Tolerances have been established for residues of endosulfan in/ on various plant and animal commodities under 40 CFR § 180.182 and in processed food commodities under 40 CFR § 185.2600. These tolerances range from 0.1  24 ppm and are currently expressed in terms of endosulfan and its metabolite, endosulfan sulfate. Adequate methods are available for data collection and tolerance enforcement. Codex maximum residue limits ( MRLs) are expressed as the sum of " and $ endosulfan and endosulfan sulfate ( fat soluble). When the U. S. tolerance expression is revised to specify the   and   isomers of the parent, Codex MRLs and U. S. tolerances will be harmonized. A numerical comparison of the Codex MRLs and the 41 corresponding reassessed U. S. tolerances is presented in Table 10 of the Revised Residue Chemistry chapter. Table 10 indicates that U. S. tolerances and the Codex MRLs for endosulfan are compatible for carrot, cottonseed, fruits, meat, pome fruits ( apples), potato, spinach, and sweet potato. For the remainder of commodities listed in Table 10, the U. S. tolerances and the Codex MRLs are incompatible because of differences in registrations or good agricultural practices [ Revised Residue Chemistry Chapter for the Endosulfan Reregistration Eligibility Decision ( RED) Document. John Punzi. February 14, 2002].

Dietary risk estimates are based, in part, on estimates of the percent usage of endosulfan on each registered crop. BEAD has estimated endosulfan use ( Quantitative Usage Analysis for Endosulfan. Steven Nako. October 13, 1999; Updated QUA. David Donaldson. September 10, 2000) based on available pesticide survey usage data for the years 1987 through 1998. BEAD estimates are provided to HED as a weighted average and as an estimated maximum. This risk assessment assumed 1% CT for any BEAD estimate less than 1%. The estimated maximum % CT for each commodity was used for the acute risk assessment and the estimated weighted average % CT for each commodity for the chronic dietary risk assessments. Where no further information was available, 100 % CT was assumed.

Endosulfan residue estimates, or anticipated residues ( AR) in this assessment are based primarily on three data sources: 1) field trial data, submitted by the registrant to support tolerances; 2) USDA PDP food sampling data; and 3) FDA Surveillance Monitoring data. Where data were not available, tolerance levels were used incorporating the % CT estimates from BEAD. The order of preference for the purpose of risk assessment is: PDP data > FDA data > field trial data > tolerance. PDP data are preferred over FDA data because the statistical design of the PDP program is specific for dietary risk assessment ( i. e. sampling is done at grocery store distribution points instead of directly from the field), and because the foods are prepared before analysis as they would typically be before consumption ( i. e. peeling, washing). Many endosulfan treated commodities not sampled by the PDP program are assessed based on translation of data from PDP sampled commodities in the same crop group, FDA surveillance data, or field trial data where available. Tolerance values were used for sugarcane and tea; however, an adjustment factor is applied to raw tea leaves to better estimate residues in drinking tea. Field trial residue data are generally considered by HED as an upper end or a worse case scenario of possible residues and are more suited to the requirements of tolerance setting, because it requires the highest rates of application and shortest PHI, than to the requirements of dietary risk assessment ( when the most realistic estimate is desired).

Potential transfer of pesticide residues from treated feed items to livestock commodities are estimated by calculating a livestock dietary burden, and are based on livestock feeding studies conducted at the appropriate dose levels. For endosulfan, HED estimated a realistic dietary burden to cattle using the following formula: Dietary burden ( ppm) = % of Diet/ % Dry Matter X Anticipated Residue ( ppm). The ARs calculated for beef cattle were also used in this dietary assessment for goat, horse, rabbit, sheep, and veal. HED used PDP data ( 1996 97) for milk which showed all residues to be less than the level of detection ( LOD 0.001 ppm). The chronic AR for milk incorporated ½ LOD for each parent (" and $ isomers) and ½ LOD for the metabolite ( endosulfan sulfate); however, for the acute dietary assessment, a residue data file 42 was used for milk which also incorporated ½ LOD for each parent (" and $ isomers) and metabolite. Potential transfer of pesticide residues from treated feed items to swine commodities were estimated by calculating a swine dietary burden based on submitted swine feeding studies. No endosulfan tolerances are established in eggs and poultry tissues. Submitted poultry feeding data ( MRID# 00003840) suggest that there is no reasonable expectation of finite residues; therefore, eggs and poultry were not included in this dietary assessment ( CFR § 180.683).

Endosulfan residues may be either concentrated or reduced by the activities of drying ( prunes etc.), processing ( juice, catsup, etc.), washing, peeling, and cooking; since processing data were limited, the Dietary Exposure Evaluation Model ( DEEM   ) default factors were used in this assessment for most commodities except apples, cottonseed, grapes, pineapples, potatoes, and tomatoes, for which acceptable processing studies were available. The Agency has reviewed additional processing data that was submitted by the ETF ( April 19, 2002). These additional processing data were deemed inappropriate for use in the dietary assessment; therefore, they were not incorporated ( D282897). The additional data were unacceptable because, among other things, duration of steaming times was missing and/ or excessive cooking and washing times were used. Washing is already incorporated into PDP monitoring data.

HED has developed procedures for handling FDA surveillance monitoring data in dietary exposure analyses with the goal of generating more realistic probabilistic dietary exposure estimates by features of version 7.76 DEEM software. Version 7.76 DEEM software now permits non representative, stratified sampling of data to be incorporated into dietary risk assessments. Currently the use of FDA surveillance monitoring data and its incorporation into HED risk assessments is " case by case" relying on the judgement of the reviewer and depends on the degree of over sampling of imported produce observed, the differences in residue concentrations between domestic and imported produce, and the sample size. If there are significant differences between domestic and import samples, either in terms of likelihood of detected residues or residue levels themselves, then it would be most desirable to " weight" the FDA data such that it better reflects the proportionate " mix" between domestic and foreign produce which the U. S. population consumes. Additional estimates of the percent of commodity imported as well as imported % CT from BEAD are also incorporated. The crops for which these procedures were incorporated are dried beans, blueberries, cauliflower, fresh sweet corn, melons ( except cantaloupe), fresh succulent peas, hot peppers, plums, and summer squash. The additional refinements include modifications to the above mentioned crops only.

4.2.2 Acute Dietary To estimate acute dietary exposure, one day consumption data were summed and a food consumption distribution was calculated for the general population and each population subgroup of interest. The consumption distribution was used with a residue distribution in a probabilistictype ( Monte Carlo) exposure assessment. Exposure estimates were expressed in mg/ kg/ day.

To assess human health risks resulting from consumption of foods that contain residues of endosulfan, estimates of acute dietary food exposure of the general U. S. population and specific population subgroups were compared to the aPAD. The risk estimate for a given 43 population is made from a comparison of the anticipated dietary food exposure of the population to the aPAD established for that population. Dietary exposure is expressed as a percentage of the aPAD ( anticipated exposure ÷ PAD x 100 = % PAD). Dietary exposure estimates that exceed the aPAD values ( i. e., that are greater than 100% of the PAD) are of concern to the Agency. The estimated maximum % CT for each commodity was used for the acute risk assessment. Where no further information was available, 100 % CT was assumed.

The results of the acute dietary food exposure and risk estimates are shown in Table 4. Based on the acute dietary exposure analysis as described above and using an aPAD of 0.0015 mg/ kg/ d for the U. S. population and all population subgroups, the acute dietary exposure to infants less than 1 year of age and children 1 6 years of age exceed the aPAD (> 100%) at the 99.9th exposure percentile. Children 1 6 years have been identified as the most highly exposed population subgroup. Estimated acute dietary exposure to infants and children does not exceed the aPAD at the 99th or 95th exposure percentiles. A complete listing of the acute dietary results is in attachment 4 of Endosulfan. New FQPA and PDP Data, Anticipated Residues, and Revised Acute and Chronic Dietary Exposure Analyses. Sherrie Kinard. April 22, 2002.

Several crops have been identified as making significant contributions to the dietary risk. Residues measured on these crops and the surveyed consumption of these crops, factored together, result in these crops taking up a significant percentage of the aPAD and thereby, making significant contributions to the risk. A number of crops had significant residues from monitoring data and are high consumption items. The significant acute contributors have been identified as succulent green beans, garden green peas, summer squash, spinach, and tomatoes. For all the significant contributors, PDP and/ or FDA monitoring data have shown measurable residues of endosulfan, some greater than tolerance.

Table 4. Acute Dietary Risk Estimates with " Weighted" FDA Data Population aPAD ( 95th percentile) ( 99th percentile) ( 99.9th percentile)

Exposure % aPAD Exposure % aPAD Exposure % aPAD U. S. Population 0.0015 mg/ kg 0.000098 < 1 0.000278 2 0.001252 8 All Infants < 1 year 0.0015 mg/ kg 0.000175 12 0.000381 25 0.001695 113 Children 1 6 years 0.0015 mg/ kg 0.000184 12 0.000492 33 0.002194 146 Children 7 12 years 0.0015 mg/ kg 0.000122 8 0.000338 23 0.001477 98 Females 13 50 years 0.0015 mg/ kg 0.000070 5 0.000228 15 0.001037 69 Males 13 19 years 0.0015 mg/ kg 0.000082 5 0.000222 15 0.000984 66 Population aPAD ( 95th percentile) ( 99th percentile) ( 99.9th percentile)

Exposure % aPAD Exposure % aPAD Exposure % aPAD 44 Males 20+ years 0.0015 mg/ kg 0.000075 5 0.000223 15 0.001018 68 Seniors 55+ years 0.0015 mg/ kg 0.000071 5 0.000265 18 0.001209 81 Exposure estimates include exposure to all endosulfan residues of toxicological concern ( i. e., " endosulfan, $ endosulfan, and endosulfan sulfate).

