### Dicrotophos Dietary Ex posure and Risk Assess ment DP No: D418103



### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CH EMICAL SAFETY AND

POLLUTION PREVENTION



### MEMORANDUM

Date: July 10

, 2014



### SUBJECT: Dicrotophos: Acute and Steady State Aggregate Dietary (Food and Drinking

Water) Expos ure and Risk Assessments to Support Registration Review

PC Code: 035201

Decision No.: 454409

Petition No.: NA DP Barcode: 0418103

Registration No .: NA

Regulatory Action: Re gist ration Review

Case No.: 0145 Risk Assessment Type: Di e tary

TXRNo.: NA CAS No.: 141-66- 2

MRIDNo.:NA



### FROM:

THROUGH:

TO: Thurston Morton, Chemist

Risk Assessment Branch IV 40 FR

·**180.299 ~** 



### Hea lth Effects Division (7509P) /

Sheila Piper

, Chemist

# ~**~** D on Wi l bur

, Chemist

## ~ Dietary Ex posure Science Advisory oun 1 

### ES AC)

And

Elissa Reaves, Ph.D., Branch Ch ief

Risk Assessment Branch IV, HED (7509P)

Russell Wasem

Risk Management and Implementation Branch 1

Pesticide R e-ev aluation Division (7508P)



### Executive Summary

Acute and steady state aggregate dietary food and drinking water exposure and risk assessments

for dicrotophos were conducted using the Dietary Exposure Evaluation Mode l and Ca lende x

software with the Food Commo dity Intake Database (FC ID). This software uses 2003

- 2008 food

consum ption data from the U.S. Department of Agricu l ture's (USDA's) Nationa l Health and

N utrition Examination Survey, What We Ea t in America

, (NHANES/WWEIA). This dietar y

analysis is updated to reflect the latest consumption data and to support regi st ration review. T hi s

memorandum was reviewed b y two peer reviewer s of th e DESAC per th e curre nt DESAC

Standard Operating Procedure (SO P ).

Page I of20

### Acute Dietary (Food and Drinking Water) Exposure Results and Characterization

Dicrotophos is a broad spectrum organophosphate insecticide. The only dicrotophos end-use

formulation currently registered is a water -m iscible formulation which may be foliarly appl i e d to

established cotton plants or used as a tree injection treatment for ornamental and non-food

producing trees.

An unrefined acute dietary exposure assessment was conducted to estimate the dietary exposure

and risk associated with registration review. The acute dietary exposure assessment incorporated

tolerance l evel residue and 100% crop treated for the acute analysis. The drinking water

concentrat i on was based on the use of dicrotophos from three cotton scenarios.

The acute aggregate dietary exposure estimates are below HED' s l evel of concern ( < 1 00 % the

acute population adjusted dose (aPAD)) for the U.S. population and a ll population subgroups.

Combined dietary exposure from food and drinking water at the 95 1 h 

### percentile of exposure is

13% ofthe aPAD for the U.S

. population and 27% ofthe aPAD for all infants (<1 yrs old), the

most highly exposed population subgroup.

Steady State Dietary (Food and Drinking Water) Exposure Results and Characterization

Organophosphate may exh ibit a phenomenon known as steady state acetylcho lin esterase (AChE)

inhibition which is the most sensitive endpo i nt for alllifestages. After repeated dosing at the

same dose, the amount of AChE inhibition in a given dose remains consistent across duration.

For this reason, a steady

- state point of departure (PoDs) was selected for oral exposure to

dicrotophos (see Tab l e 3).

An 

### unrefmed steady state dietary exposure assessment was conducted to estimate the dietary

risks associated with the registration of dicrotophos. The steady state dietary exposure

assessment incorporated tolerance level residues and 100% crop treated. The steady state

aggregate dietary exposure est i mates from Calendex are above HED's level of concern(> 100%

of t h e PAD) for the U.S. population and a ll population subgroups. Combined dietary exposure

from food and drinking water is 136% of PAD for the U.S. population and 358% of the PAD for

children 1-2 years, the most highly exposed popu l ation subgroup.

Cancer Dietary (Food and Drinking Water) Exposure Results and Characterization

Dicrotophos is classified as showing 

### "Suggestive evidence of carcinogenicity

, but not sufficient

to assess human carcinogenic potential "

. Quantitative risk assessment for dicrotophos using the

Reference Dose (RID) approach will adequately account for all chronic toxic effects, including

carcinogenicity.

Page 2 of20Page 3 of 20



### I. Introduction

Dietary risk assessment incorporates both exposure and toxicity of a given pesticide. For acute

and steady state assessments, the risk is expressed as a percentage of a maximum acceptable dose

(i.e., the dose that HED has concluded will result in no unreasonable adverse health effects).

This dose is referred to as the population adjusted dose (PAD). The PAD is equ ivalent to the

point of departure (POD, NOAEL, LOAEL, e.g.) divided by the required uncertainty or safety

factors.

For acute and non

- cancer chronic exposures, HED is concerned when estimated dietary risk

exceeds 100% of the PAD. References that discuss t he acute and chronic risk assessments in

more detail are available on the EPA/pesticides web site: “Available Information on Assessing

Exposure from Pesticides, A User’s Guide,” 21

- JUN

- 2000, web link:

http://www.epa.gov/fedrgstr/EPA

- PEST/2000/July/Day

- 12 /6061.pdf ; or see SOP 99.6 (20

- AUG

1999).

