UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: December 5, 2013 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: 2,4-DP-p (dichloroprop-p). Human Health Assessment Scoping Document in 

Support of Registration Review. 

PC Code: 031402 (2,4DP-p acid), 031403 (2,4- DP Barcode: D413488 

DP-p amine salt), and 031465 (2,4-DP-p 2-

ethylhexyl ester) 

Decision No.: 481240 Registration No.: NA 

Petition Nos.: NA Regulatory Action: Registration Review 

Risk Assess Type: Scoping Document CaseNo.: NA 

TXRNo.: NA CAS Nos.: 15165-67-0 (2,4DP-p), 104786-87-0 

(2,4-DP-p amine salt), 53404-32-3 (2,4-DP amine 

salt) and 865363-39-9 (2,4-DP-p 2-ethylhexyl 

ester) 

MRIDNo.: NA 

FROM: Ideliz Negr6n-Encamaci6n, Ph.D., Risk Assessor :Jd.[.q L ~ j 

Ronnie Bever, Jr., Ph.D., ~-i~~ ~ 9 -\l"CV fJ 

Seyed Tadayon, Chemist~~~ 

Risk Assessment Branch V 

THRU: 

Health Effects Division (7509P) 

Office of Pesticide Programs 

Linda Taylor, Ph.D., Toxicologis yc._ 

Michael Metzger, Branch Chief 

Risk Assessment Branch V 

Health Effects Division (7509P) 

Office of Pesticide Programs 

TO: Kaitlin Keller, Chemical Review Manager 

Tracy Perry, Risk Manager 

Pesticide Re-evaluation Division (7508P) 

Office of Pesticide Programs 

Page 1 of30 
EXECUTIVE SUMMARY 

The HED Registration Review Team has evaluated the most recent human health assessments 

and database for the herbicide, 2,4-DP-p [2-(2,4-dichlorophenoxy)propanoic acid] (including 

data on it amine salt and ethylhexyl ester), to determine whether sufficient data are available and 

whether any updates are needed to support Registration Review. Since 2001, there has been a 

complete transition of technical 2,4-DP acid product registrations from the racemic (mixed 

isomer) form (written as 2,4-DP) to the enriched isomer form of2,4-DP (written as 2,4-DP-p). 

Only the R isomer of2,4-DP is herbicidally active. HED has considered the most recent humanhealth risk assessments for 2,4-DP-p; updates to the toxicity, exposure, and usage databases; and 

current Agency science policy and risk assessment methodologies to determine the scope of 

work necessary to support Registration Review. 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 published. 

2,4-DP-p is a chlorophenoxy herbicide used primarily in combination with other herbicides for 

controlling broadleaf weeds in residential and commercial turf grass, golf courses, on sod farms 

as well as for noxious weed and brush control on uncultivated nonagricultural areas such as 

roadsides and rights-of-way. There are no registered food or feed uses for 2,4-DP-p acid or its 

amines or esters in the U.S. that require the establishment of tolerances. Uses of2,4-DP-p on 

pasture (municipal, state and federal lands) were identified by BEAD. Agricultural uses on 

pasture are considered a food use which is not supported by the database. The 2,4-DP-p Task 

force has indicated that there is not use on pasture land, and has expressed a willingness to 

modify labels to prohibit this use. 

Toxicity/Hazard Considerations 

The toxicity database for 2,4-DP-p is incomplete. A 90-day subchronic inhalation toxicity is 

required. The toxicity profile of 2,4-DP-p shows that the principal toxic effects are 

nephrotoxicity and hepatotoxicity. There were also reported clinical chemistry and hematology 

changes associated with the nephrotoxicity and hepatotoxicity. 2,4-DP-p has been classified as 

"not likely to be carcinogenic to humans." 2,4 DP-p was also generally not mutagenic. In the 

acute neurotoxicity study in rats, 2, 4-DP-p caused various abnormalities noted during the 

functional observational battery (FOB) and caused a decrease in motor activity; however, no 

evidence of neuropathology was observed. In the combined subchronic oral toxicity and 

neurotoxicity study, decreased fore- and hindlimb grip strength were noted in females. No 

evidence of increased susceptibility was observed following in utero exposure in rats and rabbits 

or following pre- and/or postnatal exposure in rats. Developmental toxicity was observed in the 

rat and rabbit at dose levels at and above those causing maternal toxicity. Reproductive toxicity 

was observed in the rat. The available toxicity data indicate low acute oral, dermal, inhalation, 

and primary dermal irritation toxicity for 2,4-DP-p, 2,4-DP-p EHE (2,4-DP-p ethyl hexyl ester), 

and 2,4-DP-p DMAS (2,4-DP-p dimethylamine salt; toxicity categories III and IV). 2,4-DP-p is 

a severe eye irritant (toxicity category 1). 2,4-DP-p is not a dermal sensitizer; however, 2,4-DP-p 

EHE and 2,4-DP-p DMAS are dermal sensitizers. 

Page 2 of30 
Page 3 of 30

Dietary Exposure and Risk

2,4-DP-p products are used outdoors on turf and for woody plant control in non-crop areas. 

Provided label modifications are made to prohibit use on pasture, there are no uses that would 

result in dietary exposure. Therefore, the dietary risk assessment considers drinking water 

exposures only. In the most recent dietary risk assessment, acute and chronic risks were below 

the HED level of concern, <16% aRfD and <1% cRfD, respectively (D342620; 08/13/2007). 

Updated dietary exposure assessments for 2,4-DP-p may be necessary to consider the most 

recent drinking water consumption data, and to include newly estimated drinking water 

concentrations. 

Residential Handler and Post Application Exposure and Risk

The residential exposure database is adequate to support registration review for 2,4 DP-p. 

Since 2,4-DP-p, its salts, and esters are not restricted use pesticides, HED previously conducted 

a residential handler exposure assessment for lawn use (D342620; 08/13/2007). Risk estimates 

were not of concern. The MOEs ranged from 44,000 to 7,700,000.

Previous residential post-application assessments, which assessed incidental oral exposures only, 

relied on default assumptions for turf transferrable residues following treatments. Chemicalspecific TTR data is not required to assess exposure to residues following 2,4 DP-p treatments. 

For the residential postapplication assessment, the following incidental oral exposures: hand-tomouth; object-to-mouth; incidental soil ingestion; and episodic ingestion of granules may need to 

be included in the registration review assessment, reflecting any updated doses and endpoints for 

risk assessment, HED’s Residential SOPs, and current policies. 

Aggregate Risk Assessment

In the most recent risk assessment, HED provided updated aggregate exposure and risk estimates 

for drinking water and residential exposures. Short-, intermediate- and long-term aggregate risk 

assessments were conducted. The aggregate risks for this active ingredient were below HED’s 

level of concern (i.e. MOE > 100). Aggregate exposures of 2,4-DP-p may need to be revised 

during registration review to consider updated dietary and residential exposures estimates, as 

well as to consider any updated short- or intermediate-term endpoints. 

Occupational Handler and Post Application Exposure and Risk

The occupational exposure database is adequate to support registration review for 2,4 DP-p. All 

short- and intermediate-term MOEs for agricultural handler scenarios are assessed at baseline 

PPE except for aerial applicators, who were assessed with closed cockpit (i.e., engineering 

controls) built in. All scenarios have target MOEs above 100 and thus are not a risk concern at 

baseline exposure, except for the following two scenarios: mixing and loading liquids for 

forestry applications for short- and intermediate-term duration; and mixing and loading wettable 

powder for turfgun for intermediate-term duration. However, these scenarios are not a risk 

concern with respiratory protection (i.e., a PF5 respirator or dust mask with a protection factor of 

5 when properly fitted). 

In the absence of toxicity via the dermal route, no quantitative dermal post-application risk 

assessment is required for the occupational uses of 2,4-DP-p, its salts, and esters. 
Page 4 of 30

Spray Drift

Residential exposures resulting from off-site transport (e.g., spray drift or volatilization) might 

occur as a result of applications of 2,4-DP-p. The Agency is in the process of evaluating these 

types of exposures and might, 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 2,4-

DP-p will be examined during registration review.

