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



### MEMORANDUM

Date: February 28, 2014 OFF IC E OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### SUBJECT: MCPP, MCPP-p (acid), M CPP -p DMAS, and MCPP

- p potassium salt, Hum an H ealt h Assessmen t Seep i ng Document in Support of R eg istra t ion R eview.

PC Code: 0 3150 I
, 3 1 503, 031519

, 031 52 0

, 129046 and 19046 DP Barcode: D41676 1
Decision No.: 4859 1 7 Registration No .: NA Petition Nos.: NA Regulatory Action : Regi s tration Review Ri s k Assess T ype : Scoping Document CAS

. : 16484

- 77 -8

, 66423-09-4,66423

- 05

- 0

, 7085-19-0

TXR No .: NA. MRID No. : 44655702

, 4 4 655703 an d 45033101



### FROM:

## ~L~ Seyed Ta d ayo n , Risk**Ass esso** **~** Li nda Taylor

, Ph

. D
., T oxico l ·

### ~**~c._** P eter Sa voia

, Chemist 

# -0
Ri sk Assessment Br anch

# J~d V II ")

THRU: H ealth Effects Di visi on (7509P) Office of Pesticide Program s



### Michael. S. Metzger
, Branch Chief/ 

# J 

# W.

Rt sk A ssess ment Branch 

# v and 

# viHvf::.-4..

. Health Effects Division (7509P) "'-- · Offic e of Pesticide Pro grams



### TO : Kaitlin K e ller, Chemical Review Manager Pe st i cide R e-e valuation Divi s ion (7508 P ) Offi ce of Pesticide Pro grams

EXECUTIVE SUMMARY 

# L{r

-

1

The H E D R egis tr ation Rev i ew team has eva lu ated t he most recent human h e alth assessment s a n d database for the herbic i de Mecoprop. Current registrations ofMCPP and M C PP-p i ncl ud e the aci d forms, dimeth ylam in e sa l ts, ethylhexy l esters, and potass ium salts. At t h e present, the MC PP-p T ask Force is s upporting MCPP

- p (ac id ), MCPP

- p dimeth y l am in e (MC PP-p DM S),

a nd MC PP- p potas sium. Meco prop

- p ( MCPP-p ) i s a member ofthe chlo r op h enoxy class of herbicides. It i s the enr ich e d i somer form ( R i so m er) while mecop r op (MC PP ) is a 50:50 r acemic mixture of the dextro ( R) and l evo (S) isomer s.

Pag e 1 of2 1

### HED has considered the most recent human-health 

### risk assessments for MCPP-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 li terature 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 b een published.

MCPP-p is used in combination with other herbicides for postemergence broadleaf weed and brush control. It is used primarily on turf (i.e. lawns and golf courses) and sod farms with smaller quantities used on non-turf areas such as rights-of way. T h e commercial and agricu l tural products are genera ll y formulated as liquid s and granu l ar formulations. The residential products

are typically formulated as granular weed and feed formulations, liquid concentrates, or Ready

to-Use sprays. One MCPP-p DMS residential product (EPA Reg. No. 228-190) is formulated as

an aerosol spray can

. There are no registered food uses or established or pending tolerances
at this time.

T oxicity/Hazard The toxicity database for mecoprop

- p (MCPP -p ) is incomplete. A 28-day inha l ation toxicity study is required. All other toxicity data requirements are satisfied for MCPP

- p when supplemented with the mecoprop (MCPP) databa se. Upon receipt of the MCPP-p inhalation study, HED will evaluate the toxicity database for character i zation of potential developmental, reproductive

, carcinogenetic, mutagenic, neurotoxic, and immunotoxic effects.

Dietary Exposure Since MCPP-p products are used outdoors on turf and for woody plant control in non-crop areas, the dietary risk assessment considers only drinking water exposures (no food use). In the most
recent risk assessment , acute and chronic risks were below the HED l evel of concern (0341965; 07/26/2007). Updated dietary exposu re assessments for MCPP -p may be necessary to consider the most recent drinking water consumption data, and to include newly estimated drinking water concentrat i ons. In add i tion, i f new points of departures are selected a revised dietary assessment may be needed.

Residential Exposure The residential exposure database is adequate to support registration review for MCPP-p. In the last risk assessment (D341965; 07/26/2007), the calculated risk did not exceed the l evel of

concern (MOE> 1 00). Residential hand l er sce narios may need to be updated in the registra t i on review assessment, reflecting any updated doses and endpoints for risk assessment, HED's Res id ent i al SOPs, and current po li c i es.

Previous residential post-app li cation assessments, which assessed incidental oral exposures only, relied on default assumptions for turf transferrable residues following treatments

. Chemicalspecific TTR data are not required to assess exposure to residues following MCPP -p treatments. For the residential postapplicat i on assessment, incidental oral exposures will be updated in the registration rev i ew assessment, reflecting any updated doses and endpoints for risk assessment, HED 's Residential SOPs, and current policies.

Page 

### 2 of21

### Page 3 of 21

Aggregate Assessment In the most recent risk assessment, HED provided updated aggregate exposure and risk estimates for drinking water and r esidential exposures. The exposure scenarios aggregated are: chronic drinking water with short

- term incidental oral ingestions in infants and children; and chronic drinking water with short

- term inhalation of adult residential handlers. The combined MOE’s for the scenarios examined were below HED’s level of concern (i.e. MOE > 100). Aggregate exposures of MCPP

- p will be revised during registration review to consider new dietary and residential exposures estimates.

Occupational Exposure The occupational exposure database is adequate to support registration review for MCPP

- p . No dermal hazard has been identified for MCPP

- p for short

- or intermediate

- term exposure scenarios ; therefore

, post

- application exposure and risks were not quantifie d for those exposure durations. Long

- term dermal exposure to MCPP

- p is unlikely due to the use pattern of MCPP

- p , typically applied once or twice per season. The MOEs for occupational handler exposures were calculated for short/intermediate term inhalation exposures using standard assumptions and unit exposure data. In the last risk assessment (D34 1965 ; 0 7 / 26 /2007 ), the calculated occupational handler risk did not exceed the level of concern (MOE>100). Updated occupational handler assessments may be require d during registration review reflecting any updated exposure methodology and endpoints for risk assessment. In addition, the handheld equipment applications to turf scenarios need to be updated during registration review.