The most recent dietary risk assessment for dicrotophos was conducted by B

. Daiss ( October 30,

2001, D278883 ).

II. Residue Information

Dicrotophos (dimethyl phosphate of 3

- hydroxy

- N,N

- dimethyl

- cis

- crotonamide) is a contact,

systemic acaricide/insecticide registered for use on cotton. Permanent tolerances are established

for the residues of dicrotophos and monocrotophos at 0.20 ppm in cot ton, undelinted seed and at

2.0 ppm in cotton gin byproducts (40CFR §180. 299 ).

The residues of concern in plants are dicrotophos and monocrotophos

.

Residue Data used for Acute and Steady state Dietary Assessments

An unrefined acute dietary exposure assessment was conducted using tolerance level residues

and 100% crop treated

.

The USDA Pesticide Data Program (PDP) monitored pesticide residues in catfish in 2008. PDP

analyzed 552 samples of catfish for dicrotophos residues. None of the samples contained

detectable residues. As a result, residues in fish were not included in the assessment.

I I I. Percent Crop Treated Information

The acute and steady state aggregate dietary analyses were per formed assuming 100% of each

commodity was treated with dicrotophos

.Page 4 of 20



### IV. Drinking Water Data

This assessment uses maximum rates but considers typical rates though monitoring data exceeds

the resulting EDWCs in some instances. The assessment considers a parent only approach but

al so considers the major degradates as parent in a total toxic residue (TTR) approach. Toxicity

data and acceptable environmental fate data is unavailable for dicrotophos degradates. Inclusion

of the TTR approach is provided for a complete characterization of EDWCs. Submission of

degradate environmental fate data and/or toxicity data for the identified degradates could reduce

uncertainty in the TTR approach and potentia l ly reduce acute and chronic risk

. However,

EDWCs are reduced by <10% from a TTR approa ch to a parent only approach thus other

opportunities for refinement or mitigation may reduce EDWCs further. Additionally, a single

soil metabolism study is used for the derivation of the aerobic soil metabolism input parameter

which necessitates incorpor ation of a 3x factor for use as a model input. This input parameter is

intended to represent the many varieties of soil and microbial communities that may metabolize

dicrotophos at differing rates which is the rationale for the 3x factor. Additional aero bic soil

metabolism data would allow for better characterization of the half life, remove the need for the

3x factor, and reduce uncertainty. Given current uncertainty, the following degradates are

included in the TTR approach:

Daily time series outputs for the thirty year simulation were provided to HED for use in dietary

exposure modeling.

Table 5. 3 Summary of Estimated Surface Water and Groundwater Concentrations

for Dicrotophos

.

Scenario Surface Water Conc., ppb a Groundwater Conc., ppb b

Acute 12.44 0.06

Chronic (non

- cancer) 0.80 0.06

Chronic (cancer) 0.41 0.06

a From the Tier II PRZM

- EXAMS based on 3 cotton scenarios (NC, MS, TX)

b From the PRZM

- GW model.

D399359, A. Shelby, 8/1/2013.



### V. DEEM

- FCID Program and Consumption Information

A dicrotophos acute dietary exposure assessment w as conducted using the DEEM

- FCID,

Version 3.16 , which incorporates 2003

- 2008 consumption data from USDA’s

NHANES/WWEIA. The data are based on the reported consumption of more than 20,000

individuals over two non

- consecutive survey days. Foods “as consumed” (e.g., apple pie) are

linked to EPA

- defined food commodities (e.g.

, apples, peeled fruit

- cooked; fresh or N/S; baked;

or wheat flour

- cooked; fresh or N/S, baked) using publicly available recipe translat ion files

developed jointly by USDA/ARS and EPA. For chronic exposure assessment, consumption data

are averaged for the entire U.S. population and within population subgroups . However , for acute

exposure assessment

, consumption data are retained as individual consumption events. Based on

analysis of the 2003

- 2008 WWEIA consumption data, which took into account dietary patterns

and survey respondents, HED concluded that it is most appropriate to report risk for the

following populatio n subgroups: the general U.S. population, all infants (<1 year old), childrenPage 5 of 20



### 1

- 2, children 3

- 5, children 6

- 12, youth 13

- 19, adults 20

- 49, females 13

- 49, and adults 50

- 99

years old.

For an acute exposure assessment, individual one

- day food consumption dat a are used on an

individual

- by

- individual basis. The reported consumption amounts of each food item can be

multiplied by a residue point estimate and summed to obtain a total daily pesticide exposure for a

deterministic exposure assessment, or “matched” i n multiple random pairings with residue values

and then summed in a probabilistic assessment. The resulting distribution of exposures is

expressed as a percentage of the aPAD on both a user (i.e., only those who reported eating

relevant commodities/food f orms) and a per

- capita (i.e., those who reported eating the relevant

commodities as well as those who did not) basis. In accordance with HED policy, per capita

exposure and risk are reported for a nalyses performed at all levels of refinement . However, fo r

deterministic assessments , any significant differences in user vs. per capita exposure and risk are

specifically identified and noted in the risk assessment.

