UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 Office of Prevention, Pesticides and Toxic Substances January 5, 2006 SUBJECT: Iodomethane: Revised HED Human Health Risk Assessment; DP Barcode: D325080, PC Code: 000011 FROM: Elizabeth Mendez, Ph. D, Toxicologist/ Risk Assessor 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: Mary Waller, Product Manager Registration Division Attached is HED's risk assessment of the fumigant, iodomethane. HED has evaluated the hazard and exposure data and conducted exposure assessments, as needed, to estimate the risk to human health that will result from the proposed uses of iodomethane.

This risk assessment addresses both exposures in general population and for those occupationally exposed. Exposures in the general population occur primarily via inhalation for those in proximity to treated fields( i. e., bystanders). Occupational exposures also occur via inhalation. The Agency has addressed these scenarios in this assessment. Drinking water exposure is also anticipated at some level. Although iodomethane is used as an agricultural pesticide, it is considered a non food use chemical since it is quickly degraded or metabolized and subsequently incorporated into natural plant constituents. The levels of iodide released from iodomethane degradation/ metabolism are lower than those expected to cause toxic effects. Furthermore, enforcement of tolerances would not be possible since no iodide free samples are available and residue field trials show evidence of control samples with higher iodide residues than iodomethane treated samples. Moreover, iodide is ubiquitous in the environment and a required nutrient. Finally, iodomethane residues must dissipate in the soil prior to planting. Accordingly, HED concluded tolerances are not required for iodomethane. As a result, a dietary risk assessment has not been conducted.

This risk assessment used the guidance ( RfC methodology) developed by the Agency's Office of Research and Development ( ORD) as well as a chemical specific physiologically based pharmacokinetic ( PBPK) model for the derivation of human equivalent concentrations ( HECs) for use in margin of exposure ( MOE) calculations. Furthermore, both deterministic and probabilistic methods were used to estimate exposures to bystanders around treated fields which are the key concern. The deterministic approach is based on monitoring data and the use of the EPA's Industrial Source Complex: Short Term Model ( ISCST3). Use of ISCST3 is thought to provide upper bound estimates of likely exposures predominantly because its outputs are based on a constant wind vector ( speed and direction) flowing directly downwind to those exposed. Since defining the ISCST3 method, OPP has considered three additional modeling systems that allow for the incorporation of actual meteorological data into assessments ( i. e., PERFUM, FEMS & SOFEA © ) . The FIFRA Science Advisory Panel ( SAP) evaluated these systems in August and September of 2004. PERFUM ( i. e., Probabilistic Exposure and Risk model for Fumigants) has been used herein in addition to ISCST3 in order to evaluate distributional bystander exposure. The SAP provided very similar comments for each distributional model. The Agency has used PERFUM for this assessment because modifications suggested by the SAP were complete, the inputs were readily available, and the comparative computer processing time was lower than FEMS and SOFEA © . The ISCST3 and PERFUM model runs have been summarized in the appendices of this document. Additional information can be provided other than that included in this document that can be used to detail all of the modeling analyses that have been completed ( e. g., input and output files for each). Arvesta error correction comments ( 12/ 21/ 05) have been incorporated. No significant changes outside of minor error corrections as noted specifically in their comments have been made. HUMAN HEALTH RISK ASSESSMENT Iodomethane U. S. Environmental Protection Agency Office of Pesticide Programs Health Effects Division ( 7509C) Elizabeth Mendez, Ph. D., Toxicologist/ Risk Assessor Jeffrey L. Dawson, Chemist/ Risk Assessor Date: January 5, 2006 HUMAN HEALTH RISK ASSESSMENT Iodomethane Risk Assessment Team:

Risk Assessor: Elizabeth Mendez, Ph. D. Jeffrey L. Dawson Residue Chemistry Christine Olinger Occupational and Residential Exposure: Jeffrey L. Dawson Epidemiology: Elizabeth Mendez, Ph. D Toxicology: Elizabeth Mendez, Ph. D PBPK Model Evaluation: Hugh Barton, Ph. D. Paul Schlosser, Ph. D.

Drinking Water Estimates: Faruque Khan 1.0 Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2.0 Ingredient Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 3.0 Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 3.1 Description of Primary Crop Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 3.2 Description of Livestock Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 3.3 Description of Rat Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 4.0 Hazard Characterization/ Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 4.1 Hazard Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 4.1.1 Database Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 4.1.2 Endpoints . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 4.1.3 Dose response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 <IP_ADDRESS> Inhalation Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 <IP_ADDRESS> Dietary Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 <IP_ADDRESS> Dermal Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 <IP_ADDRESS> Classification of Carcinogenic Potential . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 4.1.4 Endocrine Disruption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 4.2 Uncertainty Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 4.3 Summary of Toxicological Endpoint Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 5.0 Public Health Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 6.0 Non Occupational Exposure Assessment and Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 6.1 Residential Bystander Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 6.1.1 Bystander Exposure From Known Area Sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 <IP_ADDRESS> Bystander Exposures From Known Area Sources Calculated Using The Monitoring Data Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 <IP_ADDRESS> Bystander Exposures From Known Area Sources Calculated Using The ISCST3 Modeling Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 <IP_ADDRESS> Bystander Exposures From Known Area Sources Calculated Using The PERFUM Modeling Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 6.1.2 Ambient Bystander Exposure From Multiple Area Sources . . . . . . . . . . . . . . . . . . . 43 6.2 Bystander Risk Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 6.3 Residue Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 6.4 Water Exposure/ Risk Pathway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 7.0 Aggregate Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 8.0 Cumulative Risk Assessment and Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 9.0 Occupational Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 10.0 Data Needs and Label Requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 10.1 Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 10.2 Residue Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 10.3 Occupational and Residential Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 Appendix A: Review Of PBPK/ PD Model Appendix B: Toxicity Profile Appendix C: Methodologies for Inhalation Risk Calculations and Human Equivalent Concentration Arrays Appendix D: Analysis Of Field Volatility Data For Pre plant Field Uses Appendix E: Downwind Air Concentrations Calculated With ISCST3 For PrePlant Field Uses Appendix F: Downwind Air Concentrations Calculated With PERFUM For PrePlant Field Uses Appendix G: Occupational Risk Associated with Agricultural Fumigations 1 1.0 Executive Summary The Health Effects Division ( HED) of EPA's Office of Pesticide Programs has conducted a human health risk assessment for the active ingredient, iodomethane, also referred to as methyl iodide. The proposed use of iodomethane is as a pre plant soil fumigant in strawberries, tomatoes, peppers, perennial crop ornamentals, nurseries, cut flowers, turf, and tree and vines. Iodomethane has been identified as a possible replacement for methyl bromide ( MeBr), a fumigant with numerous registered uses.

There are no registered pesticidal uses of iodomethane at present. There are, however, some industrial and commercial uses. Currently, it is used as an intermediate in the manufacture of some pharmaceuticals, in methylation processes and in the field of microscopy.

Although iodomethane will be used as an agricultural pesticide, it is considered a non food use chemical since it is quickly degraded or metabolized and subsequently incorporated into natural plant constituents. The levels of iodide released from iodomethane degradation/ metabolism are lower than those expected to cause toxic effects. Furthermore, iodomethane residues must dissipate in the soil prior to planting to prevent phytotoxicity. Accordingly, HED concludes that tolerances are not required for iodomethane at this time. As a result, a risk assessment has not been conducted for the dietary exposure scenario. The U. S. population, however, may be exposed to iodomethane through drinking water; therefore, a qualitative drinking water risk assessment has been conducted and no risks have been identified from this potential source of exposure.

In the general population, exposure to iodomethane is anticipated to occur via inhalation or oral ( drinking water) routes but not through the dermal route. Dermal exposure to iodomethane of any significance is not expected based on the delivery systems used ( e. g., soil injection or drip irrigation), packaging ( i. e., pressurized cylinders), and emission reduction technologies ( e. g., tarping). The high vapor pressure of iodomethane also makes significant dermal exposure unlikely. The general public, however, may be exposed to fumigants in air because of their volatility following application. Specifically, fumigants can off gas into air and be transported off site by winds to those in proximity to treated fields ( i. e., bystanders). Consequently, the Agency conducted a quantitative human health risk assessment for nondietary exposure only via the inhalation route. For the purpose of conducting inhalation risk assessments, the current iodomethane database provides sufficient information to assess risks to the human population following iodomethane exposure via the inhalation route. Exposures may be acute ( less than 24 hours), short term ( 1 30 days), intermediate term ( 1 month 6 months), or long term in duration. Acute exposures have been quantitatively assessed because this duration is the key concern due to the anticipated use pattern of iodomethane, its emission profile, and the nature of its toxicity. Additionally, for these same reasons, it is believed that acute assessments are health protective for other durations of exposure.

Iodomethane has a severe to moderate acute toxicity profile; it is severely toxic via the oral route ( Toxicity Category II), corrosive to the eye ( Toxicity Category I ) and a severe dermal irritant ( Toxicity Category II). Via the inhalation route, it has been classified as a Category IV chemical ( slightly toxic) with an LC 50 of 4 mg/ L.

The pattern of toxicity attributed to iodomethane exposure via the inhalation route includes developmental toxicity ( manifested as fetal losses and decreased live births), histopathology findings ( respiratory tract lesions and salivary gland squamous cell metaplasia ), thyroid toxicity, neurotoxicity and generalized systemic toxic effects ( body weight and body weight gain decreases). The critical effects of iodomethane exposure via the inhalation route are the fetal losses observed in two developmental toxicity studies in rabbits, the 2 histopathological lesions reported in three studies, and the generalized systemic toxicity seen throughout the database. The guideline inhalation chronic toxicity/ carcinogenicity study in rats and the carcinogenicity study in mice revealed that chronic exposure to iodomethane resulted in an increased incidence of thyroid follicular cell tumors. The sustained perturbation of thyroid hormone homeostasis characteristic of iodomethane exposure ( observed in rats, mice, and rabbits) has been established as the operative mode of action ( MOA) for this tumorigenic response. As a result, HED's Cancer Assessment Review Committee ( CARC) has identified iodomethane as " not likely to be carcinogenic to humans at doses that do not alter rat thyroid hormone homeostasis."

An extensive mechanistic data set as well as a physiologically based pharmacokinetic ( PBPK) model are available for iodomethane. These data and model constitute a sophisticated effort to better characterize the toxicity profile for this compound in terms of developmental toxicity, respiratory tract lesions, and thyroid hormone perturbations identified as the critical effects of iodomethane exposure. In addition, the use of a PBPK model that takes into consideration the toxicokinetic aspect of iodomethane exposure enables the Agency to use chemical specific parameters to determine the most appropriate dose metric and internal dose in calculating human equivalent concentrations ( HECs) instead of the default inputs used in the Agency's Reference Concentration ( RfC) methodology. The Agency has reviewed these data and their usefulness to calculate human equivalent concentrations ( HECs) based on chemical specific data. In general, the model and the mechanistic studies used to provide its inputs are considered adequate and their results have been incorporated into this risk assessment.

Based on the toxicity profile and the major exposure routes of iodomethane, endpoints have been selected for the residential/ bystanders and occupational human health risk assessments. HED is currently using the reference concentration ( RfC) methodology along with a PBPK to derive the human equivalent concentration ( HEC) for inhalation exposures in this risk assessment. Under the RfC methodology and the PBPK model approach, endpoint selection is based on the HECs which are derived from the NOAELs of the selected studies. Different HECs may be derived for non occupational and occupational assessments due to the time adjustments conducted for the exposure scenarios. While non occupational exposure is presumed to potentially occur 24 hours/ day, 7days/ week; occupational exposure is presumed to occur for 8 hours/ day and 5 days/ week. The specific concentrations and endpoints for the exposure scenarios are summarized below:

° Acute inhalation: Two critical endpoints have been identified for this risk assessment: nasal histopathology in the subchronic inhalation toxicity study in rats and the fetal losses in the developmental toxicity study in rabbits. The purpose of this approach is to bracket the range of possible effects associated with iodomethane from the least to most adverse effects which have been identified. For the nasal histopathology endpoint, HED selected an HEC of 2.9 or 3.7 ppm ( bystander and occupational risk assessment, respectively) from the NOAEL of 21 ppm based on degeneration of the olfactory epithelium. For the developmental endpoint, HED selected an HEC of 4.0 ppm ( non occupational risk assessment) from the NOAEL of 10 ppm based on fetal losses and decreased fetal weights in a developmental toxicity study in rabbits at the LOAEL of 20 ppm. An uncertainty factor ( UF) of 30X defines the HED level of concern.

In the case of the nasal histopathology lesions, sustained glutathione ( GSH) depletion has been identified as a key event in the toxicity pathway leading to the lesions. Consequently, GSH depletion (# 50%) is the dose metric used in the PBPK model for the interspecies extrapolation to determine the NOAEL for the nasal lesions. Using the HECs of 2.9 or 3.7 ppm ( bystander and occupational risk assessment, respectively) results in a time weighted average GSH depletion of .25% which is below 3 the level of GSH depletion commonly cited in the literature as critical for development of nasal histopathology.

The dose metric used for the fetal losses is the level of fetal serum inorganic iodide after a single day of exposure. Based on this dose metric an HEC of 17 ppm could be used for the bystander risk assessment. However, this HEC would be based on the assumption that human fetal serum iodide levels are .75% of maternal levels. Although there is some evidence in support of this assumption in the peer reviewed literature, the Agency has concluded that the evidence is not sufficiently robust ( i. e., limited and often indirect) to establish an HEC of 17 ppm as a point of departure for the risk assessment. As a result, an HEC of 4.0 ppm is used in the risk assessment based on the assumption that there is an equivalent distribution of fetal serum iodide in rabbits and humans. The biomedical literature indicate that the " true" value is likely towards the high end of this range ( i. e., 4 17 ppm). However, there does not seem to be adequate information to establish a particular value in the higher part of that range is the most accurate value. Consequently, there is higher confidence in the use of the 4.0 ppm HEC as a point of departure for this assessment based on the endpoint of fetal losses.