1.0 FORMULATIONS AND USE PATTERNS 

HED used the Biological and Economics Analysis Division (BEAD) Label Data System to 

identify all uses of 2,4-DP-p. In addition, the BEAD Chemical Profile for Registration Review 

was used to characterize the use patterns of 2,4-DP-p (06/12/2013, B. Phillips et. al.). HED is 

currently considering products formulated with 2,4-DP-p (PC Code 031402), 2,4-DP-p dimethyl 

amine salt (PC Code 031403), and 2,4-DP-p 2-ethylhexyl ester (PC Code 031465). 

2,4-DP-p is a chlorophenoxy herbicide used primarily in combination with other herbicides for 

controlling broadleaf weeds in residential and commercial turf grass, golf courses, on sod farms,

as well as for noxious weed and brush control on uncultivated, nonagricultural areas such as 

roadsides and rights-of-way. 2,4-DP-p belongs to the class of phenoxy herbicides that includes 

2,4-D, 2,4-DB; MCPA; MCPB; and MCPP-p. 2,4-DP-p is the R-isomer enriched form of 2,4-

DP (racemic form) which is the herbicidal active component. There are no registered food or 

feed uses for 2,4-DP-p acid or its amines or esters in the U.S. that require the establishment of 

tolerances. 

2,4-DP-p, its salts, and esters are available as soluble concentrates/solid and/or liquid, 

emulsifiable concentrates, granulars, and ready-to-use liquids. They may be applied twice per 

year on commercial/industrial lawns, drainage systems, golf course turf, rights-of-way, 

ornamental lawns and turf, nonagricultural uncultivated areas, paved areas (private roads and 

sidewalks), recreational area lawns, and residential lawns. For other uses (e.g., forest plantings),

the maximum number of applications per year is not currently specified in the labels. Most of 

the registered products contain 2,4-DP-p DMAS. 

Agricultural Uses

Uses of 2,4-DP-p on pasture were identified by BEAD. The Task Force indicated that there are 

no supported broad spectrum pasture uses for 2,4-DP-p end use products and label clarifications 

will be made, as appropriate. 

Non-Agricultural and Residential Uses

2,4-DP-p is registered for use on ornamental lawns, recreational turf, sports fields, sod farms, 

roadsides, industrial sites, rights-of-way, and forests. 

Conclusions: Uses of 2,4-DP-p on pasture (municipal, state and federal lands) were identified 

by BEAD. HED emphasizes that agricultural uses on pasture are considered a food use and are 

not supported by the database. The 2,4-DP-p Task force has indicated that there is not use on 
Page 5 of 30

pasture land, and has expressed a willingness to modify lables to prohibit this use. HED notes 

that if the 2,4-DP-p Task Force, or other end use registrants, choose to support a pasture use, 

additional residue chemistry data may be required to support that food use (see Section 12.0 Data 

Requirements).

2.0 HAZARD IDENTIFICATION/TOXICOLOGY

The database for 2-(2,4-dichlorophenoxy) R-propionic acid (2,4-DP-p) is not complete. A 

subchronic inhalation toxicity (OPPTS 870.3465) study is required and has not been submitted. 

The requirement for an immunotoxicity (OPPTS 870.7800) was waived by the Hazard and 

Science Policy Council (HASPOC; 12/04/2013).

The toxicology database for the active ingredient contains studies on 2,4-DP (racemic mixture) 

and 2,4-DP-p (single R isomer). The older toxicity studies used 2,4-DP, while the newer toxicity 

studies tested 2,4-DP-p. No new toxicity and/or metabolism data have been received for 

2,4-DP-p technical since the last risk assessment (D342620, 2007). The 2,4-DP-p Task Force 

provided summaries of toxicity studies (Comparison of toxicity of racemic 2,4-DP and optically 

active 2,4-DP-p; MRID 46856706). No significant differences in toxicity between the two 

isomeric forms were identified. Several acute studies of dermal irritation, eye irritation, 

inhalation toxicity, dermal toxicity, and oral toxicity and skin sensitization were submitted for 

formulations, 2D + 2DP Amine (co-formulation), and 2,4-D DMA. 

The toxicity profile tables for 2,4-DP-p are included as Attachment 2. The 2,4-DP-p endpoints, 

points of departure (PoDs), and uncertainty/safety factors (UF/SFs) used in the most recent 

human health risk assessment are summarized in Appendix A.3. The composite uncertainty 

factors were 100X for all exposure scenarios. 2,4-DP-p does not require food tolerances and is 

considered to be a non-food use chemical; therefore, it is not subject to the amendments to the 

Federal Food, Drug, and Cosmetic Act (FFDCA) promulgated under the Food Quality Protection 

Act (FQPA) of 1996. 

Nephrotoxicity and hepatotoxicity appear to be the most prevalent effects. There were also 

reported clinical chemistry and hematology changes associated with the nephrotoxicity and 

hepatotoxicity. Nephrotoxicity was manifested in one or more studies as tubular nephrosis, 

increased relative kidney weight, foci of basophilic tubules, focal hyperplasia of the transitional 

epithelium, papillary/medullary calculi, degenerative kidney tubular vacuolization, increased 

pigment in renal tubuli, increased renal calcification, chronic nephropathy, and increased 

lipofuscin deposition in the proximal tubular cells, as well as various clinical chemistry and 

urinalysis parameter changes suggestive of nephrotoxicity. Hepatotoxicity was manifested in 

one or more studies as pronounced lobular pattern, diffuse single cell degeneration, a 

dissociation-like appearance of the hepatocytes, too homogeneous cytoplasm of the hepatocytes, 

increased liver weights, absence of fat storage, cytoplasmic eosinophilia, granular cytoplasm, 

hypertrophy, focal necrosis, and bile duct hyperplasia, as well as changes in clinical chemistry 

parameters indicative of hepatotoxicity. 2,4-DP-p has been classified as “not likely to be 

carcinogenic to humans.” 2,4-DP-p was also generally not mutagenic in the various assays 
Page 6 of 30

performed; although, induction of sister chromatid exchanges in Chinese hamsters was noted in 

one study.

In the acute neurotoxicity study in rats, 2,4-DP-p caused functional observational battery (FOB) 

effects, which included abnormal body posture (prone/lateral), palpebral closure, 

hypoactivity/apathy, ataxia, hypothermia, decreased number of rearings, increased limb splay, 

retarded righting response, decreased hindlimb grip strength, and increased landing foot splay in 

males. In addition, 2,4-DP-p caused a decrease in motor activity. However, no evidence of 

neuropathology was observed. 

The developmental studies demonstrated that rat and rabbit fetuses were no more sensitive to the 

effects of 2,4-DP-p than their dams. Developmental effects observed in rats were decreased fetal 

body weight, an increased incidence of incompletely ossified sternebra, and an increased 

incidence of rudimentary cervical ribs. Maternal effects observed in rats included decreased 

body weight, body weight gain, and food consumption. The developmental effect observed in 

rabbits was an increased incidence of 13th accessory rib(s) at the same dose where decreased 

body weight gains and food consumption, stomach mucosa ulceration, and clinical signs of 

reduced general state, lateral or abdominal position, and no defecation were observed in the 

maternal rabbit. In the 2-generation reproduction study, 2,4-DP caused parental, reproductive, 

and offspring toxicity, indicating that the offspring sensitivity to 2,4-DP was no greater than the 

parents. The reproductive effects seen were decreased mating, fertility, and gestation indices; 

and evidence of systemic offspring toxicity included increased gestation duration and severely 

decreased live birth and viability indices, as well as retarded growth and development. Parental 

systemic toxicity included the following findings: mortality and clinical signs of poor maternal 

care; decreased body weights, body weight gains, and food consumption; increased water 

consumption; and mild effects on the liver (increased weights, hypertrophy of the periacinar 

hepatocytes, focal necrosis, and bile duct hyperplasia) and kidneys (increased weights, foci of 

basophilic (regenerating) tubules, focal hyperplasia of the transitional epithelium and 

papillary/medullary calculi).

