UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 Office of Prevention, Pesticides and Toxic Substances July 30, 2002 SUBJECT: Carbaryl: Revised HED Risk Assessment  Public Comment Period, Error Correction Comments Incorporated, DP Barcode: D284580, PC Code: 056801 FROM: Jeffrey L. Dawson, Chemist/ Risk Assessor Reregistration Branch 1 Health Effects Division (7509C)

THRU: Whang Phang, PhD, Branch Senior Scientist Reregistration Branch 1 Health Effects Division (7509C)

TO: Anthony Britten, Chemical Review Manager Reregistration Branch 3 Special Review & Reregistration Division (7508C)

Attached is HED's risk assessment of the insecticide carbaryl for purposes of issuing a Reregistration Eligibility Decision (RED) Document for this active ingredient. This document is based on several disciplinary science chapters which include: Toxicology  D282980; Dietary Exposure D281419 Product and Residue Chemistry  D283328; Occupational and Residential Exposure D281418 and Estimated Environmental Concentrations  D240841. This chapter reflects recent changes in the hazard component based on the submission of additional toxicology studies (reproductive and three 21 day dermal toxicity studies); changes in endpoint selection; revision of the Q1* for cancer risk assessment; and a reduction in the FQPA SF from 10 to 1. Modifications to the occupational and residential assessment includes changes in the calculations for pet uses; the use of recently submitted ARTF transfer coefficients for greenhouse crops; and changes to the updated duration policy for delineating short and intermediate term exposures. Also, mosquito adulticide and carbaryl use on oyster beds in Washington state have been quantitatively addressed. Modifications to the dietary risk assessment include: the use of updated processing factors; deletion of some use patterns; and the use of additional residue data. This document also addresses error correction comments raised by Aventis Crop Sciences included in the document Human Health Risk Assessment and Supporting Documents Phase 1 Error Correction (July 12, 2002) that were submitted on the previous version of this assessment (D281420, Dated June 7, 2002).

Reviewers: RARC (6/ 6/ 01 Report), Revision (6/ 7/ 02) Reviewed By Paula Deschamp HUMAN HEALTH RISK ASSESSMENT Carbaryl U. S. Environmental Protection Agency Office of Pesticide Programs Health Effects Division (7509C) Jeffrey L. Dawson, Chemist/ Risk Assessor Date: July 30, 2002 HUMAN HEALTH RISK ASSESSMENT Carbaryl Risk Assessment Team:

Risk Assessor: Jeffrey L. Dawson,

Dietary Risk: Felecia Fort Product and Residue Chemistry: Felecia Fort Occupational and Residential Exposure: Jeffrey L. Dawson Epidemiology: Jerome Blondell, MPH, PhD Monica Spann, MPH Virginia Dobozy, VMD, MPH Toxicology: Virginia Dobozy, VMD, MPH Drinking Water Estimates: R. David Jones, Ph. D. E. Laurence Libelo, Ph. D. Table of Contents 1. 0 EXECUTIVE SUMMARY...................................................... 5 2.0 PHYSICAL/ CHEMICAL PROPERTIES CHARACTERIZATION ..................... 17 2. 1 Chemical Structure and Identification....................................... 17 2. 2 Physical Properties of Carbaryl ............................................ 18 3. 0 HAZARD CHARACTERIZATION .............................................. 19 3.1 Hazard Profile ......................................................... 19 3. 2 FQPA Considerations ................................................... 22 3.2.1 Determination of Susceptibility ...................................... 22 3.2.2 Degree of Concern Analysis and Residual Uncertainties .................. 23 3.3 Dose Response Assessment ............................................... 24 3.4 Endocrine Disruption .................................................... 26 4.0 NON OCCUPATIONAL RISK ASSESSMENT AND CHARACTERIZATION ........... 27 4. 1 Summary of Registered Uses.............................................. 27 4.2 Dietary Risk Assessment ................................................. 31 4.2.1 Residue Profile ................................................... 32 4.2.2 Acute Dietary Risk Assessment ...................................... 34 4.2.3 Chronic Dietary Risk Assessment .................................... 37 4.2.4 Cancer Dietary Risk Assessment ..................................... 38 4.2.5 Characterization/ Uncertainties of the Dietary Risk Estimates .............. 38 4. 3 Estimated Environmental Concentrations In Water ............................ 39 4.3.1 Environmental Fate Characteristics ................................... 39 4.3.2 Monitoring Data .................................................. 40 4.3.3 Modeling EECs .................................................. 41 4. 4 Residential Risk Assessment .............................................. 43 4.4.1 Home Uses ...................................................... 44 4.4.2 Residential Handler Risk Assessment ................................. 44 <IP_ADDRESS> Residential Handler Noncancer Risks ........................... 47 <IP_ADDRESS> Residential Handler Cancer Risks .............................. 51 4.4.3 Residential Postapplication Risk Assessment ........................... 54 <IP_ADDRESS> Residential Postapplication Exposure and Noncancer Risks .......... 59 <IP_ADDRESS> Residential Postapplication Exposure and Risks For Cancer ......... 65 4.4.4 Residential Risk Characterization .................................... 66 4.4.5 Exposure from the Use of Tobacco ................................... 69 4.4.6 Other Residential Exposures ........................................ 69 5.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION ............. 70 5. 1 Calculation of Aggregate Risks and DWLOCs ................................ 70 5. 2 Acute Dietary Aggregate Risks and DWLOCs ................................ 73 5. 3 Chronic Dietary Aggregate Risks and DWLOCs .............................. 73 5. 4 Short term Aggregate Risks and DWLOCs................................... 74 5. 5 Intermediate term Aggregate Risks and DWLOCs............................. 75 5. 6 Aggregate Cancer Risks and DWLOCs...................................... 76 5. 7 Summary of Aggregate Risks ............................................. 77 6. 0 CUMULATIVE RISK......................................................... 78 7.0 OCCUPATIONAL RISK ASSESSMENT ......................................... 79 7. 1 Occupational Handler Risk Assessment ..................................... 79 7.1.1 Occupational Handler Non Cancer Risks .............................. 84 7.1.2 Occupational Handler Cancer Risks .................................. 88 7.2 Postapplication Exposures and Risks ....................................... 92 7.2.1 Occupational Postapplication Noncancer Risks ......................... 95 7.2.2 Occupational Postapplication Exposure and Risk Estimates for Cancer ....... 98 7. 3 Occupational Risk Characterization ....................................... 101 8.0 HUMAN AND DOMESTIC ANIMAL INCIDENT DATA REVIEW .................. 104 9.0 DATA NEEDS .............................................................. 105 APPENDIX 1: Toxicology Profile APPENDIX 2: Incident Review 5 1.0 EXECUTIVE SUMMARY The Health Effects Division (HED) of EPA's Office of Pesticide Programs has evaluated the carbaryl database and conducted a human health risk assessment for the reregistration of the chemical. Carbaryl is a list A reregistration chemical. Carbaryl is also subject to court specified deadlines resulting from a Natural Resources Defense Council (NRDC) petition of the Agency. This assessment incorporates error corrections and begins phase 3 of the public participation process.

Use Patterns:

Carbaryl [1 napthyl methylcarbamate] is one of the most widely used broadspectrum insecticides in agriculture, professional turf management, professional ornamental production, and in the residential pet, lawn and garden markets. Carbaryl formulations include baits, dusts, pet collars, flowable concentrates, emulsifiable concentrates, granulars, soluble concentrates, and wettable powders. Carbaryl is used in agriculture to control pests on terrestrial food crops including fruit and nut trees (e. g., apples, pears, almonds, walnuts, and citrus), many types of fruit and vegetables (e. g., cucumbers, tomatoes, lettuce, blackberries, and grapes), and grain crops (e. g., corn, rice, sorghum, and wheat). Carbaryl is also used for direct animal treatments to control pests on companion animals such as dogs and cats. There are other uses for ornamentals and turf, including production facilities such as greenhouses, golf courses, and residential sites that can be treated by professional applicators (e. g., annuals, perennials, shrubs). Carbaryl can also be used by homeowners on lawns, for home and garden uses, and on companion animals. There are no labels for indoor uses within a residence. In agriculture, groundboom, airblast, and aerial applications are typical. Other applications can also be made using handheld equipment such as low pressure handwand sprayers, backpack sprayers, and turfguns. Homeowners can also use other types of application equipment including trigger sprayers, hose end sprayers, and ready to use dust packaging. Information on uses and application rates used in the risk assessment was provided by the registrant, Aventis Crop Science, at a SMART meeting on September 21, 1998 and from a review of current labels. The Agency's Biological and Economic Analysis Division has also concurred with the use patterns which serve as the basis for this assessment. Carbaryl also has more specialized uses that can lead to exposures in the general population such as an adulticide for mosquito control and for Ghost and Mud shrimp control in oyster beds in Washington State. These use patterns were also considered in this assessment.

Hazard Characterization:

Carbaryl is a carbamate insecticide where the mode of toxic action is through cholinesterase inhibition (ChEI). In most of the toxicology studies in which ChEI activity was measured, it was the endpoint used for setting the No Observed Adverse Effect Level (NOAEL) for risk assessment, the dose at which no adverse effects were observed. There was one exception; for chronic duration exposures, a NOAEL could not be defined in the toxicology study deemed most appropriate (i. e., chronic dog toxicity) so a Lowest Observed Adverse Effect Level (LOAEL), the dose at which the first adverse 6 effects were observed, was used for risk assessment purposes. Carbaryl is relatively acutely toxic by the oral route (Toxicity Category II) but has relatively low acute toxicity by the dermal and inhalation routes. It is not a dermal or eye irritant or a dermal sensitizer; however, there are reports of dermal irritation and dermal manifestations of an allergic response in humans exposed to carbaryl.

The Agency is required by the Food Quality Protection Act to consider the special sensitivities of various susceptible populations such as infants and children. Current Agency policy retains the factor using criteria based on exposure and toxicity considerations. For carbaryl, a traditional factor of 3 was applied only to chronic duration exposures to account for the lack of a NOAEL in the selected chronic dog toxicity study (i. e., the use of a LOAEL). The Agency decided that the special FQPA Safety Factor should be reduced to 1 and that this was adequate to protect susceptible populations because there are no residual uncertainties in the exposure databases, the toxicology database is complete, and the endpoint and NOAELs for risk assessment were well defined. Dietary exposures were calculated using FDA and PDP monitoring data, a carbamate market basket survey, and percent crop treated information. Residential exposures were calculated using a number of carbaryl specific studies. In the toxicology database, no quantitative or qualitative evidence of increased susceptibility in rat or rabbit fetuses following in utero exposure in the standard developmental studies was observed. There was a low level of concern for evidence of susceptibility seen in the developmental neurotoxicity study, and there was evidence of increased susceptibility in offspring in the 2 generation reproduction study. However, the Agency believes that the acute and chronic RfDs would be protective of these effects so the special FQPA safety factor was reduced to 1.

Carbaryl has been classified as a Group C possible human carcinogen based on an increased incidence of hemangiosarcomas and combined hemangiomas/ hemangiosarcomas in CD 1 mice at 100 ppm and above (15 and 18 mg/ kg/ day for males and females, respectively). Mechanistic metabolism studies and a study in heterozygous p53 deficient mice were considered inadequate to demonstrate a mode of action for the vascular tumors. Therefore, a linear low dose extrapolation approach was used for risk assessment; the Q1* is 8.75 x 10 4 (mg/ kg/ day) 1 based on the mouse vascular tumors according to the February 2002 Cancer Assessment Review Committee (CARC) report. Also, CARC concluded that there is a concern for mutagenicity because carbaryl has been observed to be clastogenic in vitro. However, this concern is lessened because of a lack of effects observed in vivo (i. e., micronuclei induction and chromosome aberration studies were negative).

Endpoints for acute and chronic dietary exposure risk assessments were selected by the HED Hazard Identification Assessment Review Committee (HIARC). The toxicity endpoints selected for risk assessment are neurotoxic effects associated with the inhibition of ChEI. The dose level used for the acute dietary risk assessment was a NOAEL which was defined in a developmental neurotoxicity study conducted with rats (1 mg/ kg/ day). The dose level used for the chronic dietary risk assessment was a LOAEL which was defined in a chronic dog feeding study (3.1 mg/ kg/ day). Because a NOAEL could not be defined in the chronic study, an additional factor of 3x was added to the customary 100x factor (i. e., 10x for extrapolation from animal studies to humans and 10x for intraspecies variation between the test animals and humans) to account for the uncertainty associated with a lack of a NOAEL. The acute and chronic reference doses (RfD) were 0.01 mg/ kg/ day (i. e., dose/ 100 for acute and dose/ 300 for chronic). The Population Adjusted Dose (PAD) is a modification of the acute or chronic RfD to 7 accommodate the FQPA safety factor and is calculated by dividing the RfD by the FQPA safety factor. The PADs are the values used for the acute and chronic dietary risk calculations. The Special FQPA Safety Factor was reduced to 1 as described above. Therefore, the aPAD and cPAD (i. e., PAD values for acute and chronic dietary exposures, respectively) are both 0.01 mg/ kg/ day.