° Short term and Intermediate inhalation ( bystander): HED selected an HEC of 1.25 ppm from the NOAEL of 5 ppm based on decreased pup weight and weight gain, decreased thymus weights, and delays in vaginal patency acquisition seen in the multigeneration reproduction toxicity study at the LOAEL of 20 ppm. An uncertainty factor ( UF) of 30X defines the HED level of concern.

° Short, Intermediate term inhalation ( occupational): HED selected an HEC = 3.7 ppm from the NOAEL of 21 ppm based on minimal mild degeneration of the olfactory epithelium seen at the LOAEL of 70 ppm in the subchronic inhalation toxicity study in rats. An uncertainty factor ( UF) of 30X defines the HED level of concern.

° Long term inhalation: HED selected an HEC = 0.89 ppm or 3.75 ppm ( bystander and occupational risk assessments, respectively) from the NOAEL of 5 ppm based increased incidence of salivary gland squamous cell metaplasia seen at the LOAEL of 20 ppm from the chronic toxicity/ carcinogenicity study in rats. An uncertainty factor ( UF) of 30X defines the HED level of concern.

Releases of fumigants such as iodomethane can be categorized in two distinct manners that include addressing exposures from known area sources ( e. g., a treated agricultural field) and also by evaluating available ambient air levels from multiple area sources that could occur from many applications in a region ( e. g., several farms in a specific valley).

The evaluations of bystander exposures that can result from known area sources considered field volatility data directly from several studies, results from an Agency developed Gaussian air plume model ( Industrial Source Complex Short Term Model, ISCST3), and results from PERFUM ( i. e., Probabilistic Exposure and Risk model for Fumigants) which is a new modeling system based on ISCST3 that allows for incorporation of actual meteorological data into probabilistic assessments. In fact, the FIFRA Science Advisory Panel ( SAP) evaluated three such modeling systems for fumigants ( i. e., PERFUM, FEMS & SOFEA © ) in August and September of 2004. The Agency used PERFUM for this assessment because modifications suggested by the SAP were complete, the inputs were readily available, and the comparative computer processing time was lower than FEMS and SOFEA © . 4 For known area sources ( i. e., treated agricultural fields), HED first used monitoring data to assess bystander exposures to iodomethane. Risks exceeded HED's level of concern based on these data. In addition, the Industrial Source Complex  Short Term model ( ISCST3) was used to further characterize exposures by extrapolating to conditions under which empirical data are not be available. In the ISCST3 analysis, varied meteorological conditions, field sizes, and emission rates were considered. Results demonstrate that for the cases considered, many risks exceed HED's level of concern ( MOEs < 30) for distances less than 100 meters downwind of the treated fields larger than 1 acre especially when the atmosphere is relatively stable and where wind speeds < 5 mph. MOEs decrease as field sizes increase while MOEs increase as the atmosphere becomes less stable leading to conditions where more off target drift can occur. There is not a significant impact in the results due to the two different HECs that were considered.

At the upper percentiles of the exposure distributions generated with PERFUM, the results presented in are markedly similar to those calculated with ISCST3 which supports the construct that the ISCST3 results in conservative estimates of exposure. If maximum buffer distances at the 95th percentile of exposure are considered, the lowest predicted buffer distance for 40 acre fields is approximately 65 meters ( at HEC = 4 ppm) and 120 meters ( at HEC = 2.9 ppm) while values range up to approximately 400 meters ( at HEC = 4 ppm) and 600 meters ( at HEC = 2.9 ppm). If whole field buffer distances at the 95th percentile of exposure are considered, the lowest predicted buffer distance for 40 acre fields is approximately 5 meters ( at HEC = 4 ppm) and 45 meters ( at HEC = 2.9 ppm) while values range up to approximately 140 meters ( at HEC = 4 ppm) and 230 meters ( at HEC = 2.9 ppm). Generally, Ventura California and Bradenton Florida meteorological data result in the largest buffer distances regardless of flux profile. Likewise, Flint Michigan meteorological data seems to generally result in the lowest buffer distances which is logical given its routine climate compared to the California and Florida locations ( e. g., typically cooler with potentially less atmospheric turbulence). For 40 acre fields at the 99.9th percentile, maximum buffer distances ranged as high as 875 meters ( HEC = 4 ppm) and 1380 meters ( HEC = 2.9 ppm) which both are based on the Guadalupe California drip irrigation flux information. For 40 acre fields at the 99.9th percentile, whole buffer distances ranged as high as 495 meters ( HEC = 4 ppm) and 710 meters ( HEC = 2.9 ppm) which both are based on the Guadalupe California raised bed flux information. For 1 acre fields, the vast majority of buffer distances at all percentiles of exposure considered ( up to 99.9th percentile) were less than 100 meters with most being in the 5 to 50 meter range at the upper percentiles of exposure ( i. e., 99th percentile plus) regardless of whether maximum or whole field buffers are considered. Changes in risk estimates with percentiles of exposure were examined and these analyses indicate that even at buffer distances based on the 95th percentile of exposure risks were generally not significantly less even at higher percentiles of exposure which indicates slight changes in risks with percentile of exposure ( e. g., MOEs ~ 10 were common at the 99.9th percentile of exposure with MOEs of 30 at the 95th percentile). Other factors which could potentially impact results were examined including the size and shapes of fields. As expected, larger fields yielded greater buffer distances. Ventura California meteorological data were the basis of the field shape analysis which indicates very little impact on buffer distances but it is possible different meteorological data could yield different results.

Exposures from ambient sources were qualitatively evaluated based on physical chemical properties and environmental fate characteristics. Ambient air monitoring data were not available since iodomethane is not currently widely used. Exposures to bystanders from ambient air resulting from multiple area sources ( e. g., multiple iodomethane applications in a geographic area) would typically be calculated based on ambient monitoring data if available. Ambient air exposures could potentially occur in proximity to agricultural areas where there is significant use during a particular growing season on a regional basis ( e. g., in coastal areas of California during field fumigation prior to strawberry growing season). Currently, no ambient air data are 5 available for iodomethane; however, HED does not believe that ambient air exposures to bystanders are likely to be a significant concern based on a comparison of the characteristics of iodomethane with those of methyl bromide and the ambient air monitoring data available for methyl bromide.

Iodomethane is very soluble in water, so there is the possibility of leaching to ground water and/ or transporting to surface water through runoff, if slicing or removal of the tarpaulin coincides with, or is followed soon by, a rain event. Based on environmental fate data, the residual contents in soils, and Tier I and II models estimated concentrations, HED does not expect iodomethane to adversely impact ground water or surface water.

Risks to occupational handlers, including ( tractor drivers, co pilots, shovelers, soil sealers, and tarp removers), involved in pre plant field fumigation were evaluated using iodomethane specific handler monitoring data. The data indicate that exposures exceed HED's level of concern for some workers involved in the application of iodomethane when no respiratory protection is used ( e. g., tractor drivers, co pilots, and shovelers). Air purifying organic vapor removing respirators ( APRs) which reduce exposure levels by a factor of 10 were also considered and exposures were reduced below HED's level of concern for all workers involved in application with these devices although for some application tasks APRs are not required to achieve acceptable exposure levels. Respirators would be the most practical protective equipment choice for reducing exposures for most workers in this case. This was because the field monitoring data used for this analysis already reflected the use of some engineering controls such as tarps, tractor cabs, deep injection, or other devices including fans in proximity to drivers. The duration of exposure had no impact on the results of this assessment.

For workers who entered fields days after application to prepare for planting ( e. g., tarp cutters or hole punchers), exposures were not of concern 5 days after application ( which reflects the available data) without any sort of respiratory protection. This was also the case for planters where exposures were not of concern 7 days after application without any sort of respiratory protection ( which also reflects the available data). 6 2.0 Ingredient Profile Iodomethane Empirical Formula: CH 3 I Molecular Weight: 141.95 CAS Registry No.: 74 88 4 PC Code: 000011 Chemical Class: Alkyl Iodide Iodomethane is a colorless, liquid at normal temperatures and pressures and has a sweet ethereal odor. Iodomethane has a specific gravity of 2.28 at 20 ° C, vapor pressure of 375 torr at 20 ° C, boiling point of 42.5 ° C, and octanol/ water partition coefficient ( log P ow ) of 1.51. It is soluble in water at 1.75 g/ 100 mL at 20 C, and is miscible in alcohols and ether.

Iodomethane is a pre plant soil biocide used to control insects, plant parasitic nematodes, soil borne pathogens, and weed seeds. The proposed uses are for growing strawberries, fresh market tomatoes, peppers, perennial crop ornamentals, nurseries, cut flowers, turf, and tree and vines.

Iodomethane is stored as a liquid under pressure but volatilizes rapidly following soil injection. It is applied by shallow shank broadcast flat fume ( flat fume); raised bed shallow shank injection ( raised bed); or raised bed drip irrigation ( drip irrigation). A maximum application rate of 175 lb ai/ acre has been proposed for use in various crops. This proposed application rate is the basis for the modeling completed in this assessment. [ Note: The field volatility and worker exposure monitoring data were generated at application rates which ranged between 234 and 259 lb ai/ acre. The PERFUM model calculations in this assessment accounted for these differences by scaling results based on the rate differences. Worker exposure monitoring results were not scaled based on application rate.]

3.0 Metabolism 3.1 Description of Primary Crop Metabolism Plant metabolism studies conducted on strawberries and tomatoes found iodomethane to be extensively metabolized and incorporated into the plant constituents, primarily carbohydrates. Iodide levels in the raw commodities were comparable to background levels found in control samples. 1 Robinson, DA et al. ( 2003). " Three dimensional mapping of the lesions induced by beta beta' iminodiproprionitrile, methyl iodide and methyl methacrylate in the rat nasal cavity." Toxicol. Pathol. 31( 3): 340 347. Chamberlain, MP et al. ( 1999). Methyl iodide toxicity in rat cerebellar granule cells in vitro: the role of glutathione." Toxicology 139( 2 3): 27 37. Chamberlain, MP et al. ( 1998). " Investigations of the pathways of toxicity of methyl iodide in the rat nasal cavity." Toxicology 129( 2 3): 169 181 Reed, CJ et al. ( 1995). " Olfactory toxicity of methyl iodide in the rat." Arch. Toxicol. 70( 1): 51 56 Bonnefoi, MS ( 1992). " Mitochondrial glutathione and methyl iodide induced neurotoxicity in primary neural cell cultures." Neurotoxicology 13( 2): 401 412 7 3.2 Description of Livestock Metabolism There are no significant livestock feed items concerned with this assessment so livestock metabolism studies are not required.

3.3 Description of Rat Metabolism A rat metabolism study comparing absorption after oral and inhalation administration is available. The data in this study indicate that iodomethane is quickly absorbed through both routes of exposure ( maximum blood concentration at 2 4 hours). In contrast, the elimination profile indicates that excretion of 14C labeled iodomethane is biphasic with the initial half life of 5 7 hours and a terminal half life of approximately 116 136 hours. These half lives, however, are measured on the basis of the 14C radiolabel and may not accurately reflect the amount of iodomethane or iodide remaining in the body since the methyl and iodide moieties of iodomethane are expected to quickly dissociate after administration. Radioactivity accumulates in a variety of tissues including the thyroid ( radioactivity concentration of 106 198 : g/ g tissue). A second rat metabolism study was conducted to quantify the levels of inorganic iodide in rat serum after a two day exposure ( 6 hrs/ day) via the inhalation route. The results of this study indicate that inorganic iodide serum levels increase dramatically ( 8300 1000 fold) during the exposure period and remained elevated during the 18 hours following exposure ( 863 400 fold).

4.0 Hazard Characterization/ Assessment 4.1 Hazard Characterization 4.1.1 Database Summary Studies available and acceptable ( animal, human, general literature)

The registrant has submitted a complete database via the inhalation route including an acute neurotoxicity study, developmental studies in rats and rabbits, subchronic inhalation toxicity study in rats, as well as a multigeneration reproductive toxicity study and a combined chronic/ carcinogenicity study in rats. All of the inhalation studies received to date have been classified as acceptable. At this time, subchronic oral toxicity studies have been submitted to the Agency. Since iodomethane has been classified as a non food use chemical, only a screening level assessment of the oral toxicity studies has been completed. In the peerreviewed literature there are several reports indicating that iodomethane is toxic to the central nervous system, as well as the respiratory tract. 1 Moreover, numerous published articles indicate that methyl iodide is 2 Bolt, HM and Gansewendt, B. ( 1993) " Mechanisms of carcinogenicity of methyl halides." Crit. Rev. Toxicol. 23( 3): 237 253. Xu, DG et al. ( 1993). " DNA methylation of monohalogenated methanes of F344 rats." J. Tongji Med. Univ. 13( 2): 100 104 8 genotoxic due to its methylating capabilities. 2 Interestingly, the only evidence of genotoxicity observed in the guideline studies submitted to the Agency is an induction of structural chromosome aberrations ( clastogenesis).

Since iodomethane is a new proposed pesticidal active ingredient, there are no incident reports related to agricultural uses. However, this compound is used as an intermediate in the manufacture of some pharmaceuticals, in methylation processes, and in the field of microscopy, thus sporadic reports of iodomethane poisonings are available in the open literature.

