UNITED ST A TES ENVIRONMENT AL PROTECTION AGENCY WASHINGTON, D.C. 20460

MEMORANDUM

December I 5, 20 I 5 OFFICE OF CHEMICAL SAFETY AND
POLLUTION PREVENTION

SUBJECT: Rodenticides: Summary of Hazard and Science Policy Council (HASPOC) Meeting on October 1, 2015: Recommendations on Data Requirements for
Rodenticides.

PC Codes: See Table below
Decision No.: N I A
Petition No

. : NI A
Risk Assessment Type: N I A

TXR No.: 0057326

MRID No.: N I A

FROM: Uma Habiba
Executive Secretary

, HASPOC
Health Effects Division (7509P)

THROUGH: Jeff Dawson, Co-Chair
Jaime D' Agostino, PhD., C

- HASPOC
Health Effects Division (7509P)

TO: Matthew Crowley, Biologist
Risk Assessment Branch II
Chris Schlosser

, Toxicologist
Risk Assessment Branch VI
Health Effects Division (7509P)

MEETING ATTENDEES DP Barcode: N I A Registration No.: N I A Regulatory Action: N I A

Case No.: N I A
CAS No.: See below
40 CFR: N I A

HASPOC Members: Anna Lowit, Elissa Reaves, Elizabeth Mendez, Jaime D ' Agostino, Jeff

Dawson

, John Kough, Jonathan Leshin, Matt Lloyd, Michael Metzger, P. V. Shah, Ray Kent,
Sarah Gallagher, Uma Habiba

Presenter : Barry O'Keefe

, Christopher Schlosser

, Matt Crowley

, Vincent Chen

Other Attendees: Anwar Dunbar

, Bridget Bobowiec, Chris Olinger, Christina Swart z , Don
Wilbur

, Donna Davis

, Laura Nollen, Monica Hawkins

, Yung YangPage 2 of 10 

### I. PURPOSE OF MEETING

Rodenticides are meant to kill or control mammalia n species via their acute toxicity or other means such as a birth control agent. While they have differing chemistries (i.e., there are various active ingredients) their uses and the s ubsequent exposure patterns associat ed with these uses are similar such that data requirements can be evaluated in a consistent fashion across all rodenticide ingredients. This approach pr ovides for workload efficiencies and ensures consistency for evaluating potential data requirements, which ar e summarized in the table at the end of the document. Therefore, the Hazard and Science Policy Council (HASPOC) met on October 1, 2015
to determine a consistent framework for rodenticide data requirements.

II. EXPOSURE FRAMEWORK

This section outlines the process used for id entifying the exposure scenarios required for the selection of endpoints for risk assessment.

Dietary

 All rodenticides are considered non-food uses. Therefor e, no dietary exposure assessment

will be conducted for residues on food.

 If the rodenticide has broadcast uses (e.g., aerial applications ove r fields), a drinking water assessment might be applicable and a dietary exposure assessment for water only may be conducted.

Non-dietary

 Residential

o Handler

 If the rodenticide has loose formula tions (e.g., granules, pellets, tracking powders) for consumer products, re sidential dermal and inhalation assessments will be conducted because exposure is anticipated during the application of such product (e.g., from generation of particulates resulting in dermal and inhalation exposure). Place packs, bait blocks, or sachets are examples of formulations for which a residential or occupational

handler assessment would not be co nducted because they prevent or significantly minimize expos ures to those products.

o Post-application

 If bait stations are required in hom es/residential areas, access to the product will be prevented and no reside ntial post-application oral exposure

assessment will be conducted.

 No post-application dermal or inhalation exposure assessments will be conducted in situations where the type s of formulations and use patterns prevent exposure and rodenticides are expected to be of low volatility. The following should also be considered:

 If tracking powder formulations are available, a post-application oral assessment should be conducted because access to the product following its application might be possible.Page 3 of 10 

###  If the rodenticide is limited to underground uses only, access to the product will be prevented and no re sidential post-application oral exposure assessment will be conducted.

 Occupational

o Handler

 If the rodenticide is formulated as a granule, pellet, tracking powder or other similar loose form (i.e., not in bait stations or other packaging which prevents exposure), occupationa l dermal and inhalation handler assessments will be conducted because exposure is anticipated during the application from generation of particul ates. Place packs, bait blocks, or sachets in appropriate co ntainers would be examples of formulations for which an occupational handler asse ssment would not be conducted.

o Post-application

 No post-application dermal or inhalation assessments will be conducted because the types of formulations are expected to be of low volatility and no significant contact with foliar or ot her surface residues are expected for workers to contact in areas previo usly treated with rodenticides.

