2 2009) associated with the Calif ornia data from the Californi a Department of Pesticide Regulation.

Monitoring Data

The Agency greatly appreciates receiving releva nt monitoring data a nd the associated report (Ensminger and Kelley, 2011) and analytical me thod (California Depart ment of Food and Agriculture, 2009). The Agency typically has acc ess to a vast array of toxicology data through the Ecotoxicology (ECOTOX) database maintain ed by the Agency but does not have ready access to environmental fate studies and pestic ide usage and monitoring data summarized in proprietary or state and local agency reports/databases.

Comments by MANA

Comment: EFED noted that residential uses were to be cancelled; thus, their recommendations for environmental fate and ecological effects studie s reflect this reduced usage. The initial basis for some studies, however, cited risks identifi ed in the 2008 RED as the basis for requiring studies. Lower use patterns, now in effect, may af fect how these risks are currently perceived.

EPA Response: The Agency agrees that mitigation measures ( e.g. , reduced application rates and elimination of residential use) as a result of the 2008 RED have reduced risk. EFED cited risks identified in the 2008 RED as part of the basis fo r requiring the passerine acute oral toxicity test and aquatic plant toxicity tests during Registration Review. The ecological risk assessment for

the 2008 RED was based on “information contained in the currently existing labels that the registrant has indicated they will support for re -registration” and application rates “supported by the registrant and documented in the Prometon Use Closure Memo (1/22/07).” 2 In particular, estimated exposure concentrations (EECs) were based on a maximu m single application rate of

0.23 lb a.i./ 500 ft 2 which is equivalent to 20.04 lb a.i./A. This application rate is very close to the current, highest maximum applic ation rate of 18 lb a.i./A which is applicable for all use sites except right-of-way specifically for utility poles. As a result, EFED does not anticipate EECs modeled in the 2008 RED assessment to change substantially. For example, a preliminary analysis of risk to birds via T-REX modeling us ing the reduced single ma ximum application rate of 18 lb a.i./A indicates that there is still poten tial for avian risk from acute and chronic exposure to prometon ( i.e. , acute and chronic level of concern ex ceedances). Therefore, recommendations for submission of data in the Registration Revi ew problem formulation are based on perceived risk as a result of the current, re gistered uses of prometon.

Comment: Table 4 lists triazine-relate d herbicides. Prometon is in the methoxytriazine class. There are five other methoxytriazine products in this class. The Food Quality Protection Act obligated the Agency to evaluate pesticides with a common mechanism of toxicity (US Congress, 1996). FQPA notes:

2 DP 335303, 335305. Error Correction: Drinking Water Assessment and Ecological Risk Assessment for Prometon
RED. October 24, 2007.3 "(D) FACTORS -In establishing, modifying, leav ing in effect, or revoking a tolerance or exemption for a pesticide chemical residue, the Administrator shall consider, among other

relevant factors-... "(v) available information concerning the cu mulative effects of such residues and other

substances that have a comm on mechanism of toxicity; ... "

While the Agency has concluded a cumulative risk assessment for chlorinated triazine herbicides, prometon is not chlorinated and was not considered to share a common mechanism of toxicity (US EPA, 2002, 2006). The weight of evidence used cited a specific endpoint: the disruption of the hypothalamic-pituitary-gonadal (H PG) axis. Included in this assessment were three chlorinated degradants: Desethyl atrazi ne (DEA), Desisopropyl atrazine (DIA) and diaminochlorotriazine (DACT).

It is likely that some of the triazine herbicides, thirty-four of which are noted in Table 4, share commonality other than disruption of the HPG a nd thus share similar mammalian and ecological effects. While prometon is not chlorinated, it doe s have some common degradants with atrazine, specifically GS-17791, GS-17794. We su spect sufficient data may be available, including data for triazines not currently regist ered by EPA, which effectively speak to the issues identified by the Agency.

We ask that all relevant eff ects of the triazine group be considered during the Registration Review of prometon. Integrating such data into th e review process does not require that a formal common mechanism of toxicity be establ ished for every endpoint considered.