4.2.3 Chronic Dietary For chronic dietary risk assessments, residue estimates for foods ( e. g. apples) or foodforms ( e. g. apple juice) of interest are multiplied by the averaged consumption estimate of each food/ food form of each population subgroup. Exposure estimates are expressed in mg/ kg bw/ d and as a percent of the cPAD. For the chronic dietary exposure assessment, residue data from USDA's PDP, FDA, or field trials were averaged. If a commodity had no reported detections by the PDP and FDA programs, and the expectation of no detection was confirmed by field trial data, the residue concentration was assumed to be the weighted average of one half the LOD of each residue of toxicological concern ( ½ LOD " endosulfan + ½ LOD $ endosulfan + ½ LOD endosulfan sulfate). For commodities with no detections from FDA data, half the LOQ was used for " endosulfan, $ endosulfan, and endosulfan sulfate. The weighted average estimate of % CT was incorporated into all chronic residue estimates.

The results of the acute dietary food exposure and risk estimates are shown in Table 5. Children 1 6 years of age have again been identified as the most highly exposed population subgroup. Based on the chronic dietary exposure analysis as described above and using a cPAD of 0.0006 mg/ kg/ day, chronic dietary exposure to the general U. S. population and all population subgroups does not exceed the cPAD. A complete listing of the chronic dietary results is in attachment 6 of Endosulfan. New FQPA and PDP Data, Anticipated Residues, and Revised Acute and Chronic Dietary Exposure Analyses. Sherrie Kinard. April 22, 2002.

Table 5. Chronic Dietary Risk Estimates with " Weighted" FDA Data Population cPAD mg/ kg/ day Exposure ( mg/ kg/ day) % Chronic PAD U. S. Population 0.0006 0.000040 < 1 All Infants (< 1 year) 0.0006 0.000057 10 Children 1 6 years 0.0006 0.000104 17 Children 7 12 years 0.0006 0.000063 11 Females 13 50 years 0.0006 0.000028 5 Population cPAD mg/ kg/ day Exposure ( mg/ kg/ day) % Chronic PAD 45 Males 13 19 years 0.0006 0.000043 7 Males 20+ years 0.0006 0.000030 5 Seniors 55+ years 0.0006 0.000028 5 Exposure estimates include exposure to all endosulfan residues of toxicological concern ( i. e., " endosulfan, $ endosulfan, and endosulfan sulfate).

4.2.4 Cancer Dietary Endosulfan is classified as " not likely" a human carcinogen; therefore, no dietary assessment for cancer risk was conducted.

4.3 Drinking Water Exposure/ Risk Pathway Based on the environmental fate properties of each isomer (" and $ endosulfan), technical grade endosulfan represents a mixture of two chemically distinct pesticides which differ in persistence and volatility. Endosulfan is a persistent, semi volatile compound that has been detected in nearly all environmental compartments, including surface and ground water and in areas where it is not used ( e. g., the Arctic and national parks). The end use product is a mixture of two endosulfan isomers, typically 70% " endosulfan and 30% $ endosulfan. The $ isomer is generally more persistent and the " isomer is more volatile. For both isomers, hydrolysis at pH values greater than 7 is an important degradation route; however, at pH values below 7, both isomers are rather persistent. At a pH of 7, " endosulfan and $ endosulfan hydrolyze with half lives of 11 and 19 days, respectively, and at a pH of 9, the isomers have half lives of 4 to 6 hours. Some open literature studies indicate that the hydrolysis half life may be somewhat longer ( but of the same order of magnitude) at pH 7. Under acidic conditions, both isomers are stable to hydrolysis, and microbial degradation in soils becomes the predominant route of degradation. Half lives in acidic to neutral soils range from one to two months for " endosulfan and from three to nine months for $ endosulfan under aerobic conditions. Dissipation rates observed in field studies, which capture a combination of degradation, transport, and uptake, suggest that endosulfan will persist in the surface soil for weeks to months after application. Field dissipation rates were similar to those reported in laboratory soil metabolism studies.

The major transformation products found in the fate studies are endosulfan diol ( hydrolysis) and endosulfan sulfate ( soil metabolism). Both the diol and sulfate degradates have backbone structures similar to the parent compound and are also of toxicological concern. Available data suggest that endosulfan sulfate will be more persistent than the parent under all environmental conditions. The estimated half lives for the combined toxic residues ( endosulfan plus endosulfan sulfate) ranged from roughly 9 months to 6 years. See Final EFED Risk Assessment for the Reregistration Eligibility Decision on Endosulfan ( Thiodan). Nelson Thurman, et al. February 26, 2002. Laboratory studies indicate that " and $ endosulfan have a 46 high affinity for sorption onto soil and are not expected to be highly mobile in the soil environment. However, because of endosulfan's resistance to degradation, it can persist long enough to be transported to both ground and surface waters, as monitoring studies have shown. Endosulfan can contaminate surface waters through spray drift and transport in runoff. In addition, endosulfan may move to targets beyond its use area through atmospheric transport ( via volatilization, transport on dust particles, or a combination). Within the water bodies, endosulfan tends to be sorbed onto sediment and plants. The sorbed endosulfan may be slowly released back into the water.

As mentioned above, the environmental fate profile for endosulfan indicates that both the " and $ isomers of endosulfan, as well as the endosulfan sulfate transformation product, may reach water resources. Existing water monitoring data confirm the presence of endosulfan residues in surface and ground water on a qualitative basis. Because endosulfan is persistent in neutral to acidic soils for months, the pesticide will be susceptible to transport via runoff for prolonged periods after initial application. With repeated applications, or even applications in consecutive years, endosulfan may accumulate in the soil, especially in acidic soils. Endosulfan is expected to be less persistent in alkaline soils due to its susceptibility to hydrolysis.

Its high affinity to sorb to soil indicates that endosulfan is likely to be associated predominantly with the sediment phase in runoff. Endosulfan reaching the water column, through spray drift or runoff, will have a propensity to sorb to benthic sediment, and this sediment may eventually become a source of endosulfan redistribution into the overlying waters. Published literature ( details in Final EFED Risk Assessment for the Reregistration Eligibility Decision on Endosulfan. Nelson Thurman, et al. February 26, 2002) suggests that endosulfan may also be sorbed/ taken up by macrophytes and algae, and released back into the water column when these plants die off. Because of its tendency to sorb onto soil, endosulfan should not be frequently detected in ground water; however, endosulfan is a persistent chemical, and available monitoring data have revealed endosulfan detections in wells. Aquifers below acidic soils are likely to be more vulnerable to endosulfan contamination than those below neutral or alkaline soils, due to the lack of hydrolysis under acidic conditions. Endosulfan sulfate, the major transformation product identified in soil, is more persistent than the parent. Comparative studies indicate that endosulfan sulfate is similar in mobility to the parent endosulfan.

Limited water monitoring data exist for endosulfan. Endosulfan was not included in the U. S. Geological Survey National Water Quality Assessment ( NAWQA) program. The STORET database includes a variety of monitoring reports for the endosulfan isomers and for endosulfan sulfate. The results reported in the database vary in terms of data quality, sampling and analytical methods, detection limits, and level of quality assurance/ quality control. Insufficient information exists with the reported studies to determine whether sampling occurred in actual endosulfan use areas or during times when endosulfan might potentially occur in water. Despite these limitations, the available studies have shown that endosulfan and its degradate, endosulfan sulfate, have contaminated numerous surface and ground water bodies throughout the United States. Both surface and ground water modeling simulations show that endosulfan and endosulfan sulfate may reach ecologically significant water bodies as well as drinking water supplies. 47 4.3.1 Ground Water Resources While both " and $ endosulfan appear to be persistent in most laboratory studies, particularly in acidic to neutral soils, its high affinity to sorb onto soils suggests that it should not move extensively through the soil and vadose zone to ground water. The Agency believes that the potential for endosulfan to reach ground water is limited to acidic to neutral soils and aquifers where preferential flow may be a prevalent pathway to ground water or where the ground water is shallow and is overlain by highly permeable soils. Available evidence suggests that the transformation products   endosulfan sulfate and endosulfan diol   may be persistent. Endosulfan sulfate is similar in mobility to the parent endosulfan while endosulfan diol appears to be more mobile.

The Pesticides in Ground Water Database ( USEPA OPP, 1992) reports detections of endosulfan, ranging from trace to # 20 : g/ L, in 1.3% of 2410 discrete samples ( 32 wells). Detections were reported in California, Maine, and Virginia. All sampling was conducted on or before the year 1989. The abbreviated nature of the PGWDB does not capture important factors such as depth of the water table, soil permeability, proximity of crops to wells, usage ( application) of the chemical in the years prior to sampling, suitability of the analytical methodology used and/ or limits of detection. Endosulfan sulfate was detected in 0.3% of the samples ( 6 out of 1969), with detections ranging from < 0.005 to 1.4 : g/ L. The detections were reported in Indiana and New York. Sampling occurred at or prior to 1990. No data were available for endosulfan diol.

