Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 1 of 56 **UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**

**WASHINGTON, D.C. 20460 OFFICE OF**  **CHEMICAL SAFETY AND POLLUTION PREVENTION**  **MEMORANDUM Date:**  XX - APR - 2010 **SUBJECT: Novaluron**  **:** Human - Health Risk Assessment for Proposed Section 3 Use s on

Sweet Corn and in Food - or Feed - Handling Establishments . **PC Code:** 124002 **DP Barcode s**  **:** D378387 , D377471 **Decision No s**  **.:** 432483 , 430432 **Registration No s**  **. :**  66222 - 35 , 66222 - ERT **Petition No s**  **.:** 0E7723 , 0F7708 **Regulatory Action:** Section 3 Registration **Risk Assessment Type:** Single Chemical Aggregate **Case No.:** 7615 **T XR No.:**  NA **CAS No.:** 116714 - 46 - 6 **MRID No .:**  NA **40 CFR:** §180.598 **FROM:** Lata Venkateshwara, Environmental Scientist

Julie L . Van Alstine, MPH, Environmental Health Scientist Anwar Dunbar, Ph.D., Pharmacologist Risk Assessment Branch 1 (RAB1) Health Effects Division (HED; 7509P) **THROUGH:** Dana M. Vogel, Branch Chief

George F. Kramer, Ph.D., Branch Senior Chemist RAB1/HED (7509P) **TO:** Barbara Madden/Laura Nollen (RM 05)

Registration Division (RD; 7505P) And John Hebert (RM 07)/ Jennifer Gaines RD ( 7505P) The HED of the Office of Pesticide Programs (OPP) is charged with estimating the risk to human health from exposure to pesticides. The RD of OPP has requested that HED evaluate hazard and exposure data and conduct dietary , occupational, residential, and aggregate exposure assessments, as needed, to estimate the risk to human health that will result from all registered and proposed uses of novaluron ( N - [[[3 - chloro - 4 - [1,1,2 - trifluoro - 2 - (trifluoromethoxy )ethoxy] phenyl]amino]carbonyl] - 2,6 - difluorobenzamide). A summary of the findings and an assessmentNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 2 of 56 of human risk resulting from the registered and proposed uses for novaluron are provided in this document. The risk assessment and occupational/residential exposure assessment were provided by L ata Venkateshwara (RAB1) , the residue chemistry data review and dietary

risk assessment were provided b y Julie Van Alstine (RAB1), the hazard characterization by Anw ar Dunbar (RAB1), and the drinking water assessm ent b y Iw ona Maher of the Environmental Fate and Effects Division (EFED). The most recent human - health risk assessment was conducted in conjunc tion with a request for the use of novaluron on grain sorghum (M emo, J. Van Alstine, et al. , 23 - FEB - 2010 ; D364307 ). A detailed hazard characterization for novaluron is presented in a previous HED risk assessment ( Memo, M. Clock - R

ust, et al. , 25 - MAR - 2004; D 295824 ). This document contains only those aspects of the risk assessment which are affected by the proposed Section 3 requests for use of nov aluron on sweet corn and in food - or feed - handling e stablishments .Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 3 of 56 **Table of Contents 1.0**  **EXECUTIVE SUMMARY**  **................................ ................................**  **............................... 4**  **2.0 INGREDIENT PROFILE**  **................................ ................................**  **............................... 12**  **2.1 Summar** **y of Proposed Uses ................................**  **................................ .........................**  **12 2.2**  **Structure and Nomenclature ................................**  **................................ ......................**  **14 2.3**  **Physical and Chemical Properties ................................**  **................................ ..............**  **14 3.0**  **HAZARD CHARACTERIZATION/FQPA CONSIDERATIONS .............................**  **15 3.1**  **FQ PA Considerations**  **................................ ................................**  **................................ ..**  **16 3.2**  **Endocrine Disruption ................................**  **................................ ................................**  **... 18**  **4.0 DIETARY EXPOSURE/RISK CHARACTERIZATION**  **................................ ...........**  **19 4.1**  **Food Residue Profile ................................**  **................................ ................................**  **.... 19**  **4.2 Drinking Water Residue Profile**  **................................ ................................**  **................. 25**  **4.3 Dietary Exposure and Risk**  **................................ ................................**  **......................... 26**  **4.4 Anticipated Residue and %CT Information**  **................................ .............................**  **27 5.0**  **RESIDENTIAL (NON -**  **OCCUPATIONAL) EXPOSU RE/RISK**  **CHARACTERIZATION ................................**  **................................ ................................**  **28 5.1**  **Residential Handler Exposure and Risk ................................**  **................................ ....**  **28 5.2**  **Residential Post application Exposure and Risk ................................**  **....................... 31**  **5.3 Combined Residential Risk Estimates**  **................................ ................................**  **........ 37**  **5.4 Bystander Post -**  **application Inhalation Exposure ................................**  **..................... 37**  **5.5 Spray Drift**  **................................ ................................**  **................................ ....................**  **38 6.0**  **AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION ........**  **38 6.1**  **Short -**  **Term Aggregate Risk ................................**  **................................ ........................**  **39 6.2**  **I ntermediate**  **- Term Aggregate Risk**  **................................ ................................**  **........... 40**  **6.3 Chronic Aggregate Risk**  **................................ ................................**  **.............................. 40**  **7.0 CUMULATIVE RISK**  **................................ ................................**  **................................ .....**  **41 8.0**  **OCCUPATI ONAL EXPOSURE/RISK PATHWAY**  **................................ ...................**  **41 8.1.1**  **Occupational Pesticide Handler Exposure and Risk for Sweet Corn ..................**  **41 8.1.2**  **Occupational Pesticide Handler Exposure and Risk for Crack and Crevice .....**  **44 8.2**  **Occupational Post -** **Application Worker Exposure and Risk ................................**  **... 47**  **9.0 DATA NEEDS AND LABEL RECOMMENDATIONS**  **................................ ..............**  **50 9.1**  **Toxicology ................................**  **................................ ................................**  **..................... 50**  **9.2 Residue**  **Chemistry ................................**  **................................ ................................**  **....... 50**  **9.3 Occupational and Residential Exposure**  **................................ ................................**  **.... 52**  **Appendix A: TOXICOLOGY ASSESSMENT ................................**  **................................ ........**  **53 A.1.**  **Acute Toxicity Profile ................................**  **................................ ................................**  **.. 53**  **A.2 Toxicity Profiles**  **................................ ................................**  **................................ ............**  **53**Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 4 of 56 **1.0 EXECUTIVE**  **SUMMARY** Under Section 3 of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), as amended, the Interregional Research Project No. 4 (IR - 4) has submitted a petition ( PP# 0E7723 ) to register the end - use product Rim o n ® 0.83 Emulsifiable Concentrate ( EC ) In secti ci de (EPA Reg. No. 66222 - 35) for use on sweet corn . To support the submission for permanent tolerances for residues of novaluron in/on sweet corn stover, forage, and kernel plus cob with husks removed ( K+CWHR) , IR - 4 has also propose d tolerance increases for residues of novaluron in/on milk and milk fat . Co ncurrentl y, Makhteshim - Agan of North America (MANA) has submitted a petition (PP# 0F7708 ) to register the end - use product Rimon ® Supra 10EC Insecticide (EPA Est. No. 66222 - ERT ) for indoor and outdoor control of roaches and crickets in food - and feed handlin g establishments. Both products are EC formulation s which contain 9.3% novaluron ( N - [[[3 - chloro - 4 - [1,1,2 - trifluoro - 2 - (trifluoromethoxy)ethoxy] phenyl]amino]carbonyl] - 2,6 - difluorobenzamide) b y weight [equivalent to 0.83 pound (lb) ai/gallon (gal)]. Novaluron, a benzoylphenyl urea compound, is a pesticide chemical belonging to the class of insecticides called insect - growth regulators (IGR s ) . Tolerances for residues of novaluron are established under 40 CFR §180.598 in/on a wide variety of crops at levels ranging from 0.05 to 40 ppm. Tolerances for residues of novaluron are also established in/on the following livestock commodities : eggs, milk, milk fat , the meat, fat , kidney , liver, and meat byproducts (except kidney and liver) of cattle, goat, horse, and sheep , and the meat, fat, kidney, liver, and meat by products of poultry

and hog . A time - limited tolerance, with an expiration date of 31 - DEC 2011, is established in association with a Section 18 Emergency Exemption for strawbe rries at 0.50 ppm. All existing uses for novaluron are agricultural or commercial in nature. The proposed food - and feed - handling establishment use of novaluron includes uses i n residential and commercial building s and structures , and their immediate s urroundings , and on modes of transport ation. This is the first proposed residential use of novaluron. Hazard Characterization Novaluron has low acute toxicity via the oral (Toxicity

Category IV), dermal (Toxicity

Category III), and inhalation routes ( Toxicity Category IV). No ocular (Toxicity Category IV) or dermal irritation (Toxicity

Category IV) was noted. Novaluron is not a dermal sensitizer. In subchronic and chronic toxicity

studies, novaluron primaril y produced hematotoxic effects (toxicity t o blood) such as methemoglobinemia, decreased hemoglobin, decreased hematocrit, and decreased red blood corpuscles ( RBCs or erythrocy tes) that were associated with compensatory erythropoiesis. No maternal and/or developmental toxicity was observed in anim als tested up to the limit dose in either the rat or rabbit developmental toxicity studies. In the two - generation reproductive toxicity

study , increased spleen weights were observed in parents and offspring at the same dose, and reproductive toxicity was observed in males onl y at a higher dose. Neurotoxic effects, including clinical signs, changes in functional - observation battery (FOB) parameters, and neuropathology were observed following a single dose at the limit dose only (2000 mg/kg/day) in the acut e neurotoxicity study in rats. However, no signs of neurotoxicity or neuropathology

were observed following repeated dosing in the subchronic neurotoxicity studyNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 5 of 56 in rats at similar doses , n o evidence of neuropathology was observed in subchronic and chronic to xicity studies in rats, mice, or dogs , and novaluron is not considered acutely toxic (LD 50 >5000 mg/kg) . Therefore, RAB1 toxicologists reaffirmed the HED Hazard Identification Assessment Review Committee (HIARC) conclusion that there is not a concern for neurotoxicity resulting from exposure to novaluron. There was no evidence of either carcinogenic or genotoxic potential with novaluron. Dose Response and Endpoint Selection The RAB1 toxicologists reevaluated the novaluron database , including the previous conclusion that the Food Quality Protection Act (FQPA) Safety Factor (SF) for increased susceptibility of infants and children can be reduced to 1X. RAB1 toxicologists have determined that reliable data show the safety of infants and ch ildren would be adequatel y protected if the FQPA SF were reduced to 1X. The decision was based on a lack of increased susceptibility in developmental toxicity studies at levels up to the limit dose in the rat or rabbit or in the two - generation reproductio n study

in rats . The risk assessment team concluded that the FQPA SF for increased susceptibility

of infants and children can be reduced to 1X based on toxicological considerations (above), the conservative residue assumptions used in the dietary risk ass essments, the completeness of the residue chemistry database , and conservative drinking water assessment. RAB1 toxicologists also reaffirmed the endpoints previously selected by

the HIARC (16 - DEC 2003; TXR# 0052361). There is no concern for neurotoxicity resulting from exposure to novaluron and the overall weight of evidence suggests that novaluron does not direc tly target the immune sy stem. An immunotoxicity study is required as part of the revised 40 CFR Part 158 toxicology

data requirements for novaluron; however, HED does not believe that conducting a functional immunotoxicity study will result in a lower NOAEL than the regulatory dose being used for risk assessment, and an additional UF for database uncertainty (UFDB) is not needed to account for the lack of the required immunotoxicity study. An oral acute reference dose (aRfD) for the general population, including infants and children, was not established since an endpoint of concern attributable to a single dose was not identified. The chronic reference dose (cRfD) of 0.011 mg/kg/day was determined on the basis of the chronic toxicity

/ carcinogenicity

study in the rat. An uncertainty factor (UF) of 100 (10 - fold for interspecies extrapolation and 10 - fold for intraspecies variability) was applied to the no observed - adverse - effect - level (NOAEL ) of 1.1 mg/kg/day to derive the cRfD. The lowest observed - adverse - effect - level (LOAEL) of 30.6 mg/kg/day was based on evidence of RBC damage and turnover resulting in a regenerative anemia. The FQPA SF of 1X is applicable for chronic dietary

risk assessment. Therefore, the chronic population - adjusted dose (cPAD) is 0.011 mg/kg/day . Based on the toxicological database, a short - term dermal endpoint was not selected; therefore, only intermediate - term dermal exposure was assessed. Short - and intermediate - term inhalation toxicological endpoints have been selected and are the same; therefore, the estimates of risk for short - term duration inhalation exposures are protective of those for intermediate - term inhalation duration exposures. A 10% dermal - absorption factor was based on an acceptable dermal absorption study

in rats in which the maximum total absorbed dose (expressed as percent of administered dose) ranged from approximately 0.5% to 10% of the applied dos e. The level ofNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 6 of 56 concern (LOC) for occupational and residential dermal and inhalation exposures are for margins of exposure (MOEs) < 100. In accordance with the EPA Draft Guidelines for Carcinogen Risk Assessment (JUL - 1999), novaluron is classified as “n ot likely to be carcinogenic to humans” based on the lack of evidence for carcinogenicity in mice and rats. Endpoints applicable to risk assessments performed for novaluron in this document are summarized below. Exposure Scenario Dose Endpoint Study/Effe ct Chronic dietary NOAEL = 1.1 mg/kg/day cRfD and cPAD = 0.011 mg/kg/day Combined chronic toxicity/carcinogenicity feeding study- rat - erythrocyte damage and turnover resulting in a regenerative anemia at the LOAEL of 30.6 mg/kg/day. Intermediate - term dermal (10% absorption rate) NOAEL = 4.38 mg/kg/day LOC for MOEs <100 (occupational/residential ) 90 - day feeding study- rat - clinical chemistry and histopathology at the LOAEL of 8.64 mg/kg/day. Short - term inhalation Intermediate - term inhalation Dietary Exposure Estimate An acute dietary

assessment was not conducted for novaluron because an endpoint of concern attributable to a single dose was not identified. A cancer dietary assessment was not conducted because novaluron was classified as “not likel y to be carcinogenic to humans.” A partially

refined chronic dietary

(food and drinking water) exposure and risk assessment was conducted for the proposed new uses on sweet corn and in food - and feed - handling establishments , all established uses , and drinking water. EFED provided the e stimated drinking water concentrations (EDWCs) which were incorporated into the anal ys is. A percent crop treated for new use (PCTn) memorandum for sweet corn was provided b y the Biological and Economic Anal ys is Div ision (BEAD). Additionally , data from a previousl y provided Screening Level Usage Anal ys is (SLUA) memorandum for existing uses and a PCTn memorandum for grain sorghum were used. The chronic anal ys is incorporated average percent crop treated ( %CT ) data fo r apples, cabbage, cotton, pears, and potatoes , and average PCTn data for sweet corn and grain sorghum. 100% CT was assumed for the remaining food commodities. Anticipated residues (ARs) for meat, milk, hog, and poultry commodities were calculated using average field trial residues, average PCTn for sweet corn and grain sorghum, average %CT for apple and cotton, and assumed 100% CT for sugarcane and cowpea seed . The chronic anal ys is also incorporated average field trial residues , average greenhouse trial residue s for tomatoes , empirical processing factors for apple juice (translated to pear and stone fruit juice ) , cottonseed oil, dried plums, and tomato paste and purée , and Dietary Exposure Evaluation Model (DEEM TM , ver. 7.81) default processing factors fo r the remaining processed commodities. In accordance with HED Standard Operating Procedure (SOP) 2000.1, average field trial residues were translated from representative commodities in the crop group to other commodities in that crop group as needed.Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 7 of 56 For this action, the chronic dietary (food and drinking water) exposure to novaluron is below HED’s LOC for the general U.S. population and all population subgroups. The chronic dietary exposure results in a risk estimate that is 21 % of the cPAD for the g eneral U.S. population and 72 % of the cPAD for children 1 - 2 years old, the most highly exposed population subgroup. Residential Exposure/Risk Novaluron is proposed for indoor and outdoor uses for the control of roaches and crickets (crack and crevice and spot treatments). Applications in residential areas, such as homes and apartment buildings, are allowed per label instructions. As stated earlier , thi s is the first proposed residential use of no valur on. Residential handler dermal and inhalation exposures were assessed for application via low - pressure handwands and trigger - pump sprayers. All residential handler risks do not exceed HED’s level of concern (i.e., MOE s ≥100). Residential post - application inhalation exposures were assessed for adults and children following indoor low - pressure handwand and trigger pump sprayer applications and no risks of concern were identified. Residential post - application dermal exposures were also assessed. Since there is no short - term dermal endpoint, these exposures are representative of intermediate - term exposures and are considered conservative since it has been assumed that adults and children are exposed to day- 0 residues for the length of the exposure duration (i.e., no dissipation or removal of residues has been assumed). At the maximum application rate (3.1 oz/gal and 0.1 gal per 1000 ft2 ), all dermal MOEs for adults and children are greater than the target MOE of 100 and do not exceed HED’s level of concern . Residential post - application incidental oral exposures were assessed for children (3 to <6 ye ars old). At the maximum application rate (3 . 1 oz/gal and 0.1 gal per 1000 ft2 ), short - and intermediate - term incidental oral MOEs are greater than the target MOE of 100 and do not exceed HED’s level of concern . A combined residential assessment was included for the indoor crack and crevice/spot use. The combined scenarios consisted of adul t dermal and inhalation post - application exposures as well as children (3 to <6 ye ars old) dermal, inhalation and oral (hand - to - mouth) post - application exposures. All of the combined MOEs for adults and children (3 to <6 year olds) are greater than the target MOE of 100 and do not exceed HED’s level of concern Aggregate Exposure Scenarios and Risk Conclusions For the proposed uses, human - health aggregate risk assessments have b een conducted for short term aggregate exposure (food + drinking water + resid ential), intermediate - term aggregate exposure (food+ drinking water + residential) , and chronic aggregate exposure (food + drinking water) exposure scenarios. An acute aggregate assessment was not conducted for novaluron because an endpoint of concern attributable to a single dose was not identified. A cancer aggregate risk assessment was not performed because novaluron was classified as “not likel y to be carcinogenic to humans.” All potential exposure pathway s were assessed in the aggregateNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 8 of 56 risk assessm ent as a conservative, health - protective measure. All aggregate risk estimates do not exceed HED’s level of concern for the scenarios listed above. Occupational Exposure Estimates Occu pational handler and post - application exposure from the proposed us es of novaluron are anticipated . Based on label information, exposure is expected to occur for short - and intermediate - term exposure durations . No chemical - specific handler exposure data were submitted in support of this Section 3 registration. It is the policy of HED to use data from the Pesticide Handlers Exposure Database (PHED) Version 1.1 as presented in the PHED Surrogate Exposure Guide (AU G - 19 98) to assess handler exposures for regulatory actions when chemical specific monitoring data are not available [ HED Science Advisory Council for Exposure (ExpoSAC) Draft SOP #7, dated 28 - JAN - 1999 ] . HED has determined that risks do not exceed HED’s level of concern (i.e., MOEs ≥ 100), **provided workers wear chemical**  **- resistant**  **gloves as recommended on the label** . No short term point of departure (POD) was selected for the dermal route of exposure; therefore, the risks presented for handlers are representative of intermediate - term exposures and would be considered protective of short - term exposures. The MOEs for occupational post - application exposure are all greater than the target MOE of 100 on day 0 (12 hours after application) for all crops and activities and do not exceed HED’s level of concern . Post - application dermal risks were calculated based on an intermediate - term POD and are considered highly conservative for the include d activities . Since the post - application assessment is not a concern on Day 0 (12 hours followi ng application), the restricted - entry interval (REI) is based on the acute toxicity of novaluron technical material. The proposed label for Rimon ® has a 12 - hour REI. The technical material has a Toxicity