EPA Response: In the absence of toxicity data that are specific to prometon for a particular taxon, EFED will consider data from surrogate triazi ne herbicides. For example, as stated in the Registration Review problem formulation, in the ab sence of acceptable/quantitative toxicity data

for Lemna , EFED may use the most conservative Lemna toxicity endpoints ( i.e. , EC 50 and NOEC) among the triazines to characterize the toxici ty of prometon to aquatic vascular plants; in the absence of acceptable/quantita tive data for a freshwater diatom, marine diatom, and cyanobacterium, EFED may adjust the most c onservative aquatic non-v ascular plant endpoints ( i.e. , EC 50 and NOEC) for atrazine to characterize the toxicity of prometon to aquatic nonvascular plants; and in the absence of toxicity data for a passerine species, passerine toxicity data for surrogate pesticides – starting with data for triazines and proceeding to data for less related chemicals – may be used to characterize the toxicity of prometon to passerine species.

Comment: Prometon' s MOA interferes with photosynt hesis. Based on the current acute toxicity to both freshwater and saltwater plant species, additional endpoints of toxicity can be predicted

with some measure of confidence.

EPA Response: The registrant is welcome to submit an analysis that predicts the toxicity of prometon “with some measure of confidence” to Lemna , freshwater diatoms, marine diatoms, and cyanobacteria based on what is currently known about the toxicity of prometon to freshwater plant and saltwater plant species. Such an anal ysis will be considered by EFED at the time of

submission. As stated in the Registration Review problem fo rmulation, in the absence of4 acceptable/quantitative toxicity data for Lemna , EFED may use the most conservative Lemna toxicity endpoints ( i.e. , EC 50 and NOEC) among the triazines to characterize quantitatively the toxicity of prometon to aquatic vascular plants; and in the absence of ac ceptable/quantitative data for a freshwater diatom, marine diatom, and cyanobacterium, EFED may adjust the most conservative aquatic non-vascular plant endpoints ( i.e. , EC 50 and NOEC) for atrazine to characterize the toxicity of prometon to aquatic n on-vascular plants.

Comment: We note that the Agency recently comple ted a retrospective analysis for the immunotoxicity requirement (Rowla nd, 2013). This analysis led to th e conclusion that data from the immunotoxicity study was generally unlikely to impact regulatory decisions. Accordingly, where sufficient data on immune-related endpoints we re available, the Agency indicated it would consider waivers based on a weight of evidence evaluation. Since generation of additional data is resource intensive on both registrant and Agen cy, we ask that basis for issuing DCIs be thoughtfully evaluated, considering each study's potential for aff ecting regulatory decisions and

whether collective data from a va riety of other triazines can speak to these needs. We note that EFED's Registration Review Pr oblem Formulation for prometon characterized the series of ecological studies as having a high potential to add value to the Registration Review risk assessment (Sternberg et al., 2013). Generating add itional data in the absence of valid regulatory questions may add to prometon’s database, yet provide minimal regulatory return.

EPA Response: In the Registration Review problem fo rmulation, EFED prioritized data gaps: low potential studies are unlikely to change risk determinations because alternate methods and weight of evidence may possibly be used in th e absence of data whereas high potential studies would enable the Agency to better characterize potential risks by elimina ting uncertainties that cannot be accounted for using alternate methods or weight of evidence. In addition, EFED detailed a path forward in the absence of data for studies considered data ga ps. The registrant is welcome to submit waivers based on a weight of evidence evaluation. Such waivers will be considered by EFED at the time of submission.

Comment: Guideline: 835.4300/ Aerobic aquatic metabolism MANA will address this data gap if this is requested in the Data Call-In. The Agency notes prometon is persistent in so il and does not readily undergo abiotic hydrolysis. Expected metabolites have been id entified and the toxiciti es of these are assigned "as toxic as the parent." (Mana Crop Protection, p. 4).

EPA Response: Previous risk assessments conducted by the Agency used tw ice the half-life

calculated for the aerobic soil metabolism as a conservative estimate of the aerobic aquatic

metabolism half-life. EFED will use the same method in the Registration Review risk assessment

if an aerobic aquatic metabolism is not provided.