Metabolism, toxicokinetic, mode of action data As stated above, a rat metabolism study comparing absorption after oral and inhalation administration is available. The data indicate that iodomethane or its metabolites accumulate in a variety of tissues including the thyroid ( radioactivity concentration of 106 198 : g/ g tissue) and is quickly absorbed through both oral and inhalation routes of exposure ( maximum blood concentration at 2 4 hours). Also available is a rat metabolism study intended to quantify the levels of inorganic iodide in the rat serum and describe the kinetics for serum iodide accumulation/ elimination after iodomethane exposure. As was noted in the guideline metabolism study, this special study indicated that while accumulation of iodide is rapid the elimination profile is slow and biphasic in nature.

Toxicokinetic and mode of action data have been submitted by the registrant in support of a physiologically based pharmacokinetic ( PBPK) model including: i) Mode of Action Study for Iodomethane related Fetotoxicity Study in Rabbits; ii) Combined Baseline Inhalation Exposure Study of Iodomethane Related Fetotoxicity in Rabbits; iii) In vivo Two Day Inhalation Mechanistic Toxicity Study in the Rat; iv) Iodomethane: Analysis of Select Biomarkers in Rabbit Tissue; v) Iodomethane: Pulmonary Function Study in Rabbits; vi) Iodomethane: In vitro Partition Coefficients in Rat and Rabbit Tissues and Human Blood; vii) Iodomethane: Select Biomarkers in Rabbit Tissues after Inhalation Exposure; viii) Effects of Methyl Iodide on Deiodinase Activity; ix) Derivation of Human Reference Toxicity Values for Methyl Iodide using Physiologically Based Pharmacokinetic ( PBPK) Modeling; x) Magnetic Resonance Imaging and Computational Fluid Dynamics Simulations of Rabbit Nasal Airflows; xi) Uptake of MeI by the Rabbit Nasal Cavity; xii) Uptake of MeI by the Rat Nasal Cavity; xiii) In vivo Gas Uptake in Rabbits; xiv) The Pharmacokinetics of Sodium Iodide ( NaI) in Pregnant Rabbits; xv) In vitro GSH Conjugation Study in Rat, Rabbit, and Human Blood and Tissues with MeI.

The Agency has reviewed these data and its usefulness to calculate human equivalent concentrations ( HECs) based on chemical specific data. The mechanistic studies were intended to either define the dose metric or provide compound specific inputs for the PBPK model. The model is a sophisticated effort to describe the kinetics of methyl iodide following inhalation exposure and the kinetics of iodide as a metabolite. It describes nasal tract dosimetry and glutathione ( GSH) depletion in the rat to evaluate nasal toxicity, distribution of methyl iodide to tissues including brain, and iodide kinetics in the pregnant rabbit to address developmental toxicity. The model has also been parameterized for the human and Monte Carlo analyses that were 9 performed to describe human variability. The review was carried out using the framework described in Clark et al., 2004. The results of the evaluation are described focusing on the rat and human nasal modeling , the rabbit and human pregnancy modeling, modeling human variability, and model documentation. The strengths and limitations of the modeling were identified. The nasal modeling for rat and human was concluded to be adequate to estimate a human equivalent concentration. Selection of the appropriate degree of GSH depletion to predict nasal olfactory toxicity is dependent on additional factors beyond the PBPK/ PD modeling, including judgments about the relationship of this measure with toxicity and the linkage of the time course of exposure concentrations with the prediction of GSH depletion. The pregnancy modeling was found to be adequate to estimate a range of human equivalent concentrations. The human variability analysis was considered to provide perspective on the default value of 3 to address human pharmacokinetic variability. In general, the model and mechanistic studies used to provide its inputs are considered adequate and their results have been incorporated into this risk assessment. For a more detailed description of the model evaluation, the reader is referred to Appendix A of this document Sufficiency of studies/ data At this time, the Agency is conducting a quantitative human health risk assessment for exposure via the inhalation route only. For the purpose of conducting inhalation risk assessments, the current iodomethane database provides sufficient information to assess risks to the human population following iodomethane exposure via the inhalation route.

4.1.2 Endpoints The general public may be exposed to fumigants in air because of their volatility following application. Specifically, fumigants can off gas into air and be transported by diffusion and wind off site. In addition, the U. S. population may be exposed to iodomethane through the drinking water.

The pattern of toxicity attributed to iodomethane exposure via the inhalation route includes developmental toxicity ( manifested as fetal losses and decreased live births), histopathology findings ( respiratory tract lesions and salivary gland squamous cell metaplasia ), thyroid toxicity, neurotoxicity and generalized systemic toxic effects ( body weight and body weight gain decreases).

Developmental and/ or offspring toxicity is observed in both rats and rabbits. Two developmental toxicity studies in rabbits conducted via the inhalation route have been reviewed by the Agency. In the guideline study, an increase in fetal losses was noted at the highest exposure concentration. Subsequently, the registrant conducted a phased exposure rabbit developmental toxicity study in which animals were exposed for different time periods. This second study reproduced the fetal losses seen in the guideline study and defined a narrow dosing window which may elicit this effect. Only exposure on gestation days ( GD) 23 24 or GD 25 26 resulted in fetal losses. It is noteworthy, that the time of fetal loss coincides with the time of ontogeny of fetal thyroid function in the rabbit ( GD22). Given the essential role of iodine in the proper function of the thyroid gland ( both iodine deficiency and excess can have profound effects on thyroid function and thyroid hormone biosynthesis) and the fact that iodomethane exposure may lead to an excess accumulation of iodine in the thyroid, a mode of action ( MOA) for the fetal losses involving perturbations of fetal thyroid function as a result of excess iodidehas been proposed. In the case of rats, no fetal losses were reported in the developmental toxicity study yet a decrease in the number of live births was reported in the multigeneration reproduction toxicity study. It is interesting to note, however, that while iodomethane exposure in the 3 Amiodarone printed label. Food and Drug Administration 4Zhu, Y. et al. " Excess iodine induces the expression of thyroid solid cel nests in lymphocytic thyroiditisprone BB/ W rats." Autoimmunity ( 1995) 20: 201 106 Kanno, J. et al. " Tumor promoting effects of both iodine deficiency and iodine excess in the rat thyroid" Toxicol. Path. ( 1992) 20( 2): 226 235 10 developmental study ceased on GD17 ( before ontogeny of rat fetal thyroid function), in utero exposure during the multigeneration toxicity continued until GD20 ( i. e. during ontogeny of fetal thyroid function). Thus, the data suggest that fetal losses may have occurred in the rat developmental study had exposure continued beyond GD17. Similar effects have been reported for another iodine rich compound, amiodarone ( an antiarrythmic drug), after treatment of pregnant rabbits and rats. 3 The histopathological changes caused by iodomethane exposure occurred in the respiratory tract, and the salivary and thyroid glands. The respiratory tract histopathology was characterized by lesions of the nasal cavity described as degeneration of the olfactory epithelium ( portal of entry effects). These lesions were identified in the 13 week inhalation toxicity study, the multigeneration reproductive toxicity study, and the combined chronic toxicity/ carcinogenicity study in rats and were limited to the extrathoracic region with no involvement of the tracheobronchial or pulmonary regions. Furthermore, they did not appear to progress with time ( i. e. nasal lesions of comparable severity were seen after 4, 13, and 52 weeks of exposure at the same concentration) thus suggesting the nasal lesions were the result of reaching a critical concentration ( C max ) rather than time dependent ( i. e. C x t; Haber's law). In contrast, a C x t relationship is assumed for all systemic effects.

Frank evidence of thyroid toxicity was reported in the combined chronic toxicity/ carcinogenicity study in rats, the MOA study in rabbits, and the carcinogenicity study in mice. Indications of thyroid toxicity included enlarged thyroids, increased thyroid weights, increased incidence of ultimobranchial thyroid cysts, follicular cell hyperplasia, follicular cell adenomas, and thyroid cytoplasmic vacuolation, as well as perturbations of the thyroid pituitary axis ( decreases in T3 and T4 in conjunction with increases in TSH and rT3). These results are consistent with reports in the open literature linking excess iodine to thyroid hormone perturbations and eventually thyroid tumor formation. 4 In regards to the potential role of iodomethane as a neurotoxicant, the inhalation acute neurotoxicity study in rats revealed that iodomethane exposure elicited clonic convulsions ( repetitive mouth and jaw movement), a 2 3oC decrease in body temperature, and an 80% decrease in motor activity in the absence of neuropathology. No additional guideline studies are available to evaluate the potential neurotoxicant properties of iodomethane. This effect, however, appears to be a less sensitive endpoint than the fetal losses, and nasal histopathological lesions. 5 At this time, CDPR has not conducted a risk assessment for iodomethane; thus, CDPR HECs are not available for iodomethane.

11 4.1.3 Dose response The primary exposure pathway for iodomethane is via inhalation. Exposures may be acute ( less than 24 hours), short term ( 1 30 days), intermediate term ( 1 month 6 months), or long term in duration.

<IP_ADDRESS> Inhalation Exposure The critical effects of iodomethane exposure via the inhalation route are the fetal losses observed in two developmental toxicity studies in rabbits, the histopathological lesions reported in three studies, and the generalized systemic toxicity seen throughout the database. In evaluating the risks that a compound may pose to human health after exposure via the inhalation route, different methodologies have been historically used by the USEPA and the California Department of Pesticide Regulation ( CDPR). An example of CDPR's methodology, and the species specific parameters used in this approach can be found in the CDPR website and their MeBr risk assessment, Appendix G at the following web address ( www. cdpr. ca. gov/ docs/ dprdocs/ methbrom/ append_ g. pdf). As OPP understands the importance to harmonize with other regulatory agencies, fumigant risk assessments will present HECs derived using EPA's RfC methodology as well as CDPR's methodology, when available. 5 Endpoint selection will be based on the endpoints occurring at the lowest HECs ( which may or may not be the lowest animal NOAEL).

In this risk assessment, endpoint selection will be based on the endpoints occurring at the lowest HECs ( which may or may not be the lowest animal NOAEL) derived using the RfC methodology or PBPK model. In both approaches, different HECs may be calculated for the same experimental NOAEL due to: 1) the different algorithms used to derive HECs for systemic versus portal of entry effects; 2) different dose metrics used in the PBPK model or 3) the time adjustments conducted for non occupational versus occupational exposure scenarios. The differences between systemic versus portal of entry effects, arise from the use of different calculations to estimate the inhalation risk to humans which are dependent on the regional gas dose ratio ( RGDR). In the case of systemic versus portal of entry effects, different RGDRs are derived for each type of toxicity. For non occupational versus occupational exposure, the differences arise because while it is presumed that non occupational exposure may occur 24 hours/ day, 7 days/ week; occupational exposure occurs only during the course of an average workweek ( 8 hours/ day and 5 days/ week). The iodomethane PBPK model, on the other hand, uses MOA data to derive internal dose metrics in the test species which are then used to extrapolate to humans and calculate HECs. A more detailed description and evaluation of the PBPK model are available in Appendix A of this document. For further details on the critical studies used for endpoint selection and the iodomethane toxicity profile the reader is referred to Appendix B. For additional information on the methodologies used in this risk assessment and the HEC arrays, please refer to Appendix C. The toxicity endpoints selected for risk assessment are presented below.

Acute Inhalation Exposure Endpoint selection for acute inhalation exposures was based on three co critical studies: a subchronic inhalation toxicity study in rats and two developmental toxicity studies in rabbits briefly described below:

Subchronic Inhalation Toxicity Study in rats 6 Reed, CJ et al. ( 1995). " Olfactory Toxicity of Methyl Iodide in the Rat" Arch Toxicol. 70: 51 56 12 In a subchronic inhalation toxicity study ( MRID 45593810), iodomethane ( 99.7% a. i.; Lot/ batch # 007403/ 02) was administered via whole body inhalation to Crl: CD~( SD) IGS BR rats ( 20/ sex/ concentration) for 6 hours/ day, 5 days/ week for 13 weeks at analytical concentrations of 0, 5, 21, or 70 ppm ( 0, 0.029, 0.12, or 0.41 mg/ L/ day). Ten rats/ sex/ concentration were sacrificed after 4 weeks, and the remaining 10 rats/ sex/ concentration were sacrificed after 13 weeks. There were no effects of treatment on mortality, ophthalmology, urinalysis, hematology, organ weights, or gross pathology .

The systemic LOAEL for this study is 70 ppm based on initial decreases in body weights, body weight gains, and food consumption ( males). The NOAEL is 21 ppm ( HEC = 3.8 or 15.8 ppm for nonoccupational and occupational risk assessments, respectively).

The port of entry LOAEL is 70 ppm based on degeneration of the olfactory epithelium. The NOAEL is 21 ppm ( HEC = 2.9 or 3.7 ppm for non occupational and occupational risk assessments, respectively). In a developmental toxicity study ( MRID 45593811), groups of 24 female New Zealand White rabbits were dynamically exposed to iodomethane vapor ( Lot/ batch # 007403/ 02; 99.6% a. i.) in whole body inhalation chambers at analytical concentrations of 0, 2, 10, or 20 ppm ( 0, 0.012, 0.058, or 0.12 mg/ L/ day) six hours per day on gestation days ( GDs) 6 through 28.

The maternal NOAEL is 20 ppm; no maternal LOAEL was identified. The developmental toxicity LOAEL is 20 ppm based on increased fetal losses and decreased fetal weights ( 920%). The developmental toxicity NOAEL is 10 ppm ( HEC = 4.0 for non occupational).

In a developmental toxicity study ( MRID 46077001) iodomethane ( 99.7% a. i., Batch# 02/ Lot# 007403) was administered via the inhalation route ( whole body) to 24 New Zealand White rabbits/ group at concentrations of 0 or 20 ppm during GD 6 28 ( Control and Group 2), GD 6 14 ( Group 3), GD 15 22 ( Group 4), GD 23 24 ( Group 5), GD 25 26 ( Group 6), or GD 27 28 ( Group 7) for 6 hours/ exposure day. This study was not intended to fulfill the guideline requirement or establish NOAELs and LOAELs but rather was conducted to determine the critical period of exposure during gestation that resulted in fetal loss as observed in a previously evaluated guideline developmental toxicity study in rabbits.