Category III for acute dermal and a Toxicity Category IV for acute oral and inhalation and primary

eye and skin irritation. It is not a dermal sensitizer. Per the Worker Protection Standard (WPS), a 12 - hour REIis required for chemicals classified under Toxicity Categories III and IV and is adequate for th e proposed use patterns . Environmental Justice Considerations Potential areas of environmental justice concerns, to the extent possible, were considered in this human - health risk assessment, in accordance with U.S. Executive Order 12898, “ Federal Actions to Address Environmental Justice in Minority Populations and L ow - Income Populations, ” (http://www.hss.energy .gov/nuclearsafety/ env/guidance/justice/eo12898.pdf ). As a part of every

pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well - established procedures. In line with OPP policy , HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the U.S. Department of Agriculture (USDA) under the Continuing Survey s of Food IntakesNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 9 of 56 by Individuals (CSFII) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are anal yz ed and categorized by subgroups based on age, season of the ye ar, ethnic group, and reg ion of the country . Additionally , OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non - dietary exposures based on home use of p esticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas post - application are evaluated. Further considerations are currently in development as OPP has committed resources and e xpertise to the development of specialized software and models that consider exposure to by standers and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups. Review of Human Research This risk assessment relies in p art on data from studies in which adult human subjects were intentionally

exposed to a pesticide to determine their dermal and inhalation exposure. Many such studies, involving exposure to many different pesticides, comprise generic pesticide exposure dat abases such as PHED and the Outdoor Residential Exposure Task Force (ORETF) d atabase. EPA has reviewed all the studies in these multi - pesticide generic exposure databases, and on the basis of available evidence has found them to have been neither fundamentally unethical nor significantly deficient relative to standards of ethical research conduct prevailing when they

were conducted. There is no regulatory barrier to continued reliance on these studies, and all applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied. Recommendation for Tolerances and Registration Pending submission of revised Sections B and F and new anal yt ical standard s, there are no residue chemistry , toxicology , or occupational and residential exposure issues that would preclude granting a conditional registration for the use of novaluron on sweet corn and in food and feed - handling establishments where food or feed products are held, processed, or prepared . Registration should be made conditional upon submission of an immunotoxicity study as specified in the new 40 CFR Part 158 data requirements and a 90 - day inhalation toxicity

study . The proposed uses and the submitted data support the permanent tolerances for res idues of the insecticide novaluron , including its metabolites and degradates, in or on the commodities listed below. Compliance with the tolerance levels specified below is to be determined by measuring only novaluron (

N - [[[3 - chloro - 4 - [1,1,2 - trifluoro - 2 - (trifluoromethox y)ethox y]phenyl]amino]carbonyl] - 2,6 - difluorobenzamide ) in or on the following raw agricultural commodities ( RACs ) :

Corn, Sweet, Stover ................................ ................................ ................... 50 ppm Corn, Sweet, Forage ................................ ................................ ................... 16 ppm Corn, Sweet, Kernel Plus Cob With Husks Removed ............................ 0.05 ppm Food/feed comm odities (other than those covered by a higher tolerance as a result of use on growing crops) in food/feed handling establishments ................................ ................................ ......... 0.01 ppmNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 10 of 56 Data Needs and Label Recommendations The residue chemistry , toxicology , and occupational and residential databases will support unconditional registration upon submission of data/information which adequately addresses the following issues: **Toxicology**

 A **90** - day

inhalation toxicity

study is requested for further characterization of inhalation risk. Due to the potential for repeated inhalation exposure anticipated from the proposed residential use pattern, there is concern for toxicity b y the inhalation route . An inhalation study would provide a dose and endpoint via the route of exposure of concern (i.e. route specific study) and thus would avoid using an oral study and route - to - route extrapolation.  An immunotoxicity

study is required as specified in the n ew 40 CFR Part 158 data requirements. **Residue Chemistry** 860.1200 Directions for Use A revised Section B for PP#0E7723 should be submitted which:

 prohibits the use of novaluron on turnips harvested for the root and prohibits the feeding of turnip tops to livestock as previousl y requested (Memo, J. Van Alstine, 09 - SEP - 20 09; D357060). This affects the current petition because it could result in in creased live stock dietary burdens . A revised Section B for PP#0F7708 should be submitted which:

 spec ifies an application rate of 0.1 gallons per 1000 ft2 for indoor spot, crack and crevice, space spray , and general surface applications;  states that all food processing surfaces (including equipment) and utensils should be covered during treatment or thoroughl y washed prior to use;  states the livestock feed items should be removed or covered prior to application; and  removes all references to fogger and fog applications in the label , and specifies that applications should be made with mechanical cold mist/ ultra - low volume (ULV ) equipment . 860.1550 Proposed Tolerances A revised Section F for PP# 0E7723 should be submitted which:  cites the appropriate CAS name for novaluron:

“ Tolerances are established for residues of the insecticide novaluron , including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified belo w is to be determined by measuring only novaluron (

N - [[[3 - chloro - 4 - [1,1,2 - trifluoro - 2 -Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 11 of 56 (trifluoromethox y)ethox y]phenyl]amino]carbonyl] - 2,6 - difluorobenzamide ) in or on the following raw agricultural commodities:”; and

 reflect s the recommended tolerances and commodity definitions presented in Table 4.1.1 . Additionally , a revised Section F for PP# 0F7708 should be submitted which:

 reflects the commodity definition presented in Table 4.1.1 . 860.1650 Submittal of Analy tical Reference Standards The available anal yt ical reference standards for novaluron have expired . MANA is required to submit an updated Certificate of Anal ys is ( COA ) or a new anal yt ical standard to the EPA National Pesticide Standards Repository at the following address: USEP A National Pesticide Standards Repository /Anal yt ical Chemistry

Branch/OPP 701 Mapes Road Fort George G. Meade, MD 20755 - 5350 Please note that the extended zip code is required for delivery . **Note to RD:** Based on the Chemistry Science Advisory

Council ( ChemSAC ) guidance that meat by product tolerances should be set at the highest residue level seen in any livestock commodity (minutes from 12 - JAN - 2011), several meat b yproduct tolerances in 40 CFR § 180.598(a) should be updated so that they

are based on the highest expected residue. Additionally , two commodity descriptions should be updated. The tolerances and commodity descriptions should be updated as follows: **Current Commodity Description**  **Updated Commodity Description**  **Current Tolerance (ppm)**  **Updated Tolerance**  **(ppm) 1**  Cattle, meat byproducts, except kidney and liver - 0.60 11 Goat, meat byproducts except kidney and liver - 0.60 11 Horse, meat byproducts, except kidney and liver - 0.60 11 Sheep, meat byproducts, except kidney and liver - 0.60 11 Hog, meat byproducts Hog, meat byproducts, except kidney and liver2 0.10 1.5 Poultry, meat byproducts Poultry, meat byproducts, except kidney and liver 3 0.80 7.0 1 Based on the base d on the highest expected secondary tissue residue [peritoneal fat in cattle (translated to goat, horse, and sheep); peritoneal fat in hog; abdominal fat in poultry]. 2 Separate tolerances have been established for hog, kidney (0.10 ppm) and hog, liver (0 .10 ppm). 3 Separate tolerances have been established for poultry, kidney (0.80 ppm) and poultry, liver (0.80 ppm).Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 12 of 56 **Occupational and Residential Exposure** A revised label ( Section B ) for PP#0E7723 should be submitted which :  specifies that the retreatment of sweet co rn with novaluron is prohibited (i.e., only 1 application is allowed at a rate of 0.078 lb ai/A) in California and other arid areas which receive less than 20 inches of precipitation per ye ar . A revised label ( Section B ) should also be submitted for PP#0 F7708 which :  **specifies an application rate of 0.1 gallons per 1000 ft 2**  **for indoor spot, crack and crevice, space spray, and general surface applications;**  and  requires the addition of chemical - resistant gloves . **2.0 INGREDIENT PROFILE**  **2.1 Summary of Proposed Uses**  IR - 4 and MANA have submi tt ed draft labels for Rim o n ® 0.83EC In secti ci de ( EPA Reg. No. 66222 - 35) and Rimon ® Supra 10EC Insecticide ( EPA Reg. No. 66222 - ERT ) to include the proposed new use s (see Table 2. 1 ) on sweet corn and in food - and feed - handling establishments , including residential sites . The current label for Rimon ® Supra 10EC did not include an application rate for spot, crack and crevice, surface spray , and general surface applications; HED’s application rate calculations are included in the chemistry and ORE memos . Under petition PP# 0F7708 , n ovaluron is proposed for indoor and outdoor use s for the control of roaches and crickets (spot and crack and crevice treatments) . The proposed label also rec ommends fogger applications; however, based on correspondence with the Registrant, this application is not made with an actual fogger , but rather with mechanical cold mist/ ULV equipment that deliver a very light mist that targets the treatment spots (such as , but not limited to , wooden pallet structures, under sink/counter voids, under equipment, enclosed machinery housings , etc.). This application method is not considered to be a space or aerosol spray treatment , where a fogger or vaporizer is used. The label directions recommend applying a dilute solution of 2.3 to 3.1 ounces of product per gallon of water (0.01 to 0.02 lb ai/gal) . For outdoor perimeter treatments, the label recommends ap plications at a spray

rate of 1 gal/1000 ft2 . An indoor spray rate per area was not provided on the proposed label. Based on the submitted food handling residue study (MRID 48034903) , an application rate of 0.1 gal/1000 ft2 was calculated for the proposed indoor use . HED assumed this spray rate for this assessment. It is anticipated that occupational and residential handlers will potentially be exposed through th e crack and crevice use of novaluron . In addition, residents (adults and children) may potentiall y be exposed after treatments in residential areas .Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 13 of 56 **Table 2. 1**  **. Summ ary of Proposed Use Pattern for Novaluron on Sweet Corn and in Food**  **- or Feed**  **** **Handling Establishments. Applic.**  **Equip. Form**  **ulati**

**on [EPA Reg.**  **No.] Applic.** 

**Rate (lb ai/A)**  **Max. No.**

**Applic. per**  **Season Max.** 

**Seasonal Applic. Rate**  **(lb ai/A) PHI** 

**(days) Use Directions and Limitations**  **Sweet Corn (PP#0E7723)** 

Aerial/ Ground boom 0.83 lb/gal

EC [66222 - 35] 0.058 -

0.078 5 - 6 0.39 1 Apply in sufficient volume to ensure full coverage of foliage and developing ears. Use higher rates and higher spray volumes when larvae are large or foliage canopy is tall or dense. The use of surfactants/adjuvants (including non - ionic surfactants) is prohibited. Repeat applications as needed to protect new growth, b ut not less than 7 days apart. **R esidential and**  **C om**  **mercial B**  **uilding s**  **and S**  **tructures and T**  **heir I**  **mmediate S**  **urroundings and on M**  **odes of**  **T ransport**  a (PP#0F7708)

Lo w pressure handwand, trigger sprayer , ULV sprayer c 0.83 lb/gal

EC [66222 - ERT] 0.1

gal/1000 ft2 b Not indicated 3.1 ounces

per gallon of water = 0.02 lb ai/gal Spray rate per area: 0.1 gal/1000 ft2 = 0.002 lb ai/1000 ft2 NA Prepare diluted spray solution by adding 2.3 to 3.1 ounces per gallon of water. Prior to application, remove or cover a ll food items in the area to be treated. In the home, all food - processing surfaces and utensils should be covered during treatment or thoroughly wa shed before use. Do not replace food containers or foodstuffs until spray has dried. A retreatment interval (RTI) is not specified. The label states the product is effective for 180 days (26 weeks or 6 months). a The permitted areas of use include non - food/non feed areas of stores; warehouses, transportation equipment, manufacturing si tes, industrial buildings, houses, apartment buildings, office buildings, laboratories, schools, daycare centers, nursing homes, hospitals, hotels and on vessels, railcars, aircraft, buses, trucks, and trailers . b The current label for Rimon ® Supra 10EC did not include an application rate for spot, crack and crevice, surface spray, and general surface applications; please refer to for the chemistry and ORE memos for HED’s application rate calculations . c Correspondence from MANA indicated that they do not intend to have a fogger use , b ut rather that applications should be made as a mechanical cold mist/ULV mist which targets the treatment spots. There are no unit exposures for this scenario but the available low - pressure handwand and trigger sprayer unit exposure data are protective of me chanical cold mist/ULV mist applications . Conclusions : The proposed labels are adequate to allow evaluation of the residue data relative to the proposed new uses on sweet corn and in food - and feed - handling establishments; however , a revised Section B for PP# 0E7723 should be submitted which:Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 14 of 56  specifies that the retreatment of sweet corn with novaluron is prohibited (i.e., only 1 application is allowed at a rate of 0.078 lb ai/A per grow i ng season ) in Californ ia and other arid areas , which receive less than 20 inches of precipitation per ye ar ; and  p rohibits the use of novaluron on turnips harvested for the root and prohibits the feeding of turnip tops to livestock as previousl y requested (Memo, J. Van Alstine, 09 - SEP - 2009 ; D357060). This affects the current petition because it could result in increased livestock dietary burdens. Additionally , a revised Section B is requested for PP# 0F7708 which:

 requires the additi on of chemical - resistant gloves;  specifies an application rate of 0.1 gallons per 1000 ft2 for indoor spot, crack and crevice, space spray , and general surface applications;  states that all food processing surfaces (including equipment) and utensils should be covered during treatment or thoroughl y washed prior to use;  states the livestock feed items should be removed or covered prior to application; and  removes all fogger and fog references o n the label , and specifies that applications should be made with mechanical cold mist/ULV equipment . **2.2 Structure and Nomenclature**  **Table 2.2**  **. Novaluron**  **Nom enclature**  . Chemical structure

Common name Novaluron IUPAC name 1 - [3 - chloro - 4 - (1,1,2 - trifluoro - 2 - trifluoromethoxyethoxy)phenyl] - 3 - [2,6 - difluorobenzoyl]urea CAS name N - [[[3 - chloro - 4 - [1,1,2 - trifluoro - 2 - (trifluoromethoxy)ethoxy]phenyl]amino]carbonyl] - 2,6 - difluorobenzamide CAS registry number 116714 - 46 - 6 End - use product s (EP s ) Rimo n ® 0.83EC Insecticide (0.83 lb/gal EC; EPA Reg. No. 66222 - 35) ; Rimon ® Supra 10EC Insecticide ( 0.83 lb/gal EC; EPA Est. No. 66222 - ERT) **2.3 Physical and Chemical Properties**  **Table 2.3**  **. Physicochem ical Properties of Technical Grade Novaluron.**  Parameter Value Reference Melting range 176.5 - 178.0  C DP# 315780, 3 -NOV - 2005, S. Levy pH 6.5 O N H N H O F

F Cl O O C F 3 F F FNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 15 of 56 **Table 2.3**  **. Physicochem ical Properties of Technical Grade Novaluron.**  Parameter Value Reference Density 1.56 g/cm3 at 22  C Water solubility 3 μg/L at 20  C Solvent solubility (at 25  C) 0.00 839 g/L in n - heptane 1.88 g/L in xylene 14.5 g/L in methanol 198 g/L in acetone 113 g/L in ethyl acetate 0.98 g/L in n - octanol Vapor pressure (mm Hg) 1.2 x 10 - 7 Dissociation constant, pKa Not determined due to low w ater solubility . Octanol/water partition coefficient, Log(KOW) 4.3 at 25  C UV/visible absorption spectrum Molar absorption coefficients of at 3 maximum absorbances: 15,400 L/mol  cm

at 253 nm (neutral) 9,780 L/mol  cm at 253 nm ( acidic) 20,500 L/mol  cm

at 263 nm (basic) **3.0 HAZARD CHARACTERIZATION/FQPA CONSIDERATIONS**  A detailed hazard characterization for novaluron is presented in a previous HED risk assessment ( Memo, M. Clock - R

ust, et al. , 25 - MAR - 2004; D 295824 ). Novaluron has low acute toxicity via the oral (Toxicity

