**[\<]{.mark}COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE
(7/1/2006)**[\>]{.mark} Dimethenamid-P (BAS 656-PH): new IR-4 crops
including winter squash, pumpkin, radish, turnip, rutabaga, hops.
November 28, 2006

**[\<]{.mark}EPA Registration Division contact: \[James A. Tompkins at
703-305-5697\][\>]{.mark}**

**[\<]{.mark}*INSTRUCTIONS:* Please utilize this outline in preparing
tolerance petition documents. In cases where the outline element does
not apply please insert "NA-Remove" and maintain the outline. The
comment notes that appear on the left margin represent hidden
typesetting codes designed to expedite the processing of the Federal
Register document. Please do not remove or alter these comment notes or
change the margins, font, or format in your document. Simply replace the
instructions that appear in italics and brackets, i.e., "****\[*insert
company name*\]," with the information specific to your
action.\][\>]{.mark}**

**[\<]{.mark}*TEMPLATE:*[\>]{.mark}**

**[\<]{.mark}\[Interregional Research Project Number 4
(IR-4)\][\>]{.mark}**

**[\<]{.mark}\[PP-06596, 07909, 07697, 07696, 09813,
08705\][\>]{.mark}**

**[\<]{.mark}** 21 U.S.C. 346 EPA has received a pesticide petition
**(****\[Insert petition number, PP-xxxxxx\])** from **\[Interregional
Research Project Number 4 (IR-4)\], \[500 College Road East, Suite 201
W, Princeton, NJ, 08540\]** proposing, 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 180.361 by establishing a tolerance for residues of
**\[the herbicide dimethenamid,
(R,S)-2-chloro-*N*-\[(1-methyl-2-methoxy)
ethyl\]-*N*-(2,4-dimethyl-thien-3-yl)-acetamide)\]** in or on the raw
agricultural commodity **\[winter squash, pumpkin, radish roots, radish
tops, turnip roots, turnip tops, turnip greens, rutabaga roots, rutabaga
tops, hops dried cones\]** at **\[0.01, 0.01, 0.01, 0.01, 0.01, 0.1,
0.1, 0.01, 0.1, 0.05, respectively,\]** 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 the FDDCA; 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 before EPA rules on the petition.**[\>]{.mark}**

[\<]{.mark}*A. Residue Chemistry*[\>]{.mark}

**[\<]{.mark}** 1. *Plant metabolism.* **\[BASF Corporation notes that
metabolism in plants and animals is well understood.\][\>]{.mark}**

**[\<]{.mark}** 2. *Analytical method.* **\[The proposed analytical
method uses extraction and clean-up followed by quantification with
capillary column gas chromatography using thermionic nitrogen specific
detector. A GS/MS method for identification is also available. This
method is not selective towards the dimethenamid isomer and is therefore
valid for residues from both racemic dimethenamid and the enriched
isomer dimethenamid-P. Tolerances are proposed based on a non-isomer
specific basis.\][\>]{.mark}**

**[\<]{.mark}** 3. *Magnitude of residues.* **\[Field trials in major
growing areas were carried out in order to determine the magnitude of
residues in the winter squash, radish, turnip and hop commodities. EPA
has determined that the petition contains data or information regarding
the above aforementioned crops. Field trials were conducted in the
required regions. Field trials were carried out using the maximum number
of applications, the maximum label rate and shortest pre-harvest
interval (PHI).**

**Dimethenamid-P is the biologically active isomer from the racemic
dimethenamid mixture. The analytical residue method measures both
dimethenamid and dimethenamid-P, so the residue determinations in winter
squash, radish, turnip and hops for dimethenamid-P are considered
representative of the proposed treatments with dimethenamid.**

**Due to the low levels of residue in the RAC\'s, tolerances in animal
commodities are not required.\]\>**

**[\<]{.mark}***B. Toxicological Profile***[\>]{.mark}**

**[\<]{.mark}** 1. *Acute toxicity.* **\[Based on available acute
toxicity data, dimethenamid and dimethenamid-P do not pose an acute
dietary risk. The acute toxicity studies place both technical materials
in acute toxicity category II for acute oral; in acute toxicity category
III for acute dermal, inhalation, and eye; and in acute toxicity
category IV for dermal irritation. The technical materials are both
positive skin sensitizers.\][\>]{.mark}**

