Page 1 of 13 UNITED STATES ENVIRONMEN TAL PROTECTION AGENCY WASHINGTON D.C., 20460

PC Code: 061601

DP Barcode: 399985

MEMORANDUM Date: April 18, 2012

Subject: Response to comments from Syngenta on paraquat dichloride preliminary problem formulation

To: Molly Clayton, Risk Manager

Pesticide Re-Evalu ation Division Office of Pesticide Programs

From: Kristina Garber, Senior Biologist James Lin, Environmental Engineer

Environmental Risk Branch 2

Environmental Fate a nd Effects Division Office of Pesticide Programs

Reviewed by: R. David Jones, Ph.D., Senior Agronomist Donna Judkins, Ph.D., Biologist

Environmental Risk Branch 2

Through: Brian Anderson, Chief

Environmental Risk Branch 2

Environmental Fate and Effects Division Office of Pesticide Programs

On February 21, 2012, Syngenta Crop Protection, LLC provided comments on the preliminary problem formulation for paraquat dichloride. Th ose comments are provided below. EFED has

reviewed those comments and ha s prepared responses for your c onsideration. The structure of this memo is as follows: first, EPA’s origin al statement, as provided by Syngenta; second, Syngenta’s comment; third, EFED’s response to Syngenta’s comment.

1) EPA statement (as taken from Syngenta’s co mment document): A non-guideline – Drinking water treatability study is includ ed as a data gap. EFED notes that submission of a drinking water treatability study (i.e., Ja r Test) would be of high value to drinking water assessments. With paraquat’s high adsorptive properties, traditional water treatment processes are expected to remove almost all paraquat in the water. EFED is requesting the treatability study from the registrant to confirm this property.

Syngenta’s comment (p. 4-5): “The required study has recently (November 2011) been submitted (Moore, 2006). This two-part study was conducted to evaluate the effects ofPage 2 of 13 traditional water treatment processes (including flocculation and sedimentation) on removing paraquat residues from water and to also dete rmine the mobility potential of paraquat through soil filtration columns. The results from this test demonstrate that paraquat was effectively removed by typical water treatment processes. The results of the soil column filtration tests demonstrated that paraquat applied to agricultu ral fields, even under a worst case scenario, is unlikely to leach into the groundwater due to the intrinsic property of paraquat to adhere/bind to soil particles. Instead of leaching, paraquat remains bound tight ly to soil particles in the top surface layer even under sa turated and flooding conditions.”

EFED’s response: Based on the review of the submitted study, entitled “Review of Jar Test Results for Drinking Water Assessment Pu rpose (D396402)”, EFED has concluded that paraquat in water was effectiv ely removed by a combination of typical water treatment processes conducted on a laborator y-scale: the “laboratory jar test” (coagulation using alum with either lime or soda ash, flocculati on and sedimentation), followed by duel media filtration (anthracite atop of filtering sand). Th e combination process was able to reduce the

level of 14 C-paraquat to approximate or below the limit of detection of about 0.15μg/L (ppb). The limit of detection of 0.15 μg/L (ppb) will be used for drinking water exposure

assessment.

2) EPA statement (as taken from Syngenta’ comment document): The Agency invites submission of water quality data for this pest icide. (0002/10). Any available monitoring data from the registrants and public organizations such as US EPA, USGS, Department of Pesticide Regulation (CDPR), and others will be considered in this review process. (0003/16) The drinking water assessment will also include available surface and ground water monitoring data with considerati on of changes in use patterns th at may have occurred. States are encouraged to submit monitoring data for review. (0003/31) The drinking water

assessment will also include available su rface and ground water monitoring data with consideration of changes in use patte rns that may have occurred. (0004/5,6)

Syngenta comment (p. 5-6): “Two water monito ring studies have recently (November 2011) been submitted by Syngenta demonstrating that there is minimal potential for the occurrence of detectable paraquat residues in drinking water and that if there were to be any such detection in raw water, typical water treatm ent processes effectively remove any such paraquat residues. The first of these studies (Peters, 2007a) monitored for paraquat residues

in rural communities biases to include areas of high paraquat usage. A total of 1,092 water samples were collected in this study and anal yzed for residues of paraquat. There were no quantifiable detections of paraquat from any of the surface water sources evaluated based on the analytical method’s LOQ of 0.10 ppb.