Categ ory IV), dermal (Toxicity

Category III) , and inhalation routes (Toxicity Category IV). No ocular (Toxicity Category IV) or dermal irritation (Toxicity Category IV) was noted. Novaluron is not a dermal sensitizer. In subchronic and chronic toxicity studi es, novaluron primaril y produced red blood cells effects , such as methemoglobinemia, decreased hemoglobin, decreased hematocrit, and decreased RBCs (or ery throcy tes) that were associated with compensatory erythropoiesis. Unlike white blood cells (leukocyt es) which are cells of the immune system, red blood cells function to deliver oxygen to body tissues and are not involved in eliciting an immune response. In creased spleen weights and/or hemosiderosis in the spleen were considered to be due to enhanced rem oval of damaged ery throcy tes and not to an immunotoxic effect. There was no maternal or developmental toxicity seen in the rat and rabbit developmental toxicity studies up to the limit doses. In the two - generation reproductive toxicity study in rats, both parental and offspring toxicity (increased spleen weights) were observed at the same dose. Reproductive toxicity

(decreases in epididy

mal sperm counts and increased age at preputial separation in the F 1 generation) was observed at a higher dose than the hematotoxicity . Clinical signs of neurotoxicity

and neuropathology

were seen in the rat acute neurotoxicity study at the limit dose. However, no signs of neurotoxicity or neuropathology

were observed in the subchronic neurotoxicity

study in rats at simil ar doses or in any other subchronic or chronic toxicity study in rats, mice or dogs. In addition, there were no clinical signs of toxicity observed in the acute oral toxicity

study with novaluron (LD50 >5,000 milligrams/kilogram (mg/kg)). Therefore, there is no concern for neurotoxicity resulting from exposure to novaluron . No toxicity was observed at the limit dose in the dermal study and there were no developmentalNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 16 of 56 toxicity concerns at the limit - dose; therefore, quantification of short - term dermal risk is not necessary . Aditionally , in a rat dermal penetration study the maximum total absorbed dose (expressed as per cent of administered dose and determined as the sum of radioactivity in excreta, cage wash, untreated skin, fat, blood, and residual c arcass) ranged from about 0.5% to 10% of that administered , indicating low dermal absorption . There was no evidence of carcinogenic potential in either the rat or mouse carcinogenicity studies and no evidence of mutagenic activity

in the submitted mutagen icity studies, including a bacterial (Salmonella, E. coli) reverse mutation assay , an in vitro mammalian chromosomal aberration assay , an in vivo mouse bone - marrow micronucleus assay and a bacterial DNA damage/repair assay . Based on the results of these s tudies, EPA has classified novaluron as “not likel y to be carcinogenic to humans.” **3.1 FQ**  **PA Considerations** The RAB1 risk assessment team concluded that the FQPA SF can be reduced to 1X based on the following:

 There is no evidence of increase d susceptibility in the rat or rabbit developmental toxicity studies up to the limit dose or in the two - generation reproduction study in rats .  T here are no concerns or residual uncertainties for pre - and/or postnatal toxicity .  Acute and subchronic neurotoxicity scre ening batteries were performed with novaluron in rats. Novaluron is not considered neurotoxic , since effects observed in the acute neurotoxicity

study were observ ed at the limit dose only and were not reproduced at similar , repeated doses in the subchroni c neurotoxicity study . In addition, n o evidence of neuropathology

was observed in subchronic and chronic to xicity studies in rats, mice, or dogs , and novaluron is not considered acutel y toxic (LD 50 >5000 mg/kg) .  A developmental - neurotoxicity (DNT) study is not required.  Histopathological examination of the organs of the immune sy stem (i.e., thy mus, spleen, ly mph nodes) showed an increase in spleen weight and increased incidence and severity of hemosiderosis in the spleen in the chronic studies in rats an d mice and in the reproduction study in rats. These findings were associated with the primary hematotoxicity

of novaluron , which caused secondary accumulation of damaged erythrocy tes in the spleen following removal from the blood. Therefore, these are no t considered immunotoxic effects . The overall weight of evidence suggests that novaluron does not directl y target the immune system. An immunotoxicity study is required as part of the revised 40 CFR Part 158 toxicology data requirements for novaluron; ho wever, HED does not believe that conducting a functional immunotoxicity study will result in a lower NOAE L than the regulatory dose being used for risk assessment, and an additional UF for database uncertainty (UF DB ) is not needed to account for the lack o f the required immunotoxicity

study .  T he protective residue assumptions were used in the dietary exposure risk assessment such as assuming average residues based on field trial data [maximum application rate; minimum pre - harvest interval (PHI); and sample s were frozen immediatel y after harvest]. Additionally , the current chronic analy sis could be further refined through the use of monitoring data an d preparation/cooking factors.Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 17 of 56  T he completeness of the residue chemistry database and conservative drinkin g water assessment.  The residential exposure assessment was conducted using high - end estimates of use and potential exposure providing a conservative, health protective estimate of risk. The doses and toxicological endpoints selected for human health risk assessment are summarized in Table 3.1. **Table 3.1. Summ**  **ary of Toxicological Dose and Endpoints for Novaluron. Exposure**  **Scenario Dose Used in Risk** 

**Assessment, UF FQPA SF and LOC** 

**for Risk Assessment Study and Toxicological Effects**  Ac ute Dietary (all populations) Not applicable None An endpoint of concern attributable to a single dose was not identified. An acute RfD was not established. Chronic Dietary (all populations) NOAEL = 1.1

mg/kg/day UF = 100 FQPA SF = 1X

cRfD = cPAD = 0.011 mg/kg/day Com bined chronic toxicity/carcinogenicity feeding in rat . LOAEL = 30.6 mg/kg/day based on erythrocyte damage and turnover resulting in a regenerative anemia. Short - Term Incidental Oral (1 - 30 days) NOAEL = 4.38

mg/kg/day Residential LOC for

MOE < 100 90 - day feeding study in rat . LOAEL = 8.64 mg/kg/day based on clinical chemistry (decreased hemoglobin, hematocrit , and RBC counts) and histopathology (increased hematopoiesis and hemosiderosis in spleen and liver). Intermediate - Term Incidental Oral (1 - 6 mo nths) NOAEL = 4.38

mg/kg/day Residential LOC for

MOE < 100 90 - day feeding study in rat . LOAEL = 8.64 mg/kg/day based on clinical chemistry (decreased hemoglobin, hematocrit , and RBC counts) and histopathology (increased hematopoiesis and hemosiderosis in spleen and liver). Short - Term Dermal (1 - 30 days) Not applicable None No toxicity wa s observed at the limit dose in the dermal study and there were no developmental toxicity concerns at the limit - dose; therefore, quantification of short - term dermal ris k is not necessary. Intermediate - Term Dermal (1 - 6 months) Oral NOAEL = 4.38

mg/kg/day (dermal - absorption rate = 10 %) Residential/

Occupational LOC for MOE < 100 90 - day feeding study in rat . LOAEL = 8.64 mg/kg/day based on clinical chemistry (decreased hemoglobin, hematocrit , and RBC counts) and histopathology (increased hematopoiesis and hemosiderosis in spleen and liver). Long - Term Dermal (>6 months) Oral NOAEL = 1.1

mg/kg/day (dermal - absorption rate = 10 %) Residential/

Occupational LOC for MOE < 100 Com bined chronic toxicity/carcinogenicity feeding in rat . LOAEL = 30.6 mg/kg/day based on erythrocyte damage and turnoverNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 18 of 56 **Table 3.1. Summ**  **ary of Toxicological Dose and Endpoints for Novaluron. Exposure**  **Scenario Dose Used in Risk** 

**Assessment, UF FQPA SF and LOC** 

**for Risk Assessment Study and Toxicological Effects**  resulting in a regenerative anemia. Short - Term Inhalation (1 - 30 days) Oral NOAEL = 4.38

mg/kg/day ( inhalation absorption rate = 100%) Residential/

Occupational LOC for MOE < 100 90 - day feeding study in rat . LOAEL = 8.64 mg/kg/day based on clinical chemistry (decreased hemoglobin, hematocrit , and RBC counts) and histopathology (increased hematopoiesis and hemosider osis in spleen and liver). Intermediate - Term Inhalation (1 - 6 months) Oral NOAEL = 4.38

mg/kg/day ( inhalation absorption rate = 100%) Residential/

Occupational LOC for MOE < 100 90 - day feeding study in rat . LOAEL = 8.64 mg/kg/day based on clinical chemistry (decreased hemoglobin, hematocrit , and RBC counts) and histopathology (increased hematopoiesis and hemosiderosis in spleen and liver). Long - Term Inhalation (>6 months) Oral NOAEL = 1.1

mg/kg/day ( inhalation absorption rate = 100%) Residential/

Occupational LOC for MOE < 100 Com bined chronic toxicity/carcinogenicity feeding in rat . LOAEL = 30.6 mg/kg/day based on erythrocyte damage and turnover resulting in a regenerative anemia. Cancer Not likely to be carcinogenic to humans. UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no - observed - adverse - effect - level, LOAEL = lowest - observed - adverse - effect - level, PAD = population - adjusted dose (a = acute, c = chronic) , RfD = reference dose, MOE = margin of exposure, LOC = level of concern . A **90** - day inhalation toxicity

study in the rat is requested for further characterization of inhalation risk. Due to the potential for repeated inhalation exposure anticipated from the proposed residential use pattern, there is concern for toxicity by the inhalation route. An inhalation study would provide a dose and endpoint via the route of exposure of concern (i.e. route specific study) and thus would avoid using an oral study and route - to - route extrapolation. **3.2 Endocrine Disruption**  As required under Federal Food, Drug, and Cosmetic Act ( FFDCA ) section 408(p), EPA has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced b y a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two - tiered approach to making the statutoril y required determinations. Tier 1 consists of a battery of 11 screening assay s to identify

the potential of a chemical substance to interact with the estrogen, androgen, or thy roid (E, A, or T) hormonal sy stems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal s ys tems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine relatedNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 19 of 56 effects caused b y the substance, and establish a dose - response relationship between the dose and the E, A, or T effect. Between October 2009 and February 2010, EPA is issuing test orders/data call - ins for the first group of 67 chemicals, which cont ains 58 pesticide active ingredients and 9 inert ingredients. This list of chemicals was selected based on the potential for human exposure through pathway s such as food and water, residential activity , and certain post - application agricultural scenarios. This list should not be construed as a list of known or likely endocrine disruptors. Novaluron is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide chemicals. Accordingl y, EPA anticipates issuing future EDSP test orders/data call - ins for all pesticide active ingredients . For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery , please visit our website: http://www.epa.gov/endo/. **4.0 DIETARY EXPOSURE/RISK CHARACTERIZATION**  The residue chemistry

data submitted in support of the proposed uses are summarized in the pending HED memorandum by J. L. Van Alstine ( D378631 ). The chronic dietary exposure assessment is summarized i n the pending HED memorandum by J. L . Van Alstine ( D383133 ). **4.1 Food Residue Profile**  **Nature of the Residue -**  **Plants:** HED previously concluded that the nature of the residue in plants is adequatel y understood based on acceptable metabolism studies conducted on apples, cabbage, cotton, and potatoes using [difluorophenyl - U 14 C]novaluron and [chlorophenyl - U 14 C]novaluron as the test substances (Memo, G. Kramer , 22 - MAR - 2004; D 285474) . These studies indicate that novaluron is not extensively metabolized in these crops. The parent compound, novaluron, was either the onl y residue component identified or was the predominant residue component in all anal yz ed plant matrices. The reviewed studies also indicate that novaluron, when foliarly

applied during the vegetative growth stage, is not readily translocated to mature apple fruit, potato tubers , or cottonseed (Memo, G. Kramer, 22 - MAR - 2004; D285474). Based on these studies, the Metabolism Assessment and Review Committee (MARC) determined that the residue of concern in crops for purposes of tolerance enforcement and risk assessment is novaluron only (Memo , G. Kramer et al. , 03 - FEB - 2004; D297646). **Nature of the Residue**  **- Livestock:**  HED also previously concluded that the nature of the residue in livestock is adequatel y understood based on the submitted goat and hen metabolism studies (Memo, G. Kramer, 22 - MAR - 2004; D285474). The HED MARC determined that the resid ue of concern in livestock for purposes of tolerance enforcement and risk assessment is novaluron only (Memo, G. Kramer et al. , 03 - FEB - 2004; D297646).Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 20 of 56 **Residue Analytical Enforcement Method -**  **Plant:** MANA previousl y submitted a gas chromatograph y/ electron - capture detection (GC/ECD) residue anal yt ical method for the anal ys is of novaluron residues in/on pome fruit, cabbage, and potato commodities; HED concluded that the method was adequate for gathering data on novaluron. A second method, high - performance li quid chromatograph y/ultraviolet (HPL C/UV) , was submitted for the anal ysis of novaluron residues onl y in/on cotton commodities. Both method s w ere adequatel y validated by the petitioner and b y an independent laboratory. Acceptable radiovalidation data for the GC/ECD method have been submitted and reviewed in a previous HED memorandum ( Memo, S. L ev y, 23 - AUG - 2006 ; D325183 ) and both methods were forwarded to the EPA Analy tical Chemistry Branch (ACB)/Biological and Economics Anal ys is Division (BEAD) for petition method validation (PMV; Memo, G. Kramer, 05 - DEC - 2003; D296264) . ACB concluded that based upon review of the submitted method validation data, without laboratory

validation, that the GC/ECD and HPL C/UV methods appear suitable for food tolerance en forcement in plants (apples, cabbage, and potatoes) and cotton. ACB recommended that the anal yt ical methods do not need to be laboratory validated b y EPA ( Memo, S. Lev y, 15 - SEP T - 2004 ; D306998). Both methods have been forwarded to the Food and Drug Admini stration (FDA) for inclusion in the Pesticide Anal yt ical Manual, Volume II (PAM II) as a Letter Method ( S. Lev y, 15 - SEP T - 2004; D307595). An interference study was requested and a specific single - anal yt e confirmatory method was submitted and considered acc eptable (Memo, J. Langsdale, 21 - OCT - 200 8; D 355574) . For sweet corn, the enforcement method, with minor modifications, was used for data collection and the method was adequately validated in conjunction with the sweet corn field trials. The appropriate en forcement method for food - and feed - handling establishments is Method 243C 106 (MRID 48034901), which was used for data collection for the food - handling establishment field trial and was adequately validated . **Multiresidue Methods :**  Novaluron was tested through the FDA MRM Test guidelines in PAM I, Appendix II (JAN - 1994). The results indicate that novaluron is not adequately recovered b y an y of the MRMs. This study was forwarded to FDA for further evaluation and updating of PAM Vol. I , Appen dix I (Memo, S. L ev y, 19 - OCT - 2005; D 3 22359) . **Magnitude of the Residue -**  **Livestock:** The potential for secondary transfer of novaluron residues of concern in meat, milk, and eggs exists because there are livestock feedstuffs associated with the proposed/re gistered novaluron uses. L ivestock dietary burdens of novaluron were calculated , which incorporate the proposed/registered uses of novaluron. The calculations reflected the most recent guidance from HED ( OPPTS 860.1000 Supplement, Table 1 Feedstuffs , 30 - JUN - 20 08) concerning revisions of feedstuff percentages and constructing reasonabl y balanced dietary burdens (RBDBs ) . The currently

established livestock tolerances are based on the following RBDBs for novaluron : 16.9 ppm for beef cattle and 11.9 ppm for dairy cattle (Memo G. Kramer, 22 - MAR - 2004; D285474 ) , and 2.4 ppm for poultry and 2.5 ppm for swine (Memo, J. Van Alstine, 23 - FEB - 2010 ; D 374420 ) . Based on the proposed/registered uses, the revised RBDBs for novaluron are 9.6 ppm for beef cattle, 18.3 ppm for dairy cattle, 2.4 for poultry , and 2.5 for swine. N o changes areNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 21 of 56 necessary for the tolerances for secondary residues in/on cattle, goat, horse, sheep , poultry , and swine commodities . Although IR - 4 requested increasing tolerances for residues of n ovaluron in milk from 1.0 to 1.5 ppm and milk, fat from 20 to 35 ppm, increased tolerances are not required for these commodities at this time. IR - 4 is requested to submit a revised Section F which removes the proposed changes to milk and milk fat toleran ces. Additionally , b ased on ChemSAC guidance that meat by product tolerances should be set at the highest residue level seen in any livestock commodity (minutes from 12 - JAN - 2011), several meat b yproduct tolerances in 40 CFR § 180.598(a) should be updated s o that they are based on the highest expected residue. Additionally , two commodity descriptions should be updated. The tolerances and commodity

descriptions should be updated as outlined in Table 4.1.2 . **Magnitude of the Residue –**  **Sweet Corn :**  The number and locations of field trials are in accordance with OPPTS Guideline 860.1500 for sweet corn . The field trial data reflect the proposed use rate and PHI for sweet corn . The field trial data for sweet corn stover and forage were entered into th e Agency ’s tolerance spreadsheet as specified b y the Guidance for Setting Pesticide Tolerances Based on Field Trial Data Standard Operating Procedure (SOP) to determine appropriate tolerance levels; see Appendix I I . All residues in/on K+CWHR were less than the lowest level of method validation ( LLM V ; 0.05 ppm); therefore, the recommended tolerance for sweet corn K+CWHR is 0.05 ppm. The available data support tolerances of 50 ppm, 16 ppm, and 0.05 ppm for residues of novaluron in/on sweet corn sweet corn s tover, forage, and K+CWHR , respectivel y. **Magnitude of the Residue –**  **Food -**  **Handling Establishments:** The food - handling study is adequate and reflects the use of novaluron as a space spray treatment to a simulated commercial food establishment at a rate of 3 8.75 mg ai/m 2 (3X application rate), with a product application rate of 0.1 gal/1000 ft2 [refer to the chemistry summary memo ( J. Van Alstine; D378631 ) for calculations] . An exaggerated rate was used to generate worst - case residues. The residues for all covered food matrices samples treated at a 3X application rate were below the limit of quantitation ( LO Q ; <0.010 ppm) except for one sample of bread ( 0.0142 ppm) collected 4 hours post - application . HED does not expect residues to be higher than 0. 01 ppm in covered food and feed items following treatment at a 1X application rate because 29 out of 30 measured residues were below the LOQ, even when treated at a 3X rate, and the food - handling establishment label states that food items should be removed or covered prior to treatment and that packaged food items should be stored in such a way that direct contact with foodstuff is not anticipated. The available data support the proposed tolerance of 0.01 ppm for residues in/on f ood/feed commodities (other than those covered by a higher tolerance as a result of use on growing crops) in food - and feed - handling establishments . **Processed Food and Feed:** HED does not require residue data for any processed commodities associated with sweet corn . Therefore, dat a requirements for processed fo od and feed are not relevant to sweet corn commodities. Additionally , since the food and feed handling establishment label states that food items should be removed or covered prior to treatment and that packaged food items s hould be stored in such a way that direct contact with foodstuff is not anticipated, data requirements for processed fo od and feed are not relevant to this use pattern.Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 22 of 56 **Submittal of Analytical Reference Standards :**  The available anal yt ical reference standards for novaluron expired on 22 - NOV - 2010 (personal communication with Theresa Cole, 22 -NOV 2010 ) . MANA is required to submit an updated COA or a new analy tical standard to the EPA National Pesticide Standards Repository at the fo llowing address :