4.3.2 Surface Water Resources Endosulfan can contaminate surface water through spray drift or runoff. The persistence of " and $ endosulfan is sufficient to expect accumulation on soil after repeated applications and possible accumulation from year to year. Such persistence suggests that endosulfan will be available to move to surface waters via runoff for several months or longer after application. Its high affinity to sorb onto soil indicates that endosulfan may move primarily while adsorbed to eroding soil and will preferentially partition into the sediment fraction of the surface water system. Conditions which may favor runoff include poorly draining or wet soils with readily visible slopes toward adjacent surface waters, frequently flooded areas, areas overlaying shallow ground water, areas not separated from adjacent surface water with vegetated strips, and highly erodible soils cultivated using poor agricultural practices ( such as conventional tillage).

The degradate endosulfan sulfate is probably formed in the soil and, due to its very high persistence, is likely to reach surface waters as well. Endosulfan diol may be formed in neutral to basic surface waters as a hydrolysis product. Comparative studies indicate that endosulfan sulfate will be similar in mobility to $ endosulfan, and thus have an affinity to bind to sediment, while endosulfan diol is likely to be more mobile than the parent.

A review of the STORET data for " and $ endosulfan, unspecified endosulfan residues, and endosulfan sulfate showed numerous incidences of detections. The STORET data are not 48 reliable enough to enable an accurate quantitative assessment of the endosulfan distribution throughout the U. S., but it does give some insight into where endosulfan is being found. Confirmed detections of one or more endosulfan residues were reported in 38 states. States that reported relatively high numbers of endosulfan detections ( with respect to other reporting states) included California, Florida, Louisiana, Washington, Mississippi, and Ohio. An analysis of the monitoring data which reported detects for total endosulfan show a highly skewed distribution, as would be expected with monitoring data. The mean concentration is 0.17 : g/ L, with a standard deviation of 0.98 : g/ L. The 90th percentile value was 0.31 : g/ L and the median value was 0.03 : g/ L. The mean STORET concentrations are not expected to exceed peak estimated environmental concentrations ( EECs) predicted by the PRZM/ EXAMS model because they do not necessarily represent the most vulnerable sites or sampled peak times. Little is known about actual sample conditions. In addition, the limits of detection vary widely depending on the purpose of the monitoring and the availability of analytical methods and equipment so that reported nondetections do not necessarily mean that endosulfan was not present where a non detect was reported.

The National Sediment Quality Survey ( U. S. EPA, 1997) reported detections of endosulfan residues in stream sediments in 30 out of 76 watersheds in which endosulfan was analyzed. The watersheds occurred in 12 states, ranging from Rhode Island to California and from Mississippi to Michigan. As with the STORET data, one of the sources of data used in the survey, this summary provides more of a qualitative evaluation of the extent to which endosulfan may be found in the environment rather than a quantitative assessment of endosulfan occurrence.

4.3.3 Estimated Environmental Concentrations Drinking water EECs for surface and ground water were determined from the PRZM/ EXAMS and SCIGROW models, respectively. EFED based the " and $ endosulfan drinking water EECs for surface water sources on PRZM/ EXAMS simulations with the maximum allowable application of endosulfan ( 1.0 lb a. i. / acre, 3 times per year) to a Mississippi cotton scenario with the standard index reservoir and percent crop area ( PCA) factor included. Procedures for calculating the EECs followed the method described in the section on water assessment for ecological effects in Final EFED Risk Assessment for the Reregistration Eligibility Decision on Endosulfan. Nelson Thurman, et al. February 26, 2002: for the " and $ endosulfan isomers, the output was adjusted by 70% for " endosulfan and 30% for $ endosulfan; endosulfan sulfate concentrations were determined by multiplying the total endosulfan concentration by 0.55, the median ratio of endosulfan sulfate to combined isomer concentrations found in the STORET database. Chemical specific input parameters used for the PRZM/ EXAMS simulations, as well as application specific parameters for the cotton scenario used in the drinking water assessment are given in EFED's chapter. All other parameters were used according to standard EFED practice. Both the peak and chronic surface water EECs are well within the range of measured endosulfan concentrations in the EPA STORET database ( where total endosulfan concentrations range from less than the level of detection to a maximum peak of 180 : g/ L). The groundwater EECs were generated with SCIGROW. For K oc values greater than 10,000 ml/ g, SCIGROW gives the default value of 0.006 ppb, regardless of other input parameters. The default SCIGROW value is within the range of reported groundwater 49 detections of 0 to 20 ppb ( USEPA OPP, 1992). Table 6 summarizes the estimated drinking water EECs for the " and $ isomers of endosulfan and the degradate endosulfan sulfate.

Table 6. Tier 2 EECs for Endosulfan and Endosulfan Sulfate in Drinking Water Isomer Surface Water Acutea EEC Surface Water Chronicb EEC Ground Water EEC " endosulfan 3.5 : g/ L 0.56 : g/ L  $ endosulfan 1.7 : g/ L 0.24 : g/ L  total endosulfan ("+$) 5.2 : g/ L 0.80 : g/ L 0.006 : g/ L endosulfan sulfate 2.9 : g/ L 0.45 : g/ L 0.006 : g/ L a Acute EEC represents the upper 1 in 10 year peak concentration. b Chronic EEC represents the upper 1 in 10 year mean annual concentration.

4.3.4 Drinking Water Levels of Comparison Generally, the Agency calculates Drinking Water Levels of Comparison ( DWLOC) for comparison to measured or modeled drinking water concentrations for the risk analysis. The DWLOC is the concentration in drinking water, as part of the aggregate exposure, that occupies no more than 100% of the PAD. The dietary exposure from food and the DWLOC together, cannot be greater than 100% of the PAD. Any measured or modeled drinking water estimates that are less than the DWLOC are not of concern.

The Agency has calculated DWLOCs for acute and chronic exposure to endosulfan in surface and ground water for the population subgroups; children 1 6 years ( the most highly exposed subgroup), infants < 1 year, females 13 50 years, and the general U. S. population. To calculate the DWLOC for acute or chronic ( non cancer) exposure relative to an acute or chronic toxicity endpoint, the dietary food exposure ( from DEEM   ) was subtracted from the PAD to obtain the exposure to endosulfan in drinking water that would not be of concern.

An acute DWLOC ( DWLOC acute) was calculated using the following formulae:

DWLOC acute (: g/ L) = acute water exposure ( mg/ kg/ d) x body weight ( kg) consumption ( L/ d) x 10 3 mg/: g acute water exposure ( mg/ kg/ d) = [ aPAD  acute food ( mg/ kg/ d)]

The current Agency default body weight and consumption values are 10 kg and 1 liter/ day, respectively, for all infants and children, 70 kg and 2 liters/ day for adult males, and 60 kg and 2 liters/ day for adult females. These default values and others are presently under review in the Agency ( Office of Research and Development). If at a future time, the Agency decides to change the default assumptions used, the impact of the changes on the endosulfan risk assessment will be considered. 50 A chronic DWLOC ( DWLOC chronic) was calculated using the following formulae:

DWLOC chronic (: g/ L) = chronic water exposure ( mg/ kg/ d) x body weight ( kg) consumption ( L/ d) x 10 3 mg/: g chronic water exposure ( mg/ kg/ d) = [ cPAD  ( chronic food + residential( ADD)( mg/ kg/ d))]

Where ADD = average daily dose Residential exposures were not factored into the DWLOC chronic since no residential uses are being supported by the ETF.

Table 7a. Endosulfana Drinking Water Levels of Comparison for Acute Dietary Exposure Population Subgroup Acute PAD ( mg/ kg/ day) Food Exposure ( mg/ kg/ d) @ 99.9th percentile Water Exposure ( mg/ kg/ d) DWLOC acute ( µ g/ L) Surface Water Peak EECb ( µ g/ L) Ground Water EECb ( µ g/ L)

U. S. Population 0.0015 0.0013 0.00025 8.7 8.1 0.012 Females ( 13 50 yrs) 0.0015 0.0010 0.00046 14 8.1 0.012 Infants < 1 yr 0.0015 0.0017 0 0 8.1 0.012 Children 1 6 yrs 0.0015 0.0022 0 0 8.1 0.012 a Includes " endosulfan, $ endosulfan, and endosulfan sulfate. B Estimated Environmental Concentrations.

Table 7b. Drinking Water Levels of Comparison for Chronic Dietary Exposure Population Subgroup Chronic PAD ( mg/ kg/ day) Food Exposure ( mg/ kg/ d) Max. Water Exposure ( mg/ kg/ d) DWLOC chronic ( µ g/ L) Surface Water Chronic EECb ( µ g/ L) Ground Water EECb ( µ g/ L)

U. S. Population 0.0006 0.000040 0.00056 20 1.3 0.012 Females ( 13 50 yrs) 0.0006 0.000028 0.00057 17 1.3 0.012 Infants < 1 yr 0.0006 0.000057 0.00054 5.4 1.3 0.012 Children 1 6 yrs 0.0006 0.00010 0.00050 5 1.3 0.012 a Includes " endosulfan, $ endosulfan, and endosulfan sulfate. B Estimated Environmental Concentrations. 51 4.4 Residential Exposure/ Risk Pathway 4.4.1 Home and Recreational Uses As mentioned earlier, the ETF is not supporting any uses of endosulfan in or around the home, around public buildings or recreational areas, or on rights of way. Therefore, the Agency did not include the affected non agricultural and residential uses in its revised risk assessment. Previous risk assessments showed unacceptable risks associated with home and recreational uses.