1.0 F ORMULATIONS AND 

### U SE 

### P ATTERNS



### HED used the OPPIN data base to identify all uses of the MCPP

- p forms and the number of associated end use product labels. The acid and dimethylamine (DMA) forms have the most products. The commercial products are generally formulated as liquids and standard granules. Two acid products (2217

- 784 and 2217

- 814) are wettable powders and are labeled for professional applicator use on turf. The residential products are typically formulated as granular weed and feed formulations or as liquids in concentrates or R eady

- to

- U se sprays. One dimethylamine ( DMA ) residential product (228

- 190) is formulated as an aerosol spray can

.

MCPP

- p is used in combination with other herbicides for postemergence broadleaf weed and brush control. It is used primarily on turf (i.e. lawns and golf courses) and sod farms with smaller quantit ies used on non

- turf areas such as rights

- of way. There are no registered food uses or established or pending tolerances at this time.

Agricultural Uses

None.

Non

- Agricultural and Residential Uses

MCPP

- p is registered for use on lawns, recreational t urf, sports fields, sod farms, roadsides, and rights

- of

- way.

### Page 4 of 21

2.0 H AZARD 

### I DENTIFICATION 

### /T OXICOLOGY



### Hazard Identification/Toxicology

MCPP

- p is a member of the chlorophenoxy class of herbicides that function by mimicking the action of auxins, plant growth hormones.

The toxicity database for mecoprop

- p (MCPP

- p) is incomplete. A 28

- day inhalation toxicity study is required. All other tox icity data requirements are satisfied for MCPP

- p when supplemented with the mecoprop (MCPP) database. Upon receipt of the MCPP

- p inhalation study, HED will evaluate the toxicity database for characterization of potential developmental, reproductive, carcin ogenetic, mutagenic, neurotoxic, and immunotoxic effects.

MCPP

- p is the enriched isomer form (R isomer), whereas MCPP is a 50:50 racemic mixture of dextro (R) and levo (L) isomers. MCPP

- p (acid) is reported to be the more herbicidally

- active compound. I n metabolism studies in rats, MCPP

- p and the ester ( MCPP

- p

- 2

- EHE) and amine salt (MCPP

- p

- DMA) forms were rapidly absorbed and eliminated mainly in the urine; no bioaccumulation occurred. For each compound, the major metabolite is MCPP

- OH.

The major targ et organs are the kidney and liver. Kidney toxicity is manifested as increased kidney weight (rats and mice) and chronic nephropathy in mice. Liver toxicity is manifested as increased liver weights, increased liver enzymes, and microscopic changes in rats and mice. The effects are consistent across time and species and do not appear to progress over time. Although absorption and distribution of chlorophenoxy herbicides and other organic acids are similar across all mammalian species evaluated, the decreased capacity of the dog to eliminate organic acids results in higher blood levels and a longer elimination half

- life relative to those found in the rat and other mammalian species. Consequently, effects are seen at lower dose levels in the dog than in the ra t. Because of this difference and because human metabolism is more similar to rats than dogs , the rat is a better predictor of the potential toxicity of MCPP

- p in humans than the dog, and doses and endpoints from rat studies were used in all MCPP

- p risk a ssessments.

Developmental toxicity was not observed in the rabbit following exposure to MCPP

- p and MCPP. Developmental toxicity was observed in the rat at the same dose level where maternal toxicity was observed following exposure to MCPP

- p but in the absence of maternal toxicity following exposure to MCPP. Reproductive toxicity was not observed in the rat in the MCPP

- p 1

- generation reproduction study. The main effect in the reproduction study was decreased implantations resulting in a decreased number of pups born and a decrease in male pup body weight at weaning at a dose that also caused maternal toxicity (decreased body weight). The acute neurotoxicity study results indicated that MCPP

- p produced changes in functional observation battery (FOB) param eters (closed eye lids, prone body position, hypoactivity), ataxia, increased foot splay, and decreased motor activity. However, no neurotoxic effects were seen in the subchronic neurotoxicity study with MCPP

- p. Histopathological changes were not found in either of the neurotoxicity studies.

### Page 5 of 21

MCPP

- p is classified as “suggestive of carcinogenicity, but not sufficient to assess human carcinogenic potential” by the oral route of exposure. This is based on the occurrence of liver tumors in one sex (female) of a single species (mouse) following exposure to MCPP

- p; there is
no treatment

- related increase in tumor incidence in rats of either sex following exposure to MCPP. Additionally, MCPP

- p was not found to be mutagenic in either bacteria or cultured cells. The re is no concern for immunotoxicity. MCPP

- p is not acutely toxic by the oral, dermal, and inhalation routes of exposure based on lethality studies. It is a severe eye irritant but not a dermal irritant or dermal sensitizer.

The HASPOC determined that a 28

- day inhalation toxicity study is required to better estimate risk for occupational inhalation exposure due to the potential for repeated inhalation exposure to aerosolized formulations of MCPP

- p , and based on the portal

- of

- entry findings observed in t he inhalation studies on other chlorophenoxy compounds, (TXR No. 0056865, dated 1/7/14).

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

- p. The HASPOC determined that the immunotoxicity study for MCPP

- p is not required since the target organs of MCPP

- p are the kidneys and liver; the toxicity profile provides no indication of toxicity to the immune system; and the PODs selected for overall risk assessments is based on the most sensitive endpoints and will be protective of any potential immunotoxicity TXR No. 0056865, dated 1/7/14).

The acute and subchronic/chronic toxicity profile tables for MCPP, MCPP

- p, MCPP

- p

- DMA, and MCPP

- p

- 2

- EHE are included in APPENDIX A , Attachment 1 . Toxicity endpoints, PODs, and UF/SFs were selected for oral and inhalation exposure pathways for the Human Health Risk Assessment conducted in 2007 (D341965), and these are presented in Attachment 2 ( Table A 2 .1 and Table A 2.2 ).