USEPA National Pesticide Standards Repository /Anal yt ical Chemistry

Branch/OPP 701 Mapes Road Fort George G. Meade, MD 20755 - 5350 Please note that the extended zip code is required for delivery . **Confined/Field Accumulation in Rotational Crops:**  The sweet corn commodities associated with the current petitions may be rotated. Based on the results of the submitted confined rotational crop study, the appropriate plantback interval ( PBI ) for all non - labeled crops is 30 day s. The c urrent and proposed labels include a restriction that only registered crops may

be rotated to a treated field within 30 day s of the final application , which is appropriate for this petition . Future uses that have significantl y higher application rates wil l require confined rotational crop studies at higher rates using chlorophenyl - labeled novaluron. The HED MARC has determined that for tolerance assessment and risk assessment, parent only is the residue of concern in rotational crops (Memo, G. Kramer et a l. , 03 - FEB - 2004; D297646). **Tolerance Summary:** Permanent tolerances for novaluron have been established for a variety of commodities under 40 CFR §180.598. The HED MARC determined that the residue of concern in plants (primary

and rotational crops) and livestock for purposes of tolerance enforcement and risk assessment is novaluron only (Memo, G. Kramer et al. , 03 - FEB - 2004; D297646). R evised Section F s are requested for PP# 0E7723 and PP# 0F7708 which reflect the HED - recommended tolerances and commodity definitions presented in Table 4.1.1 . Additional, the revised Section F for PP# 0E7723 should be submitted which cites the appropriate CAS name for novaluron:

“ Tolerances are established for residues of the insecticide novaluron , including its metabol ites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined b y measuring only novaluron (

N - [[[3 - chloro - 4 - [1,1,2 - trifluoro - 2 - (trifluoromethox y)ethox y]phenyl]amino]carbonyl] - 2,6 - difluorobenzamide ) in or on the following raw agricultural commodities:” No Codex, Canadian , or Mexican maximum residue limit s ( MRL s ) have been established for novaluron in/ on sweet corn stover, forage, and K+CWHR . Canada is currently in the process of reviewing the use of novaluron on sweet corn stover, forage, and K+CWHR . The EPA and the Pest Management Regulatory Agency (PMRA) tolerance recommendations have been harmonized at 0.05 ppm for sweet corn K+CWHR. The PMRA is also proposing an increase in its MRLfor milk to 1.0 ppm from 0.5 ppm, and as a result, the EPA and PMRA milk tolerances/MRLs are now harmonized. The PMRA does not recommend MRL s for livestock feed commodities; therefore it is not possible to harmonize tolerances/MRLs for sweet corn stover and sweet corn forage. The PMRA has not received a petition for the use of novaluron inNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 23 of 56 food and feed handling establishments; therefore, it is not possible to harmonize for the residues resulting from this proposed use. The Agency ’s Guidance for Setting Pesticide Tolerances Based on Field Trial Data was utilized for determining appropriate tolerance levels. **Table 4. 1.**  **1. Tolerance Summary for Novaluron.** Commodity Proposed Tolerance (ppm) HED - Recommended

Tolerance (ppm) Comments;

Correct Commodity Definition Corn, Sweet, Stover 50 50 Corn, sweet, stover Corn, Sweet, Forage 20 16 Corn, sweet, forage Corn, Sweet, Kernel Plus Cob With Husks Removed 0.05 0.05 Corn, sweet, kernel plus cob with husks removed Milk 1.5 1.0 An increase in the tolerance for residues of novaluron in milk is not needed at this time. Milk, fat 35 20 An increase in the tolerance for residues of novaluron in milk fat is not needed at this time. All food/feed items other than those covered by a higher tolerance as a result of use on growing crops 0.01 0.01 Food/feed commodities (other than those covered by a higher tolerance as a result of use on growing crops) in food/feed handling establishments **Note to RD:** Based on ChemSAC guidance that meat by product tolerances should be set at the highest residue level seen in any livestock commodity

(minutes from 12 - JAN - 2011), several meat by product tolerances in 40 CFR § 180.598(a) should be updated so that they are ba sed on the highest expected residue . Additionally , two commodity descriptions should be updated. The tolerances and commodity descriptions should be updated as outlined in Table 4.1.2 . **Table 4.**  **1. 2.**  **HED -**  **Proposed Updates to 40 CFR § 180.598 (a) Based on 12**  **- JAN**  **- 2011 ChemSAC**  **Guidance .**  **Current Commodity Definition**  **Updated Commodity Description**  **Current Tolerance (ppm)**  **Updated Tolerance (ppm)**  **1** Cattle, meat byproducts, except kidney and liver - 0.60 11 Goat, meat byproducts except kidney and liver - 0.60 11 Horse, meat byproducts, except kidney and liver - 0.60 11 Sheep, meat byproducts, except kidney and liver - 0.60 11 Hog, meat byproducts Hog, meat byproducts, except kidney and liver2 0.10 1.5 Poultry, meat byproducts Poultry, meat byproducts, except kidney and liver 3 0.80 7.0 1 Based on the base d on the highest expected secondary tissue residue [peritoneal fat in cattle (translated to goat, horse, and sheep); peritoneal fat in hog; abdominal fat in poultry].Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 24 of 56 2 Separate tolerances have been es tablished for hog, kidney (0.10 ppm) and hog, liver (0.10 ppm). 3 Separate tolerances have been established for poultry, kidney (0.80 ppm) and poultry, liver (0.80 ppm).Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 25 of 56 **4.2 Drinking Water Residue Profile**  The drinking water residues used in the dietary risk assessment were provided by EFED ( R. Miller , 29 - SEP - 2010; D 378389 ). Since the application rates for the proposed new uses are significantl y lower than the use rates for pome fruits and stone fruits, the EDWCs provided in the previous drinking water assessments dated 10 - MAR - 2009 (D357061) and 11 - FEB - 2004 (D285477) are applicable for the proposed uses. EDWCs were not generated for the food - and feed - handling establishment use s because the use pattern is not expected to result in contamination of drinking water . The HED MARC concluded that parent and the chlorophenyl urea and chloroaniline degradates are residues of potential concern to be included in the drinking water assessm ent. Monitoring data are not available for novaluron or its chlorophenylurea and chloroaniline degradates in surface water or ground water. Concentrations in surface water and ground water were estimated using standard EFED drinking water models . Tier II Pesticide Root Zone Model/Exposure Analy sis Modeling Sy stem (PRZM/EXAMS) modeling was performed to estimate drinking water concentrations for surface water for the parent novaluron. The scenarios were selected to provide high - end drinking water concentrations for each crop and represent the geographic locations where the specific crops are grown in large quantities. The most - conservative estimates were obtained for aerial applications to apples grown in PA at the max imum annual application rate of 0. 97 2 lb ai/acre, applied three times at approximately 0.32 lb ai/acre, with an interval between applications of ten day s. For surface water, the 1 - in - 10 - ye ar annual mean EDWC for the parent novaluron is 0.76 ppb. A Tier I drinking water analy sis was perfo rmed for the chlorophenylurea and chloroaniline degradates using the FQPA Index Reservoir Screening Tool (FIRST) model to obtain surface water estimates. For surface water, the annual average EDWC for chlorophenyl urea is 0.89 ppb and the annual average EDWC for chloroaniline is 2.6 ppb. The chlorophenyl urea estimate is based upon the maximum application rate in peaches [ approximately 0.32 lb ai/A applied 3 times per season every

7 day s (0.9 72 lb ai/year)] and the chloroaniline estimate is based upon the maximum application rate in apples [ approximately 0.32 lb ai/A applied 3 times per season every 10 day s (0.9 72 lb ai/year)]. For ground water, the Screening Concentration in Ground Water (SCI - GROW) model was used to predict a ground water concentration f or novaluron at the annual application rate of 0.9 72 lb ai/acre ( i.e . , three applications of approximately 0.32 lb ai/acre). The estimate for the parent novaluron is 0.0056 ppb in drinking water from shallow ground water sources. For the chlorophenylure a degradate, the predicted ground water concentration is 0.0045 ppb, and for the chloroaniline degradate , the concentration is 0.0090 ppb. These concentrations were estimated with the same assumptions used for surface water modeling, and may be considered as both the peak and annual average upper - bound exposures. These EDWC values are meant to represent upper - bound estimates of the concentrations that might be found in surface water and ground water based upon existing and proposed uses. Of the three EDW C values, chronic estimates for the terminal chloroaniline metabolite are the highest (100% conversion from parent to aniline was assumed). This is consistent with theNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 26 of 56 expected degradation pattern for novaluron. Therefore, the EDWC value for the chloroaniline degradate (2.6 ppb) was used to assess chronic aggregate risk. **Table 4.2**  **. EDWCs Resulting from the Application of Novaluron.**  **Drinking Water Source**  **(Model) Use(Modeled Rate)** 

**Application Type 1**  **- in**  **- 10**  **- Y**  **ear A**  **cute (ppb)**  **1 -**  **in -**  **10 -**  **Year**

**Chronic (ppb) 30**  **- Year Average**  **(ppb) Novaluron**  Surface Water (PRZM/EXAMS) PA Apples

(0.972 lbs ai/A/year) aerial application 4.59 1 **0.76 0.62**  GA Peach (0.972 lbs ai/A/year) aerial application **4.72** 1 0.51 0.43 Groundwater (SCIGROW) Apples/Peaches

(0.972 lbs ai/A/year) aerial application **0.0056** 0.0056 ≤0.0056

**Chlorophenyl Urea** Surface water (FIRST) Apples

(0.972 lbs ai/A/year) Aerial Application 4.55 0.86 ≤0.86 Peaches (0.972 lbs ai/A/year) Aerial Application **4.74 0.89**  **≤0.89** Groundwater (SCIGROW) Apples/Peaches

(0.972 lbs ai/A/year) Aerial Application 0.0045 0.0045 ≤0.0045 **Chloroaniline** Surface water (FIRST) Apples/Peaches

(0.972 lbs ai/A/year) Aerial Application **11.4 2**  **2.60 ≤2.60**  Groundwater (SCIGROW) Apples/Peaches

(0.972 lbs ai/A/year) Aerial Application 0.009 0.009 **≤** 0.009 1 These values exceed the measured water solubility of novaluron; i.e., 3 μg/L. 2 This value exceeds the estimated water solubility of chloroaniline; i.e., 10.6 μg/L. **4.3 Dietary Exposure and Risk**  An acute dietary

assessment was not conducted for novaluron because an endpoint of concern attributable to a single dose was not identified. A cancer dietary assessment was not conducted because novaluron was classified as “not likel y to be carcinogenic t o humans.” A partiall y refined chronic dietary

exposure and risk assessment was conducted to support Section 3 requests for use of novaluron on sweet corn and in food - and feed - handling establishments using the DEEM - FCID  , Version 2.03, which uses food co nsumption data from USDA’s CSFII from 1994 - 1996 and 1998. The partiall y refined chronic dietary exposure and risk assessment was conducted for the proposed new uses on sweet corn and in food - and feed - handling establishments, all established uses, and drinking water to support Section 3 requests for use of novaluron on sweet corn and in food - and feed - handling establishments . A PCTn memorandum for sweet corn was provided b yNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 27 of 56 BEAD. Additionall y, data from a previously provided SLUA memorandum for existi ng uses and a PCTn memorandum for grain sorghum were used. The chronic analy sis incorporated average %CT data for apples, cabbage, cotton, pears, and potatoes, and PCTn data for grain sorghum and sweet corn. 100% CT was assumed for the remaining food commodities. ARs for meat, milk, hog, and poultry commodities were calculated using average field trial residues, PCTn data for grain sorghum and sweet corn, average %CT data for apple and cotton, and assumed 100% CT for sugarcane and cowpea seed. The chronic anal ysis also incorporated average field trial residues, average greenhouse trial residue s for tomatoes, empirical processing factors for apple juice (translated to pear and stone fruit juice), cottonseed oil, dried plums, and tomato paste and purée, and DEEM  (ver. 7.81) default processing factors for the remaining processed commodities. In accordance with HED SOP 2000.1, average field trial residues were translated from representative commodities in the crop group to other commodities in that crop group as needed. The chronic dietary

(food and drinking water) exposure to novaluron is below HED’s LOC for the general U.S. population and all population subgroups. The chronic dietary exposure results in a risk estimate that is 21% of the cPAD for the g eneral U.S. population and 72% of the cPAD for children 1 - 2 years old, the most highly exposed population subgroup. **Table 4.3**  **. Summ ary of Chronic Dietary Exposure (Food and Drinking Water) and Risk for Novaluron**  **1,2 .**  Population Subgroup Ac ute Dietary Chronic Dietary Cancer Dietary Exposure (mg/kg/day) % aPAD Dietary Exposure (mg/kg/day) % cPAD Dietary Exposure (mg/kg/day) Risk General U.S. Population N/A N/A 0.002298 21 N/A N/A All Infants (<1 year old) 0.002922 27 **Children 1 -**  **2 years old 0.007955**  **72** Children 3 - 5 years old 0.005989 54 Children 6 - 12 years old 0.003676 33 Youth 13 - 19 years old 0.002098 19 Adults 20 - 49 years old 0.001632 15 Adults 50+ years old 0.001576 14 Females 13 - 49 years old 0.001570 14 1 The chronic RfD (cRfd= cPAD = 0.011 mg/kg/day). 2 The highest dietary exposure is bolded. **4.4 Anticipated Residue and %CT Information**  A SLUA memorandum entitled, “Usage Report Package in Support of Registration for the Insecticide Novaluron (124002), BEAN DP# 371221” (A. Grube, 17 -NOV - 2009) and PCTn memorandums entitled, “Percent Crop Treated for New Use (PCTn): Novaluron (124002) Use on Sorghum, DP# 371615” (C. Doucoure, et al. , 29 - DEC - 2009) and “Percent Crop Treated for Novaluron on Propos ed New Uses for Sweet Corn (PC# 124002, DP# 384687)” ( J. Alsadek et al. , 18 - FEB - 2011 ) were provided b y BEAD. The SLUA memo included %CT data for apples, cabbage, cotton, pears, and potatoes. The market leader approach was used by BEAD to determine the PC Tn for sorghum and sweet corn. New SLUA and grain sorghum PCTnNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 28 of 56 memorandums were not required because the memos were completed within approximately one ye ar of this analy sis. The chronic dietary

analy sis incorporated average %CT data for apples (15%), cabbage (10%), cotton (2.5%), pears (10%), and potatoes (2.5%) , and average PCTn data for grain sorghum (5%) and sweet corn (59%). 100% CT was assumed for the remaining food commodities. L i vestock dietary burdens of novaluron were calculated based on the proposed/registered uses, average field trial residues , average PCTn data for grain sorghum (5%) and sweet corn (59%), average %CT data for apple (15%) and cotton (2.5%), and an assumption of 100% CT for sugarcane and cowpea seed. These livestock dietary burdens were used, along with average transfer coefficients, to calculate anticipated secondary residues for meat, milk, hog, and poultry commodities which were incorporated into the chronic dietary assessment. **5.0 RESIDENTIAL (NON**  **- OCCUPATIONAL) EXPOSU**  **RE/RISK CHARACTERIZATION**  Novaluron is proposed for indoor (crack and crevice and spot treatments) and outdoor (perimeter) uses for the control of roaches and crickets. Novaluron is proposed for use in residential and commercial buildings and structures and their immediate surroundings and on modes of transportation. The permitted areas of use include non - food/non feed areas of stores, warehouses, transportation equipment, manufacturing sites, industrial buildings, houses, apartment buildings, office buil dings, laboratories, schools, daycare centers, nursing homes, hospitals, hotels and on vessels, railcars, aircraft, buses, trucks and trailers. There is a potential for exposure in residential settings during the application process for homeowners who use products containing novaluron. There is also a potential for exposure from entering novaluron treated areas that could lead to exposures to adults and children. Risk assessments have been completed for both residential handler and post - application scenarios. Only the indoor use has been assessed as this is believed to cover the outdoor perimeter treatment. The outdoor perimeter treatment is to areas that adults and children would not spend much time, such as around window frames and doors. Dermal, inhalation and incidental oral exposure is expected to be higher from the indoor crack and crevice and spot treatments. A residential exposure assessment for novaluron was prepared in a pending HED memorandum (L . Venkateshwara; D378634). See Table 2. 1 for a summary of the proposed use patterns. **5.1 Residential Handler Exposure and Risk**  Based upon the proposed use pattern, HED expects the following residential pesticide handler scenarios :  Mixing/loading/appl yi ng emulsifiable concentrate formulation s with low - pressure handwand ( PHED ) , and  Applying ready