“The second monitoring study (Peters, 2007b) was conducted in urban environments. The sites monitored in this study were biased to areas with potential paraquat exposure in surface water systems. Over the course of the 2 year monitoring period, water samples were collected at 21 scheduled intervals annually. A total of 1,056 raw water samples using immunoassay methodology were analyzed for the presence of paraquat; and with the exception of one raw water sample (with a residue of 0.252 ppb), ther e were no quantifiable residues at or above the LOQ (0.10 ppb). All samples corresponding to this single detection event includingPage 3 of 13 duplicate replicate samples of both the raw and finished water were subsequently confirmed by LC/MS/MS. The average concentrations de termined for the raw and finished water replicate samples were 0.373 ppb and <LOQ, re spectively. This single raw water sample

detection therefore did not resu lt in any detectable residue in the corresponding finished drinking water sample.

“These two studies clearly dem onstrate that use of paraquat in the monitored communities did not result in the presence of detectable paraquat residues in drinking water. Syngenta requests that results from these monitoring studies be utilized in the drinking water

assessments.”

EFED’s response: EFED will consider these st udies as part of the human health risk assessments for paraquat. Although EFED has not completed the review of the mentioned monitoring studies, as suggested in Question #1, the jar test results have demonstrated the removal of paraquat in drinking water due to it s strong binding capacity with the solids, On this basis, EFED can assess the drinking wate r from surface water sources with confidence.

3) EPA statement (as taken from Syngenta’ comm ent document): A list of the “non-agricultural

use sites” included lawns as a potential use site.

Syngenta comment (p. 7): “Paraquat is not appr oved for use in residential areas including lawns. In addition, Syngenta’s paraquat e nd-use product labels further minimize any potential for exposure to residential areas such as lawns by requiring that for ‘Sensitive Areas – The pesticide must only be applied when the potential for drift to adjacent sensitive areas (e.g. residential ar eas, bodies of water, known habitat for threatened or endangered species, non-targ et crops) is minimal (e.g., when wind is blowing away from the sensitive areas).’

“In light of the prohibitions ag ainst use in residen tial areas, Syngenta respectfully requests that lawns be removed from the list of Non-Ag ricultural Use Sites on page 2 of docket item EPA-HQ-OPP-2011-0855-0006.”

EFED’s response: The word “lawn” does not occur in the EFED’s Problem Formulation document. If the list of non-agricultural use sites includes “lawns” on page 2 of docket item EPA-HQ-OPP-2011-0855-006 - BEAD Chemical Prof ile for Registration Review: Paraquat Dichloride (Chemical Code 061610), th en the use should be removed.

4) EPA statement (as taken from Syngenta’ co mment document): Based on an evaluation of available groundwater monitoring studies, the Environmental Fate and Effects Division (EFED) recommended use of monitori ng data reported in Virginia (1.52 μ g/L) for the drinking water exposure assessment, as a high-en d, but not worst-case value for the acute and chronic analyses. The groundwater monitoring va lue was incorporated directly into the dietary assessments.

Syngenta comment (p. 7-8): EFED has recomm ended use of monitoring data reported in Virginia (1.52 μ g/L) for the drinking water exposur e assessment, as a high-end, but notPage 4 of 13 worst-case value for the acute and chronic analyses. Syngenta, as described above, has provided new monitoring data (Peters 2007a and 2007b). Syngenta is also submitting a review of the Virginia mon itoring data (Peters, 2006). As has been well documented (Roberts, 2002) paraquat is st rongly adsorbed and considered immobile in soils making it unlikely that paraquat would be detected in surface water and even more unlikely to be detected in groundwater. These physiochemical pr operties that make paraquat unlikely to be found in drinking water supplies ha s been previously cited by the Agency (EPA, 2006) in the Paraquat Dichloride: Human Health Risk Assess ment for Proposed Uses on Ginger and Okra and Amended Uses on Soybeans, Wheat, Cotton, Cucurbits, Onions, and Tanier which states:

‘Because of its very low mobility and strong tendency to bind tightly to soils, paraquat contamination of drinking water supplies deri ved from groundwater is expected to be highly unlikely. In addition, the strong bindi ng characteristics of paraquat are likely to render most residues in raw drinking wate r sources removable through sedimentation processes, which are typically included as part of standard drinki ng water treatments.’”

