EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: [ PV Shah; (703) 308

- 1846 ]

[Insert petition number]

EPA has received a pesticide petition ( [insert petition number] ) from [ Drexel Chemical Company ( Drexel; EPA Company Number 19713)

, P.O. Box 13327, Memphis,

TN 38113

- 03227 ] request ing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a

tolerance for residues of [ Dichlormid ] in or on the raw agricultural commodit ies [ listed

in Table 1] at [ 0.05 parts per million (ppm) ]

. EPA has determined that the petition

contains data or information regarding the elements set forth in section 408 (d)(2) of

FFDCA ; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be

needed befor e EPA rules on the petition.

[ Table 1: Commodities for which Drexel is requesting tolerances for Dichlormid

Commodity Tolerance Level (parts per million)

Almond hulls 0.05 Animal feed, nongrass, group 18 0.05 Asparagus 0.05 Barley, grain 0.05 Barley, hay 0.05 Barley, straw 0.05 Beet, garden, leaves 0.05 Beet, sugar, molasses 0.05 Beet, sugar, roots 0.05 Beet, sugar, tops 0.05 Brassica, head and stem, subgroup 5A 0.05 Brassica, leafy greens, subgroup 5B 0.05 Buckwheat, grain 0.05 Bushberry subgroup 13

- 07B 0.05 Caneberry, subgroup 13

- 07A 0.05
Carrots, roots 0.05
Cattle, fat 0.05 Cattle, kidney 0.05
Cattle, liver 0.05
Cattle, meat 0.05 Cattle, meat byproducts, except kidney and liver 0.05
Cilantro, leaves 0.05
Coriander, seed 0.05 Cotton, gin byproducts 0.052

Commodity Tolerance Level (parts per million)
Cotton, undelinted seed 0.05

Cucumber 0.05

Dillweed 0.05 Egg 0.05 Grain, aspirate fractions 0.05
Goat, fat 0.05 Goat, kidney 0.05
Goat, liver 0.05
Goat, meat 0.05 Goat, meat byproducts, except kidney and liver 0.05 Grass, forage 0.05 Grass, hay 0.05
Horse, fat 0.05 Horse, kidney 0.05
Horse, liver 0.05
Horse, meat 0.05 Horse, meat byproducts, except kidney and liver 0.05 Leaf petioles, subgroup 4B 0.05 Melon, subgroup 9A 0.05

Milk 0.05
Millet, forage 0.05 Millet, grain 0.05 Millet, hay 0.05
Millet, straw 0.05 Nut, tree, group 14 0.05 Oat, forage 0.05 Oat, grain 0.05 Oat, hay 0.05
Oat, straw 0.05

Okra 0.05 Onion, bulb, subgroup 3

- 07A 0.05 Onion, green, subgroup 3

- 07B 0.05

Peanut 0.05 Peanut, hay 0.05
Peanut, meal 0.05

Potato 0.05 Poultry, fat 0.05 Poultry, meat 0.05 Poultry, meat byproducts 0.05 Pumpkin 0.05 Rice, grain 0.05 Rye, forage 0.05 Rye, grain 0.053

Commodity Tolerance Level (parts per million) Rye, straw 0.05
Safflower, seed 0.05
Sesame, seed 0.05 Sheep, fat 0.05 Sheep, kidney 0.05 Sheep, liver 0.05 Sheep, meat 0.05 Sheep, meat byproducts, except kidney and liver 0.05 Sorghum, grain, forage 0.05 Sorghum, grain, grain 0.05 Sorghum, grain, stover 0.05 Sorghum, sweet, stalk 0.05 Soybean, forage 0.05 Soybean, hay 0.05 Soybean, seed 0.05 Spinach 0.05 Squash, winter 0.05
Sunflower, seed 0.05
Sunflower, meal 0.05

Tomato 0.05 Tomato, paste 0.05 Turnip, greens 0.05 Vegetable, foliage of legume, subgroup 7A, except soybean 0.05 Vegetable, fruiting, Group 8, except tabasco pepper 0.05 Vegetable, legume, group 6 0.05 Vegetable, root, except sugar beet, subgroup 1B, except carrot 0.05 Vegetable, tuberous and corm, subgroup 1C 0.05 Wheat, forage 0.05 Wheat, grain 0.05 Wheat, hay 0.05
Wheat, straw 0.05 Section 18 emergency exemptions : Tolerances with regional registrations Pepper, nonbell 0.50 Pepper, tabasco 0.504