There are many potential ways people can be exposed to carbaryl in occupational and residential settings. The Agency considers exposures for those involved in the application of carbaryl (i. e., handlers) and those who can come into contact with carbaryl residues after application (i. e., reentry or postapplication). Both cancer and non cancer risk assessments were conducted for residential handlers and for people in the general population who might be exposed postapplication from lawn, garden, or pet uses of carbaryl or from more specialized uses such as mosquito adulticide applications and uses on oyster beds in Washington state. Similarly, both handler and postapplication risks were calculated for those people who could be exposed as part of their jobs such as a grower treating their crop or someone harvesting fruit. Endpoints for occupational and residential exposures from various routes (i. e., dermal, inhalation, and incidental oral) and differing durations (i. e., short term, intermediate term, and chronic) were selected by the HIARC. Based on current policy, short term exposure was defined as 1 to 30 days, intermediate term exposures as 30 days to several months, and chronic exposures as several months to a lifetime. [Note: Not all routes and durations are applicable to each population.] The toxicity endpoints selected for these carbaryl risk assessments are again based on neurotoxic effects associated with the inhibition of ChEI. The short and intermediate term dermal risk assessments for carbaryl are based on NOAEL of 20 mg/ kg/ day defined in a dermal toxicity study in rats using technical material where decreases in red blood cell cholinesterase in males and females and brain cholinesterase in males were observed. The short term inhalation and nondietary ingestion risk assessments for carbaryl are based on a NOAEL of 1 mg/ kg/ day which was defined in a developmental neurotoxicity study in rats where alterations in FOB measurements and cholinesterase inhibition (plasma, whole blood, and brain) were observed. The intermediate term inhalation and nondietary ingestion risk assessments are based on a NOAEL of 1 mg/ kg/ day that was defined in a subchronic neurotoxicity study in rats. The chronic risk assessments, regardless of how exposures occur (e. g., skin or inhaled) are based on a LOAEL of 3.1 mg/ kg/ day that was defined in a 1 year dog feeding study. In some assessments, a dermal absorption factor is required. A rat dermal absorption study using radiolabeled 14 C carbaryl was used to define a factor of 12.7 percent; this value was used to calculate the oral equivalent dermal dose for noncancer chronic duration exposures and for the calculation of cancer risks. No inhalation toxicity studies were available for risk assessment purposes so a route to route extrapolation was used to address risks from inhalation exposures. No inhalation absorption study was conducted; therefore, a 100 percent inhalation absorption factor has been used to convert all inhalation exposures to an oral equivalent inhalation dose.

Dietary Risk Estimates:

Potential dietary exposure to carbaryl occurs through food and water. Tolerances for residues of carbaryl are currently expressed in terms of carbaryl and its hydrolysis product, 1 naphthol (calculated as carbaryl) for most raw agricultural commodities. However, HED is recommending that carbaryl per se be regulated in plants. In livestock commodities, carbaryl; 5,6 dihydro 5,6 dihydroxy carbaryl; and 1 At the present time, information from the industry sponsored Carbamate Market Basket Survey has been approved for use in dietary risk assessments with appropriate characterization of uncertainties associated with the conduct of the study. The primary concern was rubbing sampled commodities during the rinsing process except for broccoli and tomato because this created a potential for residue loss from the mechanical action associated with rubbing. A separate assessment was also completed using other sources of high quality residue data (e. g., PDP) for comparative purposes to more completely inform the risk management process.

8 5 methoxy 6 hydroxy carbaryl and all residues which can be hydrolyzed to carbaryl, 5,6 dihydro 5,6 dihydroxy carbaryl, or 5 methoxy 6 hydroxy carbaryl under acidic conditions should be included in the tolerance expression and risk assessment for all endpoints of dietary concern. Once the tolerances for plants are revised, they will be compatible with Codex MRLs except for livestock commodities.

A Tier 3/ 4 dietary risk assessment, which is the most highly refined assessment possible at this time, was conducted. Both acute and chronic dietary risk assessments were conducted. Dietary exposure was determined, considering the level of carbaryl residue on food commodities and their potential consumption by multiple subpopulations. Dietary risk was then calculated by comparing dietary exposure to the acute or chronic PADs. Data on anticipated carbaryl residues were determined based mainly on USDA Pesticide Data Program (PDP) and Food and Drug Administration (FDA) monitoring data. Field trial data were used for certain commodities. In addition, separate acute assessments were conducted incorporating the results of the Carbamate Market Basket Survey (CMBS). 1 The percentage of the crop treated (estimated maximum percentage and weighted average percentage for the acute and chronic analyses, respectively) was also considered. Food consumption data were from 2 of USDA's Continuing Surveys of Food Intakes by Individuals (CSFII) which ranged from 1989 to 1992 and from 1994 to 1998. The 1994 to 1998 data were included based on comments from the registrant, Aventis Crop Science, for comparative purposes (1989 to 1992 are normally used for risk assessment). In these surveys, 3 day mean consumption and single day consumption information were recorded for 22 demographic and socio economic subpopulations, including infants, children, and nursing women. Dietary risk assessments were conducted using the Dietary Exposure Evaluation Model (DEEM™), which incorporates exposure and consumption data to calculate risk as a percentage of the PAD. Values greater than 100 percent of the PAD exceed HED's level of concern.

Estimated acute dietary exposure for carbaryl at the 99.9 th percentile using the 1989 to 1992 CFSII data exceeds HED's level of concern for some population subgroups when CMBS data are not used and are not of concern when the CMBS are incorporated. The results of the acute dietary assessment when CMBS data have not been used indicate risks are greater than 100 percent of the aPAD for all infants (< 1 year old) and children (1 6 years old) at the 99.9 th percentile of exposure (133 % and 110% of aPAD, respectively). When CMBS data were incorporated, the highest exposed subpopulation was children (1 6 years old) at 75 percent of the aPAD. A sensitivity analysis was completed by the Agency (not using the CMBS) to evaluate the impacts of eliminating apples or peaches from the analysis and eliminating commodities with no detectable residues. Eliminating peaches appears to have the most impact as all infants in this analysis consume 72 percent of the aPAD but children (1 6 years old) still consume just over 100 percent of the aPAD (i. e., 102 percent). One comment from Aventis Crop Science was that 1994 to 1998 CFSII food consumption data should be used rather than 1989 to 1992 data. Results for most subpopulations were actually slightly worse (i. e., generally, 5 to 10 percent 9 more of the aPAD was consumed) if the 1994 to 1998 CFSII data were used.

Estimated chronic dietary risks for all population subgroups are not of concern. Estimated chronic dietary exposures for all population subgroups consumed <1 percent of the cPAD. The CMBS data were not used in this analysis because risks are low and CMBS is single serving data.

The cancer dietary exposure assessment was conducted using the Q 1* approach (i. e., linear, low dose extrapolation). Dietary exposure is determined from consumption and residue data, as was done for the acute and chronic dietary assessments. The food exposure is then multiplied by the Q 1* (8.75 x 10 4 ) (mg/ kg/ day) 1 for carbaryl to determine the increased risk of cancer from consuming carbaryl residues in food over a lifetime (70 years). Risks estimates above 1 x 10 6 are of concern. Results indicate a maximum lifetime risk of 2.8 X 10 8 for the general US population.

Concentrations in Water:

Monitoring data for carbaryl residues in ground and surface water are available, but they are of limited utility in developing estimated environmental concentrations (EECs) for the aggregate dietary (food and water) risk assessment. Therefore, computer modeling was used to estimate surface (PRZM 3.12 and EXAMS 2.97.7) and ground (SCI GROW) water concentrations expected from normal agricultural use. These model estimates were compared to drinking water levels of concern (DWLOCs), the theoretical concentration of pesticide in drinking water that would be an acceptable upper limit in light of the aggregate exposure to that pesticide from other sources (food and residential use). The maximum calculated acute and chronic surface water EECs (494 ppb and 28 ppb, respectively) resulted from use on citrus in Florida. In Florida, the majority of drinking water is derived from groundwater (> 90%) so high surface water concentrations do not necessarily indicate high exposure. As a result, both Florida and the results for Oregon apples (the next highest EECs) have been considered in the aggregate assessment (144 and 9 ppb for acute and chronic, respectively). Groundwater EECs for the acute and chronic assessments were both 0.8 ppb as calculated with SCI GROW.

Use of Consumer Products (Residential Handlers):

The noncancer risks of short term dermal and inhalation exposure to residential handlers were calculated using Margins of Exposure (MOEs) in which the doses were selected from the 21 day dermal toxicology study using technical material and the developmental neurotoxicity study, respectively. The target (acceptable) MOE for residential short term risk assessments is 100 based on the customary 100x uncertainty factor (i. e., 10x for inter and 10x for intra species) and the FQPA Safety Factor of 1. Calculated MOEs that equal or exceed the target MOE of 100 are not of concern. Combined (dermal and inhalation) risks were calculated for 17 scenarios (i. e., 52 site/ area/ rate combinations within those scenarios) considered representative of the residential uses, application rates and application equipment on carbaryl labels. For residential handlers, MOEs associated with most (40 of 52 considered) are 10 generally not of concern because they exceed the Agency's target MOEs for noncancer risk assessments (i. e., MOE = 100). The scenarios of concern involve the use of dusts (in gardens and on pets) and for some liquid sprays on gardens.

The risk of cancer in residential handlers was calculated considering one application of carbaryl per year for 50 years. The annual frequency for use was reported to be 1 to 2 times per year (60 th percentile) and 5 times per year (84 th percentile) by the registrant, the Aventis Crop Science, at the SMART meeting held with the Agency. Risks were calculated by multiplying the Lifetime Average Daily Dose (LADD), which represents dermal and inhalation exposure amortized over a lifetime, by the Q1*. The risk considered acceptable is 1 x 10 6 , which means that an individual receiving a lifetime exposure to a pesticide increases their chance of developing cancer by one in a million. Based on a single day of exposure, cancer risks for most scenarios are in the 10 8 to 10 10 range although there is one scenario where the risk exceeds 1x10 6 (dusting dogs) even for a single day of use. Cancer risks have also been calculated using another approach where the number of days per year of exposure required to exceed a risk of 1x10 6 has been defined. There are 5 scenarios where the allowable days per year of exposure is less than or equal to 5 which should be considered in conjunction with the use/ usage data from Aventis Crop Science that indicates 5 uses per year is the 84 th percentile. In all cases, cancer risk estimates require less restrictive risk mitigation measures than do the corresponding results for noncancer concerns (i. e., noncancer risks appear to be driving the need for risk mitigation).

Residential Postapplication Exposures:

HED considered a number of residential postapplication exposure scenarios for toddlers, youthaged children and adults. Short term and intermediate term risks from declining residues were calculated for multiple scenarios, including exposures to treated lawns (toddlers and adults), golf courses (adults), gardens (adults and youth aged children) and pets (toddlers). Exposures from more limited uses such as a mosquito adulticide and for use in oyster beds were also considered. Short and intermediate term dermal risks were calculated using the NOAEL from the 21 day dermal toxicity study (i. e., 20 mg/ kg/ day). Risks from short and intermediate term nondietary ingestion (e. g., mouthing behaviors) were calculated using NOAELs from the developmental neurotoxicity study in rats and the subchronic neurotoxicity study in rats where the NOAELs both happen to be 1 mg/ kg/ day. The target MOE is also 100 for all scenarios considered. MOEs were calculated over the amount of time it took residues to dissipate or out to a 30 day interval whichever applied depending upon the data. Short term MOEs were calculated based on the residue concentrations for each day while intermediate term risks were calculated using a 30 day average. The Agency has short term risk concerns for exposures to adults doing heavy yardwork, for toddlers playing on treated lawns, and for toddlers that have contact with treated pets. Activities associated with home gardening (e. g., harvesting) and golfing for adults, home gardening for youth aged children or any age or activity considered in the adulticide mosquito control or oyster assessment do not have risk concerns even on the day of application (i. e., MOEs $ 100 on the day of application). For adults, the MOEs for heavy yardwork do not meet or exceed risk targets (i. e., MOE $ 100) up to 5 days after application. For toddlers, the Agency has concerns for pet treatments and also for lawn uses. In fact, pet uses never reach acceptable levels even 30 days after application and not until 18 days at the maximum application rate considered on turf. Toddler MOEs from pet and turf uses represent total exposures from multiple pathways. For the pet uses, dermal and 11 hand to mouth exposures essentially both equally contribute to the overall estimate. For the turf uses, dermal and hand to mouth exposures are also the key contributors to the overall estimates. The Agency does not have intermediate term risk concerns for adults and youth aged children for any of the uses considered including lawncare, home gardens, golfing, and any aspect of adulticide mosquito control or uses in oyster beds. In contrast, the Agency does have intermediate term risk concerns for all toddler exposure scenarios considered (i. e., pet treatments and lawncare uses). As with the short term MOEs, pet and turf uses represent total exposures where the significant contributions to overall exposures are again made equally from the dermal and hand to mouth exposure pathways.

Ingestion of carbaryl granules is also a potential source of exposure because children can eat them if they are found in treated lawns or gardens. This scenario is considered episodic by the Agency and is generally not recommended as a basis for risk management decisions. For illustrative purposes, if one considers a 2 percent formulation and the density of soil (0.67 mL/ gram, many granulars are claybased), only 0.005 mL of formulation would need to be ingested to have a risk concern (i. e., 7.5 mg * 1g/ 1000mg * 0.67 mL/ gram). [Note: This volume is orders of magnitude less than a teaspoon of granular formulation (i. e., 0.1% of a teaspoon where a tsp. = 5 mL).]

Use in Tobacco:

In addition to the routine residential risk assessment, HED calculated the risks of carbaryl exposure in tobacco because a pyrolysis study was submitted by the registrant that quantified residues of carbaryl at a level of 44.58 ppm in tobacco smoke (side stream and main stream combined). Since this is a composited sample of main stream and side stream smoke, it greatly exaggerates the actual exposure to the smoker, whose primary route of exposure is via main stream smoke. HED further assumed that 100 percent inhaled is absorbed (i. e., that none of the residue is exhaled along with the smoke). The MOE for consuming 15 cigarettes per day is 104 even with the conservative basis of the assessment.

Aggregate Risks and DWLOCs:

The Food Quality Protection Act requires that the Agency consider exposures from different sources (i. e., food water, and residential) that results in an aggregate risk for each chemical. Aggregate risks are calculated by considering food or food and residential (depends upon the specific scenario), subtracting these from the allowable exposure limit, and, if the exposure limit has not been exceeded, then calculating Drinking Water Levels of Concern (DWLOCs) to compare to surface or groundwater Estimated Environmental Concentrations (EECs). In many residential scenarios, MOEs exceed the Agency's risk targets making the calculation of DWLOCs and aggregate risks for those scenarios inappropriate because the allowable exposure limits have already been exceeded. Additionally, acute dietary risks were also exceeded for infants and children (1 to 6 years old) at the 99.9 th percentile when the Carbamate Market Basket Survey (CMBS) was not considered in the assessment (133 % of aPAD). However, the risk picture could substantively change if residential risks are refined based on updated use information from the carbaryl use survey yet to be submitted to the Agency, and the Agency uses the CMBS data even with the caveats associated with that study. Keeping this in mind, the Agency completed DWLOC 12 and aggregate risk calculations for illustrative purposes using a number of representative exposure scenarios where the residential and dietary risk estimates did not already exceed the Agency's level of concern. For example, an acute assessment with CMBS data and short term assessments where residential handler risks weren't already of concern were completed.