EFED’s response: After further review of th e original reference us ed for drinking water assessment, EFED has determined that the ground wa ter value of 1.52 μ g/L is invalid; therefore, the drinking water assessment will be based on the accepted jar test results as

discussed in the recent review of the jar test (D396402; January, 2012).

5) EPA statement (as taken from Syngenta’ comm ent document): EFED recommends that PRD require acute and chronic toxicity data for one species of sediment-dwelling invertebrates for paraquat. Paraquat dichloride registrants must submit a study protocol for review by the Agency prior to initiation of the chronic toxicity study with se diment dwelling invertebrates.

Syngenta Comment (p. 13): “Syngenta concurs with the fact that the half -life of paraquat in

soil under aerobic conditions is >10 days. It is well establis hed that paraquat binds very strongly to soil and sediment and is only re leased after reflux under acidic conditions (Roberts 2002). Paraquat bound to sediment w ould thus not be bioa vailable for sedimentdwelling invertebrates as previous ly stated in the Paraquat RED: ‘Due to paraquat dichloride’s strong adsorption to soil whic h makes it biologically unavailable, chronic testing on estuarine and marine organisms is not required.’ (EPA 1997 pg 130).

“The reduced bioavailability and toxicity of pa raquat in the presence of sediments has been demonstrated in a number of lab studies, both with plants in the water column and with

benthic invertebrates. In one example with the alga Navicula pelliculosa , the most sensitive algal species discussed by EPA in the prelim inary problem formulation, alga cells were inoculated into test medium containing pa raquat at concentrations ranging from 0.9-900 μ g paraquat technical/L equivalent to 0.29-290 μ g paraquat ion/L (Smyth and Shillabeer, 2000). Subsamples of this inoculated medium were th en added to test vessels containing 3 g of a sandy loam sediment. The Navicula were thus exposed to the concentrations of paraquat before being added to the test vessel containing the sediment. The alga was cultured under

standard test conditions for 120 hours and the effects on algal growth determined every 24 hours during this period. After 96 hours, growth effectively stopped, lik ely due to the algal growth medium being exhausted. There were no t significant effects on algal growth at anyPage 5 of 13 concentration and so the EC 50 of paraquat to Navicula pelliculosa in the presence of sediment

was >290 μ g paraquat ion/L, and the NOEC was 290 μ g/L. This is approximately 725x greater than the 960h EC 50 of 0.4 μ g paraquat in the absence of sediment (Smyth et al., 1992).

“A study was conducted with the aquatic midge Chironomus riparius in which larvae were exposed to radiolabeled ( 14 C) paraquat in sediment-water systems using a formulated sediment (Hamer, 1998). Test systems were pr epared by applying paraquat to a nominal concentration of 100 mg pa raquat ion/kg sediment (dry weight). First-instar C. riparius were introduced to the test systems and observations made for emerging adults. Results indicated no difference in the pattern of emergence be tween control and treated systems. Total emergence was 97 and 99% for the control and 100 ppm paraquat ion/kg sediments, respectively, with mean emerge nce times of 14.1 and 14.0 days.

“The physicochemical properties of paraquat that result in very tight bi nding of paraquat to sediments render paraquat biol ogically unavailable to sedime nt-dwelling organisms and, as such, a chronic toxicity study with sediment dw elling invertebrates is of limited benefit.”

EFED’s response: The sediment toxicity studi es referenced by Syngenta have not been

submitted to EPA. EFED recommends that PRD re quest that the registrant submit the studies involving exposures of the algae N. pelliculosa (Smyth and Shillabeer, 2000) and the midge C. riparius (Hamer 1998) so that they can be reviewed. Upon completion of these reviews, EFED can consider whether additional toxicitydata for sediment-dwelling invertebrates is necessary for paraquat. The citations given by Syngenta for these studies are as follows:

Hamer, MJ (1998) Sediment toxicity test with Chironomus riparius. Report RJ2649B. (Unpublished study from Zeneca Agrochemicals).