Dose and Endpoint for Risk Assessment: Two critical endpoints have been identified for this risk assessment: nasal histopathology in the Subchronic Inhalation Toxicity Study in rats and fetal losses in two developmental toxicity studies in rabbits. Using the iodomethane PBPK model developed by Arysta ( iodomethane registrant) and reviewed by the Agency, the HEC for nasal histopathology is 2.9 or 3.7 ppm for nonoccupational and occupational risk assessments, respectively. In the case of fetal losses, the PBPK model indicates that an HEC of 4.0 would be appropriate for the non occupational risk assessment.

The nasal histopathology was reported after a 13 week exposure to iodomethane, however, data from the published literature indicate that nasal lesions can occur after acute exposures (. 2 hrs. at 100 ppm) if the time profile of the exposure concentration leads to an overall iodomethane exposure of $ 200 ppm/ hr. 6 Based on this information in conjunction with the iodomethane PBPK and PERFUM models, HED and ORD scientists have concluded that an HEC of 2.9 or 3.7 ppm for non occupational and occupational risk assessments, 13 respectively, is appropriate for this risk assessment.

The proposed MOA for nasal histopathology involves glutathione ( GSH) depletion as a key event in the toxicity pathway leading to damage of the nasal olfactory epithelium. Consequently, GSH depletion (# 50%) is the dose metric used in the PBPK model for interspecies extrapolation to determine the NOAEL for the nasal lesions. Using the HEC of 2.9 ppm for non occupational risk assessments results in a 24 hr timeweighted average GSH depletion of .25% ( i. e. below the level of GSH depletion commonly cited in the literature as critical for development of nasal histopathology). It should be noted, however, that the emission profile of iodomethane suggests that during peak emissions GSH depletion may be higher than 25% ( e. g. 38%). However, it is the sustained decrease in GSH levels that is critical thus and HEC of 2.9 ppm is considered protective of the effects of concern in the respiratory tract. Similarly, using an HEC of 3.7 ppm for the occupational risk assessment results in an 8 hr time weighted average GSH depletion of .25%.

The endpoint of fetal losses identified in the developmental toxicity studies in rabbits is also considered appropriate for this risk assessment since it is presumed that developmental effects may be the outcome of an acute exposure. In the case of iodomethane, this presumption has been substantiated by the results of the phased developmental toxicity study in rabbits in which fetal losses were observed after two 6 hr exposures. Excess serum iodide has been implicated as a critical element in the MOA proposed for this endpoint. In a MOA study submitted by the registrant, excess iodide has been shown to lead to fetal thyroid hormone disruptions ( Wolff Chaikoff effect) resulting in fetal loss. Consequently, the dose metric used for this assessment is the area under the concentration curve ( AUC) for fetal serum inorganic iodide during a single day of exposure. Based on this dose metric, an HEC of 17 ppm is calculated for the non occupational risk assessment. This HEC, however, is based on the assumption that human fetal serum iodide levels are 75% of the maternal levels. Although data in support of this presumption are available from the peer reviewed literature, the Agency has concluded that the evidence is not sufficiently robust ( i. e. limited and often indirect) to establish an HEC of 17 ppm as a point of departure for the assessment. Thus, although the HEC of 17 ppm may represent a high or perhaps even a reasonable estimate of the human fetal serum iodide AUC, an HEC of 4 ppm which assumes an equivalent distribution of fetal serum iodide in rabbits and humans is used in this risk assessment. This HEC likely represents a lower bound estimate of the true dose metric. The bulk of the biomedical literature indicate that within the range of these estimate ( i. e. 4 17 ppm), the " true" value is likely towards the higher part of the range. But, there does not appear to be adequate information to establish that a particular value in the higher part of that range is the most accurate value. Consequently, there is higher confidence in the use of the 4 ppm HEC as a point of departure for this assessment based on the endpoint of fetal losses. An UF of 30X defines HED's level of concern for both endpoints.

Note: For a more detailed description of the PBPK evaluation, refer to Appendix A of this risk assessment. 14 Short, and Intermediate term Inhalation Exposure Non occupational Exposure In a two generation reproduction toxicity study, iodomethane ( 99.7% a. i.; Lot/ batch # 007403/ 02) was administered via whole body inhalation to Crl: CD ® ( SD) IGS BR rats ( 30/ sex/ concentration) for 6 hours/ day at nominal concentration levels of 0, 5, 20, or 50 ppm ( equivalent to analytical concentrations of 0, 5, 21, and 50 ppm). The P animals were exposed to the test article for at least 70 days prior to mating to produce the F 1 litters. Exposure of the P males continued throughout mating and until the day prior to euthanasia. The P females continued to be exposed throughout mating and through gestation day ( GD) 20, at which point exposure was discontinued. Daily exposure of the P females was reinitiated on lactation day ( LD) 5 and continued until the day prior to euthanasia. After weaning, F 1 animals ( 30/ sex/ concentration) were selected, equalized by sex, to become the parents of the F 2 generation and, beginning on post natal day ( PND) 28, were exposed to the same concentration test atmosphere as their dam.

The systemic parental NOAEL is 20 ppm ( HEC = 5 ppm) and the LOAEL is established at 50 ppm based on decreases in body weight, body weight gain, changes in organ weights ( adrenal glands, testis, cauda epidymis, epidydimis, and thymus) as well as gross pathology and histopathology findings.

The port of entry NOAEL is 20 ppm ( HEC = 3.2 ppm) and the LOAEL is 50 ppm based on minimalmild degeneration of the olfactory epithelium.

The offspring NOAEL is 5 ppm ( HEC = 1.25 ppm) and the LOAEL is 20 ppm based on decreases in body weight, body weight gain, as well as lower absolute and relative thymus weights.

The reproductive NOAEL is 5 ppm ( HEC = 1.25 ppm) and the LOAEL is 20 ppm based on delays in attainment of vaginal patency.

Dose and Endpoint for Risk Assessment: HEC of 1.25 ppm based on decreased pup weight and weight gain, decreased thymus weights, and delays in vaginal patency acquisition. The duration of exposure in the multigeneration reproduction toxicity is appropriate for short and intermediate term risk assessments and it yields the lowest HEC ( ie. most health protective exposure concentration) for these exposure scenarios. An UF of 30X defines HED's level of concern in accordance with guidance provided in the RfC methodology ( see section 4.2 below).

Occupational Exposure See non occupational exposure above for brief executive summary. Different HECs have been calculated for occupational exposures due to the time adjustments made for the exposure scenarios.

Systemic parental NOAEL is 20 ppm ( HEC = 15 ppm). Port of entry NOAEL is 20 ppm ( HEC = 3.7 ppm). Offspring NOAEL is 5 ppm ( HEC = 3.75 ppm). Reproductive NOAEL is 5 ppm ( HEC = 3.75 ppm). 15 Dose and Endpoint for Risk Assessment: HEC of 3.7 ppm based on minimal mild degeneration of the olfactory epithelium. The duration of exposure in the multigeneration reproduction toxicity is appropriate for short and intermediate term risk assessments and it yields the lowest HEC ( ie. most health protective exposure concentration) for these exposure scenarios. An UF of 30X defines HED's level of concern in accordance with guidance provided in the RfC methodology ( see section 4.2 below).

Long term Inhalation Exposure Non occupational and Occupational Exposure In a combined chronic toxicity/ carcinogenicity study in rats ( MRID 45612401), iodomethane ( 99.7% a. i., Batch No. 02/ Lot # 007403) was administered to Crl: CD ® ( SD) IGS BR rats via whole body inhalation at concentrations of 0, 5, 20, or 60 ppm for 6 hours/ day 5 days/ week. Sixty animals/ sex/ concentration were exposed to 0, 5, or 20 ppm iodomethane while 70/ sex were exposed at the 60 ppm level. Animals were observed for moribundity and mortality twice daily and clinical observations once daily. Once a week a detailed physical examination was conducted including but not limited to evaluations of changes in appearance, autonomic activity ( e. g. lacrimation, piloerection, pupil size, breathing patterns), gait, posture, response to handling, stereotypic and/ or bizarre behavior. In addition, evaluations of clinical chemistry, hematology, urinalysis, gross pathology and histopathology parameters were conducted.

The systemic NOAEL is 5 ppm ( HEC = 0.89 or 3.75 ppm for non occupational and occupational risk assessments, respectively); the LOAEL is established at 20 ppm based on increased incidence of salivary gland squamous cell metaplasia.

The NOAEL for port of entry effects ( respiratory tract) is 20 ppm ( HEC = 3.2 or 4.2 ppm for nonoccupational and occupational risk assessments, respectively) and the LOAEL is 60 ppm based on degeneration of the olfactory epithelium.

Dose and Endpoint for Risk Assessment: HEC of 0.89 ppm or 3.75 ppm for non occupational and occupational risk assessments, respectively based on increased incidence of salivary gland squamous cell metaplasia. This is the study of the longest duration available in the iodomethane database and it yields the lowest HEC ( ie. most health protective) for this exposure scenario. An UF of 30X defines HED's level of concern in accordance with guidance provided in the RfC methodology ( see section 4.2 below).

<IP_ADDRESS> Dietary Exposure Although iodomethane is used as an agricultural pesticide, it is considered a non food use chemical since it is quickly degraded or metabolized and subsequently incorporated into natural plant constituents. The levels of iodide released from iodomethane degradation/ metabolism are lower than those expected to cause toxic effects. Furthermore, enforcement of tolerances would not be possible since no iodide free samples are available and residue field trials show evidence of control samples with higher iodide residues than iodomethane treated samples. Moreover, iodide is ubiquitous in the environment and a required nutrient. Finally, iodomethane residues must dissipate in the soil prior to planting. Accordingly, HED concluded tolerances are not required for iodomethane. As a result, a risk assessment has not been conducted 16 for this exposure scenario. The U. S. population, however, may be exposed to iodomethane through drinking water; therefore, a qualitative drinking water risk assessment was conducted and no risks were identified from this potential exposure.

<IP_ADDRESS> Dermal Exposure Exposure to iodomethane is anticipated via inhalation or oral ( drinking water) routes but not through the dermal route. Dermal exposure to iodomethane of any significance is not expected based on the delivery systems used ( e. g., soil injection or drip irrigation), packaging ( i. e., pressurized cylinders), and emission reduction technologies ( e. g., tarping). The high vapor pressure of iodomethane also makes significant dermal exposure unlikely and quantifying any potential low level exposures very difficult. Therefore, a quantitative dermal exposure assessment has not been completed. Since HED does not have adequate data to quantify dermal risk, PPE for dermal protection should be based on the acute toxicity of the end use product as described in the Worker Protection Standard and mitigation measures for dermal exposure described in PR Notice 93 7.

<IP_ADDRESS> Classification of Carcinogenic Potential The Cancer Assessment Review Committee ( CARC) evaluated the rodent bioassays and mechanistic data available for iodomethane. Evidence of carcinogenicity in the iodomethane database manifested as an increased incidence of thyroid follicular cell tumors observed in both the Inhalation Chronic Toxicity/ Carcinogenicity Study in Rats and the Carcinogenicity Study in Mice. The committee concluded that the key event influencing the thyroid tumor response is the sustained stimulation of cell proliferation by TSH, consistent with the increase in thyroid follicular cell tumors only. Based on the evidence that rats are substantially more sensitive than humans to the development of thyroid follicular cell tumors in response to thyroid hormone imbalance, the CARC classified iodomethane as " not likely to be carcinogenic to humans at doses that do not alter rat thyroid hormone homeostasis."

4.1.4 Endocrine Disruption Following the recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee ( EDSTAC), EPA determined that there was scientific bases for including, as part of the endocrine disruption screening 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. As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program ( EDSP).

Evidence of thyroid hormone perturbation is available in the iodomethane database. A chronic toxicity/ carcinogenicity study in rats, as well as a MOA study in rabbits, and a carcinogenicity study in mice indicate that iodomethane exposure elicits sustained perturbation of thyroid hormone homeostasis. When the appropriate screening and/ or testing protocols being considered under the Agency's EDSP have been developed, iodomethane may be subjected to additional screening and/ or testing to better characterize effects related to endocrine disruption. 7 A 3X UF for interspecies extrapolation is retained to account for the PD differences between animals and humans which are not accounted for in the RfC methodology or the PBPK model.

17 4.2 Uncertainty Factors Iodomethane has been classified as a non food use pesticide. Consequently, this chemical is not subject to the FQPA ( 1996) and the 10X FQPA factor does not apply.

When conducting inhalation risk assessments, the magnitude of the UFs applied is dependent on the methodology used to calculate risk. This risk assessment is based on the RfC methodology developed by the Office of Research and Development ( ORD) and the PBPK model developed by the registrant for the derivation of inhalation reference concentrations ( RfCs) and human equivalent concentrations ( HECs) for use in margin of exposure ( MOE) calculations. Since both of these approaches take into consideration the pharmacokinetic ( PK) but not pharmacodynamic ( PD) differences between test species and humans, the UF for interspecies extrapolation may be reduced to 3X while the UF for intraspecies variation is retained at 10X. 7 Thus, when using the RfC methodology the overall UF is customarily 30X.

4.3 Summary of Toxicological Endpoint Selection Table 1: Summary of Toxicological Dose and Endpoints for Use in Iodomethane Human Health Inhalation Risk Assessment Risk Assessment Study NOAEL/ LOAEL Endpoint HED HECs CPDR HECs ¶

Acute Nonoccupational Subchronic Inhalation Toxicity Study in Rat NOAEL = 21 ppm LOAEL = 70 ppm Degeneration of the olfactory epithelium 2.9 ppm UF= 30 N. A.

