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

MEMORANDUM OFFICE OF CHEM I CAL SAFETY AND POLLUTION PREVENTION

PC Code: 129022

DP Barcode: D412039

Date: December 12; 2013

SUBJECT: Response to Public Comments on the Preliminary Ecological Risk Assessment for
Fosthiazate.

TO: James Parker, Chemical Review Manager

FROM: . Thomas Moriarty, Team Leader
Neil Anderson, Branch Chief Registration Division (7508P)

Melissa Panger, Ph.D., Senior Biologist
Environmental Risk Branch 3
Environmental Fate and Effects Division (7507P)

This memorandum provides EFED's responses to comments from ISK Biosciences Corporation (ISK B C) on the preliminary ecological risk assessment conducted for fosthiazate (PC Code 129022) as p art of registration review. In addition to comments, ISKBC also provided some addit i onal data to be considered as part of the ecological risk assessment for fosthiazate. ISKBC

was the onl y stakeholder to comment on the EFED risk assessment.

Spec i ficall y for EFED, ISKBC submitted the following studies: acute toxicity studies on carabid
beetle (MRID 49134007), earthworms (MRID 49134005), spiders (MRID 49134006), and honey
bees ( MRID 49134004)

. The submitted data are addressed in EFED's responses to ISKBC's

comments. ISKBC's comments and the respective Environmental Fate and Effects Division (EFED) responses are shown below.

Also, in reconsidering the honey bee toxicity data

, EFED realized that t he toxicity values
available fo r fosthiazate and honey bees [i.e.

, LD 5 o = 0

. 247 1-1g a.i./bee ( contact) and LDso = 0.61 1-1g a.i./bee ( oral, based on the recently submitted data)] trigger the need for hazard label lang u age fo r honey bees, since the LD 50 values are less than 2 1-1g a.i./bee (this was inadvertently 

## n

..**-rt.-(~**2 missed while conducting the PRA for fosthiazate). EFED recommends the following hazard
statement be added to fosthiazate labels:

“ This product is potentially to xic to honey bees through tran slocated residues in pollen
and nectar.”

ISKBC COMMENT:

ISKBC states that there are several differe nces between the pre liminary ERA (PRA) for fosthiazate and previous assessments conducted for fo sthiazate. They furthe r state that most of
the differences are due to a more extensive assessment of vertebrate species ingesting contaminated food items. They note that the PR A states, “(c)urrently, there are no standard methods for quantitatively assessing risks to soil -dwelling invertebrates from direct exposure to pesticides via drip irrigation...” which is the on ly currently labeled use pattern for fosthiazate.

EFED RESPONSE:

The primary differences between previous fosthiazate risk assessments and the assessment
conducted for the PRA was the consideration of new data and risk assessment tools that were not available for previous assessments. Most notab ly, there are currently data available on the translocation of fosthiazate in tomato plants tr eated via drip irrigation (the same application method currently registered and assessed in the PRA) ( i.e., Mukherjee, et al . 2011; Sharma and Kumar, 2011; Wu, et al. 2012). These data allowed for a refi nement on the potential exposure to non-target organisms that might eat treated plan ts. Additionally, the Earthworm Fugacity Model was used to help estimate potential exposure to non-target vertebrates that might eat
contaminated earthworms.

As ISKBC notes, the PRA does state, “(c)u rrently, there are no standard methods for quantitatively assessing risks to so il-dwelling invertebrates from direct exposure to pesticides via drip irrigation...” But that sentence is immediately followed in the PRA by, “(t)herefore, potential risks to non-target terrestrial anim als will not be assessed using the standard methodology.” (p. 20). Ecological risk assessments are conducted for pe sticides used outdoors regardless of whether or not ‘standard’ methods are available to assess the risks associated with
their use.

ISKBC COMMENT:

ISKBC states that screening models (such as T-REX and the Earthworm Fugacity Model) are expected to represent an upper bound of exposure, and in many cases predict concentrations much higher than those ever found in actual field c onditions. They further st ate that it is possible to refine the exposure values for fosthiazate by th e use of residue values obtained in a study of residue levels in soil-dwelling invert ebrates, corn and soil (MRID 42791101).

EFED RESPONSE:

The PRA did not rely solely on screening-level a ssessment tools to assess potential risks to nontarget organisms from fosthiazate exposure. To estimate potential exposure to soil-dwelling3 invertebrates from direct contac t to fosthiazate from its use on tomatoes via drip irrigation under plastic mulch, the expected concentration in the treated irrigation water was used. The calculation used was simply the amount of a.i. that can be applied per acre divided by the amount of irrigation water that can be used based on the current label [ i.e ., 1.5 lb a.i./acre = 680,389 mg a.i./acre; 0.5 inch of irrigation water per acre = 51,395 L; 680,389 mg a.i./51,395 L = a concentration of 13.2 mg a.i./L (o r 13.2 ppm)]. This concentrati on is not expected to be “much higher than those ever found in actual field conditions”, as suggested by ISKBC, but the actual concentration expected in the field based on labeled rates.