V I

. CALENDEX

- FCID Program

Calendex

- FCIDTM provides a focus detailed profile of potential expo sures to individuals across a

calendar year. A calendar

- based approach provides the ability to estimate daily exposures from

multiple sources over time to an individual and is in keeping with two key tenets of agg regate

risk assessment: 1) that exposures w hen aggregated are internally consistent and realistic; and 2)

that appropriate temporal and geographic linkages or correlations/associations between exposure

scenarios are maintained

. Calendex also enables HED to identify potential risks caused by co

occ urrence of exposures from multiple routes and pathways (e.g., near simultaneous same

- day

exposures throug h drinking water and residential uses)

.

HED’s steady state assessment considers the potential risk from a 21

- day exposure duration

using a 3

- week ro lling average (sliding by day) across the year. For this assessment, the same

food residue values used in the acute assessment were used for the 21

- day duration. In the

Calendex software, one diary for each individual in the WWEIA is selected to be paired with a

randomly selected set of residue values f or each food consumed

. For the water residue values,

Calendex incorporates PRZM

- EXAMs drinking water residue by selecting a year at random

from those available in the designated drinking water residue file. It then retrieves the residue

value assigned to the day being evaluated and multiplies it to the food

- based water consumption

value as designated during the analysis setup by the user. For weekly exposure (e.g. exposure

averaged over one week) which use s 30 years of PRZM

- EXAMs data, Calendex will randomly

choose a year for the first iteration. It will then take the residue from the first day of the week

and multiply it by the consumption amount for the individual from the WWEIA. Calendex will

continue this process for the entire week (several sequential days) and average the exposures to

estimate a weekly exposure. Calendex will randomly choose another year and continue the

process until all of the iterations designated for this analysis have been comp leted.Page 6 of 20



### V I I. Toxicological Information

Dicrotophos is a member of the organophosphate (OP) class of pesticides. Like other OPs , the

initiating event in the adverse outcome pathway (AOP), also often called the mode of action

(MOA), for dicrotophos involves inhibition of the enzyme acetylcholinesterase (AChE) via

phosphorylation of the serine residue at the active site of the enzym e. This inhibition leads to

accumulation of acetylcholine and ultimately to neurotoxicity in the central and/or peripheral

nervous system . For dicrotophos, AChE inhibition is the most sensitive endpoint in the

toxicology database in multiple species, du rations, lifestages, and routes . AChE inhibition is the

focus of this hazard characterization ; t he availability of reliable AChE inhibition dose response

data is one of the key determinants in evaluating the toxicology database. In general, OPs reach

ste ady state within 2

- 3 weeks but this can vary among OPs. In the case of dicrotophos , the

results show a clear pattern of steady state reached at or near 1 5 days of exposure. In addition to

the consistency across durations, the data across multiple studies (repeat CCA study, gestational

data from the DNT, subchronic neurotoxicity study, and subchronic rat toxicity study) are

similar. Although the durations of the toxicity and exposure assessments may differ, an exact

match is not necessary and would sugge st a level of precision that the toxicity data do not

support. Furthermore, humans would be expected to be slower and closer to the typical 2

- 3

week window of duration. Given this, the 21

- day and longer exposure assessment is

scientifically supportable and also provides consistency across the OPs. Given the results in

Table 3 , for dicrotophos , acute (single day) and steady state durations are appropriate for human

health risk assessment. HED’s ToxSAC met ( 07/18/2013 ) to consider the endpoints of

toxicological concern for the dietary exposure

.

Table 3. Summary of Toxicological Doses and Endpoints for Dicrotophos for use in Human Health

Risk Assessments

. Exposure/

Scenario Point of

Departure Uncertainty/

FQPA Safe ty

Factors RfD, PAD, Level

of Concern for

Risk Assessment Study and Toxicological

Effects

Acute Dietary (all

populations,

including females

13

- 49) BMDL 10 =

0.07mg/kg/day UF A = 10x

UF H = 10x

FQPA SF =

1x Acute PAD =

0.0007 mg/kg/day CCA Study (MRID 4615205)

in the rat

– PND 8, 15, & 22

Inhibition of brain ChE in

male and female rat pups.

Steady

- State

Dietary (all

populations) BMDL 10 =

0.03 mg/kg/day UF A = 10x

UF H = 10x

FQPA SF =

1x Steady State PAD

= 0.0003

mg/kg/day Subchronic and chronic

toxicity studies (OP CRA

2002, 2006; MRID’s

43980201 and 44527802)

Inhibition of brain ChE in

adult rat

Cancer (oral,

dermal,

inhalation) Classification: "Suggestive evidence of carcinogenicity, but not sufficient to assess

human carcinogenic potential ”

.

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. BMDL 10 = benchmark dose lower limit for 10% response. UF A = extrapolation from animal to human

(interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies).