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

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

Conclusions: The toxicity data base for MCPP

- p is considered incomplete. A repeat dose inhalation toxicity study is required. All other toxicity data requirements are satisfied for MCPP

p. Once the inhalation toxicity study has been received and reviewed and considered in light of current policies and procedures, its’ impact on the endpoints, PODs, and UF/SFs for the inhalation exposure risk assessment s will be considered d uring registration review.

3.0 D IETARY 

### E XPOSURE



### There is no registered food or feed uses for MCPP

- p products , and thus no food

- related dietary risk assessments were conducted. However, since MCPP

- p

- 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), the risk assessment considers drinking water exposures. In the most recent assessment ( J. Hetrick, 6/26/2006, D322772 ) , ground water residues we re low in comparison to surface water.

### Page 6 of 21

The conservative screening

- level drinking water assessment for surface water predicted acute and chronic EDWCs using the Tier II PRZM

- EXAMS

- Index Reservoir model for uses on turf

, the use resulting in the highest E DWCs. Acute and chronic dietary exposure estimates were below the HED level of concern (i.e. < 100% of the acute and chronic population adjusted dose) for the general population and all population subgroups.

Conclusions: D ietary exposure assessments f or MCPP

- 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 (WWEA) , and to include newly estimated drink ing water concentrations. In addition, if new endpoints are selected a revised dietary assessment may be needed

.

4.0 R ESIDENTIAL 

### E XPOSURE



### Residental e xposure to MCPP

- p may occur from uses on turfgrass and golf courses.

Residential Handler Since MCPP

- p , its salts, and esters are not restricted use pesticides, HED previously conducted a residential handler exposure assessment for lawn use ( D34 1965 ; 0 7 / 26 /2007 ). The scenarios assessed were: h and a pplication of g ranules (spot treatment)

, b elly g rinder a ppl ication (spot treatment)

, l oad/ a pply g ranules with a b roadcast spreader

, m ix/ l oad/ a pply with a h ose

- end

s prayer ( m ix your own)

, m ix/ l oad/ a pply with a h ose

- end s prayer ( r eady to u se)

, m ix/ l oad/ a pply with h and h eld Pump and m ix/ l oad/ a pply with r eady to u se s prayer . The inhalation MOE’s ranged from 190,000 to 9,900,000 and r isk estimates were not of concern.

For residential handlers, the following exposure scenarios may need to be included in the registration review assessment for both broadcast and spot trea tment of turf in accordance with the 2012 Residential SOPs (revised since the last assessment) :

 hand application of 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

. Residential Post Application There is potential for residential post

- application exposure to registered turf uses. Exposure scenarios include contact with treated turf and playing golf on treated golf courses. Q uantitative residential dermal post

- application risk assessment s w ere no t 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 ( D34 1965 ; 0 7 / 26 /2007 ). All of the short

- term MOEs for these exposures were greater than 100, and thus are not of risk concern (MOE’s ranged from 1,900 to 580,000)

. Chemical

- specific TTR data are available ( MRID 44655702, 44655703 and 45033101 ) , and will be used to estimate dermal hand loading to calculate incident al oral exposure. Exposure and risk estimates will be assessed in registration review in

### Page 7 of 21

accordance with the revised 2012 Residential SOPs. Incidental oral exposure scenarios include hand

- to

- mouth; object

- to

- mouth; incidental soil ingestion; and episodic ingestion of granules.

Spray Drift Residential exposures resulting from off

- site transport (e.g., spray drift or volatilization) might occur as a result of applications of MCPP

- p . The Agency is in the process of evaluating these types of exposures and m ight, 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 M CPP

- p will be examined during registration review.

Conclusions: Updated residential exposure assessments may be needed during registration review . Moreover, exposure and risk estimates may be assessed in accordance with the 2012 Residential SOPs during registration review. As necessary, a post

- application risk assessment
may be conducted in accordance with the development of relevant HED policies for risk assessment (e.g., spray drift, or volatilization).

5.0 A GGREGATE 

### E XPOSURE AND 

### R ISK 

### A SSESSMENT



### In accordance with the Food Quality Protection Act (FQPA), HED must consider and aggregate pesticide exposures and risks from three major sources: food, drinking water, and residential
exposures. In the most recent risk assessment ( D341965; 07/26/2007 )

, the aggregate exposure and risk estimates included only exposure via drinking water and residential exposures through the inhalation and incidental oral routes because there are no food use s and a dermal exposure
assessment is not required

. Quantification of dermal risk is not required because there is no toxicity via the dermal route of exposure

.

Acute It should be noted that individual acute assessments were performed for acute drinking water exposure and acute exposure for children resulting from con suming granules. Since there is little likelihood that these two scenarios would occur simultaneously, it is not appropriate to aggregate these two exposure and risks estimates. The acute aggregate assessment is based on acute dietary exposure only, in t his case only exposure via drinking water as there is no registered food

uses

. The acute risk was not of concern.

### Page 8 of 21

Chronic The chronic aggregate assessment include s exposure via drinking water only since no chronic residential scenarios were identified. There was no chronic risk of concern for drinking water.

Short

- term The exposure scenarios aggregated are chronic drinking water with short

- term incidental oral ingestions in infants and children and chronic drinking water with short

- term inhalation of a dult residential handlers. The toxicity endpoints for short

- term incidental oral and inhalation exposures were derived from a rat subchronic feeding/neurotoxicity study with a NOAEL of 35 mg/kg/day. The aggregate risk for residential handlers, and infants and children are obtained by comparing this NOAEL to the sum of the exposure values to calculate the MOE and comparing the calculated MOE to the target MOE of 100. The aggregated MOE’s for the scenarios examined were below HED’s level of concern ( i.e. MOE > 100).

B ased on the use pattern for MCPP

- p on turf, there are no intermediate

- or long

- term residential exposure scenarios.

Conclusions: Aggregate exposures of MCPP

- p may be revised during registration review to consider new dietary and residential exposures estimates or changes in toxicological endpoints

.