The available toxicity data indicate low acute oral, dermal, inhalation, and primary dermal 

irritation toxicity for 2,4-DP-p, 2,4-DP-p EHE, and 2,4-DP-p DMAS (toxicity categories III and 

IV). 2,4-DP-p is a severe eye irritant (toxicity category I). 2,4-DP-p is not a dermal sensitizer; 

however, 2,4-DP-p EHE and 2,4-DP-p DMAS are dermal sensitizers. 

Oral metabolism studies in rats showed that 2,4-DP-p was absorbed rapidly, and the majority of 

the administered dose was excreted in urine as unchanged parent compound. Oral metabolism 

studies in rats with 2,4-DP-p-ethylhexyl ester (EHE) and 2,4-DP-p-dimethylamine (DMAS) 

showed that both the ester and amine forms are quantitatively converted to the acid prior to 

absorption. The metabolism of 2,4-DP-p EHE and 2,4-DP-p DMAS in rats is similar to the 

metabolism of 2,4-DP-p. The major component in the urine was 2,4-DP-p, and neither 2,4-DP-p 

EHE nor 2,4-DP-p DMAS was detected in urine or feces. The 2,4-DP DMAS (racemic mixture) 

also has registered uses that are being considered; however, the toxicity profile is expected to be 

similar to that of the 2,4-DP-p DMAS.
Page 7 of 30

Conclusions: The database for 2,4-DP-p is not complete. A subchronic inhalation toxicity 

(OPPTS 870.3465) studies is required and has not been submitted. The subchronic inhalation 

toxicity is important because this represents a possible exposure route (aerosol application) and 

portal-of-entry effects were noted in the subchronic inhalation toxicity study on the similar 

chemical, 2,4-D. The available oral toxicity studies may not be protective of these portal of 

entry effects, which, in the case of 2,4-D, included squamous metaplasia and epithelial 

hyperplasia with increased mixed inflammatory cells within the larynx (and this condition was

not totally resolved following a 4-week recovery period). The results of the subchronic 

inhalation study may impact the endpoints, PODs, and UF/SFs for the inhalation exposure 

assessment.

3.0 DIETARY EXPOSURE

There are no registered food or feed uses for 2,4-DP-p acid, its amines or esters, and thus no 

food-related dietary risk assessments were conducted. However, since 2,4-DP-p products are 

used outdoors on turf (golf courses, lawns, parks, etc.) and for woody plant control in non-crop 

areas (utility rights-of-way, firebreaks, fence rows, forests, and industrial sites), the risk 

assessment considers drinking water exposures. In the most recent assessment, ground water 

residues were low in comparison to surface water. The conservative screening-level drinking 

water assessment for surface water predicted acute and chronic EDWCs using the Tier II PRZMEXAMS - Index Reservoir model for uses on Christmas trees, the use resulting in the highest 

EDWCs. Acute and chronic dietary exposure estimates were below the HED level of concern, 

(i.e. < 100% of the acute and chronic reference dose), <16% aRfD and <1% cRfD, respectively,

for the general population and all population subgroups. 

Conclusions: Dietary exposure assessments for 2,4-DP-p may be necessary to consider the most 

recent drinking water consumption data from the 2003-2008 U.S. Department of Agriculture’s 

National Health and Nutrition Examination Survey, What We Eat in America, and to include 

newly estimated drinking water concentrations.1 

4.0 RESIDENTIAL EXPOSURE

Residential exposure to 2,4-DP may occur from uses on turfgrass and golf courses.

Residential Handler

In the last risk assessment (D342620; 08/13/2007), the estimated residential handler risk did not 

exceed HED’s level of concern of 100 (MOEs>100). The MOEs ranged from 44,000 to 

7,700,000. However, subsequent to that assessment substantial changes have occurred regarding 

the exposure methodology HED uses to conduct residential assessments; therefore, for 

residential handlers, the following high-end exposure scenarios for both broadcast and spot 

treatment of turf may need to be reassessed under registration review: hand application of 

 

1 Registration Review: Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered 

Species, and Drinking Water Exposure Assessments for 2,4-DP-p Containing R Isomer Compounds (2,4-DP-p acid, 

2,4-DP-p Amine salt, and 2,4-DP-p 2-ethylhexyl ester). Khan, Faruque, and Radtke, Meghan., In Progress. 
Page 8 of 30

granules; belly grinder application; load/apply granules with a broadcast spreader; 

mix/load/apply with a hose-end sprayer (mix your own); mix/load/apply with a hose-end sprayer 

(ready to use); mix/load/apply with hand held pump sprayer; and mix/load/apply with ready to 

use sprayer. Exposure and risk estimates may need to be assessed in registration review in 

accordance with the 2012 Residential SOPs.

Residential Post Application 

Quantitative residential dermal post-application risk assessments were not conducted based on 

the absence of toxicity via the dermal route. However, an incidental oral exposure assessment 

for children was conducted in the most recent risk assessment (D342620; 08/13/2007). All of the 

short-term MOEs for these exposures were greater than 100, and thus are not of risk concern. 

Exposure and risk estimates may need to be assessed in registration review in accordance with 

the 2012 Residential SOPs.

Spray Drift

Residential exposures resulting from off-site transport (e.g., spray drift or volatilization) might 

occur as a result of applications of 2,4-DP-p. The Agency is in the process of evaluating these 

types of exposures and might, 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 2,4-

DP-p will be examined during registration review.

Conclusions: Updated residential handler and post application exposure and risk assessments 

may be needed during registration review in accordance with the 2012 Residential SOPs during 

registration review. Updated assessments should consider current HED policies and procedures 

and include any updated endpoints as appropriate. As necessary, an inhalation post-application 

risk assessment could be conducted in accordance with the development of relevant HED 

policies for risk assessment (e.g., spray drift, or volatilization).

5.0 AGGREGATE EXPOSURE AND RISK ASSESSMENT

In the most recent risk assessment, HED only provided updated aggregate exposure and risk 

estimates for drinking water and residential exposures through the inhalation and incidental oral 

routes. There are two reasons. First, 2,4-DP-p has no food use. Second, a dermal exposure 

assessment was not conducted, because no systemic toxicity was seen at limit dose (1000 mg/kg) 

with 2,4-DP-p or its ester or salt in 21-day dermal toxicity studies and no developmental toxicity 

was found with prenatal exposure with 2,4-DP-p. Acute, short-term, and chronic aggregate 

assessments were conducted. Based on the current use-pattern for 2,4-DP-p on turf, there are no 

intermediate-term residential exposure scenarios; therefore, an intermediate term assessment was 

not required. The exposure scenarios aggregated are: 
Page 9 of 30

Acute – drinking water only

Short-term: adults – short-term inhalation handler exposure with chronic (average) 

drinking water exposure; children - short-term incidental oral ingestion with chronic

(average) drinking water. The combined MOE’s for the scenarios examined ranged from 

360 to 29,800; therefore, below HED’s level of concern (i.e. MOE > 100). 

Chronic – drinking water only

Conclusions: Acute, short-term, and chronic aggregate risks are not of concern; however, 

updated aggregate assessments may be required to support registration review that consider 

updated dietary and residential exposures estimates or changes in toxicological endpoints. 

6.0 OCCUPATIONAL EXPOSURE 

2,4-DP-p, its salts, and esters may be applied using aerial (sod farms only), groundboom, handheld spray, and granular spreader equipment. The personal protective equipment (PPE) required 

for handlers consists of a single layer of clothing (long sleeve shirt, long pants, and socks plus 

shoes) and chemical resistant gloves. The restricted entry interval (REI) for 2,4-DP-p is 12

hours.