FQPA SF = FQPA Safety Factor. RfD = reference dose.Page 7 of 20



### VI I I. Results/Discussion

As stated above, for acute and steady state assessments, HED are concerned w hen dietary risk

exceeds 100% of the PAD. The DEEM

- FCID and Calendex

- FCID analyses estimate the dietary

exposure of the U.S. population and various population subgroups. The results reported in t able s

4 and 5 are for the general U.S. Population, all infa nts (<1 year old), children 1

- 2, children 3

- 5,

children 6

- 12, youth 13

- 19, females 13

- 49, adults 20

- 49, and adults 50

- 99 years.

For food and drinking water, the acute dietary risk estimate is below HED’s level of concern at

the 9 9.9 th 

### percentile of expo sure. The acute dietary exposure using DEEM was estimated for

the U.S. population is 13 % of the aPAD and 27 % of the aPAD for all infants (<1 yrs old)

, the

most highly exposed population subgroup. The steady state aggregate dietary (food and

drinking water) exposure estimates using Calendex are above HED’s level of concern for the

U.S. population and all population subgroups. Combined dietary exposure from food and

drinking water is 136 % of PAD for the U.S. population and 3 58 % of the PAD for children 1

- 2

years, the most highly exposed population subgroup.

Results of Acute Dietary Exposure Analysis for Dicrotophos (Food and Drinking Water) MS Cotton Typical Rate

Population Subgroup aPAD

(mkd)* 95 th Percentile 99 th Percentile 99.9 th Percentile

Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD

General U.S. Population

0.0007 0.000035 5.1 0.000091 13 0.000236 34

All Infants (< 1 year old) 0.000069 10 0.000237 34 0.00630 90

Children 1

- 2 years old 0.000060 8.6 0.000150 21 0.000400 57

Children 3

- 5 years old 0.000057 8.1 0.000128 18 0.000320 46

Children 6

- 12 years old 0.000042 6.0 0.000101 14 0.000244 35

Youth 13

- 19 years old 0.000030 4.3 0.000076 11 0.000190 27

Adults 20

- 49 years old 0.000032 4.6 0.000087 12 0.000209 30

Adults 50

- 99 years old 0.000030 4.3 0.000077 11 0.000190 27

Females 13

- 49 years old 0.000032 4.6 0.000085 12 0.000213 30Page 8 of 20

Results of Acute Dietary Exposure Analysis for Dicrotophos (Food and Drinking Water) MS Cotton Max Rate

Population Subgroup aPAD

(mkd)* 95 th Percentile 99 th Percentile 99.9 th Percentile

Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD

General U.S. Population

0.0007 0.000047 6.7 0.000132 19 0.000360 51

All Infants (< 1 year old) 0.000103 15 0.000362 52 0.001037 150

Children 1

- 2 years old 0.000076 11 0.000214 31 0.000547 78

Children 3

- 5 years old 0.000071 10 0.000181 26 0.000468 67

Children 6

- 12 years old 0.000052 7.5 0.000145 21 0.000333 48

Youth 13

- 19 years old 0.000037 5.3 0.000107 15 0.000287 41

Adults 20

- 49 years old 0.000045 6.4 0.000127 18 0.000340 49

Adults 50

- 99 years old 0.000042 6.1 0.000117 17 0.000309 44

Females 13

- 49 years old 0.000044 6.3 0.000126 18 0.000343 49

Results of Acute Dietary Exposure Analysis for Dicrotophos (Food and Drinking Water) TX Cotton Typical Rate

Population Subgroup aPAD

(mkd)* 95 th Percentile 99 th Percentile 99.9 th Percentile

Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD

General U.S. Population

0.0007 0.000034 4.8 0.000086 12 0.000224 32

All Infants (< 1 year old) 0.000065 9.3 0.000219 31 0.000613 88

Children 1

- 2 years old 0.000057 8.2 0.000141 20 0.000402 57

Children 3

- 5 years old 0.000055 7.8 0.000122 17 0.000320 46

Children 6

- 12 years old 0.000040 5.8 0.000096 14 0.000237 34

Youth 13

- 19 years old 0.000029 4.2 0.000072 10 0.000180 26

Adults 20

- 49 years old 0.000031 4.4 0.000082 11 0.000198 28

Adults 50

- 99 years old 0.000029 4.1 0.000072 10 0.000182 26

Females 13

- 49 years old 0.000030 4.4 0.000080 11 0.000203 29Page 9 of 20

Results of Acute Dietary Exposure Analysis for Dicrotophos (Food and Drinking Water) TX Cotton Max Rate

Population Subgroup aPAD

(mkd)* 95 th Percentile 99 th Percentile 99.9 th Percentile

Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD

General U.S. Population

0.0007 0.000045 6.5 0.000126 18 0.000342 49

All Infants (< 1 year old) 0.000096 14 0.000344 49 0.001005 140

Children 1

- 2 years old 0.000074 11 0.000206 29 0.000517 74

Children 3

- 5 years old 0.000069 9.9 0.000174 25 0.000441 63

Children 6

- 12 years old 0.000050 7.2 0.000141 20 0.000323 46

Youth 13

- 19 years old 0.000036 5.2 0.000103 15 0.000273 39

Adults 20

- 49 years old 0.000043 6.2 0.000121 17 0.000322 46

Adults 50

- 99 years old 0.000041 5.8 0.000111 16 0.000299 43

Females 13

- 49 years old 0.000043 6.1 0.000120 17 0.000327 47

Results of Acute Dietary Exposure Analysis for Dicrotophos (Food and Drinking Water) NC Cotton Typical Rate