A. Residue Chemistry

[ Nature of the residue (NOR) and magnitude of the residue (MOR) studies have been conducted in support of the existing dichlormid permanent tolerances on corn

commodities. For this petition, Drexel has submitted a white paper detailing the rationale

for not conducting any additional NOR or MOR residue studies to support the additional requested tolerances listed in Table 1

. ]

1. Plant metabolism. [ An NOR study was conducted in corn at a nominal rate of 5 lb

ai/A on pre

- emergence soil, or post

- emergence foliar application . The residues were readily extractable from forage and stover but there was poor extractability for grain. The overall results of the study indicated that the metabolism of dichlormid was qualitatively similar in all corn matrices

. The total ra dioactive residue was low. EPA determined that the study was adequate to support permanent tolerances and that the residue of concern was the parent dichlormid. Based on the results of this and other residue studies (summarized below), EPA

determined that the tolerance expression for dichlormid includes potential metabolites and degradates of dichlormid, and compliance with the tolerance is measurement of dichlormid only. ]

2. Analytical method. [ The original analytical method (l imit of quantitation (LOQ)

of 0.05 ppm) for dichlormid is well defined and has been validated by EPA, supporting the 0.05 ppm tolerance level. A revised method, lowering the LOQ to 0.01 has also been reviewed and approved by EPA. ]

3. Magnitude of residues. [ Eight MOR trials on corn were conducted with dichlormid applied post

- emergence to 5

- 9 inch plants at a rate of 0.5 lb dichlormid/A. Eight additional trials were also conducted with dichlormid applied

to 9

- 12 inch plants at a rate of 0.48 lb dichlormid/A. The highest average field trial (HAFT) values were below analytical LOQ of either 0.003 ppm or 0.01 ppm dichlormid (depending on the trial) in all samples of forage, grain and stover

. ]

B. Toxicological Profile

[ The toxicology database for dichlormid is complete and has previously been reviewed by EPA for prior tolerance approvals. ]

1. Acute toxicity

. [ The acute toxicity of dichlormid is low to moderate depending on the route of exposure. Oral and dermal exposure studies results show moderate toxicity, while inhalation toxicity and eye irritation are low. ]

2. Genotoxicty. [ Five of the six genotoxicity studies conducted with dichlormid showed no evidence of genotoxic potential. In one study, an in vitro mouse lymphoma cell study, the study results indicated that dichlormid was mutagenic in
the cells tested with and without S9 activation, but these results were seen at dose levels that were cytotoxic. Even with one positive result at cytotoxic levels, the5

battery of studies indicate that dichlormid is not mutagenic. ]

3. Reproductive and developmental toxicity. [ Reproductive and developmental

studies were conducted on rats and rabbits.

a. Rat d evelopmental toxicity: In the rat study, the d oses tested were 0, 10, 40, 160 mg/kg/day. The maternal NOAEL was 10 mg/kg/day and

the maternal LOAEL w as 40 mg/kg/day, based on decreased mean absolute body weight, body weight gains, and food consumption. The developmental NOAEL in the rat study was 40 mg/kg/day and the

d evelopmental LOAEL was 160 mg/kg/day based on a marginal

increase in skeletal abnormalities.

b. Rabbit d evelopmental toxicity: In the rabbit study, the d oses tested

were 0

, 5, 30, 18 0 mg/kg/day. The maternal NOAEL was 30 mg/kg/day and the maternal LOAEL was 180 mg/kg/day, based on increased incidence of alopecia, decreased mean materna l body weight gain, and decreased food consumption. The developmental NOAEL was 30 mg/kg/day and the developmental LOAEL was 180 mg/kg/day

based on an increase in post

- implantation loss and increased number of early and late resorptions/doe, decreased numb er of live fetuses/litter, and a slight decrease in mean fetal body weight.