**[\<]{.mark}** 2. *Genotoxicty.* **\[The following testing was
performed with dimethenamid for genotoxicity. A Modified Ames Test:
Negative; [In Vitro]{.underline} CHO/HGPRT Mammalian Cell mutation
Assay: Negative; [In Vitro]{.underline} Cytogentics - CHO Cells (1
Study; Chromosome Aberrations): Weakly Positive; [In Vitro]{.underline}
UDS Test Using Rat Hepatocytes (3 Studies; DNA damage and repair): 2
Negative; 1 Equivocally Positive, Mouse Micronucleus Assay (2 Studies;
Chromosome Aberrations): Negative, Rat Dominant Lethal Assay : 1 study
equivocally positive, 1 study negative. Overall dimethenamid has been
tested in 14 genetic toxicology assays. The weight of-the-evidence
demonstrates that dimethenamid is not genotoxic.**

**The following testing was performed with dimethenamid-P for
genotoxicity. A Modified Ames Test (3 Studies; point mutation):
Negative; [In Vitro]{.underline} CHO/HGPRT Mammalian Cell mutation Assay
(1 Study; point mutation): Negative; [In Vitro]{.underline}
Cytogentics - CHO Cells (1 Study; Chromosome Aberrations): Negative; [In
Vitro]{.underline} UDS Test Using Rat Hepatocytes (1 Study; DNA damage
and repair): Negative; Mouse Micronucleus Assay (1 Study; Chromosome
Aberrations): Negative**

**Dimethenamid-P has been tested in a total of 7 genetic toxicology
assays. These assays were performed both in vitro and in vivo and
multiple assays were conducted for each of the three EPA Guideline
requirement categories. Based on the data presented above, the data
indicates that dimethenamid-P does NOT induce gene mutations, is not
clastogenic and does not induce other effects indicative of
genotoxicity. Therefore, dimethenamid-P does not pose a mutagenic hazard
to humans.\][\>]{.mark}**

**[\<]{.mark}** 3. *Reproductive and developmental toxicity.*
**\[Developmental toxicity - Rat**

**A developmental rat study testing dimethenamid via oral gavage at
doses of 0, 50, 215, and 425 mg/kg/day resulted in a development
toxicity NOAEL of 215 mg/kg/day and a maternal toxicity NOAEL of 50
mg/kg/day based on based on the following: (1) signs of maternal
toxicity, in the form of reduced body weight gain and food consumption,
increased liver weight and clinical observations were observed at dose
levels [\>2]{.underline}15 mg/kg/day with an increase in effects to the
upper dose level; (2) at doses ≥215 mg/kg/day, slight decreases in fetal
body weights were observed and (3) at the 425 mg/kg/day dose level a
slight increase in resorptions was observed, and two fetuses had
incomplete ossified manubria. These findings are not indicative of a
teratogenic effect and developmental toxicity was only observed at doses
with maternal toxicity.**

**A developmental rat study using dimethenamid-P via oral gavage tested
at doses of 0, 25, 150, and 300 mg/kg/day with a development toxicity
NOAEL of 25 mg/kg/day and a maternal toxicity of 25 mg/kg/day based on
the following: (1) signs of maternal toxicity, in the form of decreased
body weights and food consumption were observed at dose levels
[\>]{.underline}150 mg/kg/day with an increase in effects to the upper
dose level; (2) at the 150 mg/kg/day dose level slight decreases in
fetal body weights and retarded ossification of the pelvis pubis were
observed; and (3) at the 300 mg/kg/day dose level slight decreases in
fetal body weights, microphthalmia in two fetuses/two litters, distended
ureters, and retarded ossification of the 2nd sternal centra and pelvis
pubis were observed. These findings are not indicative of a teratogenic
effect and developmental toxicity was observed only at doses with
maternal toxicity.**

