicity

... . .. .. ...... . .. .. . .... . .. .. .. .. . . ... .. ... . .. .. ......... ... . .. . . .... . ..... . .. . ............ . .. . 8 

### 4.2.3 Evidence of Sensitivity /Susceptibility in the Developing or Young Animal.

.............. 8 4

. 2.4 Residual U ncertainty in the E xposure Database

............ .. .. . ....... .. .. .. . ... ...... . ... .. . ... .. . ... .. 8 4

. 3 T oxicity E ndpoint and Point of Departur e Selections

.. .. . ...... . ....... .•.

. . ... . .. .. . . . ... . ... .. .. . ... 9 5.0 Dietary E xposure and Risk Assessment

... . . . ... ...... ...... . .. ....... . ... . .. .. .. . ....... . . .. .. .. ............ 11 

### 5.2 Food Residue Profile

....... ... ............. .. ......... . ... .. ...... . ....... .. . . ... .. .. . ... . ... .. . . ...... .. .... .. . .. .... .. . 11 5.3 Water Residue Profile

................................ . ..... . ..... . . . ....... . ... .... .... ..... .... . .. .. . . .... . .. . ....... .. 11 5.4 Dietal)' Risk Assessment

......... . . . ... . ........... .. . .. .......... . .... . . ............... . .... . ....... . .... . .. . ..... . ... 11 

### 6.0 Residentia l (Non-Occupationa l ) Exposure/Risk Characterization

....... . . ... . .. ........ . . .. 12 6.1 Residential Handler and Po s t-Application Exposure

............ . .. . .... . .. .. ... . . . . ... .. . ... . .. . . . .. 12 6.2 Spray Drift and By-Stander E xposure

. . . .. . .... . ... . .. .. ... .. . . ............ . .. . ............ . .. . .............. 12 7.0 Aggregate E xposur e /Risk Characterization

.. . ............. ... ... . . . .... .. . .. .. . ... .. . ... .. .. .. .. .. ... . ... 12 8.0 Cumulative E xposure/Risk Characterizat i on

.... . .............. .. . . .... . .. .. .. . .... . . . .. .. .. ....... ...... 1 3 9.0 Occupational Exposure/Risk Characterization

....... . ...................... . ... . .... .. ..... . ........... 13 10.0 Public Health and Pesticide Epidemiology Data

. . .. .. .. . ............................ . .. .. . . .. .......... 16 Appendix A. Toxicology Profile and E xecutive Summaries

. .. .. ..... ... . .. .. .. ....... . .. ... . .. .............. 17 A.1 Toxicology Data Requirements

..................... .. ...... . ....... . ... .... ....... . .. ..•

... . . . . . . ... . . ..... . . ... .. 17 A.2 T oxicity Profiles

. . ... . . .. .. ... . .. ... . . . .. .... ..... . .. . .... . ........................ .. ....... . .. ... . ..... .. . . ..... .. .. ... . ... . 18 

### Appendix B: Toxicity Studies with 4-chlorophenoxyacetic acid (4- C PA) and Str uctures Related to 4-CP A .

. .. .. . . .......... . ........................................... . ............. ... . .. .......... .. ... . .... . .. .... .... ..... ... 22 

### Appendix C. Physical/Chemical Properties

. .. .. . ... ... . .. .. .. . ... . ...... ... . .. . ... .. . . ......•.

. .. . .. . .... ... . ..... .... . 30 Appendix D. Chronic Dietary Asse s sment for 4-Chlorophenoxyacetic Acid

.. . .. . . . .. ........... . . 31 Appendix E. International Residue Limits

....... . .. . .. .. ........... . . .. . .. ... . ............ . .•.

. ..... . . . .. .. ... .... .... . 32

Page 2 o f 3 2

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 3 of 32 1.0 Executive Summary

The HED Registration Review Team has prepared a preliminary human health risk assessment to support registration review for the uses o f 4

- c hlorophenoxyacetic acid (4

- CPA ) . In addition, as the scoping phase was performed in conjunction with the ri sk assessment, H ED has considered updates to the toxicity, exposure, and usage databases . C urrent Agency science policy and risk assessment methodologies were employed . In addition, HED conducted an open literature search to look for new literature relevant to the human health risk assessment. The results of the literature search showed that no new information relevant to the human health risk assessment has been publ ished. When writing this risk assessment, HED primarily considered the following
two documents: The HED Chapter of the Reregistration Eligibility D ecision (RED) for 4

- CPA ( Mary R.A. Clock ; 12/22/1994 ); The Reregistration Eligibility Decision for 4

- CPA (M arch 1997); and The HED Chapter for the Tolerance Reregistration Eligibility Decision (TRED) ( C. Christensen

, 3 / 12 /20 0 3 , D 288835 )

.

4

- CPA is currently registered for use as a root suppression agent for mung bean sprouts. 4

- CPA is formulated in end

- use pro ducts as a dry amorphous powder. It is dissolved in boiling water and applied by direct pour or by closed delivery systems to a water bath to soak the beans.

Tolerances are established in the 40 CFR §180. 202 for residues of 4

- CPA in/on bean, mung, sprouts at 0.2 ppm

. Residue chemistry deficiencies were not identified in the 2003 TRED and new uses have not been registered since then. T he tolerance expression needs to be modified to exclude measurement of the metabolite

, 4

- chlorophenol, and include the language recommended in the new Interim Guidance on Tolerance Expressions.

Chronic dietary assessment (food only) was conducted. R isk estimates were below HED’s level of concern for the general population and for all population subgroups.

There are currently no registered residential uses for 4

- CPA . The registered uses for 4

- CPA are not expected to result in residential exposure; therefore, a quantitative residential exposure assessment has not been conducted. In addition, due to the limited use in indoor facilities

, by

stander exposure and spray drift are not likely.

Since there are no residential uses and drinking water exposure is not expected, the aggregate exposure and risk includes food only. Food

- only risks are not of concern.

HED co nducted a quantitative occupational exposure and risk assessment

. The occupational handler exposure and risk assessment indicates that the risk estimates (i.e., the margins of exposures; MOEs) are below the Agency’s Level of Concern (i.e., MOEs > LOC of 1 00). There is a potential for post

- application exposure for workers but is expected to be lower than that of applicators.

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 4 of 32 2.0 HED Recommendations

2.1 Data Deficiencies

None.

2.2 Tolerance Considerations and International Harmonization

A tolerance of 0.2 ppm is established in the 40 CFR §180.202 for residues of 4

- CPA in/on bean, mung, sprouts

. The tolerance expression includes measurement of residues of 4

- chlorophenoxyacetic acid and it metabolite 4

- chlorophenol in/on mung beans. The RED (March 1997) and HED Chapter for the RED (W. Smith, D198945, 10/14/1994) recommended approval of a registrant petition for the elimination of the metabolite 4

- chlorophenol from the tolerance expression as it was not considered a metabolite of risk concern

. The tolerance expression needs to be updated to reflect this change.

HED established interim guidance on writing tolerance expressions for enforcement purposes (S. Knizner, 27/May/2009). In order to add clarity to the language used to establish the co verage of the tolerance expression and measurement of the level of the residue in the Raw Agricultural Commodity (RAC) the text in the 40 CFR § 180. 202 should read: “(a) General. (1) Tolerances are established for residues of p

- chlorophenoxyacetic acid , i ncluding its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring p

- chlorophenoxyacetic acid in or on the commodity.”

Where possible, EPA encourages the harmonization of the US Tolerances and Maximum Residue Limits (MRLs) in key export markets. A table with the US tolerances, the Canada MRLs, Mexico MRLs and Codex MRLs for 4

- CPA in mung beans is provided in Appendix E

- International Residue Limits . There are currently no established Codex and Mexican MRLs for 4

- CPA in/on mung beans . Canada has a MRL of 2 ppm for residues of 4

- chlorophenoxyacetic acid in/on mung beans. Based on communication with Canada the data submit ted to the USA that resulted in the current tolerance has not been submitted to them

.

Conclusions: The residue chemistry database is adequate to support uses in mung beans. The tolerance expression needs to be modified to exclude measurement of the me tabolite 4

- chlorophenol, and to reflect the language recommended in the interim guidance for writing tolerance expressions.

2.3 Label Recommendations

None.