The acute aggregate assessment indicates that even with the use of the CMBS, aggregate risks when surface water is the source of drinking water, are still of concern for all infants, children (1 to 6 years old) and children (7 to 12 years old) regardless of whether or not Florida citrus or Oregon apple EECs are used. If Florida citrus surface water EECs are solely considered, aggregate risks are of concern for all subpopulations. [Note: For characterization of the EECs, surface water EECs for Florida citrus exceed exposure limits alone without even considering corresponding food intakes for all populations. Additionally, the surface water EECs for Oregon apples alone also exceed exposure limits, even without including food intakes, for infants and children.] Acute aggregate risks for all subpopulations are not of concern if groundwater is the source of drinking water. Chronic aggregate risks were not of concern for any subpopulation regardless of the source of drinking water, even considering the Florida surface water EECs. In the short term assessment, the Agency selected representative scenarios where residential risks alone were not of concern including mosquito control, oyster harvesting, golfing, garden harvest, and several handler scenarios (handlers all at average rates, max rate scenarios were of concern for residential exposures alone). If surface water EECs based on Oregon apples or groundwater EECs from SciGrow are considered, aggregate risks are not of concern for the selected scenarios. If EECs from Florida citrus are considered, aggregate risks are not of concern for the selected scenarios except for application of dusts to gardens. Separate intermediate term aggregate risk and DWLOC calculations were not completed for carbaryl because the short term aggregate risk estimates essentially present the same results since the hazard inputs are numerically identical. The only major differences would be the postapplication results where, instead of a single day exposure estimate, the exposures represent a 30 day average (i. e., risks would be accordingly lower since an average rather than a single high end day was considered). Aggregate cancer risks were not of concern for any subpopulation regardless of the source of drinking water, even considering the Florida surface water EECs.

Cumulative Risks:

Carbaryl is a member of the carbamate class of pesticides. This class also includes the aldicarb, methomyl and oxamyl among others. HED did not perform a cumulative risk assessment as part of this reregistration review for carbaryl because HED has not yet initiated a review to determine if there are any other chemical substances that have a mechanism of toxicity common with that of carbaryl. For purposes of this reregistration decision, EPA has assumed that carbaryl does not have a common mechanism of toxicity with other substances. 13 Occupational Handlers:

There is significant potential for exposure to carbaryl users in a variety of agricultural and commercial settings. Tasks associated with occupational carbaryl use include mixing, loading and applying the chemical or guiding aerial applications (flaggers). All these activities are collectively referred to as handler tasks. A total of 28 scenarios were considered representative of the range of handler activities, crops or acres treated and equipment used. The risks from short and intermediateterm dermal exposures and short and intermediate term inhalation exposures in these scenarios were calculated and then added together to obtain overall risk estimates at varying levels of personal protection. The target MOEs were 100 for short term and intermediate term exposures. [Note: Does not include FQPA Safety Factors as they are not applicable to occupational exposures.] Risks from longterm (chronic) exposures were also calculated for a limited number of scenarios in the ornamental/ greenhouse industry. The short and intermediate term risk assessments were conducted, as described above. The long term risk assessment for carbaryl was based on a 1 year dog feeding study where effects (ChEI) were observed at 3.1 mg/ kg/ day (LOAEL). The target MOE was 300 (customary 100x plus 3x for use of LOAEL). Risks were calculated assuming one of eight possible levels of personal protection equipment, ranging from a baseline of typical work clothing (long sleeved shirt and long pants, no respiratory protection and no chemical resistant gloves) to engineering controls, such as a closed cab or closed loading system. Current carbaryl labels typically require that handlers wear long pants, long sleeved shirts, and gloves but do not require respirators. For most scenarios, the noncancer risks for this personal protection ensemble do not meet Agency risk requirements and additional levels of personal protection are required to achieve Agency risk targets. In fact, in many cases engineering controls such as closed loading systems or closed cab tractors are needed. The Agency does have risk concerns over the use of carbaryl in some agricultural and other occupational settings regardless of the level of personal protection used (i. e., MOEs at any level of personal protection are <targets). As would be expected, these scenarios with the highest associated risk also have high daily chemical use amounts based on application rates or high acreages treated or the exposures for the scenarios in question are relatively high. Generally, the areas that appear to be problematic include: large acreage aerial and chemigation applications in agriculture or for wide area treatments such as mosquito control; airblast applications at higher rates; pet grooming; and the use of certain handheld equipment for applications to turf or gardens (e. g., bellygrinder). This general trend was essentially the same for exposures of any duration. Several data gaps were also identified in many different use areas that include: dust use for animal grooming and in agriculture; various specialized hand equipment application methods (e. g., powered backpack, power hand fogger, and tree injection); and nursery operations such as seedling dips.

The risk of cancer for occupational handlers was calculated for two populations, private growers (10 applications per year) and commercial applicators (30 applications per year), using the same 28 scenarios. According to Agency policy, acceptable cancer risks for occupational exposure to pesticides can vary from 1x10 4 to 1x10 6 , depending on the course of action taken by the Agency as outlined in the 2 The Agency has defined a range of acceptable cancer risks based on a policy memorandum dated August 14, 1996, by Office of Pesticide Programs Director Dan Barolo. This memo refers to a predetermined quantified "level of concern" for occupational carcinogenic risk. Occupational carcinogenic risks that are 1 x 10 6 or lower require no risk management action. For those chemicals subject to reregistration, the Agency is to carefully examine uses with estimated risks in the 10 6 to 10 4 range to seek ways of cost effectively reducing risks. If carcinogenic risks are in this range for occupational handlers, increased levels of personal protection are warranted as is commonly applied with noncancer risk estimates (e. g., additional PPE or engineering controls). Carcinogenic risks that remain above 1.0 x 10 4 at the highest level of mitigation appropriate for that scenario remain a concern.

14 the subject policy 2 . Risks for corresponding scenarios based on cancer concerns were generally less than the corresponding noncancer results across all scenarios. In fact, in all but one scenario, cancer risks were <1x10 4 at current carbaryl label requirements of single layer clothing, gloves, and no respirator for both private growers and commercial applicators (i. e., mixing/ loading wettable powders for wide area aerial applications). Higher levels of personal protection reduce this risk to <1x10 4 in both populations. If a 1x10 6 risk level is specified as a concern, results are similar in that risks for a majority of scenarios are <1x10 6 at current label requirements. In fact, only 8 of the 128 scenarios considered for private applicators have cancer risks >1x10 6 (and less than 1x10 4 ) even with the most protective ensembles of protective clothing or engineering controls. For commercial applicators, results indicate that risks for about half of the scenarios considered are <1x10 6 at current label requirements and that only 21 of the 128 scenarios considered have cancer risks >1x10 6 (and less than 1x10 4 ) even with the most protective ensembles of either protective clothing or engineering controls.

Occupational Postapplication (Reentry Workers):

Workers can be exposed to carbaryl residues when entering previously treated areas to perform certain activities, such as harvesting. Current label requirements specify 12 hour Restricted Entry Intervals (REIs) while Pre Harvest Intervals (PHIs) are less than 7 days for most crops with some as long as 28 days. Non cancer risks from short and intermediate term dermal postapplication exposure were calculated for 18 representative crop groupings using the MOE approach. The risks from long term dermal exposures were calculated for only a limited number of scenarios in the greenhouse and floriculture industries. For each scenario, the risk on the day of application was calculated, along with the time required to reach the target MOE, allowing for dissipation of the carbaryl residues. For all but the lowest exposure scenarios in some crops, MOEs do not meet or exceed target MOEs until several days after application. If short term risks are considered, MOEs meet or exceed target MOEs generally in the range of 3 to 5 days after application for lower to medium exposure activities and from 8 to 12 days after application in most higher exposure scenarios. If intermediate term risks are considered, MOEs are not of concern based on a 30 day average exposures except for higher level exposures such as harvesting in some crops. Chronic exposures are of concern for the cut flower industry but not for other general greenhouse and nursery production activities based on the most recent data.

Cancer risks were calculated for private growers and professional farmworkers with the only difference being the annual frequency of exposure days. Cancer risks for private growers and commercial farmworkers are generally in the 10 8 to 10 6 range on the day of application. If a 1x10 4 cancer risk is the target, the current REI would be adequate for all scenarios considered in the 15 assessment. If a 1x10 6 cancer risk is used, then durations longer than the current REI should be considered for some cases which are not considered low to medium exposures. It should be noted that the cancer risk calculations are less restrictive than noncancer risk estimates for the same scenarios in all cases. Many mechanized or partially mechanized processes are possibly associated with the use of carbaryl that may limit or eliminate exposures (e. g., combines for grain harvest).

Human and Domestic Animal Incidents:

HED evaluated reports of human carbaryl poisonings and adverse reactions associated with its use from the following sources: OPP Incident Data System (IDS); Poison Control Centers' Toxic Exposure Surveillance System; California Department of Pesticide Regulation; the National Pesticide Telecommunications Network (NPTN); open literature; and an unpublished study submitted by the registrant. The data from IDS indicated that a majority of cases from carbaryl exposure involved dermal reactions. A number of other cases involved asthmatics and people who experienced hives and other allergic type reactions. It is noted that the dermal sensitization study in the guinea pig was negative. Reports of allergic type reactions in humans could be evidence of a difference in species sensitivity or could be attributable to inert ingredients in the marketed formulations. It is recommended that labels for products should advise that carbaryl can cause sensitizing effects in some people. According to California data, about half of the cases involved skin and eye effects in handlers. About a quarter of the skin reactions were due to workers that were exposed to residues on crops. Reports from the literature are very limited but tend to support the finding that carbaryl has irritant properties. The Poison Control Center cases involving non occupational adults and older children showed an increased risk in five of the six measures used for comparing carbaryl incidents to all other pesticides. The carbaryl cases were almost twice as likely to require serious health care (hospitalization or treatment in a critical care unit) and were two and a half times more likely to experience major medical outcome (life threatening effects or significant residual disability) than other pesticides. This pattern of increased risk was not seen among occupational reports or in young children. This may mean that careless handling by non professionals is a particular hazard. Five case report studies suggested that carbaryl may be a cause of chronic neurological or psychological problems. Some of these effects appear to be consistent with those reported from organophosphate poisoning. However, unlike organophosphates, no controlled studies have been undertaken. If such effects occur as a result of over exposure to carbaryl, they appear to be relatively rare. The effects reported among the five case reports are too inconsistent to draw any conclusions, but do suggest the need for further study. The epidemiologic study submitted by the registrant compared mortality rates in plant workers exposed to carbaryl to the general population. HED concluded that the sample of workers was too small and the period of follow up too short to permit definitive conclusions.

The incident reports on domestic animals in IDS were evaluated. Based on limited data, there is some evidence that young kittens may be susceptible to adverse reactions to carbaryl. It is recommended that all labels for carbaryl products used on cats contain the age restriction stated in PR Notice 96 6 (should not be used in kittens less than 12 weeks of age). 16 Issues For Consideration:

There are population based monitoring studies in the published literature or available from various governmental agencies in which carbaryl metabolites are measured in body fluids or environmental media. For example, the Agency's Office of Research and Development, along with other Agencies, has funded a project entitled Pesticide Exposure in Children Living in Agricultural Areas along the United States Mexico Border Yuma County, Arizona. Preliminary results of this study indicate that carbaryl residues were identified in the dust of 20 percent of the 152 houses sampled and in approximately 24 percent in 25 samples collected in 6 schools in the same region. With regard to this specific example, current Agency policy is not to use house dust estimates to calculate risks because of a lack of an appropriate exposure model. Also, in a 1995 study conducted by the Centers For Disease Control (Hill et al) entitled Pesticide Residues In Urine Of Adults Living In The United States: Reference Range Concentrations, 1000 adults were monitored via urine collection. One of the analytes measured in that study (1 naphthol) is a potential metabolite of carbaryl as well as of napthalene and napropamide which may be a confounding factor. This metabolite (1 naphthol) was identified in 86 percent of the 1000 adults monitored. Data from this study were not used quantitatively in the risk assessment for carbaryl because of the uncertainties associated with them, such as the exact contribution of each possible compound to the overall levels and no linked exposure information. HED instead considered them a qualitative indicator that exposures in the general population are likely to occur. As more data become available, the Agency will consider the information in an effort to refine the assessment. It should also be noted that Aventis Crop Science has completed and is in the process of submitting to the Agency a biomonitoring study of individuals in residences following the application by a member of the household to the lawn and either the vegetable garden or ornamental flowers. A biomonitoring study of field workers during harvesting and hand thinning operations in apples and cherries will also be submitted to the Agency. Based on personal communication with Aventis Crop Science scientists, preliminary results from the residential biomonitoring study indicate that the highest percentiles of the distribution of the younger children in the homes were similar to those predicted in the Agency's turf risk assessment for toddlers that are intended to represent the higher percentiles of the exposure distribution. Preliminary field worker results also appear to not be significantly different from Agency estimates.

The database for carbaryl contains good quality studies which are sufficient for conducting a risk assessment for the reregistration of the chemical. However, certain key information, which would help refine the risk assessment, is missing. The one toxicology data gap includes a 90 day inhalation study in the rat. The elimination of poultry from the acute and chronic dietary risk assessment significantly reduced the risks. For residential postapplication risk assessments, there are no data on the amount of residues transferrable from treated pets to humans. Additional residue data on turf would also help refine the hand to mouth and object to mouth toddler exposures. For the occupational handler risk assessments, several handler scenarios lack high quality data. For postapplication workers, additional residue dissipation data along with data from practices not well represented in Agency Policy 003 (Transfer Coefficients) are needed to refine the assessment (e. g., partially mechanized practices that could involve contact). 17 O O N H CH 3 2.0 PHYSICAL/ CHEMICAL PROPERTIES CHARACTERIZATION The product chemistry chapter was prepared by Felicia Fort of the Health Effects Division (November 14, 2000  DP Barcode 240989). All information below is excerpted from that chapter unless specifically noted. Section 2.1: Chemical Structure and Identification presents the nomenclature and structures associated with carbaryl and its metabolites. Section 2.2: Physical Properties of Carbaryl presents information about the properties of carbaryl.