4.4.2 Other The Agency's current approach for completing residential exposure assessments ( when applicable) is based on the guidance provided in the Draft: Series 875 Occupational and Residential Exposure Test Guidelines, Group B Postapplication Exposure Monitoring Test Guidelines, the Draft: Standard Operating Procedures ( SOPs) for Residential Exposure Assessment, and the Overview of Issues Related to the Standard Operating Procedures for Residential Exposure Assessment presented at the September 1999 meeting of the FIFRA Scientific Advisory Panel ( SAP). The Agency is, however, currently in the process of revising its guidance for completing these types of assessments. Modifications to this assessment shall be incorporated as updated guidance becomes available. This will include expanding the scope of the residential exposure assessments by developing guidance for characterizing exposures from other sources not already addressed, such as from spray drift; residential residue track in; exposures to farm worker children; and exposures to children in schools.

5.0 AGGREGATE RISK ASSESSMENT AND RISK CHARACTERIZATION 5.1 Overview Risk is a function of exposure multiplied by hazard ( Risk = Exposure x Hazard). Exposure may be measured or modeled, depending on the available data. Ideally the exposure data would be chemical specific occupational or residential monitoring data, at the tap drinking water data, and close to the plate food residue data on all crops. In the absence of an ideal data set, surrogate data, and other factors are incorporated into the exposure assessments ( dietary and non dietary) to present a reasonable exposure picture based on the best available data. The hazard portion of the risk equation has several layers of safety built into it to provide a cushion between exposure and the dose at which adverse effects were seen in an animal study. Generally, endpoints are based on the dose at which no observable adverse effect is seen in an animal study. This is the No Observable Adverse Effect Level ( NOAEL). The Lowest Observable Adverse Effect Level ( LOAEL) is the next highest dose in an animal study, up from the NOAEL, at which the adverse effect of concern is seen. Since the toxicity studies used for endpoint selection are conducted in animals, and there are differences between individual humans, additional uncertainty factors for inter and intra species variability are integrated into the hazard portion of the risk equation. Since the passage of the FQPA, an additional layer of 52 protection is factored in ( when appropriate) to provide an even greater safety cushion between exposure and toxic effects for particularly sensitive populations. It is in this light that expressions of risk ( risk numbers) should be viewed with an understanding that they are not portrayals of imminent toxic effects to humans but as a measure of the distance between potential exposure and possible toxic effects.

In accordance with current HED policy ( effective 03/ 11/ 99) the acute and chronic dietary endpoints are expressed as acute Population Adjusted Dose ( aPAD) and chronic PAD ( cPAD), and no longer as an adjusted Reference Dose ( RfD).

RfD = acute or chronic NOAEL Uncertainty Factor ( UF)

Generally, an UF of 100 is applied for intra and inter species differences.

PAD = acute or chronic RfD FQPA factor The use of the PAD will apply whether the FQPA factor is retained ( 10x or 3x) or not ( 1x). When a PAD is used, such as in the dietary assessment, the risk is expressed as a percentage of the PAD which is equal to the measured exposure divided by the PAD and then multiplied by 100 or:

Risk (% PAD) = Exposure x 100 PAD Occupational, residential ( when applicable), and the aggregate risk ( when appropriate) will still be expressed as the Margin of Exposure ( MOE).

MOE = NOAEL ( mg/ kg/ d Exposure ( mg/ kg/ d)

Current HED policy requires that FQPA safety factors be retained for dietary and nonoccupational exposures, when appropriate, not occupational exposures ( Memorandum, Special Report of the FQPA Safety Factor Committee, B. Tarplee and J. Rowland, April 15, 1998). Therefore, an MOE of > 100 is needed in the occupational exposure risk assessment.

Due to the availability of acceptable/ guideline oral, dermal, and inhalation studies using endosulfan, the dietary and occupational risk assessments were conducted using route specific endpoints. However, to fully characterize the hazard and potential risk from exposures to endosulfan, subchronic neurotoxicity and developmental neurotoxicity studies in rats, are requested. The acute dietary endpoint is based primarily on neurotoxicity. The neurotoxicity is believed to result from over stimulation of the CNS. Characteristic clinical signs of endosulfaninduced neurotoxicity include, in part: hyperactivity, tonic contractions, involuntary muscle movements, pronounced sensitivity to noise and light, incoordination, seizures, and convulsions. 53 These clinical signs are observed in humans accidentally exposed to endosulfan, and in animal studies of varying treatment durations following different routes of exposure and in different animal species. The chronic dietary, and short, intermediate, and long term dermal and inhalation endpoints are based on the toxic effects observed in animals following subchronic or chronic exposure and include: neurotoxicity, hematological effects, and nephrotoxicity. In some animal studies, endosulfan inhibited plasma cholinesterase at the highest doses tested. Endosulfan is not a dermal sensitizer, nor is it mutagenic or carcinogenic (" Not Likely" a human carcinogen).

5.2 Acute Risk 5.2.1 Aggregate Acute Risk Assessment The acute aggregate risk estimate includes the contribution of risk from dietary ( food + drinking water) sources only. Acute risk estimates from exposures to food, associated with the use of endosulfan exceed the Agency's level of concern at the 99.9th exposure percentile for infants less than 1 year of age ( 113% aPAD) and children 1 6 years of age ( 146% aPAD). The acute Tier 3 dietary risk analysis estimated the distribution of single day exposures for the overall U. S. population and certain population subgroups and evaluated exposure to endosulfan for each food commodity. The input values included the ARs, incorporating % CT and processing factors, for commodities on which endosulfan is used. Chemical specific monitoring data on food were used for the majority of commodities. Where monitoring data were not available, translations from similar commodities or field trial data were used.

Some chemical specific water monitoring data are available but they are limited and not at the tap data. Though they may be indicative of surface and ground water levels of endosulfan under limited conditions, the Agency believes that they are unsuitable to be quantitatively included in aggregate risk assessment. Therefore, estimated environmental concentrations ( EECs) were calculated by EFED to estimate the potential contribution to the acute exposure from drinking water, and the EECs were compared to the acute DWLOCs.

5.2.2 Acute DWLOC Calculations Taking into account the present uses and uses proposed in this action, the Agency can conclude with reasonable certainty that residues of endosulfan and endosulfan sulfate, combined, in drinking water would likely result in an acute dietary risk above the Agency's level of concern, particularly to infants and children. The Agency based this determination on a comparison of estimated concentrations of endosulfan in surface waters to back calculated " levels of comparison" for endosulfan in drinking water. The estimates of endosulfan in surface waters were derived from water quality models that used conservative assumptions ( healthprotective regarding the pesticide transport from the point of application to surface and ground water, and were supplemented with limited monitoring data.

Modeled Tier 2 ( PRZM/ EXAMS) estimates of endosulfan and endosulfan sulfate concentrations in surface water, combined, were above the acute DWLOCs and are of concern. 54 Since exposures to endosulfan in food alone pose a potential risk of concern for children 1 6 years of age and infants, additional exposures from water would increase the concern and therefore the DWLOCs for these populations are " 0." The EECs calculated by EFED were based on the maximum allowable application of endosulfan ( 1 lb a. i/ acre, 3 times/ year) to a Mississippi cotton scenario with the standard index reservoir and percent crop area factor included. The available monitoring data indicate that 90th percentile values would not be expected to exceed peak EEC values. One should keep in mind that these estimates, as well as the available monitoring data, do not represent dilution from source to tap nor concentrations after drinking water treatment, and may actually be lower. Common drinking water treatment methods such as flocculation and sedimentation are known to remove some organochlorines but no endosulfan specific treatment data are available.

The ground water EECs were generated using the SCIGROW ( Tier 1) model applied to the Mississippi cotton scenario and appropriate fate and transport factors. The ground water estimates of endosulfan and endosulfan sulfate concentrations, combined, as well as available monitored concentrations, are low. However, the DWLOCs for infants and children 1 6 years of age are " 0" and therefore, exposures from groundwater are of concern.

5.3 Short and Intermediate term Aggregate Risk Aggregate short and intermediate term risk includes the contribution of risk from dietary ( food + water) and residential sources to the total risk. Since residential uses are not being supported by the ETF, exposures from these uses were not included in the risk assessment. Steps have already been taken to remove residential uses from endosulfan labels, but further steps are needed.

5.4 Chronic Risk 5.4.1 Aggregate Chronic Risk Assessment Aggregate chronic ( noncancer) risk estimates include the contribution of risk from dietary sources ( food + water) and residential sources; however, as mentioned above, no residential uses are being supported. Chronic risk estimates from exposures to food, do not exceed the Agency's level of concern for the U. S. general population and all population subgroups. The chronic dietary ( food only) risk estimate is 17% of the cPAD, for the most highly exposed population subgroup, children ages 1 6 years of age.

As in the acute aggregate assessment, EECs were calculated by EFED to estimate the potential contribution to the chronic exposure from drinking water, and the EECs were compared to the chronic DWLOCs.

