UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON D.C., 20460 

MEMORANDUM 

OFFICE OF 

CHEMICAL 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 

(ISKBC) on the preliminary ecological risk assessment conducted for fosthiazate (PC Code 

129022) as part of registration review. In addition to comments, ISKBC also provided some 

additional data to be considered as part of the ecological risk assessment for fosthiazate. ISKBC 

was the only stakeholder to comment on the EFED risk assessment. 

Specifically 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 the toxicity values 

available for fosthiazate and honey bees [i.e. , LD5o = 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 

language for honey bees, since the LD50 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 toxic to honey bees through translocated residues in pollen 

and nectar.” 

ISKBC COMMENT: 

ISKBC states that there are several differences between the preliminary ERA (PRA) for 

fosthiazate and previous assessments conducted for fosthiazate. They further state that most of 

the differences are due to a more extensive assessment of vertebrate species ingesting 

contaminated food items. They note that the PRA 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 only 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 notably, there are currently data available on the 

translocation of fosthiazate in tomato plants treated 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 refinement on the potential exposure to 

non-target organisms that might eat treated plants. 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)urrently, there are no standard methods for 

quantitatively assessing risks to soil-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 animals will not be assessed using the standard 

methodology.” (p. 20). Ecological risk assessments are conducted for pesticides 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 conditions. They further state that it is possible 

to refine the exposure values for fosthiazate by the use of residue values obtained in a study of 

residue levels in soil-dwelling invertebrates, corn and soil (MRID 42791101). 

EFED RESPONSE: 

The PRA did not rely solely on screening-level assessment tools to assess potential risks to nontarget organisms from fosthiazate exposure. To estimate potential exposure to soil-dwelling 
3 

invertebrates from direct contact 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 (or 13.2 ppm)]. This concentration 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 concentrations of fosthiazate on 

potential soil-dwelling arthropods that may be ingested by birds, mammals, and other 

invertebrates. As described in the PRA: 

“To account for the mass of the ingested invertebrate(s), the average fresh weight of an 

adult honey bee of 128 mg (Mayer and Johansen, 1990) is used as a surrogate for the 

mass of soil-dwelling arthropods. Adjusting for 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 potential residues on food items (which are typically 

upper-bound values), it was instead used to calculate exposures to birds and mammals eating 

contaminated, soil-dwelling arthropods 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 the standard allometric 

equations for birds and mammals). Therefore, the exposure values based 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 those birds and mammals feeding on soil-dwelling 

arthropods at the site of application. 

To explore the potential risks associated with the ingestion of earthworms specifically, the 

Earthworm Fugacity Model was used. To bound the potential concentrations in earthworms at 

the treatment site, a range of both Koc values (25 and 285) and modeled depths (1.0 cm 

and 10.0 cm) were used. Because the modeling was conducted using a range of input 

parameters instead of just relying on input parameters 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 estimate potential exposures for terrestrial 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 concentration). This concentration was used in TREX to estimate potential exposure to birds and mammals that might eat plants that had been 
4 

treated with fosthiazate. Again, because the residues were based on field data, the estimated 

exposures are not expected to be “much higher than 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 residue levels in soil-dwelling invertebrates, corn and soil (MRID 

42791101), EFED revisited the study. In this pilot study, two plots seeded with corn were 

treated with 4 lb a.i./acre of fosthiazate via banded application followed immediately by soil 

incorporation to a depth of 4 inches. One plot was used to sample invertebrates and emerging 

corn seedling samples and one plot was used for non-target plant samples. IKSBC states that, 

“(t)his application technique closely 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 technique used in the residue study “closely approximates” the 

currently registered use of 1.5 lb a.i./acre via drip irrigation to tomato 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 ‘supplemental’. However, “... the study was determined to 

be inadequate to estimate potential residue levels 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)]. Additionally, 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 result of accidental contamination 

(due to imperfectly washed garments) by the individual who collected the samples. 

One of the soil samples from Plot 2 also had a higher than expected concentration of fosthiazate 

(i.e., 24.8 ppm). This was thought to be due to a layer 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 indicates that local conditions (e.g., the presence of a clay pan) and the 

application method (e.g., disking to 2 versus 4 inches) can have considerable impacts on the 

resulting soil concentrations. Therefore, how the results from this 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 fosthiazate 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 application of fosthiazate as applied under the 

conditions of the study (i.e., 4 lb a.i./acre, 12-in. band, 4-in. incorporation). Because of 

the limitations cited in the review, however, 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 conclusions regarding this study are correct. The 

data from this study are not adequate for assessing 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 data” for terrestrial invertebrates, ISKBC submitted 

acute toxicity studies on carabid beetle, earthworms, spiders, and honey bees that were 

conducted for the European registration of fosthiazate. 

EFED RESPONSE: 

EFED appreciates the submission of the additional data. The 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 LD50 values for the contact and oral portions of the study are 0.75 μg a.i./bee and 0.61 μg 

a.i./bee, respectively. The contact LD50 (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 LD50 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 food 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 for terrestrial invertebrates of 

0.05. 

ISKBC COMMENT: 

In the PRA it is stated that risks to non-target terrestrial invertebrates are expected but not able to 

be quantified. The registrant states that, “(w)hile suppression 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 other non-target organisms 

than to... the honeybee” the registrant provided additional data, required for European 

registration, on non-target beneficial organisms. 

EFED RESPONSE: 

To clarify, the PRA does quantify risk to soil-dwelling arthropods. However, 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 data available at the time of the 

PRA. Using the recently submitted acute oral toxicity data for honey bees and fosthiazate 
6 

(MRID 49134004), an RQ of 0.15 can now be calculated, which exceeds the current interim 

LOC of 0.05. 

It is unclear to EFED what specifically ISKBC 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 expected (which is supported by the available toxicity data on honey 

bees). As stated in the PRA, any potential adverse effects to non-target organisms (including 

invertebrates) would be limited to the site of application. 

Although the recently submitted invertebrate studies 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 LC50 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 effects were reported in either study; however, the 

tested concentration (10 ppm) is below the estimated concentration for the currently registered 

fosthiazate use (i.e., 13.2 ppm, see above).