3.0 In troduction

3.1 Chemical Identity

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 5 of 32 Table 3.1 Test Compound Nomenclature

Chemical Structure

Empirical Formula C 9 H 9 ClO 3 IUPAC name 2

- (4

- chloro

- 2

- methylphenoxy)acetic acid
CAS Name 4

- Chlorophenoxyacetic acid CAS Registry Number 122

- 88

- 3
End

- use product/EP Amorphous powder
Chemical Class Chlorophenoxy 1

1 Pesticides in this class are herbicides but 4

- CPA is used as a plant growth regulator.



### 3.2 Physical/Chemical Characteristics

4

- CPA is highly soluble in water (957 mg/L) and has an estimated vapor pressure of 3.2 x10

- 4 

### mm Hg at 25 deg C

. Based on 4

- CPA pKa of 3.56, it will ioniz e in water at neutral and basic pHs resulting in the formation of 4

- chlorophenoxyacetate which is not expected to volatilize. Refer to Appendix C for the physicochemical properties of 4

- CPA.

3.3 Pesticide Use Pattern

The use pattern has not change d since December 1999 . The chemical 4

- CPA is used in the food industry as a plant growth regulator to restrict root growth during seed germination of mung beans. The end

- use product is limited to indoor use. The active ingredient 4

- CPA is formulated in end

- use products as a dry amorphous powder (96.2% ai) . It is dis solved in boiling water and the solution applied by direct pour or by closed delivery to the water bath where the beans are soaked, resulting in a concentration of 2

- 3 ppm of 4

- CPA. After the b eans have soaked for 6

- 8 hours, they are washed to remove the surface residues, and are then germinated indoors for several days. After sprouting, the hulls and roots are discarded, and the remaining portion is packaged and sold for human consumption.

Co nclusions: According to information provided by the registrant, the average annual use of 4CPA in the USA is 20 pounds active ingredient per year (M. Clayton, PRD minutes of first team meeting 02/18/2014) . Current uses of 4

- CPA include mung bean only. I f, in the future, the use profile changes additional data may be required.

3.4 Anticipated Exposu re Pathways

The Pesticide Reevaluation Division has requested an assessment of human health risk to support the registration review risk assessment of 4

- CPA. Humans may be exposed to 4

- CPA in food, since 4

- CPA is applied directly to beans before germination . Application is indoors and the use is limited; therefore, 4

- CPA is not likely to reach surface and ground water sources of drinking water. There are no residential uses of 4

- CPA, so there is not likely to be exposure in residential

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 6 of 32 or non

- occupational settings. In an occupational setting, applicators may be exposed while handling the pesticide prior to application, as well as during application. There is a potential for post

- application exposure for workers but is expected to be lower than that of applicators.

Risk assessments have been previously conducted for 4

- CPA, but no new toxicity data have been received since the previous risk assessment. A detailed description of the toxicity data and metabolism information may be found in the risk assessment dated 3/12/2003 (C. Christensen

, D 288835 ). This risk assessment considers all of the aforementioned exposure pathw ays based on the registered use of 4

- CPA.

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Ad dress Environmental Justice in Minority Populations and Low

- Income Populations," ( http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf

. As a part of every pesticide risk
assessment , OPP considers a large variety of consumer subgroups according to well

- established procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water cons umption, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the USDA under the National Health and Nutrition Examination Survey, What We Eat in America, (N HANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non

- dietary exposures based on home use of pesticide products and associated risks for adu lt applicators and for toddlers, youths, and adults entering or playing on treated areas post

- application are evaluated. Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized sof

tware and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Characterization and Dose

- Response Assessment

4.1 Summary of Toxicological Effects

The mod e of action in plants for 4

- CPA is growth regulation (auxin), but the mode of action for toxicity in animals is unknown.

The toxicology database for 4

- CPA is adequate for risk assessment. A cceptable, guideline studies for the subchronic oral toxicity in rats, developmental in rats, and mutation battery were submitted. These studies are briefly described below. All other toxicity study requirements have been waived (see the Hazard and Science Policy Council ( HASPOC; 5/28/2014 )

. S e e A

ppe n d i x A f

o r t h e T o x i c o l o g i ca l P r o f

il e o f 4

- C P A

. O t h e r s t r u c t u r a l a n a l o gs

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 7 of 32 o f 4

- C P A we r e r e v i ewe d t o b e tt e r c h a r ac t e r i z e t h e to x i c it y o f 4

- C P A

. I n t h a t r e v i ew , 4

- C P A

wa s a m o n g t h e l ea s t to x i c o f t h e a n a l o gue s , S e e A ppe n d i x B

.

I n a s u b c h

r o n i c to x i c it y s t ud y w i t h r a t s , t h e NO A E L was 132 m g/kg/da y , and t h e L O A E L was 517 m g/kg/da y b a s e d o n dec r ea s e d b o d y we i g h t i n b ot h s e x e s , dec r ea s e d f oo d c o n s u m

p t i o n i n f e m a l e s , i n c r ea s ed u r i n e v o l u m e i n f e m a l e s , a n d i n c r ea s e d i n c i d e n c e o f s li g h t h e p a t i c lym p h o h i s t i o c y

t i c i n fil t r a t e s a n d s li g h t i n d i v i dual h e pa to ce ll u l a r n ec r o s i s

.

I n a s u b c h

r o n i c to x i c it y s t udy w i t h d o g s , t h e NO A E L was 1 7.4 m g/kg/da y ( 500 ppm )

, t h e h i g h e s t d o s e t e s t ed . T ransient e ff ec t s in the dog study i n c l

uded dec r ea s ed b o dy we i g h t ga i n a n d f oo d c o n s u m

p t i o n du r i n g t h e f

i r s t f o ur weeks at t h e h i g h e s t d o s e ( w h i c h m a y h a v e b ee n r e l a t e d
t o p a l a t a b ilit y

) a n d s li g h t l y h i g h e r i n c i d e n c e o f v o mit i n g. Ma l n u t r i t i o n was n ot e d at 1600 a n d 3200 ppm i n a r a n ge

- f

i n d i n g s t ud y in dogs

.

I n a de v e l o p m

e n t a l to x i c i t y s t udy i n r a t s , m a t e r n al toxicity was observed at a LOAEL of 1000 mg/kg/day including mortality, and clinical signs of neurotoxicity: t r e m o r s , u n c oo r d i n a t e d

m o v e m e n t s , r ecu m

b e n t p o s t u r e , l a n gu i d n e ss , c o l d b o d y, and yellow staining in the anogenital area. The NO A E L was 600 m g/kg/da y . The de v e l o p m

e n t a l L O A E L of 600 mg/kg/day wa s b a s e d o n decreased fetal body weights and u n o ss i f i e d s t e r n e b r ae

. The NOAEL was 300 mg/kg/day. Thus, increased susceptibility was noted in the offspring compared to the adults.

4

- CPA tested in an in vitro mammalian mutation assay did not induce forward mutations in mouse lymphoma cells. In the Ames Salmonella/mammalian

- microsom al reverse mutation assay, 4

- CPA was not mutagenic, with or without activation. This chemical was not clastogenic in an in vivo mouse micronucleus assay. Due to the lack of chronic toxicity and carcinogenicity studies, a number of structurally similar chemical compounds were evaluated to better characterize the hazard potential of 4

- CPA. Only 1 out of 16 mutagenicity stud ies available for the structural analogs was positive for mutation. See Appendix B.

The Office of Pollution and Prevention and Toxics (OPPT) Structural Activity Relationship (SAT) workgroup evaluated 4

- CPA and its associated analogues for carcinogenic p otential. The workgroup concluded that there is a low, marginal concern for the carcinogenicity of this compound

. Chlorophenoxy compounds are well absorbed from the gastrointestinal tract. They are less well absorbed from the lung. Cutaneous absorption appears to be minimal. The compounds are not significantly stored in fat. Excretion occurs almost entirely by way of urine , and the excretion process is saturable

. Apart from some conjugation of the acids, there is limited biotransformation in the body. The compounds are highly protein bound. Also, it is known that the chemicals 2,4

- D and 4

- CPA have substantially similar metabolism patterns. Specifically, the dog is not able to excrete the phenoxy acids as rapidly as the rat

.

