Guideline No. Study Type MRID #( s) Results Category 870.1100 Acute Oral 41925601 LD50 ( M& F) = 2800 mg/ kg III 870.1200 Acute Dermal 41892701 LD50 > 2000 mg/ kg III 870.1300 Acute Inhalation 41892702 LC50 ( 4 hr): combined = 4.9 mg/ L; M = 5.8 mg/ L & F = 4.0 mg/ L IV 870.2400 Primary Eye Irritation 41892703 Primary eye irritant  conjunctival redness in 1 hr. In al animals; persisted for 24 hrs. In 1/ 6 animals. III 870.2500 Primary Skin Irritation 41892704 Negligible irritation in 0.5 hr. Cleared 24  48 hrs. IV 870.2600 Dermal Sensitization 41892705 Not a sensitizer N/ A 4.3.3 FQPA Hazard Considerations Acceptable developmental studies in rats and rabbits along with a two generation reproductive toxicity study are available for DMA. Developmental toxicity was noted only at doses resulting in maternal toxicity; NOAELs were established for maternal and developmental toxicity. As such, results of developmental and reproductive toxicities studies provided no indication of increased susceptibility of rat or rabbit. Changes in organ weights for reproductive organs ( e. g., ovarian weight changes without pathological changes in the reproductive toxicity study) and testicular pathology ( dermal study only) were noted only at very high doses and were not replicated in other studies. The toxicology database is considered complete for the evaluation of sensitivity of the developing young. As the developing nervous system does not appear to be a target organ for DMA, a developmental neurotoxicity study is not required. Regarding potential Page 53 of 125 thyroid toxicity, a comparative thyroid study in adult and juvenile animals is not expected to provide endpoints more sensitive than the bladder mode of action studies currently available. The bladder is a sensitive target organ and special mode of action studies provide health protective endpoints for DMA toxicity at low doses. Thus, a comparative thyroid study in juvenile and adult animals is not required. Based on the overall weight of the evidence, the FQPA safety factor is not needed.

4.3.4 Dose Response, Hazard Identification and Toxicity Endpoint Selection Toxicological endpoints are needed to assess potential risk to DMA from the following durations and routes of exposure:

  Acute and chronic dietary exposure,   Acute , short and intermediate term incidental oral exposure,   Short and intermediate term dermal exposure, and   Short and intermediate term inhalation exposure.

As mentioned above, the mode of action for the development of bladder tumors in rats has been elucidated. As described in USEPA ( 2006), this mode of action is expected to be relevant to humans. The key steps involved include conversion of DMAV to DMAIII resulting in urothelial cytotoxicity and the ensuing regenerative proliferation to replace the dead cells. The amount of proliferation is expected to be a function of the amount of cell killing since the tissue will undergo regenerative proliferation in response to cell killing. As the severity of cytotoxicity increases with increasing levels of DMAV ( DMAIII), regenerative proliferating is the rate limiting step for tumor formation. Thus, a tumor dose response curve would be influenced by the induced cell proliferation curve. Cell proliferation is not likely to occur after a single, acute exposure but has been shown after one week of exposure. As such, special mode of action data  specifically regenerative cell proliferation provide an appropriate endpoint for oral exposure ranging in duration from short term to chronic.

As described in detail in EPA's science issue paper, the Agency performed a benchmark dose ( BMD) analysis of available data for key events leading to the development of bladder tumors in rats. Overall, this analysis was supported by the SAB. The SAB did not, however, support the use of a 1% benchmark response ( BMR) but instead suggested a 10% BMR was more scientifically supported due to uncertainties associated with extrapolating below the observed data. Thus, the Agency has developed its BMD estimates for regenerative proliferation based on a 10% BMR. BrdU labeling data measured at 10 weeks of DMA exposure in the feed to female rats ( Arnold et al, 1999) was used for the BMD analysis. Using the Hill model from EPA's Benchmark Dose Software ( BMDS), the results indicate that the BMD10 and BMDL10 ( i. e. the lower 95% confidence limit on the BMD10) are 0.92 mg/ kg/ day and 0.43 mg/ kg/ day, respectively. Consistent with the Agency's draft BMD guidance and the cancer guidelines ( USEPA, 2000 & 2005c), the point of departure should be based on a BMDL. Therefore, the point of departure for the short and intermediate term incidental oral and the chronic dietary risk assessments is based on a BMDL10 of 0.43 mg/ kg/ day. Page 54 of 125 The Agency historically applies 10x uncertainty/ extrapolation factors, for both inter and intraspecies variation ( 10X for intra species; 10X for inter species). In the case of DMA, for oral exposures ranging from short term to chronic in duration, the current database supports reduction of the default 10X for inter species ( animal to human) extrapolation to 3X. The rationale for this is as follows: The key events of the rat bladder tumor mode of action are expected to be operational in humans. Based on the results of in vitro studies, it is further expected that at a similar dose at the target site ( i. e. bladder urothelial), that humans and rats are expected to respond pharmacodynamically similar. Based on the pharmacodynamic characteristics, the default 10X can be reduced to 3X for DMA. In the draft report ( December 27, 2005) of the SAB, the panel provides support for reducing the default 10X interspecies factor to " some number less than 10" and that the " EPA could assemble a case for toxicodynamic equivalency between the test species, rats, and humans from existing experimental data."

