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### Toxicological Endpoints

The endpoints that were used to complete th is assessment are summari zed in the Table 1 and are unchanged from those used in the prev ious ORE assessment for the RED (D318630). Endpoints were selected only for incidental oral and inhalation exposures. No endpoints were selected for dermal exposure because no effect s were observed at the limit dose in the 21 day dermal study in rabbits. The target MOE (i.e. level of concern) for short term inhalation exposures is 100. The target MOE for interm ediate/long term inhalation exposures is 1000 because an additional safety factor of 10 is a dded to account for the lack of a NOAEL. The target MOEs for inhalation exposures are th e same for both occupational and residential exposures. The target MOE for short term inci dental oral exposures is 300 which include an FPQA database uncertainty factor of 3X to accoun t for the lack of a DNT. The target MOE for intermediate/long term incide ntal oral exposures is 100.

Table 1 –Endpoints for Assessing Occupati onal and Residential Risks for Pyrethrins

Exposure Scenario Dose Used in Risk Assessment Level of Concern (LOC) for Risk Assessment Study and Toxicological Effects

Incidental Oral – Short-Term (1-30 days) NOAEL= 20 mg/kg/day Residential MOE = 300 Occupational MOE= N/A Acute neurotoxicity study in rats LOAEL = 63 mg/kg/day based on tremors in females

Incidental Oral - Intermediate-Term (1- 6 months) NOAEL= 6.4 mg/kg/day Residential MOE = 100 Occupational MOE = N/A Two generation reproduction study in rats LOAEL = 65 mg/kg/day based on decreased F1b pup body weight/body-weight gain during lactation

Dermal Exposure - Short, Intermediate & Long Term No endpoint for this exposure scenario was identified following repeated [21 day] dermal exposure to rabbits at the limit dose.

Inhalation - Short-Term NOAEL= 7.67 mg/kg/day [0.03 mL/kg/day] Residential MOE = 100 Occupational MOE = 100 Subchronic inhalation toxicity study in rats LOAEL = 25.56 mg/kg/day based on tremors, labored breathing, hyperactivity, secretory signs, matted coat, decreased body weight/body-weight gain

Inhalation - Intermediate & Long-Term LOAEL= 2.56 mg/kg/day [0.01 mL/kg/day] Residential MOE = 1000 Occupational MOE = 100 Subchronic inhalation toxicity study in rats LOAEL = 2.56 mg/kg/day based on respiratory tract lesions



### Occupational Handler Exposure and Risk

The occupational handler risks were assessed for the pet spray use using the same exposure data, assumptions and calculation methods that were used in the ORE assessment for the RED (D316630) with the only difference being the in creased application rate. As was done previously, only inhalation exposur es have been assessed for th e occupational handlers applying pyrethrin pet sprays. Dermal exposures were not assessed because no dose or endpoints were selected for dermal exposure. The MOE for th e occupational handler exposure scenario is included in Table 1. The short term MOE is above the target MOE of 100 and therefore the short term risk is not of concern. The intermediate /long term MOE of 1000 is above the target MOE of 1000 and therefore the intermediate/l ong term risk is not of concern.Page 3 of 4 

### Table 1 - Pyrethrin Inhalation MOEs for Occupational Handlers (Pet Groomers and Veterinary Technicians)

Exposure Scenario Inhalation Unit Exposure (μg/lb ai) Application Rate (lb ai/16 oz can) Amount Ai Used Inhalation Dose (mg/kg/day) Short Term MOE Intermediate/ Long Term MOE

Aerosol Can Application of

Pet Sprays 1300 0.002 0.008 lb 0.00015 51,000 17,000

* Baseline inhalation unit exposures represent no resp irator. The unit exposure value is from PHED. * The application rate is based on the maximu m label rate 0.20 % ai for pet spray uses. * The amount ai used is based upon the application of 8 ounces of product applied per animal ti mes 8 animals treated per day. * Inhalation dose = [unit exposure value * 0.001 mg/gm * A pplication rate* Amount Used)] / Body weight (70 kg). * MOE = NOAEL/Dose where the NOAEL is 7.67 mg/kg/day for short term exposures and 2.56 mg/kg/da y for intermediate/long term exp osures. * The target MOE is 100 for short term inhalation exposur es and 1000 for intermediate/l ong term inhalation exposures.



### Occupational Post Application Exposure and Risk

As was the case for the previous ORE assessmen t, occupational post appl ication exposures were not assessed for pet spray uses because no dermal endpoints were selected.

Residential Hander Exposure and Risk

As was the case for the previous ORE assessmen t, only short term exposures were assessed for residential handlers applying pet sprays because the pyrethrins are applied to pets only on an intermittent basis. The exposure and risk estimat e for the residential handler pet spray scenario is included in Table 2. The MOE is greater than the target MOE of 100, therefore the risks are not of concern.

Table 2 - Pyrethrin Inhalation MOE for Residential Handlers (Application of Pet Sprays)

Exposure Scenario Inhalation Unit Exposure (μg/lb ai) Application Rate (lb ai/16 oz can) Amount Ai Used Inhalation Dose (mg/kg/day) Short Term MOE

Aerosol Can Application of

Pet Sprays 1300 0.002 0.001 lb 0.000019 400,000

* Baseline inhalation unit exposures represent no resp irator. The unit exposure value is from PHED. * The application rate is based on the corrected va lue of 0.20 % ai provided by the registrants. * The amount ai used is based upon the application of 8 ounces of product applied per animal ti mes 1 animal treated per day. * Inhalation dose = [unit exposure value * 0.001 mg/gm * A pplication rate* Amount Used)] / Body weight (70 kg). * MOE = NOAEL/Dose where the NOAEL is 7. 67 mg/kg/day for short term exposures. * The target MOE is 100 for short term inhalation exposur es and 1000 for intermediate/l ong term inhalation exposures.Page 4 of 4 

### Residential Post Application Exposure and Risk

The residential post application e xposures to toddlers playing w ith pets after treatment were assessed in the same manner as was done in the ORE assessment for the RED (D318630) with the only difference being the increased application rate. Only incidental oral exposures were assessed because dermal endpoints were not selecte d. The risk for this scenario is included in Table 3. The MOE is greater than the target MOE of 300, therefore the risk is not of concern.

Table 3 - Pyrethrin Post-application Risk to Toddlers Playing with Pets after Treatment with Spray Formulations

Application

Method AR (mg ai/cm 2 ) Transferable Residue (mg/cm 2 ) Daily Oral Dose (mg/kg/day) Short Term MOE*

Aerosol Can 0.076 0.015 0.010 2000

Daily Oral Dose = TR * SEF * SA hands * Freq where: AR = Application Rate or amount applied to animal in a single treatment (mg ai/animal) = 1⁄2 of 16 oz spray container with maximum of 0.2% ai per 6000 cm 2 /animal TR = Transferable Residue (AR * 20%) SA pet = Surface Area of a treated dog (6000 cm 2 /animal) SEF = Saliva Extraction Factor (50%) SA hands = Surface Area of the hands (20 cm 2 ) Freq = Hand-to-Mouth Events (1 event/day) BW = 15 kg for toddler

MOE = Short Term Oral NOAEL (20 mg/kg/day)/Daily Oral Dose (mg/kg/day)