Smyth, D, Shillabeer N. (2000) Paraquat Dichlo ride: Toxicity to the freshwater diatom Navicular pelliculosa in the presence of sedimen t: Lab Project Number: BL6800/B

6) EPA statement (as taken from Syngenta’ comm ent document): EFED recommends that PRD require acute and chronic toxicity data for one species of sediment-dwelling invertebrates for paraquat. Paraquat dichloride registrants must submit a study protocol for review by the Agency prior to initiation of the chronic toxicity study with se diment dwelling invertebrates.

Syngenta Comment (p. 13): “The EPA aquatic ri sk assessment does not take into account the effect of adsorption in reducing the bioavail ability, and thus the pot ential toxicity of paraquat. This extreme adsorption property of pa raquat is a critical f actor that should be considered in the environmental exposure assessments.”

EFED’s response: When assessing risks of a pes ticide in sediment to benthic invertebrates,

EFED uses PRZM/EXAMS to estimate concentra tions of the pesticide in pore water. This approach uses the soil water partitioning coefficient (K d ) to determine the pesticide concentration in pore water. As a cation, paraqua t binds electrostatically to the negativelyPage 6 of 13 charged surfaces of clay particles in soil. PR ZM only considers organic adsorption, this type of cation binding is not considered.

7) EPA statement (as taken from Syngenta’ comm ent document): EPA anticipates requiring the following data for use in conducting an ecologica l risk assessment for the registration review of paraquat dichlori de: 835:4400 – anaerobic aquatic metabolism

Syngenta Comment (p. 14): “Syngenta suggests that conducting an anaerobic aquatic metabolism study is unlikely to provide additiona l information that would be useful in an ecological risk assessment for the following reasons:

- Paraquat is known to be stable to degradati on in anaerobic soils (Vickers, J.; Hurt, A.; Bewick, D. (1989)

- Paraquat is hydrolytically st able from pH 5 – 9 at 40 o C (Upton, B.; Hendly, P.; Skidmore, M., 1988)

- Paraquat does not degrade photolytically in aqueous solutions (EPA 1997; Parker, S.; Leahey, J. 1988)

“In addition, one study (Coats, et al. 1964) condu cted on a simulated pond system (soil:water in a plastic pool) showed that paraquat was removed from the water column with a ‘resident half-life of <2 weeks’ which suggests that pa raquat would be readily removed from the water of anaerobic sediment system by rapidly bindi ng to the sediment. For these reasons, it is unlikely that new degradate(s) would be formed in any significant amount or that additional information would be gained from what is already known about pa raquat by conducting an anaerobic aquatic metabolism study.”

EFED’s response: The first comment that by combining the study resu lts of anaerobic soils, hydrolysis and aquatic photolysis will yield th e results for anaerobic aquatic metabolism is not correct. Otherwise, the guideline requireme nt will not be needed if the three mentioned

studies have been fulfilled.

As for the second comment that paraquat will be removed from the wate r into the sediment and no need to investigate further, EFED is concerned about any possi ble degradates formed in the sediment layer, the study referenced above has not addressed this adequately. Therefore, the anaerobic aquatic metabolism study is needed.

8) Syngenta Comment (p. 15): “Syngenta is prep aring scientific comments to the CRLF [California Red-Legged Frog] assessment which will be submitted to EPA shortly.”

EFED’s response: The EFED effects determinat ion for exposures of the CRLF to paraquat was completed in June 2009. Syngenta is we lcome to submit comments on the assessment.

9) EPA statement (as taken from Syngenta’ co mment document): Based on use patterns of paraquat dichloride, its fate and transport poten tial, and the sensitivity of non-target aquatic and terrestrial species, paraquat has the poten tial to reduce survival , reproduction, and/or growth in non-target terrestrial and aquatic organisms when used in accordance with labels.Page 7 of 13 These non-target organisms include Federally- listed threatened and endangered species as well as non-listed species.