to use formulations via trigger - pump sprayer (ORETF). Assessing exposures and risks resulting from residential uses is very similar to a ssessing occupational exposures and risks, except that a tiered approach for personal protection usingNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 29 of 56 increasing levels of personal protective equipment PPE is not used in residential handler risk assessments. Homeowner handler assessments are based on the assumption that individuals are wearing shorts, short - s leeved shirts, socks, and shoes. No chemical - specific data were available with which to assess potential exposure to residential pesticide handlers. The estimates of exposure to pesticide handlers are based upon surrogate study data available in the PHED (v. 1.1, 1998) and ORETF . MANA is a member of ORETF. F or the purposes of assessing a crack and crevice exposure scenario, HED used the mixing/loading/appl yi ng wettable powders with a low - pressure handwand scenario as a surrogate to assess handler exposure to the emulsifiable concentrate formulation . Usually , HED would use surrogate dat a for liquid formulations as surrogate for EC formulation. However, the unit exposure values provided fo r the wettable powder formulation are based on actual exposures measured during crack and crevice applications; whereas, the unit exposure values for the liquid formulation are based on applications to chicken houses and greenhouses. Therefore, although the proposed product is formulated as an emulsifiable concentrate, HED believes that the use of unit exposure values resulting from crack and crevice applications provides a more accurate representation of handler exposure. Daily dermal or inhalation handl er exposures are estimated for each applicable handler task with the application rate, the area treated in a day , and the applicable dermal or inhalation unit exposure using the following formula: Daily Exposure (mg ai/day) = Unit Exposure (mg ai/lb ai handled) x Application Rate (lb ai/area) x Daily Area Treated (area/day) Where: Daily Exposure = Amount (mg ai/day) deposited on the surface of the skin that is available for dermal absorption or amount inhaled that is available for inhalation absorptio n; Unit Exposure = Unit exposure value (mg ai/lb ai) derived from August 1998 PHED or ORETF data; Application Rate = Normalized application rate based on a logical unit treatment, such as acres; and Daily Area Treated = Normalized application area base d on a logical unit treatment such as acres (A/day). The daily dermal or inhalation dose is calculated by normalizing the daily

exposure by

body weight and adjusting, if necessary , with an appropriate dermal or inhalation absorption factor using the foll owing formula: Average Daily Dose (mg/kg/day) = Daily Exposure (mg ai/day) x (Absorption Factor (%/100)) / Body Weight (kg) Where: Average Daily Dose = Absorbed dose received from exposure to a pesticide in a given scenario (mg ai/kg body we ight/day);Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 30 of 56 Daily Exposure = Amount (mg ai/day) deposited on the surface of the skin that is available for dermal absorption or amount inhaled that is available for inhalation absorption; Absorption Factor = A measure of the amount of chemical that crosses a biological boundary such as the skin or lungs (% of the total available absorbed); and Body Weight = Body w eight determined to represent the population of interest in a risk assessment (kg). Non - cancer dermal and inhalation risks for each ap plicable handler scenario are calculated using an MOE, which is a ratio o f the NOAEL to the daily dose. All MOE values were calculated using the formula below:

MOE = NOAEL or LOAEL (mg/kg/day) / Average Daily Dose (mg/kg/day) . Dermal and inhalation risk s were combined in this assessment, since the toxicological effects for these exposure routes were similar. Dermal and inhalation risks were combined using the following formula: Total MOE = NOAEL / (Dermal + Inhalation Dose) . Table 5.1 provides estimates of short - term exposure and risk for residential handlers. Since there is no short - term dermal endpoint, these exposures are representative of intermediate - term dermal exposures and are considered conservative since i ntermediat e - term exposures are not likely because of the intermittent nature of applications by homeowners. Although a PoD from an oral study was used to assess residential handler inhalation risks for novaluron, HED does not believe this assessment is under - protec tive of adult handlers. The inhalation MOEs calculated for residential handlers were all > 1 million, thus providing an ample margin of safety to account for any uncertainties in route - to - route extrapolation. The MOE calculated exceeds the LOC of 100 and, therefore, is not of concern. **Table 5.1. Residential Handler Exposure and Risk for Novaluron .**  Application Rate (lb ai/gallon) a Amount

Handled (gallons) b Unit Exposure

(mg/lb ai) c Dose (mg/kg/day) e,f MOE g,h Baseline Dermal d Baseline

Inhalation d Baseline

Dermal Baseline

Inhalation Combined

Baseline Dermal + Baseline Inhalation Baseline

Dermal Baseline

Inhalation Baseline

Dermal + Baseline Inhalation **Mi xing/Loading/Applying Wettable Powders with**  **Low -**  **pressure Handw**  **and (PHED)** 0.02 0.5 100 0.03 0.0014 0.0000043 0.0014 3,100 1,000,000 3,100 **Applying R** **eady to U**  **se F**  **ormulations V** **ia T**  **rigger P**  **ump S**  **prayer (ORETF)** 0.02 0.125 54 0.019 0.00019 6.8E - 07 0.0002 23,000 6,500,000 23,000 a. Application rate based on proposed use on label for novaluron product RIMON ® EC I nsecticide (Reg. No. 66222 - ERT) . Maximum rate = 3.1 oz/gal (0.02 lb ai/gal). b. ExpoSAC Policy #12 . Assumed 16 - oz bottle for trigger pump sprayer (16 oz * 128 oz/gal = 0.125 gallon) .Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 31 of 56 c. Unit Exposures for low- pressure handwand scenario based on PHED Version 1.1. For purposes of assessing a crack and crevice

exposure scenario, HED used the mixing/loading/applying wettable powders with a low- pressure handwand scenario as a surrogate to assess handler exposure to the l iquid formulation . See text above table for full explanation. Unit exposures for trigger - pump sprayer scenario based on ORETF (OMA006; MRID 444598 - 01). d. Baseline Dermal: Short - sleeve shirt, shorts, and no gloves . Baseline I nhalation: no respirato r. e. Dermal Dose (mg/kg/day) = daily unit exposure (mg/lb ai) * application rate (lb ai/gallon) * amount handled (gallons) * dermal

absorption factor (10%) / body weight (70 kg). f. Inhalation Dose (mg/kg/day) = daily unit exposure (mg/lb ai) * applica tion rate (lb ai/gallon) * amount handled (gallons) * inhalation absorption (100%) / body weight (70 kg). g. MOE = NOAEL (short - and intermediate - term = 4.38 mg/kg/day) / daily dose (mg/kg/day). LOC = 100. h. Baseline Dermal + Baseline I nhalation MOE = NOAEL (mg/kg/day) / (Baseline Dermal dose + Baseline I nhalation dose). **5.2 Residential**  **Post -**  **application Exposure and Risk** HED believes that short and intermediate residential post - application exposures are likely from the proposed use . Intermediate - term exposures have been estimated using Day- 0 residue values along with an intermediate - term POD (applicable for exposures up to 6 months), which is considered a conservative assumption for longer- term exposures since residue values would be expected to dissipate over time. For the proposed indoor use, HED anticipates that dermal (adults and children ) , inhalation (adults and children) , and incidental oral ( children only) exposure s are possible. **Post -**  **application Inhalation** Post - application inhalation exposure can result from the proposed indoor use. The saturation concentration in air for novaluron was calculated and used as a screening level air concentration for the inhalation post - application exposure assessment. The following equation was used to estimate the saturation concentration for novaluron: C sat = (VP * CF1 * MW * CF2 * CF3) / (R * T) Where : C sat = Saturation concentration (mg/m3 ), VP = Vapor pressure (mmHg), MW = Molecular weight (g/mol), R = Gas constant = 0.0821 L - atm/mol - K, T = Tem

perature of the air (296 K), CF1 = Conversion factor (atm/760 mm Hg), CF2 = Conversion factor (10 3 mg/g), and CF3 = Conversion factor (10 3 L/m3 ). The vapor pressure of novaluron is 1.2 x 10 - 7 mm Hg at 20 o C and the molecular weight is 4 92.7 g/mol . The saturation concentration was then used to calculate post - application inhalation exposure using the following assumptions:

 inhalation rate = 0.55 m 3 /hr for adults and 0.36 m 3 /hr for toddlers based on ExpoSAC Policy

#12, and  exposure time = 16 hours based on mean time spent in a residence from the U.S EPA Exposure Factors Handbook (1997). Post - application inhalation dose is calculated as follows:Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 32 of 56 Dose (mg/kg/day) = C sat * IR * ET / BW Where: C sat = Saturation concentration (mg/m3 ), IR = Inhalation rate (m3 /hr), ET = Exposure time (hr/day), and BW = Body weight (kg). All post - application inhalation scenarios resulted in MOEs greater than 100 and do not exceed HED’s level of concern . Table 5.2.1 summarizes the post - application inhalation exposure and risk from the indoor uses of novaluron . Although a PoD from an oral study was used to assess residential post - application inhalation risks for novaluron, HED does not believe this assessment is under - protective. The post - application inhalati on MOEs calculated were all > 3,000, thus providing an ample margin of safety to account for any uncertainties in route - to - route extrapolation. Further, c alculating postapplication inhalation exposure and risk using the saturation concentration should be c onsidered a very conservative approach. The saturation concentration represents what would occur if a large amount of chemical were spilled in a non ventilated room and allowed to evaporate until equilibrium is reached. **Table 5.2.1 .**  **Post -**  **application Inhalation Exposure for Children and Adults**  **.** Population C sat

(mg/m3 ) a IR (m3 /hr) ET (hr) Inhalation Dose (mg/kg/day) b Inhalation MOE c Short - and Intermediate - term Adult 0.0032 0.55 16 0.0004 11,000 Children (3 to <6 years old) 0.36 16 0.0012 3,6 00 a. C sat = [Vapor pressure (1. 2 X 10 - 7 mmHg) * Conversion factor (atm/760 mm Hg) * Molecular Weight (492.7 g/mol) * Conversion

factor (10 3 mg/g) * Conversion factor (10 3 L/m 3 )] / [R (Gas constant = 0.0821 L - atm/mol - K)* Temperature (296 K)] . b. Inhalation Dose (mg/kg/day) = C sat * Inhalation Rate (m 3 /hr) * Exposure Time (hr) / Body Weight (kg). c. Inhalation MOE = NOAEL (Short - and intermediate - term = 4.38 mg/kg/day) / Dose (mg/kg/day) . **Post -**  **application Dermal** Post - application dermal exposure can result from pesticide residue transfer to the skin of individuals who contact previously treated indoor surfaces (e.g., carpets, floors, furniture, and other surfaces) during standard activities. Such exposure is assumed to occur for adults and children . An assessment has been conducted for dermal exposures from the proposed indoor use (crack and crevice/spot). Since there is no short - term dermal endpoint, these exposures are representative of intermediate - term exposures . **Crack and Crevice**

**/Spot Use**  T he following data, assumptions, and equations were used to assess dermal post - application exposure from the proposed indoor crack and crevice/spot use:

 Deposited residue: o Maximum application rate: 3.1 ounces per gallon (0.02 lb ai/gal) ,Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 33 of 56 o Based on information from a Registrant submitted food handling residue study (MRID 48034903), assumed a spray rate of 0.1 gallon per 1000 sq feet , o Dermal post - application exposure assessed using the following deposited residue value:  0.02 lb ai/gal and 0.1 gal/1000 ft2 = 0.002 lb ai/1000 ft2 = 1.18 ug/cm 2 ,  Fraction of ai available for transfer: 0.05 for carpet and 0.1 for hard surfaces ,  Transfer coefficient: 16,700 cm 2 /hr for adults and 6,000 cm2 /hr for children ,  Exposure time : 8 hours/day for carpet and 4 hours/ day for hard surfaces , and  Individuals contact previously treated carpets or hard surfaces on the same day a pesticide is applied. Dermal exposure for adults and children contacting treated indoor surface residue was calculated with the following equation : ISR = DepR * F Where: ISR = Indoor surface transferable residue (μg/cm2 ), DepR = Deposited residue (ug/cm2 ), and F = Fraction of ai available for transfer from carpet or hard surface (unitless). D = (ISR * CF1 * TC * ET * DAF) / BW Where: D = Dermal dose (mg/day), ISR = Indoor surface transferable residue (μg/cm2 ), CF1 = Conversion factor (0.001 mg/μg), TC = Transfer coefficient (cm2/hr), ET = Exposure time (hr/day), DAF = Dermal absorption factor, and BW = Body

w eight (kg). Dermal MOEs w ere calculated as follows: Dermal MOE = NOAEL (mg/kg/day) / Dermal Dose (mg/kg/day). Table 5.2.2 summarizes the dermal post - application exposure and risk from the crack and crevice/spot use at the maximum application rate allowed on the proposed label . At the maximum application rate (3.1 oz/gal and 0.1 gallon/1000 ft2 ), all dermal MOEs for adults and children are greater than the target MOE of 100 and do not exceed HED’s level of concern . **Table 5.2.2 .**  **Post -**  **application Derm al Exposure for Children (3 to <6 year old**  **s ) and Adults for Novaluron Crack**  **and Crevice/Spot Use .**  Surface Type Population Application rate per 1000 square feet a Surface

Residue b (ug/cm2 ) Fraction

transferred Transfer

Coefficient (c m2/hr) Exposure

time (hr/day) Dermal

Dose c (mg/kg/day) Dermal

MOE d I - T 3. 1 oz/gal = 0.02 lb ai/gal and 0. 1 gal/1000 ft2 = 0. 00 2 lb ai/1000 ft2 Carpet Adult 0. 00 2 a 1.18 0.05 16,700 8 0.0 11 390Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 34 of 56 **Table 5.2.2 .**  **Post -**  **application Derm al Exposure for Children (3 to <6 year old**  **s ) and Adults for Novaluron Crack**  **and Crevice/Spot Use .**  Surface Type Population Application rate per 1000 square feet a Surface

Residue b (ug/cm2 ) Fraction

transferred Transfer

Coefficient (c m2/hr) Exposure

time (hr/day) Dermal

Dose c (mg/kg/day) Dermal

MOE d I - T Children (3 to<6 year olds) 6,000 0. 019 230 Hard Surfaces Adult 0.10 16,700 4 0.0 11 390

Children (3 to<6 year olds) 6,000 0. 019 230 a. Maximum application rate is 3.1 oz/gal. The maximum spray rate per area assumed to be 0.1 gallon per 1000 sq ft based on a

Registrant submitted food handling study (MRID 48034903). b . Surface residue = conversion of the application rate from lb ai per sq ft to ug/cm2 using two conversion factors (4.5 x 10 8 ug/lb and

1.08 x 10 - 3 ft2/cm2 ). c . Dose (mg/kg/day) = Surface residue (ug/cm 2 ) * Fraction trans ferred * Transfer coefficient (cm2/hr) * Exposure time (hr/day) * Conversion factor (0.001 mg/ug) * Dermal Absorption Factor (10%) / Body Weight (70 kg for adults and 15 kg for children ). d . MOE = NOAEL (mg/kg/day) / Dose (mg/kg/day), where intermediate - term ( I - T ) dermal NOAEL = 4.38 mg/kg/day. **Post -**  **application Incidental Oral** Post - application incidental oral exposure resulting from hand - to - mouth activity can occur as a result of the indoor crack and crevice/spot use. The hand - to - mouth exposure scenario was assessed using the HED Draft SOP’s for Residential Exposure Assessments ( 2000 ), and the Revisions to the SOP’s for Residential Exposure Assessment ( ExpoSAC Policy # 12). Th i s scenario assume s pesticide residues are transferred to the skin of children during post - application contact with treated indoor areas and are subsequently ingested as a result of hand - to - mouth transfer. The following assumptions, factors, equations and calculations were used to estimate hand - to - mouth transfer exposure:

 Deposited residue: o Maximum application rate: 3.1 ounces per gallon (0.02 lb ai/gal) , o Based on information from a registrant - submitted food handling residue study (MRID 48034903), assumed a spray rate of 0.1 gallon per 1000 sq feet, o Dermal post - applicati on exposure assessed using the following deposited residue value:  0.02 lb ai/gal and 0.1 gal/1000 ft2 = 0.002 lb ai/1000 ft2 = 1.18 ug/cm 2 ,  Fraction of ai available for transfer: 0.05 for carpet and 0.1 for hard surfaces ,  The median surface area of both hands for children: 20 cm 2 ,  The mean rate of hand - to - mouth activity : 20 times/hour for short - term exposure scenarios and 9.5 events per hour for inter mediate - term exposure scenarios,  Duration of exposure for children: 4 hours per day ,  The saliva extraction factor: 50%, and  Toddlers are assumed to weigh 15 kg. In cidental hand - to - mouth exposure for children contacting treated surfaces was calculated with the following equation : ISR = DepR x F Where:Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 35 of 56 ISR = Indoor surface transferable residue (μg/cm2 ), DepR = Deposited residue (ug/cm2 ), and F = Fraction of ai available for transfer from carpet or hard surface (unitless). D = (ISR x SA x FQ x ET x SE x CF1) / BW Where: D = Dermal dose (mg/kg/day), ISR = Indoor surface transferable residue (ug/cm2 ), SA = Surface area of the hands (cm2 /event), FQ = Frequency of hand - to - mouth activity (events/hr), ET = Exposure time (hr/day), CF1 = Conversion factor (0.001 mg/ug), SE = Saliva extraction factor, and BW = Body weight (15 kg). In cidental oral MOEs were calculated as follows :