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 8 of 32 4. 2 Safety F actor for Infants and Children (FQPA Safety Factor)

The FQPA Safety Factor was removed (i.e., 1X)

, since : developmental toxicity in rats manifested only at a relatively high dose (600 mg/kg/day) ; the re is limited dietary exposure ; there is no exposure to infant s and children resulting from residential uses; and the chronic reference dose will be protective of the devel opmental concerns and neurotoxic effects

.

4.2.1 Completeness o f the Toxicology Database

The toxicology database is considered adequate for ris k assessment. In 1997, the Agency granted waivers for the chronic toxicity, carcinogenicity and reproductive toxicity due to the lack of overt toxicity in subchronic dietary studies, the low volume/minor use status and the lack of acute dietary exposure co ncerns of 4

- CPA (EPA738 R

- 97

- 001).

On April 24, 2014, HED’s Hazard Science Policy Council (HASPOC) concurred with the waivers for the long

- term studies and further granted waivers to the neuro

- , dermal

- , inhalation, and immunotoxicity studies using a wei ght of evidence approach considering all of the available 4

- CPA hazard and exposure information

. Using tolerance level residue values for mung bean, and assuming 100% of crop treated, the chronic dietary risk was <1 % of the cPAD for the general population and all population subgroups. An assessment of occupational handler showed that risk estimates are n ot of concern (i.e., dermal MOE = 95,000 and inhalation MOE = 8,148,000 ) . Similarly, a screening level of occupational handler inhalation exposure and ri sk considering this value resulted in an MOE of 170,000 at label PPE (TXR No. 0056953)

.

4.2.2 Evidence of N eurotoxicity

The tremors, uncoordinated movements, recumbent posture, languidness, and cold body noted in mothers in a developmental toxicity study in rats were seen only at the Limit Dose (1000 mg/kg/day). No clinical signs of neurotoxicity were seen in the subchronic toxicity studies in rats and dogs

.

4.2.3 Evidence o f Sensitivity/Su sceptibility in the Develop ing o r Young Animal

There was evidence for increased susceptibility in the developmental toxicity study in rat where developmental toxicity ( decreased fetal body weights and u n o ss i f i e d s t e r n e b r ae) was observed in the absence of maternal toxicity. However, there is low concern for the observed effects since they occurred at 600 mg/kg/day which is higher than one

- half of the Limit Dose and the chronic RfD would be protective of these effects.

4.2.4 Residual Uncertainty in the Exposure Datab ase

T h e r e a r e n o u s e s o f 4

- C P A i n t h e r e s i de n t i a l e nv i r o n m e n t , and dietary exposure to the chemical will not be underestimated

.

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 9 of 32 4. 3 Toxicity Endpoint and Point of D eparture Selections

The NOAEL from the rat subchronic toxicity study was selected as the Point of Departure for the chronic dietary and occupational risk assessments. There are no residential uses for this chemical; therefore, no endpoints were identified for these exposure scenarios. Additionally, HED has determined that post

- applica tion exposure will be minimal, and no quantitative risk assessment for such exposure is necessary.

Table 4

. 3 .1 Summary of Toxicological Doses and Endpoints for 4

- CPA for Use in Dietary Human Health Risk Assessments a

Exposure/ Scenario Point of

Departure Uncertainty/FQP

A Safety Factors RfD, PAD,

Level of Concern for Risk Assessment Study and Toxicological Effects

Acute Dietary (General Population, including Infants and Children) No effect was identified from the supplied studies.

Acute Dietary (Females 13

- 49 years of age) No effect was identified from the supplied studies.

Chronic Dietary (All Populations) NOAEL=

132 mg/kg/day UF A = 10 x

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

= 1

. 32 mg/kg/day

cPAD = 1

. 32 mg/kg/day MRID 42968301: 90

- day oral toxicity

study in rat NOAEL = 132/153 mg/kg/day in males and females, respectively.
LOAEL = 517/626 mg/kg/day in males and females, respectively, based on decreased body weight s in males and females and lymphohistiocytic infiltration and individual hepatocyte necrosis in males and increased urine volume in females. Cancer (oral, dermal, inhalation) Classification: No t evaluated. Waivers were granted for the c arcinogenicity studies

.

1 There are n o residential uses of 4

- CPA. 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 ob served 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 L = use of a LOAEL to extrapolate a NOAEL. UF S = use of a short

- term study for long

- term risk assessment. UF DB = to account for the absence of key dat a (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. N/A = not applicable.

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 10 of 32 Table 4. 3 .2 Summary of Toxicological Doses and Endpoints for 4

- CPA for Use in Occupational Human Health Risk Assessments a
Exposure/ Scenario Point of

Departure Uncertainty

Factors Level of Concern

for Risk Assessment Study and Toxicological Effects

Dermal Short

Term (1

- 30 days) NOAEL =

132 mg/kg/day UF A =10x

UF H =10x Occupational

LOC for MOE = 1 00 MRID 42968301: 90

- day oral toxicity

study in rat NOAEL = 132/153 mg/kg/day in males and females, respectively.
LOAEL = 517/626 mg/kg/day in males and females, respectively, based on decreased body weight s in males and females and lymphohistiocytic infiltration and individual hepatocyte necrosis in males and increased urine volume in females.

Dermal Intermediate

Term (1

- 6 months) NOAEL =

132 mg/kg/day UF A =10x

UF H =10x Occupational

LOC for MOE = 1 00 MRID 42968301: 90

- day oral toxicity

study in rat NOAEL = 132/153 mg/kg/day in males and females, respectively. LOAEL = 517/626 mg/kg/day in males and females, respectively, based on decreased body weight s in males and females and lymphohistiocytic infiltration and individual hepatocyte necrosis in males and increased urine volume in females.

Inhalation Short

- Term (1

- 30 days) NOAE L =

132 mg/kg/day UF A =10x

UF H =10x Occupational

LOC for MOE = 1 00 MRID 42968301: 90

- day oral toxicity

study in rat NOAEL = 132/153 mg/kg/day in males and females, respectively. LOAEL = 517/626 mg/kg/day in males and females, respectively, based on decreased body weight s in males and females and lymphohistiocytic infiltration and individual hepatocyte necrosis in males and increased urine volume in females.

Inhalation Intermediate

term (1

- 6 months) NOAEL =

132 mg/kg/day UF A =10x

UF H =10x Occupational

LOC for MOE = 1 00 MRID 42968301: 90

- day oral toxicity

study in rat NOAEL = 132/153 mg/kg/day in males and females, respectively. LOAEL = 517/626 mg/kg/day in males and females, respectively, based on decreased body weight s in males and females and lymphohistiocytic infiltration and individual hepatocyte necrosis in males and increased urine volume in females. Cancer (oral, dermal, inhalation) Classification: Not evaluated. Waivers were granted for the carcinogenicity stud ies

.

a The dermal and inhalation absorption factors are very conservatively assumed to be 100%. No study was presented to establish the absorption factors.

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 11 of 32 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 ob served 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 L = use of a LOAEL to extrapolate a NOAEL. UF S = use of a short

- term study for long

- term risk assessment. UF DB = to acc ount for the absence of key data (i.e., lack of a critical study). MOE = margin of exposure. LOC = level of concern. N/A = not applicable.



### 5.0 Dietary Exposure and Risk Assessment

5 .2 Food Residue Profile

The metabolism of 4

- CPA is adequately understood in plants and in animal co mmodities based upon previously submitted and reviewed plant an d animal metabolism studies . Currently, the only use registered is in mung beans for which a tolerance of 0.2 ppm has been established. In addition, residue analytical methods, storage stabili ty, magnitude of the residue in plants, processed food/feed, and in meat, milk, poultry and eggs, and confined field rotation studies are either acceptable or not required, based upon the use pattern. See the March 199 7 RED for more detail.

5.3 Water Res idue Profile

No exposure f

rom drinking water is expected due to the limited indoor use of 4

- CPA.

5.4 Dietary Risk Assessment

Chronic aggregate dietary (food only) exposure and risk assessments was conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM

- FCID) Version 3.16

. This software uses 2003

- 2008 food consumption data from the U.S. Department of Agriculture’s (USDA’s) National Health and Nutrition Examination Survey, What We Eat in America, (NHA NES/WWEIA). The dietary exposure assessment utilized tolerance level residue values of 0.2 ppm for mung bean to assess the exposure to 4

- CPA. The dietary exposure assessment included the chronic exposure scenario only with a chronic population adjustment dose (cPAD ) of 1

. 32 mg/kg/day based on the NOAEL from the subchronic toxicity study in rats and uncertainty factors of 100 for intraspecies and interspecies differences

. Using tolerance level residue values for mung bean, and assuming 100% of crop treated, the chronic dietary risk was < 1 % of the cPAD for the general population and all population subgroups

.