5.4.2 Chronic DWLOC Calculations Taking into account the present uses and uses proposed in this action, the Agency can conclude with reasonable certainty that residues of endosulfan and endosulfan sulfate, 55 combined, in drinking water would not likely result in a chronic dietary risk to infants, children, and adults above the Agency's level of concern.

Modeled Tier 2 ( PRZM/ EXAMS) estimates of endosulfan and endosulfan sulfate concentrations in surface water, combined, were below the chronic DWLOCs and are not of concern. Again, the EECs calculated by EFED were based on the maximum allowable application of endosulfan to a Mississippi cotton scenario with the standard index reservoir and percent crop area factor included. Since the SCIGROW model does not allow for the generation of chronic ground water estimates, the acute values are used, resulting in a highly conservative estimate. Even these highly conservative ground water estimates of endosulfan and endosulfan sulfate concentrations, combined, were below the chronic DWLOCs and are not of concern.

6.0 CUMULATIVE RISK Endosulfan, as well as its metabolite endosulfan sulfate, belong to the chlorinated cyclodiene ( organochlorine) class of insecticide/ acaricides. The Agency does not currently have data available to determine with certainty whether endosulfan or endosulfan sulfate have a common mechanism of toxicity with any other substances. For the purposes of this human health risk assessment, the Agency has not assumed that endosulfan or endosulfan sulfate have a common mechanism of toxicity with other pesticides. The Agency has proposed guidance for conducting cumulative risk assessment ( proposal is available on EPA's website, USEPA, 2002). When the guidance is finalized, endosulfan and its metabolite( s) will be revisited to assess the cumulative effects of exposure to multiple organochlorines.

7.0 OCCUPATIONAL EXPOSURE 7.1 Handler Exposure Scenarios The Agency has determined that there are potential exposures to mixers, loaders, applicators, and other handlers during usual use patterns associated with endosulfan. Based on the use patterns, 21 major occupational exposure scenarios were identified for endosulfan: ( 1a) mixing/ loading liquid formulations for aerial application; ( 1b) mixing/ loading liquid formulation for chemigation; ( 1c) mixing/ loading liquid formulations for groundboom application; ( 1d) mixing/ loading liquid formulations for airblast application; ( 1e) mixing/ loading liquid formulations for rights of way sprays; ( 1f) mixing/ loading liquid formulations for plant and root dip; ( 2a) mixing/ loading wettable powders for aerial application; ( 2b) mixing/ loading wettable powders for groundboom application; ( 2c) mixing/ loading wettable powders for airblast application; ( 2d) mixing/ loading wettable powder for rights of way spray application; ( 2e) mixing/ loading wettable powders for plant and root dip; ( 3) applying sprays with aerial equipment; ( 4) applying sprays with a groundboom sprayer; ( 5) applying sprays with an airblast sprayer; ( 6) applying sprays with a rights of way sprayer; ( 7) 56 applying dip treatment to roots, or whole plants; ( 8) mixing/ loading/ applying liquids with a low pressure hand wand; ( 9) mixing/ loading/ applying wettable powders with a low pressure handwand; ( 10) mixing/ loading/ applying liquids with a high pressure hand wand; ( 11) mixing/ loading/ applying liquids with backpack sprayer; and ( 12) flagging aerial spray applications.

On current endosulfan labels, personal protective equipment ( PPE) requirements range from no PPE listed, to long sleeved shirt and long pants, waterproof gloves, shoes, socks, chemical resistant headgear, respirator with either an organic vapor removing cartridge with a prefilter or canister approved for pesticides. Mixers and loaders must also wear a chemical resistant apron.

Submitted Data/ Information In support of the reregistration process for endosulfan, AgrEvo USA submitted a worker exposure study for review by the Agency. The 1987 study, Exposure of Mixer/ Loader/ Applicators to Thiodan ® 3EC Insecticide Applied to Fruit Trees by Airblast Equipment in California was originally submitted as MRID# 410485 02. The registrant subsequently made revisions and resubmitted the study in 1990 as MRID# 417152 01. The Agency determined that both the original and revised study do not meet Agency guidelines for acceptability under Series 875 of the Occupational and Residential Test Guidelines. Therefore, the data in MRID# s 410485 02 and 417152 01 were not used in the assessment. Instead, surrogate based exposure assessments for each scenario were developed, where appropriate data were available, using the Pesticide Handlers Exposure Database ( PHED) Version 1.1.

The registrant also submitted a risk assessment titled, Evaluation of the Human Hazards and Risks Associated with the Application of Endosulfan dated March 1989 ( MRID# 410485 01). This submission was not used in this risk assessment for the following reasons: the exposure data used was from the above study ( MRID# 417152 01) which was found to be unacceptable, acres treated per day used were not justified and vary widely from the Agency standard values, and the monkey dermal penetration study which is critical in interpreting the biological monitoring data was not acceptable.

The Agency has reviewed Aventis' Submission of an Application Exposure Assessment for Endosulfan and an Evaluation of Possible Endocrine Effects in Mammalian Species dated August 4, 1999 ( MRID# 449391 01) and concludes that the submission does not follow standard Agency policies or use Agency standard default values. The Agency calculates highend single day exposures to occupational workers, based on maximum label application rates and standard values for the number of acres that can be treated in a single day by various types of agricultural equipment. These standard acres treated per day values are representative of most crops treated with endosulfan, including both low ( strawberries) and high ( potatoes) acreage crops, and are protective of commercial applicators who may treat multiple farms or fields in one day. Although the 1992 U. S. Census of Agriculture data used by Aventis does represent the national average crop acreage per farm, it is only representative of individual farmers and not of commercial applicators, who are likely to treat more acres in a day than individual growers. 57 Aventis' exposure assessment incorporates a 50% reduction factor to dermal exposure for workers, based on the label requirement for chemical resistant headgear. HED does not assign a reduction factor to dermal exposure due to the use of chemical resistant headgear. Although HED agrees that chemical resistant headgear may reduce pesticide exposure, a protection factor has not been established for the use of such headgear, due to a lack of data. Therefore, HED does not quantitatively reduce exposure risk estimates to take chemical resistant headgear into account.

Occupational Exposures and Risks HED notes that the revised dermal endpoints are based on the 21 dermal study in the rat for the short term and intermediate term ( postapplication only) exposure durations. This study replaces the two year chronic toxicity/ carcinogenicity study in rats that was originally used to assess for intermediate term dermal exposure. The Agency considered Aventis' submission for inclusion in the endosulfan assessment, but because of the aforementioned discrepancies, it was not included in this assessment.

Handler exposure assessments were completed using a baseline exposure scenario and, if required, increasing levels of risk mitigation ( PPE and engineering controls) in an attempt to achieve an appropriate margin of exposure. The baseline scenario generally represents a handler wearing long pants, a long sleeved shirt, no respirator, and no chemical resistant gloves ( there are exceptions pertaining to the use of gloves, and these are noted).

It is desirable that short term occupational risks, expressed as margins of exposure ( MOEs), be > 100. MOEs below 100 are of concern. In accordance with current Agency guidance, the FQPA factor is not retained for the occupational risk assessment ( Memorandum, Special Report of the FQPA Safety Factor Committee. Brenda Tarplee and Jess Rowland. April 15, 1998). Dermal and inhalation risks for handlers were assessed separately since the end effects for the toxicological endpoints chosen for these exposures are dissimilar and Agency policy prevents aggregation of the risks ( inhalation plus dermal) if the toxicological effects are not the same. Handler exposures to endosulfan are expected to be short term only ( 1 30 days).

Of the 21 identified occupational handler exposure scenarios, 5 of them are a risk of concern, having calculated MOEs less than the target MOE of 100, at the highest level of mitigation for short term dermal exposure. For short term inhalation exposure, 4 of the 21 identified occupational handler exposure scenarios are a risk of concern, having calculated MOEs less than the target MOE of 100, at the highest level of mitigation. See Table 9a, Summary of Occupational Handler Risks. Three scenarios lack data to assess their risk. Data are needed to assess the following occupational handler scenarios: applying dip treatments to trees and roots or whole plants and mixing/ loading/ applying wettable powders with a backpack sprayer and a high pressure handwand.

Several issues must be considered when interpreting the occupational exposure risk assessment. These include:

C Several generic protection factors ( PF) were used to calculate handler exposures ( e. g., 58 90% PF over baseline for inhalation unit exposure to account for use of an organic vapor removing respirator). These protection factors are considered conservative, but have not been completely evaluated by HED.

° Low confidence data, based on PHED grading criteria, were used to calculate the risks to handlers from the following scenarios for any body part and/ or level of mitigation: Mixing/ loading wettable powders, applying sprays with an airblast sprayer ( enclosed cabs), applying sprays with a rights of way sprayer, mixing/ loading/ applying liquids and wettable powders with a low pressure handwand, mixing/ loading/ applying liquids with a high pressure handwand and backpack sprayer, and flagging aerial applications.

7.2 Postapplication The Agency has determined that there are potential short and intermediate term postapplication exposures to individuals entering treated fields. Current endosulfan labels show a restricted entry interval ( REI) requirement of 24 hours with the following early entry PPE required: coveralls, waterproof gloves, shoes, socks and chemical resistant headgear for overhead exposures.