Incidental oral MOE = NOAEL (mg/kg/day) / Incidental Oral Dose (mg/kg/day). Table 5.2.3 summari zes the MOEs for hand - to - mouth transfer of pesticide residues from the indoor crack and crevice/spot use at the maximum application rate allowed on the proposed label . At the maximum application rate (3.1 oz/gal and 0.1 gallon/1000 ft2 ), short - and interm ediate - term incidental oral MOEs are greater than the target MOE of 100 and do not exceed HED’s level of concern .Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 36 of 56 **Table 5.2.3. Post -**  **application Incidental Oral (Hand -**  **to -**  **Mouth) Exposure for Children (3 to <6 year olds) for Novaluron Crack and Crevice/Spot Use**  **.** Type of Surface Application

Rate (lb ai/1000 sq ft) a Fraction ai

dislodgeable Surface

area of the hand (cm2 ) Exposure Frequency

(events/hr) Saliva

Extraction Factor Exposure

Time (hrs/day) Surface

Residue (ug/cm2 ) Average Daily Oral Dose

(mg/kg/day) b Incidental Oral MOE c Short term Intermediate term Short term Intermediate term Short term Intermediate term 3. 1 oz/gal = 0.02 lb ai/gal and 0.1 gallon/1000 ft2 = 0. 0 02 lb ai/1000 ft2 Carpet 0. 0 02 0.05 20 20 9.5 50% 8 1.18 0. 006 0.0 03 690 1,500 Hard surfaces 0. 0 02 0.10 20 20 9.5 50% 4 1.18 0.0 06 0.0 03 690 1,500 a. Maximum application rate is 3.1 oz/gal. The maximum spray rate per area assumed to be 0.1 gallon per 1000 sq ft based on a Registrant submitted food handling study (MRID 48034903). b . Dose (mg/kg/day) = Surface residue (ug/cm 2 ) * Fraction transferred * Surface area of hands (cm 2/event) * Exposure frequency (events/hr) * Exposure time (hr/day) x Saliva extraction factor x Conversion factor (0.001 mg/ug) / Body Weight (15 kg for children ). c . MOE = NOAEL (mg/kg/day) / Dose (mg/kg/day), where short - and intermediate - term (S - T and I - T ) incidental oral NOAEL = 4.38 mg/kg/day.Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 37 of 56 **5.3 Combined Residential Risk Estimates**  HED combines risk values resulting from separate residential exposure scenarios when it is likely they can occur simultaneously based on the use - pattern and the behavior associated with the exposed population. Furthermore, since similar endpoints were selected for dermal, inhalation and oral exposures, risks from the three exposure routes may be combined. Therefore, all non - dietary

sources of post - application exposure were combined to obtain an estimate of potential combined exposure which could be used for the aggregate a ssessment. A combined residential assessment has been included here based on the indoor crack and crevice/spot use . These scenarios consisted of adult dermal and inhalation handler and post application exposures , as well as children (3 to <6 years old) dermal, inhalation and oral (hand to - mouth) pos t - application exposures. All of the combined MOEs for adult and children (3 to <6 ye ar olds) are greater than the target MOE of 100 and do not exceed HED’s level of concern . Table 5 .3.1 provides a summary of the combined residential post - application indoor crack and crevice exposures and risks for adult and children and handler indoor crack and crevice exposures and risks for adults . **Table 5.3.1. Com bined Residential Exposure and Risk Estim**  **ates from the In**  **door Crack and Crevice/Spot Use**  **.** Short - term Intermediate - term Population Combined

Dose 1 Combined

MOE 2 Population Combined Dose 1 Combined

MOE 2 Residential Handler Exposure 3 Adults (inhalation only) 0.0000043 1,000,000 Adults (dermal + inhalation) 0.0014 3,100 Residential Post - Application Exposure Adults (inhalation only) 0.0004 11 , 000 Adults (dermal + inhalation) 0.0114 380 Children (inhalation + HTM) 0.0 072 580 Children (dermal + inhalation + incidental oral) 0.023 190 1 Combined Dose = see Table 5.1 for handler exposures and Tables 5.2.1 through 5.2.3 for post - application exposures. 2 Combined MOE = NOAEL (mg/kg/day) / Combined Dose (mg/kg/day); where S - T and I - T NOAEL = 4.38 mg/kg/day. **3 The values for the w**  **ettable powder**  **exposure scenario were used because the wettable powder baseline doses were larger than the ready**

**to use formulation baseline doses for both baseline inhalation and baseline combined (dermal + inhalation). 5**  **.4 Bystander Post**  **- application**  **Inhalation Exposure** Based on the Agency's current practices, a quantitative residential b ys tander post - application inhalation exposure assessment was not performed for novaluron at this time. However, volatilization of pesticides may be a potential sourc e of post - application inhalation exposure to individuals nearb y to pesticide applications. The Agency sought expert advice and input on issues related to volatilization of pesticides from its FIFRA Scientific Advisory Panel (SAP) inNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 38 of 56 December 2009. The Ag ency received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly /SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report and may , as appropriate, develop policies and procedures, to identify

the ne ed for and, subsequently , the way to incorporate post - application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative post - application inhalation expo sure assessment for novaluron. **5 .**  **5 Spray Drift**  Spray drift is alway s a potential source of exposure to residents nearby to spraying operations. This is particularly

the case with aerial application but, to a lesser extent, could also be a potential source of exposure from the ground application method additionally employed for novaluron. The Agency

has been working with the Spray Drift Task Force, EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the bes t spray drift management practices. The Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/labeling. The Agency has completed its evaluation of the new database submitted b y the Spray Drift T ask Force, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriatel y apply the data and the AgDRIFT ® computer model to its risk assessments for pesticides applied by air, orchard airblast , and ground h ydraulic methods. After the policy is in place, the Agency

may impose further refinements in spray

drift management practices to reduce off - target drift and risks associated with aerial as well as other application types where appropriate. **6 .0**  **AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION** In accordance with the FQPA, HED must consider and aggregate pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. In an aggregate assessment, exp osures from relevant sources are added together and compared to quantitative estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When aggregating exposures and risks from various sources, HED considers both the route and duration of exposure. In the case of novaluron , a ggregate risk assessments were performed for short - term aggregate exposure (food + drinking water + residential), intermediate - term aggregate exposure (food + drinking water + residential), and chronic aggregate exposure (food + drinking water). Residential long - term exposure wa s not assessed because there are no chronic residential exposure scenarios for the registered and proposed uses, and was therefore not incorporated into the chronic aggregate exposure assessment . An acute aggregate assessment was not conducted for novaluron because an endpoint of concern attributable to a single dose was not identified. Additionally , a cancer aggregate assessment was not conducted because novaluron was classified a s “not likely

to be carcinogenic to humans.” All potential exposure pathway s were assessed in the aggregate risk assessment.Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 39 of 56 **6.1 Short**  **- Term Aggregate Risk**  The short - term aggregate risk assessment estimates risks likely to result from 1 - to 30 - day exposures to novaluron residues from food, drinking water, and residential pesticide uses. Short term estimates of residential exposure are combined with background food and drinking water exposures. Short - term aggregate risk assessments are necessary for both adults and children as there is potential for both short - term dermal and inhalation handler exposure and short - term post application exposure from the residential uses of novaluron . For the short - term aggregate risk assessment, potential residential post - application exposures were combined with food and drinking water exposures. A short - term dermal endpoint has not been selected for novaluron; therefore the short - term adult and child aggregate risk estimates do not include dermal exposures. Specificall y, for young children, the short - term aggregate assessment combines dietary exposure with potential inhalation and incidental oral exposure (from hand - to - mouth contact with treated surfaces) resul ting from the crack and crevice uses . The short - term aggregate assessment for adults combines dietary exposures with exposure from potential post application inhalation exposure s resulting from indoor crack and crevice uses. See Table 5.3. 1 for more info rmation on combined exposures. This is the first proposed residential use of novaluron; therefore, the short - term crack and crevice post - application exposure estimates were aggregated with the chronic dietary (food) to provide a worst - case estimate of s hort - term aggregate risk for the U.S. population and children 1 - 2 years old (the child population subgroup with the highest estimated chronic dietary food exposure) . As the short - term aggregate MOEs are greater than 100, risks do not exceed HED’s level of concern . **Table 6**  **. 1**  **. Short -**  **Term Aggregate Risk Calculations for**  **Novaluron Using Post -**  **Application Exposure Estimates**  **.** Population Subgroups Short - Term Scenario 1

NOAEL (mg/kg/day) LOC 2 Max Exposure 3 (mg/kg/day) Average Dietary

Exposure (mg/kg/day) Residential

Exposure 4 (mg/kg/day) Aggregate MOE

(dietary and residential) 5 U.S. Population 4.38 100 0.04 0.002298 0.0004 1600 Children 1 - 2 years old 4.38 100 0.04 0.007955 0.0072 290 1 A short - term dermal endpoint has not been selected for novaluron ; therefore dermal exposure was not included in the short - term aggregate assessment. Additionally post - application inhalation exposure estimates were used for adults as opposed to handler inhalation exposure estimates because the post - application inhalati on dose was higher than the handler inhalation dose and resulted in a more conservative estimate of aggregate risk. 2 The LOC (target MOE) includes 10X for interspecies extrapolation and 10X for intraspecies variation. 3 Maximum Exposure (mg/kg/day) = NO AE L/Target MOE. 4 Residential Exposure = [Oral exposure + Inhalation Exposure]. 5 Aggregate MOE = [NOAEL ÷ (Avg. Dietary Exposure + Residential Exposure)] .Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 40 of 56 **6.2 I**  **ntermediate -**  **Term Aggregate Risk** The intermediate - term aggregate risk assessment estimates risks likely to result from 1 to 6 month exposures to novaluron residues from food, drinking water, and residential pesticide uses. Intermediate - term estimates of residential exposure are combined with background fo od and drinking water exposures. Intermediate - term aggregate risk assessments are necessary for both adults and children as there is potential for both intermediate - term dermal and inhalation handler exposure and intermediate term post - a

pplication exposure from the residential uses of novaluron . For the intermediate - term aggregate risk assessment, potential residential post - application exposures were combined with food and drinking water exposures. Specificall y, f or young children, the intermediate - term aggregate assessment combines dietary exposure with potential dermal , inhalation , and incidental oral exposure ( from hand - to - mouth contact with treated surfaces ) resulting f rom the crack and crevice uses . The intermediate - term aggregate assessment for adults combines dietary exposures with exposure from potential post - application dermal and inhalation exposure s resulting from indoor crack and crevice uses. See Table 5.3. 1 for more information on combined exposures. This is the first pro posed residential use of novaluron; therefore, the intermediate - term crack and crevice exposure estimates were aggregated with the chronic dietary (food) exposures to provide a worst - case estimate of intermediate - term aggregate risk for the U.S. population and children 1 - 2 years old (the child population subgroup with the highest estimated chronic dietary food exposure) . As the intermediate - term aggregate MOEs are greater than 100, risks do not exceed HED’s level of concern . **Table 6.2**  **. Interm ediate**  **- Term Aggregate Risk Calculations for**  **Novaluron Using Post -**  **Application Exposure Estimates**  **.** Population Subgroups Intermediate - Term Scenario 1

NOAEL (mg/kg/day) LOC 2 Max Exposure 3 (mg/kg/day) Average Dietary

Exposure (mg/kg/day) Residential

Exposure 4 (mg/kg/day) Aggregate MOE

(dietary and residential) 5 U.S. Population 4.38 100 0.04 0.002298 0.0114 320 Children 1 - 2 years old 4.38 100 0.04 0.007955 0.023 140 1 Combined post - application exposure estimates were used as opposed to combined handler exposure estimates because the combined post - application dose was higher than the combined handler dose and resulted in a more conservative estimate of aggregate risk. 2 The LOC (target MOE) includes 10X for interspecies extrapolation and 10X for intraspecies variation. 3 Maximum Exposure (mg/kg/day) = NOAEL/Target MOE. 4 Residential Exposure = [Oral exposure + Dermal exposure + Inhalation Exposure]. 5 Aggregate MOE = [ NOAEL ÷ (Avg . Dietary Exposure + Residential Exposure)]. **6.3 Chronic Aggregate Risk**  The chronic aggregate risk assessment takes into account average exposure estimates from dietary consumption of novaluron (food and drinking water) and residential uses. ResidentialNovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 41 of 56 long - term exposure wa s not assessed because there are no chronic residential exposure scenarios for the registered and proposed uses of novaluron, and was therefore not incorporated into the chro nic aggregate exposure assessment . As a result, the chronic aggregate risk assessment considered exposure from food and drinking water only . The chronic dietary exposure estimates are below HED’s LOC (<100% cPAD) for the general U.S. population ( 21 % of the cPAD) and all population subgroups (see Table 4.3 ). The most highly exposed population subgroup is children 1 - 2 years old, at 72 % of the cPAD. Therefore, the chronic aggregate risk associated with the proposed use s of novaluron does not exceed HED’s L OC for the general U.S. population or any

population subgroups. **7.0 CUMULATIVE RISK**  Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to novaluron and any other substances and novaluron does not appear to produce a toxic metabolite produced b y other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that novaluron ha s a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released b y EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/. **8 .0**  **OCCUPATIONAL EXPOSURE/RISK PATHWAY**  An occupational exposure assessment for the proposed use of novaluron on sweet corn was prepared in a pending HED memorandum (L. Venkateshwara ; D37 8630 ). An occupational and residential exposure assessment for a proposed crack and c revice use was also prepared in a pending HED memorandum (L . Venkateshwara; D378634) . See Table 2. 1 for a summary of the proposed use patterns. **8 .1**  **. Occupational Pesticide Handler Exposure and Risk**  **8.1.1 Sweet Corn Use**  Occupational handler and post - application exposure s from the proposed use of novaluron on sweet corn are anticipated. Based on label information, exposure is expected to occur for short and intermediate - term exposure durations (e.g., maximum of 6 applications, 7 day s apart) . O ccupational h an dler’s exposure and risk were estimated for the following scenarios: Mixer/L oader: 1. Mixing/loading liquids for aerial application;Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 42 of 56 2. Mixing/loading liquids for groundboom application; Applicator: 3. Applying spray s via aerial applications; 4. Appl yi ng spray s via groundboom applications; and Flagger: 5. Flagging to support aerial applications. No chemical - specific data were available with which to assess potential exposure to pesticide handlers. The estimates of exposure to pesticide handlers are based upon surrogate study data available in the PHED (August, 1998). For occupational pesticide handlers, HED presents estimates of dermal exposure for “baseline” (i.e., workers wearing a single layer of work clothing consisting of a long - sleeved shirt, long pants, shoes plus socks, and no protective gloves), as well as for “baseline” and the use of protective gloves or other PPE, as might be necessary . The novaluron product labels direct applicators and other handlers to wear a long sleeved shirt, long pants, protective eyewear, chemical - resistant gloves, and shoes plus socks. Handler exposure is expected to be short - and intermediate - term based on information provided on the proposed label for sweet corn (e.g., maximum of 6 applications, 7 day s ap art) . There is no short - term dermal POD ; therefore, onl y intermediate - term dermal exposure has been assessed and is anticipated to be protective of short - term dermal exposure. Short - and intermediate - term inhalation exposures have been assessed. T he short - and intermediate - term inhalation toxicological points of departure are the same; therefore, the estimates of risk for short - term duration inhalation exposures are protective of those for intermediate - term inhalation duration exposures. The average adult body weight of 70 kg was used for estimating inhalation and dermal dose. Long - term exposures are not expected ; therefore, a long - term assessment was not conducted. Exposures, doses and MOEs were calculated using the equations presented in the residential section (Section 5.1). Table 8 .1 .1 presents the estimated risks for workers based on the intermediate - term dermal and short - and intermediate - term inhalation expo sures at baseline and with PPE. HED has determined that risks do not exceed HED’s level of concern (i.e., MOEs ≥ 100), **provided workers wear**  **chemical -**  **resistant gloves as recommended on the label**  . No short - term POD was selected for dermal exposure ; therefo re, the risks presented for handlers are representative of intermediate - term exposures and would be considered protective of short - term exposures. It should be noted that only engineering control data are available to assess dermal and inhalation risks to handlers operatin g aircraft (enclosed cockpit). The risks do not exceed HED’s level of concern for pilots using enclosed cockpits.Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 43 of 56 **Table 8**  **.1. 1.**  **Occupational Handler Dermal and Inhalation Exposures and Risks from the Use on Sweet Corn**  **.** Dermal and Inhalation Unit Exposures (mg/lb ai) Application

rate (lb ai/A) 1 Area

Treated Daily (A) 2 Short - and

Intermediate - term Doses (mg/kg/day) 3 Total Dose 4 Short - and Intermediate term MOE Total MOEs 5 **(1) Mixer/Loader –**  **Groundboom Application** Dermal Baseline: 2.9 Single layer w/gloves: 0.023 Inhalation Baseline: 0.0012 0.078 80 Dermal Baseline 6 : 0.026 Single layer w/gloves 8 : 0.00021 Baseline Dermal + Inhalation 0.026 Single layer w/gloves + Inhalation 0.00032 Dermal