**Developmental toxicity - Rabbits**

**A developmental study in rabbits tested dimethenamid via oral gavage
at doses of 0, 37.5, 75, and 150 mg/kg/day (HDT) with a development
toxicity NOAEL of 75 mg/kg/day and a maternal toxicity of 37.5 mg/kg/day
based on: (1) decreased body weight, food consumption, and
absorption/premature delivery in the 75 and 150 mg/kg/day dose groups;
and (2) effects on fetal development including a low incidence of
absorption/premature delivery and an increased incidence of minor
skeletal ossifications in the 150 mg/kg/day dose group. These findings
are not indicative of a teratogenic effect and developmental toxicity
was observed only at a dose that also demonstrated maternal toxicity.**

**Reproduction Toxicity:**

**A two-generation reproduction study using dimethenamid with rats fed
dosages of 0, 7.5, 38, and 155 mg/kg/day (average mg/kg/day dose levels
for both male and female rats) with a reproductive NOAEL of 38 mg/kg/day
and with a parental NOAEL of 38 mg/kg/day based on: (1) parental
toxicity as evident by reduction in body weight and food consumption and
significant increases in absolute and/or relative liver weights in both
males and female rats in the 155 mg/kg/day dose group; and (2)
significant reductions in pup weight during lactation were observed in
the 150 mg/kg/day dose group. No changes in pregnancy rates, fertility
or length of gestation were observed at all dose levels tested.**

**As stated above, the NOAEL of 5 mg/kg/day from the chronic rat study
used to set the RfD is \~8x lower than the maternal NOAEL established in
the rat reproduction study. Therefore, no additional safety factor is
needed for children.\][\>]{.mark}**

**[\<]{.mark}** 4. *Subchronic toxicity.* **\[The short-term toxicity of
dimethenamid was investigated in an oral 28-day range-finding study in
rats as well as in 3-month studies in rats, mice, and dogs. In addition
the short-term toxicity following dermal exposure was determined in a
21-day study in rabbits.**

**The signs of toxicity observed in the three species tested were
overall similar with the liver as the target organ. The effects observed
typically included the increase in one or more serum liver enzymes and
changes in cholesterol. Pathology confirmed the liver to be a target
organ. Increased liver weights were observed in all three species
probably indicative of an adaptive response to exposure. Histologically,
hepatocyte hypertrophy was observed in rats and hepatocyte vacuolation
and dilatation of liver sinusoids occurred in dogs.**

**In a 3-week dermal toxicity study in rabbits no substance-related
systemic findings were detected up to the highest dose level tested of
1,000 mg/kg bw.\][\>]{.mark}**

**[\<]{.mark}** 5. *Chronic toxicity.* **\[Chronic Feeding - Dogs**

**A 1-year feeding study in dogs fed dimethenamid at dosages of 0, 2,
9.6, or 49 mg/kg/day with a No-Adverse-Effect Level (NOAEL) of 9.6
mg/kg/day based on the following effects: (1) slight decreases in body
weights for both the high dose male and female dogs as compared to
controls; (2) a variable degree of periportal hepatocyte vacuolation in
the high-dose male and female dogs; (3) minimal or mild hepatocyte
enlargement was similarly observed in the high-dose dogs; and (4) the
liver changes at the high-dose group correlated with increase in serum
alkaline phosphatase activity and cholesterol levels and increased
liver-to-body weight ratios in both male and female dogs.**

**Chronic Feeding/Oncogenicity - Rats**

**A combined chronic feeding/oncogenicity study was performed in rats at
doses of 0, 5.1, 36, and 80 mg/kg/day (males) and 0, 6.8, 49, and 109
mg/kg/day (females) with a NOAEL of 5.1 mg/kg/day (males) and 6.8
mg/kg/day (females) based on the following effects: (1) decreased body
weights in both males and female rat at dose levels [\>]{.underline}36
mg/kg/day dose groups with a slight progression of severity to the upper
level; (2) decreased food consumption in both males and female rats at
dose levels [\>]{.underline}36 mg/kg/day dose groups with a slight
progression of severity to the upper dose level; (3) minimal
hematological and clinical chemistry changes at dose levels
[\>]{.underline}36 mg/kg/day; (4) increased absolute liver weights for
females at dose levels [\>]{.underline}49 mg/kg/day; (5) microscopic
findings were observed in the liver, parathyroid, and stomach of
high-dose males, only, and ovaries of high-dose females; and (6) an
increased incidence of benign tumors in the liver of male animals at the
highest dose level tested. Overall, the slight increase in the benign
liver tumor in high dose males does not indicate that dimethenamid is
carcinogenic. The increase was not statistically significant, was within
historical control range for Sprague-Dawley rats and was most likely due
to the considerable increase in survival at that dose.**