For the purpose of conducting this assessment, crops were grouped in order to assign the most representative dislodgeable foliar residue ( DFR) data to the crops. The crop groups listed below were chosen because appropriate residue data were available ( MRID 444031 02). The crop groups and corresponding surrogate residue data sources are as follows:

° Tree Crops: DFR data for peaches were used, based on a study using an application rate of 3 lbs. ai/ acre, to determine exposure from postapplication activities associated with all tree crops ( 15 tree crops other than peaches). This application rate is consistent with the application rates for most fruit and nut trees. For the crops where the application rates were not 3 lbs. ai/ acre, the DFR data were adjusted ( linear) to the appropriate application rate for the individual crops.

° Grape Harvesting, Girdling and Irrigating: This scenario was based on DFR data for grapes using an application rate of 1.5 lbs ai/ acre. This is the labeled application rate for grapes.

° Field Crops: DFR data for melons were used and were assumed to be representative of exposure from postapplication activities associated with all the remaining crops registered for endosulfan ( 37 crops other than melons) except for grapes and tree crops. The DFR data were based on an application rate of 1 lb. ai/ acre. However, most of the labeled application rates for these crops range from 0.25 to 3 lbs. ai/ acre. Thus, the DFR data were adjusted ( linear) to the appropriate application rate for the individual crops.

Submitted Data A DFR study was conducted for endosulfan and its metabolites, $ endosulfan and endosulfan sulfate. The study evaluated dislodgeable residue dissipation for endosulfan applied 59 to peaches, grapes, and melons ( MRID# 444031 02). In summary, the DFR study completed in support of the regulatory requirements for endosulfan did not completely meet the criteria contained in Series 875, Occupational and Residential Test Guidelines. Despite the uncertainties associated with the study ( see Third Revision of " Occupational and Residential Exposure Assessment and Recommendations for the Reregistration Eligibility Decision Document for Endosulfan." Renee Sandvig. February 26, 2002), the Agency used the data from the DFR study in assessing the appropriate postapplication exposure from agricultural activities using endosulfan ( fruit trees and low growing fruit crops).

A second DFR study ( MRID# 403039 01) was conducted for endosulfan. This study examined DFR residues on apples, apricots, processing tomatoes, and cherry tomatoes. However, this study was unacceptable and was not used in estimating the postapplication exposures. All postapplication exposure estimates were based on MRID# 444031 02. It should be noted that the half lives from the unacceptable study were similar to or higher than the half lives from the study used to determine postapplication exposure in this assessment. This indicates that the DFR data from the unacceptable study would result in restricted entry interval calculations similar to or even longer than the ones calculated in this assessment.

Short and Intermediate term Postapplication Exposures and Risks Short and intermediate term postapplication exposure is expected because endosulfan is registered for over 50 crops and postapplication workers may move from treated field to treated field. This is especially possible when application is repeated every seven days for two to three applications, as is allowable on current labels. A dose and an MOE are determined from the declining predicted DFR values until the LOC or target MOE of 100 is reached for every crop for both the EC and WP formulations. The NOAEL used in the short and intermediate term dermal assessment is 12.0 mg/ kg/ day. For short and intermediate term exposure to the EC formulation, the day after treatment when the calculated MOE equals or exceeds the LOC or target MOE of 100 ranges from 0 days ( day of application) for pruning pecan trees to 17 days for detasseling corn at an application rate of 1.5 lbs ai/ acre. For short and intermediate term exposures to the WP formulation, the day after treatment when the calculated MOE equals or exceeds the target MOE of 100 ranges from 0 days for pruning pecan trees to 30 days for girdling grapes at an application rate of 1.5 lbs ai/ acre. Occupational postapplication risks from dermal exposure are of concern. See Table 9b for a summary. 60 7.3 Incident Data The Agency has reviewed the Incident Data System ( IDS), the Poison Control Center, the California Department of Food and Agriculture ( Department of Pesticide Regulation), and the National Pesticide Telecommunications Network ( NPTN) databases for reported incident information for endosulfan ( Review of Endosulfan Incident Reports. Jerome Blondell & Monica Spann. January 18, 2000). A number of accidental human poisonings from exposure to endosulfan in both occupational and residential settings have been reported. The data from these sources often lacked specific information on the extent of exposure and the circumstances of exposure. Collectively, however, the incidence information indicate definite poisoning risks from misuse of products that contain endosulfan, or from not wearing personal protective equipment.

Several incidents of acute accidental human exposure to endosulfan have been reported. The clinical signs and symptoms observed in humans following acute accidental exposure to endosulfan are similar to those observed in acute toxicity studies in animals. In humans, acute toxicity caused by endosulfan is characterized by nervousness, agitation, tremors, convulsions, and death. In one incident, a 70 year old woman died about three hours after she swallowed " drops" of an endosulfan formulation. Prior to death the woman experienced vomiting, diarrhea, agitation, tonoclonic convulsions, dyspnea, cyanosis, and loss of consciousness. In another incident, nine workers experienced at least one convulsion after bagging a 50% wettable powder formulation of endosulfan. Five of the men were said to be wearing a respirator and protective clothing at the time of exposure. Prodromal symptoms included malaise, vomiting, dizziness and confusion. California data show a consistent risk of skin illness among field workers who come into substantial contact with foliage.

Brandt et al. ( 2001) reported on a forty three year old farmer in Kentucky that mixed and sprayed endosulfan on tobacco for five hours and had repeated hand, and possibly oral, contact. The farmer, who did not wear gloves or a respirator, mixed about five or six quarts of endosulfan concentrate with three hundred gallons of pond water without washing or wiping off his hands. The tank mix was blown into his face by the wind while he was pulling a boom sprayer behind an unenclosed tractor. The farmer's clothes were soaked with spray and he did not shower or change his clothes immediately after being exposed to the product. While driving the tractor from the tobacco field, the farmer slumped forward and displayed jerking motions. The tractor then overturned and pinned his legs underneath. About twenty minutes later, medical personnel arrived to transport him to the hospital. The farmer reported repeated convulsions for five or six hours, hypoxia, acidosis, and status epilepticus. A lumbar puncture revealed bloody cerebrospinal fluid. The man was transferred to a tertiary medical center three days after exposure. About three days after being exposed to the product, blood samples were taken and were analyzed two weeks later. Endosulfan was not detected in a residual aliquot. There was a concern about the validity of the negative endosulfan test because the handling and storage of the residual aliquot could not be verified with the external laboratory that was responsible for the test. About four weeks after exposure, a fat biopsy was performed that did not detect endosulfan. Five years after exposure, the farmer was profoundly impaired neurologically and under full custodial care. 61 Available incidence data clearly show that flagrant misuse of concentrated formulations of endosulfan could result in exposures that cause serious, life threatening poisoning, or permanent neurological toxicity. Both handler and postapplication workers have experienced moderate systemic poisoning as a result of exposure to endosulfan. In addition, the California data in particular show that there appears to be a consistent risk of skin rash or irritation among field workers who have substantial contact with treated foliage. There are also reports of poisoning from endosulfan exposure occurring in other countries. Though many of these cases involve misuse of endosulfan, they should not be characterized as just " anecdotal," as the ETF suggests ( February 28, 2002). These cases are investigated and documented by scientists in peer reviewed literature. The Agency often uses cases in other countries to establish what health effects may occur among those over exposed and these cases can be valuable in determining precautionary labeling. Endosulfan does not appear to pose risks of concern from spray drift exposure. Results from the incidence data indicate that all skin surfaces should be protected when workers are handling endosulfan formulations, particularly concentrated formulations. Special effort is warranted to keep concentrated endosulfan away from the lay public who may misuse it in a manner leading to life threatening or fatal poisoning. Restricted entry intervals sufficient to minimize substantial contact with treated foliage are warranted.

8.0 DATA NEEDS/ LABEL REQUIREMENTS Additional data needs/ requirements have been identified in the referenced discipline chapters and are summarized here.

8.1 Toxicology Two additional toxicity studies are warranted as a result of the uncertainties regarding increased sensitivity of infants and children to endosulfan following prenatal or postnatal exposure. These toxicity studies are:

1) a subchronic neurotoxicity study ( 870.6200) and;

2) a developmental neurotoxicity ( 870.6300) assay.

Note: Protocols for these studies have been received.

8.2 Product Chemistry Product chemistry data requirements that remain outstanding for the 7 registered technicals include specific details pertaining to the process used to manufacture endosulfan: a statement as to whether the process is batch or continuous; the duration of each step of the process; the relative amounts of the materials used; a description of the manufacturing equipment; a more complete description of the reaction conditions controlled during each step of the process; a description of the sampling regimen and quality control procedures necessary to assure product consistency; an updated confidential statement of formula ( CSF) including 62 nominal concentrations for the active ingredient and impurities present in concentrations greater than 0.1%.

8.3 Residue Chemistry The existing residue chemistry database is incomplete. Label revisions are required for many crops in order to reflect the parameters of use patterns for which residue data are available. Most of the required label revisions pertain to the establishment of preharvest intervals and livestock feeding and/ or grazing restrictions.

The reregistration requirements for magnitude of the residue in/ on the following RACs have not been fulfilled, and field trial data are required: barley hay, and pearled barley; oat forage, hay, and rolled oats; rye forage; wheat forage, and hay.

The reregistration requirements for magnitude of the residue in/ on tobacco have not been fulfilled and field trial data and a pyrolysis study are required.