2.1 Chemical Structure and Identification Chemical Name: 1 naphthyl methylcarbamate Empirical Formula: C12H11NO2 Molecular Weight: 201.2 CAS Registry No.: 63 25 2 Chemical ID No.: 056801 Structures of carbaryl and major metabolites are shown below in Figure 1.

Figure 1. Structures of Carbaryl and Major Metabolites Name Structure Carbaryl 1 Naphthyl N methylcarbamate 5,6 dihydro 5,6 dihydroxy carbaryl Figure 1. Structures of Carbaryl and Major Metabolites Name Structure 3 From the EPA Technology Transfer Network, Office of Air Quality Planning and Standards, Air Toxics Website (www. epa. gov/ ttn/ atw)

18 OH 5 methoxy 6 hydroxy carbaryl 1 Naphthol 2.2 Physical Properties of Carbaryl Physical state: white to light tan solid Melting point: 142 0 C Solubility: water (40 ppm at 25 C), dimethyl formamide ( 45 g/ 100 mL); acetone, cyclohexanone, and isophorone ( 25 g/ 100 mL); methylethyl ketone ( 20 g/ 100 mL); dichloromethane ( 15 g/ 100 mL); ethanol and ethyl acetate ( 10 g/ 100 mL); mixed aromatic solvents and xylene ( 3 g/ 100 mL); and kerosene ( 1 g/ 100 mL). Vapor pressure: 0.000041 mm Hg at 26 0 C 3 Specific gravity: 1.23 at 20 0 C Octanol/ water partition coefficient (Kow): 217 19 3.0 HAZARD CHARACTERIZATION The hazard component of the risk assessment is presented in this section. Section 3.1: Hazard Profile presents a discussion of the available toxicity data for carbaryl. Section 3.2: FQPA Considerations discusses the susceptibility of sensitive populations such as children and the uncertainties associated with that analysis. Section 3.3: Dose Response Assessment describes which data were selected for risk assessment purposes. Section 3.4: Endocrine Disruption describes issues related to EDSTAC and the screening process for possible chemicals of concern.

3.1 Hazard Profile The updated Toxicology Chapter of the RED was prepared by Dr. Virginia Dobozy (D282980). The toxicology data base is of good quality and is essentially complete. A 90 day inhalation study with cholinesterase measurements is required. The database provides sufficient information for selecting toxicity endpoints for risk assessment and therefore, supports a reregistration eligibility decision for the currently registered uses.

Carbaryl is a carbamate insecticide. Its primary mode of toxic action is through cholinesterase inhibition (ChEI) after single or multiple exposures. In most of the toxicology studies in which ChEI was measured, it was the endpoint used to set the Lowest Observed Adverse Effect Level (LOAEL).

The acute toxicity studies showed that carbaryl was relatively toxic with acute oral dosing (Tox. Category II); but the acute dermal and inhalation toxicities were low (Tox. Categories III and IV, respectively). Carbaryl was not a dermal or eye irritant and was not a dermal sensitizer in animal studies (Table 1). However, human incidents of dermal irritation and dermal manifestations of an allergic response have been reported (see section 7.4 below for more information).

Table 1: Acute Toxicity of Carbaryl Guideline No. Study Type MRIDs # Results Toxicity Category 81 1 Acute Oral  rat (99% a. i.) 00148500 LD50 for males = 302.6 mg/ kg; for females = 311.5 mg/ kg; combined = 307.0 mg/ kg II 81 2 Acute Dermal rabbit (99% a. i.) 00148501 LD50 > 2000 mg/ kg III 81 3 Acute Inhalation  rat (99% a. i.) 00148502 LC50 > 3.4 mg/ L IV 81 4 Primary Eye Irritation rabbit (99% a. i.) 00148503 not a primary eye irritant IV 81 5 Primary Skin Irritation rabbit (99% a. i.) 00148504 not a primary skin irritant IV Table 1: Acute Toxicity of Carbaryl Guideline No. Study Type MRIDs # Results Toxicity Category 20 81 6 Dermal Sensitization guinea pig (99% a. i.) 00148505 negative NA 81 7 Acute Delayed Neurotoxicity (Hen) * negative at 2000 mg/ kg (approximate LD50) NA 81 8 Acute Neurotoxicity rat 43845201 43845204 systemic LOAEL = 10 mg/ kg for males and females based on significant inhibition of RBC, plasma, whole blood and brain cholinesterase; NOAEL < 10 mg/ kg a. i. = active ingredient * Carpenter, C. P., Weil, C. S., Palm, P. E., Woodside, N. W., Nair, J. H. and Smyth, H. F. Mammalian Toxicity of 1 napthyl Nmethyl carbamate (Sevin Insecticide). J. Agric. Food Chem. 9( 1): 30 39, 1961.

The neurotoxicity data showed that carbaryl was not a delayed neurotoxicant in the hen. In the acute neurotoxicity study in the rat after a single dose of 10 mg/ kg carbaryl, ChEI was observed in plasma, whole blood, red blood cells (RBC) and brain. At the next higher dose (50 mg/ kg), clinical signs typical of carbamate toxicity were observed. In the subchronic neurotoxicity study after 90 days of administration, clinical signs of toxicity were seen at the same dose (10 mg/ kg/ day) as plasma, whole blood, RBC and brain ChEI. There was no evidence of structural neuropathology in these studies.

No subchronic studies in the rat or dog are available, except for the subchronic neurotoxicity study in rats and 4 week dermal toxicity studies in rats (one with technical chemical and two with formulations). One of the dermal toxicity studies was useful for risk assessment. In this study, the systemic NOAEL was 20 mg/ kg/ day based on decreased RBC ChEI in males and females and brain ChEI in males at 50 mg/ kg/ day. The chronic toxicity data showed that, in dogs, decreases in plasma, RBC and brain ChEI were observed at 10 mg/ kg/ day; clinical signs of toxicity were also observed in both sexes at 31 mg/ kg/ day. Brain and plasma ChEI were decreased in female dogs at 3.1 mg/ kg/ day. In the mouse, clinical signs of toxicity were not typical of ChEI, but there was ChEI (plasma, RBC and brain) at 146 mg/ kg/ day. In the chronic toxicity study in rats, carbaryl at the highest dose (350 mg/ kg/ day in males and 485 mg/ kg/ day in females) caused a variety of toxic effects in the liver, kidneys and urinary bladder. It also induced an increase in the incidence of thyroid follicular cell hypertrophy and degeneration of sciatic nerves and skeletal muscle. RBC ChEI was decreased in males at 60 mg/ kg/ day and in females at 79 mg/ kg/ day. The lowest LOAEL in the chronic studies was in the chronic dog study, i. e., 3.1 mg/ kg/ day, which was the lowest dose in females. In a follow up 5 week study in dogs to clarify the NOAEL for ChEI, plasma ChEI was decreased in males at 3.83 mg/ kg/ day; no effects were observed at 1.43 mg/ kg/ day. 21 In a prenatal developmental toxicity study in the rat, maternal toxicity was observed at the same dose (10 mg/ kg/ day) as developmental toxicity; the NOAEL was 4 mg/ kg/ day. Developmental effects included decreased fetal body weight and increased incomplete ossification of multiple bones. In a prenatal developmental toxicity study in the rabbit, the maternal and developmental LOAELs were 50 mg/ kg/ day and 150 mg/ kg/ day, respectively. The respective NOAELs were 5 mg/ kg/ day and 50 mg/ kg/ day. The only evidence of developmental toxicity was a decrease in fetal body weight. These studies showed no evidence of a qualitative or quantitative increased susceptibility. In the reproduction study, there was evidence of a quantitative offspring susceptibility. The LOAEL for parental systemic toxicity was 1500 ppm (92.43 124.33 mg/ kg/ day for males and 110.78 135.54 mg/ kg/ day for females) based on decreased body weight, weight gain, and feed consumption. The NOAEL was 300 ppm (23.49 31.34 mg/ kg/ day for males and 26.91 36.32 mg/ kg/ day for females). The LOAEL for offspring toxicity was 300 ppm (23.49 31.34 mg/ kg/ day for males and 26.91 36.32 mg/ kg/ day for females) based on increased numbers of F2 pups with no milk in the stomach and decreased pup survival. The NOAEL was 75 ppm (4.67 5.79 mg/ kg/ day for males and 5.56 6.41 mg/ kg/ day for females). In the developmental neurotoxicity study, there was evidence of qualitative susceptibility. Clinical signs of toxicity and plasma and brain ChEI were seen in maternal animals at the same dose (10 mg/ kg/ day) as changes in brain morphometric measurements (decreases in cerebellar measurements in females on Day 11 post partum) were observed in offspring; however, brain measurements were not conducted at the next lower dose.

The Health Effects Division's (HED) Cancer Assessment Review Committee (CARC)( 11/ 7/ 01) classified carbaryl as Likely to be carcinogenic in humans based on an increased incidence of hemangiosarcomas in male mice at all doses tested (100, 1000 and 8000 ppm). The Q1*, based on the CD 1 mouse dietary study with ¾ Interspecies Scaling Factor, is 8.75 x 10 4 (mg/ kg/ day) 1 in human equivalents. In addition to the required carcinogenicity studies in mice and rats, the registrant submitted a special study in genetically modified mice. Carbaryl was administered to heterozygous p53 deficient (knockout) male mice in the diet at concentrations of up to 4000 ppm (716.6 mg/ kg/ day) for six months. There was no evidence of neoplastic or preneoplastic changes in the vascular tissues of any organ. A model validation study demonstrated that vascular tumors occur in heterozygous p53 deficient mice within six months of administration of a known genotoxic carcinogen (urethane).

A recent review of the data from the submitted studies and the published literature show that carbaryl is clastogenic in vitro. The wide variety of induced aberrations (both simple and complex) was consistent between the submitted micronucleus study and the open literature. However, there are inconsistencies relative to the requirement for S9 activation. Nevertheless, the two in vivo studies for micronuclei induction or chromosome aberrations were negative. Similarly, the 6 month p53 knockout transgenic mouse bioassay was negative. Carbaryl was also negative for DNA binding in the livers of mice treated with 8000 ppm for 2 weeks. Metabolism studies identified epoxide intermediates of carbaryl which were found to be conjugated to glucuronide, rapidly metabolized and excreted as any endogenous epoxide would be. Overall, these findings indicate that carbaryl produces epoxides and its DNA reactivity is manifested as chromosomal aberrations in cultured mammalian cells. Other in vitro 22 studies indicate carbaryl's effects on karyokinesis and cytokinesis, as well as stress genes associated with oxidative damage. Based on these considerations, the CARC concluded that there is a concern for mutagenicity, which is somewhat lessened because of the lack of an effect in in vivo mutagenicity studies.

The metabolism data in the rat indicated that radiolabeled carbaryl was readily absorbed with oral dosing, distributed to various organs, metabolized and formed conjugated metabolites with compounds such glucuronic acid. A total of 20 components was found, and 2 major metabolites were identified, naphthyl sulfate and naphthyl glucuronide. Much of the radioactivity was eliminated within 24 hours after dosing (86% in urine and 11% in feces). Seven days post dosing, negligible amounts of the administered dose were found in tissues. Several special metabolism studies were conducted to explore a mechanism for the increase in tumor incidence in mice. The results appear to show that high doses of carbaryl treatment (1154 mg/ kg) led to a "phenobarbital" type of induction of liver xenobioticmetabolizing enzymes and interaction of carbaryl with chromatin protein in mice. A dermal absorption study indicated that 12.7% of a carbaryl formulation (43.9% a. i.) was absorbed.

The toxicology profile for carbaryl is presented in Appendix 1.

3.2 FQPA Considerations The HIARC (February 19, 2002 meeting) concluded that there is a concern for pre and/ or postnatal toxicity resulting from exposure to carbaryl.

3.2.1 Determination of Susceptibility There was no evidence of quantitative or qualitative susceptibility following in utero exposures in developmental studies in the rat and rabbit.

In the reproduction study, there was evidence of quantitative susceptibility of offsprings. The LOAEL for parental systemic toxicity was based on decreased body weight, weight gain, and feed consumption; the NOAEL was 27 mg/ kg/ day in males and 30 mg/ kg/ day in females. In the offspring the LOAEL was based on increased numbers of F2 pups with no milk in the stomach and decreased pup survival; the NOAEL was 5 mg/ kg/ day in males and 6 mg/ kg/ day in females. No adverse effects were observed in the reproductive parameters.

In the developmental neurotoxicity study, there was evidence of qualitative susceptibility. For maternal toxicity, the LOAEL was based on decreased body weight gain, alterations in Functional Observational Battery measurements and inhibition of plasma, whole blood and brain cholinesterase activity; the NOAEL was 1 mg/ kg/ day. For developmental neurotoxicity, the LOAEL was based on the morphometric changes seen in the brain of the offsprings; the NOAEL was 1 mg/ kg/ day. 23 3.2.2 Degree of Concern Analysis and Residual Uncertainties The HIARC concluded that there is no residual concern in the two generation reproduction study because the dose response effects in pups are well characterized and the NOAEL for the offspring effects is above that which was used for establishing the chronic Reference Dose (RfD) for chronic dietary risk assessment.

The HIARC selected the LOAEL of 3.1 mg/ kg/ day established in the chronic toxicity study in dogs for establishing the chronic RfD. Since a LOAEL was used, an additional uncertainty factor of 3X was applied (i. e, lack of a NOAEL) to the LOAEL. Although a NOAEL was not established in this study, the HIARC determined that a 3X was adequate (as opposed to a higher value) because: 1) cholinesterase inhibition in females was not accompanied by clinical signs; 2) no inhibition was seen for any cholinesterase compartment in males at this dose; 3) the magnitude of inhibition of plasma cholinesterase inhibition (12 23% decrease) was comparable to the magnitude of inhibition (22%) seen in the 5 week study in dogs indicating no cumulative effects following long term exposure; 4) the study was well conducted and there are sufficient data from subchronic and chronic duration studies in the other species which support cholinesterase inhibition as the critical effect.