Developmental Study in Rabbits NOAEL = 10 ppm LOAEL = 20 ppm Developmental effects: fetal loss 4.0 ppm UF = 30 Occupational Subchronic Inhalation Toxicity Study in Rat NOAEL = 21 ppm LOAEL = 70 ppm Degeneration of the olfactory epithelium 3.7 ppm UF= 30 Short, Intermediate Term, Inhalation ( 1 6 months exposure) Nonoccupational Multigeneration Reproductive Toxicity Study in Rats NOAEL = 5 ppm LOAEL = 20 ppm Offspring effects: decreased body weight, weight gain, and thymus weights Reproductive effects: Delays in vaginal patency 1.25 ppm UF = 30 N. A.

Occupational Subchronic Inhalation Toxicity Study in Rats NOAEL = 20 ppm LOAEL = 50 ppm Degeneration of the olfactory epithelium 3.7 ppm UF = 30 Table 1: Summary of Toxicological Dose and Endpoints for Use in Iodomethane Human Health Inhalation Risk Assessment Risk Assessment Study NOAEL/ LOAEL Endpoint HED HECs CPDR HECs ¶

8Hermouet, C. et al. " Methyl iodide poisoning: Report of two cases" Am. J. Ind. Medicine ( 1996) 30: 759 764 & Appel, G. B. et al. " Methyl iodide intoxication" Annals of Int. Med ( 1975) 82: 534 536 18 Long term (> 6 months) Nonoccupational Chronic/ Carcinogenicity Study in Rats NOAEL = 5 ppm LOAEL = 20 ppm Squamous cell metaplasia 0.89 ppm UF = 30 N. A.

Occupational Chronic/ Carcinogenicity Study in Rats NOAEL = 5 ppm LOAEL = 20 ppm Squamous cell metaplasia 3.75 ppm UF = 30 Cancer Not likely to be carcinogenic to humans at doses that do not alter rat thyroid hormone homeostasis ¶ At this time, CDPR has not conducted a risk assessment for iodomethane ( pending submission of additional data).

5.0 Public Health Data Over the past century, only 11 incidents of iodomethane poisoning have been reported in the published literature8. In general, symptoms of iodomethane intoxication in humans were related to effects on the nervous system ranging from somnolence to ataxia, seizures, delirium and coma in severe cases. In some patients, cerebellar lesions and damage of the third, fourth, or sixth cranial nerve pathways as well as spinal cord lesions producing motor and sensory disturbances have been reported. Latent symptoms of iodomethane intoxication include psychological disorders such as depression. In addition to neurological effects, iodomethane exposure has also been linked to congestive changes in the lungs and oliguric renal failure. It is noteworthy, however, that in most of these incidents the precise iodomethane exposure concentration is unknown though it appears that exposure was to high levels ( due in part to use of inadequate protective devices) resulting from industrial uses and far exceeding those proposed for regulatory purposes in this risk assessment or anticipated agricultural uses.

6.0 Non Occupational Exposure Assessment and Characterization This section describes the potential exposure scenarios associated with the use of iodomethane. These include residential bystander exposure from two key sources: a known area source ( e. g., at the edge of a treated field), as well as from multiple area sources within a region ( e. g., ambient air). There are no residential uses of iodomethane by homeowners so this aspect of the risk assessment focuses on those types of exposures that may occur from the proposed commercial uses of iodomethane. HED also considered the potential for dietary exposures from food and drinking water. 19 6.1 Residential Bystander Exposure Residential bystander exposure may occur because of emissions from treated fields. These emissions can travel to non target areas which could lead to negative impacts on human health and are referred to as bystander or off target risks.

Exposures from known uses or point sources have been estimated based on controlled field volatility studies conducted in agricultural fields. Exposures have been calculated in three distinct ways involving direct use of the monitoring data and through two modeling approaches including the Industrial Source Complex: Short Term model ( ISCST3) and the Probabilistic Exposure and Risk Model For Fumigants ( PERFUM) which was developed and evaluated by the FIFRA Science Advisory Panel ( SAP) in August of 2004. ISCST3 is a standard Agency model which was used in conjunction with the monitoring data available for iodomethane, and other inputs such as a series of standard weather conditions. ISCST3 is a Gaussian plume model developed by the Office of Air and Radiation which allows better characterization of air concentrations that result from the application of iodomethane at different distances from the emission source that is not possible with direct use of the data. However, ISCST3 outputs are also limited because they are based on a constant wind vector ( speed and direction) flowing directly downwind to those exposed. Since the initial assessment using ISCST3 was completed, OPP has also considered three different modeling systems that allow for the incorporation of actual meteorological data into assessments ( i. e., PERFUM, FEMS & SOFEA © ) . The FIFRA Science Advisory Panel ( SAP) evaluated these modeling systems in August and September of 2004. PERFUM ( i. e., Probabilistic Exposure and Risk model for Fumigants) has been used herein in addition to ISCST3 in order to better evaluate distributional bystander exposure. The SAP provided very similar comments for each. The Agency has used PERFUM for this assessment because modifications suggested by the SAP have been completed, the inputs were readily available, and the comparative computer processing time was lower than FEMS and SOFEA © . Complete descriptions of each new probabilistic model along with the associated SAP reports are posted at www. epa. gov/ scipoly/ sap/ index. htm.

For exposures from multiple area sources or ambient air, air concentrations of iodomethane have not been quantitatively assessed due to a lack of appropriate data. However, a qualitative discussion is provided below.

Exposures for bystanders from known area sources are described below in Section 6.1.1 while exposures from ambient or multiple area sources are described below in Section 6.1.2.

6.1.1 Bystander Exposure From Known Area Sources As stated above, residential bystander exposure from known area sources may occur because of emissions from treated fields. The following sections describe the data and modeling approaches used to estimate these types of exposures.

HED considered several field volatility studies in the development of the bystander assessment for iodomethane. Two studies quantified emissions from tarped broadcast, flat fume applications in California ( i. e., Manteca and Watsonville, California). Three studies quantified emissions from tarped 20 drip irrigation application in California ( i. e., La Selva, Camarillo, and Guadalupe, California). The three remaining studies quantified emissions from tarped, raised bed shallow shank injection applications in California and Florida ( i. e., Plant City, Florida and Oxnard and Guadalupe, California). The citations and summary of the data are included in Appendix D. Each of these studies was considered to be a sufficient quality for risk assessment purposes. [ Note: All flux studies included the use of tarps; for brevity, the use of tarps is implied and will no longer be noted further in this assessment as it is implied in the results.]

As indicated above, three methods were used for estimating air concentration of fumigants from area sources such as a treated field: direct use of air monitoring data from controlled volatility studies in treated fields referred to as the Monitoring Data Method, the use of ISCST3 referred to as the ISCST3 Modeling Method, and the use of PERFUM referred to as the PERFUM Modeling Method. Each of these are described separately below.

Monitoring Data Method: In the monitoring data method, air concentrations are estimated using actual air monitoring data from controlled volatility studies. In these studies, the fumigant is applied to a field and air samplers positioned in and around the treated area continuously sample the air by pulling the air through a filter ( e. g., charcoal) or a vacuum chamber is used which captures the chemical for later analysis. Sampling times can vary but generally range from about 4 to 12 hours, so that the samples represent the average air concentrations for the sampling intervals used. Usually shorter times are used at the beginning of the sampling period because fumigants tend to volatilize soon after application.

There are several uncertainties associated with the use of the direct sampling method which limit its utility. First, the air concentrations represent only those for the conditions under which the study is carried out. Air concentrations around treated fields, buildings, or other areas are influenced by a number of factors including how a chemical is applied, application rate, techniques to control emissions ( e. g., tarps), and weather conditions. Varying weather conditions, for example, can significantly change the air concentrations at specific sites around a treated area; and since there is such a large range of potential weather conditions which can exist, it is not possible for these studies to represent the entire range of potential exposures that can result from different weather situations. Second, the air concentrations are measured by fixed samplers positioned at various directions around the treated area, both downwind and upwind, as well as at points in between. Air concentrations downwind will be relatively high since the fumigant plume will be pushed by the wind in that direction, while concentrations upwind will be low or close to zero since the plume is pushed by the wind in the opposite direction. Therefore, there can be a very large difference between upwind and downwind air concentrations. For areas where there is a predominant wind direction, averaging of the air concentrations from these various samplers should not be done since persons around treated areas will generally be in one location relative to the wind and not exposed to an average of these concentrations. Third, samplers are positioned at specific distances from the treated area, and represent air concentrations only at those distances. Since air concentrations vary greatly by distance, the air concentrations estimated from direct measures represent a very narrow range of the possible levels to which people can be exposed. Results based on the Monitoring Data Method are presented below in Section <IP_ADDRESS>. 21 ISCST3 Modeling Method: The modeling method uses the Agency model, Industrial Source Complex Short Term ( ISCST3) together with information about emissions from a treated field, building or structure ( i. e., known as flux) to model the range of concentrations which may be found under different conditions of application rate, weather, source size and shape ( e. g., field size in acres), and distance from the treated field, building or structure. Before a modeling analysis can be done, one of the most important parameters for ISCST3, the flux rate, which is the quantity of pesticide which is emitted from the treated fields, buildings or structures per unit area per unit time, must be determined. As an example, for field applications it is usually expressed in units of micrograms per square meter per second ( ug/ m2/ sec). In essence, flux represents how quickly the pesticide moves or volatilizes into the surrounding atmosphere. Numerous factors can influence flux rates such as application rate, depth of soil injection, type of application ( e. g., drip vs. soil injection), techniques used to control emissions ( e. g., tarps), temperature, wind and weather conditions, soil type, and others. Flux is also difficult to determine. Three general methods are used to calculate flux which are discussed briefly below. The first two of these measure flux from sampling directly in treated fields, and the third is indirect in that it calculates flux using samples from downwind locations. For iodomethane, flux estimates were completed using the indirect back calculation method.

Method 1, Flux Chamber: The first direct method for estimating flux uses field fumigant emission data measured in a flux chamber. A flux chamber is basically a box which encloses a small defined area of a treated field, from which air samples are obtained representing defined durations ( e. g., air is pulled through a charcoal trap collecting emitted pesticide over a continuous length of time such as 4 hours). Since the surface area is defined by the area of the chamber, and the quantity of pesticide emitted per unit time is defined by the air concentration, this method directly measures flux. A possible issue with flux chambers is that the conditions within the chamber ( e. g., temperature, wind, air stability) are not generally identical to those outside the chamber in the treated field; since flux rates can be significantly affected by these factors, flux rates measured in these chambers may not always represent actual flux rates in the field. Flux chambers are not often used for estimating flux rates.

Method 2, Aerodynamic Flux Method: The second direct method used is the aerodynamic flux method. In this method, air samplers are set up in the treated field at various heights on a mast ( e. g., 15, 30, 90, and 150 cm from the ground). Using measured air concentrations at these various heights, a vertical gradient of concentrations can be estimated for different time points, which can be integrated across all heights to estimate the flux rate at each time point after application. Some studies are available using this method to determine flux rates.

Method 3, Back Calculation: The method most often used to determine flux rates is an indirect method known as the back calculation method. This method uses measured air concentrations taken in a typical field fumigation study in which air samplers are located at various positions around the field. The measured air concentrations, together with information about weather conditions which occurred when the samples were obtained, are used as inputs into the Industrial Source Complex Short Term model ( ISCST3). The model assumes that these air concentrations result from a Gaussian 22 plume, the plume being distributed around the treated field as a result of the wind and weather conditions measured. The model then calculates the flux rate which would be required to emit the plume in that manner and to obtain the air concentrations measured.

Determination of the flux rate for all situations to be considered in an assessment is necessary before ISCST3 can be run. After these are defined, other key inputs must be defined such as the size and shape of a treated field, wind direction, wind speed, and atmospheric stability. ISCST3 calculates downwind air concentrations using hourly meteorological conditions, that include wind speed and atmospheric stability. The lower the wind speed and the more stable the environment, the higher the air concentrations are going to be close to a treated field. Conversely, if wind speed increases or the atmosphere is less stable, then air concentrations are lower in proximity to the treated field. Atmospheric stability is essentially a measure of how turbulent the atmosphere is at any given time. Stability is affected by solar radiation, wind speed, cloud cover, and temperature, among other factors. If the atmosphere is unstable, then more off field movement of airborne residues is possible because they are pushed up into the atmosphere and moved away from the field, thereby lowering the air concentration in proximity to the field. To simplify modeling the transport of soil fumigant vapors from a treated field, a single wind direction, wind speed, and stability category are used for a given 24 hour period. The Agency has not determined if a particular set of meteorological conditions should be used for regulatory purposes, so risk assessments generally present exposures and potential risks representing a variety of different conditions.

Modeling with ISCST3 produced high end estimates of air concentration and resulting risks for a number of reasons. First, only the downwind direction is considered. Most people will not be directly downwind from a treated field. Secondly, the model runs are based on constant wind speed, wind direction, and atmospheric stability for a 24 hour period. This will rarely occur resulting in overestimates of air concentrations and risks. However, the model is useful because it allows for estimation of air concentrations reflecting different conditions based on changing factors such as application rates, field sizes, downwind distances, wind and weather conditions, and other factors, which cannot be done using the monitoring data method described above. Therefore, results using the ISCST3 model should be considered to be potential exposures to the most highly exposed, upper percentile of the population, but are not representative of exposures to most of the population around a treated field. The Agency believes that using ISCST3 to predict exposures over more extended periods is inappropriate because constant meteorological conditions over such periods will not occur and will yield highly conservative, physically unlikely results. Results based on the ISCST3 Modeling Method are presented below in Section <IP_ADDRESS>.