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 12 of 32 Table 5.4.6. Summary of Dietary (Food Only ) Exposure and Risk for 4

- Chlorophenoxyacetic Acid

Population Subgroup Acute Dietary (XX.X Percentile) Chronic Dietary Cancer

Dietary Exposure (mg/kg/day) % aPAD* Dietary Exposure (mg/kg/day) % cPAD* Dietary Exposure (mg/kg/day) Risk

General U.S. Population



### N/A 0.000000 < 1

All Infants (< 1 year old) 0.000000 < 1



### N/A N/A Children 1

- 2 years old 0.000000 < 1

Children 3

- 5 years old 0.000000 < 1

Children 6

- 12 years old 0.000000 < 1

Youth 13

- 19 years old 0.000001 < 1

Adults 20

- 49 years old 0.000001 < 1

Adults 50+ years old 0.000000 < 1

Females 13

- 49 years old 0.000000 < 1 *The values for the highest exposed population are bolded.



### Conclusion: Dietary exposure assessment for 4

- CPA s howed risks below HED’s level of concern for the general population and all population subgroups.

6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

6.1 Residential Handler and Post

- Application Exposure

A residential handler and post

- application exposure assessment is not needed for Registration Review because there are no registered residential uses of 4

- CPA.

6. 2 Spray Drift and By

- Stander Exposure

The use of 4

- CPA is limited to indoor uses; therefore, there is no need for spray drift and volatilization risk asses sment as a result of applications of 4

- CPA.

7.0 Aggregate Exposure/Risk Characterization

Since there are no residential uses and drinking water exposure is not expected, the aggregate exposure and risk includes food only. Food

- only risks are not of con cern.

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 13 of 32 8.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as
to 4

- CPA and any other substances

, and 4

- CPA does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, there fore, EPA has not assumed that 4

- CPA has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common me chanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

A quantitative occupational exposure risk assessment was not conducted during the 1997 reregistration process due to the potentially low worker exposure associated with the growing of mung beans and the low mammalian toxicity profile of 4

- CPA. However, at present, as part of the chemical’s registration review process , HED conducted a quantitative occupational exposure and risk assessment. There is potential for short

- and intermediate

- term occupational exposure to 4

- CPA during handling (mixing, loading, a nd applying) and post

- application activities. 4

- CPA is applied by direct pour or by closed delivery to the water bath to soak the beans.

Occupational Handlers The potential for worker exposure associated with growing mung beans is very low. However, 4

- CP A is a severe eye irritant and is classified as Toxicity Category I for eye irritation in mammalian species. Personal Protective Equipment (PPE) for handlers is based on the acute toxicity of the end

- use product. The registered 4

- CPA label requires occupa tional handlers to wear long

- sleeved shirts, long pants, shoes, socks, and protective eyewear (goggles).

An assessment of occupational handler exposure and risk was performed based on a value of 1 32 mg/kg/day. The NOAEL in the subchronic rat study was 1 32/153 mg/kg/day in males/females. Using the updated exposure methodology and current ORE policies indicates that occupational handler risk estimates are not of concern (i.e., dermal MOE = 95 ,000 and inhalation MOE= 8,148 ,000) at label PPE. See Table 9. 1.

Furthermore, given the fact that the chemicals 2,4

- D and 4

- CPA are both members of the phenoxyacetic herbicide class of pesticides, and have substantially similar chemical structures and metabolism patterns, HED conducted an assessment of occupational hand ler inhalation exposure and risk utilizing the point of departure (PoD) of 2,4

- D (i.e., Human Equivalent Dose (HED) of 2.68 mg/kg/day). 1 

### A screening level of occupational handler inhalation exposure and risk considering this value resulted in an MOE of 17 0,000 at label PPE (i.e., without a respirator). This risk value estimate is very conservative and could be considered worse than a “worst case scenario”. Portal

- of

- entry effects have been a source of concern for 2,4

- D and

1 For details regarding the calculation of the Human Equivalent Dose , se e D389455 (LaMay, A., 08/08/2013).

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 14 of 32 MCPA (other chlorphenoxy compoun ds); however, HASPOC decided that an inhalation toxicity study was not needed for 4

- CPA due to its low exposure and toxicity. See Table 9. 2.

Occupational Post

- Application There is a possibility for workers to have post

- application dermal exposure to 4

- CPA following its uses. Occupational post

- application exposure was not quantitatively assessed; however, based on 4

- CPA’s use pattern and low exposure potential the occupational handler assessment is expected to be protective of potential worker post

- applicat ion exposure.

Conclusion : The occupational exposure database is complete for 4

- CPA

. No risks of concern

were identified in the occupational handler and post

- application assessment s

.

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 15 of 32 Table 9. 1. Occupational Handler Non

- Cancer Exposure and Risk Estimates for 4

- CPA.

Exposure Scenario Crop or Target Inhalation Unit Exposure (μg/lb ai) 1 Dermal unit

exposure (μg/lb ai) 1 Maximum

Application Rate 2 Area Treated

Daily 3 Inhalation Dermal Combined MOE Mitigation Level: Baseline (No gloves, no respirator) Dose (mg/kg/day) 4 MOE 5 Dose (mg/kg/day) 4 MOE 5

Mixer/Loader

Mixer/Loader, Wettable powder Mung Beans 43 3700 2.2 E

- 05 lb ai/gallon 1

, 150 gallons 0.0000162 8,148,000 0.00139 95,000 95,000

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013); Level of mitigation: Base line. 2 Based on 4

- CPA Registered Label EPA Reg. No. 8906

- 1. 3 Based on 4

- CPA Registered Label EPA Reg. No. 8906

- 1. 4 Dose = Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Am ount Handled Daily (gal/day) ÷ BW (kg). 5 MOE = NOAEL ( 132 mg/kg/day) ÷ Dose (mg/kg/d ay).

Table 9. 2. Occupational Handler Non

- Cancer Exposure and Risk Estimates for 4

- CPA (using 2,4 D PoD).

Exposure Scenario Crop or Target Inhalation Unit Exposure (μg/lb ai) 1 Maximum

Application Rate 2 Area Treated Daily 3 Inhalation

Mitigation Level: No respirator Dose (mg/kg/day) 4 MOE 5

Mixer/Loader
Mixer/Loader, Wettable powder Mung Beans 43 2.2 E

- 05 lb ai/gallon 1150 gallons 0.0000162 170,000

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013); Level of mitigation: Baseline. 2 Based on 4

- CPA Registered Label EPA Reg. No. 8906

- 1. 3 Based on 4

- CPA Registered Label EPA Reg. No. 8906

- 1. 4 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (gal/day) ÷ BW (kg). 5 Inhalation MOE = Inhalation NOAEL (PoD= 2.68 mg/kg/day ) ÷ Inhalation Dose (mg/kg/day)

.

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 16 of 32 10.0 Public Health and Pesticide Epidemiology Data

Adapted from: E. Evans and S. Recore

, D 421138 , 06/26/2014



### T he OPP Incident Data System (IDS) and the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System for Occupational Risk

- Pesticides (SENSOR) databases were consulted for pesticide incident data on the active ingredient 4

- CPA, and salts (PC C ode: 019401, 019402 ). The purpose of the database sea rch is to identify potential patterns i n the frequency and severity of the health effects attributed to 4

- CPA, and salts exposure.

Conclusions: There does not appear to be a concern at this time that would warrant further investigation, since there were no incidents involving 4

- chlorophenox yacetic acid (4

- CPA), and salts reported to either IDS or SENSOR

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

.