The 13.2 mg a.i./L concentration was also used to estimate concentratio ns of fosthiazate on potential soil-dwelling arthr opods that may be ingested by birds, mammals, and other
invertebrates. As described in the PRA:

“To account for the mass of the ingested invert ebrate(s), the average fresh weight of an adult honey bee of 128 mg (Mayer and Johans en, 1990) is used as a surrogate for the mass of soil-dwelling arthropods. Adjusting fo r the weight of the bee exposed to 13.2 ppm of fosthiazate, results in a concentration of 1.7 ppm/arthropod (13.2 mg a.i./L x 0.128 mg). This number can then be used as the estimated environmental exposure (EEC) for arthropods in T-REX (v 1.5).” (p. 21).

T-REX in this case was not used to estimate pot ential residues on food items (which are typically upper-bound values), it was insteadused to calculate exposures to birds and mammals eating contaminated, soil-dwelling arthropo ds based on standard allometric equations for ingestion rates and the 1.7 ppm concentration on arthropods ( i.e ., T-REX was used so that the ingestion rates, and thus potential exposures, did not need to be hand-calculated using th e standard allometric equations for birds and mammals). Therefore, the exposure values base d on T-REX calculations and used in the PRA are not expected to be “much higher than those ever found in actual field conditions”, as suggested by ISKBC, for thos e birds and mammals feeding on soil-dwelling arthropods at the site of application.

To explore the potential risks associated withthe ingestion of earth worms specifically, the Earthworm Fugacity Model was used. To bound th e potential concentrations in earthworms at the treatment site, a range of both K oc values (25 and 285) and modeled depths (1.0 cm and 10.0 cm) were used. Because the mode ling was conducted using a range of input parameters instead of just relying on input parame ters that would result in the most conservative results, the estimated exposures are not expected to be “much higher than those ever found in actual field conditions”, as suggested by ISKBC.

As discussed in the PRA, to es timate potential exposures for terr estrial animals feeding on parts of tomato plants to which fosthiazate has been translocated, we relied on data from fosthiazate uptake studies in tomatoes that had been transplanted into treated soil ( i.e ., Sharma and Kumar, 2011; Sharma and Kumar, 2011b; and Wu, et al ., 2012). Based on these data and data available on the estimated mass of tomato plants in a typical field (see the PRA for details), a peak fosthiazate concentration of 0.32 ppm was estimated in the tomato plants ( it is assumed that all parts of the plant have this same fosthiazate co ncentration). This concentration was used in TREX to estimate potential exposure to birds and mammals that might eat plants that had been4 treated with fosthiazate. Agai n, because the residues were based on field data, the estimated exposures are not expected to be “much higher th an those ever found in actual field conditions”, as suggested by ISKBC.

Regarding potential refinements to the exposure values used for soil-dwelling arthropods using the results from the study of resi due levels in soil-dwelling inve rtebrates, corn and soil (MRID 42791101), EFED revisited the study. In this p ilot study, two plots seed ed with corn were
treated with 4 lb a.i./acre of fosthiazate via banded applic ation followed immediately by soil incorporation to a depth of 4 in ches. One plot was used to sa mple invertebrates and emerging corn seedling samples and one plot was used for non-target plant samples. IKSBC states that, “(t)his application technique clos ely approximates the current label practice of drip irrigation via banded rows, although the test plots were not covered with plastic mulch”. It is not clear why IKSBC believes the application t echnique used in the residue study “closely approximates” the currently registered use of 1.5 lb a.i./acre via drip irrigation to to mato plants grown using plastic mulch – no explanation is provided.

This study (MRID 42791101) had previously been reviewed by the EPA. The study was classified as scientifically sound and ‘supplementa l’. However, “... the study was determined to be inadequate to estimate potential residue leve ls on terrestrial food items in the environment.” In addition to several issues identified in the DER, the invertebrate residue results from this pilot study are based on fairly limited data [ e.g., one plot, limited timeframe (5 days), one use pattern (including soil incorporation to 4 inches)]. A dditionally, one of the pooled vegetation samples taken from one of the plots (Plot 2) prior to fosthiazate application was found to contain fosthiazate (0.14 ppm). This was explained as likely being the resu lt of accidental contamination (due to imperfectly washed garments) by th e individual who collected the samples.

One of the soil samples from Plot 2 also had a hi gher than expected concentration of fosthiazate ( i.e ., 24.8 ppm). This was thought to be due to a la yer of clay found 2 inches below the surface that the disking did not penetrate, and, thus, soil cores were only taken to a depth of 2 inches
instead of 4 inches. This i ndicates that local conditions ( e.g ., the presence of a clay pan) and the application method ( e.g ., disking to 2 versus 4 inches) ca n have considerable impacts on the resulting soil concentrations. Therefore, how the results fromthis study relate to the use assessed in the PRA ( i.e. , applications via drip irrigation under plastic mulch) or can be used to estimate potential residue exposure on insects, or exposure to birds and mammals that may eat
insects that are contaminated with fosthia zate residues, is not clear.