III. Toxicity Framework

This section outlines the process used for determining whether the database for a chemical contains appropriate studies for selection of endpoints for risk assessment. The categories presented below are based on the exposure conditi ons which were described in Section I.

Negligible Overall Exposure - No occupational, residential or dietary ex posures are anticipated (qualitative assessment)

If no exposures are expected from the use patterns of these chemicals, the HASPOC
recommends that no further studies be submitted to support registration review. However, if the use pattern were to change such that exposure is expected, then the Ag ency may revisit this
conclusion.

Occupational Exposure Only

Based on the use pattern, only occupational handler exposures are expected. In this scenario no residential handler or post-app lication exposures are expected, nor are any dietary exposures expected. Therefore, based on a weight-of- evidence approach, the HASPOC recommends that the following studies are not required for this group of rodenticides:

 870.3100, 90-Day oral rodent (conditi onally required for non-food)

 870.3150, 90-Day oral non-rodent (cond itionally required for non-food)

 870.7485, Metabolism and pharmacokinetics (conditionally required for non-food)

Additionally, the available toxicity databases we re evaluated and the HASPOC determined that the following studies were not required if they were not expected to provide a lower point ofPage 4 of 10 

### departure (POD) for risk assessment (i.e., rodentic ides with a well-established toxicity profile
such as the 1 st 

### and 2 nd 

### generation anti-coagulants). Rationale for each rodenticide is provided in the summary table.

 870.3700a, Prenatal developmental study in rat

 870.3700b, Prenatal developmental study in rabbit

 870.3800, Reproduction and fertility effects

 870.6200a, Acute neurotoxicity

 870.6200b, Subchronic neurotoxicity

 870.7800, Immunotoxicity

Furthermore, inhalation and dermal toxicity studies were not require d by the HASPOC if an acceptable oral study, which properly addresses a chemical’s toxicity profile (i.e., correct duration of exposure and endpoints measured) was available and use of the oral study did not result in Margins of Exposure (MOE) above the Level of Concern (LOC), including a 10x database uncertainty factor when an oral study was used to pr edict toxicity derived from the
inhalation route. Rationale for each roden ticide is provided in the summary table.

A mutagenicity battery was required for all chem icals unless sufficient literature or structure activity relationship (SAR) data were availabl e to characterize potential mutagenicity.

Occupational, Residential and/or Dietary (drinking water) exposure

For rodenticide chemicals with occupational handler and resi dential handler and/or postapplication exposure or dietary e xposure via drinking water, a cri tical evaluation of the toxicity
database was conducted.

1. If the current database provided sufficient info rmation to characterize the oral toxicity of the chemical, the HASPOC determined that the following studies were not required:

o 870.3100, 90-Day oral rodent (conditi onally required for non-food)

o 870.3150, 90-Day oral non-rodent (cond itionally required for non-food)

o 870.7485, Metabolism and pharmacokinetics (conditionally required for nonfood)

2. Additionally, the HASPOC determined that th e following studies were not required if they were not expected to provide a lower POD for risk assessment (e.g., rodenticides that have a well-established toxicity profile such as the 1 st 

### and 2 nd 

### generation anticoagulants). Rationale for each rodentic ide is provided in the summary table.

o 870.3700a, Prenatal developmental study in rat

o 870.3700b, Prenatal developmental study in rabbit

o 870.3800, Reproduction and fertility effects

o 870.6200a, Acute neurotoxicity

o 870.6200b, Subchronic neurotoxicityPage 5 of 10 

### o 870.7800, Immunotoxicity

Furthermore, inhalation and dermal toxicity studies were not require d by the HASPOC if an acceptable oral study was available and use of the oral study did not result in MOEs above the LOC, including a 10x database uncerta inty factor when an oral study was used to predict toxicity
derived from the inhalation route. Rationale fo r each rodenticide is provided in the summary
table.

A mutagenicity battery was required for all chem icals unless sufficient literature or SAR data were available to characterize potential mutagenicity.