Syngenta Comment (p. 15): “The transport po tential for paraquat is limited due to the extremely tight binding of the paraquat cation to soil and other particulates. Bound particles,

even if available for offsite movement with su spended soil particles, are not biologically available based upon the nearly irreversible bind ing of paraquat to soil /particulate matrices. During more than 40 years of use, in over 100 countries covering many and varied agronomic practices, there have been no reports of the reactivation of adsorbed paraquat residues due to desorption (Robe rts, 2002). Paraquat is 99.99% soil-bound, does not come off

the soil unless refluxed in hot acid and is th erefore biologically unava ilable (Roberts, 2002). Any residues of paraquat in soil that may be present from prior use will be very strongly

bound and not be bioavailable and thus do not have the potential to reduce survival, reproduction, and/or growth in non-target terrestrial and aquatic organisms.”

EFED’s response: EFED accepts the point that on ce paraquat is bounded to soil, it will not be bioavailable through contact exposure. However, organisms that consume soil may be exposed.

10) EPA statement (as taken from Syngenta’ comment document): The conceptual model presented in figure 1 indicates furthe r exposure once paraquat reaches soil.

Syngenta Comment (p. 16): “The post-soil e xposure component in the model should be modified to reflect that upon contact with soil, paraquat resi dues are no longer bioavailable. The transport and exposure potential for paraquat is extremely limited due to the extremely tight binding of the paraquat cation to soil a nd other particulates. The soil bound particles, even if available for offsite movement, are not biologically available based upon the nearly irreversible binding of paraquat to soil/particulate matrices. The conceptual model for paraquat (Figure 1) should be modified for so il exposure in a similar manner as Figure 2 which indicates through the dotted lines that repr esent transport pathways that are assumed to have a low likelihood of occurring and/or of contributing to ecological risk.”

EFED’s response: EFED concurs with Syngenta’ s comments that paraquat does bind tightly with the soil particle s, and therefore is not generally bioavailable via contact exposure. However, organisms that consume soil and se diment may be exposed. The soil exposure pathway in the conceptual model will be modified.

11) EPA statement (as taken from Syngenta’ co mment document): Paraquat dichloride is generally applied as a flowable solution. As a result, paraquat dichloride is already dissociated into its cation, pa raquat. Therefore, assessments involving paraquat dichloride will focus on the paraquat cation as the stresso r of concern. All EECs and toxicity values will be reported in terms of the paraquat cation.

Syngenta Comment (p. 17): “Paraquat dichloride (t echnical) is registered in the form of a concentrate (Paraquat Concentrate ES, EPA Reg. No. 100-1067). Paraquat Concentrate ESPage 8 of 13 contains 45.6% (w/w) paraquat dichloride equi valent to 33.0% (w/w) paraquat cation. This product is considered the “t echnical grade active ingred ient” (TGAI) and should be considered as the test substance for testing wh ere the TGAI is required. For risk assessment purposes, Syngenta agrees that stressor of c oncern should be reporte d in terms of the paraquat cation.”

EFED’s response: EFED appreciates the clarif ication of the nature of TGAI paraquat.

12) EPA statement (as taken from Syngenta’ co mment document): EPA lists a number of aquatic ecotoxicology data gaps in Table 11, on page 37 of the EFED Preliminary Problem

Formulation.

Syngenta Comment (p. 17): “850:1400 Saltwater a nd freshwater early life- stage fish tests are identified as data gaps.

“Chronic aquatic exposure to para quat is very unlikely due to the uses and physiochemical

characteristics of this herbicide. In addition, the acute aquatic t oxicity to animals is generally slight to moderate. Syngenta s uggests that a single freshwater ELS study could be used with

the acute fish data that will be available to estimate a saltwater NOEC using the EPA’s Acute to chronic Ratio (ACR) method.”

EFED’s response: If the registrant submits acceptable acute (guideline 850.1075) and chronic (guideline 850.1400, early life stage test) studies with the same freshwater fish species exposed to TGAI paraquat, EFED will consider using an ACR for that freshwater fish test species to estimate a chronic endpoi nt for a saltwater fish species.

13) EPA statement (as taken from Syngenta’ co mment document): EPA lists a number of aquatic ecotoxicology data gaps in Table 11, on page 37 of the EFED Preliminary Problem

Formulation.

Syngenta Comment (p. 17): “850.1735 and non-guideli ne freshwater invertebrate acute and chronic sediment toxicity tests.