The need for additional tolerances and for revisions to dietary exposure/ risk assessments will be determined upon receipt of the required residue chemistry data.

8.4 Occupational Exposure Data gaps exist for the following scenarios:

C Applying dip treatments to trees and roots or whole plants.

° No exposure data exist for mixing/ loading/ applying wettable powders with a high pressure handwand and a backpack sprayer. These two scenarios are expected to have risks of concern since similar scenarios assessed in this document, mixing/ loading wettable powders and mixing/ loading/ applying liquids with a high pressure handwand, have risks of concern.

If the registrant is interested in refining the Agency's calculated REIs, additional DFR data and/ or worker exposure monitoring data may be submitted.

9.0 ATTACHMENTS Assessment of the Dietary Cancer Risk of Hexachlorobenzene and Pentachlorobenzene as impurities in Chlorothalonil, PCNB, Picloram, and several other pesticides. William Smith. February 26, 1998. 63 Endosulfan: Evaluation of Registrant Submission, Endosulfan: Evaluation of Possible Endocrine Effects in Mammalian Species. Elizabeth Mendez, December 11, 2000.

Endosulfan. New FQPA and PDP Data, Anticipated Residues, and Revised Acute and Chronic Dietary Exposure Analyses. Sherrie Kinard. April 22, 2002.

ENDOSULFAN ( PC Code: 079401). Toxicology Disciplinary Chapter for the Reregistration Eligibility Document. Robert F. Fricke. May 9, 2002.

Endosulfan, Product Chemistry Chapter for Reregistration Eligibility Decision. Ken Dockter. December 18, 1998.

Endosulfan: Re evaluation of Toxicology Endpoint Selection for Dermal and Inhalation Risk Assessments and 3X Safety Factor for Bioaccumulation  Report of the Hazard Identification Assessment Review Committee. Robert Fricke. February 28, 2002.

Endosulfan Report of the FQPA Safety Factor Committee. Carol Christensen. February 14, 2002.

ENDOSULFAN  Supporting documentation for findings of FQPA Safety Committee on February 11, 2002. Elizabeth Méndez. May 9, 2002.

Quantitative Usage Analysis for Endosulfan. Steven Nako. October 13, 1999.

Quantitative Usage Analysis for Endosulfan, Updated. David Donaldson. September 10, 2000.

Review of Endosulfan Incident Reports. Jerome Blondell and Monica Spann. January 18, 2000.

Revised Residue Chemistry Chapter for the Endosulfan Reregistration Eligibility Decision ( RED) Document. John Punzi. February 14, 2002.

Third Revision of Occupational and Residential Exposure Assessment and Recommendations for the Reregistration Eligibility Decision Document for Endosulfan. Renee Sandvig. February 26, 2002. 64 Table 8. Use Pattern Summary for Endosulfan.

Formulation types (% ai) Equipment used Use sites Application Rates Range Timing and Frequency of Application Technical grade manufacturing product ( 95%

active ingredient [ ai]),

emulsifiable concentrate ( 9 to 34% ai), and a wettable powder ( 1 to 50% ai). Commercial use:

groundboom sprayer,

fixedwing aircraft, chemigation ( potatoes only), airblast sprayer, rights of way sprayer, low pressure handwand, high pressure handwand, backpack sprayer, & dip treatment. Alfalfa ( seed only), barley,

beans ( dry and succulent),

blueberries, broccoli, brussel sprouts, cabbage, carrots,

cauliflower, celery, clover ( seed only), collards, cotton,

corn ( fresh only),

cucumbers, eggplants,

grapes, kale, kohlrabi ( seed only), lettuce, melons,

mustard greens, oats, peas,

peppers, pineapples,

pistachio nuts, potatoes,

pumpkins, radish ( seed only), rutabaga ( seed only),

rye, spinach, squash, sweet potatoes, strawberries,

tobacco, tomato, turnip,

wheat, apples, apricots,

almonds, cherries, filberts,

macadamia nuts, nectarines,

pecans, peach, pear, plums,

prunes, walnuts, shade trees,

citrus ( non bearing &

nursery stock), shrubs,

nursery stock, Christmas tree plantations, & root dip ( cherry, peaches, & plum roots & crowns, whole strawberry plants). Application rates range from 0.5 lbs ai/ acre for clover to 3 lbs ai/ acre for apricots. Endosulfan can be applied at any time of the growing season. It may be applied from 1 to 6 times a year,

with an average of 2 times per year. 65 Table 9a. Summary of Occupational Handler Risks Exposure Scenario ( Scenario #) Crop Type/ Usea Range of Application Rates ( lb ai/ A) b Amount Handled per Dayc Baselinef Minimum PPEg Maximum PPEh Engineering Controlsi Dermal MOEd Inhalation MOEe Dermal MOEd Inhalation MOEe Dermal MOEd Inhalation MOEe Dermal MOEd Inhalation MOEe Mixer/ Loader Exposures Mixing/ Loading Liquid Formulations for Aerial Application ( 1a) clover 0.5 lb ai/ A 350 Acres 2 67 210 330

pineapple 2.0 lb ai/ A 0.41 17 52 83 71 170 140

pecans 3.0 lb ai/ A 0.28 11 35 56 47 110 93

small grains 0.75 lb ai/ A 1200 Acres 0.32 13 41 65 55 130 110

cotton 1.5 lb ai/ A 0.16 7 20 32 27 65 54 94 Mixing/ Loading Liquid Formulation for Chemigation ( 1b) potatoes ( Idaho) 1.0 lb ai/ A 350 Acres 0.83 33 100 170

Mixing/ Loading Liquid Formulations for Groundboom Application ( 1c) clover 0.5 lb ai/ A 80 Acres 7 290 910

pineapple 2.0 lb ai/ A 2 73 230 360

small grains 0.75 lb ai/ A 200 Acres 2 78 240 390

cotton 1.5 lb ai/ A 1 39 120 190

Mixing/ Loading Liquid Formulations for Airblast Application ( 1d) Ornamental Trees/ Shrubs 1.0 lb ai/ A 10 Acres 29 1,200 3,700

Hazelnuts 2.0 lbs ai/ A 40 Acres 4 150 460

pecans 3.0 lb ai/ A 2 97 300 490

Mixing/ Loading Liquids for Rights of way Spray Application ( 1e) grapes 0.005 lb ai/ gal 1000 Gallons 58 2,300 7,300

cherry 0.04 lb ai/ gal 7 290 910

Mixing/ Loading Liquids for Plant and Root Dip ( 1f) cherry, peach and plums 0.05 lbs ai/ gal 100 Gallons 58 2,300 7,300      Table 9a. Summary of Occupational Handler Risks ( continued)

Exposure Scenario ( Scenario #) Crop Type/ Usea Range of Application Rates ( lb ai/ A) b Amount Handled per Dayc Baselinef Minimum PPEg Maximum PPEh Engineering Controlsi Dermal MOEd Inhalation MOEe Dermal MOEd Inhalation MOEe Dermal MOEd Inhalation MOEe Dermal MOEd Inhalation MOEe 66 Mixing/ Loading Wettable Powders for Aerial Application ( 2a) beans 1.0 lb ai/ A 350 Acres 0.65 0.93 14 5 18 10 240 170 sweet potato 2.0 lb ai/ A 0.32 0.47 7 2 9 5 120 83 peach 3.0 lb ai/ A 0.22 0.31 5 2 6 3 82 56 small grains 0.75 lb ai/ A 1200 Acres 0.25 0.36 6 2 7 4 95 65 cotton 1.5 lb ai/ A 0.13 0.18 3 1 4 2 48 32 Mixing/ Loading Wettable Powders for Groundboom Application ( 2b) beans 1.0 lb ai/ A 80 Acres 3 4 62 20 81 41 1,100 730 sweet potato 2.0 lb ai/ A 1.4 2 31 10 40 20 540 360 small grains 0.75 lb ai/ A 200 Acres 1.5 2 33 11 43 22 570 390 cotton 1.5 lb ai/ A 0.76 1 16 5 22 11 290 190 Mixing/ Loading Wettable Powders for Airblast Application ( 2c) Ornamental Trees/ Shrubs 1.0 lb ai/ A 10 Acres 23 33 490 160

hazelnuts 2.0 lb ai/ A 40 Acres 3 4 62 20 81 41 1,100 730 peaches 3.0 lb ai/ A 2 3 41 14 54 27 710 490 Mixing/ Loading Wettable Powders for Rights of way Spray Treatment ( 2d) grapes 0.005 lb ai/ gal 1000 Gallons 45 65 990 330

walnut 0.02 lb ai/ gal 11 16 250 81  160

Mixing/ Loading Wettable Powders for Plants and Root Dip ( 2e) cherry, peach,

and plum 0.05 lb ai/ gal 100 Gallons 45 65 990 330

Applicator Exposures Applying Spray with Aerial Equipment ( 3) clover 0.5 lb ai/ A 350 Acres See Eng. Controls See Eng. Controls See Eng.

Controls See Eng.

Controls See Eng.

Controls See Eng.