A final summary outlining the HASPOC’s decisions for each rodenticide and data requirements
are shown in the table below.Page6of10RodenticideAnticipated QuantitativeExposure AssessmentsMissing StudiesDataRequired?RationaleAlpha-chlorohydrin1(PC code: 117101)None870.1100, Acute oral toxicity in ratNoNegligible exposuresbased on current usepattern (formulations,bait stations and nonresidential use sites)870.1200, Acute dermal toxicity870.1300, Acute inhalation toxicityin rat870.2400, Primary eye irritation inrabbit870.2500, Primary dermal irritation870.2600, Dermal sensitization870.3100, 90-Day oral rodent870.3150, 90-Day oral non-rodent870.3200, 90-Day dermal870.3465, 90-Day inhalation- rat870.3700a, Prenatal developmentalstudy in rat870.3700b, Prenatal developmentalstudy in rabbit870.3800, Reproduction and fertilityeffects870.5100, Bacterial reverse mutationassay870.5300 and 870.5375,In vitromammalian cell assay870.5385 and 870.5395,In vivocytogenetics870.6200a, Acute neurotoxicity870.6200b, Subchronic neurotoxicity1Previously reviewed by HASPOC (U.Habiba 9/29/15; TXR #0057207)Page7of10870.7485, Metabolism andpharmacokinetics870.7600, Dermal penetration870.7800, ImmunotoxicityContrapest2(PC Codes: 081700and 081800)None870.1100, Acute oral toxicity in ratNoNegligible exposuresbased on current usepattern (formulations,bait stations and nonresidential use sites)870.1200, Acute dermal toxicity870.1300, Acute inhalation toxicityin rat870.2400, Primary eye irritation inrabbit870.2500, Primary dermal irritation870.2600, Dermal sensitization870.3100, 90-Day oral in rodent870.3150, 90-Day oral in non-rodent870.3200, 28-Day dermal870.3465, 90-Day inhalation870.3700a, Prenatal developmentalstudy in rat870.3700b, Prenatal developmentalstudy in rabbit2Previously reviewed by HASPOC (U.Habiba 8/19/14; TXR #0056988)Page8of10870.3800, Reproduction and fertilityeffects870.4200b, Carcinogenicity study inmouse870.4300, Chronictoxicity/carcinogenicity in rat (or870.4100 and 870.4200 in rat)870.5100, Bacterial reverse mutationassay870.5300 and 870.5375,In vitromammalian cell assay870.5385 and 870.5395,In vivocytogenetics870.6200a, Acute neurotoxicity870.6200b, Subchronic neurotoxicity870.7485, Metabolism andpharmacokinetics870.7800, ImmunotoxicityChlorophacinone(PC code: 067707)870.3100, 90-Day oral in rodentNoAvailable studiesadequately characterizetoxicity for anyquantitative riskassessment870.3800, Reproduction and fertilityeffects870.6200a, Acute neurotoxicity870.6200b, Subchronic neurotoxicity870.7800, ImmunotoxicityPage9of10870.3465, 90-Day inhalation YesDue to the absence oftracking powder useinformation, theavailable toxicity dataare not sufficient tocharacterize risks frominhalation exposure.Diphacinone(PC code: 067701)-Occupational handler-Residential postapplication oral870.3700b, Prenatal developmentalstudy in rabbitNoAvailable oraladministration studiesadequately characterizetoxicity for anyquantitative riskassessments870.3800, Reproduction and fertilityeffects870.6200a, Acute neurotoxicity870.6200b, Subchronic neurotoxicity870.7800, Immunotoxicity870.3465, 90-Day inhalation NoUse of available oraltoxicity studies result inMOEs > 10,000 forrelevant inhalationexposure scenarios.Warfarin(PC code: 086002)None870.1100, Acute oral toxicity in rats870.1200, Acute dermal toxicity870.1300, Acute inhalation toxicityin rats870.2400, Primary eye irritation inrabbits870.2500, Primary dermal irritation870.2600, Dermal sensitization870.3100 90-Day oral rodent870.3150 90-Day oral non-rodent870.3200, 90-Day dermalNoNegligible exposuresbased on current usepattern (bait in baitstations or packaged intamper-resistant baitstations).In addition, warfarin, asynthetic analogue ofvitamin K, is a memberof the coumarin familyof blood anticoagulantsPage10of10870.3465 90-Day inhalation in rats870.3700a, Prenatal developmentalstudy in rats870.3700b, Prenatal developmentalstudy in rabbits870.3800, Reproduction and fertilityeffects870.5100, Bacterial reverse mutationassay870.5300 and 870.5375,In vitromammalian cell assay870.5385 and 870.5395,In vivocytogenetics870.6200a, Acute neurotoxicity870.6200b, Subchronic neurotoxicity870.7485 Metabolism andpharmacokinetics870.7600 Dermal penetration870.7800, Immunotoxicityand is used as ananticoagulant in thetreatment of individualswith hyper-coagulationproblems. Its toxicity,mechanism of action,and treatment ofoverdose in humans arewell established.