There are known pharmacokinetic differences between rats and humans. These pharmacokinetic differences include: sequestration of DMAIII by rat hemoglobin, long retention time in the rat compared to humans or mice, and the increased urinary output of TMAO in rats compared to humans. Because of uncertainties regarding quantifying the tissue dose in humans using rat data, and in the absence of a fully developed PBPK model, an inter species extrapolation factor of 3x will be applied. The noted pharmacokinetic differences between rats and humans suggest that in the rat that the target tissue is likely exposed to DMAIII for a longer duration compared to the human. There are, however, uncertainties regarding the quantitative differences between rat and human which prevents further reduction of the inter species factor. Thus, for short and intermediate term incidental oral and chronic dietary risk assessment of DMA, a 30X uncertainty/ extrapolation factor ( 10X for intra species; 3X for inter species) has been applied in this risk assessment.

Regarding acute dietary and incidental oral exposure, regenerative proliferation is not expected to occur after a single exposure. Effects noted in the developmental toxicity studies in rat and rabbit provide an appropriate endpoint for acute dietary risk assessment. In both the rat and rabbit developmental toxicity studies, the maternal and developmental NOAELs are 12 mg/ kg/ day. The LOAELs are 36 and 48 mg/ kg/ day, respectively, for rat and rabbit. As the effects noted in the developmental studies are not related to the mode of action for bladder tumors, the default uncertainty factor for inter species variability can not be reduced. A 100X uncertainty/ extrapolation factor ( 10X for intra species; 10X for inter species) has been applied to the acute dietary and incidental oral risk assessment.

Pharmacokinetics of absorption and metabolism can differ among oral, dermal, and inhalation exposures. Because of this, it is preferred to use route specific studies for risk assessment purposes. Regarding dermal exposure, the DMA dermal toxicity study in rat indicates a NOAEL of 300 mg/ kg/ day based on effects noted at 1000 mg/ kg/ day. Regarding inhalation exposures, the rat inhalation study with DMA has been selected. In the 90 day inhalation toxicity study with DMA, port of entry effects, not systemic ones, are the most sensitive. A 100X uncertainty/ extrapolation factor ( 10X for intra species; 10X for inter species) was applied to dermal and inhalation risk assessments. Page 55 of 125 <IP_ADDRESS> Acute Reference Dose ( aRfD)  General Population & Acute Incidental Oral Exposure There are two co critical studies ( rat and rabbit developmental toxicity) which provide the basis for the point of departure for acute dietary risk assessment.

a. In a developmental toxicity study ( MRID# 40625701), cacodylic acid ( 99.8%) was administered in distilled water by gavage to groups of pregnant Charles River Sprague Dawley rats ( 22/ dose) at dose levels of 0, 4, 12, and 36 mg/ kg/ day during gestation days 6 through 15. The maternal toxicity NOAEL is 12 mg/ kg/ day; the maternal toxicity LOAEL = 36 mg/ kg/ day, based on decreased body weights, body weight gains, food consumption and gravid uterine weights. The developmental toxicity NOAEL is 12 mg/ kg/ day; developmental toxicity LOAEL is 36 mg/ kg/ day, based on decreased fetal weights, shorter crown rump length, the suggestion of diaphragmatic hernia, and delayed/ lack of ossification of numerous bones.

b. In a developmental toxicity study ( MRID# 40663301), cacodylic acid ( 99.8%, a. i.) was administered in water by oral gavage to groups of pregnant New Zealand White rabbits ( 15/ dose) at dose levels of 0, 3, 12 or 48 mg/ kg/ day on gestation days 7 through 19. The maternal toxicity NOAEL is 12 mg/ kg/ day; the maternal toxicity LOAEL is 48 mg/ kg/ day, based on increased mortality, abortions, body weight loss, and reduced food consumption. The developmental toxicity NOAEL is 12 mg/ kg/ day and a developmental toxicity LOAEL was not established since no pregnant rabbit survived to the gestation day 29 scheduled sacrifice.