Potentially, conducting an aerobic aquatic metabolism study for prometon might produce a

shorter half-life than twice the aerobic soil metabolism half-life, which would decrease EFED’s estimates of risk from prometon uses. As noted in the Registration Revi ew problem formulation,5 fulfilling this data requirement has a high potential to add value to the Registration Review ecological risk assessment.

Comment: Guideline: 835.4400/ Anaerobic aquatic metabolism MANA will address this data gap if this is requested in the Data Call-In. An anaerobic aquatic study was cited by th e Agency (MRID 40145501) in the 2008 RED (cited also as an aerobic soil metabolism study). This st udy will be reviewed for its relevance to this anticipated data need.

EPA Response: The ecological risk assessment in s upport of the Reregistration Eligibility Decision (RED) used the half-lif e calculated for the anaerobic soil metabolism as the anaerobic aquatic metabolism half-life. However the study is conducted with both an aerobic and anaerobic phases in the same study. In the an aerobic phase the parent and degr adates were stable (did not degrade). The anaerobic soil metabolism half-lif e was calculated across both the aerobic and anaerobic phases of the same study. Therefore in the RED, the anaerobic soil metabolism halflife actually refers to degradation that only occurred under aerobic conditions. Under current EFED guidance, prometon would be considered stable to anaerobic soil metabolism, and

therefore stable to anaerobic a quatic metabolism, if EFED used this study to estimate an anaerobic aquatic metabolism half-life.

Potentially, conducting an anaerobic aquatic me tabolism study for prometon would show some degradation, which would decrease EFED’s estimates of risk from prometon uses (compared to an assumption of stable for anaerobic aquatic me tabolism). However, if the registrant believes

that the result of an anaerobic aquatic metabolism study woul d only show that prometon does not degrade by anaerobic aquatic metabolism, then the registrant could submit a waiver request that states that the registrant believes that pr ometon will not degrade under anaerobic aquatic conditions. In that case, EFED would consider prometon stable to anaerobic aquatic metabolism and the registrant would be spar ed the expense of this study. As noted in the Registration Review problem formulation, fulfilling th is data requirement has a high potential to add value to the Registration Review ecological risk assessment.

Comment: Guideline: 835.1400/ Fish Early Life Stage Toxici ty Test, Rainbow Trout MANA will address this data gap if this is requested in the Data Call-In. We note MRID 41810902 (Fish Early Life Stage) was cited as data supporti ng the re-registration of prometon. This study was conducted with fathead minnow (Pimephales promelas). This study will be reviewed for its relevance to this anticipated data need.

EPA Response: The registrant is welcome to revi ew MRID 41810902 for its relevance to the anticipated data need. Such a review will be considered by EFED at the time of submission. As noted in the Registration Revi ew problem formulation, the chr onic, early life stage endpoint of 19.7 mg/L for freshwater fish (fathead minnow; MRIDs 41810902, 42318202) is approximately equal to the most sensitive acute endpoint of 19.6 mg/L for freshwater fish (rainbow trout; MRID 41609108). This discrepancy is probably due to the different species used in the tests ( i.e. , fathead minnow in the chronic test and ra inbow trout in the acute test). Making6 extrapolations from chronic data to acute data or vice versa to establish the sensitivity of another fish species ( e.g. , the acute toxicity of prometon to a more sensitive freshwater fish such as the fathead minnow; the chronic toxici ty of prometon to es tuarine/marine fish) requires at least one set of paired tests (acu te and chronic) with a common species . This can involve the performance of either an acute toxicity test with fathead minnow or a chronic test ( e.g. , early life stage toxicity test) with rainbow trout.

Comment: Guideline: 850.4400/ Aquatic Plant Toxicity Test using Lemna spp. MANA will address this data gap if this is requested in the Data Call-In. Acute toxicity to plants (SW diatom) is 0.25 mg/L (LC 50 ). The citation, ECOTOX 9211 refers to a study (judged qualitative) of the effect of herbicides on pho tosynthesis and growth of marine unicellular algae. The Agency also notes that the LC 50 for freshwater non-vascular aquatic plants ( e.g. , green alga) is 0.098 mg/L, signi ficantly more toxic than to diatoms. Prometon’s mode of action (interfering with photosynthe sis by disrupting carbon dioxide fixation and other actions) is consistent with its marked aquatic plant toxicity.