In follow-up communication with the fosthiazate registrant in response to the original data evaluation record (DER) for this study, it was concluded by EPA that:

“The information, although limited in time, area, and scope, will be considered when EEB assesses exposure to wildlife from an appl ication of fosthiazate as applied under the conditions of the study ( i.e ., 4 lb a.i./acre, 12-in. band, 4-i n. incorporation). Because of the limitations cited in the review, howev er, EEB may not rely solely on these preliminary estimates when assessing exposure of fosthiazate to wildlife.” (p. 1 - 2, USEPA, 1993).5 EFED believes that the DER and previous EPA c onclusions regarding this study are correct. The data from this study are not adequate for a ssessing exposure to wildlife from the currently registered use of fosthiazate ( i.e ., application via drip irrigation under plastic mulch).

ISKBC COMMENT :

To “address the stated lack of oral toxicity da ta” for terrestrial invertebrates, ISKBC submitted acute toxicity studies on carab id beetle, earthworms, spiders, and honey bees that were conducted for the European registration of fosthiazate.

EFED RESPONSE :

EFED appreciates the submissi on of the additional data. Th e only study that specifically contains acute oral data is the honey bee study (both contact and oral exposures were tested) (MRID 49134004). This study has not yet been fully reviewed; however, a preliminary review of the study did not identify any obvious issues that would invalidate the study. The reported 48-
hr LD 50 values for the contact and oral portions of the study ar e 0.75 μg a.i./bee and 0.61 μg a.i./bee, respectively. The contact LD 50 (0.75 μg a.i./bee) from this study is higher than the one currently being used in the PRA (0.247 μg a.i./bee ), therefore, it would not change the current
risk conclusions in the PRA.

For the oral portion of the study, the oral LD 50 value (reported as 0.61 μg a.i./bee) can be compared to the estimated concentration of fosthiazate in treated tomato plants ( i.e ., 0.32 mg a.i./kg, see above) to estimate the potential risks for terrestrial invertebrates that may ingest treated plants. The daily ingestion rate of a nectar-foraging bee is 292 mg food/bee. If a bee ingested 292 mg of f ood from a treated tomato plant, the estimated exposure would be 0.093 μg a.i./bee (0.32 mg a.i./kg = x mg a.i./0.000292 kg = 0.093 μg/bee). This results in a risk quotient (RQ) of 0.15 (0.093/0.61), which is above the current interim LOC fo r terrestrial invertebrates of
0.05.

ISKBC COMMENT :

In the PRA it is stated that risks to non-target te rrestrial invertebrates are expected but not able to be quantified. The registrant st ates that, “(w)hile s uppression of some harmful insects (sweet potato whitefly, tomato pinworm, beet armyworm ) for a limited period (21-30 days) is specified on the current product labels, fosthiazate efficacy is limited to nematodes and to a lesser extent, wireworms...” To “demonstrate the lower toxicity of fosthiazate to othe r non-target organisms than to... the honeybee” the re gistrant provided additional data, required for European registration, on non-target beneficial organisms.

EFED RESPONSE :

To clarify, the PRA does quantify risk to soil-d welling arthropods. Howeve r, the registrant is correct that risks to non-soil-dwelling, terrestrial invertebrates that may ingest treated tomato plants were not quantified because there were no oral toxicity da ta available at the time of the PRA. Using the recently submitted acute oral toxicity data for honey bees and fosthiazate6 (MRID 49134004), an RQ of 0.15 can now be calcu lated, which exceeds the current interim
LOC of 0.05.

It is unclear to EFED what specifically IS KBC means when they state that fosthiazate ‘suppresses’ some insects but is ‘efficacious’ to nematodes (and a “lesser extent, wireworms”). These claims seem to imply some pesticidal activity ( i.e. , suppression) to at least some insects
and that adverse effects to some invertebrate species that are exposed to fosthiazate from the registered use would be expect ed (which is supported by the available toxicity data on honey bees). As stated in the PRA, any potential a dverse effects to non-targ et organisms (including invertebrates) would be limited to the site of application.

Although the recently submitted invertebrate studie s have not been fully reviewed, they were screened. The honey bee study submitted is discussed above. The submitted toxicity study on earthworms reports a 14-day LC 50 of 209 mg/kg of soil and a NOAEC of 100 mg/kg of soil based on reduced body weight (MRID 49134005). Both the submitted study with spiders (MRID 49134006) and the study submitted for carabid beetles (MRID 49134007) were contact studies tested at a rate of 10 mg a.i./L. No ef fects were reported in either study; however, the tested concentration (10 ppm) is below the esti mated concentration for the currently registered fosthiazate use ( i.e ., 13.2 ppm, see above).