<IP_ADDRESS> Chronic Reference Dose ( cRfD) & Incidental Oral Exposure The Agency performed a BMD analysis for regenerative proliferation based on a 10% BMR ( USEPA 2006). BrdU labeling data measured at 10 weeks of DMA exposure in the feed to female rats ( Arnold et al, 1999) was used for the BMD analysis. Using the Hill model from EPA's Benchmark Dose Software ( BMDS), the results indicate that the BMD10 and BMDL10 ( ie, the lower 95% confidence limit on the BMD10) are 0.92 mg/ kg/ day and 0.43 mg/ kg/ day, respectively. Therefore, the point of departure for the short and intermediate term incidental oral, and the chronic dietary risk assessments is based on a BMDL10 of 0.43 mg/ kg/ day.

<IP_ADDRESS> Dermal Exposure ( Short and Intermediate Term)

In a 21 day dermal toxicity study ( MRID# 41872801; HED Doc. No. 010410) cacodylic acid ( 99.95%, a. i.) was applied dermally under occlusive bandage to 5 New Zealand White rabbits/ sex/ group at doses of 0, 100, 300 or 1000 mg/ kg once daily, five days a week for 3 weeks. The systemic toxicity NOAEL = 300 mg/ kg/ day; the LOAEL = 1000 mg/ kg/ day, based on body weight changes in females, and reduced testicular weights and associated histopathological changes in males. Page 56 of 125 <IP_ADDRESS> Inhalation Exposure ( Short and Intermediate Term)

In a 90 day toxicity study ( MRID# 44700301), DMA [( Cacodylate 3.25) ( active ingredients: cacodylic acid ( 4.9%) and sodium cacodylate ( 28.4%); batch 095/ 93)] was administered by inhalation to 10 rats/ sex/ dose at aerosol concentrations of 10, 34 and 100 mg/ m3 ( analytical concentrations 0.01, 0.034, or 0.1 mg/ L). The inhalation NOAEL is 0.010 mg/ L/ day; the inhalation LOAEL is 0.034 mg/ L/ day in both male and female rats based on the presence of moderate and marked intracytoplasmic eosinophilic granules ( IEG) in the cells of the nasal turbinates.

Table 4.3.4: Summary of Toxicological Doses and Endpoints for Chemical for Use in Human Risk Assessments of DMA Exposure Scenario Dose Used in Risk Assessment FQPA SF* and Level of Concern for Risk Assessment Study and Toxicological Effects Acute Dietary ( females 13 49 and general population) NOAEL = 12 mg/ kg/ day Acute RfD = 0.12 mg/ kg/ day Developmental Toxicity  Rat ( 40625701); LOAEL = 36 mg/ kg/ day based on decreased fetal weights, shorter crown rump length, the suggestion of diaphragmatic hernia and delayed/ lack of ossification of numerous bones. Developmental Toxicity  Rabbit ( 40663301); LOAEL = 48 mg/ kg/ day based on mortality, abortions, body weight loss and reduced food consumption.

Chronic Dietary ( all populations) BMDL10 = 0.43 mg/ kg/ day Chronic RfD = 0.014 mg/ kg/ day BMD10 of 0.92 mg/ kg/ day for BrdU labeling from Arnold et al ( 1999)

Incidental Oral Acute Term ( 1 day) NOAEL = 12 mg/ kg/ day LOC = 100 Developmental Toxicity  Rat ( 40625701); LOAEL = 36 mg/ kg/ day based on decreased fetal weights, shorter crown rump length, the suggestion of diaphragmatic hernia and delayed/ lack of ossification of numerous bones. Developmental Toxicity  Rabbit ( 40663301); LOAEL = 48 mg/ kg/ day based on mortality, abortions, body weight loss and reduced food consumption.