**iii. Oncogenicity - Mice**

**A carcinogenicity study using dimethenamid in mice tested doses of 0,
3.8, 41, 205, and 431 (HDT) mg/kg/day (males) and 0, 4.1, 41, 200, and
411 (HDT) mg/kg/day (females) with a NOAEL of 41 mg/kg/day for male and
female mice based on the following effects: (1) decreased body weights
and food consumption were observed in both males and female mice at the
highest dose tested; (2) increased liver weights were observed for male
and female mice at the highest dose tested at an interim sacrifice and
increased weights for kidney and liver were observed for female mice at
dose levels [\>]{.underline}200 mg/kg/day at terminal sacrifice; (3)
microscopic findings were observed in the liver and stomach for both
male and female mice at the upper dose levels; (4) concerning the
finding in the stomach, EPA has determined that this finding was
attributed to irritation of the material and the finding was not
toxicology significant; and (4) no increased incidence of neoplasms
occurred at any dose levels tested in this study. EPA has concluded that
this product is [not]{.underline} oncogenic under the conditions of this
study.\][\>]{.mark}**

**[\<]{.mark}** 6. *Animal metabolism.* **\[Dimethenamid was well
absorbed (\>90%) and extensively metabolized by rats. Excretion was
rapid primarily by bile. In 7 hr, 45% to 64% of the oral dose was
excreted in bile. By 168 hours after treatment, an average of 90% of the
administered dose was eliminated by all routes. The radioactivity level
in blood decreased slowly in rat and was associated with some blood
components., however, binding to blood components was demonstrated to
not occur in human blood. Levels in other tissue after 168 hr were
small, and there was no evidence for a bioaccumulation potential.**

**The unchanged dimethenamid in excreta accounted for only 1-2% of the
dose. There were over 40 metabolites detected in excreta. Over 20
metabolites were structurally identified by MS and NMR, and confirmed
with the synthesized reference standards. Metabolism was primarily via
glutathione conjugation pathways. Dimethenamid was also metabolized via
reductive dechlorination, oxidation, hydroxylation, O-demethylation, and
cyclization. There was no significant difference in absorption,
distribution, elimination and metabolism between sexes. There was also
no significant difference in percent absorption between the low dose of
10 mg/kg and the high dose of 1,000 mg/kg, or between the single and
multiple doses. However, it appeared the elimination via bile was
saturated at 1,000 mg/kg because the elimination via kidney increased
for the high dose.\][\>]{.mark}**

**[\<]{.mark}** 7. *Metabolite toxicology*. **\[The dimethenamid
metabolites M23 and M27 were tested in acute oral toxicity studies and
in the Ames mutagenicity assay and the mouse micronucleus assay. Both
compounds had low acute oral toxicity with LD50's greater than 5,000.
Both compounds were also negative in both the Ames assay and the mouse
micronucleus assay.\][\>]{.mark}**

**[\<]{.mark}** 8. *Endocrine disruption*. **\[No specific tests have
been performed with dimethenamid-P or dimethenamid to determine whether
the chemical may have an effect in humans that is similar to an effect
produced by naturally occurring estrogen or other endocrine effects.
However, there are no significant findings in other relevant toxicity
studies, i.e. teratology and multi-generation reproductive studies,
which would suggest the dimethenamid produces endocrine related
effects.\][\>]{.mark}**