Population Subgroup aPAD

(mkd)* 95 th Percentile 99 th Percentile 99.9 th Percentile

Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD

General U.S. Population

0.0007 0.000034 4.8 0.000085 12 0.000218 31

All Infants (< 1 year old) 0.000066 9.4 0.000216 31 0.000588 84

Children 1

- 2 years old 0.000057 8.2 0.000141 20 0.000400 57

Children 3

- 5 years old 0.000055 7.8 0.000120 17 0.000319 46

Children 6

- 12 years old 0.000040 5.8 0.000094 13 0.000233 33

Youth 13

- 19 years old 0.000029 4.2 0.000071 10 0.000175 25

Adults 20

- 49 years old 0.000031 4.4 0.000081 12 0.000193 28

Adults 50

- 99 years old 0.000028 4.1 0.000071 10 0.000176 25

Females 13

- 49 years old 0.000030 4.3 0.000078 11 0.000193 28Page 10 of 20

Results of Acute Dietary Exposure Analysis for Dicrotophos (Food and Drinking Water) NC Cotton Max Rate

Population Subgroup aPAD

(mkd)* 95 th Percentile 99 th Percentile 99.9 th Percentile

Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD Exposure

(mkd) %

aPAD

General U.S. Population

0.0007 0.000046 6.6 0.000127 18 0.000339 48

All Infants (< 1 year old) 0.000100 14 0.000348 50 0.000980 140

Children 1

- 2 years old 0.000074 11 0.000207 30 0.000518 74

Children 3

- 5 years old 0.000070 10 0.000175 25 0.000442 63

Children 6

- 12 years old 0.000051 7.3 0.000140 20 0.000323 46

Youth 13

- 19 years old 0.000037 5.2 0.000104 15 0.000270 39

Adults 20

- 49 years old 0.000044 6.3 0.000122 17 0.000316 45

Adults 50

- 99 years old 0.000041 5.9 0.000113 16 0.000293 42

Females 13

- 49 years old 0.000043 6.2 0.000121 17 0.000318 45

### Dicrotophos Dietary Exposure and Risk Assessment DP No: D418103

______________________________________________________________________________

Page 11 of 20 

### For the steady state dietary exposure analyses, All infants <1 yr old was the population subgroup with the highest exposure r anging

from 40 to 63 % ssRfD at the 70 th 

### percentile of exposure. At the 90 th 

### percentile of regulation, All infants <1 yr old was t he population

subgroup with the highest exposure ranging from 87 to 150 % ssRfD . And at the 95 th 

### percentile of exposure, All infants <1 yr old was

the population subgroup with the highest exposure ranging from 120 to 210 % ssRfD

.

Results of Steady State Dietary Exposure Analysis for Dicrotophos (Food and Drinking Water) MS Cotton Max Rate

Population Subgroup PAD

(mkd)* 70 th Percentile 90 th Percentile 95 th Percentile 99.9 th Percentile

Exposure

(mkd) % PAD Exposure

(mkd) % PAD Exposure

(mkd) %

PAD Exposure

(mkd) %

PAD

General U.S. Population

0.0003 0.000150 50 0.000221 74 0.000277 92 0.000750 250

All Infants (< 1 year old) 0.000179 60 0.000440 150 0.000632 210 0.001863 620

Children 1

- 2 years old 0.000166 55 0.000279 93 0.000367 120 0.001220 410

Children 3

- 5 years old 0.000160 53 0.000249 83 0.000315 110 0.000950 320

Children 6

- 12 years old 0.000152 51 0.000205 68 0.000258 86 0.000690 230

Youth 13

- 19 years old 0.000149 50 0.000192 64 0.000237 79 0.000600 200

Adults 20

- 49 years old 0.000155 52 0.000222 74 0.000277 92 0.000650 220

Adults 50

- 99 years old 0.000124 41 0.000178 59 0.000228 76 0.000590 200

Females 13

- 49 years old 0.000154 51 0.000223 74 0.000281 94 0.000680 230Page 12 of 20

Results of Steady State Dietary Exposure Analysis for Dicrotophos (Food and Drinking Water) MS Cotton Typical Rate

Population Subgroup PAD

(mkd)* 70 th Percentile 90 th Percentile 95 th Percentile 99.9 th Percentile

Exposure

(mkd) % PAD Exposure

(mkd) % PAD Exposure

(mkd) %

PAD Exposure

(mkd) %

PAD

General U.S. Population

0.0003 0.000150 50 0.000188 63 0.000206 69 0.000480 160

All Infants (< 1 year old) 0.000119 40 0.000289 96 0.000399 130 0.001086 360

Children 1

- 2 years old 0.000152 51 0.000211 70 0.000262 87 0.000840 280

Children 3

- 5 years old 0.000149 50 0.000191 64 0.000229 76 0.000660 220

Children 6

- 12 years old 0.000145 48 0.000186 62 0.000197 66 0.000480 160

Youth 13

- 19 years old 0.000144 48 0.000185 62 0.000195 65 0.000410 140

Adults 20

- 49 years old 0.000146 49 0.000188 63 0.000206 69 0.000420 140

Adults 50

- 99 years old 0.000116 39 0.000149 50 0.000160 53 0.000360 120

Females 13

- 49 years old 0.000146 49 0.000188 63 0.000208 69 0.000430 140Page 13 of 20

Results of Steady State Dietary Exposure Analysis for Dicrotophos (Food and Drinking Water) NC Cotton Max Rate