The occupational uses of 2,4-DP-p, its salts, and esters result in short-term (1 - 30 days) and 

intermediate-term (1 - 6 months) occupational exposures. Based on the current use patterns, no 

long-term residential or occupational exposures are anticipated; therefore, no long-term dermal 

or inhalation risk assessments have been conducted. 

Occupational Handler Exposure

The registrant has not submitted chemical-specific exposure data to estimate handler exposures. 

In the absence of chemical-specific data, it is HED policy to use the best available data to assess 

handler exposures. Sources of such generic (surrogate) handler data include Pesticide Handlers 

Exposure Database Version 1.1 (PHED 1.1), and the Agricultural Handler Exposure Task Force 

(AHETF) database, or other registrant-submitted occupational exposure studies. Some of these 

data are proprietary (e.g., AHETF data), and subject to the data protection provisions of Federal 

Insecticide, Fungicide, and Rodenticide Act (FIFRA).

All short- and intermediate-term MOEs for agricultural handler scenarios are assessed at baseline 

PPE except for aerial applicators, who were assessed with closed cockpit (i.e., engineering 

controls) built in. All scenarios have target MOEs above 100 and thus are not a risk concern at 

baseline exposure (MOE,s ranged from 200 to 37,000) , except for the following two scenarios: 

mixing and loading liquids for forestry applications for short- and intermediate-term duration

(MOE’s were 41 and 29 respectively); and mixing and loading wettable powder for turfgun for 

intermediate-term duration (MOE was 78) . However, these scenarios are not a risk concern 

with respiratory protection (i.e., a PF5 respirator or dust mask with a protection factor of 5 when 

properly fitted). 

Occupational Post-application Exposure

In the absence of toxicity via the dermal route, no quantitative dermal post-application risk 
Page 10 of 30

assessment is required for the occupational uses of 2,4-DP-p, its salts, and esters. The REI on 

registered labels is considered appropriate based on the toxicity of the technical ingredient. 

Although HED would typically require dislodgeable foliar residue (DFR) studies based on the 

existing use pattern, no studies are required due to a lack of toxicity via the dermal route.

Conclusions: Updated occupational handler exposure assessments may be needed during 

registration review if a new inhalation dose and endpoint for risk assessment are selected and to 

consider the most current exposure data and SOPs. 

7.0 PUBLIC HEALTH AND PESTICIDE EPIDEMIOLOGY DATA 

The 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 ingredients Dichlorprop, 2,4-DP-p, 2,4-DP-p, amine salt, 

Dimethylamine-2-(2,4-dichlorophenoxy) propionate, Isooctyl 2-(2,4-dichlorphenoxy)propionate, 

Propionic acid, 2-(2,4-dichlorophenoxy)-, 2-ethylhexyl ester, and 2,4-DP-p, 2-ethylhexyl ester

(E. Evans and S. Recore, D415950, 11/07/2013).

HED has evaluated the available incident data and concludes that based on the low frequency 

and severity of incident cases reported for the active after mentioned ingredients in both IDS and 

SENSOR-Pesticides, 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 risk assessment.

8.0 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 Address 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 consumption, 

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 Continuing 

Survey of Food Intake by Individuals (CSFII) 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 adult 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 software and models that consider exposure to 
Page 11 of 30

bystanders and farm workers, as well as lifestyle and traditional dietary patterns among specific 

subgroups.

9.0 CUMULATIVE RISK ASSESSMENT

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 2,4-DP-p and any other substances and 2,4-DP-p does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that 2,4-DP-p 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 mechanism 

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.

10.0 HUMAN STUDIES

Past 2,4-DP-p risk assessments rely in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. 

Many such studies, involving exposure to many different pesticides, comprise generic pesticide 

exposure databases such as the Pesticide Handlers Exposure Database (PHED) and the 

Agricultural Reentry Task Force (ARTF) Database. EPA has reviewed all the studies supporting 

these multi-pesticide generic exposure databases, and has found no clear and convincing 

evidence that the conduct of any of them was either fundamentally unethical or significantly 

deficient relative to the ethical standards prevailing at the time the research was conducted. All 

applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 

CFR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on 

these studies.

11.0 DATA REQUIREMENTS

A subchronic inhalation toxicity study (OPPTS Guideline 870.3465) is needed based on the 

requirements of 40 CFR §158 by the decision of the HASPOC (12/04/13).

Residue data and toxicity data for 2,4-DP-p are not available to support agricultural uses on 

pasture feed to livestock. In the event that the registrants want to pursue uses on pasture (e.g. 

broadcast uses on federal rangeland) additional toxicity (see Appendix A.1.) and residue 

chemistry (OPPTS Guideline 860.1500 for field trials on pasture, 860.1300 for nature of residue, 

determination, and if necessary OPPTS Guideline 860.1480 to determine the residue level that 

may incur in livestock commodities) data requirements would apply. 

Turf Transferable Residue (TTR): In accordance with the updated Part 158 data requirements 

(2007), a TTR study is required for all occupational (e.g., sod farms, golf courses, parks, and 
Page 12 of 30

recreational areas) or residential turf uses. At this time, 2,4 DP-p does not have a dermal 

hazard/endpoint, therefore, chemical-specific TTR data are not necessary. 
Page 13 of 30

Appendix A: Toxicology Profile 

A.1 Toxicology Data Requirements

The requirements to support current uses except pasture are in the table below. These are the requirements (40 CFR 

158.500) for food use for 2,4-DP-p. Note that although there are no food uses of 2,4-DP-p, dietary exposure is 

assessed to consider residues in drinking water. Use of the new guideline numbers does not imply that the new 

(1998) guideline protocols were used.

Test Technical

Required Satisfied

870.1100 Acute Oral Toxicity............................................ 

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

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

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

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

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

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)................................... 

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

870.3200 21-Day Dermal.................................................. 

870.3250 90-Day Dermal.................................................. 

870.3465 90-Day Inhalation.............................................. 

yes

no

no

yes

yes

yes

yes

yes

NA2

no

870.3700a Developmental Toxicity (rodent)....................... 

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

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

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)................................... 

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

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

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

870.4300 Chronic/Carcinogenicity...................................... 

no1

no1

no1

no1

no1

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial......... 

870.5300 Mutagenicity—Gene Mutation - mammalian..... 

870.5375 Mutagenicity—Structural Chromosomal 

Aberrations...................................................... 

870.5385 Mutagenicity—Mammalian Bone Marrow 

Chromosomal Aberration Test.......................... 

870.5395 Mutagenicity— Mammalian erythrocyte micronucleus 

test............................................. 

yes

yes

yes

yes

yes

yes

yes 

yes

no3

yes

870.6100a Acute Delayed Neurotox. (hen)........................ 

870.6100b 90-Day Neurotoxicity (hen)............................... 

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

870.6200b 90-Day Neuro. Screening Battery (rat)............... 

870.6300 Developmental Neuro. ................................................ 

no

no

yes

yes

no

no

no

yes

yes

no

870.7485 General Metabolism......................................... 

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

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

yes

no

no 4

yes

no

no

1 Not required under the registered use patterns.

2 The 21-Day dermal study is sufficient to satisfy this requirement.

3 There are mutagenicity studies which evaluate both somatic and germinal cells, which is considered sufficient to 

satisfy CFR requirements.

4 HASPOC waived this requirement.
Page 14 of 30

The requirements to support uses on pasture and the current uses are in the table below. These are requirements (40 

CFR 158.500) for food use for 2,4-DP-p. Note that although there are no food uses of 2,4-DP-p, dietary exposure is 

assessed to consider residues in drinking water. Use of the new guideline numbers does not imply that the new 

(1998) guideline protocols were used.

Test Technical

Required Satisfied

870.1100 Acute Oral Toxicity............................................ 

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

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

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

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

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

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)................................... 

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

870.3200 21-Day Dermal.................................................. 

870.3250 90-Day Dermal.................................................. 

870.3465 90-Day Inhalation.............................................. 

yes

yes

yes

yes

yes

yes

yes

yes

NA1

no

870.3700a Developmental Toxicity (rodent)....................... 