Incidental Oral Short Term ( 1  30 days)

Intermediate Term ( 1  6 months) BMDL10 = 0.43 mg/ kg/ day LOC = 30 BMD10 of 0.92 mg/ kg/ day for BrdU labeling from Arnold et al ( 1999)

Dermal Short Term ( 1  30 days)

Intermediate Term ( 1  6 months) Dermal NOAEL= 300 mg/ kg/ day LOC = 100 21 Day Dermal  Rabbit ( 41872801); LOAEL = 1000 mg/ kg/ day based on decreased body weight gain in females, and decreased testicular weights, hypospermia, and tubular hypoplasia in males.

Dermal Long Term (> 6 months) Not required Inhalation Short Term ( 1  30 days)

Intermediate Term ( 1  6 months) Inhalation NOAEL= 0.01 mg/ L ( 4.38 mg/ kg/ day) LOC = 100 90 Day Inhalation  Rat ( 44700301); LOAEL = 0.034 mg/ kg/ L ( 14.95 mg/ kg/ day) based on presence of moderate and marked intracytoplasmic eosinophilic granules ( IEG) in the nasal turbinate cells of male and female rats.

Inhalation Long Term (> 6 months) Not required Cancer ( oral) Not carcinogenic at doses that do not result in enhanced cell proliferation UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose ( a = acute, c = chronic) RfD = reference dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable Page 57 of 125 4.3.5 Recommendation for Aggregate Exposure Risk Assessments The FQPA ( 1996) requires that EPA aggregate risks from multiple pathways as part of tolerance reassessment. OPP aggregates risk from multiple pathways and routes in cases where the toxic effect of interest is common among or between the routes of interest. In the case of DMA, exposures from the oral route ( food, water, incidental oral) may be aggregated. The bladder was not noted as a target organ in the dermal or the inhalation toxicity studies. As such, it is inappropriate to aggregate risks from dermal and inhalation exposures.

4.3.6 Classification of Carcinogenic Potential As described in the special issue paper for DMA, the mode of action for the development of bladder tumors in rats has been established and supports a nonlinear dose response assessment. This mode of action is expected to be functional in humans. A key step in this mode of action is that sufficient DMAIII is available at the target site to cause cell killing. This cytotoxicity must be sustained to result in regenerative proliferation. Each of these key steps is necessary for the development of bladder tumors. Based on EPA's 2005 ( USEPA 2005b) cancer guidelines, DMA is considered " not likely to be carcinogenic to humans at doses that do not result in enhanced cell proliferation"

4.3.7 Endocrine Disruption EPA is required under the FFDCA, as amended by FQPA, to develop a screening program to determine whether certain substances ( including all pesticide active and other ingredients) " may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." Following recommendations of its Endocrine Disruptor and Testing Advisory Committee ( EDSTAC), EPA determined that there was a scientific basis for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA authority to require the wildlife evaluations. As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program ( EDSP). Limited changes in organ weights for reproductive organs ( e. g. ovarian weight changes without pathological changes in the reproductive toxicity study) and testicular pathology ( dermal study only) were noted only at very high doses with DMA. These effects were not replicated in other studies. Regarding potential thyroid toxicity, the changes in thyroid follicular cell height do not progress to longer term health outcomes. The bladder is a sensitive target organ and special mode of action studies provide health protective endpoints for DMA toxicity at low doses. Page 58 of 125 5.0 Public Health Data 5.1 Incident Reports OPP draws from 4 different databases to determine what, if any, poisoning incidents have occurred that can be related to pesticidal/ herbicidal use. A summary of the databases follows.

1) Office of Pesticide Program's Incident Data System ( IDS)  includes reports of incidents from various sources, including required Federal Insecticide Fungicide and Rodenticide Act ( FIFRA) Section 6 ( a) ( 2) registrants, other federal and state health and environmental agencies and individual consumers, submitted to the Agency since 1992. Reports submitted to the IDS represent anecdotal reports or allegations only, unless otherwise stated. Typically no conclusions can be drawn implicating the pesticide as a cause of any of the reported health effects. Nevertheless, sometimes with enough cases and/ or enough documentation risk mitigation measures may be suggested.

2) American Association of Poison Control Centers ( AAPCC)  as the result of Data Call Ins issued in 1993, the Agency received Poison Control Center data covering the years 1985 through 1992 for 28 organophosphate and carbamate chemicals. Most of the national Poison Control Centers ( PCCs) participate in a national data collection system, the Toxic Exposure Surveillance System which obtains data from about 70 centers at hospitals and universities. PCCs provide telephone consultation for individuals and health care providers on suspected poisonings involving drugs, household products, pesticides, etc.