6.0 O CCUPATIONAL 

### E XPOSURE



### There is potential for occupational handler and post

- application exposure from registered use s on recreational turf (golf course) , sports fields, sod farms, ro adsides, and rights

- of

- way. MCPP

- p , its salts, and esters may be applied using aeria l (sod farms only), groundboom, hand

held 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) with no respirator

. The Restricted Entry Interval for MCPP

- p is 48 hours because it is a severe eye irritant (i.e. Toxicity Category I)

. The occupational uses of MCPP

- p , its salts, and esters result in short

- term (1

- 30 days) and intermediate

- term (1

- 6 months) occupational exposures.

Occupational Handler Exposure There is potential for occupational handler exposure during mixing/lo ading and applying

. Occupational handler scenarios were previously assessed ( D341965; 07/26/2007). All short

- and intermediate

- term inhalation MOEs for agricultural handler scenarios were assessed at baseline PPE except for aerial applicators, who were ass essed with closed cockpit (i.e., engineering controls) built in. All scenarios have MOE s above the target MOE of 100 (ranged from 445 to 410,000) and thus are not a risk concern at baseline exposure

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

- exposure

- data.html ). As

### Page 9 of 21

more reliable data become available, the Agency will continue to replace existing data. Revised assessments which incorporate these new exposure monitoring data may be required during registration review.

Occupational Post

- application Exposure There is potential for occupational post

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

- application risk assessment is required for the occupational uses of MCPP

- p , its salts, and esters. The REI of 48 hours is on registered labels and is considered appropriate based on the toxicity of the technical ingredient. A quantitative dermal post

- application risk assessment is not required due to the lack of toxicity via the dermal
route

. Since there is no use on agricultural crops , Dislodgeable Foliar Residue (DFR) is not required.

Conclusions: Updated occupational handler exposure assessments may be needed during registration review if a new inhalation dose and endpoint for risk assessment are selected

, an d to consider the most current exposure data.

7.0 P UBLIC 

### H EALTH AND 

### P ESTICIDE 

### E PIDEMIOLOGY 

### D ATA


### There are no incidents reported for MCPP as a single chemical only, but there is a high absolute number of incidents reported involving MCPP with another active ingredient (D417595,S Recore, 02/04/2014). Although vast majority of these incidents w ere of low severity, some high severity outcomes are reported in the IDS database. It is important to note that since most of these reported incidents involve mor e than one active ingredient (i.e. MCPP and another active ingredient), the incidents that were reported were not necessarily attributable to MCPP. Further, while incident information can be an important source of feedback to the Agency, reports of advers e health effects allegedly due to a specific pesticide exposure ( i.e. , an “incident”) are largely self

- reported and therefore, generally speaking, neither exposure to a pesticide or reported symptom (or the connection between the two) is validated or other wise confirmed. Typically, causation cannot be determined based on incident data. Nevertheless, based on the absolute number of incidents and the few high severity outcomes that are reported, these incident data may warrant further analysis in the prelim inary risk assessment phase of Registration Review. Obtaining additional information on current usage data for MCPP would improve future assessments.

8.0 C UMULATIVE 

### R ISK 

### A SSESSMENT



### Unlike other pesticides for which EPA has followed a cumulative risk appro ach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to MCPP

- p and any other substances and MCPP

- p does not appear to produce a toxic metabolite produced by other substances. For the purposes of this risk assessment, therefore, EPA has not assumed that MCPP

- 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/.

### Page 10 of 21

D ATA 

### R EQUIREMENTS



### Toxicity Studies

 Repeat dose (28

- day) inhalation study in the rat (870.3465) Chemistry Studies

 None Exposure Studies

 None

REFRENCES

MCPP

- p (acid), MCPP

- p DMAS, & MCPP

- p potassium salt : Revised HED Human Health Risk Assessment, PC Code: 129046 (MCPP

- p (acid)), 031520 ( MCPP

- p DMAS ), 119046 (MCPP

- p potassium salt) ( D341965; 07/26/2007)

Mecoprop

- p (MCPP

- p): Summary of Hazard and Science Policy Council ( HASPOC): Recommendations on the R equirement of a n Immunotoxicity and Subchronic Inhalation Toxicity Study for mecoprop

- p (MCPP

- p) TXR # 0056865 (1/7/2014)

. FQPA Drinking Water Assessment for Mecoprop

- p (MCPP

- p). Memorandum from J. Hetrick to M. Goodis. June 26, 2006 (DP Barcode 322772)

### Page 11 of 21

Appendix A: Toxicology Profile

Attachment 1

Table A 1 .1 . Acute Toxicity Profile

– MCP P

- p (acid).

Guideline No. Study Type MRID Results Toxicity Category

870.1100 Acute oral [rat] 42947801 LD 50 = 775 mg/kg III

870.1200 Acute dermal [rat] 42947802 LD 50 > 2000 mg/kg III

870.1300 Acute inhalation [rat] 42947803 The study is unacceptable. Unclassified A

870.2400 Acute eye irritation [rabbit] 42947804 Opacity, redness, discharge for 72 hr I

870.2500 Acute dermal irritation [rabbit] 42947805 Redness and sloughing at 10 days III

870.2600 Skin sensitization 43749601 Non

- sensitizer N/A

A New acute inhalation studies have been submitted since the 2007 assessment

Table A 1

. 2 Acute Toxicity Profile

– MCP P

- p DMAS

. Guideline No. Study Type MRID Results Toxicity Category

870.1100 Acute oral [rat] 42614701 LD 50 = 763 mg/kg III

870.1200 Acute dermal [ra bbi t] 42614703 LD 50 > 2000 mg/kg III

Table A 1

. 3

. Subchronic and Chronic Toxicity Profile

– MCPP

- p

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

870.3100 90

- Day oral toxicity ( Mouse ) MCPP

- p 43059201 (1993) Acceptable/guideline 0, 100, 1000, 2500 ppm Male:0, 20, 220, 740 mg/kg/day Female: 0, 30, 330, 930 mg/kg/day NOAEL = 20/30 mg/kg/day LOAEL = 220/330 mg/kg/day, based on decreased body weight (9%). At HDT, increased liver enzymes, increased liver and kidney weights, slight increase in urea