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

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

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)................................... 

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

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

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

870.4300 Chronic/Carcinogenicity...................................... 

yes

yes

yes

yes

no

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial......... 

870.5300 Mutagenicity—Gene Mutation - mammalian..... 

870.5375 Mutagenicity—Structural Chromosomal 

Aberrations...................................................... 

870.5385 Mutagenicity—Mammalian Bone Marrow 

Chromosomal Aberration Test.......................... 

870.5395 Mutagenicity— Mammalian erythrocyte micronucleus 

test............................................. 

yes

yes

yes

yes

yes

yes

yes 

yes

no2

yes

870.6100a Acute Delayed Neurotox. (hen)........................ 

870.6100b 90-Day Neurotoxicity (hen)............................... 

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

870.6200b 90-Day Neuro. Screening Battery (rat)............... 

870.6300 Developmental Neuro. ................................................ 

no

no

yes

yes

no

no

no

yes

yes

no

870.7485 General Metabolism......................................... 

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

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

yes

no

no

3

yes

no

no

1 The 21-Day dermal study is sufficient to satisfy this requirement.

2 There are mutagenicity studies which evaluate both somatic and germinal cells, which is considered sufficient to 

satisfy CFR requirements.

3 HASPOC waived this requirement.
Page 15 of 30

A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile of 2,4-DP-p, 2,4-DP-p DMAS and 2,4-DP-p EHE (a)

Guideline 

No. Study Type

2,4-DP-p 2.4-DP-p DMAS 2,4-DP-p EHE

Results

Toxicity 

Category Results

Toxicity 

Category Results

Toxicity 

Category

870.1100 Acute Oral – Rat 567 mg/kg III 637 mg/kg III 825 mg/kg III

870.1200 Acute Dermal –

Rat

LD50 

>2000 

mg/kg

III >2000 

mg/kg III >2000 mg/kg III

870.1300 Acute Inhalation 

– Rat > 2.7 mg/L IV >5.28 mg/L IV >4.1 mg/L IV

870.2400

Primary Eye 

Irritation –

Rabbit

A severe 

eye irritant I NA NA

870.2500

Primary Skin 

Irritation –

Rabbit

A slight or 

mild irritant IV NA NA

870.2600

Dermal 

Sensitization –

Guinea Pig

Not a skin 

sensitizer

N/A A skin 

sensitizer

N/A A skin 

sensitizer

N/A

NA = Not available

Table A.2.2 Acute Toxicity Profile of 2,4-DP Technical a

Guideline 

No. Study Type MRID(s) Results

Toxicity 

Category

870.1100 Acute Oral – Rat 40955602 825 < LD50 < 1,470 mg/kg III

870.1200 Acute Dermal – Rat 40955603 LD50 > 4 g/kg III

870.1300 Acute Inhalation – Rat 41231201 LC50 > 7.4 mg/L IV

870.2400 Primary Eye Irritation –

Rabbit 40955605 a severe to corrosive ocular irritant I

870.2500 Primary Skin Irritation –

Rabbit 40955604 a mild to moderate dermal irritant III

870.2600 Dermal Sensitization –

Guinea Pig 40982202 skin sensitizer N/A

 a 2,4-DP technical (pc 031401) is a racemic mixture: 3 forms of 2,4-DP supported by registrants in the 2,4-DP-p 

Task Force are 2,4-DP-p (pc code 031402); 2,4-DP-p EHE (pc code 031465) and 2,4-DP DMAS (pc code 

031409)
Page 16 of 30

Table A.2.3 Acute Toxicity Profile of 2,4-DP-p Technical a

Guideline 

No. Study Type MRID(s) Results

Toxicity 

Category

870.1100 Acute Oral – Rat 42985308 567 mg/kg III

870.1200 Acute Dermal – Rat 42985309 LD50 >2000 mg/kg III

870.1300 Acute Inhalation – Rat 42985310 > 2.7 mg/L IV**

870.2400 Primary Eye Irritation 

– Rabbit 42985311 A severe eye irritant I

870.2500 Primary Skin Irritation 

– Rabbit 42985312 A slight or mild irritant IV

870.2600 Dermal Sensitization 

– Guinea Pig 43749701 Not a skin sensitizer N/A

a

 The acute inhalation study report provided EAD (equivalent aerodynamic diameter).

Table A.2.3. Acute Toxicity Profile of 2,4-DP-p EHE Technical

Guideline 

No. Study Type MRIDs # Results

Toxicity 

Category

870.1100 Acute Oral – Rat 42614602 824 mg/kg III

870.1200 Acute Dermal – Rat 42614604 >2000 mg/kg III

870.1300 Acute Inhalation – Rat 42937001 >4.1 mg/L IV

870.2400 Primary Eye Irritation 

– Rabbit 42729101 A mild eye irritant IV

870.2500 Primary Skin Irritation 

– Rabbit 42729103 A slight or mild irritant IV

870.2600 Dermal Sensitization 

– Guinea Pig

43749702 A skin sensitizer N/A

Table A.2.4. Acute Toxicity Profile of 2,4-DP-p DMAS Technical

Guideline 

No. Study Type MRIDs # Results

Toxicity 

Category

870.1100 Acute Oral – Rat 42614601 637 mg/kg III

870.1200 Acute Dermal – Rat 42614603 >2000 mg/kg III

870.1300 Acute Inhalation – Rat 42914501 >5.28 mg/L IV

870.2400 Primary Eye Irritation 

– Rabbit

Not 

submitted NA NA

870.2500 Primary Skin Irritation 

– Rabbit 42729102 A very slight irritant IV

870.2600 Dermal Sensitization 

– Guinea Pig 43749703 A skin sensitizer N/A
Page 17 of 30

Table A.2.2 Subchronic, Chronic, and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (Year)/ 

Classification/Doses

Results

870.3100 90-Day oral 

toxicity (rat)

00250351 (1981)

Acceptable/guideline

0, 100, 300, 1000, 3000 

ppm

(0, 5, 15, 50, 150 

mg/kg/day)

50/50 racemic mixture of 

2,4-DP

NOAEL = 15 mg/kg/day

LOAEL = 50 mg/kg/day based on:

changes in clinical chemistry and hematology 

parameters

Males

↑ ALP, total bilirubin, albumin and 

albumin/globulin ratio

↓ globulin

 

Females

↑ albumin/globulin ratio

↓ hematocrit and hemoglobin concentration, 

erythrocyte count, and globulin

870.3100 90-Day oral 

toxicity (rat)

00116494 (1981)

Acceptable/non-guideline

0, 100, 500, 2500 ppm

(0, 5, 25, 125 mg/kg/day)

50/50 racemic mixture of 

2,4-DP

NOAEL not observed

LOAEL = 5 mg/kg/day (lowest dose tested) 

based on:

↑ Kidney lesions (slight tubular nephrosis)

Incidence of slight tubular nephrosis: 

1/15, 5/15, 6/15, 4/15 in 0, low-, mid-, highdose males

0/15, 3/15, 1/15, and 2/15 in 0, low-, mid-, 

high-dose females 

25 mg/kg/day

liver lesions:

pronounced lobular pattern (♂ only) 

diffuse single cell degeneration (♀ only) 

125 mg/kg/day ♂ and ♀

↓ body wt., food consumption

changes in clinical chem, hematology, and 

urinalysis

liver lesions:

pronounced lobular pattern (♂ only) 

diffuse single cell degeneration (♀ only)

a dissociation-like appearance of the 

hepatocytes

too homogeneous cytoplasm of the hepatocytes
Page 18 of 30

Table A.2.2 Subchronic, Chronic, and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (Year)/ 

Classification/Doses

Results

870.3100 90-Day oral 

toxicity (rat)

41653801 (1987)

Acceptable/guideline

0, 100, 500, 2500 ppm

(0, 5, 25, 125 mg/kg/day)

2,4-DP-p

NOAEL = 5 mg/kg/day

LOAEL = 25 mg/kg/day based on: 