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 17 of 32 A ppendix A

. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements The requirements (40 CFR 158.340) for food use of 4

- CPA are in Table 1. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Study Technical
Required Satisfied 870.1100 Acute Oral Toxicity

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

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

................................ .............. 870.2400 Acute Eye Irritation

................................ ....................... 870.2500 Acute Dermal Irritation

................................ ................. 870.2600 Skin Sensitization

................................ .......................... yes
yes
yes
yes
yes
yes y es

yes
yes
yes
yes
yes 870.3100 90

- Day Oral Toxicity in Rodents

................................ .. 870.3150 90

- Day Oral Toxicity in Nonrodents

............................. 870.3200 21/28

- Day Dermal Toxicity

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

- Day Dermal Toxicity

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

- Day Inhalation Toxicity

................................ ........... yes
yes
yes

no
yes yes

yes
yes a

--- yes a 870.3700a Prenatal Developmental Toxicity (rodent)

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

.............. 870.3800 Reproduction and Fertility Effects

................................ yes
yes
yes yes

yes a

yes a 870.4100a Chronic Toxicity (rodent)

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

................................ ........ 870.4200a Carcinogenicity (rat)

................................ ...................... 870.4200b Carcinogenicity (mouse)

................................ ............... 870.4300 Combined Chronic Toxicity/Carcinogenicity

............... yes

no
yes
yes
yes yes a

--- yes a

yes a

yes a 870.5100 Mutagenicity

— Bacterial Reverse Mutation Test

.......... 870.5300 Mutagenicity

— Mammalian Cell Gene Mutation Test

.. 870.5 375 Mutagenicity

— In vitro mammalian cell assay

.............. 870.5 385 Mutagenicity

— In vivo cytogenetics

.............................. 870.539 5 Mutagenicity

— In vivo mouse micronucleus

................. yes
yes
yes
yes
yes yes

yes
yes a

yes a

yes 870.6200a Acute Neurotoxicity Screening Battery (rat)

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

- Day Neurotoxicity Screening Battery (rat)

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

................................ ....... yes
yes
yes yes a

yes a

yes a
870.7485 Metabolism and Pharmacokinetics

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

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

................................ ............................. yes
yes
yes yes a

yes a

yes a

a Although this study is normally required for a food

- use chemical, HASPOC con cluded the study can be waived for 4

- CPA (HASPOC memo finalized on 5/28/2014 ).

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 18 of 32 A.2 Toxicity Profile s

Table A.2.1 Acute Toxicity Profile

- Test Substance

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral [ rat ] 41837001 LD 50 = 2703 mg/kg III

870.1200 Acute dermal [ rabbit ] 42522601 LD 50 > 2000 mg/kg III

870.1300 Acute inhalation [ rat ] 42968201 LC 50 > 5.25 mg/L IV

870.2400 Acute eye irritation [ rabbit ] 42339101 Severe irritation I

870.2500 Acute dermal irritation [ rabbit ] 42306801 Non

- irritating IV

870.2600 Skin sensitization [ guinea pig ] 42339102 Non

- sensitizing NA



### Table A.2.2 Subchronic, Chronic and Other Toxicity Profile a
Guideline No./Study Type MRID No. (year)/

Classification /Doses Results

870.3100a 90

- Day oral toxicity rodents

– rat 42902501 (1993) Acceptable, guideline 0

, 100

, 200 0, o r 800 0
ppm M : 0

, 6

. 6

, 132

. 4

, 516

. 9 m g/kg/d a y F : 0

, 7

. 99, 153

, 625

. 9

m g/kg/d a y NOAEL = 132/153 mg/kg/day in males and females, respectively. LOAEL = 517/626 mg/kg/day in males and females, respectively, based on decreased body weight s in males and females and lymphohistiocytic infiltration and individual hepatocyte necrosis in males and increased urine volume in females.

870.3150b 90

- Day oral (diet) toxicity

non

- rodents

– dog 42968301 (1993) Acceptable, guideline 0

, 20

, 10 0 o r 50 0
ppm M ; 0

, 0

. 80

, 3

. 3 a n d 18

. 6 m g/kg/d a y F ; 0

, 0

. 78

, 4

. 0 o r 17

. 4 m g/kg/d a y A v e r a g e f

o r m ale s a n d f e m a l e s; 0

, 0

. 792

, 3

. 67

a n d 18

. 0 m g/kg/d a y

. NOAEL = 18.6/17.4 mg/kg/day for males and females (HDT) LOAEL = not observed

870.3200 28

- Day dermal toxicity

– rat - No study available or required a

870.3465 90

- Day inhalation toxicity - No study available or required a

### 4

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Page 19 of 32 Table A.2.2 Subchronic, Chronic and Other Toxicity Profile a
Guideline No./Study Type MRID No. (year)/

Classification /Doses Results

870.3700a Prenatal developmental

– rat 42322602 (1992) Acceptable, guideline F: 0, 150, 300, 600 or 1000 mg/kg/day Maternal NOAEL = 60 0 mg/kg/day Maternal LOAEL = 10 00 mg/kg/day based on mortality and clinical signs of neurotoxicity ( tremors, uncoordinated movements, recumbent posture, languidness, and cold body

, yellow staining of anogenital region)

Developmental NOAEL = 30 0 mg/kg/day Development al LOAEL = 6 00 mg/kg/day based on unossified sternebrae and decreased fetal body weight
870.3700b Prenatal developmental

– rabbit 00144733 (1965) Unacceptable, guideline F: 0, 5, 10, 25 mg/kg/day (range

finding study, 5 rabbits/group) Maternal NOAEL = 25 mg/kg/day Maternal LOAEL = not observed

. Developmental NOAEL = 25 mg/kg/day Developmental LOAEL = not observed.

870.3800 Reproduction and fertility effects

– rat 00083274 (1964) Unacceptable, guideline 0

, 25

, 50

, 25 0 ppm 0

, 1

. 25

, 2

. 5

, 12

. 5

m g/kg/d a y Parental/Systemic NOAEL = 12.5 mg/kg/day Parental/Systemic LOAEL = not observed Reproductive/Offspring NOAEL = 12.5 mg/kg/day Reproductive/Offspring LOAEL = not observed

870

. 4100a Ch r oni c toxi c ity

r od e nts - No study available or required a

870.4200b Carcinogenicity

–
mouse - No study available or required a

870.4300 Chronic toxicity/ Carcinogenicity

– rat - No study available or required a

870.5100 Bacterial reverse mutation test 41837002 (1990) Acceptable, guideline 0, 100

- 5000 μg/plate (+/

- S9). A dose range of 0

- 5000 μg/plate of 4CPA was used for strains TA98, TA100, TA 1535, TA 1537, and TA 1538 of S. typhimurium . The test was negative up to cytotoxic doses of 5000 μg/plate with no activation (

- S9), and up to doses of 5000 μg/plate wit h activation (+S9) where no cytotoxicity

was seen.

### 4

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Page 20 of 32 Table A.2.2 Subchronic, Chronic and Other Toxicity Profile a
Guideline No./Study Type MRID No. (year)/

Classification /Doses Results

870.5300 Mouse lymphoma cell/mammalian activation gene forward mutation assay (L5178Y HGPRT ) 41837004 (1991) Acceptable, guideline 100, 500, 1000, 1600, 2000, 2500, 3000, 3500, or 4000 μg/mL (

- S9) 10, 50, 100, 250, 300, 750, 1000, 1300, 1600, or 2000 μg/mL (+S9) 4

- C P A ( 99 % ) w a s e v a l u a t e d f o r p o t e nti a l to indu ce d f o r wa r d mut a ti o ns a t the T K + /

- l o c us in L

5178Y T K

+ /

-
ce lls in two ind e

p e nd e ntly p e r f

o r m e d t r i a l s

. W ith o ut S 9

a c ti v a ti o n, 4

- C P A w a s n o t mut a g e nic a t d o s e s up to 4000 μg/m L : high e

r l e v e ls ( 5000 μg/m L

) w e r e s e v e r e ly

c y t o t ox i c

. I n the p r e s e n c e o f S 9 a c ti v a ti o n a t 10, 50, 100, 250, 300, 750, 1000, 1300, 1600, o r 2000 μg/mL ( c y t o t ox i c a t d o s e s 1300 μg/m L )

, n o n

- d o s e r e l a t e d in c r e a s e s in mut a ti o n f

r e qu e n c y ( M F ) w e r e o bt a in e d in b o th t r i a l s

. Alth o ugh th e

r e w a s a t e nd e n c y f

o r e l e v a t e d M F s a t d o s e s r a nging f

r o m 300 to 1600 μg/mL + S 9, d o ubling o f the M F ov e

r c o n c u rr e nt c o nt r o ls w a s o nly

s ee n a t 600 μg/mL ( T

r i a l 1) a nd 1000 μg/mL ( T r i a l 2 )