Non

- guideline 7

- Week feeding (Rat) MCPP

- p 41013910 (1986) Acceptable/non

- guideline 0, 50, 400 ppm 0, 4.8, 36 mg/kg/day NOAEL = 36 mg/kg/day LOAEL = not identified

870.3200 21

- Day dermal toxicity (Rabbit) MCPP

- p 42916401 (1993) Acceptable/guideline 0, 10, 100, or 1000 mg/kg/day NOAEL = 1000 mg/kg/day (HDT) LOAEL = not identified

870.3465. Datagap (can be satisfied with a 28

- day HASPOC memo (TXR No. 0056865, dated 1/7/14)

### Page 12 of 21

Table A 1

. 3

. Subchronic and Chronic Toxicity Profile

– MCPP

- p

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

Inhalation toxicity (Rat)
MCPP

- p repeat exposure study)

870.3700a Prenatal Developmental (Rat) MCPP

- p 42815302 (1993) Acceptable/guideline 0, 20, 50, 100 mg/kg/day Maternal NOAEL = 50 mg/kg/day Maternal LOAEL = 100 mg/kg/day , based on decreased body weight and food consumption Developmental NOAEL = 50 mg/kg/day Developmental LO AEL = 100 mg/kg/day, based on increased incidence of rudimentary cervical ribs 870.3700b Prenatal Developmental (Rabbit) MCPP

- p 42815301 (1993) Acceptable/guideline 0, 5, 20, 50 mg/kg/day Materna l NOAEL = 50 mg/kg/day , highest dose tested Maternal LOAEL = not identified Developmenta l NOAEL = 50 mg/kg/day Developmental LOAEL = not identified 870.3800. Reproduction (Rat) MCPP

- p 46591804 (2003) Acceptable/non

- guideline 0, 500, 800, 1200 ppm (pre

- mate) Male: 0, 35, 54, or 83 mg/kg/day Female: 0, 40, 63, or 94 mg/kg/day 0, 300, 530, or 790 ppm (lactation) Female: 0, 48, 86, 130 mg/kg/day Parental NOAEL = 54/63 mg/kg/day Parental LOAEL = 83/94 mg/kg/day, based on decreased body weight (8%)

Reproduction NOAEL = 83/94 mg/kg/day Reproduction LOAEL = not identified

Offspring NOAEL = 63 mg/kg/day Offspring LOAEL = 94 mg/kg/day, based on decreased mean # implants resulting in decreased # of pups born, decreased male pup body weight at week 4 (↓9%) 870.4100 Chronic toxicity (Dog) MCPP

- p 44642401 (1997) Acc eptable/guideline 0, 60, 180, or 600 ppm Male: 0, 2, 5, or 18 mg/kg/day Female: 0, 2, 6, or 19 mg/kg/day NOAEL 18/19 mg/kg/day (HDT) LOAEL = not identified

870.4200 Carcinogenicity (Mouse) MCPP

- p 44953601 (1996) 44895501 (1999) Acceptable/guideline 0, 25, 250, 700/800, or 2500 ppm Male: 0, 4, 40, 112, or 592 mg/kg/day Female: 0, 4, 46, 188, or 732 mg/kg/day NOAEL = 4 mg/kg/day LOAEL = 46 mg/kg/day, based on increased absolute/relative kidney weight and chronic nephropathy in females. At 112/188 mg/kg/d ay, decreased body weight (females), increased absolute/relative kidney weight (females), increased liver weight (both sexes), and an increase in chronic nephropathy (both sexes). At 592/732 mg/kg/day, excess mortality 870.5100 Gene Mutation: Ames assay MCPP

- p 41013909 (1984) Acceptable/guideline Tested in strains TA1535, TA1537, TA1538, TA100, TA98 ± S9 at concentrations up to 5000 ug/plate. Negative.

870.5100 Gene Mutation: Ames assay MCPP

- p 42980101 (1990) Acceptable/guideline Tested in strains TA15 35, TA1537, 1538, TA100, TA98 ± S9 at concentrations up to 1000 ug/plate. Negative

870.5100 42860803 (1993) Negative

### Page 13 of 21

Table A 1

. 3

. Subchronic and Chronic Toxicity Profile

– MCPP

- p

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

Gene Mutation: Ames assay MCPP

- p Acceptable/guideline Tested in strains TA1535, AT1537, TA98, and TA100 at concentrations up to 5000 ug/plate ±S9. 870.5300 Gene Mutation: HGPRT MCCP

- p 42947807 (1990) Acceptable/guideline Tested in Chinese Hamster lung fibroblast V79 cells at concentrations up to 4000 ug/mL

- S9 and up to 4500 ug/mL +S9. The 2 higher concentrations were cytotoxic. Negative for mutagenicity

870.5300 Gene Mutation: HGPRT MCPP

- p 43113401 (1993) Acceptable/guideline Tested in CHO cells up to cytotoxic concentrations (800 ug/mL +/

- S9). Negative for mutagenicity.

870.5300 Gene Mutation: HGPRT MCPP

- p 42936802 (1993) Tested in CHO cells at concentrations up to 3000 ug/mL

- S9 and up to 2500 ug/mL +S9. The highest concentration was cytotoxic. Negative for mutagenicity

870.5375 In Vitro Cytogenetics: Chromosomal Aberrations (human lymphocytes) Mecoprop

- p 4 2947806 (1990 ) Acceptable/guideline Tested in human lymphocytes at concentrations up to 400 ug/mL,

- S9, and up to 1600 ug/mL +S9. Aberration s increased at 1600 ug/mL +S9, but 76% decrease in mitotic index (MI) and value (4%) was within historical control range ( 0

- 5%).