↑ Relative kidney wt in males (dose-related)

At 125 mg/kg/day

↓ body weight

↑ absolute liver wt

↑ relative liver and kidney wt

Alterations in blood chemistry

870.3100 90-Day oral 

toxicity (mouse)

43103201 (1993)

Acceptable/guideline

0, 100, 1000, 2500 ppm

(♂: 0, 20, 224, 683 

mg/kg/day)

(♀: 0, 33, 380, 1043 

mg/kg/day)

2,4-DP-p

NOAEL = 224 mg/kg/day

LOAEL = 683 mg/kg/day based on: 

↓ Body weight, body weight gain, and food 

efficiency

Clinical chemistry parameters: 

↑ ALP

↑ cyanide-insensitive palmitoyl-CoAoxidation

Histopathological findings:

eosinophilic hepatocytes 

marked cytoplasmic eosinophilia in renal 

tubule cells
Page 19 of 30

Table A.2.2 Subchronic, Chronic, and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (Year)/ 

Classification/Doses

Results

870.3100 

and 

870.6200

Combined 

subchronic oral 

toxicity and 

neurotoxicity (rat)

43915101 (1995)

Acceptable/guideline

0, 100, 500, 2000 ♂/3000 

♀ ppm

(♂: 0, 7, 35, 144 

mg/kg/day)

(♀: 0, 8, 42, 245 

mg/kg/day)

2,4-DP-p

NOAEL = 35 mg/kg/day

LOAEL = 144 mg/kg/day based on: 

↓ Body wts, body wts gains, food consumption 

↑ Water consumption

↑ Liver and relative brain wt (♀), relative liver 

and kidney wt (♂/♀)

↑ ALP, ALT (♀), creatinine

 (♂), total bilirubin (♂)

↓ globulin, triglyceride, cholesterol, 

↑ WBC count, monocyte, polymorphonuclear neutrophil counts (♀)

↑ urine volume and presence of RBCs (♀)

↓ urine specific gravity

↓ RBC, hemoglobin, hematocrit

Liver microscopic findings (♂/♀):

Absence of fat storage 

Cytoplasmic eosinophilia (moderate to 

severe )

Granular cytoplasm (moderate to 

severe) 

Slight central hypertrophy (♀ only)

FOB: 

↓ fore- and hindlimb grip strength (♀)

motor activity:

effects were not treatment-related 

870.3150 90-Day oral 

toxicity (dog)

43462601 (1994)

Acceptable/guideline

0, 25, 175, 525 ppm

(♂: 0, 0.7, 5.1, 15.7 

mg/kg/day)

(♀: 0, 0.8, 5.8, 18.1 

mg/kg/day)

2,4-DP-p

NOAEL = 5.1 mg/kg/day

LOAEL = 15.7 mg/kg/day based on:

Frequent diarrhea (up to 11 times) occurred

in 4/5 males and 2/5 females during 1 to10

weeks.

↓ red blood cell count, triglyceride levels
Page 20 of 30

Table A.2.2 Subchronic, Chronic, and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (Year)/ 

Classification/Doses

Results

870.3200 21-Day dermal 

toxicity (rat)

43706401 (1995)

Acceptable/guideline

0, 15, 150, 1000 

mg/kg/day

2,4-DP-p EHE

(93.2% a.i. as EHE; 65% 

a.i. as acid)

Systemic

NOAEL = 1000 mg/kg/day (limit dose)

LOAEL = Not observed

Dermal

NOAEL = 120 mg/kg/day

LOAEL = 1000 mg/kg/day based on:

Sporadic skin irritation at 1000 mg/kg/day. No 

irritation was seen after cessation of treatment

870.3200 21-Day dermal 

toxicity (rat)

43634401 (1988)

Acceptable/guideline

0, 12, 120, 1000 

mg/kg/day

2,4-DP-DMAS

(75.3% a.i. as DMAS salt; 

60% a.i. as acid)

Systemic

NOAEL = 1000 mg/kg/day (limit dose)

LOAEL = Not observed

Dermal

NOAEL = 120 mg/kg/day

LOAEL = 1000 mg/kg/day based on:

Sporadic skin irritation at 1000 mg/kg/day. No 

irritation was seen after cessation of treatment

870.3200 21-Day dermal 

toxicity (rabbit)

42914301 (1993)

Acceptable/guideline

0, 10, 100, 1000 

mg/kg/day

2,4-DP-p

Systemic

NOAEL = 1000 mg/kg/day (limit dose)

LOAEL = Not observed

Dermal

NOAEL = Not determined

LOAEL = 10 mg/kg/day based on:

Induced slight erythema (1/5 males and 1/5 

females). Microscopically, minimal diffuse 

acanthosis (3/5 females) accompanied by 

minimal diffuse inflammatory cells in the 

superficial dermis (1 female). 

100 and 1000 mg/kg/day induced

well defined dermal irritation (erythema, 

edema, beige staining of the treatment site and 

sloughing)

870.3250 90-Day dermal 

toxicity (species)

NA NA

870.3465 90-Day inhalation 

toxicity (species)

NA NA
Page 21 of 30

Table A.2.2 Subchronic, Chronic, and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (Year)/ 

Classification/Doses

Results

870.3700a Prenatal 

developmental(rat

)

42845805 (1993)

Acceptable/guideline

0, 20, 80, 160 mg/kg/day

2,4-DP-p

Interim report is found in 

MRID 42615001 (1992)

Maternal NOAEL = 20 mg/kg/day

LOAEL = 80 mg/kg/day based on:

↓ body wt., body wt. gain, food consumption

Developmental NOAEL = 80 mg/kg/day

LOAEL = 160 mg/kg/day based on:

↓ fetal body wt

↑ incidence of incompletely ossified sternebra 

↑ incidence of rudimentary cervical ribs

870.3700b Prenatal 

developmental(rab

bit)

42845804 (1993)

Acceptable/guideline

0, 20, 50, 100 mg/kg/day

2,4-DP-p

Maternal NOAEL = 50 mg/kg/day

LOAEL = 100 mg/kg/day based on:

↑ Clinical signs (reduced general state, lateral 

or abdominal position and no defecation)

↓ Body wt. gains (-69%) , food consumption 

(-14%) during dosing period

Ulceration of the stomach mucosa.

Developmental NOAEL = 50 mg/kg/day

LOAEL = 100 mg/kg/day based on:

↑ Incidence of 13th accessory rib(s) (9 in 6 

litters vs. 1)

870.3800 Reproduction and 

fertility effects

(rat)

46721401 (1992)

Acceptable/guideline

0, 80, 400, 2000 ppm

(♂: 0, 8.0, 40.1, 219.6 

mg/kg/day)

(♀: 0, 8.7, 43.0, 233.0 

mg/kg/day)

Racemic (50:50) mixture 

of 2,4-DP

Recent range finding 

study for 2,4-DP-p, MRID 

46591904 (2001) is 

referenced in this DER

Parental/Systemic NOAEL = 40 mg/kg/day

LOAEL = 219 mg/kg/day based on:

Mortality and clinical signs (poor maternal 

care); decreased body weights, body weight 

gains, and food consumption; increased water 

consumption; and mild effects on the liver 

(increased weights, hypertrophy of the 

periacinar hepatocytes, focal necrosis, and bile 

duct hyperplasia) and kidneys [increased 

weights, foci of basophilic (regenerating) 

tubules, focal hyperplasia of the transitional 

epithelium and papillary/medullary calculi]. 

Reproductive NOAEL = 40 mg/kg/day

LOAEL = 219 mg/kg/day based on:

Decreased mating, fertility, and gestation 

indices. Severely decreased live birth index.

Offspring NOAEL = 40 mg/kg/day

LOAEL = 219 mg/kg/day based on:

Severely decreased viability indices and 

retarded growth and development.