Population Subgroup PAD

(mkd)* 70 th Percentile 90 th Percentile 95 th Percentile 99.9 th Percentile

Exposure

(mkd) % PAD Exposure

(mkd) % PAD Exposure

(mkd) %

PAD Exposure

(mkd) %

PAD

General U.S. Population

0.0003 0.000152 51 0.000213 71 0.000265 88 0.000750 250

All Infants (< 1 year old) 0.000188 63 0.000413 140 0.000590 200 0.001774 590

Children 1

- 2 years old 0.000166 55 0.000277 92 0.000356 120 0.001250 420

Children 3

- 5 years old 0.000159 53 0.000242 81 0.000302 100 0.000950 320

Children 6

- 12 years old 0.000151 50 0.000201 67 0.000250 83 0.000720 240

Youth 13

- 19 years old 0.000148 49 0.000191 64 0.000230 77 0.000600 200

Adults 20

- 49 years old 0.000153 51 0.000212 71 0.000263 88 0.000650 220

Adults 50

- 99 years old 0.000122 41 0.000168 56 0.000215 72 0.000551 180

Females 13

- 49 years old 0.000153 51 0.000214 71 0.000265 88 0.000650 220Page 14 of 20

Results of Steady State Dietary Exposure Analysis for Dicrotophos (Food and Drinking Water) NC Cotton Typical Rate

Population Subgroup PAD

(mkd)* 70 th Percentile 90 th Percentile 95 th Percentile 99.9 th Percentile

Exposure

(mkd) % PAD Exposure

(mkd) % PAD Exposure

(mkd) %

PAD Exposure

(mkd) %

PAD

General U.S. Population

0.0003 0.000144 48 0.000187 62 0.000197 66 0.000480 160

All Infants (< 1 year old) 0.000120 40 0.000261 87 0.000369 120 0.001038 350

Children 1

- 2 years old 0.000151 50 0.000202 67 0.000251 84 0.000800 270

Children 3

- 5 years old 0.000148 49 0.000190 63 0.000219 73 0.000630 210

Children 6

- 12 years old 0.000144 48 0.000186 62 0.000196 65 0.000470 160

Youth 13

- 19 years old 0.000143 48 0.000184 61 0.000195 65 0.000390 130

Adults 20

- 49 years old 0.000145 48 0.000186 62 0.000197 66 0.000420 140

Adults 50

- 99 years old 0.000115 38 0.000148 49 0.000156 52 0.000346 120

Females 13

- 49 years old 0.000145 48 0.000187 62 0.000197 66 0.000420 140Page 15 of 20

Results of Steady State Dietary Exposure Analysis for Dicrotophos (Food and Drinking Water) TX Cotton Max Rate

Population Subgroup PAD

(mkd)* 70 th Percentile 90 th Percentile 95 th Percentile 99.9 th Percentile

Exposure

(mkd) % PAD Exposure

(mkd) % PAD Exposure

(mkd) %

PAD Exposure

(mkd) %

PAD

General U.S. Population

0.0003 0.000150 50 0.000211 70 0.000261 87 0.000690 230

All Infants (< 1 year old) 0.000182 61 0.000415 140 0.000573 190 0.001588 530

Children 1

- 2 years old 0.000170 57 0.000268 89 0.000345 120 0.001080 360

Children 3

- 5 years old 0.000159 53 0.000239 80 0.000244 81 0.000890 300

Children 6

- 12 years old 0.000150 50 0.000199 66 0.000245 82 0.000650 220

Youth 13

- 19 years old 0.000148 49 0.000190 63 0.000225 75 0.000540 180

Adults 20

- 49 years old 0.000180 60 0.000212 71 0.000259 86 0.000600 200

Adults 50

- 99 years old 0.000123 41 0.000166 55 0.000210 70 0.000490 160

Females 13

- 49 years old 0.000153 51 0.000214 71 0.000264 88 0.000590 200Page 16 of 20

Results of Steady State Dietary Exposure Analysis for Dicrotophos (Food and Drinking Water) TX Cotton Typical Rate

Population Subgroup PAD

(mkd)* 70 th Percentile 90 th Percentile 95 th Percentile 99.9 th Percentile

Exposure

(mkd) % PAD Exposure

(mkd) % PAD Exposure

(mkd) %

PAD Exposure

(mkd) %

PAD

General U.S. Population

0.0003 0.000140 47 0.000186 62 0.000197 66 0.000440 150

All Infants (< 1 year old) 0.000119 40 0.000265 88 0.000360 120 0.000929 310

Children 1

- 2 years old 0.000150 50 0.000199 66 0.000246 82 0.000720 240

Children 3

- 5 years old 0.000147 49 0.000189 63 0.000217 72 0.000590 200

Children 6

- 12 years old 0.000144 48 0.000185 62 0.000196 65 0.000440 150

Youth 13

- 19 years old 0.000143 48 0.000184 61 0.000195 65 0.000360 120

Adults 20

- 49 years old 0.000145 48 0.000186 62 0.000196 65 0.000390 130

Adults 50

- 99 years old 0.000116 39 0.000149 50 0.000157 52 0.000310 100

Females 13

- 49 years old 0.000145 48 0.000186 62 0.000197 66 0.000390 130

### Dicrotophos Dietary Exposure and Risk Assessment DP No: D418103

______________________________________________________________________________

Page 17 of 20 

### IX

. Characterization of Inputs/Outputs

HED has conducted unrefined acute and steady state dietary risk assessments for coumaphos.