Baseline 6 : 170 Single layer w/gloves 8 : 21,000 Baseline

Dermal + Inhalation 170 Single layer w/gloves + Baseline Inhalation 14,000 Inhalation Baseline 7 : 0.00011 Inhalation Baseline 7 : 41,000 **(2) Mixer/Loader –**  **Aerial Application** Dermal Baseline: 2.9 Single layer w/gloves: 0.023 Inhalation Baseline: 0.0012 0.078 350 Dermal Baseline: 0.11 Single layer w/gloves: 0.00090 Baseline

Dermal + Inhalation 0.11 Single layer w/gloves + Inhalation 0.0014 Dermal

Baseline: 39 Single layer w/gloves: 13,000 Baseline

Dermal + Inhalation **39** Single layer w/gloves + Baseline Inhalation 3,200 Inhalation Baseline: 0.00047 Inhalation Baseline: 9,400 **(3) Applicator –**  **Groundboom Application** Dermal Baseline: 0.014 Inhalation Baseline: 0.00074 0.078 80 Dermal Baseline: 0.00012 Baseline Dermal + Inhalation 0.0002 Dermal

Baseline: 35,000 Baseline

Dermal + Inhalation 23,000 Inhalation Baseline: 0.000066 Inhalation Baseline: 66,000 **(4) Applicator –**  **Aerial Application** Dermal Engineering Control: 0.0050 Inhalation Engineering Control: 0.000068 0.078 350 Dermal Engineering control: 0.0002 Com

bined Engineering Control 0.00023 Dermal

Engineering control: 22,000 Com

bined Engineering Control 20,000 Inhalation Engineering control: 0.000027 Inhalation Engineering control: 170,000Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 44 of 56 **Table 8**  **.1. 1.**  **Occupational Handler Dermal and Inhalation Exposures and Risks from the Use on Sweet Corn**  **.** Dermal and Inhalation Unit Exposures (mg/lb ai) Application

rate (lb ai/A) 1 Area

Treated Daily (A) 2 Short - and

Intermediate - term Doses (mg/kg/day) 3 Total Dose 4 Short - and Intermediate term MOE Total MOEs 5 **(5) Flagger –**  **Aerial Application** Dermal Baseline: 0.011 Inhalation Baseline: 0.00035 0.078 350 Dermal Baseline: 0.00043 Baseline Dermal + Inhalation 0.0006 Dermal

Baseline: 10,000 Baseline

Dermal + Inhalation 7,700 Inhalation Baseline: 0.00014 Inhalation Baseline: 32,000 1 Application rate is the maximum recommended rate provided on the novaluron product label. 2 Area treated per day values are HED estimates based on ExpoSAC Policy #9 “Standard Values for Daily Acres Treated in Agriculture,” industry sources, and HED estimates. 3 Dose (mg/kg/day) = Unit exposure (mg/lb ai) x App Rate (lb ai/acre) x Area Treated (acres/day) x % Absorption (10% dermal and 100% inhalation assumed) / Body weight. The body weight is 70 kg for the inhalation and dermal dose. 4 Total Dose = Dermal + Inhalation Dose. 5 Short - /Intermediate - term MOE = Intermediate - t erm dermal or Short/Intermediate - term inhalation NOAEL (4.38 mg/kg/day) / Dermal or Inhalation dose (mg/kg/day) 6 Total MOE = NOAEL (4.38 mg/kg/day)/Total Dose. 7 Baseline Dermal: long - sleeved shirt, long pants, no gloves. 8 Baseline Inhalation: no respi rator. 9 Single layer with gloves: single layer baseline attire plus chemical - resistant gloves. **8 .1**  **.2 Crack and Crevice** **/Spot Use** There is also a potential for occupational handler exposure from the proposed use for indoor and outdoor control of roaches and crickets . Occupational h andler’s exposure and risk were estimated for the following scenarios:

 Mixing/loading/appl yi ng emulsifiable concentrate formulations with low - pressure handwand ( PHED), and  Applying ready

to use formulations via trigger - pump sprayer (ORETF). Chemical - specific data were not submitted to the Agency in support of this Section 3 application. It is HED policy

to use data from PHED Version 1.1 and/or the ORETF to assess handler exposures when chemical - specific data are not submitted. As with the residential assessment f or purposes of assessing a crack and crevice exposure scenario for commercial applicators, HED used the mixing/loading/applying wettable powders with a low - pressure handwand scenario as a surrogate to assess handler exposure to the emulsifiable concentrate formulation . Usually , HED would use surrogate data for liquid formulation as surrogate for EC formulation. However, The unit exposure values provided for the wettable powder formulation are based on actual exposures measured during crack and crevice applications; whereas, the unit exposure values for the liquid formulation are based on applications to chicken houses and greenhouses. Therefore, although the RIM ON ® SUPRANovaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 45 of 56 10EC Insecticide is formulated as an EC , HED believes that the use of unit exposure values resulting from crack and crevice applications provides a more accurate representation of handler exposure . There is no short - term dermal POD ; therefore, only intermediate - term dermal exposure has been assessed and should be considered protective of short - term dermal exposure. Short - and intermediate - term inhalation exposures have been assessed. In addition, the short - and intermediate - term inhalation toxicological points of departure are the same; therefore, the estimates of risk for short - term duration inhalation exposures are protective of those for intermediate - term inhalation duration exposures . The average adult body weight of 70 kg was used for estimating inhalation and dermal dose. A 10% dermal - absorption factor was used to estimate dermal exposure for all durations. Long - term exposures are not expected ; therefore, a long - term assessment was not conducted. Exposures, doses and MOEs were calculated using the equat ions presented in the residential section (Section 5.1). Table 8 . 1. 2 present s a summary of the short - and intermediate - term occupational handler exposures and risks . T he results of the occupational handler exposure and risk assessment indicate that MOEs do not exceed HEDs LOC ( i.e., MOEs ≥100) with either baseline attire (i.e., single layer of clothing, no respirator) or with the addition of gloves. There is no unit exposure data for the mixing/loadin g/appl yi ng wettable powders scenario with baseline attire and no gloves; therefore, this scenario was onl y assessed assuming handlers were wearing gloves. The proposed label for novaluron does not currently recommend any

personal protective equipment for handlers. **HED recommends RD require the addition of chemical -**  **resistant gloves to the label**  **.**Novaluron DRAFT Human - Health Risk Assessment DP#: 378387

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 46 of 56 **Table 8**  **. 1.2.**  **Short -**  **and Intermediate -**  **Term Occupational Handler Exposure and Risk for Novaluron .**  Application Rate a Amount

applied Daily b Unit Exposures (mg/lb ai) c Dose (mg/kg/day) f,g Short - and I ntermediate - term MOEs h,i Baseline Dermal d Baseline

Inhalation d PPE - G

Dermal e Baseline

Dermal Baseline

Inhalation PPE - G

Dermal Baseline

Dermal Baseline

Inhalation PPE - G

Dermal Total MOE

Baseline Dermal + Baseline Inhalation PPE - G Dermal +

Baseline Inhalation **Mixing/Loading/Applying Wettable Powders with Low -**  **Pressure Handwand (PHED )**  0.02 lb ai/gal 40 gallons No Data 1.1 8.6 N/A 0.013 0.0098 N/A 350 450 N/A 200 **Applying Ready -**  **to -**  **Use Formulations via Trigger -**  **Pum p Sprayer (ORETF)**  0.02 lb ai/gal 2 gallons 42 0.019 1.8 0.0024 0.000011 0.0001 1,800 400,000 43,000 1,800 39,000 a. Application rate based on proposed use on label for novaluron product RIMON ® EC In secticide (Reg. No. 66222 - ERT ) . Maximum rate = 3.1 oz/gal (0.02 lb ai/gal). b. ExpoSAC Policy # 9.1 . c. Unit Exposures for low- pressure handwand scenario based on PHED Version 1.1. For purposes of assessing a crack and c revice exposure scenario for commercial applicators,

HED used the mixing/loading/applying wettable powders with a low- pressure handwand scenario as a surrogate to assess handler exposure to the liquid formulation . See text above table for full explanatio n. Unit exposures for trigger - pump sprayer scenario based on ORETF (OMA006; MRID 444598 - 01). d. Baseline Dermal: Long - sleeve shirt, long pants, and no gloves (none is specified on the label) ; Baseline I nhalation: no respirator. Unit exposure data for the mixing/loading/applying wettable powders with low pressure handwand scenario at baseline with no gloves is not available; therefore, this scenario was only assessed with the use of gloves. e. PPE - G Dermal : Baseline plus chemical - resistant gloves. f. Dermal Dose (mg/kg/day) = daily unit exposure (mg/lb ai) * application rate (lb ai/ gallon ) * amount handled (gallons) * dermal absorption factor ( 10 %) / body weight ( 7 0 kg). g . Inhalation Dose (mg/kg/day) = daily unit exposure (m g/lb ai) * application rate (lb ai/ gallon ) * amount handled (gallons) * inhalation absorption (100%) / body weight ( 7 0 kg). h . MOE = NOAEL ( short - and intermediate - term = 4.38 mg/kg/day) / daily dose (mg/kg/day). LOC = 100. i . Total MOEs = NOAEL (mg/kg/day) / (Dermal dose + I nhalation dose) .Novaluron DRAFT Human - Health Risk Assessment DP#: 364307

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 47 of 56 **8 .2**  **Occupational Post -** **Application Worker Exposure and Risk 8**  **.2.1 Occupational Post**  **- Application Worker Exposure and Risk for Sweet Corn**  The proposed use is for a post emergent ap plication; therefore, a dermal post - application exposure assessment was conducted. The registrant submitted two studies: Willard, T. (2002) Foliar Dislodgeable Residue Dissipation of Novaluron in Cotton: Final Study Report: Lab Project Number: AA010705: R- 13884:989W. Unpublished study prepared by American Agricultural Services, Inc. 214 p. {OPPTS 875.2100} Willard, T. (2002) Foliar Dislodgeable Residue Dissipation of Novaluron in Apple: Lab Project Number: AA01076: R- 13883: AA010706.CA. Unpublished study prepared by American Agricultural Services, Inc. 204 p. {OPPTS 875.2100} HED decided not to use the apple st udy due to some study

limitations and differences in the use pattern (different application rate and application equipment used) and differences in plant/leaf morphology

(apple versus corn). HED did use chemical - specific data provided in the cotton study . This study was designed to determine the dissipation of dislodgeable foliar residues (DFR) of novaluron applied to cotton foliage at two test sites located in Porterville, C alifornia and Washington, L ouisiana . Three applications of Rimon ® 10EC, an EC formulation containing novaluron (0.83 lb ai/gal) were made to cotton foliage at a target rate of 0.091 lb ai/A/application. The re - treatment interval was 7 day s. Applications were made as a foliar broadcast spray at a spray

volume of approximately 21 to 28 gallons of spray

solution per acre ( GPA) using groundboom equipment. There were no surfactants/adjuvants included in the spray mixtures. At the California site, the highest average DFR value occurred immediatel y after the third application ( 0.673 μg/cm 2 ). The residues declined to an average of 0.361 μg/cm2 by Day 21 after the third application, and then increased to an average of 0.483 μg/cm 2 by Day 35 after the third application. At the Louisiana site, the highest average DFR value occurred immediately after the third application (0.142 μg/cm 2 ). The residues then declined to below the LOQ by Day 28 after the third application. The regi strant generated dissipation curves using a linear first order kinetic model of the natural log transformed data. The analy sis was conducted using the individual DFR values collected immediately after the third application through the last day of sampling . The registrant’s calculated half - lives for novaluron in cotton foliage were 59 days for the California site and 8 day s for the Louisiana site. This difference in dissipation is due to the difference in climate , with L ouisiana being a more humid climate (more rainfall) , and California being a more arid climate (less rainfall) . In California and other arid areas which receive less than 20 inches of precipitation per ye ar , the residues are not expected to dissipate, and therefore onl y 1 application of nov aluron should be required . The registrant should submit a revised label which specifies that the retreatment of sweet corn with novaluron is prohibited (i.e., only 1 application is allowed at a rate of 0.078 lb ai/A) in California and other arid areas whi ch receive less than 20 in ches of precipitation per ye ar. See Memo, L. Venkateshwara, 29 - MAR - 2011; D387931 for the analy sis of the data from the CA site , and see memo, L. Venkateshwara, 29 - MAR - 2011; D387932 for the anal ys is of the data from the LA site.Novaluron DRAFT Human - Health Risk Assessment DP#: 364307

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 48 of 56 Post - application exposures have been assessed using the submitted dislodgeable foliar residue data as well as dermal transfer coefficients from HED’s ExpoSAC Policy Number 3.1 “Agricultural Transfer Coeffici ents” (August, 2000). Table 8 .2.1 summarizes the scenarios assessed. In addition, the following assumptions were used in the calculations:

 Application Rate = 0.078 lb ai/A  Exposure Duration = 8 hours per day  Body Weight = 70 kg for adult male  Dermal Absorption = 10%  Dislodg eable foliar residue (DFR) = chemical - specific data from MRID # 456384 - 16. **Table 8**  **.2.1 .**  **Anticipated Post -**  **application Activities and Derm al Transfer Coefficients**  **.** Proposed Crop Policy Crop Group Category Transfer Coefficients (cm2/hr) Activities Sweet Corn Field/row crop tall 100 Hand weeding 1000 Irrigation and scouting 17000 Detasseling and hand harvest Equations/Calculations: Daily dermal exposures were calculated on each post - application day after application using the following equation: Daily Dermal Dose t = [DFRt (μg/cm 2 ) x 0.001 mg/μg x TC (cm 2 /hr) x DA x ET (hrs)] / BW (kg) Where : DFRt = dislodgeable foliage residue on day "t" (ug/cm 2 ); TC = transfer coefficient (cm2 /hr); DA = dermal absorption factor ( 100%) ; ET = exposure time (8 hr/day); and BW = body

weight ( 7 0 kg). Once dail y exposures are calculated, the calculation of daily absorbed dose and the resulting M O Es use the same algorithms that are described above for the handler exposures. These calculations are comple ted for each day or appropriate block of time after application. Table 8 .2.2 presents a summary of occupational post - application risks associated with use of novaluron at the Louisiana site and Table 8 .2.3 presents the summary of the occupational post app lication risks associated with use of novaluron at the California site .Novaluron DRAFT Human - Health Risk Assessment DP#: 364307

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 49 of 56 **Table 8**  **.2.2 . Post**  **- application Risks for Novaluron Using Data from** **the Louisiana Site .**  Crop Application Rate

(lb ai/A) Transfer Coefficient (cm 2/hr) DFR 1

(ug/cm2 ) Day s After

Treatment Daily Dose 2

(mg/kg/ d ay) MOE 3 Sweet Corn 0.078 100 0.118 12 hours (0 days) 0.000137 32,000 1,000 0.00137 3,200 17000 0.023 190 The information in the table is based on proprietary and non -proprietary data. 1 DFR calculated from MRID #456384 - 16 Louisiana site . 2 Daily Dose = [DFR (ug/cm2 ) x TC (cm2/hr) x 0.001 mg/μg x Dermal Absorption (10%) x 8 hrs/day] ÷ Body Weight (70 kg) . 3 NOAEL/Daily Dose (Intermediate - term NOAEL = 4.38 mg/kg/day) . **Table 8**  **.2.3 . Post**  **- application Risks for**  **Novaluron Using Data from the California Site**  **.** Crop Application Rate

(lb ai/A) Transfer Coefficient (cm 2/hr) DFR 1

(ug/cm2 ) Day s After

Treatment Daily Dose 2

(mg/kg/ d ay) MOE 3 Sweet Corn 0.078 100 0.58 12 hours (0 days) 0.00066 6,600 1,000 0.0066 660 17000 0.113 39 The information in the table is based on proprietary and non -proprietary data. 1 DFR calculated from MRID #456384 - 16 California site . 2 Daily Dose = [DFR (ug/cm2 ) x TC (cm2/hr) x 0.001 mg/μg x Dermal Absorption (10%) x 8 hrs/day] ÷ Body Weight (70 kg) . 3 NOAEL/Daily Dose (Intermediate - term NOAEL = 4.38 mg/kg/day) . Based on the differences in DFR data from the Louisiana site (a more humid climate) and the California site (a dry

climate), HED is recommending two different retreatment intervals , one for humid climates and one for arid climates. For humid climates a retreatment interval of 7 day s is acceptable ; however, for arid climates where DFR data show that there is no dissipation , only 1 application should be allowed at a rate of 0.078 lb ai/A . Table 8.2.4 shows the calculations for the MOE at the California site after one application. The MOE at the highest TC is 175, which is greater than 100. **Table 8**  **.2.4 . Post**  **- application Risks for Novaluron**  **at California Site after 1 Application .**  Crop Application

Rate (lb ai/A) Transfer Coefficient

(cm 2/hr) DFR

(ug/cm2 ) Day s After

Treatment Daily Dose 1

(mg/kg/ d ay) MOE 2 Sweet Corn 0.078 100 0.1 3 12 hours (0 days) 0.000 15 2 9 ,000 1,000 0.00 15 2, 9 00 17000 0.0 2 5 1 75 The information in the table is based on proprietary and non -proprietary data. 1 Daily Dose = [DFR (ug/cm2 ) x TC (cm2/hr) x 0.001 mg/μg x Dermal Absorption (10%) x 8 hrs/day] ÷ Body Weight (70 kg) 2 NOAEL/Daily Dose (Intermediate - term NOAEL = 4.38 mg/kg/day) **Inhalation** Based on the Agency's current practices, a quantitative occupational post - application inhalation exposure assessment was not performed for novaluron at this time. However, there are multiple potential sources of post - application inhalation exposure to individuals performing post application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Ag ency sought expert advice and input on issues related to volatilization of pesticides from its FIFRANovaluron DRAFT Human - Health Risk Assessment DP#: 364307