“The sorption of paraquat to sediments is ne arly irreversible, and the herbicide is not bioavailable in sediments, as discussed above. A chronic Chironomus riparius study (Hamer, 1998) was conducted at 100 mg paraquat ion/L, a nd demonstrated no effects on survival or emergence. Syngenta suggests that additional sediment toxicity testing will not provide

additional information for risk assessment. If sediment testing is required, then Syngenta suggests that both acute and chr onic studies are not necessary.”

EFED’s response: As noted above, the sediment toxicity study referenced by Syngenta has not been submitted to EPA. EFED recommends that PRD request that the registrant submit the study involving the midge C. riparius (Hamer 1998) so that it can be reviewed. Upon completion of these reviews, EFED can cons ider whether additional toxicity data for sediment-dwelling invertebrates is necessary for paraquat.Page 9 of 13 14) EPA statement (as taken from Syngenta’ comment document): Table 4 presents the Environmental Fate Parameters of Paraquat including the parameter, value cited and

reference for the cited value. The follow ing Syngenta comments refer to table 4.

Syngenta Comment (p. 18): “Table 4 presents th e log octanol-water partition coefficient (log Kow) as 2.44 citing Platford (1983). The octano l/water partition coeffieint for paraquat dichloride in the Platford pub lication is reported as -4.22±0.05 . The -4.2 value is consistent with other published values for the octanol-wat er coefficient for paraquat including in the - 4.5 value cited in the RED (EPA, 1997 pg 91) and the FAO Specifications for paraquat (FAO, 2003). Please verify the log octanol-w ater partition coefficient for paraquat.”

EFED’s response: EFED will revise the value of log Kow as needed.

15) EPA statement (as taken from Syngenta’ comment document): Table 4 presents the Environmental Fate Parameters of Paraquat including the parameter, value cited and

reference for the cited value. The follow ing Syngenta comments refer to table 4.

Syngenta Comment (p. 18): “The hydrolysis stud y by Upton, et al does not have an MRID number. However, inclusion of the study in the reference section (section 12) should be

considered.

“Upton, B.; Hendly, P.; Skidmore, M. (1985) Pa raquat: Hydrolytic Stab ility in Water at pH 5, 7 and 9, Laboratory Project RJ0436B. Unp ublished study prepared by ICI Plant Protection Division, 20 p.”

EFED’s response: The mentioned study w ill be considered for hydrolysis study.

16) EPA statement (as taken from Syngenta’ comment document): Table 4 presents the Environmental Fate Parameters of Paraquat including the parameter, value cited and

reference for the cited value. The follow ing Syngenta comments refer to table 4.

Syngenta Comment (p. 18): “In the row presen ting the aqueous photolysis half-life, the review by Jordan, 2/14/1986 is not included in the references. In clusion of the review in the reference section (section 12) should be considered.

EFED’s response: EFED will consider the above mentioned reference.

17) EPA statement (as taken from Syngenta’ comment document): Table 4 presents the Environmental Fate Parameters of Paraquat including the parameter, value cited and

reference for the cited value. The follow ing Syngenta comments refer to table 4.

Syngenta Comment (p. 18): In the row pres enting the adsorption/desorption study; the conclusions are referenced by MRID 40762701 howev er this report is not included in the reference section (Section 12). Please add the reference as:Page 10 of 13 MRID 40762701 Robbins, A., Lane, M., Riley, D. (1988) Paraquat: Adsorption and Desorption Equilibrium in Soils, Laboratory Project RJ0662B. Unpublished study prepared by ICI Plant Protection Division, 15 p.”

EFED’s response: EFED will consider the above mentioned reference.

18) EPA statement (as taken from Syngenta’ comment document): Paraquat did not photodegrade when mixed with a sterile soil solution and expose d to natural sunlight for 85 weeks (Pack, 1982).

Syngenta Comment (p. 19): “The sampling peri ods for the Pack (1982) study were 0, 6, 12,

18 and 24 months as cited in Table 3 of the study. A sampling period of 85 weeks was mentioned in the summary of the Pack study but that was citing a sampling period of an earlier study (Day, S.; Hemingway, R., 1981). Th erefore, Syngenta suggests changing the sentence to read ‘paraquat did not photodegrad e when mixed with a sterile soil solution and exposed to natural sunlight for 2 years (Pack, 1982).’ ”

EFED’s response: EFED will revise this sent ence if after re-evalua tion of the mentioned study confirms the results.