PERFUM Modeling Method: The monitoring data and ISCST3 methods described above are deterministic methods which provide high end point estimates of risk. OPP is coordinating with EPA's Office of Air, the California Department of Pesticide Regulation ( CDPR), and other stakeholders to develop modeling approaches which determine the distribution of potential bystander exposures, and thus more fully characterize the range of potential risks to bystanders around treated fields. In this assessment, the PERFUM model has been used in order to calculate differing percentiles of exposure ( see Section 6.1 above for more details concerning PERFUM use and other possible models).

ISCST3 is an integral part of the PERFUM model. As a result, many of the inputs used for PERFUM 23 Figure 1: Receptor Grid For a 5 Acre Field [ Note: 5 Acre field in center, line is a spoke] are similar to those used for the ISCST3 analysis described above ( e. g., field sizes and back calculated flux rates). The key differences are that PERFUM addresses the uncertainty associated with flux profiles in its calculations by sampling the coefficient of variation for those measurements but this does not account for important factors such as field to field differences. It also incorporates 5 years of meteorological data to generate a distribution of daily average concentrations that represent the possible range of downwind air concentrations based on changing wind vectors from the measured data in a series of receptor locations described in Table 2 and Figure 1 below. PERFUM analyses were completed for several field sizes ( i. e., 1 to 40 acres) but in most cases only the results for 1 and 40 acres were processed which represent the possible range of outcomes. In other cases, all results were processed so the impacts of changing field sizes could be more readily apparent. It is also thought that the general trend would apply generically to most situations. Field geometry ( i. e., shape) was also investigated by completing analyses for 5 acre fields shaped like a square and a rectangle oriented on its side and also top to bottom. [ Note: The maximum distance for which calculations are performed on each spoke in PERFUM is 1440 meters from the edge of the treated field.]

Table 2: Receptor Points for Various Field Sizes In PERFUM Grid Type Field Size ( acres) Number of Spokes Number of Rings Number of Receptors ( Spokes* Distances)

Fine 1 96 28 2,688 5 132 28 3,696 10 152 28 4,256 20 188 28 5,264 40 232 28 6,496 Coarse 1 24 28 672 5 33 28 924 10 38 28 1,064 20 47 28 1,316 40 58 28 1,624 Notes: Fine grid option was used for iodomethane analysis. The maximum distance used for PERFUM calculations on each spoke is 1440 meters. 24 Figure 2: Distribution of Daily Average Windspeeds At Selected Meteorological Stations Since actual meteorological data are integrated into PERFUM for each analysis, data representative of the locations where iodomethane use is anticipated were identified and used in the analysis. It is anticipated that the initial major uses for iodomethane could be as a methyl bromide alternative in California and Florida on tomatoes, strawberries and similar crops. Some use in Michigan ( or elsewhere in that region) is also anticipated. As a result, the following locations and sources of meteorological data were used in this assessment:

° Bakersfield California ( Source: ASOS or Automated Surface Observing System operated by the FAA) to represent inland California locations; ° Ventura California ( Source: CIMIS or California Irrigation Management Information System) to represent coastal California locations; ° Flint Michigan ( Source: NWS or National Weather Service) to represent central Michigan and other upper midwest locations; ° Tallahassee Florida ( Source: NWS or National Weather Service) to represent inland Florida locations; and ° Bradenton Florida ( Source: FAWN or Florida Automated Weather Network) to represent coastal Florida.

In this assessment, 5 years or 1825 days of meteorological data were considered in each calculation ( i. e., data are available for all days with no sampling errors). Most data were in the range of 1997 through 2003 but Tallahassee was in the late 1980s through early 1990s. [ Note: Please refer to the SAP background documents for PERFUM for further information concerning these data including how they were processed for incorporation into PERFUM and any quality control issues related to these data.] Figure 2 provides a comparison of the distributions of daily average windspeeds for selected stations in California and Florida. These can be used to help characterize the deterministic assessments and to illustrate different PERFUM results for the different stations. [ Note: As an example, CADPR regulated methyl bromide at 1.4 m/ s windspeed.] 25 Flux ( i. e., field volatility or emissions) data were treated in a manner similar to that used for the ISCST3 analysis described above. Data from each of the 8 flux studies were used in conjunction with appropriate meteorological information. In some cases, studies that quantified emissions from the same application method were available in both Florida and California. In those cases, only meteorological data from the same state were used in the PERFUM analysis. PERFUM also considers the uncertainties associated with daily flux profiles by probabilistically sampling flux based on the range defined by the coefficient of variation associated with those data. Table 3 below provides a summary of the analyses that were completed using PERFUM. There is a significant difference with PERFUM compared to ISCST3 with regard to flux values. ISCST3 used a single emission ratio which does not account for changes over time in flux. Alternatively, PERFUM samples flux distributions over time periods of interest. The Agency verified the flux distributions based on the monitoring data.

Table 3: Summary Of PERFUM Analyses Completed For Iodomethane Weather Station Location Flux Study Summary Watsonville CA Flat Fume Manteca CA Flat Fume Plant City FL Raised Bed Oxnard CA Raised Bed Guadalupe CA Raised Bed La Selva CA Drip Irrigation Camarillo CA Drip Irrigation Guadalupe CA Drip Irrigation Ventura CA X X NA X X X X X Bakersfield CA X X NA X X X X X Flint MI X X X X X X X X Tallahassee FL X X X NA NA X X X Bradenton FL X X X NA NA X X X X = analysis completed, NA = analysis not appropriate; Tarps were used in all cases. Note: All analyses completed using both 2.9 & 4.0 ppm HECs.

PERFUM calculates outputs based on each day's worth of meteorological data and the result is illustrated by Figure 3 which shows the distances from the field where airborne concentrations meet a threshold of concern around the entire perimeter of the field for each spoke in the model ( i. e., the irregularly shaped line). The concentric circle represents a 95th percentile distance value around the perimeter ( i. e., MOEs are not of concern for 95% of those exposed). The cross hatch area represents the locations where distances exceed the 95th percentile value ( i. e., MOEs are of concern at these distances for 5% of those exposed). These exceedances have been examined using the PERFUM MOE program which was used in conjunction with the air model itself ( see SAP site for more details). 26 Figure 3: Example Daily PERFUM Output For A 5 Acre Field PERFUM generates the type of output illustrated by Figure 3 for each day over a 5 year period ( i. e., 1825 days) then summarizes the information by providing two types of results including the " Maximum Buffer" distance and the " Whole Field Buffer" distance. Each is reported as a distribution. The " Maximum Buffer" distribution is based on the maximum distance needed to reach a threshold level of concern ( i. e., HEC adjusted by uncertainty factor) calculated using PERFUM for each day ( i. e., the farthest single point on the irregular line for each day). This results in a distribution that contains 1825 values, and in this assessment, the results have been reported for selected percentiles from those distributions. The " Whole Field Buffer" is based on values from each day as well except the distances on which the distribution is based include those on each spoke where the threshold concentration is achieved for each day ( i. e., distances on all spokes where threshold is achieved or the distances on the irregular line where it intersects each spoke). The number of values in these distributions varies and it is based on 1825 days multiplied by the number of spokes around the field which relates to field size ( see Table 2 above). As with the " Maximum Buffer" distances, results from selected percentiles from the distribution have been reported.

Results based on the PERFUM Modeling Method are presented below in Section <IP_ADDRESS> ( also refer to analysis plan described in Table 3).

<IP_ADDRESS> Bystander Exposures From Known Area Sources Calculated Using The Monitoring Data Method Exposures of and the risks to bystanders from pre plant agricultural field fumigations calculated using monitoring data are presented in this section. Air concentrations based on volatility data were generally reported on a per sample basis ( e. g., 4 hour duration air samples) and as 24 hour time weighted averages ( TWAs). These were calculated using field volatility data that were usually collected around the perimeter of treated sites including downwind locations. Samples were collected at mast sites 27 located within 150 feet or so from the perimeter of the treated field, depending upon the study design. It is clear, as described above that downwind locations will have higher concentrations associated with them because emitted plumes will be pushed in that direction if there is a prevailing wind. For the data considered in this assessment, wind directions varied which makes defining " downwind locations" for the available data complex. There are other micrometeorological and site specific factors ( e. g., topography and roughness) which also add to the complexity of the analysis.

Given these difficulties, and to ensure that this assessment is health protective the Agency has calculated acute MOEs using the 24 hour maximum TWA from the monitoring data for each site where data are available. These maximum TWAs were compared to both of the acute HECs to calculate MOEs based on each toxicological endpoint of concern. The highest TWAs were always observed in the first 24 hours after application.

For the majority of the pre plant field volatility data collected ( 10 of 18 site/ HEC combinations), risks do not exceed HED's acute level of concern ( i. e., MOEs > 30). Results for the maximum monitored values from each treated field are presented below in Table 4. The field volatility monitoring data upon which this analysis is based are presented and summarized in Appendix D: Analysis Of Field Volatility Data For Pre plant Field Uses contains these data.

Table 4: Iodomethane 24 Hour TWA Concentrations Based On Pre Plant Agricultural Field Volatility Data Flux Data Source: Field Location & Application Method Maximum 24 Hour TWA ( ppm) Acute MOEs Based On Each HEC 2.9 ppm HEC 4.0 ppm HEC Manteca CA Broadcast Flat Fume 1.988 ( site near/ in field while others on perimeter  represents worst case) 1.5 2.0 Watsonville CA Broadcast Flat Fume 0.061 48 66 Plant City FL* Raised Bed 0.066 44 60 Oxnard CA Raised Bed 0.347 8.4 12 Guadalupe CA Raised Bed 0.103 28 39 La Selva CA Drip Irrigation 0.071 41 56 Camarillo CA Drip Irrigation 0.06 48 66 Guadalupe CA Drip Irrigation 0.12 24 33 Note: The Agency is aware that additional field volatility monitoring data have been completed by the registrant for iodomethane. Also, the application rates for these studies ranged from 234 to 259 lb ai/ acre and the data were not adjusted for rate and samplers were located from 12 to 30 feet from the treated field.

* There was a rain event during this study 24 hours after application or so. The TWAs are presented here for comparative purposes. 28 <IP_ADDRESS> Bystander Exposures From Known Area Sources Calculated Using The ISCST3 Modeling Method Exposures to bystanders from pre plant agricultural field fumigations and their associated risks, calculated using a modeling approach, are presented in this section. The previous section <IP_ADDRESS> describes exposures based on actual field volatility monitoring data. However, these data are limited because they represent only the conditions in which the studies were actually conducted. Therefore, in order to better characterize the risks associated with the use of iodomethane for various conditions ( e. g., distance from emission source, atmospheric conditions, application method, etc.), exposures have also been calculated using the Agency's ISCST3 model.

The risk estimates ( MOEs or Margins of Exposure) presented below represent results for the acute duration of exposure because they compare 24 hour concentrations calculated with ISCST3 to both of the acute HECs of concern ( i. e., 2.9 or 4.0 ppm with a total uncertainty factor of 30 applied to both).

Results for various field sizes, application methods ( with distinct emission ratios or fraction of the applied material emitted per unit of time); wind speed; atmospheric stability and distances downwind are presented below in Table 5. Table 5 demonstrates that for the cases considered, many risks exceed HED's level of concern ( MOEs < 30) for distances less than 100 meters downwind of the treated field especially when the atmosphere is relatively stable and/ or fields are larger than 1 acre. MOEs decrease as field sizes increase while MOEs increase as the atmosphere becomes less stable leading to conditions where more off target drift can occur. There is not a significant impact in the results due to the two different HECs that were considered. The results in this table summarize the analysis presented in Appendix E: Downwind Air Concentrations Calculated With ISCST3 For PrePlant Field Uses. [ Note: Appendix E contains a summary of the outputs generated by ISCST3 for more distances downwind and field sizes. It does not contain detailed input and output files needed to complete calculations with ISCST3. If so required, these can be provided for review and validation purposes.]