c. Rat reproduction toxicity: In the rat reproduction study the doses

tested were M 0 : 0, 1.5, 7.4, 48.5 mg/kg/day; M 1 : 0, 1.8, 8.9, 59.4 mg/kg/day; F 0 : 0, 1.6, 8.0, 52.1 mg/kg/day; and F 1 : 0, 1.9, 9.4, 63.0 mg/kg/day. The parental/systemic NOAEL s were 7.4 mg/kg/day (male), and 8.0 mg/kg/day (female) and the parental/systemic

LOAEL s were 48.5 mg/kg/day (male) and 52.1 mg/kg/day (female) based on minimal increased liver weight, minimal decreased weight gain, and a minimal decrease in food consumption. The reproductive

NOAEL s were 48.5 mg/kg/day (male) and 52.1 mg/kg/day (female), and the reproductive LOAEL s was not determined. The offspring

NOAEL s were 7.4 mg/kg/day (male) and 8.0 mg/kg /day (female) and the offspring LOAEL s were 48.5 mg/kg/day (male) and 52.1 mg/kg/day (female) based on increased liver weight. ]

4. Subchronic toxicity. [ Subchronic studies have been conducted on the rat and the dog by oral and inhalation routes. A subchronic neurotoxicity study has also been

conducted in the rat. No 90

- day dermal study was conducted so EPA assumes 100% as a default value for dermal absorption.

a. Rat s ubchronic oral toxicity : In the rat study , the d oses tested were 0, 1.4, 14, 140 mg/kg/day (male) and 0, 1.6, 16, 150 mg/kg/day (female).

The NOAEL s were 1.4 mg/kg/day (male) and 14 mg/kg/day (female)

and the LOAEL s were 14 mg/kg/day (male) and 16 mg/kg/day (female) b ased on a minor decrease in body weight gain and food efficiency in females, a nd increased liver weight s and non

- statistically significant liver lipidosis in males

.6

b. Dog subchronic oral toxicity: In the dog study , d oses tested were 0, 1, 5, 25, 50 mg/kg/day . The NOAEL was 5 mg/kg/day (male and female)

and the LOAEL was 25 mg/kg/day (male and female) b ased on decreased body weight gain, hematological and clinical chemistry alterations, liver toxicity, and voluntary muscle pathological changes

.

c. Rat sub c hronic inhalation toxicity: In the rat study , d oses tested were 0, 2, 19.2, 192.5 mg/L/day . The NOAEL was 2 mg/L/day (male and female) and the LOAEL was 19.9 mg/L/day (male and female) b ased on clinical signs, gross pathology, ophthalmology, liver and kidney weights and non

- neoplastic histology

. d. Rat subchronic neurotoxicity: In the 2011 dichlormid EPA Human Health Risk Assessment (Dichlormid: Human Health Risk Assessment for the Purpose of Making Time

- Limited Tolerances of Field Corn Commodities Permanent; DP Barcode D385691; January 13, 2011)

EPA noted that although the study was not acceptable, no additional study was required to be conducted. ]

5. Chronic toxicity. [ Chronic studies have been conducted in the rat, mouse and dog, No information on the chronic dog study details or results is available in EPA risk

assessment document s so it is not summarized here or in the petition

.

a. Rat carcinogenicity: In the rat study , d oses tested were 0, 1.3, 6.5, 32.8 mg/kg/day (male) and 0, 1.5, 7.5, 37.1 mg/kg/day (female). The NOAELs were 6.5 mg/kg/day (male) and 7.5 mg/kg/day (female) and the LOAELs were 32.8 mg/kg/day (male) and 37.1 mg/kg/day (female) based on decreased body weight gain, increased liver weight,

and liver histopathology. Dichlormid was not carcinogenic.

b. Mouse carcinogenicity: In the mouse study

, doses tested were 0, 1.4, 7.0, 70.7 mg/kg/day (male) and 0, 1.8, 9.2, 92.4 mg/kg/day (female). The NOAELs were 7.0 mg/kg/day (male) and 9.2 mg/kg/day (female) and the LOAELs 70.7 mg/kg/day (male) and 92.4 mg/kg/day (female) based on changes in repr oductive organs and kidney changes in

males. ]