In addition, based on the cholinesterase inhibition data, the dog appears to be more sensitive than the rat in long term studies. Furthermore, use of the LOAEL of 3 mg/ kg/ day from the 1 year dog study with an uncertainty factor of 300 results in a NOAEL of 1 mg/ kg/ day. This extrapolated NOAEL is identical to that of the offspring NOAEL of 1.0 mg/ kg/ day established in the developmental neurotoxicity study.

Thus, the NOAEL of 1 mg/ kg/ day used for establishing the chronic RfD is below the NOAEL of 5 mg/ kg/ day for offspring toxicity, and the chronic RfD would be protective of the effects of concern for infants and children following chronic dietary exposures.

With regard to the developmental neurotoxicity study, the HIARC concluded that there was a low level of concern based on the following residual uncertainties:

° The first uncertainty was the lack of a demonstrated effect level since morphometric measurements of brains in the offsprings were not performed at the mid dose (1 mg/ kg/ day). However, this concern was negated since even at the high dose of 10 mg/ kg/ day, the morphometric changes were minimal and therefore, it is unlikely that adverse effects would be seen at 1 mg/ kg/ day, which is 10% of the LOAEL. 24 ° The second uncertainty was the lack of comparative data in adults and offspring for cholinesterase inhibition. This concern was negated since no FOB alterations were seen in pups. Other studies in the data base have shown that when FOB alterations were seen in adult animals, they are usually accompanied with cholinesterase inhibition. Also, the results of the National Institute for Environmental Health Sciences study (discussed above) showed no difference in cholinesterase inhibition in pups and adults. There was a dose related decrease in cholinesterase activity in the brain and blood of dams at gestation day 19 and fetuses taken at this time also showed a very similar level of fetal brain cholinesterase.

The HIARC concluded that the NOAEL of 1 mg/ kg/ day selected for establishing the acute RfD would address the low level of concern for the residual concerns and would be protective of the effects of concern for infants and children following a single oral exposure.

3.3 Dose Response Assessment The HIARC evaluated the toxicology data base of carbaryl, reassessed the Reference Dose (RfD) established in 1994 and selected the toxicological endpoints for acute dietary, as well as occupational and residential exposure risk assessments at a meeting on July 7, 1998. Re evaluations of the FQPA Safety Factor recommendation were done on April 28 and November 15, 1999, after the submission of prenatal developmental toxicity studies in the rat and rabbit, respectively. A re evaluation of the endpoints for risk assessment was conducted on March 1, 2001, February 19, 2002 and April 25, 2002. Table 2 contains a summary of the hazard doses and endpoints selected for use in the various human health risk assessments. Endpoints were selected for a broad spectrum of risk assessments, including acute and chronic dietary, short, intermediate and long term dermal and inhalation exposures and short and intermediate term incidental exposure. For the chronic dietary and the long term dermal and inhalation exposure endpoints, a LOAEL was selected, which necessitated an additional 3x uncertainty factor.

A common toxicological endpoint exists for the dermal, inhalation and incidental oral routes. Therefore, the Margins of Exposure (MOEs) can be combined for occupational and residential risk assessments. For acute, short , intermediate and long term aggregate risk assessments, the oral, dermal and inhalation routes can be combined because of the common toxicity endpoint (ChEI).

Table 2. Summary of Toxicological Dose and Endpoints for Carbaryl for Use in Human Risk Assessment Exposure Scenario Dose (mg/ kg/ day) & Total UF Hazard Based Special FQPA Safety Factor Endpoint for Risk Assessment Dietary & Nondietary Ingestion Risk Assessments Acute Dietary general population including infants and children NOAEL = 1 UF = 100 1 Developmental Neurotoxicity  rat LOAEL = 10 mg/ kg/ day based on an increased incidence of FOB changes on the first day of dosing in maternal animals Acute RfD and aPAD = 0.01 mg/ kg/ day Table 2. Summary of Toxicological Dose and Endpoints for Carbaryl for Use in Human Risk Assessment Exposure Scenario Dose (mg/ kg/ day) & Total UF Hazard Based Special FQPA Safety Factor Endpoint for Risk Assessment 25 Chronic Dietary all populations LOAEL= 3.1 UF = 300 1 Chronic toxicity  dog LOAEL = 3.1 mg/ kg/ day based on plasma and brain cholinesterase inhibition in females.

Chronic RfD and cPAD = 0.01 mg/ kg/ day [Note: A NOAEL could not be defined in this study. Therefore, an additional factor of 3 has been applied to account for the data deficiency.]

Short term Incidental Oral (1  30 Days) [Residential Only] NOAEL= 1 Res. UF = 100 1 Developmental Neurotoxicity  rat LOAEL = 10 mg/ kg/ day based on an increased incidence of FOB changes and decreases in RBC, whole blood, plasma and brain cholinesterase Intermediate Term Incidental Oral (1  several months) [Residential Only] NOAEL= 1 Res. UF = 100 1 Subchronic Neurotoxicity  rat LOAEL = 10 mg/ kg/ day based on increased incidence of FOB changes; decrease in RBC, whole blood, plasma and brain cholinesterase.

Non Dietary Risk Assessments Short Term Dermal (1  30 days) NOAEL= 20 Res. UF = 100 Occ. UF = 100 1 4 week dermal toxicity with technical  rat systemic LOAEL = 50 mg/ kg/ day based on statistically significant decreases in RBC cholinesterase in males and females and brain cholinesterase in males.

Intermediate term Dermal (30 days  several months) NOAEL= 20 Res. UF = 100 Occ. UF = 100 1 4 week dermal toxicity with technical  rat systemic LOAEL = 50 mg/ kg/ day based on statistically significant decreases in RBC cholinesterase in males and females and brain cholinesterase in males.

Long Term Dermal (Several months to a lifetime) LOAEL= 3.1 Res. UF = 300 Occ. UF = 300 1 Chronic toxicity  dog LOAEL = 3.1 mg/ kg/ day based on plasma and brain cholinesterase inhibition in females.

[Note: A NOAEL could not be defined in this study. Therefore, an additional factor of 3 has been applied to account for the data deficiency. Also, this study is not route specific as it was conducted via oral administration. Route to route extrapolation is required using an adsorption factor of 12.7 percent which is based on a rat dermal absorption study.]

Short Term Inhalation (1  30 days) NOAEL= 1 Res. UF = 100 Occ. UF = 100 1 Developmental Neurotoxicity  rat LOAEL = 10 mg/ kg/ day based on an increased incidence of FOB changes and statistically significant decreases in RBC, whole blood, plasma and brain cholinesterase [Note: This study is not route specific as it was conducted via oral administration. Route to route extrapolation is required using an adsorption factor of 100 percent.] Table 2. Summary of Toxicological Dose and Endpoints for Carbaryl for Use in Human Risk Assessment Exposure Scenario Dose (mg/ kg/ day) & Total UF Hazard Based Special FQPA Safety Factor Endpoint for Risk Assessment 26 Intermediate Term Inhalation (30 days  several months) NOAEL= 1 Res. UF = 100 Occ. UF = 100 1 Subchronic Neurotoxicity  rat LOAEL = 10 mg/ kg/ day based on increased incidence of FOB changes; decrease in RBC, whole blood, plasma and brain cholinesterase.

[Note: This study is not route specific as it was conducted via oral administration. Route to route extrapolation is required using an adsorption factor of 100 percent.]

Long Term Inhalation (Several months to a lifetime)

[Occupational only] LOAEL= 3.1 Occ. UF = 300 1 Chronic toxicity  dog LOAEL = 3.1 mg/ kg/ day based on plasma and brain cholinesterase inhibition in females.

[Note: A NOAEL could not be defined in this study. Therefore, an additional factor of 3 has been applied to account for the data deficiency. Also, this study is not route specific as it was conducted via oral administration. Route to route extrapolation is required using an adsorption factor of 100 percent.]

Cancer Classification: C Q1* = 8.75 x 10 4 (mg/ kg/ day) 1 3.4 Endocrine Disruption EPA is required under the Federal Food Drug and Cosmetic Act, as amended by FQPA, to develop a screening program to determine whether certain substances (including all pesticide active and other ingredients) "may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." Following the recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), EPA determined that there were scientific bases for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA authority to require the wildlife evaluations. As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program (EDSP).

When the appropriate screening and/ or testing protocols being considered under the Agency's EDSP have been developed, carbaryl may be subjected to additional screening and/ or testing to better characterize effects related to endocrine disruption. 27 4.0 NON OCCUPATIONAL RISK ASSESSMENT AND CHARACTERIZATION This section of the risk assessment addresses exposures to individuals in the general population that are not exposed as part of their employment. These exposures can occur through the diet and/ or they can occur because people have contact with carbaryl residues while using consumer products containing carbaryl or by being in areas that have been previously treated. Section 4.1: Summary of Registered Uses below summarizes available products and also describes the uses of those products. Products intended for commercial sales (e. g., in agriculture) and consumer products are included as each type of product can contribute to non occupational exposures through the diet, via residential use, or through commercial use in areas frequented by the general population such as golf courses. Section 4.2: Dietary Risk Assessment describes the residue and consumption data used in the dietary risk assessment, the risks associated with various populations of interest through the diet, and characterization of those risks. Section 4.3: Water Risk Assessment describes how water concentrations were determined, calculation of risks, and characterization of those risks. Section 4.4: Residential Risk Assessment describes how risks were calculated for people who use consumer products containing carbaryl and for those who are exposed as a result of being in areas that have been previously treated.

4.1 Summary of Registered Uses All products (e. g., manufacturing and various end use formulations) and the associated use patterns for carbaryl are described below. A brief overview of the types of equipment and application rates is also provided. The information in this section summarizes all use patterns of carbaryl as both commercial products and products intended for sale to homeowners can both contribute to exposures in the general population through the diet, drinking water, direct use (i. e., for homeowners only in this aspect of the risk assessment) and as a result of people frequenting areas that have been previously treated by either homeowners (e. g., lawns or gardens) or other public places that could have been commercially treated (e. g., golf courses). The need to have a thorough understanding of the use patterns for consumer products is self explanatory. Understanding the use of commercial products is key for the development of the dietary and drinking water assessments. It is also critical for evaluating some residential postapplication exposures such as for golfers.

Carbaryl (1 naphthyl N methyl carbamate) is a broad spectrum carbamate insecticide marketed in a variety of end use products for both occupational and homeowner use. End use product names include Adios, Bugmaster, Carbamec, Carbamine, Crunch, Denapon, Dicarbam, Hexavin, Karbaspray, Nac, Rayvon, Septene, Sevin, Tercyl, Tornado, Thinsec, and Tricarnam. Use sites include but are not limited to the following: fruit and nut trees; vegetable crops; field and forage crops; grapes; forestry; lawns and other turf such as golf courses; ornamental trees, shrubbery, annuals, and perennials; wide area treatment targets such as residential mosquito adulticide uses and oyster beds; poultry production facilities; and companion animals (e. g., dogs and cats). Table 3 summarizes all (homeowner and occupational products) currently available technical and manufacturing products along with their corresponding EPA registration numbers. 28 Table 3: Technical and Manufacturing Carbaryl Products Formulation EPA Reg. No. (% active ingredient)

Technical 34704 707 (99%); 45735 24 (99%); 264 324 (99%), 325 (97.5%); 19713 75 (99%)

Manufacturing Product 264 328 (80%); 264 325 (97.5%) 769 971 (80%); 5481 190 (46%) 19713 369 (50 %); 432 982 (97.5%); 73049 238 (1%)

Based on a review (2/ 27/ 01) of the Office of Pesticide Programs – Reference Files System (REFS), there are over 300 active product labels (i. e., includes both homeowner and occupational products). Carbaryl formulations include dusts, emulsifiable concentrates, soluble concentrates, water dispersible granulars, flowable concentrates, wettable powders, granulars, baits, pet dips and pet shampoos, aerosol sprays, ready to use pump sprayers, and pet collars (i. e., treated articles). Table 4 summarizes the approximate number of Section 3 registered products in each formulation category and the range of percent active ingredient. A complete listing of all the registration numbers under each category can be found in the Occupational/ Residential Exposure Assessment chapter (D281418). This chapter also includes in the Appendices, the Qualitative Usage Analysis For Carbaryl and the RED Use Profile Report prepared by the Agency's Biological and Economic Analysis Division. Many of the products described can be used in a variety of settings ranging from agriculture and commercial facilities to residential areas.

Table 4: Carbaryl End Use Product Formulations Formulation Type Number of Products Range of Percent Active Ingredient Emulsifiable Concentrates & Flowable Concentrates 57 0.3  80 Wettable Powders & Soluble Granules 36 0.5  95 Dusts 130 0.3  80 Granular 45 1.43  15 Bait 55 1.3  13 Dips, Shampoos 2 0. 5  60 Pet collars (treated articles) 2 8. 5  16 Ready to Use Pump Sprayers & Aerosol Cans 6 0. 12  1 29 Equipment used to apply carbaryl in residential settings includes dust shaker cans, garden hoseend sprayers, trigger sprayers, low pressure handwands, belly grinders, push type spreaders, aerosol cans, and pet collars. In an occupational setting, carbaryl can be applied by airblast, aerial application, chemigation, groundboom, power duster, low and high pressure handwand, backpack, compressed air sprayer, fogger, hand held duster, hose end sprayer, duster cans, and aerosol can. Depending on the crop, the maximum number of carbaryl applications per season can range from 1 to 8. A variety of application rates are available on the carbaryl labels, ranging from 1 lb ai/ acre for curcurbits to 16 lb ai/ acre for a foliar treatment of citrus in California. Some products are marketed in a single marketplace while others are sold for use in various settings. Based on sales information provided by Aventis CropScience at the SMART meeting with EPA on September 24, 1998, it appears that approximately 34 percent of carbaryl use is by homeowners in residential settings, 59 percent is used in agriculture, and the remaining 7 percent is used in the nursery, landscape and golf course industries.

The application parameters for major crop groups or application targets were defined by the physical nature of the use site, the physical nature of the formulation, the equipment needed for application and the application rate. Selected crop groupings and application targets along with corresponding typical (if available) and maximum application rates that are used in the risk assessment are presented in Table 5 below.