Table 5: MOEs Calculated for Various Distances Downwind For Pre Plant Agricultural Field Fumigations Using ISCST3 Flux Data Source App. Method ER Fld Size ( A) Distance ( M) MOEs For Differing Meteorological Conditions 1 m/ s 2.3 mph 1.4 m/ s 3.1 mpha ( a) 1.8 m/ s 4 mph 2.2 m/ s 5 mph 2.7 m/ s 6 mph 3.1 m/ s 7 mph 3.6 m/ s 8 mph 4.0 m/ s 9 mph 4.5 m/ s 10 mph 4.5 m/ s 10 mph Stab D Stab C Stab C Stab C Stab C Stab C Stab C Stab C Stab C Stab B MOEs Based On HEC = 2.9 ppm ( 16802 µ g/ m3)

Manteca CA Shank Injection, Broadcast, Flat Fume 0.47 1 25 8 17 22 27 33 38 44 49 55 79 100 18 43 55 67 82 94 109 122 137 230 500 99 352 452 553 679 779 905 1006 1131 2644 1000 286 1142 1469 1795 2203 2530 2938 3264 3672 9774 40 25 3 7 9 11 14 16 18 20 23 33 100 5 12 15 19 23 26 30 34 38 56 500 12 30 38 47 57 66 77 85 96 170 1000 18 54 70 86 105 121 140 156 175 395 Table 5: MOEs Calculated for Various Distances Downwind For Pre Plant Agricultural Field Fumigations Using ISCST3 Flux Data Source App. Method ER Fld Size ( A) Distance ( M) MOEs For Differing Meteorological Conditions 1 m/ s 2.3 mph 1.4 m/ s 3.1 mpha ( a) 1.8 m/ s 4 mph 2.2 m/ s 5 mph 2.7 m/ s 6 mph 3.1 m/ s 7 mph 3.6 m/ s 8 mph 4.0 m/ s 9 mph 4.5 m/ s 10 mph 4.5 m/ s 10 mph Stab D Stab C Stab C Stab C Stab C Stab C Stab C Stab C Stab C Stab B 29 Watsonville CA Shank Injection, Broadcast, Flat Fume 0.35 1 25 11 23 30 36 45 51 60 66 74 106 100 24 57 74 90 111 127 147 164 184 310 500 133 474 6609 744 914 1049 1218 1353 1523 3559 1000 385 1538 1977 2416 2965 3405 3954 4393 4942 13155 40 25 4 10 12 15 19 21 25 28 31 45 100 7 16 21 24 31 35 41 46 51 75 500 16 40 52 63 77 89 103 115 129 228 1000 24 73 94 115 141 162 188 209 236 532 Oxnard CA Shallow Shank Injection, Raised Bed 0.37 1 25 10 22 28 34 42 48 56 62 70 99 100 23 54 69 84 103 119 138 153 172 290 500 125 443 570 696 854 981 1139 1266 1424 3329 1000 360 1438 1849 2260 2773 3184 3698 4109 4622 12304 40 25 4 9 12 14 17 20 23 26 29 42 100 6 15 19 23 29 33 38 43 48 71 500 15 38 48 59 72 83 96 107 121 213 1000 22 69 88 108 132 152 176 196 220 497 La Selva CA Drip Irrigation, Raised Bed 0.51 1 25 13 28 36 44 54 62 72 80 90 127 100 29 69 89 108 133 153 177 197 222 373 500 160 571 734 897 1100 1263 1467 1630 1834 4287 1000 464 1852 2381 2910 3572 4101 4763 5292 5953 15846 40 25 5 12 15 18 22 26 30 33 37 54 100 8 19 25 30 37 43 49 55 62 91 500 19 48 62 76 93 107 124 138 155 275 1000 29 88 113 139 170 195 227 252 284 640 MOEs Based On HEC = 4.0 ppm ( 23176 µ g/ m3)

Manteca CA Shank Injection, Broadcast, Flat Fume 0.47 1 25 11 24 31 37 46 53 61 68 76 108 100 25 59 76 92 113 130 151 168 189 317 500 137 485 624 763 936 1075 1248 1387 1560 3647 1000 395 1576 2026 2476 3039 3489 4052 4502 5065 13482 40 25 4 10 13 16 19 22 25 28 32 46 100 7 16 21 26 32 36 42 47 53 77 500 16 41 53 65 79 91 106 117 132 234 1000 25 75 97 118 145 166 193 215 241 545 Table 5: MOEs Calculated for Various Distances Downwind For Pre Plant Agricultural Field Fumigations Using ISCST3 Flux Data Source App. Method ER Fld Size ( A) Distance ( M) MOEs For Differing Meteorological Conditions 1 m/ s 2.3 mph 1.4 m/ s 3.1 mpha ( a) 1.8 m/ s 4 mph 2.2 m/ s 5 mph 2.7 m/ s 6 mph 3.1 m/ s 7 mph 3.6 m/ s 8 mph 4.0 m/ s 9 mph 4.5 m/ s 10 mph 4.5 m/ s 10 mph Stab D Stab C Stab C Stab C Stab C Stab C Stab C Stab C Stab C Stab B 30 Watsonville CA Shank Injection, Broadcast, Flat Fume 0.35 1 25 15 32 41 50 62 71 82 91 103 146 100 33 79 102 124 152 175 203 226 254 427 500 184 653 840 1027 1260 1447 1680 1867 2100 4909 1000 531 2121 2727 3333 4090 4696 5454 6060 6817 18146 40 25 6 13 17 21 26 29 34 38 43 62 100 9 22 28 35 42 49 57 63 71 104 500 21 55 71 87 107 123 142 158 178 315 1000 33 101 130 159 195 224 260 289 325 733 Oxnard CA Shallow Shank Injection, Raised Bed 0.37 1 25 14 30 38 47 58 66 77 85 96 137 100 31 74 95 116 143 164 190 211 238 399 500 172 611 786 960 1179 1653 1571 1746 1964 4591 1000 497 1984 2550 3117 3826 4392 5101 5668 6376 16972 40 25 6 12 16 20 24 28 32 36 40 58 100 9 21 26 32 40 46 53 59 66 97 500 20 52 67 81 100 115 133 148 166 294 1000 31 95 122 149 182 209 243 270 304 686 La Selva CA Drip Irrigation, Raised Bed 0.51 1 25 18 38 49 60 74 85 99 110 124 176 100 40 95 122 150 184 211 245 272 306 514 500 221 787 1012 1237 1518 1743 2024 2249 2530 5913 1000 640 2555 3285 4015 4927 5657 6569 7299 8212 21858 40 25 7 16 21 25 31 36 41 46 52 74 100 11 27 34 42 51 59 68 76 85 125 500 26 67 86 105 129 157 171 190 214 379 1000 40 122 157 191 235 270 313 348 391 883 a. Standard atmospheric conditions used by CDPR in their risk assessments.

<IP_ADDRESS> Bystander Exposures From Known Area Sources Calculated Using The PERFUM Modeling Method Exposures to bystanders from pre plant agricultural field fumigations and their associated risks, calculated using a modeling approach based on PERFUM, are presented in this section. The previous sections <IP_ADDRESS> and <IP_ADDRESS> describe exposures based on actual field volatility monitoring data and a deterministic modeling approach using ISCST3. However, these data are limited because they represent only the conditions in which the studies were actually conducted or the constrained meteorological conditions in ISCST3. Therefore, in order to better characterize the risks associated 31 with the use of iodomethane for various conditions ( e. g., distance from emission source, actual meteorological conditions, application method, etc.), exposures have also been calculated using PERFUM.

The risk estimates presented below represent results for the acute duration of exposure because they compare 24 hour concentrations calculated with PERFUM to the two acute HECs of concern ( i. e., 2.9 ppm or 4.0 ppm, each with a total uncertainty factor of 30). Results for selected percentiles of exposure are reported and in many cases results are based on 95th percentile values as an example ( e. g., MOE exceedance analysis). Use of the 95th percentile ( or results for any other percentile) for reporting purposes does not imply a selection of these estimates for regulatory purposes. Additional analysis based on other percentiles of exposure could be completed if so needed. The results presented in Appendix F: Downwind Air Concentrations Calculated With PERFUM For PrePlant Field Uses are summarized in this section. Please refer to Appendix F for additional details. [ Note: Appendix F itself contains a summary of the outputs generated by PERFUM for both HECs of concern. It does not contain detailed input and output files needed to complete calculations with PERFUM. If so required, these can be provided for review and validation purposes. Also, note in tables specific cells are highlighted for illustrative purposes throughout this section ( e. g., 95th % tile results at maximum rate and maximum buffer distances).]

Appendix F contains several sub appendices ( Appendices F1a through F5f) that include a series of spreadsheets that summarize the results of each analysis described above in Table 3 ( i. e., various combinations of meteorological data and flux/ application methods). [ Note: Appendix F6 contains a series of summary analyses used to develop many of the graphics and tables provided below. Please refer there for further information regarding the details of the summary calculations.] Table 6 and Figure 4 below provide an example of how the results were summarized for each meteorological/ flux data combination considered in this analysis using Ventura California and Watsonville flux data. Table 6 contains results for both HECs considered. Figure 4 represents only the results for the HEC = 4 ppm and an uncertainty factor of 30. The general trend is similar for the results based on the HEC of 2.9 ppm Table 6: Buffer Distances For Ventura CA Weather And Watsonville CA Flat Fume Flux % tiles Results Based On HEC = 2.9 ppm Results Based On HEC = 4.0 ppm Max ( 175 lb/ Acre) 75% ( 131 lb/ Acre) 50% ( 88 lb/ Acre) Max ( 175 lb/ Acre) 75% ( 131 lb/ Acre) 50% ( 88 lb/ Acre)

1 Acre Square 40 Acres Square 1 Acre Square 40 Acres Square 1 Acre Square 40 Acres Square 1 Acre Square 40 Acres Square 1 Acre Square 40 Acres Square 1 Acre Square 40 Acres Square Maximum Buffer Distances ( meters) 50 0 50 0 15 0 5 0 10 0 5 0 0 75 5 90 0 40 0 5 0 35 0 5 0 5 90 5 150 5 80 0 15 5 75 0 30 0 5 95 5 210 5 125 0 40 5 115 0 50 0 5 97 5 265 5 165 0 65 5 155 0 80 0 10 99 15 375 5 275 5 140 5 265 5 170 0 65 99.9 60 700 35 510 5 360 35 495 5 395 5 225 99.99 65 710 45 565 5 385 45 550 5 405 5 275 Table 6: Buffer Distances For Ventura CA Weather And Watsonville CA Flat Fume Flux % tiles Results Based On HEC = 2.9 ppm Results Based On HEC = 4.0 ppm Max ( 175 lb/ Acre) 75% ( 131 lb/ Acre) 50% ( 88 lb/ Acre) Max ( 175 lb/ Acre) 75% ( 131 lb/ Acre) 50% ( 88 lb/ Acre)

1 Acre Square 40 Acres Square 1 Acre Square 40 Acres Square 1 Acre Square 40 Acres Square 1 Acre Square 40 Acres Square 1 Acre Square 40 Acres Square 1 Acre Square 40 Acres Square 32 Iodomethane: M aximum Distance Buffers Ventura CA C IM IS & Watsonville F lat Fume ( M RID 455937 10)

0 100 200 300 400 500 600 5 15 25 35 45 55 65 75 85 95 99 99.9 9 Percentile of Exposure Buffer Distance ( meters)

1A Max 40A Max 1A 75%

40A 75%

1A 50%

40A 50%

Figure 4: Maximum Distance Buffers For Ventura California Weather And Watsonville Flat Fume Flux Based On HEC = 4 ppm & UF = 30 Whole Field Buffer Distances ( meters) 50 0 0 0 0 0 0 0 0 0 0 0 0 75 0 5 0 5 0 0 0 5 0 0 0 0 90 0 40 0 10 0 5 0 10 0 5 0 0 95 5 70 0 30 0 5 0 25 0 5 0 5 97 5 90 0 45 0 5 0 40 0 10 0 5 99 5 155 5 90 0 30 5 85 0 40 0 5 99.9 15 350 5 260 5 145 5 250 5 165 0 50 99.99 55 630 30 475 5 350 25 465 5 355 5 220 The information in Table 6 ( and Appendix F for each analysis) can be used to determine the range of buffers calculated by PERFUM for each analysis ( see Table 3). As expected, 1 acre fields have significantly smaller buffer distances than 40 acre fields. Additionally, reductions in application rate impact the amount of iodomethane volatilizing into the atmosphere from treated fields and also lower buffer distances. The differences between considering " Maximum Buffer" versus " Whole Field Buffer" distances can also be defined. Differences in HECs also impact the results with the higher HEC producing lower buffer distances as expected but it should be noted that the general trends associated with this analysis do not change regardless of which of the two HECs are considered. Figure 4 summarizes the " Maximum Buffer" results for all of the percentiles included in the calculation for 1 and 40 acre fields at varying application rates for Ventura California and using the Watsonville Flat Fume flux data based on an HEC = 4 ppm. The types of results described above can be reviewed in more detail in Appendix F of this document.

PERFUM is also capable of examining the changes observed in MOEs ( Margins of Exposure) under different conditions. For example, the cross hatched area in Figure 3 which represents exceedances can be examined. [ Note: The overall PERFUM analysis considered meteorological data from 5 different 33 Iodomethane: MOE Analysis For 95% tile Max Rate Ventura CA CIMIS & Watsonville Flat Fume ( MRID 455937 10)

1 10 100 1000 90 95 97 99 99.9 Percentile o f Exposure Margins Of Exposure ( Target = 30) Max 100%

Whole 100%

Max 75%

Whole 75%

Max 50%

Whole 50%

Figure 5: MOE Analysis For 95th Percentile Maximum Buffer Distance of 115 Meters Based On Ventura CA Meteorological And Watsonville Flat Fume Flux Data ( HEC = 4 ppm) regions of the country including coastal and inland locations in California and Florida as well as a location in Michigan. Several of the trends in the results are expected to be similar regardless of the location considered so for the purposes of this assessment, as such, only results for Ventura California were considered. PERFUM outputs are available for all locations if additional analyses are required.] Table 7 and Figure 5 below present the results of the MOE analysis for Ventura California and Watsonville flux data as an example using both HECs of concern. Also, note that the MOE analyses have only been completed using 40 acre fields which allow for better determination of the trends. The general trend illustrated in Figure 5 is similar for the results based on the HEC of 2.9 ppm.

Table 7: MOE Analysis For 95th Percentile Buffer Distance( 260 meters) In A 40 Acre Field Using Ventura California Meteorological And Watsonville Flat Fume Flux Data Percentiles Max ( 175 lb/ Acre) 75% ( 131 lb/ Acre) 50% ( 88 lb/ Acre) Max Buffer Whole Field Max Buffer Whole Field Max Buffer Whole Field Results Based On HEC = 2.9 ppm 50 59 1000 79 1000 118 1000 75 46 1000 62 1000 92 1000 90 36 76 48 102 72 149 95 29 57 38 77 58 115 97 24 49 32 66 49 98 99 17 35 23 48 35 71 99.9 8 18 11 24 17 37 99.99 Not. Calc. 9.9 Not. Calc. 13 Not. Calc. 20 Results Based On HEC = 4.0 ppm 50 57 1000 77 1000 115 1000 75 45 124 60 1000 90 1000 90 35 67 47 90 70 135 95 29 53 39 70 58 105 97 25 45 33 61 50 91 99 17 33 23 45 35 67 99.9 8 17 10 23 16 35 99.99 Not. Calc. 9.4 Not. Calc. 12 Not. Calc. 18 Note: MOE analysis is based on the 95th percentile maximum buffer distance at the maximum application rate which is 210 and 115 meters, respectively for HECs = 2.9 and 4.0 ppm ( see Table 6 above). The results shown in this table are actual MOEs and the target uncertainty factor is 30 ( i. e., 29 in this case from rounding in PERFUM) which is reported here at the corresponding 95th percentile. This table illustrates how MOEs would change if whole field buffers, different application rates, or different percentiles of exposure were considered for risk management purposes. 34 The information in Table 7 and Figure 5 ( and Appendix F for each analysis) show that MOEs increase at a fixed point ( e. g., 115 meters in this example) if application rates decrease or whole field buffers are considered instead of maximum distance buffers. Figure 5 also clearly illustrates the rates of change in MOEs over different percentiles of exposure. Even at percentiles of exposure greater than the 95th, MOEs are not substantially lower ( i. e., most MOEs are still $ 10). Thus suggesting that risks are not changing dramatically at the higher percentiles of exposure.