**[\<]{.mark}***C. Aggregate Exposure***[\>]{.mark}**

**[\<]{.mark}** 1. *Dietary exposure.* **\[An assessment was conducted
to evaluate the potential risk due to acute dietary exposure of females
13-49 yrs of age and chronic dietary exposure of the U.S. population and
all sub-populations to residues of Dimethenamid. Tolerance values that
have previously been established are listed in U.S. 40 CFR § 180.464.**

**This analysis included all crops with established tolerance values,
crops pending tolerance assignment (grass grown for seed) and proposed
new crops from IR-4 (including winter squash, pumpkin, radish, turnip,
rutabaga and dried cone hops).**

**The dietary assessments were conducted using tolerance level for all
commodities, default processing factors, and 100% crop treated factors.
These assumptions are conservative because it assumes all commodities
will be at tolerance level and 100% of the crop has been treated with
dimethenamid. Inadvertent residues in animal commodities (i.e. meat,
meat byproducts, milk, eggs) were not considered because studies have
shown that dimethenamid does not accumulate in animal tissues or milk
and tolerance values for these commodities are not required by the
EPA.\]**[\>]{.mark}

[\<]{.mark} i. *Food.* **\[[Acute Dietary Exposure
Assessment]{.underline}**

**The EPA has concluded that an acute assessment is only required for
females ages 13-49 years old. An acute assessment for other
sub-populations is not required. The acute dietary exposure assessment
was conducted using the Dietary Exposure Evaluation Model software with
Food Commodity Intake Database (DEEM-FCID). The acute population
adjusted dose (aPAD) used for females 13-49 years of age was 0.75 mg/kg
bw/day. Using the exposure assumptions discussed above, dimethenamid
acute dietary exposure from food is less than 0.1 % aPAD. The results of
the acute dietary assessment for females 13-49 years of age are
presented in Table 1.**

+----------------------------+--------------------------+--------------+
| **Table 1. Results for     |                          |              |
| Dimethenamid Acute Dietary |                          |              |
| Exposure Analysis Using    |                          |              |
| DEEM-FCID at the 95^th^    |                          |              |
| Percentile.**              |                          |              |
+----------------------------+--------------------------+--------------+
| Population                 | Exposure Estimate        | %aPAD        |
|                            |                          |              |
| Subgroups                  | (mg/kg bw/day)           |              |
+----------------------------+--------------------------+--------------+
| Females 13-49 years        | 0.000075                 | \< 0.1       |
+----------------------------+--------------------------+--------------+
|                            |                          |              |
+----------------------------+--------------------------+--------------+

**[Chronic Dietary Exposure Assessment]{.underline}**

**A chronic assessment was conducted for all sub-populations. The
chronic dietary exposure assessment was conducted using the Dietary
Exposure Evaluation Model software with Food Commodity Intake Database
(DEEM-FCID). The chronic population adjusted dose (cPAD) used for all
sub-populations was 0.05 mg/kg bw/day. Using the exposure assumptions
discussed above, dimethenamid chronic dietary exposure from food is less
than 0.3 % cPAD for all sub-populations. The results of the chronic
dietary assessment are presented in Table 2.**

+----------------------------+--------------------------+--------------+
| **Table 2. Summary of      |                          |              |
| Chronic Dietary Exposure   |                          |              |
| Assessment considering     |                          |              |
| crops with established and |                          |              |
| proposed tolerances  for   |                          |              |
| Dimethenamid.**            |                          |              |
+----------------------------+--------------------------+--------------+
| **Population**             | **Exposure Estimate**    | **%cPAD**    |
|                            |                          |              |
| **Subgroups**              | **(mg/kg b.w./day)**     |              |
+----------------------------+--------------------------+--------------+
| **U.S. Population**        | **0.00004**              | **0.1**      |
+----------------------------+--------------------------+--------------+
| **All Infants**            | **0.0000650**            | **0.1**      |
+----------------------------+--------------------------+--------------+
| **Children 1-2 years**     | **0.0000870**            | **0.2**      |
+----------------------------+--------------------------+--------------+
| **Children 3-5 years**     | **0.0000870**            | **0.2**      |
+----------------------------+--------------------------+--------------+
| **Children 6-12 years**    | **0.0000630**            | **0.1**      |
+----------------------------+--------------------------+--------------+
| **Youth 13-19 years**      | **0.0000440**            | **0.1**      |
+----------------------------+--------------------------+--------------+
| **Females 13-49 years**    | **0.0000320**            | **0.1**      |
+----------------------------+--------------------------+--------------+
| **Adults 20-49 years**     | **0.0000330**            | **0.1**      |
+----------------------------+--------------------------+--------------+
| **Adults 50+ years**       | **0.0000270**            | **0.1**      |
+----------------------------+--------------------------+--------------+
|                            |                          |              |
+----------------------------+--------------------------+--------------+