Table5: Application Rates Considered in Risk Assessment Crop or Target Occupational Products Residential Products lb ai/ 1000 ft 2 (units may vary) lb ai/ A/ acre (units may vary) max. apps/ season lb ai/ season Average Rates Alfalfa, clover, trefoil 1. 5 1/ cutting 1. 5/ cutting 1. 1 Asparagus 2 4  postharvest 3  broadcast 2  postharvest 6  broadcast 10  postharvest 0.9 0. 023 0. 094 Beans (fresh & dried), cowpeas, peas 1.5 4 6 0. 9 0.012 0.047 Beets, carrot, horseradish, radish, parsnip 2  foliar 2.2  soil broadcast 6  foliar 4  soil 6 0. 8 0.012 0.047 Blueberries 2  foliar 0.5 lb/ 1000 ft 2  soil 5 10 1. 7 0.012 0.047 Cole Crops (broccoli, brussel sprouts, cabbage, cauliflower, chinese cabbage, collards, kale, kohlrabi, mustard greens) 2  foliar 2.2  soil broadcast 4 6 0.8 0. 012 0.047 Caneberries 2  foliar 2.2  soil broadcast 5 4 10 Not specified 1.7 0. 012 0.047 Celery, Dandelion 2  foliar 2.2  soil broadcast 4 6 1.0 0. 012 0.047 Citrus 16 (foliar in CA only) 10 (foliar in FL only) 7.5  foliar 1 lb/ 100 gal. 1 Not specified 8 Not specified 20 Not specified 20 Not specified 2.7 to 3.4 (lemons & oranges) 0.023 0.176 Corn (field and pop) 2 4 8 1.0 0. 012 0.047 Table5: Application Rates Considered in Risk Assessment Crop or Target Occupational Products Residential Products lb ai/ 1000 ft 2 (units may vary) lb ai/ A/ acre (units may vary) max. apps/ season lb ai/ season Average Rates 30 Corn (sweet) 2  foliar 2.2  soil broadcast 8 4 16 Not specified 1.3 0. 012 0.047 Cranberry 2 5 10 2.0 0. 012 0.047 Cucurbits (cucumber, melon, pumpkin, squash) 1 6 6 1.1 0. 012 0.047 Fruiting Vegetable (tomato, eggplant, pepper) 2 7 8 1.0 0. 012 0.047 Grapes 2 5 10 1.4 0. 012 0.047 Grasses Grown For Seed 1.5 2 3 0. 8 (based on hay) Leafy Vegetable (head and leaf lettuce, endive, mustard green) 2  foliar 2.2  soil broadcast 5 4 6 Not specified 1.1 0. 012 0.047 Nuts (almond, chestnut, pecan, pistachio, walnut, etc.), foliar or dormant/ delayed 5 4 15 2.5 (pecans) 0.047 0.12 Nuts (almond, chestnut, pecan, walnut), foliar in CA 1 lb ai/ 100 gal Not specified Not specified Not specified 0.047 0.12 Ornamental 2.2 or 2% solution   1. 5 0.023 Oyster beds (SLN only) 10 Not specified Not specified  Peanut 2 5 8 0.8 0. 012 0.047 Pome fruit 3 8 15 1. 2 (based on apples) 0.012 0.07 Potatoes & Tubers (turnips) 2 6 6 0.8 Rangeland pastures 1 1 1 0.9 Rice 1.5 2 4 1. 1 Right of Way 1. 5 3 0. 4 Sorghum 2 4 6 1.1 Stone fruit (apricot, cherry, nectarine, peach, plum/ prune), foliar or dormant/ delayed 3 4  CA only 3 foliar & 1 dormant/ delayed 14 1.1 0. 047 0.12 Stone fruit (apricot, cherry, nectarine, peach, plum/ prune), foliar 1 lb ai/ 100 gal Not specified Not specified Not specified 0.047 0.12 Strawberries 2 5 10 1.4 0. 012 0.047 Sugar beets 1. 5 to 2 2 to 4 4 1.3 0. 012 0.047 Sweet Potatoes 2 foliar 8 lb/ 100 gal drip 8 foliar Not specified 8 foliar 1.2 1.6 foliar Not specified 0.012 0.047 Sunflower 1. 5 2 3 0.7 0. 012 0.047 Tobacco 2 4 8 1.1

Tree farm 1  2 0. 7

Turf/ golf 8 liquids 9 granulars  0. 8/ 1000sf 2 to 4 0. 047 to 0.25 (lawns) [maximum levels for different products] Wheat, flax 1.5 2 3 0. 8

Ants 2% sol    2% sol Mosquito Control 2

Outdoor Banding 2% sol    2% sol Table5: Application Rates Considered in Risk Assessment Crop or Target Occupational Products Residential Products lb ai/ 1000 ft 2 (units may vary) lb ai/ A/ acre (units may vary) max. apps/ season lb ai/ season Average Rates 4 At the present time, information from the industry sponsored Carbamate Market Basket Survey has been approved for use in dietary risk assessments with appropriate characterization of uncertainties associated with the conduct of the study. The primary concern was rubbing sampled commodities during the rinsing process except for broccoli and tomato because this created a potential for residue loss from the mechanical action associated with rubbing. A separate assessment was also completed using other sources of high quality residue data (e. g., PDP) for comparative purposes to more completely inform the risk management process.

31 Domestic Animals (e. g., cats/ dogs) Dust 0.2 lb ai/ dog Sha. 0.01 lb ai/ dog    Dust 0.2 lb ai/ dog Sha. 0.01 lb ai/ dog Domestic Animals (e. g., cats/ dogs) 1.3 oz/ dog collar    1.3 oz/ dog collar Note: In many cases an application rate per area (e. g., 1000 ft 2 ) is provided but a 1 to 2 % ai w/ v solution can be used to make similar applications where volume outputs are difficult to regulate (i. e., handheld equipment where area treated is difficult to define).

4.2 Dietary Risk Assessment The Product and Residue Chemistry Chapters (D283328; May 30, 2002) and the Dietary Exposure Analysis (D281419; April 28, 2002) were prepared by Felecia Fort. Potential exposure to residues of carbaryl in the diet occurs through food and water. Carbaryl is used late in the season at maximal seasonal rates of 6 12 lb ai/ acre. [Note: There is also a section 3 registration that allows use on citrus up to 16 lb ai/ acre only in the state of California.] Post harvest intervals (PHIs) range from 1 29 days but most are one week or less. The qualitative nature of carbaryl residues in plants and animals is adequately understood. The carbaryl residue to be regulated in plants is carbaryl per se. The residues of concern in meat and milk are the free and conjugated forms of carbaryl, 5,6 dihydro 5,6 dihydroxy carbaryl, and 5 methoxy 6 hydroxy carbaryl. Adequate Pesticide Data Program (PDP) and Food and Drug Administration (FDA) monitoring residue data are available for the vast majority (> 80%) of commodities. Detectable residues were found in 31 of 42 crops. In field trials, residues were less than the Limit of Quantitation (LOQ) in 5 crops but were quantifiable in all other raw agricultural commodities (RACs).

The dietary exposure assessment is a Tier 3/ 4 assessment, which is the most highly refined assessment that can be conducted at this time. HED has provided anticipated residues (ARs) for carbaryl based on USDA PDP and FDA monitoring data, along with field trial data, for many commodities. In addition, separate acute assessments were conducted incorporating the results of the Carbamate Market Basket Survey (CMBS) 4 . 32 Carbaryl and its degradate 1 naphthol are fairly mobile but are not likely to persist or accumulate in the environment. Available non targeted monitoring studies were of limited utility in developing estimated environmental concentrations (EECs) of carbaryl in water. Therefore, screening models were utilized in assessing carbaryl residues in drinking water (see Section 4.3 below for more details).

Section 4.2.1: Residue Profile provides information on the residue data used to complete the dietary risk assessments. Section 4.2.2: Acute Dietary Risk Assessment presents the acute assessment with and without the CMBS data. Section 4.2.3: Chronic Dietary Risk Assessment presents the results for this duration of exposure. Section 4.2.4: Cancer Dietary Risk Assessment presents cancer risks. Section 4.2.5 Characterization/ Uncertainties of the Risk Estimates provides information that should be considered along with the numerical results of this assessment.

4.2.1 Residue Profile Tolerances for residues of carbaryl are currently expressed in terms of carbaryl (1 naphthyl Nmethylcarbamate including its hydrolysis product 1 naphthol, calculated as carbaryl, for most raw crop commodities (RACs) [40 CFR §180.169( a)]. The established tolerances for residues in/ on pineapples, pome fruits, avocados, and fresh dill are expressed in terms of carbaryl per se [40 CFR §180.169( d) and (e)]. Tolerances for residues in livestock commodities are expressed as carbaryl, including its metabolites 1 naphthol (naphthyl sulfate), 5,6 dihydrodihydroxy carbaryl, and 5,6 dihydrodihydroxy naphthol, calculated as carbaryl [40 CFR §180.169( b) and (c)]. A tolerance for residues in pineapple bran is expressed in terms of carbaryl per se [40 CFR §186.550]. The HED Metabolism Committee concluded that the carbaryl residue to be regulated in plants is carbaryl per se (DP Barcode D221979, S. Hummel, 2/ 8/ 96). The Committee also concluded that carbaryl, 5,6 dihydro 5,6 dihydroxy carbaryl, 5 methoxy 6 hydroxy carbaryl and all residues which can be hydrolyzed to carbaryl, 5,6 dihydro 5,6 dihydroxy carbaryl and 5 methoxy 6 hydroxy carbaryl under acidic conditions should be included in the tolerance expression and risk assessment for all endpoints of dietary concern for livestock commodities only. (C. Olinger, D255855, 6/ 21/ 99). An interim tolerance of 0.5 ppm has been established for carbaryl and its 1 naphthol metabolite in eggs [40 CFR §180.319]. Tolerances of 2 ppm and 10 ppm have been established for residues of carbaryl in pineapples and bananas, respectively. The registrant intends to support the tolerances for residues of carbaryl in/ on these commodities as import tolerances.

Currently, the Codex MRLs and U. S. tolerances are not compatible because the U. S. tolerance expression includes metabolites. Once the U. S. tolerance definition is amended, it will be compatible with the definition for Codex MRLs. The Metabolism Committee has also recommended that the tolerance expression for livestock commodities include the free and conjugated forms of carbaryl; 5,6 dihydro 5,6 dihydroxy carbaryl; and 5 methoxy 6 hydroxy carbaryl. The Codex MRLs and U. S. tolerances cannot be made compatible for livestock commodities with respect to the tolerance definition.

The reregistration requirements for plant and livestock metabolism are fulfilled. Acceptable metabolism studies depicting the qualitative nature of residues in lettuce, radish, soybeans, ruminants and poultry have been submitted and evaluated. For the purpose of reregistration, adequate magnitude of the residue data are available on the following crops: alfalfa, almond, asparagus, beans (dried and succulent), blueberry, broccoli, cabbage, celery, cherry, citrus fruits, clover, corn (sweet and field), 33 cucurbits (cantaloupes, cucumbers and squash), cranberry, flax, grape, head and leaf lettuce, mustard greens, okra, peanut, peas (dried and succulent), pecan, pepper, pistachio, pome fruits, potato, prickly pear cactus, raspberry, rice, sorghum, soybean, spinach, stone fruits, strawberry, sunflower, sweet potato, tobacco, tomato, walnut. Geographical representation is adequate and a sufficient number of trials reflecting representative formulation classes were conducted. Carbaryl residues were <LOQ in/ on sweet potato, sugar beets, corn grain, flax seed, and peanuts. Quantifiable residues were detected in all other RACs. For a given crop, residue levels were quite variable overall, probably owing to climactic variations, but were generally consistent within any specific field trial location. There are data gaps which are listed in Section 8.0: Data Needs/ Label Requirements.

Adequate PDP monitoring data were available for the commodities potatoes, carrots, sweet potato, celery, spinach, lettuce (head), broccoli, succulent peas (processed) , succulent beans, soybean, tomatoes, cantaloupe, winter squash, orange, orange juice, apple, apple juice, pear, peach, wheat, sweet corn, banana, grape, grape juice and milk. FDA monitoring data were used for the commodities, lettuce (leaf), cabbage, eggplant, succulent peas (fresh), non bell pepper, bell pepper, cucumber, watermelon, summer squash, cherries, raspberry, blueberry, asparagus, cranberries, pineapple, and strawberry. Monitoring data were translated to similar crops when possible, generally according to the HED SOP 99.3 "Translation of Monitoring Data". Monitoring data from the years 1994 through 1998 (PDP) and the years 1992 through 1998 (FDA) were considered. Field trial data were used for the commodities, garden beets, turnips, mustards, dried beans, almonds, pecans, walnuts, field corn grain, rice, flax seed, okra, olive, peanuts, pistachio, sugar beets, dried peas, and sunflower.

HED conducts dietary risk assessments using the Dietary Exposure Evaluation Model (DEEM™), which incorporates consumption data generated in USDA's Continuing Surveys of Food Intakes by Individuals (CSFII), 1989 1992. In this assessment, CFSII data from 1994 to 1998 were also considered along with the earlier data for comparative purposes. Routinely, the 1989 to 1992 data are used for risk assessments; however, the Aventis Crop Science commented that the 1994 to 1998 data should also be considered. The Agency completed the analysis using both sets of consumption data in response to this comment. In these surveys, both 3 day mean consumption and single day consumption information were recorded for 22 demographic and socio economic subpopulations including infants, children, and nursing women. For acute dietary risk assessments, the entire distribution of consumption events for individuals is multiplied by a randomly selected distribution of residues (probabilistic analysis, referred to as "Monte Carlo" ) to obtain a distribution of exposures in mg/ kg/ day. For chronic dietary risk assessments, the 3 day average for each subpopulation is combined with average residues in commodities to determine average exposures (mg/ kg/ day).

Anticipated residue estimates were prepared using USDA Pesticide Data Program (PDP) data, if available. Alternatively, FDA surveillance monitoring data from the years 1992 98 were used if sufficient samples were available. Data from crop field trials were used if there were insufficient PDP or FDA monitoring data. In addition, separate acute assessments were conducted incorporating the results of the CMBS as described above (i. e., rubbing fruit may reduce residues, use of other high quality data leads to a more informed risk management decision).