EPA Response: The Agency conducts assessments on uni cellular and aquatic macrophytes ( i.e.

, aquatic non-vascular and vasc ular plants, respectively). Algae and duckweed ( Lemna spp.) represent distinct taxonomic groups in the risk assessment, and as such, duckweed data are preferred over algae data to represent aquatic vascular plants. In previous risk asse ssments, an ECOTOX open literature study (E081431) was referenced for characterizing the toxicity of prometon to aquatic vascular plants ( i.e.

, Lemna spp.). However, this study has been classified as qualitative for use in the Registration Review ecological risk assessment because of the lack of experimental details ( e.g. , replication, test concentrations). Therefore, there are currently no acceptable/quantitative data available for use in characterizing the toxicity of prometon to aquatic vascular plants. In the absen ce of this data, the most conservative Lemna toxicity endpoints ( i.e. , EC 50 and NOEC) among the triazines may be used to characterize the toxicity of prometon to aquatic vascular plants.

Comment: Guideline: 850.2100/ Avian Oral Toxicity, passerine species MANA will address this data gap if this is requested in the Data Call-In. Avian acute toxicity and dietar y toxicity studies have been conducted on the quail, as well as reproduction study in the duck. The Agency notes the greatest prometon residues and exposure levels are likely to occur in th e surface soil and on plant foliag e, seeds and insects on treated areas immediately following applications . Bioaccumulation is not expected.

EPA Response: In addition to acute oral toxicity data for ei ther a waterfowl or upland game species ( e.g. , mallard duck or bobwhite quail, respectiv ely), acute oral toxicity data for a passerine species are now re quired under the new 40 CFR Pa rt 158. As noted above, a preliminary analysis of risk to birds via T-REX modeling usi ng the reduced single maximum application rate of 18 lb a.i./A indicates that th ere is still potential for avian risk from acute and chronic exposure to prometon ( i.e. , acute and chronic level of concern exceedances). Passerine birds may utilize metabolic pathways that are different from larger birds and therefore be more sensitive to prometon. Furthermore, passerines e xhibit behavioral responses to pesticide dosing7 that are potential indicators of reduced fitness in the field ( e.g. , regurgitation of contaminated diet) even when direct biochemically-mediated le thal toxicity is not apparent. Therefore, fulfilling this data requirement has a high potential to add value to the Registration Review ecological risk assessment as the generated data will allow the Agency to be protective of passerine species.

Comment: Guideline: 850.4550/ Cyanobacteria (Anabaena flosaqua) toxicity MANA will address this data gap if this is requested in the Data Call-In. This data gap is based on the 2008 RED identif ying a risk concern fo r aquatic non-vascular plants. We note there is an array of both freshw ater and saltwater aquati c plant studies (Table 16 of the 2008 RED). We will in tegrate these data with other data on triazines in considering this data gap.

EPA Response: The registrant is welcome to submit an analysis that integrates existing prometon toxicity data for freshwater and saltwate r aquatic plant studies in considering this data gap. Such an analysis will be considered by EFED at the time of submission.

References

Ensminger, M. and K. Kelley. 2011. Monitoring Urba n Pesticide Runoff in Northern California,

2008-2009. California Environmental Protecti on Agency, Department of Pesticide Regulation, Environmental Monitoring Bran ch, Surface Water Protection Program. Report 249. March 2011. 53 pp.

California Department of Food and Agriculture . 2009. Determination of Atrazine, Bromacil, Cyanazine, Diuron, Hexazinone, Metribuz in, Norflurazon, Prometon, Prometryn, Simazine, Deethyl Atrazine (DEA), Deisopropyl Atrazine (ACET), Diamino Chlorotraizine ( DACT), Tebuthiuron a nd the metabolites Tebuthiuron-104, Tebuthiuron106, Tebuthiuron-107 and Tebuthiuron-108 in We ll Water and River Water By Liquid Chromatography- Atmospheric Pressure Ch emical Ionization Mass Spectrometry.” Center for Analytical Chemistry. Environm ental Analysis Section. EM 62.9. Revision 2. Revision Date: 1/09/09. 26 pp.