870.4100a Chronic toxicity

(species) NA NA
Page 22 of 30

Table A.2.2 Subchronic, Chronic, and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (Year)/ 

Classification/Doses

Results

870.4100b Chronic toxicity 

(dog)

44638401 (1997)

Acceptable/guideline

0, 120, 240, 720 ppm 

(♂: 0, 3.5, 7.0, 22.2 

mg/kg/day)

(♀: 0, 3.9, 7.7, 26.1 

mg/kg/day) 

2,4-DP-p

NOAEL = 7 mg/kg/day

LOAEL = 22 mg/kg/day based on:

↓ Body weight gain changes (16%lower than 

controls) in females 

Microscopic changes in one male 

--epididymides (chronic inflammation of the 

epididymides with slight amounts of cellular 

debris in the lumen, moderate flattening of the 

epididymal duct epithelium, and slight 

oligospermia)

-- kidneys (slight degenerative kidney tubular 

vacuolization)

--prostate gland (moderate chronic 

inflammation)

870.4200b Carcinogenicity

(mouse)

44900801 (1996) and 

44888201 (1998)

Acceptable/guideline

0, 40, 400 ppm 

(♂: 0, 6, 59 mg/kg/day)

(♀: 0, 8, 78 mg/kg/day) 

2000 ppm males and 

3500 ppm females for 9 

months

0 or 800 ppm (equivalent 

to 0 and 143 mg/kg/day) 

for up to 18 months

2,4-DP-p

NOAEL = 6 mg/kg/day

LOAEL = 59 mg/kg/day based on:

Decreased body weights, body weight gains, 

food consumption, and food efficiency in 

males, increased pigment in renal tubuli in 

males, increased renal calcification in both 

sexes, and increased kidney weight and chronic 

nephropathy in females. 

Treatment related increase in tumor incidence 

was not found. Dosing was considered 

adequate based on decreases in body weights, 

body weight gains, food consumption, food 

efficiency, and nephrotoxicity.

(no) evidence of carcinogenicity

870.4300 Combined chronic 

toxicity/

carcinogenicity 

(rat)

00146394 (1984)

Acceptable/guideline

0, 100, 300, 1000, 3000 

ppm 

(♂: 0, 3.6, 11.0, 36.5, 116 

mg/kg/day)

(♀: 0, 4.4, 13.1, 45.7, 147 

mg/kg/day) 

2,4-DP-p

NOAEL = 3.6 mg/kg/day

LOAEL = 11 mg/kg/day based on:

↓ Specific gravity and protein in urine

Treatment related increase in tumor incidence 

was not found.

In 36.5 m/k/d groups, 

↓ urine specific gravity and protein

↑ lipofuscin deposition in the proximal tubular 

cells of the kidneys (both sexes). 

↑ alkaline phosphatase and SGPT
Page 23 of 30

Table A.2.2 Subchronic, Chronic, and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (Year)/ 

Classification/Doses

Results

Genetic 

Toxicity 

870.5100

Bacterial reverse 

mutation test

42985313 (1990)

Acceptable/guideline

5-500 μg/plate ±S9

2,4-DP-p

Not genotoxic

Genetic 

Toxicity 

870.5300

In vitro 

mammalian cell 

gene mutation test

42985315 (1990)

Acceptable/guideline

Trial 1: 6.4 - 4000 μg/mL 

±S9

Trial 2: 7.2 - 4500 μg/mL 

±S9

2,4-DP-p

Not genotoxic

Genetic 

Toxicity 

870.5375

In vitro 

mammalian 

chromosome 

aberration test

40581901 (1988)

Acceptable/guideline

75.1, 100, 501, 751, 1000 

μg/ml without S9;

1000, 1500, 2000, 2500, 

3000 μg/ml with S9

racemic (50:50) mixture 

of 2,4-DP

Positive in the presence of S9 and only at 

cytotoxic concentrations

Negative in the absence of S9

Genetic 

Toxicity 

870.5375

In vitro 

mammalian 

chromosome 

aberration test

42985314 (1990)

Acceptable/guideline

8, 40, 200, 1000, 5000 

μg/mL (±S9)

2,4-DP

Negative for clastogenic activity

Genetic 

Toxicity 

870.5375

In vitro 

mammalian 

chromosome 

aberration test

43189401 (1994)

Acceptable/guideline

10, 30, 100, 300 μg/mL 

(±S9)

2,4-DP-p

Negative response in the absence and presence 

of S9

Genetic 

Toxicity 

870.5395

Mammalian 

erythrocyte 

micronucleus test

42985316 (1991)

Acceptable/guideline

4, 20, 100 mg/kg

2,4-DP-p

Negative for clastogenic or aneugenic effects

Genetic 

Toxicity 

870.5550

Unscheduled 

DNA synthesis in 

mammalian cells 

in culture

44900802 (1994)

Acceptable/guideline

50, 200, 500 mg/kg

2,4-DP-p

Negative – did not induce UDS in the 

hepatocytes of treated rats
Page 24 of 30

Table A.2.2 Subchronic, Chronic, and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (Year)/ 

Classification/Doses

Results

Genetic 

Toxicity 

870.5915

In vivo sister 

chromatid 

exchange assay

41646803 (1985)

Acceptable/guideline

47, 280, 1780 mg/kg

Racemic (50:50) mixture 

of 2,4-DP

Positive for induction of SCE’s in Chinese 

hamsters

870.6200a Acute 

neurotoxicity 

screening battery

43770901 (1995)

Acceptable/guideline

0, 125, 250, 400, 500 

mg/kg

2,4-DP-p

NOAEL = 125 mg/kg/day

LOAEL = 250 mg/kg/day based on:

FOB findings 

Males and females

abnormal body posture (prone/lateral), 

palpebral

closure, hypoactivity/apathy, ataxia,

hypothermia, decreased number of rearings

Males

increased limb splay, retarded righting 

response,

decreased hindlimb grip strength, increased

landing foot splay

↓ motor activity
Page 25 of 30

Table A.2.2 Subchronic, Chronic, and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (Year)/ 

Classification/Doses

Results

870.6200b 

and 

870.3100

Combined 

subchronic oral 

toxicity and 

neurotoxicity (rat)

43915101 (1995)

Acceptable/guideline

0, 100, 500, 2000 ♂/3000 

♀ ppm

(♂: 0, 7, 35, 144 

mg/kg/day)

(♀: 0, 8, 42, 245 

mg/kg/day)

2,4-DP-p

NOAEL = 35 mg/kg/day

LOAEL = 144 mg/kg/day based on: 

↓ Body wts, body wts gains, food consumption 

↑ Water consumption

↑ Liver and relative brain wt (♀), relative liver 

and kidney wt (♂/♀)

↑ ALP, ALT (♀), creatinine

 (♂), total bilirubin (♂)

↓ globulin, triglyceride, cholesterol, 

↑ WBC count, monocyte, polymorphonuclear neutrophil counts (♀)

↑ urine volume and presence of RBCs (♀)

↓ urine specific gravity

↓ RBC, hemoglobin, hematocrit

Liver microscopic findings (♂/♀):

Absence of fat storage 

Cytoplasmic eosinophilia (moderate to 

severe )

Granular cytoplasm (moderate to 

severe) 

Slight central hypertrophy (♀ only)

FOB: 

↓ fore- and hindlimb grip strength (♀)

motor activity:

effects were not treatment-related 

870.6300 Developmental 

neurotoxicity NA NA

870.7485 Metabolism and 

pharmacokinetics

(rat)

116493 (1978) 

Acceptable/non-guideline

single oral gavage dose 

(117 mg/kg) or 14-day 

repeated oral doses at 1 

mg/kg

2,4-DP

Total radioactivity recovered within 4 days 

after dosing: 85-90% of dose.

Urine accounted for 74-82% of dose.

Highest conc. of dichlorprop derived

radioactivity was found in kidneys.

No radioactivity in expired air.