The Biological and Economic Analysis Division (BEAD) provided information (F. Hernandez, 34 7/ 21/ 98) on the percent crop treated (% CT). For the chronic analysis, the weighted average %CT was incorporated; for the acute analysis, the estimated maximum %CT was used when appropriate. In acute analyses (except blended commodities) the adjustment for %CT is incorporated in the residue distribution files (RDFs) via addition of zero residue values corresponding to the % of crop not treated. For blended/ not furthered processed commodities where monitoring data are available, the entire distribution of monitoring data with no further adjustment for %CT were used. For blended/ processed commodities where monitoring data are available and for all blended commodities where field trial data were used, %CT is incorporated into a point estimate. For the chronic analyses, the %CT is listed as Adjustment Factor 2 in the DEEM analysis. One half the weighted average of the limits of detection was used in the dietary assessment for all treated non detectable residues. Detectable residues from composite monitoring data for non blended food forms were used to generate residue values in single units using the methods described in the H. Allender paper dated 5/ 26/ 99 "Statistical methods for Use of Composite Data in Acute Dietary Risk Assessment." The "decomposited" residues were then included in residue distribution files (RDF) for the probabilistic analysis. BEAD supplied percent crop treated data were incorporated into the anticipated residue or residue distribution file when appropriate. [Note: Single serving peach PDP data were used for non blended peach food forms instead of data that had been previously decomposited (Allender method).]

A separate dietary assessment was conducted utilizing the CMBS results. The CMBS Task Force conducted a year long, national survey of carbamate residues on selected food commodities purchased at grocery stores. Residue data from a market basket survey are considered close approximations to residues potentially found at most `dinner plates'. These data are generally considered the most appropriate survey type for use in pesticide risk and exposure assessment. The CMBS collected up to 400 single serve samples of 8 different crops (apple, banana, broccoli, grape, lettuce, orange, peach and tomato). These data were used in the acute dietary analysis directly via RDFs incorporating %CT for all food forms which are considered to be partially or not blended. For blended commodities, the entire distribution of data with no further adjustment for % CT was used. If CMBS data were not available, then PDP or FDA monitoring or field trial data were used. CMBS data were translated to similar commodities when feasible; however, if PDP monitoring data were available for the processed commodity, then CMBS data were not translated (i. e., PDP orange juice data were used instead of CMBS data for oranges). The dietary risk assessments were completed with and without the results of the CMBS for comparative purposes, again as described above (i. e., rubbing fruit may reduce residues, use of other high quality data leads to a more informed risk management decision).

Most of the carbaryl processing factors were obtained from processing studies submitted by the registrant. The rice processing factors were from a review by Thurston Morton (D216242, 9/ 17/ 98).

4.2.2 Acute Dietary Risk Assessment The following equations were used to calculate dietary exposure and non cancer risk for carbaryl.

Dietary exposure (mg/ kg/ day) = consumption x residue 35 Dietary risk (% PAD) = dietary exposure (mg/ kg/ day) x 100 population adjusted dose (mg/ kg/ day)

The population adjusted dose (PAD) is the adjusted RfD reflecting the retention or removal of the FQPA safety factor. For carbaryl, the FQPA safety factor has been reduced to 1x. The resulting acute PAD (aPAD) and chronic PAD (cPAD) are both 0.01 mg/ kg/ day. The doses and endpoints selected by the HIARC for these risk assessments are discussed in more detail in Section 3.3: Dose Response Assessment above.

For this Tier 3/ 4 Assessment, estimated acute dietary exposure at the 99.9 th percentile of exposure exceeds HED's level of concern without incorporating the CMBS results for all infants and children (1 6 years) based on 1989 to 1992 CFSII data (Table 6). The highest exposed subpopulation incorporating all commodities using PDP and FDA monitoring data without CMBS data was all infants at 133 percent of the aPAD while children (1 6 years) were at 110 percent of the aPAD. The same general trend applied when the 1994 to 1998 CFSII data were considered but risks were actually higher for all subpopulations (infants at 134 percent of the aPAD and children (1 to 6 years old) at 138 percent of the aPAD). The Agency routinely uses the 1989 to 1992 CFSII data for risk assessments. However, Aventis Crop Science commented that 1994 to 1998 CFSII data should also be considered so the Agency used both for comparative purposes. Prior to the calculation of these risk estimates, residues in poultry were the key contributors to the risks for various populations. Since then, Aventis Crop Science has indicated that poultry uses will be deleted (i. e., poultry uses were not considered in this assessment). As such, it appears that consumption of apples and peaches are the critical contributors to acute dietary risks. A sensitivity analysis was conducted using 1989 to 1992 CFSII by eliminating these crops and crops where no detectable residues were found (Table 7). This analysis showed that risk estimates were not significantly affected by assuming zero in place of ½ LOD on samples reported as not detectable. Eliminating apples reduced exposures of children (1 6 years) to 82 percent of the aPAD but did not significantly impact the risks for all infants which were still at 118 percent of the aPAD. Eliminating peaches had the greatest impact. Risks to children (1 6 years) still exceeded 100 percent of the aPAD at 102 percent. Risks for all infants, however, were reduced to 72 percent of the aPAD.

Table 6: Results of the Carbaryl Acute Dietary Analyses (Market Survey Data Not Included)

Pop. Subgroup 99.9 th Percentile 99 th Percentile 95 th Percentile Exposure (mg/ kg/ day) % aPAD Exposure (mg/ kg/ day) % aPAD Exposure (mg/ kg/ day) % aPAD All Commodities (1989 92 Consumption Data)

Gen. Population 0. 005989 60 0.001381 14 0.000505 5 All Infants 0. 013251 133 0.003683 37 0.000864 9 Children 1  6 0. 010974 110 0.002552 26 0.001309 13 Children 7  12 0.008721 87 0.001644 16 0.000722 7 Females 13  50 0.004444 44 0.000918 9 0. 000318 3 Males 13 19 yrs 0. 003596 36 0.000899 9 0. 000428 4 Table 6: Results of the Carbaryl Acute Dietary Analyses (Market Survey Data Not Included)

Pop. Subgroup 99.9 th Percentile 99 th Percentile 95 th Percentile Exposure (mg/ kg/ day) % aPAD Exposure (mg/ kg/ day) % aPAD Exposure (mg/ kg/ day) % aPAD 36 Males 20+ yrs 0. 004223 42 0.000929 9 0. 000318 3 Seniors 55+ yrs 0.005789 58 0.001068 11 0.000307 3 All Commodities (1994 98 Consumption Data)

Gen. Population 0. 006150 62 0.001467 15 0.000508 5 All Infants 0. 013420 134 0.004027 40 0.000922 9 Children 1  6 0. 013812 138 0.003282 33 0.001460 15 Children 7  12 0.007073 71 0.001473 15 0.000685 7 Females 13  50 0.004794 48 0.000997 10 0.000322 3 Males 13 19 yrs 0. 005181 52 0.000929 9 0. 000420 4 Males 20+ yrs 0. 003940 39 0.000922 9 0. 000336 3 Seniors 55+ yrs 0.005442 54 0.001003 10 0.000313 3 Table 7. Results of the Carbaryl Sensitivity Analyses.

Acute  All Commodities at the 99.9th percentile of exposure (Market Basket Survey Data Not Included)

Pop. Subgroup All commodities Eliminating Peaches Eliminating Apples Eliminating Commodities with No Detectable Residues Exposure (mg/ kg/ day) % aPAD Exposure (mg/ kg/ day) % aPAD Exposure (mg/ kg/ day) % aPAD Exposure (mg/ kg/ day) % aPAD Gen. Population 0. 005989 60 0.005451 55 0.004943 49 0.005870 59 All Infants 0. 013251 133 0.007188 72 0.011784 118 0.012965 130 Children 1  6 0. 010974 110 0.010164 102 0.008201 82 0.0010765 108 Children 7  12 0.008721 87 0.008243 82 0.006867 69 0.008555 86 Females 13  50 0.004444 44 0.004262 43 0.003890 39 0.004434 44 Males 13 19 yrs 0. 003596 36 0.003535 35 0.003014 30 0.003802 38 Males 20+ yrs 0. 004223 42 0.003949 39 0.003575 36 0.004178 42 Seniors 55+ yrs 0.005789 58 0.005456 55 0.005094 51 0.005703 57 When the CMBS data were included in the assessment, the acute risk picture for carbaryl significantly changed as risks for all population subgroups considered were less than 100 percent of the aPAD (Table 8). If 1989 1992 CFSII data are used, all infants and children (1 6 years) again had the highest associated risk levels at 73 percent and 75 percent of the aPAD, respectively. For 1994 1998 CFSII data, all infants and children (1 6 years) also have the highest risks at 81 and 93 percent of the 37 aPAD, respectively. At the present time, information from the industry sponsored Carbamate Market Basket Survey has been approved for use in dietary risk assessments with appropriate characterization of uncertainties associated with the conduct of the study. Hence, the use of these data in this assessment should be considered with associated caveats (e. g., rubbing fruit).

Table 8. Results of the Carbaryl Acute Dietary Analyses (Market Basket Survey Data Included)

Pop. Subgroup 99.9 th Percentile 99 th Percentile 95 th Percentile Exposure (mg/ kg/ day) % aPAD Exposure (mg/ kg/ day) % aPAD Exposure (mg/ kg/ day) % aPAD All Commodities (1989 92 Consumption data)

Gen. Population 0. 004580 46 0.001251 13 0.000465 5 All Infants 0. 007272 73 0.002875 29 0.000593 6 Children 1  6 0. 007546 75 0.002283 23 0.001242 12 Children 7  12 0.006126 61 0.001355 14 0.000682 7 Females 13  50 0.003672 37 0.000863 9 0. 000300 3 Males 13 19 yrs 0. 002735 27 0.000818 8 0. 000409 4 Males 20+ yrs 0. 003416 34 0.000842 8 0. 000298 3 Seniors 55+ yrs 0.004601 46 0.000921 9 0. 000277 3 All Commodities (1994 98 Consumption data)

Gen. Population 0. 004759 48 0.001310 13 0.000468 5 All Infants 0. 008051 81 0.002624 26 0.000653 7 Children 1  6 0. 009274 93 0.002819 28 0.001352 14 Children 7  12 0.004831 48 0.001226 12 0.000646 6 Females 13  50 0.004194 42 0.000898 9 0. 000301 3 Males 13 19 yrs 0. 004430 44 0.000876 9 0. 000403 4 Males 20+ yrs 0. 003254 33 0.000840 8 0. 000313 3 Seniors 55+ yrs 0.004427 44 0.000836 8 0. 000281 3 4.2.3 Chronic Dietary Risk Assessment Chronic dietary risks were calculated using the same equations as described above for the acute dietary risk estimates with different inputs appropriate for this exposure duration. Chronic dietary risks are not of concern as risks were <1 percent of the cPAD for all population subgroups considered (Table 9). The Carbamate Market Basket Survey (CMBS) was not used in the calculation of chronic dietary risks because risks were low without considering it and it is not appropriate because it is for single serving data. 38 Table 9: Results of the Carbaryl Chronic and Cancer Dietary Analyses.

Chronic Pop. Subgroup 1989 92 1994 1998 Exposure (mg/ kg/ day) % cPAD Exposure (mg/ kg/ day) % cPAD Gen. Population 0. 000032 <1 0.000035 <1 All Infants 0. 000054 <1 0.000059 <1 Children 1  6 years 0. 000057 <1 0.000074 <1 Children 7  12 years 0. 000036 <1 0.000034 <1 Females 13  50 years 0. 000026 <1 0.000028 <1 Males 13 19 years 0. 000022 <1 0.000026 <1 Males 20+ years 0. 000031 <1 0.000032 <1 Seniors 55+ 0.000031 <1 0.000030 <1 Cancer Gen. Population 0. 000032 2.8 x 10 8 0.000035 3.04 X 10 8 4.2.4 Cancer Dietary Risk Assessment The following equations were used to calculate dietary exposure and cancer risk using the Q1* approach for carbaryl (i. e., linear, low dose extrapolation). Cancer risks were only calculated for the general population.

Dietary exposure (mg/ kg/ day) = consumption x residue Dietary cancer risk = average food exposure (mg/ kg/ day) x Q1* (mg/ kg/ day) 1 Risk estimates above 1 x 10 6 are considered to be of concern. Results indicate a maximum lifetime risk of 2.8x10 8 for the general US population if the 1989 to 1992 CFSII data were used. If 1994 to 1998 CFSII data are considered, results are similar for the general U. S. population where cancer risks are 3.04x10 8 (Table 9). The Carbamate Market Basket Survey (CMBS) was not used in the calculation of chronic dietary risks.

4.2.5 Characterization/ Uncertainties of the Dietary Risk Estimates ° No detectable residues were found in/ on several commodities: carrots, chicory, flax seed, horseradish, parsnip, salsify, potato, celery, canned spinach, head lettuce, leaf lettuce, rhubarb, sugarbeets, Swiss chard, brussels sprouts, cabbage, kohlrabi, soybean, corn, banana, peanuts, meat, meat fat, and milk. Sensitivity analyses conducted by eliminating crops where no detectable residues were found showed that risk estimates were not significantly affected by assuming zero in place of ½ LOD on samples reported as not detectable. 39 ° The consumption database routinely used for dietary exposure analysis, CSFII 1989 1992, has a limited number of individuals for the age group infants less than one year old. The USDA has conducted the Supplemental Children's Survey (approximately 5000 children). For comparative purposes, based on comments from the registrant, the CSFII 1994 1998 data have also been used for risk calculations. The trends in the results essentially did not change significantly regardless of which data were used. Risks, in all cases, were slightly higher for all subpopulations using the 1994 to 1998 data.

° The latest cooking and processing factors that were available have been used in the assessment (e. g., processing grapes to raisins, cooking and washing factors for peas, and oil production for peanuts).

° The results of the Critical Exposure Contribution analysis showed that peaches and apples comprised a large percentage of the residues found in the upper percentile tails of the acute exposure distribution for both infants and children (i. e., they were the major risk contributors for children and infant exposure at the upper percentiles).