. T he e v id e n c e s ugg e s ting a mut a g e nic r e s p o n s e , w a s h o w e v e r , in s u ff

i c i e nt to c o n c lude the 4

- C P A wa s p o s iti v e

. T h e t e st m a t er i al w as n o t m u t ag e n i c in t h is in vi t

r o

m a mm alian ce ll a ss a y . 870.5375 In vitro mammalian cell assay - No study available or required a

870.5385 In vivo cytogenetics - No study available or required a

870.5395 In vivo mouse micronucleus 41837003 (1991) Acceptable, guideline M & F: 0, 0, 450, 900 or 1800 mg/kg I n a n I C R m o u s e b o ne m a rr o w mi c r o nu c l e us a ss a y , 5/ s e x / g r o up w e

r e t r e a t e d g a v a ge with 4

- CPA ( 99 % ) a t d o s e s o f 0, 450, 900 o r 1800 mg/kg

- bw. B o ne m a rr o w

ce lls w e r e h a r v e s t e d a t 24, 48, a nd 72 h o u r s p o s t

t r e a tm e nt.

T h e r e w e r e s i gns o f t ox i c it y

, l a nguidn e s s a nd p r o s t r a ti o n,

a nd m o s t a nim a ls di e d within 24 h o u r s a t 1800 mg/kg du r ing the s t ud y

. He m a t o p o i e s i s w a s a d v e r s e l y a ff ec t e d a t 1800 mg/kg. T

h e r e w e r e 5000 p o l y

c h r o m a tic e

r y t h r o c y t e s

a nd < 5 mi c r o nu c l e a t e d p o l y c h r o m a tic e r y

t h r o c y t e s ( M P E )
p e r g r o up with no d o s e r e s p o n s e

. 4

- C P A w a s t e s t e d a t a n

a d e qu a te d o s e b a s e d o n m o r t a lit y

. T he p o s iti v e c o nt r o l indu ce d the a pp r o p r

i a t e r e s p o n s e

. T h er e w as n o

s i g n i f i c a n t i n cre a s e i n t h e f

re q u e n c y o f m i cr o nu c l e a t ed
p o l y c h r o m a t i c er y t h r o c y t e s i n b o n e m a rr o w a f t e r a n y t re a t m e n t t i m e . 870.6200a Acute Neurotoxicity with parent

– rat - No study available or required a

870.6200b Subchronic neurotoxicity screening battery

– rat - No study available or required a

870.6300 Developmental neurotoxicity study

– rat - No study available or required a

### 4

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Page 21 of 32 Table A.2.2 Subchronic, Chronic and Other Toxicity Profile a
Guideline No./Study Type MRID No. (year)/

Classification /Doses Results

870.7485 Metabolism and pharmacokinetics

– rat - No study available or required a

870.7600 Dermal penetration

- rat - No study available or required a

870.7800 Immunotoxicity

– rat - No study available or required a

a No other toxicity stud ies (including conditionally required studies) are available. HASPOC has determined that the studies which are typically required for a food

- use pesticide are not required for 4

- CPA (HASPOC memo finalized on 5/28/2014 )

.

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 22 of 32 A pp e n di x B : T ox i c i t y S t u di es w i t h 4

- c h l o r o p h e n ox yace t i c ac i d ( 4

- C P A) a n d S t r u c t u res Re l a t ed t o 4

- C P A.

The following are brief summaries of the cancer findings for each of the structural analogs for which there are studies. In some cases the Cancer Assessment Review Committee (CARC) has not evaluated the pesticide. Comparison of the results from toxicity studies are made for 4

- CPA and the four analogs, 2,4

- dichlorophenoxyacetic acid, 2

- methyl

- 4

- chlorophenoxyacetic acid, 3

- chlorophenoxy

- 2

- propionic acid, and 2

- methyl

- 4

- chlorophenoxybutyric acid ( Table 1). More structurally remote chlorophenoxy acid pesticides are: (1) 2,4

- dichlorophenoxybutyric (not carcinogenic in rats or mice), (2) 2,4

- dichlorophenoxy

2

- propionic acid (not carcinogenic in rats or mice), (3) 2,4,5

- trichlorophenoxyacetic a cid (evidence of carcinogenicity in total tumors in female mice, but not rats), and (4) 2,4,5

- trichlorophenoxy

- 2

- propionic acid (no studies available). These latter pesticides are not shown and not summarized further. [Information from Carcinogenicity Peer Review (4 th 

### ) of 2,4

- D, 1/29/97.]

Structure of 4

- chlorophenoxyacetic acid (4

- CPA) (PC 019401)

Although there are no carcinogenicity studies on 4

- CPA, the weight of the evidence does not suggest that 4

- CPA would be carcinogenic in life

- time studies at reasonable doses not causing excessive toxicity.

S t r u c t u r e of 2 , 4

- dich l o r opheno x yace t ic acid ( 2 , 4

- D )( P C 030001)

The following is a summary of the findings from the fourth and last cancer assessment of 2,4

- D. This pesticide has the largest toxicity data base of all the analogs. The Cancer Peer Review Committee (CPRC) concluded that 2,4

- D should remain classified as a “Group D”

— Not classifiable as to a human carcinogenicity. That is, the evidence is inadequate and cannot be interpreted as showing either the presence or the absence of a carcinogenic effect. 2,4

- D was initially classified as a possible human carcinogen, based on a significant increased trend for brain astrocytomas in male Fisher 344 rats and suggestive to weak and conflicting evidence of no n

- Hodgkin’s lymphoma from several epidemiological studies. There was no evidence of tumor induction in female rats or male or female B6C3F1 mice, however, the CPRC concluded that the highest dose tested in both studies was sufficiently toxic to adequately test for carcinogenicity. Repeat studies were conducted in rats and mice at adequate doses, but neither study showed statistically significantly increased tumor incidence in either species or sex. Mutagenicity studies showed consistently negative results w ithout activation and positive and negative result with activation. The CPRC concluded that although cytogenic activity was seen, there was no concern for mutagenicity. Metabolism studies in the rat indicated that 85 to 94% of the parent was excreted uncha nged in the urine with 0%

- 1.3% of 2 uncharacterized compounds and 4 to 10% was excreted as the parent in feces. Total excretion (98 to 99.5%) occurred within 48 hours. The CPRC and SAP agreed on a “Group D” classification. [Information from Carcinogenicity Peer Review (4 th 

### ) of 2,4

- D, 1/29/97.]

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 23 of 32 St r u c t u r e an d r e s u l t s o n 2

- m e thy l

- 4

- c h l o r oph e no x ya ce t ic acid ( M C P A) ( P C 030501)

MCPA has not been reviewed by the CARC, but a toxicology reviewer indicated that no dose related tumors were seen in rats or mice at adequate doses to test for carcinogenicity. A battery of mutagenicity studies shows a positive study for chromosomal aberrations in human lymphocyte cells and weakly mutagenic response in an in vivo sister chromatid exchange study. The rema ining 6 in vivo and in vitro mutagenicity studies conducted were negative. The metabolism studies in the rat shows that MCPA is excreted in the urine (74

- 86%; 53%

- 69% as the parent and 7

- 13% as the hydroxymethyl metabolite and 2

- 5% in the feces). Total exc retion occurred within 192 hours (98%). [Information from the 1

- liners and Paul Chin reviewer].

St r u c t u r e an d r e s u l t s o n s o diu m 3

- c h l o r o ph e no x y - 2

- p r opiona t e ( c l op r op, s odium s a l t ) ( P C 021201)

Life

- time carcinogenicity studies have been conducted with cloprop, but there are no definitive conclusions. There was a statistically significantly increasing trend and pair

- wise comparison with control for mortality in male and female rats at the top dose. The registrant refused to submit historical control data on morality among the rats used in the carcinogenicity study. Consequently the Peer Review of cloprop was canceled and the pesticide withdrawn. In the mouse study, there was statistically significantly pair

- wise comparison of male liver adenomas/carcinoma s and male liver carcinomas at the highest dose tested and in females for liver adenomas and carcinomas at the two lowest doses tested, but not at the highest dose tested. One reviewer believed that there was no evidence for carcinogenicity in mice, howeve r another reviewer believed there was evidence of liver cancer in mice. The issue has never been resolved because the pesticide was withdrawn. Cloprop is negative in a battery of mutagenicity studies. There are no metabolism studies in rats, but in goats, cloprop is excreted as the parent. [Information from 1

- liners and a memorandum from John Redden.]