19) EPA statement (as taken from Syngenta’ comment document): The LD 50 for northern bobwhite ( Colinus virginianus ) is listed as 124 mg cation/kg-bw.

Syngenta Comment (p. 19): “In the avia n acute oral toxicity study, the LD 50 for northern bobwhite ( Colinus virginianus ) is listed as 124 mg cation/kg-bw (Fink, R.; Beavers, J.B.; Grimes, J.; et al. (1979). According to the DER (Hopkins, 1980), the AI-corrected LD 50 is 164 mg paraquat dichloride/kg-bw. This is equi valent to 127 mg cation/kg-bw rather than 124 mg cation/kg-bw as reported in Ta ble 6. Syngenta requests that the LD 50 for northern bobwhite ( Colinus virginianus ) be verified.”

EFED’s response: EFED recently re-reviewed this study and verified the LD 50 as 124 mg cation/kg-bw. An addendum to the original DER for this study (MRID 29001) was included in a memo to PRD that was sent on December 9, 2011 (DP barcode 392076).

20) EPA statement (as taken from Syngenta’ co mment document): Table 6 [of the Problem Formulation] cites a rat acute oral toxi city study (Rittenhouse, MRID 00054573) with an LD50 of 91 mg cation/kg bw.

Syngenta Comment (p. 20): “A more recent acute rat oral toxicity study by L. Duerden (MRID 43685001) was submitted, and a DER was prepared by EPA-HED (Hurley, 1996).

The LD 50 for female Wistar rats was calculated to be 283 mg/kg equivalent to 206 mg/kg cation. According to the DER, this study was classified as acceptable and satisfied the guidline (81-1) requirement. Th e study also cited as the relevant endpoints for acute oral toxicity in the Paraquat RED for the Acute oral LD 50 (rat) as well as in the April 19, 2000Page 11 of 13 report of the Hazard Identification Assessmen t Review Committee. (EPA, 2000) This study

should be the basis of the acute oral LD 50 for small mammals.”

EFED’s response: EFED will consider both acut e oral toxicity studies when selecting the appropriate endpoint for mammals. EFED will use the most sensitive endpoint from the available scientifically valid studies.

21) EPA statement (as taken from Syngenta’ co mment document): Table 6 [of the Problem Formulation] cites and acute inhalati on rat study (MRID 00046105) by Gage (1968). The reported LC 50 from this study is 0.001 mg/L.

Syngenta Comment (p. 20): “A more recent acu te inhalation rat study (Rattray, 2005) is available and will be submitted under a separate cover for the Agency’s review. This study was conducted according to OECD guideline reference 403 (1981) and United States Environmental Protection Agency, Health Effects Test Guidelines, OPPTS 870.1300 (1998) for Acute Inhalation Toxicity. The results of this study were that nose-only exposure for 4 hours to paraquat ion at concentrations of 0.36, 1.58 or 2.49 μg/L resulted in 0, 1, and 5 deaths respectively. It is concl uded that the median lethal co ncentration of paraquat ion was 1.79 μg/L for females only (equivalent to 2.47 μg paraquat dichloride/L or 5.36 μg paraquat dichloride technical material). In this study since males were only exposed to the lowest atmospheric concentration (0.3 μg paraquat i on/L) to demonstrate equivalence with the females, the MLC for males was not calculate d. Syngenta recommends the data from this study be considered in determining the most relevant acute inhalation endpoints for paraquat.”

EFED’s response: If the registrant submits th e more recent acute inha lation study with the rat (Rattray, 2005), these data can be reviewed by OPP and potentially considered for use in risk assessments of paraquat.

22) EPA statement (as taken from Syngenta’ co mment document): Table 6 [of the Problem Formulation] cites a honey bee ( Apis millifera ) acute contact and oral toxicity study (MRID 43942603) by Bull and Wilkinson (1987). The reported contact LD 50 for honey bees is given as 52 μg cation/bee.

Syngenta Comment (p. 21): “The original study report and DER (Vaughan, 1996) reported the contact LD50 as 51 μg cation/bee. Syngenta re quests that the correct value be verified.”