**\]**[\>]{.mark}

[\<]{.mark} ii. *Drinking Water.* **\[Since the models used are
considered to be screening tools in the risk assessment process, the
Agency does not use estimated drinking water concentrations (EDWCs) from
these models to quantify drinking water exposure and risk as %PAD.
Instead, drinking water levels of comparison (DWLOCs) are calculated and
used as points of comparison against the model estimates of a
pesticide's concentration in water. A DWLOC is the theoretical upper
allowable limit of a pesticide\'s concentration in drinking water and is
calculated with considering the aggregate exposure to a pesticide from
food and residential uses. A DWLOC will vary depending on the toxic
endpoint, drinking water consumption, body weights, and pesticide
uses.**

**Different populations will have different DWLOCs. If the DWLOC is
greater than the model water concentrations, the EPA concludes that
exposure from drinking water is not a risk issue. The modeled water
concentration is obtained from FIRST model for surface water and SCIGROW
for groundwater. The values used for comparison to the DWLOC are the
maximum concentrations for any use. When the EDWC's are less than the
calculated DWLOCs, EPA concludes with reasonable certainty that
exposures to the pesticide in drinking water would not result in
unacceptable levels of aggregate human health risk.**

**Based on the PRZM/EXAMS and SCIGROW models, the EDWCs of dimethenamid
for acute exposure are estimated to be 49 ug/L (ppb) in surface water
and 0.42 ug/L in shallow ground water. The EDWCs for chronic exposure
are estimated to be 7.9 ug/L in surface water and 0.42 ug/L in shallow
ground water. The 36-year average of dimethenamid in surface water that
was estimated by PRZM/EXAMS for use in the chronic/cancer risk
assessment is 5.1 ug/L/. These EDWC values are the maximum modeled
considering all dimethenamid uses.**

**[Acute Aggregate Exposure and Risk (Food and water)]{.underline}**

The aggregate acute risk includes residues of dimethenamid from food and
water. Exposures from residential uses are not included in the acute
aggregate assessment. The EDWCs for dimethenamid in surface and ground
water are lower than the DWLOCs for all sub-populations (Table 3).

+---------+--------+--------+---------+---------+---------+---------+
| # Tabl  |        |        |         |         |         |         |
| e 3. Ac |        |        |         |         |         |         |
| ute Dri |        |        |         |         |         |         |
| nking W |        |        |         |         |         |         |
| ater Le |        |        |         |         |         |         |
| vels of |        |        |         |         |         |         |
|  Compar |        |        |         |         |         |         |
| ison fo |        |        |         |         |         |         |
| r Dimet |        |        |         |         |         |         |
| henamid |        |        |         |         |         |         |
+---------+--------+--------+---------+---------+---------+---------+
| **Pop   | **aPAD | **Food | Max.    | Acute   | Acute   | **DWLOC |
| ulation | (      | Exp    | Water   | Ground  | Surface | (       |
| Sub     | mg/kg/ | (      | Exp     | Water   | Water   | ug/L)** |
| group** | day)** | mg/kg/ | (mg/    | EDWC    | EDWC    |         |
|         |        | day)** | kg/day) | (ug/L)  | (ug/L)  |         |
+---------+--------+--------+---------+---------+---------+---------+
| Females | 0.75   | 0.     | 0       | 49      | 0.42    | 22497   |
| 13-49   |        | 000075 | .749925 |         |         |         |
| years   |        |        |         |         |         |         |
+---------+--------+--------+---------+---------+---------+---------+
|         |        |        |         |         |         |         |
+---------+--------+--------+---------+---------+---------+---------+