S t r u c t u r e and r e s u l t s on 2

- m e t h y l

- 4

- ch l o r opheno x ybu ty r ic acid ( M C P B ) ( P C 019201)

No life

- time carcinogenicity studies have been conducted with MCPB. A battery of mutagenicity studies are negative. One study for chromosomal abnormalities with S9 produced chromosomal abnormalities at high doses. There are no adequate metabolism studies, but a reference from the literature suggest that bacteria split off ac etic acid from the butyric acid residue in plants and

cows. [Information from 1

- liners and DERs.]

St r u c t u r e an d r e s u l t s o n 2(4

- c h l o r o ph e no x y )

- 2

- m e t hy l p r o panoi c a c i d e t hy l e s t e r ; th e D r ug C l o f i b r a t e ( l o we r s p l a s m a t r i g l y ce r i d e s a n d c h o l e s t e r o l )

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 24 of 32 An International Agency for Research on Cancer (IARC) Monograph on clofibrate states that there is inadequate evidence in humans for carcinogenicity and limited evidence in animals for carcinogenicity. Clofibrate is peroxisome proliferator and is excreted rap idly in human urine as the parent. (http://193.51.164.11/htdocs/monographs/vol66/clofibrate.html).

St r u c t u r e an d r e s u l t s o n m ec o p r o p [2

- (2

- m e t hy l

- 4

- c h l o r o ph e no x y)p r opioni c a c id ] ( P C 031501)

The acute toxicity of mecoprop is similar to that of 4

- CPA. The NOAEL/LOAEL in the rat 90

- day feeding study was lower than the NOAEL/LOAEL in rat 90

- day neurotoxicity study, which showed no neurotoxic effects, in addition to being lower than 4

- CPA in a rat 90

- day feeding study. A rabbit developmental toxicity study sh owed a maternal NOAEL/LOAEL of 30/75 mg/kg/day, but no developmental toxicity at the highest dose tested. The rat developmental toxicity study showed developmental toxicity in the form of decreased crownrump lengths, decreased ossification of sternebrae an d increased intrauterine death at the highest dose tested, which was a maternally toxic dose. The rat developmental effects occurred at a lower dose than the effects from 4

- CPA in a rat developmental toxicity study. No 90

- day feeding study in dogs is avail able. Potential carcinogenic effects have not been fully evaluated as yet, but there is suggestive evidence for increased liver tumors in mice. The rat carcinogenicity study was negative. A reverse gene mutation study was acceptable and negative and chromo somal aberrations study was acceptable and negative for clastogenicity (MRID# 41013909, TXR# 009589). The remaining mutagenicity studies were unacceptable.

### 4 -CPA Human Health Risk Assessment DP No. D419151

Page 25 of 32 T

a bl

e I : Comparison o f t o xi c i ty st u di es/ re s

u lts for 4-chlorophenoxyaoe t i c ac i d ( 4-C P A ) an d f o ur ana l ogs o f 4-C P A**ru t** **4-c -ph~n** **xy c~** **ric -dic** **blor ph~n** **2- 2-~** **y1-4- hl** **ro-** sod ium ( 3-**thyl** acid ( 4-C P A )**ac~ri c**  acid ( 2,4

- D )**ph~n 2-ac~ric**  ad d**rop ~n** **y)** - 2-**ch roph** **y)** 01 9 401 0 3 0001 (i\ ICPA )**pi on** **~** butyr ic acid (l\ I C PB ) D a ta fr o mD E R s &**~• ·**  D a ta fr o m**1-Lin~r** &**~r** 030 5 01 ( d o pr o p , s odium s alt ) 0 1 9 20 1**R~,. Y**  D a ta fr o m**Lin~r** & 0 212 0 1 D a ta fr o m**-L in~r**  Paul Chin Data f r o m**Lin~r** N o i n fo in Ar c hiw s 

# C

I 'Q C I 'C( 

# C l v

c o**~** I : o"l(o "

## ~ C H**~c~** 

### o & "l(OH & if'YOH 

### o A.YOH•

0 0 C H

, 0 0 0

R es u l ts on (a. i. ) Re sul t s o n ( a .i

. ) R es u lt s on ( a.i

. ) R es u l ts on (a .i

. ) R es u l ts on (a. i. )

8 70. 1 100 Ac u t e O r al ToxicitylD50 2703 m g/kg 3 73 O m g/kg 3500 mg/kg 1567 m g/kg 1570 m g/kg 8 70. 1 200 Ac u t e Der m al T oxic i ty/ID50 > 2000 m g/kg > 2000 mg/kg > 2000 m g/kg

- I 000 m g/kg 8 70. 1 300 Ac u t e In h a l ation T oxic i ty/LC50 > 5

. 25 m g/L > 1. 8 m g/L 4 h r > 6.3 m g/L

- 1.1 mg/L (acetone 8 70.2400 P r i mary E ye Irri t at i o n

. Severe Mod/Seve r e Mod/Severe

- vehicle) 8 70.2500 Pr i mary D erm al Irri ta t i o n No t ir ritat i n g No n e Irri tati n g S li g h t

- Mod/Severe 8 70.2600 Der m al Sensitizat i o n Not sensitizing Not sens i t i zi ng Not s en sit izin g - -

-

870.3100 O r al S u bchrooic ( r at)

. NIL = i5 2/ 517 m kd

, B w t NIL= i 5 /1 00mkd tes t es , NIL=50 11 50pp m - NIL= 1 58 /

- mlk/d HDT dec & uri n e vo l u m e li ver , t h yroid weigh t i n c & NIL=2

. 5 n .5 m kd inc pa l ata b ili ty n o t ed; i n c , li ver i ndividua l spleen h i sto p ki dney weigh t wit h i

ncr ki dney weigh t incr

, cell n ecrosis c re at i ni ne HDT

, no lti stop n eg lti stop

870.3150 Oral S u b c h ronic (dog )

. NIL=18

. 6 /

- mkd H O T N / L = i.0 / 3.0 mkd

, l ive r , N IL = O. 6 / 2 .4 mkd li ver NIL = l2.5 / 50 mk d, NIL= 1 2/ 40 mk d I nc BS P ( P eer Rev) ; ki dney & t es t es lti s t o i ntla nuu atio n & cl inica l bwt dee r , li ver , r et en t i on, dec NIL = 3.3 / 19 mk d b wt & chemis t ry (MC P A

- kid n ey & sp l een sp emt atogeoic act i vity

, f ood deer ; n o h is t o p Dint eth ylaini n e) weigh tin c r p r os ta t e & t e s t es ru b u l ar
c h anges seen (DER ) at r op h y

870.3200 21

- D a

. y D erm al (rab b i t )

. - NIL = 1000 /

- mkd Sys t NIL=IOO /I OOOmkd Mi nera l ization kidney - -

t u b ules Irr

i t atiouNIL= 870.3250 90 -D a

. y D erma l

. . . . · · · · - - - 10 / i OOmkd

- - 870.3 4 65 90 -D a

. y In h alat i o n

.