870.5375 In Vitro Cytogenetics: Chromosomal Aberrations (human lymphocytes) Mecoprop

- p 43189501 (1994) Acceptable/guideline Tested in human lymphocytes at concentrations up to 600 ug/mL,

- S9, and up to 2000 ug/mL +S9. Dose

- related trend for clastogenic activity

- S9 only. Reduction (>50%) in MI at 600 ug/mL (20 hrs and 44 hrs) and at 300 ug/mL (44 hrs), but at 300 ug/mL (20 hrs) increase in chromosomal aberrations (chromatid and chromosome breaks).
870.5385 Chromosomal Aberration in Bone Mar row Chinese hamsters
mecoprop

- p 41013908 (1985) Acceptable/guideline Dosed up to 2600 mg/kg Negative for clastogenicity; clinical signs at all dose levels; 2 deaths at HDT

870.5395 Micronucleus assay Mecoprop

- p 42947808 (1991) Acceptable/guideline Dose u p to 500 mg/kg Negative. Clinical signs at 500 mg/kg.

870.xxxx In Vivo UDS Wistar rats MCPP

- p Tested up to toxic dose (500 mg/kg) No evidence of unscheduled DNA synthesis. Clinical signs at HDT.

870.6200a Acute Neurotoxicity Study (Rat) MCPP

- p 43770801 (1995) Acceptable/guideline 0, 175, 350, or 700 mg/kg NOAEL = 175 mg/kg LOAEL = 350 mg/kg, based on FOB changes (closed eyelids, prone body position, hypoactivity, ataxia, decreased number of rearings in females, increased landing foot splay in males, and decreased motor activity). Similar effects at

### Page 14 of 21

Table A 1

. 3

. Subchronic and Chronic Toxicity Profile

– MCPP

- p

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

HDT 870.6200b Subchronic Neurotoxicity /subchronic feeding (Rat) MCPP

- p 43908201 (1995) Acceptable/guideline 0, 75, 500, 2500 (♂)/3000 (♀)
ppm Male: 0, 5, 35, 189 mg/kg/day Female: 0, 6, 41, 240 mg/kg/day NOAEL = 35/41 mg/kg/day LOAEL = 189/240 mg/kg/day, based on decreased body weight, increased water consumption, decreased hematological parameters, decreased adrenal weight and lipid storage in adrenals, increased liver enzymes (females), increased liver w eight, and microscopic changes , kidney cells in urine (males). 870.7485 Metabolism (rat)
MCPP

- p 44362701 (1997) Acceptable/guideline 5 mg/kg/day and 100 mg/kg/day Absorption was rapid and peak plasma concentration was attained at 1.8 & 4.2 h ou rs for low

- and high

- dose groups, respectively. Elimination was fast and complete regardless of dose levels; >90% of the administered dose was eliminated by 24 hrs and approximately 100% by 168 hrs. Major route of elimination was via urine (61

- 76%). A majo r metabolite was MCPP

- OH HDT: highest dose tested ; BW: body weight ; FOB: functional observation battery

Table A 1

. 4

. Subchronic and Chronic Toxicity Profile

– MCPP

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

870.3100 90

- Day oral toxicity (Rat) MCPP 00158359 (1985) Acceptable/guideline 0, 50, 150, 450 ppm male: 0, 4

, 1 2, 37 mg/kg/day female: 0, 5, 14, 41 mg/kg/day NOAEL = 12 mg/kg/day LOAEL = 37 mg/kg/day , based on increased absolute and relative kidne y weight

Non

- guideline 7

- Week feeding (Rat) MCPP 41013910 (1986) Acceptable/non

- guideline 0, 50, 400 ppm 0, 4.8, 36 mg/kg/day NOAEL = 36 mg/kg/day LOAEL = not identified

870.3700a Prenatal Developmental (Rat) MCPP 00164569 (198 0 ) Acceptable/guideline 0, 2 0

, 5 0, 1 25 mg/kg/day Maternal NOAEL = 1 25 mg/kg/day Maternal LOAEL = not identified Developmental NOAEL = 5 0 mg/kg/day Developmental LOAEL = 1 25 mg/kg/day

, based on increased intrauterine death, decreased crown

- rump length,

a nd incomplete/absent sternebrae ossification 870.3700b Prenatal Developmental (Rabbit) MCPP 00144282 (1980) Acceptable/guideline 0, 12, 30, 75 mg/kg/day Materna l NOAEL = 30 mg/kg/day Maternal LOAEL = 75 mg/kg/day based on decreased body weight gain Developmenta l NOAEL = 75 mg/kg/day Developmental LOAEL = not identified 870.4100 Chronic toxicity ( Rat ) MCPP 40937501 (1986) Acceptable/guideline 0, 20, 100, or 450 ppm Male: 0, 1.1, 5.5, 22.2 mg/kg/day Female: 0, 1.4, 6.9, or 27.9 mg/kg/day NOAEL = 6 mg/kg/day LOAEL = 22 mg/kg/day, based on increased absolute/relative kidney weight in males; no changes in body weight, hematology, clinical chemistry, or urinalysis

870.5100 00158361 (1981) Negative

.

### Page 15 of 21

Table A 1

. 4

. Subchronic and Chronic Toxicity Profile

– MCPP

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

Gene Mutation: Ames assay MCPP Acceptable/guideline strains TA1535, TA1537, TA1538, TA100, TA98 ± S9 at concentrations up 5000 ug/plate. 870.5375 In Vitro Mammalian Cytogenetics: Chromosomal Aberrations ( human lymphocytes ) MCPP 42936803 (1993) Acceptable/guideline Tested at concentrations up to 1000 ug/mL (

- S9) and up to 5000 ug/mL (+S9). Clastogenic with activation, but only at a cytotoxic concentration (2500 ug/mL) Negative with

- S9. Only chromatid and chromosome breaks were seen. Evidence of chromosomal aberrations at cytotoxic concent ration with S9. 870.5385 Chromosomal Aberration in Bone Marrow Chinese hamsters M ecoprop 00158362 (1985 ) Classified inconclusive due to deficiencies

. dosed up to 3800 mg/kg MCPP was weakly positive for clastogenic activity in HDT animals sacrificed at 6 hours and accompanied by a 56% decrease in mitotic index (MI). Considered equivocal because the types of induced aberrations (chromatid and chromosome breaks) would likely induce cell killing and would be lost from the daug hter cells. At 24 hours, aberrations were increased in HDT animals, but not with statistical significance. One death and clinical signs at HDT.