EFED’s response: Syngenta is correct that the contact LD50 from MRID 43942603 is 51 μg

cation/bee.

23) EPA statement (as taken from Syngenta’ comm ent document): In Table 7 [of the Problem Formulation] the seedling emergence NOAEC and EC25 values for cocklebur ( Xanthium sp ) are given as 0.37 and 0.67 lb cation/ A for the cited study (MRID 42639601).

Syngenta Comment (p. 21): “Those values provided in Table 7 are not consistent with the endpoints reported in the DER (Mossler, 1993) for this study. The revi ewer calculated thePage 12 of 13 NOEL and EC25 as 0.59 and 1.17 lb ai/A, respectivel y. Syngenta respectfully requests that

these values be verified.”

EFED’s response: EFED reviewed the endpoint s for the vegetative vigor study involving

cocklebur and confirms that the NOAEC and EC 25 values should be 0.59 and 1.17 lb a.i./A, respectively.

24) EPA statement (as taken from Syngenta’ co mment document): Table 7 [of the Problem Formulation] cites a vegetative vigor study (Canning, L. and J.S. White., 1992) with NOAEC

and EC25 values of 0.064 and 0.16 lb cat ion/A, respectively, for corn ( Zea mays ).

Syngenta Comment (p. 21): “These NOAEC and EC 25 values are not consistent with the endpoints in the study report (C anning, L. and J.S. White. 1992). The reported NOEL for corn is 100 g ai/ha (0.0892 lb ai/A), and the EC25 is 274 g ai /ha (0.244 lb ai/A) based on dry weight. The NOAEC and EC25 for cocklebur ( Xanthium sp ) from the same study were calculated to be ~5 g ai/ha (0.0044 lb ai/A) and 19.6 g ai/h a (0.0174 lb ai/A), respectively, based on dry weight. The field rates (lb ai/A) were extrapolated from Tables 23-24 of the study report and are not consistent with th e values reported in Table 7 (EPA-HQ-OPP-2011- 0855). Syngenta requests that the in dicated values be verified.”

EFED’s response: EFED recently re-reviewed this study (MRID 42601001) and verified the endpoints, which are provided in the table belo w. An addendum to the original DER for this study was included in a memo to PRD that was sent on December 9, 2011 (DP barcode 392076).

Updated endpoints – Dry weight [lbs cation/A]

Sci. name Common name EC25 NOAEC*

Xanthium strumarium Cocklebur 0.014 (95% CI 0.01-0.019) 0.0065

Zea mays Corn 0.16 (95% CI 0.073-0.36) 0.064
( ) 95% Confidence Interval

* For Cockelbur an EC 05 was calculated and used in place of a NOAEC

25) EPA statement (as taken from Syngenta’ co mment document): 1) The dietary exposure assessment is adequate based on current met hodologies but may need to be revised to incorporate changes to toxicity endpoints and/or changes to the drinking water assessment. 2) The drinking water exposure assessment needs to be revised based on current methodologies. 3) The occupational exposure a ssessment needs to be updated to reflect current policy. Use of chemical specific biom onitoring data should be reevaluated. 4) The aggregate risk assessment is adequate base d on existing uses and methodologies but may need to be revised to incorporate changes to the dietary and/or drinking water assessment,

Syngenta Comment (p. 22): “As the Agency intends to conduct updated exposure assessments for dietary, residential, aggregate and occupational exposure scenarios, Syngenta requests EPA to use the best available data to pr oduce refined, realistic risk assessments such as the recently submitted water treatment data (Moore, 2006) and water monitoring data (Peters, 2007a and 2007b).Page 13 of 13 EFED’s response: Based on the review of the submitted study, entitled “Review of Jar Test Results for Drinking Water Assessment Pu rpose (D396402), EFED has concluded that paraquat in water was effectiv ely removed by a combination of typical water treatment processes conducted on a laborator y-scale: the “laboratory jar test” (coagulation using alum with either lime or soda ash, flocculati on and sedimentation), followed by duel media filtration (anthracite atop of filtering sand). Th e combination process was able to reduce the

level of 14 C-paraquat to approximate or below the limit of detection of about 0.15μg/L (ppb). The limit of detection of 0.15 μg/L (ppb) will be used for drinking water exposure

assessment.