. · · · · - - - - -

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 26 of 32

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 27 of 32

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 28 of 32

### 4 -CPA Human Health Risk Assessment DP No. D419151

Page 29 of 32**Study!T~s t** **4-<h oro** **-ph~noxy ~ric** **2,4-dichloroph~no~")-2- (2** **-~ hyl-4** **chloro-** sod i um ( 3-**(2- ~thy** **l** a cid (4-C P A)**ac~ ri** **c** a cid (2 ,4

- D)**ph~no~}2-ac~ric** acid**ch oroph~noxy)**  - 2

-**oph~noxy**

019401 0 3 000 1 (i\ICPA)**prop on** **at ~**  butyr ic a ci d (l\ ICPB ) D ata from D I R s &**~r** D ata from**Lin~r** &**~r** 030501 (doprop, sodium salt) 0 1 920 1**~,- R~Y**  D ata from**Lin~r** & 021201 Data fro m**-Li ~r**  P a ul Chin Data f ro m**Li ~r**  No i n fo in Arc h iws**~** 

# C I 'C( C I 'Gl

c o**<><** I : 0 -"J(o H I : ifj(CH

## ~ C H 0

### ~c~ o & -"J(CH 

# oAYOH'

0 0 C H

, 0 0 0
870 .7 485 General Metabo li sm**(L~b#** - Excreted as pa r ent i n urine Mos tl y excreted as Excreted as pa r ent
, Lit.; Bact-Splits off 1 5 21 5 1 7 ) ( 86

- 94%)

, 4

- 11% i n t

h e MCPA

, 7

- 1 3% mo s tl y acet i c acid from t he fece s hydroxy l ated me

. thyl wunetabolized i n t he b u tyr i c ac id resid u e i n Small amooots of MCPA. 98%excreted goat p l ant s a n d cows metabolites (0.6%

- 1

. 3% )

. wi t hi n 1 92 hr. 

### uc UA 98

- 99.5% reco v ered Excreted m ostly llll

w i t

h i

n 48 h r. met abo l ized Excreted mostly t m

metabolized 870 .7 60 0 Dermal Penetra t i o n - - -

- - Carcogenic i ty No studies " D " no t classifia bl

e as a Classification

. . . h u man carcinogen No t like l y t

o be a hlllll3U carcinogen

, b u t no HIARC: Rat s (his t ori cal contro l requ ired ) Chem No carcinogenicity studies

or CARC r e view yet w i th dra wn

M i

ce increased pair

- wis e hepa t ocellu l ar carcinomas at H DT Unclassifie d by C;\RC

1 This 3 -geueratiou r eproduction study w i th 4-CP A is re asonably w ell co nduc t ed b u t th e

. doses w er

e t oo low ( the highest dose t est

ed was 1 2.5% of t he NO;\E L fron 1 t he 90-day s ubchronic st ud

y in
rats .)

. Th e

. high e st d ose t es

t ed was 250 ppm and th e

. NOAEL in a 90

- <l a y ra t s m d y was 2000 ppm

. In addi ti on, th e

. co l ony showed r espiratory prob l ems w it h weigh t los s with rec o very an d re la t ed marked canni b alism

, and p u p dea t h due t o ma t ern al death

. The mater i al t

es

t e d appeared t o be reasona bl y pure from aci d e

q u iv a l en t measuren1eu ts, b u t since no uni ts w er

e

. reported

, this c3llllo t be verifi ed

. The study w as conducted prior t o GLP s and t he t e st ma teria l in t he die t was not mea s u red. Therefore the study is tmaccepta ble/

not u pgrada bl

e. NIL = NOAELILOAEL followed b y effect s a

t L

OAEL u nless otherwise specified; mkd = m glkg/day

. - = No smdy con d uc t

ed or availa bl

e; UA = Unacceptable smdy; UC = Unclassified s m d y;

a

.

i. = ac ti ve ingredien t. inc=increase; dec=decr e ase ; histop=histopathology; DER = data evalua ti on r ecord; n e g=ne.ga ti ve; p os =p o sitiv e ; Sys t = sys temi c ; HDT = highest dose tested; mod = modera t e; B wt= b ody weight; u n o s s=tmossified; o ss=ossifi ca ti on; M=ma t erual ; D=de velop menta l; UA = u

naccep t ab l e ; P=parental ; O:ff=offspring; FOB = Func tiOflal Observa ti on Battery; CARC=Cancer Assessment Re vi

e w Committee

.

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 30 of 32 Appendix C

. Physical/Chemical Properties

Table C1. Physico

- Chemical Properties 1

Parameter Value Reference

Molecular Weight 186.59 Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V1: 115

Water solubility (2 5 °C) 957 mg/L Yalkowsky, S.H., He, Yan., Handbook of Aqueous Solubility Data: An Extensive Compilation of Aqueous Solubility Data for Organic Compounds Extracted from the AQUASOL dATAbASE. CRC Press LLC, Boca Raton, FL. 2003., p. 461 Vapor pressure (25°C) 3.2 x 10

- 4 mm Hg EPA; Estimation Program Interface (EPI) Suite. Ver.3.12. Nov 30, 2004 Dissociation constant, pKa 3.56 Bailey GW, White JL; Res Rev 10: 97

- 123 (1965) Octanol/water partition coefficient, log K OW (25°C) 2.25 Hansch, C., Leo, A., D. Hoekman. Exploring QSAR

- Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 38
1 Information obtained from ToxNet on 2/25/2014 (http://toxnet.nlm.nih.gov/cgi

bin/sis/search/a?dbs+hsdb:@term+@DOCNO+3944 ). Original references specified in the website were included.

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 31 of 32 Appendix D . Chronic Dietary Assessment for 4

- Chlorophenoxyacetic Acid

Input File
US EPA Ver. 3.16, 03

- 08

- d
DEEM

- FCID Chronic analysis for 4

- CHLOROPHENOXYACETIC ACID Residue file: F: \ Dietary Assessments \ 4

- CPA \ 4CPA_Dietary_chronic.r08 Adjust. #2 NOT used Analysis Date 05

- 21

- 2014 Residue file dated: 05

- 21

- 2014/11:36:45 Reference dose (RfD) = 1.32 mg/kg bw/day Comment:Mung Beans only; no EDWCs due to limited use

---------------------------------------------------------------------------------- Food Crop Residue Adj.Factors EPA Code Grp Food Name (ppm) #1 #2

---------- ---- ------------------------------- ---------- ------ ------ 0603039000 6C Bean, mung, seed 0.200000 1.000 1.000

Results File US EPA Ver. 3.16, 03

- 08

- d
DEEM

- FCID Chronic analysis for 4

- CHLOROPHENOXYACETIC ACID NHANES 2003

- 2008 2

- day Residue file name: F: \ Dietary Assessments \ 4

- CPA \ 4CPA_Dietary_chronic.r08 Adjustment factor #2 NOT used. Analysis Date 05

- 21

- 2014/11:37:12 Residue file dated: 05

- 21

- 2014/11:36:45 Reference dose (RfD , Chronic) = 1.32 mg/kg bw/day COMMENT 1: Mung Beans only; no EDWCs due to limited use

=============================================================================== Total exposure by population subgroup

------------------------------- ------------------------------------------------

Total Exposure

----------------------------------- Population mg/kg Percent of Subgroup body wt/day Rfd

-------------------------------------- ------------- ---------------- Total US Population 0.000000 0.0% Hispanic 0.000000 0.0%
Non

- Hisp

- White 0.000000 0.0%
Non

- Hisp

- Black 0.000000 0.0%
Non

- Hisp

- Other 0. 000003 0.0% Nursing Infants 0.000000 0.0%
Non

- Nursing Infants 0.000000 0.0% Female 13+ PREG 0.000000 0.0% Children 1

- 6 0.000000 0.0% Children 7

- 12 0.000000 0.0% Male 13

- 19 0.000001 0.0% Female 13

- 19/NP 0.000000 0.0% Male 20+ 0.000001 0.0% Female 20+/NP 0.000000 0.0% Seniors 55+ 0.000000 0.0% All Infants 0.000000 0.0% Female 13

- 50 0.000000 0.0% Children 1

- 2 0.000000 0.0% Children 3

- 5 0.000000 0.0% Children 6

- 12 0.000000 0.0% Youth 13

- 19 0.000001 0.0% Adults 20

- 49 0.000001 0.0% Adults 50

- 99 0.000000 0.0% Female 13

- 49 0.000000 0.0%

-------------------------------------------------------------------------------

### 4

- CPA Human Health Risk Assessment DP No. D419151

Page 32 of 32 Appendix E

. International Residue Limits



## 4

- Chlorophenoxyacetic acid (PC Code 019401 )

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 

### Codex 40 CFR 180.202: (a) General. A tolerance is established for the combined residues of the plant regulator p

chlorophenoxyacetic acid and its metabolite p

chlorophenol to inhibit embryonic root development

. 

### (4

- chlorophenoxy) acetic acid None

Commodity 1 

### Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 2 

### Codex Bean, mung, sprouts 0.2 2

Completed: M. Negussie; 02/06/2014

1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the applicant.

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