Table A 1

. 5

. Subchronic and Chronic Toxicity Profile

– MCPP

- p - DMA

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

870.3200 21

- Day dermal toxicity (Rat)
MCPP

- p DMAS 43638102 (1995) Acceptable/guideline 9, 12, 120, 1000 mg/kg/day NOAEL = 1000 mg/kg/day (HDT) LOAEL = not identified

870.5100 Gene Mutation: Ames assay MCPP

- p

- DMA 42860801 (1993) Acceptable/guideline strains TA1535, AT1537, TA98, and TA100 at concentrations up to 5000 ug/plate ±S9. Negative

870.5395 Micronucleus assay (mouse) Mecoprop

- p

- DMA 42860804 (1993) Acceptable/guideline Doses up to 576 mg/kg Negative assay. Clinical signs seen at MDT and HDT 48 hours after treatment.

870.5375 In Vitro Mammalian Cytogenetics: Chromosomal Aberrations in human lymphocytes Mecoprop

- p

- DMA 42936803 (1993) Acceptable/guideline Tested in human lymphocytes at concentrations up to 1000 ug/mL (

- S9 ) and up to 5000 ug/mL ( +S9 )

. Clastogenic with activation, but only at a cytotoxic concentration (2500 ug/mL) Negative with

- S9. Only chromatid and chromosome breaks were seen. Evidence of chromosomal aberrations at cytotoxic concentration with S9.

870.7485 Metabolism (rat)
MCPP

- p DMAS 44362702 (1997) Acceptable/guideline 5 mg/kg (single dose) MCPP

- p DMAS was rapidly absorbed. Maximum plasma concentrations were attained at 2 hours. Within 24 hours, 83% of the dose was eliminated, & elimination half

- time

was 6.6 hours . Urine was the primary route of elimination, accounting for 86% of the administered dose over a 168

- hour time period. Most of the eliminated radioactivity was associated with parent compound. A hydro xylated

### Page 16 of 21

Table A 1

. 5

. Subchronic and Chronic Toxicity Profile

– MCPP

- p - DMA

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

metabolite, MCPP

- OH, accounted for 22% of the administered dose detected in the urine.
870.7485 Metabolism (rat)
MCPP

- p DMAS 43717201 (1995) Acceptable/non

- guideline ( 14 C)

- MCPP

- p DMAS was incubated in vitro with rat plasma, stomach content, gastro

- intestinal tract (GIT) or post

- mitochondrial liver fraction (S9) for 30 minutes. All incubated extracts were subjected to HPLC analysis. Results indicated that all of the administered ( 14 C)

- MCPP

- p DMAS in plasma, s tomach contents, gastro

intestinal tract and liver (S9) was present as the ionized form of ( 14 C)

- MCPP

- p.

### Page 17 of 21

Table A 1

. 6

. Subchronic and Chronic Toxicity Profile

– MCPP

- p - EHE

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

870.3200 21

- Day dermal toxicity (Rat)
MCPP

- p EHE 43638101 (1995) Acceptable/guideline 0, 15, 150, 1000 mg/kg/day NOAEL = 1000 mg/kg/day (HDT) LOAEL = not identified

870.5100 Gene Mutation: Ames assay MCPP

- p

- 2

- EHE 42860802 (1993) Acceptable/guideline Tested in strains TA1535, AT1537, TA98, and TA100 at concentrations up to 5000 ug/plate ±S9. Negative

870.5300 Gene Mutation: HGPRT Mecoprop

- p

- 2

- EHE 42936804 (1993) A cceptable/guideline Tested in CHO cells at concentrations up to 2 50 ug/mL

- S9 and up to 500 ug/mL +S9. Negative up to cytotoxic and/or solubility limits.

870.5395 Micronucleus assay (mouse) Mecoprop

- p

- 2

- EHE 42860805 (1993) Acceptable/guideline Dosed up to 3128 mg/kg Negative asses. Clinical signs and mortality at HDT.

870.5375 In Vitro Mammalian Cytogenetics: Chromosomal Aberrations in human lymphocytes Mecoprop

- p

- 2

- EHE 42936805 (1993) Acceptable/guideline Tested in human lymphocytes at concentrations up to 80 ug/mL (

- S 9 ) and up to 320 ug/mL ( +S9 )

. MCPP

- p

- EHE induced structural aberrations (chromatid and chromosome breaks) at the highest +S9 concentration, which was insoluble but non

- cytotoxic.

870.7485 Metabolism (rat)
MCPP

- p EHE 44362702 (1997) Acceptable/guideline 5 mg/kg (single dose) MCPP

- p EHEs was rapidly absorbed ; m aximum plasma concentrations were attained at 3.6 hours

. Within 24 hours, 68% of the dose was eliminated, & elimination half

- time was 8.4 h ou rs. Urine was the primary route of el imination, accounting for 71% of the administered dose ove r a 168

- hour time period. Most of the eliminated radioactivity was associated with parent compound. A hydroxylated metaboli te, MCPP

- OH, accounted for 16% of the administered dose detected in the urine.



### Toxicology Data Requirements

The toxicology data requirements (40 CFR 158.340) for the non

- food uses of MCPP

- p are presented below. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Study Technical
Required Satisfied

870.1100 Acute Oral Toxicity

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

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

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

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

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

................................ ..................... yes yes yes yes yes yes yes yes yes 2

yes yes yes

### Page 18 of 21 Study Technical
Required Satisfied

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

................................ ......................... CR CR

no yes
yes yes yes yes yes 3

no 4
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/Oncogenicity

................................ ................... CR 1
CR 1
CR 1
CR 1 CR 1 yes yes

- yes

- 870.5100 Mutagenicity

— Gene Mutation

– bacterial

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

— Structural Chromosomal Aberrations

.. 870.5550 Mutagenicity

— Other Genotoxic Effects

...................... yes yes yes yes yes yes 870.6100a Acute Delayed Neurotoxicity (hen)

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

- Day Neurotoxicity (hen)

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

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

- Day Neurotoxicity Screening Battery (rat)

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

................................ ....... CR CR
yes yes CR -

- yes yes

- 870.7485 General Metabolism

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

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

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

- 5

1 Not required under the registered use patterns ; 2 submitted since last risk assessment; 3 satisfied by 28

- day dermal study;
4 HASPOC determined study is required (TXR No . 0056865, dated 1/7/14); 5 HASPOC waived this requirement (TXR No. 0056865, dated 1/7/14)

.