Controls 960 1,200 pineapple 2.0 lb ai/ A 240 290 pecans 3.0 lb ai/ A 160 200 small grains 0.75 lb ai/ A 1200 Acres 190 230 cotton 1.5 lb ai/ A 93 110 Table 9a. Summary of Occupational Handler Risks. ( Continued)

Exposure Scenario ( Scenario #) Crop Type/ Usea Range of Application Rates ( lb ai/ A) b Amount Handled per Dayc Baselinef Minimum PPEg Maximum PPEh Engineering Controlsi Dermal MOEd Inhalation MOEe Dermal MOEd Inhalation MOEe Dermal MOEd Inhalation MOEe Dermal MOEd Inhalation MOEe 67 Applying Sprays with a Groundboom Sprayer ( 4) clover 0.5 lb ai/ A 80 Acres 1,500 470

pineapple 2.0 lb ai/ A 380 120

small grains 0.75 lb ai/ A 200 Acres 400 130

cotton 1.5 lb ai/ A 200 63  310

Applying Sprays with an Airblast Sprayer ( 5) ornamental trees1.0 lb ai/ A 10 Acres 230 310

hazelnuts 2.0 lb ai/ A 40 Acres 29 39 48 190 48  550

pecans 3.0 lb ai/ A 19 26 32 130 32  370

Applying Sprays with a Rights of way Sprayer ( 6) grapes 0.005 lb ai/ gal 1000 Gallons 130 720     NF NF cherries 0.04 lb ai/ gal 16 90 54 450 72  NF NF Applying Dip Treatment to Roots, or Whole Plants ( 7) cherry, peach,

plum roots 0.05 lb ai/ gal 100 gallons No Data No Data ND ND ND ND ND ND Mixer/ Loader/ Applicator Exposure Mixing/ Loading/ Applying Liquid Formulations with a Low Pressure Handwand ( 8) tobacco ( drench) 0.005 lb ai/ gal 40 Gallons 42 2,300 9,800    NF NF tomato ( greenhouse) 0.01 lb ai/ gal 21 1,200 4900    NF NF cherries 0.04 lb ai/ A 5 290 1,200    NF NF Mixing/ Loading/ Applying Wettable Powders with a Low Pressure Handwand ( 9) tomato/ tobacco 0.005 lb ai/ gal 40 Gallons 140 64  320   NF NF walnut 0.02 lb ai/ gal 36 16 120 80  160 NF NF Mixing/ Loading/ Applying Liquid with a High Pressure Handwand ( 10) tobacco ( drench) 0.005 lb ai/ gal 1000 Gallons 48 23 67 120 110  NF NF tomato ( greenhouse) 0.01 lb ai/ gal 24 12 34 58 53 120 NF NF cherries 0.04 lb ai/ gal 6 3 9 15 13 29 NF NF Mixing/ Loading/ Applying Liquid with Backpack Sprayer ( 11) tobacco ( drench) 0.025 lb ai/ gal 40 Gallons 1,700 2,300     NF NF Exposure Scenario ( Scenario #) Crop Type/ Usea Range of Application Rates ( lb ai/ A) b Amount Handled per Dayc Baselinef Minimum PPEg Maximum PPEh Engineering Controlsi Dermal MOEd Inhalation MOEe Dermal MOEd Inhalation MOEe Dermal MOEd Inhalation MOEe Dermal MOEd Inhalation MOEe 68 tomato ( greenhouse) 0.01 lb ai/ gal 840 1,200     NF NF cherries 0.04 lb ai/ gal 210 290     NF NF Flagger Exposures Flagging Aerial Spray Applications ( 12) clover 0.5 lb ai/ A 350 Acres 440 230

pineapple 2.0 lb ai/ A 110 57  290

pecans 3.0 lb ai/ A 73 38 67 190 80  3,600

Footnotes:

a Crops named are index crops which are chosen to represent all other crops at or near that application rate for that use. See the application rates listing in the use summary section of this document for further information on application rates used in this assessment.

b Application Rates are based on the maximum application rates listed on the endosulfan labels.

c Daily amount treated are based on Science Advisory Council for Exposure Policy # 9.1.

d Short term Dermal MOE = Short term NOAEL ( mg/ kg/ day)/ Daily Dermal Dose ( mg/ kg/ day).

e Short term MOE = Short term NOAEL ( mg/ kg/ day)/ Daily Inhalation Dose ( mg/ kg/ day).

f Baseline clothing: long pants, long sleeved shirt, shoes, socks. Chemical resistant gloves are included for mixing/ loading/ applying liquids with a backpack sprayer and wettable powders with a low pressure handwand ( scenarios 9 and 11).

g Minimum PPE clothing: Baseline clothing plus dust/ mist respirator, and chemical resistant gloves.

h Maximum PPE clothing: Baseline clothing plus organic vapor respirator, double layer of clothes, and chemical resistant gloves.

i Engineering controls: Enclosed mixing/ loading, closed cab, truck or cockpit. Baseline level clothing. Chemical resistant gloves for airblast sprayer application and mixing/ loading liquid formulation ( scenarios 1 and 5).

 Scenario's calculated MOE exceeds the target MOE at the previous level of mitigation. ( MOE > 100)

NF = Not feasible for this scenario ( no available engineering controls). ND = No data.

Bolded MOE values show a risk of concern at the highest possible level of mitigation for the corresponding scenario. 69 Table 9b. Summary of Short and Intermediate term Postapplication Exposures and Risks Cropa Maximum Label Application Rate ( lbs ai/ acre) d Transfer Coefficiente ( cm2/ hr) Activityf Day after Application When MOE $ 100g WPb ECc WPb ECc Table Grapes / Raisins 1.5 1.5 10,000 Cane turning and tying, and girdling 30 6 Juice Grapes 1.5 1.5 5,000 Tying, training, hand harvesting, hand pruning,

and thinning. 20 0 Grapes, Table and Juice 1.5 1.5 1,000 Scouting and irrigating 0 0 Apple, Apricot, Cherry, Nectarines, Peach, Pear, Plum,

Prune, Christmas Trees, Ornamental Trees / Shrubs including Evergreen Trees and Non bearing Citrus Trees. 3 3 3,000 Thinning, staking, topping, training, hand harvest,

hand pruning and seed cone harvesting 5 0 Apple, Apricot, Cherry, Nectarines, Peach, Pear, Plum,

Prune, Ornamental Trees / Shrubs including Evergreen Trees, Non bearing Citrus Trees. and Christmas Trees. 3 3 1,000 Scouting and irrigating 0 0 Macadamia nuts, Pistachio Nuts, Pecans Hazelnut, Almonds and Walnut 2 3 2,500 Hand harvesting, pruning, and thinning 0 0 500 Scouting and irrigating 0 0 Blueberries, Kohlrabi, Broccoli, and Cabbage. 2 2 5,000 Hand harvesting, pruning, thinning, and irrigating. 14 9 Kohlrabi, Broccoli, and Cabbage. 2 2 4,000 Scouting and irrigating 12 7 Blueberries 2 2 1,000 Scouting and irrigating 3 0 Brussel Sprouts and Cauliflower 1 1 5,000 Topping, irrigating, hand harvesting, and tying. 9 4 4,000 Scouting and irrigating 7 2 Corn 1.5 1.5 17,000 Detassling 21 17 1,000 Scouting and irrigating 1 0 Cucumber, Melons, Pumpkin, Squash, Beans, Peas, Celery,

Lettuce, Spinach, and Carrots. 1 1 2,500 Hand harvesting, pruning, thinning, turning, and leaf pulling 4 0 Alfalfa, Barley , Clover, Oats, Rye, Wheat, White Potatoes,

Cucumber, Melon, Pumpkin, Squash, Bean, Peas, Celery,

Lettuce, and Spinach. 1 1 1,500 Scouting and irrigating 0 0 Carrots 1 1 300 Scouting and irrigating 0 0 Pepper, Eggplant, and Tomato 1 1 1,000 Hand harvesting, staking, tying, pruning, thinning,

and training. 0 0 700 Scouting and irrigating 0 0 Pineapple 2 2 1000 Hand harvesting 3 0 Cropa Maximum Label Application Rate ( lbs ai/ acre) d Transfer Coefficiente ( cm2/ hr) Activityf Day after Application When MOE $ 100g WPb ECc WPb ECc 70 500 Scouting and irrigating 0 0 Strawberry 2 2 1,500 Hand harvesting, pinching, pruning, and training. 5 0 400 Scouting and irrigating 0 0 Cotton, Collard Greens, Kale, Mustard Greens, Sweet Potato, Radish, Rutabaga, and Turnip. 2 2 2500 Hand harvesting, pruning, and thinning. 9 3 Cotton, Collard Greens, Kale, Mustard Greens and Sweet Potato. 2 2 1,500 Scouting and irrigating 5 0 Radish, Rutabaga, and Turnip. 2 2 300 Scouting and irrigating 0 0 Tobacco 1.5 1 2,000 Hand harvesting, pruning, striping, thinning,

topping, and hand weeding 5 0 1,300 Scouting and irrigating 2 0 Footnotes:

Day 0 = day of application after sprays have dried ( 12 hours).

a Crops were grouped according to similar application rates, transfer coefficients, and surrogate DFR data sources.

b WP = wettable powder formulation c EC = emulsifiable concentrate formulation d maximum application rates as stated on current endosulfan labels.

e Transfer Coefficients from Science Advisory Council on Exposure Policy 3.1 f Activities are from Science Advisory Council on Exposure Policy 3.1. Each activity many not occur for every crop listed in group.

g Day after application when the calculated MOE is greater than the target MOE of 100.