6. Animal metabolism. [ In a rat study, d ichlormid was well absorbed, extensively metabolized and excreted primarily in the urine within 24 hours. Up to 11% of the

dose was exhaled as CO 2

. In an NOR study in the goat, very low measured residues were found in goat tissues (<0.001

- 0.023 ppm) when dosed at approximately 200X of 0.05 ppm tolerance level. EPA concluded that no animal tolerances were required for dichlormid based on the results of the goat study . In

an NOR study in the hen, very little dichlormid was detected in tissues, and a very

small fraction of the total radioactive residues was identified in each matrix analyzed. ]7

7. Metabolite toxicology

. [ Not Applicable/Not required ]

8. Endocrine disruption

. [ A study to assess the endocrine disruption potential of

dichlormid has not been conducted. The database of studies conducted with dichlormid do not indicate any adverse effects associated with endocrine disruption. Furthermore, dichlormid was not included on EPA’s July 2015 list of Tier 1 screening assays for the first 52 chemicals assessed in the Endocrine Disruptor Screening Program

. ]

C. Aggregate Exposure

[ To examine aggregate exposure, available information concerning exposures from the pesticide residu e in food and all other non

- occupational exposures, including drinking water from groundwater or surface water and exposure through pesticide use in gardens, lawns, or buildings (residential and other indoor uses) is considered.

On the basis of dichlormi d data, the proposed use patterns (which do not include residential uses) and the results of a conservative dietary exposure and risk assessment it is unlikely that humans (adults and children) would be exposed to significant residues of

dichlormid via foo ds and in drinking water. A p revious EPA risk assessment ( Human

Health Risk Assessment for Dichlormid . Petition Number 4F6950. DP Barcode D321927, November 15 , 2005 ) indicated that acute and chronic aggregate risk were
below the level of concern, and short and intermediate term aggregate risk assessments

were not conducted because of the lack of residential uses. ]

1. Dietary exposure. [ As the request for expansion of tolerances for dichlormid includes a more extensive list of crops than were previousl y evaluated, Drexel conducted updated acute and chronic dietary (including drinking water) exposure and risk assessments. These conservative Tier 1 assessments incorporated all current tolerances and all the proposed additional crops. Tolerance level resid ues of 0.05 ppm, default processing factors, and 100% crop treated were used in the acute and chronic

risk assessments. The acute and chronic risks are below 100% of their respective acute and chronic reference doses (aRfD = 0.1 mg/kg bw/day; cRfD = 0.065 mg/kg bw/day ). In 2011, EPA reduced all FQPA factors for this compound to 1X, these results meet the reasonable certainty of no harm standard

. ]

i. Food. [ The available data demonstrate that the chronic dietary (food and drinking water) exposures for dic hlormid are well below EPA’s established level of concern for all U.S. subpopulations. ]

ii. Drinking water

. [ Drinking water is included in the assessment conducted with the tolerance petition. Exposure to dichlormid from drinking water is expected to be negligible. ]

2. Non

- dietary exposure

. [ None ]8

D. Cumulative Effects

[ N o data are available to determine whether dichlormid has a common mechanism of toxicity with other substances. Because of this lack of data and the absence of the ability

to include it in a cumulative risk assessment, EPA has assumed for previous tolerance reviews and approvals that there is no common mechanism of toxicity with other
substances. Drexel believes that, in the continued absence of additional information, EPA

should conti nue to make the assumption for the risk assessments associated with this tolerance amendment petition that no common mechanisms exist. ]

E. Safety Determination

1. U.S. population. [A dietary exposure assessment for dichlormid was conducted.

Based on th e conservative dietary exposure estimates, there is a reasonable certainty that no harm will result to the US population from the aggregate exposure to

dichlormid

. ]

2. Infants and children

. [ The FQPA Safety Factor for dichlormid is 1X because there

are no uncertainties in the database of studies

. The dietary exposure risk assessment (including drinking water), includes analysis of the %RfD for the entire US population and all subpopulations (including infants and children). The risk assessment shows that, for infants and children, there is a reasonable certainty that no harm will result from the aggregate exposure to dichlormid. ]

F. International Tolerances

[ There are no known international tolerances for dic h lormid.]