**The results in the Table 3 demonstrate that there are no safety
concerns for any sub-population based on established and new uses, and
that the results clearly meet the FQPA standard of reasonable certainty
of no harm.**

**[Chronic Aggregate Exposure and Risk (food and water)]{.underline}**

**The aggregate chronic risk includes residues of dimethenamid from food
and water. Exposures from residential uses are not included in the
chronic aggregate assessment. The EDWCs for dimethenamid in surface and
ground water are lower than the DWLOCs for all sub-populations (Table
4).**

+---------+--------+--------+---------+---------+---------+---------+
| #       |        |        |         |         |         |         |
|  Table  |        |        |         |         |         |         |
| 4. Chro |        |        |         |         |         |         |
| nic Dri |        |        |         |         |         |         |
| nking W |        |        |         |         |         |         |
| ater Le |        |        |         |         |         |         |
| vels of |        |        |         |         |         |         |
|  Compar |        |        |         |         |         |         |
| ison fo |        |        |         |         |         |         |
| r Dimet |        |        |         |         |         |         |
| henamid |        |        |         |         |         |         |
+---------+--------+--------+---------+---------+---------+---------+
| **Pop   | **cPAD | **Food | **Max.  | **Acute | **Acute | **DWLOC |
| ulation | (      | Exp    | Water   | Ground  | Surface | (       |
| Sub     | mg/kg/ | (      | Exp     | Water   | Water   | ug/L)** |
| group** | day)** | mg/kg/ | (mg/kg  | EDWC    | EDWC    |         |
|         |        | day)** | /day)** | (       | (       |         |
|         |        |        |         | ug/L)** | ug/L)** |         |
+---------+--------+--------+---------+---------+---------+---------+
| **U.S.  | **     | **0.0  | **0.    | **7.9** | *       | *       |
| Popul   | 0.05** | 0004** | 04996** |         | *0.42** | *1749** |
| ation** |        |        |         |         |         |         |
+---------+--------+--------+---------+---------+---------+---------+
| **All   | **     | **0.00 | **0.0   |         |         | **499** |
| Infants | 0.05** | 0065** | 49935** |         |         |         |
| (\< 1   |        |        |         |         |         |         |
| yr      |        |        |         |         |         |         |
| old)**  |        |        |         |         |         |         |
+---------+--------+--------+---------+---------+---------+---------+
| **C     | **     | **0.00 | **0.0   |         |         | **499** |
| hildren | 0.05** | 0087** | 49913** |         |         |         |
| 1-2     |        |        |         |         |         |         |
| years** |        |        |         |         |         |         |
+---------+--------+--------+---------+---------+---------+---------+
| **C     | **     | **0.00 | **0.0   |         |         | **499** |
| hildren | 0.05** | 0087** | 49913** |         |         |         |
| 3-5     |        |        |         |         |         |         |
| years** |        |        |         |         |         |         |
+---------+--------+--------+---------+---------+---------+---------+
| **C     | **     | **0.00 | **0.0   |         |         | **499** |
| hildren | 0.05** | 0063** | 49937** |         |         |         |
| 6 -- 12 |        |        |         |         |         |         |
| years** |        |        |         |         |         |         |
+---------+--------+--------+---------+---------+---------+---------+
| **Youth | **     | **0.00 | **0.0   |         |         | *       |
| 13-19   | 0.05** | 0044** | 49956** |         |         | *1499** |
| years** |        |        |         |         |         |         |
+---------+--------+--------+---------+---------+---------+---------+
| **      | **     | **0.00 | **0.0   |         |         | *       |
| Females | 0.05** | 0032** | 49968** |         |         | *1499** |
| 13-49   |        |        |         |         |         |         |
| years** |        |        |         |         |         |         |
+---------+--------+--------+---------+---------+---------+---------+
|         |        |        |         |         |         |         |
+---------+--------+--------+---------+---------+---------+---------+

**The results in Table 4 demonstrates that there are no safety concerns
for any subpopulation based on established and new uses, and that the
results clearly meet the FQPA standard of reasonable certainty of no
harm.**