### Page 19 of 21

A ttachment 2

. MCPP

- p Endpoints and Doses for Risk Assessment

Table A. 2

. 1 Toxicological Doses and Endpoints for MCPP

- p for Exposure Assessment Exposure/ Scenario Point of

Departure Uncertainty

Factors RfD

Level of Concern Study and Toxicological Effects

Acute Dietary (Females 13

- 49 years of age) NOAEL =

50 mg/kg/day UF A 

### = 10x

UF H 

### = 10x aRfD = 0.5

mg/kg/day Developmental toxicity in rats with

MCPP

- p. LOAEL = 100 mg/kg/day based on an increased incidence of rudimentary cervical rib s

. Acute Dietary (General Population, including infants and children) NOAEL =

175 mg/kg/day UF A 

### = 10x

UF H 

### = 10x aRfD = 1.75

mg/kg/day Acute neurotoxicity in rats with MCPP

p. LOAEL = 350 mg/kg/day based on FOB changes (closed eyelids, prone body position, hypoactivity, ataxia); decr eased rearings in females; incr eased landing foot splay in males and decr motor activity. Chronic Dietary (All Populations) NOAEL =

4 mg/kg/day UF A 

### = 10x

UF H 

### = 10x cRfD = 0.04

mg/kg/day Mouse carcinogenicity study with

MCPP

- p. LOAEL = 46 mg/kg/day based on incr eased kidney wt and chronic nephropathy in females. Incidental Oral Short

- Term (1

- 30 days) and Intermediate

Term (1

- 6 months) NOAEL =

35 mg/kg/day UF A 

### = 10x

UF H 

### = 10x LOC = 100 Subchronic feeding/ Subchronic neurotoxicity study in rats with MCPP

p. LOAEL = 189 mg/kg/day based on decr eased body weight

, incr eased water consumption; decr eased hematolog ical parameters , decr eased abs olute adrenal

w eigh t and lipid storage in adrenals, incr eased liver enzymes ( females ), incr eased abs ol ute /rel ative liver w eigh t and micro scopic changes; kidney cells in urine of high

- dose males. Dermal (all durations) N/A N/A N/A No toxicity at 1000 mg/kg/day and no developmental toxicity concerns by dermal route. Inhalation (short

- term, intermediate

term) NOAEL =

35 mg/kg/day UF A 

### = 10x

UF H 

### = 10x UF DB 

### = 10X Inhalation absorption rate = 100% LOC = 100 Subchronic feeding/Subchronic neurotoxicity study in rats

– see above.

Cancer Classification: "Suggestive Evidence of Carcinogenicity, but Not Sufficient to Assess

Human Carcinogenic Potential" Point of Departure (POD) = A data point or an estimated point derived from dose

- response data which is used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human
exposures.

### Page 20 of 21

NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF= uncertainty factor; UF A = extrapolation from animal to human (interspecies). UF H = potential variation in

sen sitivity among members of the human population (intraspecies). UF DB = database uncertainty factor for lack of the subchronic inhalation toxicity study. aRfD = acute reference dose. cRfD=chronic reference dose; LOC = level of concern. N/A = not applicabl e.



### Table A. 2 .2 Toxicological Doses and Endpoints for MCPP

- p for Occupational Exposure Assessment Exposure/ Scenario Point of

Departure Uncertainty

Factors Level of

Concern Study and Toxicological Effects

Dermal (all durations) N/A N/A N/A No toxicity at 1000 mg/kg/day and there are no developmental concerns for this route of exposure. Inhalation (all durations) NOAEL =

35 mg/kg/day UF A 

### = 10x

UF H 

### = 10x LOC = 100 Subchronic feeding/Subchronic neurotoxicity in rats with MCPP

- p. LOAEL = 189 mg/kg/day based on decr eased body weight , incr eased water consumption; decr eased hematological parameters, decr eased abs olute adrenal

w eigh t and lipid storage in adrenals, incr eased liver enzymes ( females ), incr eased abs olute /rel ative liver w eight and micro scopic changes; kidney cells in urine of high

- dose males. Cancer Classification: "Suggestive Evidence of Carcinogenicity, but Not Sufficient to Assess

Human Carcinogenic Potential" Point of Departure (POD) = A data point or an estimated point derived from dose

- response data which is 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 l evel. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). MOE = margin of exposure. LOC = level of concern. N/A = not applica ble.

### Page 21 of 21

Appendix B: Chemistry

1.0 Identification of Active Ingredient

T able B.1.1 

### Test Compound Nomenclature

Chemical Structure



### Empirical Formula C 10 

### H 11 

### ClO 3 

### Common name Mecoprop

- p, MCPP

- p Company experimental name (R)

- (+)

- 2

- (4

- chloro

- 2

- methylphenoxy)propanoic acid
IUPAC name (R)

- 2

- (2

- methyl

- 4 chlorophenoxy)propionate CAS Registry Number 16484

- 77

- 8, 66423

- 09

- 4, 66423

- 05

- 0
Chemical Class Chlorophenoxy

2.0 Physical and Chemical Properties

Table B.1.2 

### Physicochemical Properties of MCPP

- p Parameter Value Reference Molecular Weight 214.6g/mole D263488 Melting point/range 93.5

- 97.5 o 

### C D263488 pH 2.9 (1% w/v suspension) D263488 Density 500

- 700 g/L EFED Risk Assessment Water solubility (20°C) 620 mg/L @ 20 o 

### C EFED Risk Assessment Solvent solubility (20°C) >100 g/100g in acetone, ethanol Farm Chemical Handbook 2002 Vapor pressure (25°C) 5.1x 10 - 5 

### torr EFED Risk Assessment Dissociation constant, pKa 2.0x10 - 4 

### (pK a 

### =3.7) D263488 Octanol/water partition coefficient, logP OW 

### - 0.19 @ pH 7 MCPP

- p Task Force