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 50 of 56 SAP in December 2009. The Agency received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly /SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report as well as available post - application inhalation exposure data generated b y the Agricultural Reentry Task Force and may , as appropriate, develop policies and procedures, to identify the need for and, subsequently , the way to incorporate occupational post - application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post - application inh alation exposure assessment for novaluron . **Restricted Reentry Interval** Novaluron is classified as acute T oxicity C ategory I II for acute dermal toxicity . It is classified as T oxicity C ategory

IV for primary

eye irritation and primary skin irritation. Therefore, the interim WPS REIof 12 hours is adequate to protect agricultural workers from post - application exposures to novaluron . **8 .2.**  **2 Crack and Crevice** **/Spot Use** Based on the proposed use sites associated with the indoor crack and crevice/spot use, HED believes the presence of commercial workers in treated areas is minimal after application. Therefore, an occupational quantitative post - application assessment for this product was not conducted. **9 .0**  **DATA NEEDS AND LABEL RECOMMENDATIONS 9**  **.1 Toxicolo**  **gy**  A **90** - day

inhalation toxicity

study is requested for further characterization of inhalation risk. Due to the potential for repeated inhalation exposure anticipated from the proposed residential use pattern, there is concern for toxicity b y the inhalatio n route. An inhalation study would provide a dose and endpoint via the route of exposure of concern (i.e. route specific study) and thus would avoid using an oral study and route - to - route extrapolation. An immunotoxicity

study is required as specified in the new 40 CFR Part 158 data requirements.  An immunotoxicity

study is required as specified in the new 40 CFR Part 158 data requirements . **9 .2**  **Residue Chemistry**  860.1200 Directions for Use o A revised Section B for PP# 0E7723 should be submitted which:  p rohibits the use of novaluron on turnips harvested for the root and prohibits the feeding of turnip tops to livestock as previously requested (Memo, J. Van Alstine, 09 - SEP - 2009 ; D357060). This affects the current petition because it could result in increa sed livestock dietary burdens. o A revised Section B for PP# 0F7708 should be submitted which:Novaluron DRAFT Human - Health Risk Assessment DP#: 364307

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 51 of 56  specifies an application rate of 0.1 gallons per 1000 ft2 for indoor spot, crack and crevice, space spray , and general surface applications;  states that all food processing surfaces (including equipment) and utensils should be covered during treatment or thoroughl y washed prior to use;  states the livestock feed items should be removed or covered prior to application; and  removes all references to fogger and fog ap plications in the label and specifies that applications should be made with mechanical cold mist/ULV equipment .  860.1550 Proposed Tolerances o A revised Section F for PP# 0E7723 should be submitted which:  cites the appropriate CAS name for novaluron:

“ Tolerances are established for residues of the insecticide novaluron , including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined b y measuring only novaluron ( N - [[[3 - chloro - 4 - [1,1,2 - trifluoro - 2 - (trifluoromethox y)ethox y]phenyl]amino]carbonyl] - 2,6 - difluorobenzamide ) in or on the following raw agricultural commodities:”; and

 reflect s the recommended tolerances and commodity definitions presented in Table 14. o Additionally , a revised Section F for PP# 0F7708 should be submitted which:  reflects the commodity definition presented in Table 14.  860.1650 Submittal of Analy tical Reference Standards o The available anal yt ical reference standards for novaluron have exp ired . MANA is required to submit an updated COA or a new analytical standard to the EPA National Pesticide Standards Repository at the following address: USEPA National Pesticide Standards Repository /Anal yt ical Chemistry

Branch/OPP 701 Mapes Road Fort George G. Meade, MD 20755 - 5350 Please note that the extended zip code is required for delivery . **Note to RD:** Based on ChemSAC guidance that meat by product tolerances should be set at the highest residue level seen in any livestock commodity

(minutes from 12 - JAN - 2011), several meat by product tolerances in 40 CFR § 180.598 (a) should be updated so that they are based on the highest expected residue. Additionally , two commodity descriptions should be updated. The tolerances and commodity descriptions sho uld be updated as follows:Novaluron DRAFT Human - Health Risk Assessment DP#: 364307

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 52 of 56 **Current Commodity Description**  **Updated Commodity Description**  **Current Tolerance (ppm)**  **Updated Tolerance (ppm)**  **1** Cattle, meat byproducts, except kidney and liver - 0.60 11 Goat, meat byproducts except kidney and liver - 0.60 11 Horse, meat byproducts, except kidney and liver - 0.60 11 Sheep, meat byproducts, except kidney and liver - 0.60 11 Hog, meat byproducts Hog, meat byproducts, except kidney and liver2 0.10 1.5 Poultry, meat byproducts Poultry, meat byproducts, except kidney and liver 3 0.80 7.0 1 Based on the base d on the highest expected secondary tissue residue [peritoneal fat in cattle (translated to goat, horse, and sheep); peritoneal fat in hog; abdominal fat in poultry]. 2 Separate tolerances have been establish ed for hog, kidney (0.10 ppm) and hog, liver (0.10 ppm). 3 Separate tolerances have been established for poultry, kidney (0.80 ppm) and poultry, liver (0.80 ppm). **9 .3**  **Occupational and Residential Exposure**

 A revised label (Section B) for PP#0E7723 should be submitted : o which specifies that the retreatment of sweet corn with novaluron is prohibited (i.e., only 1 application is allowed at a rate of 0.078 lb ai/A) in California and other arid areas which receive less than 20 inches of precipitation per year .  A revised label (Section B) should also be submitted for PP#0F7708 which : o **specifies an application rate of 0.1 gallons per 1000 ft 2**  **for indoor spot, crack and crevice, space spray, and general surface applications;**  and o requires the addition of chemical - resistant gloves. Attachments: Appendix A: TOXI COLOGY ASSESSMENT A.1 Acute Toxicity

Profile . A.2 Toxicity

Profiles . cc: L. Venkateshwara, J. Van Alstine, RDI: RAB1 Branch ( 03 / 09 /1 1 ); G. Kramer ( 3 / 7 /1 1 ); D. Vogel ( 03 / 09 /1 1 ) L . Venkateshwara:S10 956 :Potomac Yard 1 :703 - 308 - 2722:7509P:RAB1Novaluron DRAFT Human - Health Risk Assessment DP#: 364307

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 53 of 56 **Appendix A: TOXICOLOGY ASSESSMENT A.1**  **. Acute Toxicity Profile**  **Table A.1.**  **Acute Toxicity of Novaluron .**  **Guideline No.**  **Study Type MRID #(s)**  **Results Toxicity Category**  870.1100 (81 - 1) Ac ute Oral (rat) 44961001 LD 50 > 5000 mg/kg IV 870.1200 (81 - 2) Ac ute Dermal (rat) 45003201 LD 50 > 2000 mg/kg III 870.1300 (81 - 3) Ac ute Inhalation (rat) 45003202 LC 50 > 5.15 mg/L IV 870.2400 (81 - 4) Primary Eye Irritation (rabbit) 45003203 Not an eye irritant IV 870.2500 (81 - 5 ) Primary Skin Irritation (rabbit) 45003204 Not a dermal irritant IV 87.2600 (81 - 6) Dermal Sensitization (guinea pig) 45084001 Not a dermal sensitizer N/A **A.2 Toxicity Profiles**  **Table A.2**  **. Toxicity**  **Profile of Novaluron**  **. Guideline No/**  **Study type MRID No.(year)/Doses**  **/C lassification**  **Results** 870.3100 90 - Day oral toxicity rodents 45651504/45651503 (1993/1990) ;

Acceptable/guideline Study I: 0, 50, 100, 200 , or 400 ppm (equivalent to 0, 3.52, 6.93, 13.03 , and 27.77 mg/kg bw

/day , respectively in males and 0, 4.38, 8.64, 17.54 , and 34.39 mg/kg b w/day, respectively in females) Study II: 0, 10, 320 , or 10,000 ppm (equivalent to 0, 0.7, 22.2 , and 713 mg/kg bw/day, respectively in males and 0, 0.8, 24.3 , and 754 mg/kg bw/day, respectively in females) NOAEL = 320 ppm (22.2 mg/kg/day) in males an d 50 ppm (4.38 mg/kg/day) in females . LOAEL = 400 ppm

(27.77 mg/kg/day) in males based on increased occurrence of extramedullary hematopoiesis and hemosiderosis in spleen; and 100 ppm (8.64 mg/kg/day) in females based on reduction in hemoglobin, hematocrit , and RBC count; increased occurrence of extramedullary hematopoiesis in the spleen and hemosiderosis in the spleen and liver.

870.3200 28 - day Dermal Toxicity - rat 45288501 (1998);

0, 75, 400, 1000 mg/kg/day **Acceptable/Guideline** Sy stemic NOAEL = 1000 mg/kg/day; LOAEL = not established . Dermal NOAEL = 1000 mg/kg/day; LOAEL = not established . 870.3700 Prenatal Developmental in rodents - Rat 45082602 (1997);

0, 250, 500, 1000 mg/kg/day **Acceptable/Guideline** Maternal NOAEL = 1000 mg/kg/day ; LOAEL = not established . Developmental NOAEL = 1000 mg/kg/day ; LOAEL = not established .Novaluron DRAFT Human - Health Risk Assessment DP#: 364307

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 54 of 56 **Table A.2**  **. Toxicity**  **Profile of Novaluron**  **. Guideline No/**  **Study type MRID No.(year)/Doses**  **/C lassification**  **Results** 870.3700 Prenatal Developmental in nonrodents Rabbit 45638316, 45638318, 45638317

(1997,1998); 0, 100, 300, 1000 mg/kg/day **Acceptable/Guideline** Maternal NOAEL = 1000 mg/kg/day ; LOAEL = not established. Developmental NOAEL = 1000 mg/kg/day ; LOAEL = not established . 870.3800 Reproduction and fertility - rat 45651505 (Main Study, 1999),

45638319 (Preliminary Study, 1998) ; 0, 1000, 4000 , or 12,000 ppm ; M: 0, 74.2, 297.5 , or 894.9 mg/kg/day F: 0, 84.0, 336.7 , or 1009.8 mg/kg/day **Acceptable/Guideline** Parental NOAEL = Not established; LOAEL (M/F) = 74.2/84.0 mg/kg/day based on increased absolut e and relative spleen weights. Offspring NOAEL = Not established; LOAEL (M/F) = 74.2/84.0 mg/kg/day based on increased absolute and relative spleen weights. Reproductive NOAEL (M/F) = 74.2/1009.8 mg/kg/day; LOAEL (M) = 297.5 mg/kg/day based on decreased epididymal sperm counts and increased age of preputial separation in the F 1 generation ; Reproductive LOAEL for females was not established. 870.4100 Chronic toxicity - dog 45638320 (1999);

0, 10, 100, 1000 mg/kg/day **Acceptable/Guideline** NOAEL = 10 mg/kg/day . LOAEL = 100 mg/kg/day based on hematologic changes associated with histopathological changes in liver and spleen . 870.4300 Chronic/ Carcinogenicity

- rat 45651506 (1995);

0, 25, 700, or 20,000 ppm test material; M: 0, 1.1, 30.6, and 884.2 mg/kg/day F: 0, 1.4, 39.5, and 1113.5 mg/kg/day **Acceptable/Guideline** NOAEL (M/F) = 1.1/1.4 mg/kg/day . LOAEL (M/F) = 30.6/39.5 mg/kg/day based on e rythrocyte damage and turnover resulting in a regenerative mild anemia . 870.4300 Chronic/ Carcinogenicity

- mo use 45651507/45877901 (2000/2003);

0, 30, 450, or 7000 ppm test material; M: 0, 3.6, 53.4, or 800.0 mg/kg/day F: 0, 4.3, 63.3, or 913.4 mg/kg/day **Acceptable/Guideline** NOAEL (M/F) = 3.6/4.3 mg/kg/day . LOAEL (M/F) = 53.4/63.3 mg/kg/day based on increased erythrocyte turnover due to hemoglobin oxidation and resulting in a mild anemia . 870.5100 Salmonella typhimurium and Escherichia coli Reverse Mutation Assay 44961013 (1997) ;

0, 312.5, 625, 1250, 2500, or 5000 μg/plate in the presence and absence of metabolic activation (±S9) **Acceptable/Guideline** Novaluron, tested up to the limit of solubility (2500 μg/plate) and the limit dose (5000 μg/plate), wa s not cytotoxic with or without S9 activation in four S. typhimurium strains and one strain of E. coli , and did not induce a genotoxic response in any strain . 870.5100 Salmonella typhimurium bacterial reverse gene mutation assay 45030003 (1986) ;

0, 10, 33, 100, 333, 1000, or 3333 μg/plate in the presence and absence of mammalian metabolic activation (±S9) Novaluron, tested up to the limit of solubility (3333 μg/plate), was not cytotoxic with or without S9 activation in five S. typhimurium strains, and did not induce a genotoxic response in any strain.Novaluron DRAFT Human - Health Risk Assessment DP#: 364307

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 55 of 56 **Table A.2**  **. Toxicity**  **Profile of Novaluron**  **. Guideline No/**  **Study type MRID No.(year)/Doses**  **/C lassification**  **Results**

**Acceptable/Guideline** 870.5300 Gene Mutation 45638321(1989);

0, 50, 100, 125, 150, 175 , or 200 μg/mL with and without metabolic activation (S9 - mix) in two independent assays. **Acceptable/Guideline** There was no evidence of biologically significant induction of mutant colonies over background .

870.5375 In vitro mammalian chromosome aberration test 44961015 (1992) ;

40, 200, and 1000 μg/mL, with and without metabolic activation (±S9) **Acceptable/Guideline** Novaluron produced no evidence of clastogenic activity in primary human lymphocytes, in the presence or absence of S9 activation . 870.5395 Mammalian erythrocyte micronucleus test in mice 45638322(1989);

0, 1250, 2500 , or 5000 mg/kg body weight **Acceptable/Guideline** There was no statistically significant increase in the frequency of micronucleated polychromatic erythrocytes in mouse bone marrow at any dose or harvest time . 870.5500 Mutagenicity

– Rec assay with Bacillus subtilis 44961014 (1998) ;

50, 150, 500, 1,500, or 5,000 μg/plate, with and without mammalian metabolic activation (±S9) **Acceptable/Guideline** Novaluron was equivocal for bacterial DNA damage in the absence of S9 activation, and negative for bacterial DNA damage in the presence of S 9 activation . 870.5550 Unscheduled DNA Synthesis in HeLa S3 Human Epitheliod cells 45030002 (1988) ;

0.125, 0.25, 0.5, 1, 2, 4, 8, 16, 32, 64, 128, or 256 μg/mL (±S9) **Acceptable/Guideline** Novaluron wa s considered not to show any evidence of causing DNA damage to HeLa S3 epithelioid cells in this unscheduled DNA synthesis test for mutagenic potential . 870.6200 Ac ute Neurotoxicity screening battery - rat 45082601 (1999);

0, 200, 650, 2000 mg novaluro n/kg **Acceptable/Guideline** NOAEL = 650 mg/kg/day; LOAEL = 2000 mg/kg/day based on clinical signs (piloerection, irregular breathing), FOB parameters (increased head swaying, abnormal gait) and neuropathology (sciatic and tibial nerve degeneration). 870.6200 Subchronic Neurotoxicity screening battery - rat 46086204 (2002);

0, 17.5 /20.5 , 174 /207 , 1752 /2000 mg/kg/day (M/F) **Acceptable/Guideline** NOAEL (M/F) = 1752/2000 mg/kg/day; LOAEL = not established .

870.7485 Metabolism - rat 45638401 (2000), 45638323 (1998);

single dose of 2 mg/kg or 1000 mg/kg, or 14 multiple 2 mg/kg/day doses of unlabeled novaluron (Lot no. 970211/4, 99.3% chemical purity) followed by a single dose of radiolabeled novaluron . Novaluron exhibited marginal absorp tion (16 - 18%), relatively rapid and complete excretion within 48 hours primarily via the feces and to a lesser extent via urine in rat. Biliary contribution for fecal excretion appears to be insignificant. Absorption appeared to be approaching saturation at high doses. Peak plasma conce ntrationNovaluron DRAFT Human - Health Risk Assessment DP#: 364307

________________________________________________________________________ ______________________________________________________________________________________________ _____________________

Page 56 of 56 **Table A.2**  **. Toxicity**  **Profile of Novaluron**  **. Guideline No/**  **Study type MRID No.(year)/Doses**  **/C lassification**  **Results**

**Acceptable/Guideline** occurred at 2 - 5 hours. Urinary metabolite profiles revealed 15 components and 8 components following administration of [chlorophenyl 14 C] novaluron or [difluorophenyl 14 C] novaluron , respectively. The most prevalent urinary metabolite was 2,6 - difluorobenzoic acid represented the majority of the urinary radioactivity. Other components individually represented no more than 5.9% of the dose and mo st represented considerably le ss than 1%. Parent compound was the most prevalent contributor in the feces. The fecal metabolite profile revealed two metabolites; 3 - chloro - 4 - (1,1,2 - trifluoro - 2 - trifluoromethoxyethoxy)aniline, and 1 - [3 - chloro - 4 - (1,1,2 - trifluoro - 2 - trifluoromethoxyethoxy)phenyl]urea. Quantitatively, thes e were minor components accounting for <2% of the dose. In the repeated dose group , some tissues such as fat contained measurable radioactivity at 168 hours post dose but did not appear to suggest significant potential for bioaccumulation or sequestration at the doses tested. 870.7600 Rat Dermal Penetration 45638415 (2000);

1.0, 0.067, 0.0048, or 0.0003 mg/cm2 **Acceptable/Guideline** Recovery of administered radioactivity was an acceptable 90.19 - 105.26%. The maximum total absorbed dose (expressed as per cent of administered dose and determined as the sum of radioactivity in excreta, cage wash, untreated skin, fat, blood, and residual carcass) ranged from about 0.5% to 10% of that administered.