**In summary, we can conclude with reasonable certainty that no harm
will occur from chronic aggregate or acute aggregate exposure to
dimethenamid.**

**[Short- and Intermediate Term Aggregate Exposure and Risk (Food, Water
and Residential Exposure)]{.underline}**

**Short- and intermediate-term aggregate exposure takes into account
residential exposure plus chronic exposure from food and water.
Residential exposure is used to refer to non-occupational and
non-dietary exposure. Dimethenamid is not registered on any sites that
would result in residential exposure. Therefore, the aggregate risk is
the sum of the risk from food and water, which do not exceed a level of
concern.\]**[\>]{.mark}

[\<]{.mark} 2. *Non-dietary exposure*. **\[Dimethenamid is not
registered for use on any sites that would result in residential
exposure.\]**[\>]{.mark}

[\<]{.mark}*D. Cumulative Effects*[\>]{.mark}

[\<]{.mark} **\[Section 408(b)(2)(D)(v) requires that, when considering
whether to establish, modify, or revoke a tolerance, the Agency consider
''available information'' concerning the cumulative effects of a
particular pesticide's residues and ''other substances that have a
common mechanism of toxicity.''**

**BASF has considered the potential for cumulative effects of
dimethenamid and other substances that have a common mechanism of
toxicity. BASF is aware of several other chloroacetanilide herbicides
that have been considered structurally similar to dimethenamid, these
being: acetochlor, propachlor, butachlor, metolachlor, and alachlor.
However, BASF believes that consideration of a common mechanism of
toxicity to these products is not appropriate or valid. This conclusion
was based on the presentation EPA made to the EPA FIFRA Science Advisory
Panel (SAP) on March 20, 1997. The title of the presentation was
"Grouping of Chloroacetanilide Pesticides Based on a Common Mechanism of
Toxicity." In this presentation EPA showed the structure of several
chloroacetanilides that included dimethenamid. BASF is identifying
Chlor- 7 as dimethenamid. EPA concluded that Chlor-7 should not be
considered to have a common mechanism to the other chloroacetanilides
based on the following reasons:**

**Except for Chlor-7 all other members of this case study have a
potential to generate a quinine imine. The quinone imine intermediate is
capable of reacting with macromolecules.**

**Chlor-7 has not produced nasal nor thyroid tumors in rats, thus does
not support inclusion in the group for a common mechanism for these
tumor types.**

**For liver tumors, Chlor-1, Chlor-7, Chlor-5, and Chlor-6, can be
potentially grouped for a common mechanism, but EPA determined that
there is no knowledge of a common mechanism of toxicity or of a common
toxic species responsible for the effect. Therefore, EPA concluded that
because a mechanism can not be postulated, it believes that sufficient
evidence is not available to support a common mechanism for this tumor
type with these materials.**

**Therefore, BASF agrees with the position put forward by the Agency and
confirmed by the SAP that a common mechanism is inappropriate for
dimethenamid (Chlor-7) and the other chloroacetanilides mentioned above.
Therefore, based on the above discussion BASF has considered only the
potential risks of dimethenamid in its exposure
assessment.\]**[\>]{.mark}

[\<]{.mark}*E. Safety Determination*[\>]{.mark}

[\<]{.mark} 1. *U.S. population.* **\[Based on this risk assessment,
BASF concludes that there is a reasonable certainty that no harm will
result to the general population from the aggregate exposure to
dimethenamid residues.\]**[\>]{.mark}

[\<]{.mark} 2. *Infants and children*. **\[Based on this risk
assessment, BASF concludes that there is a reasonable certainty that no
harm will result to infants or children from the aggregate exposure to
dimethenamid residues.\][\>]{.mark}**

**[\<]{.mark}***F. International Tolerances***[\>]{.mark}**

**[\<]{.mark} \[Maximum residue levels (MRLs) have been established for
Dimethenamid-P and its enantiomer in the registered crops by the Codex
Alimentarius Commission as of January 2006. The recommended MRLs are
0.01 mg/kg and the residue definition could apply to residues arising
from the use of either dimethenamid-P or dimethenamid.\][\>]{.mark}**