° Detectable residues from composite monitoring data for non blended food forms were used to generate residue values in single units using the Allender method. Though there is a statistical basis for using these data, some degree of uncertainty can be associated with this method. [Note: Peaches are a risk driver in this assessment and this analysis is based on single serving 2000 PDP data instead of data that have been decomposited.]

4.3 Estimated Environmental Concentrations In Water Dr. Laurence Libelo of the Environmental Fate and Effects Division (EFED) provided an analysis of the available monitoring data and a screening level assessment using simulation models to estimate the potential Estimated Environmental Concentrations (EECs) of carbaryl in ground and surface water (June 28, 2001). Section 4.3.1: Environmental Fate Characteristics provides a summary of the fate characteristics of carbaryl. Section 4.3.2: Monitoring Data provides a summary of the monitoring data that were considered in this assessment. Section 4.3.3: Modeling EECs presents the EECs used for comparison to the DWLOCs (Drinking Water Levels of Concern) calculated for the aggregate risk assessment (presented in Section 5 below).

4.3.1 Environmental Fate Characteristics Carbaryl is considered to be moderately mobile and not likely to persist or accumulate in the environment and its degradate, 1 naphthol, appears to be less persistent and mobile than carbaryl itself. Under acidic conditions with limited microbial activity they may persist.

Carbaryl dissipates in the environment by abiotic and microbially mediated degradation. The major degradation products are CO2 and 1 naphthol, which is further degraded to CO2. Carbaryl is stable to hydrolysis in acidic conditions but hydrolyzes in neutral (t1/ 2 = 12 days) and alkaline 40 environments (pH= 9, t1/ 2 = 3.2 days). Carbaryl is degraded by photolysis in water (t1/ 2 = 21 days). Under aerobic conditions, the compound degrades rapidly by microbial metabolism, with half lives of 4 to 5 days in soil and aquatic environments. In anaerobic environments metabolism is much slower with ½ lives on the order of 2 to 3 months. Carbaryl is moderately mobile in the environment (Kf = 1.7 to 3.5).

The major metabolite of carbaryl degradation by abiotic and microbially mediated processes is 1 naphthol. This degradate represented up to 67 percent of the applied carbaryl in degradation studies. It is also formed in the environment by degradation of napthalene and other polyaromatic hydrocarbons. Only limited information is available for the environmental transport and fate of 1 naphthol. While guideline studies were not specifically submitted for 1 naphthol, open literature data suggest it is less persistent and less mobile than carbaryl.

4.3.2 Monitoring Data Monitoring data for groundwater and surface water are limited, and targeted data are not available. As reported in the U. S. E. P. A. Pesticides in Groundwater Database, carbaryl was detected in 0.4% of wells sampled. Carbaryl was detected in California (2 out of 1433 wells), Missouri (11 out of 325 wells), New York (69 out of 21027 wells) Rhode Island (13 out of 830 wells) and Virginia ( 11 out of 138 wells) (Jacoby et al., 1992). The maximum concentration detected was 610 µg/ L in NY, though typically the measured concentrations were significantly lower.

The EPA STORET database contains 9389 records indicating that analysis was done for carbaryl. Of these, only 4 were reported concentrations above the detection limits. These analyses were all from one well in Cleveland, OK in 1988. The 4 reported concentrations were between 0.8 and 1 ppb.

Carbaryl was detected at greater than the detection limit (0.003 : g/ L) in 1.1% of groundwater samples in the USGS NAWQA program. The maximum observed concentration was 0.021 : g/ L. Detections were mainly from three settings: wheat (5.8 % of well samples from wheat land use), orchards and vineyards (1.7 % of well samples from orchard and vineyard land use), and urban (1.8% of urban groundwater samples).

A number of field studies have reported detectable carbaryl concentrations in surface waters. Because of limitation in the analytical methods used, there is some question as to the accuracy of carbaryl analysis. Poor analytical methods probably have resulted in lower detection rates and lower concentrations than actually present.

Carbaryl was detected in surface water in 46% of the 36 NAWQA study units between 1991 and 1998. Carbaryl (along with carbofuran) was one of the two most widely detected insecticides. A significant portion of the total carbaryl applied was apparently transported to streams. Out of 5220 surface water samples analyzed, 1082 or about 21 percent were reported as having detections greater than the minimum detection limit (MDL). The maximum reported concentration was 5.5 ug/ L. For samples with positive detections the mean concentration was 0.11 : g/ L with a standard deviation of 0.43 : g/ L. In areas with high agricultural use, the load measured in surface waters was relatively 41 consistent 42 across the country at about 0.1 percent of the amount used in the basins. Streams draining urban areas showed more frequent detections and higher concentrations than streams draining agricultural or mixed land use areas.

Aventis CropScience submitted interim results of an on going surface water monitoring study of carbaryl residues in surface water in areas with high agricultural and residential use. In this limited drinking water study, raw water was collected at 16 sites in agricultural areas and four in areas draining suburban areas. Samples at municipal water treatment facilities were collected for 8 12 months. When raw water showed positive detections for carbaryl, finished water samples collected at the same time were analyzed.

In raw water samples from suburban sites, detectable residues in raw water ranged from 0.002 to 0.023 : g/ L. In samples from agricultural sites, 9 out of 15 water sources had some detectable level of carbaryl. The detections were generally at low levels with one of about 0.16 : g/ L and one of 0.031 : g/ L. The rest were below the level of quantitation (< 0.03 : g/ L). Samples from finished water were generally lower than raw water though it appears that raw and finished water sampling did not evaluate the same mass of water. The data do not give a good indication of the effectiveness of treatment because samples exiting and entering the treatment plant were different. In several cases, finished water had higher concentrations than raw water and finished water had detectable carbaryl when the raw did not. The highest concentration measured was in finished water (0.16 : g/ L). Raw water sampled at the same time had a much lower concentration (0.010 : g/ L). This illustrates that carbaryl contamination is transient, and that it is unlikely that any sampling would catch the actual peak concentration. That, and the limited number of sites sampled, limit the usefulness of this study. Non targeted monitoring, such as the NAWQA program has shown that much higher concentrations occur. This study, while useful, does not provide sufficient information to allow estimation of actual peak and mean concentrations that actually occur in all areas or of the effect of treatment.

4.3.3 Modeling EECs Because of the relatively limited persistence of the compound in the environment, it is highly unlikely that the non targeted monitoring studies which have been completed detected the maximum concentrations that occur. As a result, the non targeted monitoring data have been determined to be of limited utility in developing estimated environmental concentrations (EECs) for ecological and human health risk assessment. Therefore, computer modeling was used to estimate surface water and groundwater concentrations that could be expected from normal agricultural use (Table 10). The results of the modeling are supported by the available monitoring data. These results have been characterized as conservative, though not unreasonable estimates of possible concentrations in drinking water.

Surface Water Modeling: Computer modeling with the EPA PRZM3.12 and EXAMS 2.97.7 programs were used to estimate the concentration of carbaryl in surface water. Index reservoir scenarios corrected for Percent Cropped Area (PCA) for representative crops were used. Three different application rates were used in modeling: the maximum allowed on the label for the specific crop, an "average" rate and the maximum rate reported to actually be used. EECs varied greatly depending on the geographic location, crop and application rate. The maximum calculated acute and chronic EECs 43 (494 ppb and 28 ppb, respectively) resulted from use on citrus in Florida. Modeling "average" and maximum resulting use rates gave EEC values generally 40 60% lower than maximum. The source of drinking water in relation to the EECs must be carefully considered when using these data. In this case, the results for Florida provided the highest estimates, however; in Florida the majority of drinking water is derived from groundwater (> 90%) so high surface water concentrations do not necessarily indicate high exposure. As a result, both Florida and the results for Oregon apples have been considered in the aggregate assessment (see Section 5.0 for more information). The EECs for Oregon apples are the next highest values for both the acute and chronic estimates.

Ground Water Modeling: SCI GROW was used to calculate a groundwater screening exposure value to be used in determining the potential risk to human health. Carbaryl chemical properties are outside the range of values for which SCI GROW was developed (i. e., aerobic metabolism is faster and its partition coefficient is larger which equates to less leaching than the reference compounds  both factors indicate carbaryl degrades faster). SCI GROW estimates for groundwater EECs may not predict with complete accuracy, maximum levels because the concentrations calculated are 90 day averages. It is possible; therefore, that groundwater concentration peaks could not be identified. Groundwater levels are anticipated, however, to be more stable over time than surface water concentrations.

Table 10: Carbaryl Drinking Water Estimated Environmental Concentrations (EECs)

Crop Application Rate Descriptor Number of Applications per Year Pounds A. I. per application Water Acute (ppb) (1 in 10 year peak single day concentration) Water Chronic (ppb) (1 in 10 year annual average concentration)

Source: Surface Water (PRZM/ EXAMs)

Sweet Corn (OH) (PCA = 0.46) Maximum 1 8 2 37 3.2 Average 2 2 3. 4 45 2.2 Maximum 3 Reported 3 1 15 0.9 Source: Surface Water (PRZM/ EXAMs)

Field Corn (OH) (PCA = 0.46) Maximum 1 4 2 30 2.1 Average 2 2 1 13 0.6 Maximum 3 Reported 2 1. 520 1 Source: Surface Water (PRZM/ EXAMs)

Apples (OR) (PCA = 0.87) Maximum 1 5 2 144 9 Average 2 2 1. 2 12 0.7 Maximum 3 Reported 2 1. 625 1 Source: Surface Water (PRZM/ EXAMs)

Sugar Beats (MN) (PCA = 0.87) Maximum 1 2 1. 519 2 Average 2 1 1. 5 12 1.1 Maximum 3 Reported 1 1. 2 9 0. 9 Source: Surface Water (PRZM/ EXAMs)

Citrus (FL) (PCA = 0.87) Maximum 1 4 5 494 28 Average 2 2 3. 4 246 11 Table 10: Carbaryl Drinking Water Estimated Environmental Concentrations (EECs)

Crop Application Rate Descriptor Number of Applications per Year Pounds A. I. per application Water Acute (ppb) (1 in 10 year peak single day concentration) Water Chronic (ppb) (1 in 10 year annual average concentration)

44 Maximum 3 Reported 3 4. 26 411 16 Source: Surface Water Monitoring 5.5 (Maximum Observed Concentration)

Source: Groundwater (SCI GROW) Maximum 1 5 40. 8 0. 8 Source: Groundwater (NAWQA Monitoring Data) 0.02 0.02 1 Maximum application rate on label 2 Average application rate from Quantitative Usage Analysis for Carbaryl, prepared July 21, 1998 by Frank Hernandez, OPP/ BEAD 3 Maximum rate of application reported in DOANES survey data 4.4 Residential Risk Assessment The residential risk assessment addresses exposures that individuals receive through their use of consumer products that contain carbaryl and those exposures one could receive from frequenting areas that have been previously treated with carbaryl such as a home lawn, a garden, or a golf course. Carbaryl can also be applied in wide area treatments such as on oyster beds or as a mosquito adulticide. These exposures have also been addressed in this assessment. The Occupational and Residential Exposure Assessment (D281418) was prepared by Jeff Dawson with the exception of the tobacco assessment completed by Dr. Virginia Dobozy. The document D281418 contains detailed descriptions of the data used, methods, and risks calculated for each scenario. Please refer to that document for more specific information.

Section 4.4.1: Home Uses provides more specific information pertaining to how carbaryl consumer products are used in addition to the information presented above in Section 4.1: Summary of Registered Uses as it applied more directly to the residential risk assessment. Section 4.4.2: Residential Handler Risk Assessment describes the data, methods, and risk results (both cancer and noncancer) associated with the use of consumer products which contain carbaryl. Section 4.4.3: Residential Postapplication Risk Assessment describes the data, methods, and risk results associated with exposures to the general population including adults, infants, and youth aged children that occur from frequenting treated areas. Section 4.4.4: Residential Risk Characterization provides information pertaining to the quality of the assessment including data used, uncertainties with the methods, and any other information 45 that might be used to describe the quality of the results. Section 4.4.5: Risks Associated With Use In Tobacco describes how risks were calculated for smokers who may consume carbaryl treated tobacco in their cigarettes. Section 4.4.6: Other Residential Uses characterizes other potential sources of exposure outside of those quantitatively described in this assessment.

4.4.1 Home Uses Carbaryl is a widely used consumer product. Available products include liquids, wettable powders, and dusts for insect control on fruits, vegetables, ornamentals, and lawns. Products for flea control on pets are also available. Some of the equipment used in application includes dust shaker cans, garden hose end sprayers, trigger sprayers, low pressure handwands, belly grinders, push type spreaders, aerosol cans, and pet collars. In addition to the information presented in Section 4.1: Summary Of Registered Uses, Aventis Crop Science at the time of the September 24, 1998 SMART Meeting also presented the following information that is key to interpreting the residential risk assessment. Carbaryl accounted for approximately 9 percent of the total residential insecticide market and was ranked fourth on the list behind the pyrethroids, chlorpyrifos, and diazinon. In addition, the registrant also presented the following:

° According to the registrant, insect control on vegetables (~ 58% of users), annuals (~ 50% of users), lawns (~ 35% of users), trees/ shrubs (~ 34% of users) account for the majority of homeowner uses for carbaryl. Pet uses also accounted for ~13 percent of users.

° The annual frequency of use, for all crops/ targets, was reported to be at the 60 th percentile for 1 to 2 times per year and at the 84 th percentile for 5 times per year.

° Aphids, ants, fire ants, fleas, and slugs/ snails are predominant pests controlled by residential carbaryl users (~ 30 down to 15% of users, respectively).

° Most (75%) of vegetable gardens treated with carbaryl are <800 ft 2 but ~8 percent are between 800 and 1500 ft 2 , ~9 percent are between 1500 and 5000 ft 2 , and ~6 percent are greater than 5000 ft 2 . Tomatoes, peppers, cucumbers, beans, and fruit trees represent the most treated garden plants.

° Most (82%) of flower gardens treated with carbaryl are <500 ft 2 but ~10 percent are between 500 and 1200 ft 2 , and ~8 percent are greater than 1200 ft 2 . Roses, shrubs, and certain annuals represent the most treated flowering/ ornamental plants.

° Dusts (65%) and liquid concentrates (25%) account for most carbaryl sales in the residential annual market of 2 million pounds per year.