OPs exhibit a phenomenon known as steady state AChE inhibition and for coumaphos a steady

state endpoint was selected. Although

, there are rat data at a shorter time period (i.e., 1 5 days)

than 21 days, exposure assessments of 21 days and longer w ere conducted for all routes of

exposure (i.e., oral, dermal and inhalation) for all single chemical OP assessments usi ng

Calendex

. Gi ven this, the 21

- day and longer exposure assessment is scientifically supportable

and also provides consistency across the OPs

.

The acute aggregate dietary exposure for food and drinking water were below HED level of

concern for U.S. population and all p opulation subgroup s

. The steady state aggregate dietary

(food and drinking water) exposure estimates are above HED’s level of concern for the U.S.

population and all population subgroups. The acute critical exposure contribution (CEC)

analysis shows that drinking water is the driver

. Drinking water PR ZM/EXAMS time series

for dicrotophos were based on 3 cotton scenario s

.

X. Conclusions

Th ese unrefined analys es demonstrate that the requested uses for dicrotophos will not result in

acute dietary risk es timates that exceed HED ’s level of concern for any of the regulated

population subgroups, including those comprised of infants and children. However, the steady

state dietary exposure estimates are above HED’s level of concern for the U.S. population and all

population subgroups

.

X I

. List of Attachments

Attachment 1 : Example Acute (Food + Drinking Water) Residue Input File

Attachment 2 : Example Acute (Food + Drinking Water

- PR ZM

- EXAM ) Results File

Attachment 3 : Example Steady State (Food + Drinking Water

- PR ZM

- EXAM ) with Steady State

Endpoint Results File with CalendexPage 18 of 20



### Attachment 1 : Example Acute (Food + Drinking Water) Residue Input File

Filename: C: \ Documents and Settings \ tmorton \ My Documents \ MyFiles \ DEEM Files \ 035201

Dicrotophos \ 2013 Working Files USE THESE \ 035201 Acute MS Cotton Max Rate.R08

Chemical: Dicrotophos

RfD(Chronic): .0003 mg/kg bw/day NOEL(Chronic): 0 mg/kg bw/day

RfD(Acute): .0007 mg/kg bw/day NOEL(Acute): 0 mg/kg bw/day

Date created/last m odified: 02

- 06

- 2013/06:53:57 Program ver. 3.16, 03

- 08

- d

----------------------------------------------------------------------------------- RDL indices and parameters for Monte Carlo Analysis:

Index Dist Parameter #1 Param #2 Param #3 Commen t

# Code

----- ---- ------------ -------- -------- ------- 1 6 DrinkingWaterDicrotophosMScottonMaxRate Parent Only.rdf

EPA Crop Commodity Name Def Res Adj.Factors RDLComment

Code Grp (ppm) #1 #2 Pntr

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

2003128000 20C Cottonseed, oil 0.200000 1.000 1.000

2003128001 20C Cottonseed, oil

- babyfood 0.200000 1.000 1.000

8601000000 86A Water, direct, all sources 0.012600 1.000 1.000 1

8602000000 86B Water, indirect, all sources 0.012600 1.000 1.000 1



### Attachment 2 : Example Acute (Food + Drinking Water

- PR ZM

- EXAM ) Results File

U.S. EPA Ver. 3.16, 03

- 08

- d

DEEM

- FCID ACUTE Analysis for DICROTOPHOS NHANES 2003

- 2008 2

- Day

Residue file: 035201 Acute MS C otton Max Rate.R08 Adjustment factor #2 NOT used.

Analysis Date: 02

- 06

- 2013/07:05:23 Residue file dated: 02

- 06

- 2013/06:53:57

RAC/FF intake summed over 24 hours

MC iterations = 1000; MC list in residue file; MC seed = 50; RNG = MS VB

Run Comment: ""

==== ===========================================================================

Summary calculations

-- per capita:

95th Percentile 99th Percentile 99.9th Percentile

Exposure % aRfD Exposure % aRfD Exposure % aRfD

---------- -------- ---------- -------- ---------- -------- Total US Population:

0.000047 6.72 0.000132 18.84 0.000360 5 1.40

All Infants:

0.000103 14.67 0.000362 51.64 0.001037 148.14

Children 1

- 2:

0.000076 10.91 0.000214 30.60 0.000547 78.09

Children 3

- 5:

0.000071 10.19 0.0001 81 25.90 0.000468 66.88

Children 6

- 12:

0.000052 7.47 0.000145 20.77 0.000333 47.64

Youth 13

- 19:

0.000037 5.34 0.000107 15.27 0.000287 40.98

Adults 20

- 49:

0.000045 6.43 0.000127 18.13 0.000340 48.61

Adults 50

- 99:

0.000042 6.05 0.000117 16.77 0.000309 44.12

Female 13

- 49:

0.000044 6.32 0.000126 17.94 0.000343 49.06Page 19 of 20



### Attachment 3 : Example Acute (Food + Drinking Water

- PR ZM

- EXAM ) with Steady State

E ndpoint Results File with Calendex

CALENDEX

- FCID Analysis for STEADY STATE WITH TX COTTON MAX RATE GEN POP

Analysis Date 02

- 27

- 2013/13:38:13/0

Exposure analysis for 3 combined weeks: starting on day 1

Exposure amounts adjusted for body weight

Dietary Residue file: C: \ Documents and Settings \ tmort on \ My Documents \ MyFiles \ DEEM

Files \ 035201 Dicrotophos \ 2013 Working Files with New Version 914 \ Steady State with TX

Cotton Max Rate.R08 Last saved: 2/6/2013 6:57:41 AM

Dietary Adjustment factor #2 used.

Dietary Matching File not used.

No non

- dietary (resid ential) analysis

PRZM

- EXAMS file: C: \ Documents and Settings \ tmorton \ My Documents \ MyFiles \ DEEM Files \ 035201

Dicrotophos \ 2013 Working Files with New Version 914 \ dicrotophos TX cotton max parent

only1961 deleted.PE1 Last saved: 1/23/2013 7:03:28 AM

PE Anal ysis applied to Direct Water

PE Analysis applied to Indirect Water

RfD Oral = 0.0003 mg/kg

- BodyWt/day

Est'd max exposure: Oral = 100 mg/kg

- BodyWt/day

MC iterations = 5 MC seed = 50 RNG = Microsoft VB

NHANES Stat Wghts used.

Analyst Comments:

------------------------------------------------------------------------------- Population parameters: Ages 0 to 100 All Seasons

All Regions Sex: M F

- all

All Races

Nursing Status: Nursing and Non

- Nursing

Summary calculations (mg/kg

- BodyWt/day, per capi ta):

Mean 95th Percentile 99th Percentile 99.9th Percentile

Exposure % of RfD Exposure % of RfD Exposure % of RfD Exposure % of RfD

---------- --------- ---------- --------- ---------- --------- ---------- --------- Dietary Exposure

0.000005 2 0.000096 32 0.000100 33 0.000101 34

PRZM

- EXAMS Water Exposure

0.000000 0 0.000000 0 0.000000 0 0.000000 0

Dietary + PRZM

- EXAMS Wat er Exposure

0.000005 2 0.000096 32 0.000100 33 0.000101 34

===============================================================================

========================================================================== =====

ver. 9.14, 03

- 08

- d

CALENDEX

- FCID Analysis for STEADY STATE WITH TX COTTON MAX RATE GEN POP

Analysis Date 02

- 27

- 2013/13:38:36/0

Exposure analysis for 3 combined weeks: starting on day 2

Exposure amounts adjusted for body weight

Dietary Residue file: C: \ Documents and Settings \ tmorton \ My Documents \ MyFiles \ DEEM

Files \ 035201 Dicrotophos \ 2013 Working Files with New Version 914 \ Steady State with TX

Cotton Max Rate.R08 Last saved: 2/6/2013 6:57:41 AM

Dietary Adjustment factor #2 used.

Dietary Matching File not used.

No non

- dietary (residential) analysis

PRZM

- EXAMS file: C: \ Documents and Settings \ tmorton \ My Documents \ MyFiles \ DEEM Files \ 035201

Dicrotophos \ 2013 Working Files with New Version 914 \ dicrotophos TX cotton max parent

only1961 deleted.PE1 Last saved: 1/23/2013 7:03:28 AM

PE Analysis applied to Direct Water

PE Analysis applied to Indirect WaterPage 20 of 20

RfD Oral = 0.0003 mg/kg

- BodyWt/day

Est'd max exposure: Oral = 100 mg/kg

- BodyWt/day

MC iterations = 5 MC seed = 50 RNG = Microsoft VB

NHANES Stat Wghts used.

Analyst Comments:

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

Popu lation parameters: Ages 0 to 100 All Seasons

All Regions Sex: M F

- all

All Races

Nursing Status: Nursing and Non

- Nursing

Summary calculations (mg/kg

- BodyWt/day, per capita):

Mean 95th Percentile 99th Percentile 99.9th Perc entile

Exposure % of RfD Exposure % of RfD Exposure % of RfD Exposure % of RfD

---------- --------- ---------- --------- ---------- --------- ---------- --------- Dietary Exposure

0.000005 2 0.000096 32 0.000100 33 0.000101 34

PRZM

- EXAMS Water Exposure

0.000000 0 0.000000 0 0.000000 0 0.000000 0

Dietary + PRZM

- EXAMS Water Exposure

0.000005 2 0.000096 32 0.000100 33 0.000101 34

===============================================================================

===============================================================================