Urine:

 Major component is parent (75% of 

dose)

Feces:

 Metabolites were not analyzed
Page 26 of 30

Table A.2.2 Subchronic, Chronic, and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (Year)/ 

Classification/Doses

Results

870.7485 Metabolism and 

pharmacokinetics

(rat)

44187601 (1996) 

Acceptable/guideline

single oral gavage dose (5 

or 100 mg/kg) or 14-day 

repeated oral doses at 5 

mg/kg

2,4-DP-p

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

44187602 (1996) 

Acceptable/guideline

single oral gavage dose 5 

mg/kg

2,4-DP-p-DMAS and 2,4-

DP-p EHE

Total radioactivity recovered within 5 days 

after dosing: 91-100% of dose.

Urine accounted for 87-96% of dose.

Urine and feces:

 Major component in urine is parent

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

2,4-DP-p-DMAS and 2,4-DP-p-2EHE

Total radioactivity recovered within 7 days 

after dosing: 91-96% of dose.

Urine accounted for 83 of dose.

Urine:

 Major component is 2,4-DP-p

870.7600 Dermal 

penetration (rat)

44229301 (1997)

Unacceptable/guideline

2,4-DP-p-DMAS and 

2,4-DP-p EHE

Test material migrated from the application site 

to the covering material in an unpredictable 

manner throughout the exposure duration thus 

making it impossible to determine the actual 

dose.

870.7800 Immunotoxicity NA NA
Page 27 of 30

Appendix A.3. 2,4-DP-p Endpoints and Doses for Risk Assessment

Table A.3.1. Toxicological Doses and Endpoints for 2,4-DP-p for Use in Dietary and Occupational Human 

Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty 

Factors

RfD/Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

All 

populations

including 

infants and 

children 

NOAEL = 

5.1 

mg/kg/day

UFA = 10x

UFH = 10x

aRfD = 0.05 

mg/kg/day

90-Day Oral Toxicity study in Dogs (MRID 

43462601)

LOAEL = 15.7 mg/kg/day based on frequent 

diarrhea in 4/5 males and 2/5 females during 

weeks 1-10

Chronic 

Dietary

All 

populations

including 

infants and 

children 

NOAEL = 

3.6 

mg/kg/day

UFA = 10x

UFH = 10x

cRfD = 0.036 

mg/kg/day

2-year Chronic Toxicity Study in rats (MRID 

146394)

LOAEL = 11 mg/kg/day based on decreases in 

specific gravity and protein in urine. Considering 

the kidney toxicity [increases in lipofuscin

deposition in the proximal tubular cells of the 

kidneys] seen in the higher dose levels, this effect 

was considered treatment-related. Kidney effects 

were also observed in the following studies: 

subchronic toxicity study in rats at 5 

mg/kg/day (increased incidence of slight 

tubular nephrosis), 

1-year chronic study in dogs at 22 

mg/kg/day (slight degenerative kidney 

tubular vacuolization),

subchronic neurotoxicity study in rats at 

144 mg/kg/day (decrease in urine specific 

gravity),

2-generation reproduction study in rats at 

219 mg/kg/day [increased weights, foci of 

basophilic (regenerating) tubules, focal 

hyperplasia of the transitional epithelium 

and papillary/medullary calculi] 

Incidental 

Oral ShortTerm (1-30 

days)

NOAEL = 

5.1 

mg/kg/day

UFA = 10x

UFH = 10x

Residential 

LOC for 

MOE = 100

90-Day Oral Toxicity study in Dogs (MRID 

43462601)

LOAEL = 15.7 mg/kg/day based on frequent 

diarrhea in 4/5 males and 2/5 females during 

weeks 1-10

Incidental 

Oral 

IntermediateTerm (1-6 

months)

NOAEL = 

3.6 

mg/kg/day

UFA = 10x

UFH = 10x

Residential 

LOC for 

MOE = 100

2-year Chronic Toxicity Study in rats (MRID 

146394)

LOAEL = 11 mg/kg/day based on decreases in 

specific gravity and protein in urine. Considering 

the kidney toxicity [increases in lipofuscin 

deposition in the proximal tubular cells of the 

kidneys] seen in the higher dose levels, this effect 

was considered treatment-related. (See chronic 

dietary RfD discussion) 
Page 28 of 30

Table A.3.1. Toxicological Doses and Endpoints for 2,4-DP-p for Use in Dietary and Occupational Human 

Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty 

Factors

RfD/Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Dermal Shortand 

IntermediateTerm (1-30 

days; 1-6 

months)

No quantification is required because no hazard was identified. 

Inhalation 

Short-Term 

(1-30 days)

NOAEL = 

5.1 

mg/kg/day

UFA = 10x

UFH = 10x

Residential/

Occupational 

LOC for 

MOE = 100

90-Day Oral Toxicity study in Dogs (MRID 

43462601)

LOAEL = 15.7 mg/kg/day based on frequent 

diarrhea in 4/5 males and 2/5 females during 

weeks 1-10

Inhalation 

IntermediateTerm (1-6 

months)

NOAEL = 

3.6 

mg/kg/day

UFA = 10x

UFH = 10x

Residential/

Occupational 

LOC for 

MOE = 100

2-year Chronic Toxicity Study in rats (MRID 

146394)

LOAEL = 11 mg/kg/day based on decreases in 

specific gravity and protein in urine. Considering 

the kidney toxicity [increases in lipofuscin 

deposition in the proximal tubular cells of the 

kidneys] seen in the higher dose levels, this effect 

was considered treatment-related. (See chronic 

dietary RfD discussion)

Cancer (oral, 

dermal, 

inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant tumor 

increases in two adequate rodent carcinogenicity studies.

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). MOE = margin of exposure. LOC = level of 

concern.
Page 29 of 30

Appendix B: Chemistry

1.0 Identification of Active Ingredient

TABLE B.1.1 Test Compound Nomenclature—2,4-DP-p

Chemical Structure

Empirical Formula C9H8Cl2O3

Common name 2,4-DP-p or dichlorprop

IUPAC name R-2-(2,4-dichlorophenoxy)propionic acid

CAS name (2R)-2-(2,4-dichlorophenoxy)propionic acid

CAS Registry Number 15165-67-0

PC Code 031402

Chemical Class Phenoxypropionic herbicide

TABLE B.1.2 Test Compound Nomenclature—2,4-DP-p DMAS1

Chemical Structure

Empirical Formula C9H8Cl2O3. C2H7N

Common name 2,4-DP-p, dimethylamine salt

IUPAC name (R)-2-(2,4-Dichlorophenoxy)propanoic acid, dimethylamine salt

CAS Registry Number 104786-87-0

PC Code 031403

1 The 2,4-DP dimethylamine salt (racemic mixture; PC Code 031419; CAS No 53404-32-3) also has registered uses 

that are being considered under this registration review schedule.
Page 30 of 30

TABLE B.1.3 Test Compound Nomenclature-2,4-DP-p-2EHE

Chemical Structure

Empirical Formula C17H24Cl2O3

Common name 2,4-DP,2-ethylhexyl ester

IUPAC name (R)-(2,4-Dichlorophenoxy)propanoic acid, 2-ethylhexyl ester

CAS Registry Number 865363-39-9

PC Code 031465

2.0 Physical and Chemical Properties

TABLE B.2 Physicochemical Properties for 2,4-DP-p

Parameter Value Reference

Molecular Weight 235.1 46591916; Cornell University 

Cooperative Extension PMEP

Melting point/range 122.5-124.5° C Comb 2002, MRID 45698103

Density 1.42 g/ml

Water solubility (20°C) 590 mg/L 46591916

Solvent solubility (temperature not 

specified)

Highly soluble in acetone, benzene, 

carbon tetrachloride, diesel oil and 

kerosene

Henry’s Constant 2.43E-10 atm m3/mol 46591916

Vapor pressure (25°C) 4.65E-7 torr 46591916

Octanol/water partition coefficient, 

logPOW (25°C)

1.029 at pH 5

-0.562 at pH 7

-0.873 at pH 9

Cameron et al. 1992; MRID 

42916202

pKa 3.67 EFSA 2006