The analyses completed with PERFUM are based on 5 weather station locations and 8 flux studies. In order to broadly understand how differing application methods and the impact of use in different regions ( i. e., climates) can impact buffer zone distances, it is necessary to group the outputs from PERFUM for comparative purposes. Table 8 and Figure 6 are examples of the results for both maximum and whole field buffers in Ventura California at different application rates for all flux studies available for iodomethane rather than just based on the Watsonville study as described above in Table 7 and Figure 5. Results are presented based on both acute HECs of concern ( i. e., 2.9 and 4.0 ppm) for comparative purposes. An analysis of MOE changes under different conditions was also completed using Ventura Meteorological data and all appropriate flux studies. These are presented below in Table 9 and Figure 7. The MOE analysis uses the results for the HEC of 4 ppm based on the results in Table 8 which indicate that the trends would be similar for the results of both HECs.

Table 8: Summary Of PERFUM Buffer Results For Ventura California Meteorological Conditions And All Flux Types For 1 And 40 Acre Square Fields Percen tiles Results Based On HEC = 2.9 ppm Results Based On HEC = 4.0 ppm Maximum PERFUM Buffers ( meters) Whole PERFUM Buffers ( meters) Maximum PERFUM Buffers ( meters) Whole PERFUM Buffers ( meters) Max ( 175 lb/ A) 75% ( 131 lb/ A) 50% ( 88 lb/ A) Max ( 175 lb/ A) 75% ( 131 lb/ A) 50% ( 88 lb/ A) Max ( 175 lb/ A) 75% ( 131 lb/ A) 50% ( 88 lb/ A) Max ( 175 lb/ A) 75% ( 131 lb/ A) 50% ( 88 lb/ A) 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres Flux  Watsonville CA Flat Fume 75 5 90 0 40 0 5 0 5 0 5 0 0 0 35 0 5 0 5 0 5 0 0 0 0 90 5 150 5 80 0 15 0 40 0 10 0 5 5 75 0 30 0 5 0 10 0 5 0 0 95 5 210 5 125 0 40 5 70 0 30 0 5 5 115 0 50 0 5 0 25 0 5 0 5 99 15 375 5 275 5 140 5 155 5 90 0 30 5 265 5 170 0 65 5 85 0 40 0 5 99.9 60 700 35 510 5 360 15 350 5 260 5 145 35 495 5 395 5 225 5 250 5 165 0 80 Flux  Manteca CA Flat Fume 75 5 145 5 75 0 15 0 25 0 5 0 0 5 70 0 25 0 5 0 5 0 5 0 0 90 5 210 5 125 0 45 0 75 0 35 0 5 5 115 0 55 0 5 0 30 0 5 0 5 95 5 275 5 175 0 75 5 110 0 60 0 10 5 165 5 90 0 20 0 55 0 20 0 5 99 35 480 5 340 5 195 5 210 5 130 0 55 5 330 5 225 0 105 5 125 0 70 0 15 99.9 60 800 35 545 5 330 30 420 5 310 5 185 35 525 5 355 5 210 5 300 5 205 0 110 Flux  Oxnard CA Raised Bed 75 5 320 0 200 0 80 0 20 0 5 0 0 0 190 0 100 0 5 0 5 0 5 0 0 90 5 465 0 315 0 155 0 115 0 65 0 10 5 300 0 185 0 65 0 60 0 20 0 5 95 5 565 0 390 0 200 0 215 0 135 0 50 5 370 0 235 0 95 0 125 0 65 0 5 99 45 730 0 515 0 295 5 440 0 300 0 155 5 490 5 330 0 175 5 285 0 180 0 70 99.9 80 960 5 680 0 410 30 665 0 485 0 280 15 655 5 460 0 230 5 465 0 320 0 165 Flux  Guadalupe CA Raised Bed 75 5 335 5 220 0 95 0 40 0 15 0 5 5 205 0 115 0 25 0 15 0 5 0 0 90 5 480 5 330 0 170 0 135 0 80 0 25 5 315 0 195 0 80 0 75 0 35 0 5 95 30 590 5 410 0 225 5 230 0 145 0 60 5 395 5 260 0 115 0 140 0 75 0 10 99 65 775 25 560 5 335 5 445 5 310 0 170 15 540 5 370 0 210 5 300 0 190 0 85 99.9 95 1120 60 805 5 510 50 710 15 510 5 315 55 775 5 560 5 320 10 495 5 350 0 195 Flux  La Selva CA Drip 75 5 220 0 120 0 30 0 10 0 5 0 0 0 115 0 45 0 5 0 5 0 0 0 0 90 5 350 0 220 0 90 0 75 0 35 0 5 0 210 0 110 0 50 0 30 0 5 0 5 95 5 480 5 315 0 145 0 145 0 80 0 20 5 300 0 175 0 85 0 75 0 30 0 5 99 40 660 5 455 0 245 5 320 5 215 0 100 5 435 5 285 0 175 5 205 0 115 0 60 99.9 65 850 5 615 5 345 20 580 5 410 0 225 5 590 5 390 0 260 5 395 5 255 0 165 Percen tiles Results Based On HEC = 2.9 ppm Results Based On HEC = 4.0 ppm Maximum PERFUM Buffers ( meters) Whole PERFUM Buffers ( meters) Maximum PERFUM Buffers ( meters) Whole PERFUM Buffers ( meters) Max ( 175 lb/ A) 75% ( 131 lb/ A) 50% ( 88 lb/ A) Max ( 175 lb/ A) 75% ( 131 lb/ A) 50% ( 88 lb/ A) Max ( 175 lb/ A) 75% ( 131 lb/ A) 50% ( 88 lb/ A) Max ( 175 lb/ A) 75% ( 131 lb/ A) 50% ( 88 lb/ A) 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 1 Acre 40 Acres 35 Flux  Camarillo CA Drip Irrigation 75 0 85 0 35 0 5 0 5 0 5 0 0 0 30 0 5 0 5 0 5 0 0 0 0 90 5 145 0 75 0 25 0 35 0 5 0 5 0 65 0 20 0 5 0 5 0 5 0 0 95 5 195 0 105 0 50 0 65 0 25 0 5 0 100 0 40 0 5 0 20 0 5 0 5 99 5 350 5 230 0 145 5 150 0 85 0 35 5 220 0 135 0 70 0 75 0 30 0 5 99.9 50 625 5 460 5 325 5 325 5 225 0 160 5 440 5 305 0 215 5 215 0 140 0 80 Flux  Guadalupe CA Drip Irrigation 75 5 190 5 110 0 35 0 40 0 15 0 5 5 105 0 50 0 5 0 15 0 5 0 0 90 15 270 5 175 5 75 5 100 0 55 0 10 5 165 5 90 0 20 0 50 0 20 0 5 95 20 330 5 220 5 110 5 145 5 85 0 30 5 210 5 125 0 45 5 80 0 35 0 5 99 55 640 30 445 5 280 10 265 5 175 5 85 20 435 5 305 5 160 5 170 5 100 0 35 99.9 105 1380 70 910 35 545 45 545 25 410 5 260 65 875 405 605 5 355 20 395 5 265 5 160 Table 9: Summary Of Ventura California MOEs For All Flux Studies And 40 Acre Fields Using 95th Percentile Maximum Buffer Distances ( HEC = 4 ppm) Percentiles MOEs For Ventura California Meteorological Conditions And All Flux Studies Max ( 175 lb/ Acre) 75% ( 131 lb/ Acre) 50% ( 88 lb/ Acre) Max Whole Max Whole Max Whole Watsonville Flat Fume  95th Percentile Maximum Distance = 115 Meters 75 45 124 60 100 90 1000 90 35 67 47 90 70 135 95 29 53 39 70 58 105 99 17 33 23 45 35 67 99.9 8 17 10 23 16 35 Manteca Flat Fume  95th Percentile Maximum Distance = 165 Meters 75 43 127 58 1000 87 1000 90 35 65 47 87 70 131 95 29 52 39 69 58 103 99 17 34 24 46 36 69 99.9 9 18 11 24 16 37 Oxnard Raised Bed  95th Percentile Maximum Distance = 370 Meters 75 45 1000 61 1000 91 1000 90 33 102 45 136 67 1000 95 29 62 39 83 58 124 99 23 35 31 47 46 71 99.9 18 24 24 32 36 49 Guadalupe Raised Bed  95th Percentile Maximum Distance = 395 Meters 75 45 1000 61 1000 91 1000 90 34 98 46 131 69 1000 95 29 63 39 84 58 126 99 22 36 30 49 45 73 99.9 16 24 22 32 33 48 La Selva Drip  95th Percentile Maximum Distance = 300 Meters 75 49 1000 65 1000 98 1000 90 36 111 48 149 73 1000 95 29 70 39 93 58 139 99 22 38 29 51 44 77 99.9 16 24 21 32 31 48 Camarillo Drip Irrigation  95th Percentile Maximum Distance = 100 Meters 75 43 108 57 145 86 1000 90 33 62 45 83 68 124 95 29 49 39 66 58 98 99 18 32 24 44 37 65 99.9 9 18 11 24 17 36 Guadalupe Drip Irrigation  95th Percentile Maximum Distance = 210 Meters 75 45 1000 61 1000 91 1000 90 34 98 46 131 69 1000 95 29 63 39 84 58 126 99 22 36 30 49 45 73 99.9 18 24 22 32 33 48 36 9 5 th P e r c e n t i le Io d o m e th a n e B u f fe r R e s u lts F o r 4 0 A c r e F ie ld s F o r V e n tu r a C A & A ll F lu x P ro f ile s ( H E C 4 p p m & U F = 3 0 )

0 5 0 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0 3 5 0 4 0 0 4 5 0 M a x R a te / D is t 7 5 % R a te / M a x D is t . 5 0 % R a te / M a x D is t . M a x R a te / W h o le 7 5 % R a te / W h o le 5 0 % R a te / W h o le A p p lic a tio n R a te & P E R F U M F ie ld A p p ro a c h Buffer Distance ( m)

F la t F um e  W a ts o n . F la t F um e  M a n t e c a R a is e d B e d  O x n a rd R a is e d B e d  G u a d . D r i p  L a S e l va D r ip  C a m a r .

D r ip  G u a d .

Figure 6: 95th Percentile Iodomethane Buffer Distances For 40 Acre Fields, Ventura California Meteorological Data, All Applicable Flux Profiles, Varied Application Rates, And HEC = 4 ppm.

0 20 40 60 80 100 120 140 160 180 200 MOEs At 95th Percentile Maximum Buffer Distance Watson. 115M Manteca 165 M Ox nard 370 M Guad. RB 395 M LaSelva 300 M Camar . 100 M Guad. Dr 210 M Flux Source & 95th Percentile M aximum Buffe r ( m) Max ( 175 lb/ Acre) Max Max ( 175 lb/ Acre) Whole 75% ( 131 lb/ Acre) Max 75% ( 131 lb/ Acre) Whole 50% ( 88 lb/ Acre) Max 50% ( 88 lb/ Acre) Whole Figure 7: 95th Percentile MOE Analysis For 40 Acre Fields, Ventura California Meteorological Data, All Available Flux Profiles, Varied Application Rates , And HEC = 4 ppm The information in Table 8 and Figure 6 ( and Appendix F for each analysis) shows that buffers decrease if application rates decrease or whole field buffers are considered instead of maximum distance buffers. Figure 6 also clearly illustrates that fields where raised bed flux is used as an application method tend to emit more iodomethane than the other methods considered in this analysis. It also appears that at least for La Selva, California that drip irrigation also emits faster than in the other locations considered. It is unclear, however, that drip irrigation inherently emits faster than flat fume techniques based on the Camarillo drip irrigation study. Table 9 and Figure 7 indicate that similar trends in MOE changes with conditions are noted with the Ventura California meteorological data regardless of the flux profile under consideration. It is likely that similar conclusions would be drawn for other weather station locations but the relative differences might be affected.

Along with evaluating the trends among different types of flux results ( i. e., application methods) at a specific location, it is also important to understand how regional weather differences might impact buffer distances. The results for the maximum application rate of 175 lb ai/ acre have been summarized in Tables 10 and 11 as well as Figures 8 through 11 below for all weather stations and flux profiles available for this analysis ( 5 weather stations and 8 flux profiles). Table 10 presents the results for 37 maximum buffer distances for each HEC of concern and all flux rates for 1 and 40 acre fields at differing percentiles of exposure. Figures 8 and 9 present for both HECs of concern the maximum buffer results only for 40 acre fields. Table 11 and Figures 10 and 11 are similar except that they present the whole field buffer results. These tables and figures provide the broadest overall results for the PERFUM analysis that has been completed for iodomethane because they can be used to compare differences based on HEC, region, field size, and flux rate.