3) California Pesticide Illness Surveillance Program  California has collected uniform data on suspected pesticide poisonings since 1982. Physicians are required, by statute, to report to their local health officer all occurrences of illness suspected of being related to exposure to pesticides. The majority of the incidents involve workers. Information on exposure ( worker activity), type of illness ( systemic, eye, skin, eye/ skin and respiratory), likelihood of a causal relationship, and number of days off work and in the hospital is provided.

4) National Pesticide Telecommunications Network ( NPTN)  NPTN is a toll free information service supported by the Agency's Office of Pesticide Programs. A ranking of the top 200 active ingredients for which telephone calls were received during calendar years 1984 1991, inclusive has been prepared. The total number of calls was tabulated for the categories; human incidents, animal incidents, calls for information, and others.

5.1.1 Cacodylic Acid Incidents For the purposes of this assessment the focus was on those human incidents that are directly, or probably, related to exposures to cacodylic acid or sodium cacodylate per se. Drawing from four data sources, there were reported poisoning incidents involving children < 6 years of age, but none were hospitalized, and no specifics were given about the activity associated with the exposures. Incidents reported for adults involved both agricultural and non agricultural uses, and resulted in days off from work and, in a few cases, hospitalization. The symptoms ranged from systemic, to skin and eye irritation, to respiratory system effects. Some cases involved multiple Page 59 of 125 symptoms. The uses included lawn, turf, ornamentals, weeds, and cotton. For more details see Allen 2000a.

5.1.2 MSMA/ DSMA Incidents HED searched the four databases discussed above for reports of incidents occurring resulting from exposures to MSMA or DSMA. There were incidents reported for both MSMA and DSMA, involving both adults and children. Most were treated on an outpatient basis but a few required hospitalizations. Some reports described symptoms such as dizziness, sinusitis, rhinitis, memory loss, numbness, tingling, rash, and fever, after aerial applications, but many were nonspecific about the source of exposure. Other reports described effects such as systemic allergic symptoms, nausea, dizziness, and eye irritation for both agricultural and non agricultural uses. Specific details may be found in Allen 2000b.

There are only scattered reports for MSMA/ DSMA among the four data systems used by the Agency's epidemiology group to evaluate human poisoning incidents. The sparsity of data could be due to low usage, and/ or poor reporting to surveillance programs. From the limited information available, systemic allergic reactions and eye irritation are possible targets for preventive intervention.

5.1.3 CAMA Incidents HED searched the same four databases for evidence of poisoning incidents connected with the use of CAMA and found none. Currently, CAMA has no agricultural uses. See Allen 2001.

5.2 Other No scientific literature pertinent to additional health effects of the organic arsenicals in humans was located.

6.0 Exposure Characterization/ Assessment 6.1 Dietary Exposure/ Risk Pathway Arsenic speciation in the environment is complex, and exists in both inorganic and organic forms with interconversion between species depending on varying conditions within the soil ( i. e., phosphorus levels in the soil, pH, microbial environment, etc.). When determining residue values for arsenic in food and drinking water, it is important to understand how arsenic is taken up from the soil by the roots and metabolized within plants. In plant metabolism, limited evidence suggests that plants may metabolize iAs through biomethylation to MMA, DMA, tetramethylarsonium ions ( TETRA) and trimethylarsonium oxide ( TMAO), and further metabolize to arsenocholine, arsenobetaine, and arsenosugars. However, it has not been proven whether these compounds are products of plant metabolism or if they are simply taken up from the soil in those forms. To further complicate the residue picture, metabolism is also dependant on a number of other factors, such as the plant's ability to uptake the compounds, the plant's ability to synthesize arsenic species ( some plants may have arsenic resistance due to evolution), Page 60 of 125 and the presence of arsenic species adsorbed to the outside surface of the plant roots. Therefore, determining residues of arsenic in food and drinking water is extremely complex. There are insufficient data at this time to determine specific amounts of the various arsenic compounds in plants on a national level since the background levels are highly variable and speciation is dependent on so many different factors, all of which are present in a given environment. Human and other mammal metabolism of arsenic is also variable and complex ( see section 3.0).

6.1.1 Residue Profile Cacodylic Acid Use: Cacodylic acid and its salt are nonselective, contact herbicides. The only food/ feed use of cacodylic acid is as a defoliant on cotton. All registered cacodylic acid MPs and EPs, registered for use on cotton, contain cacodylic acid and its sodium salt in combination at a ratio of approximately 1: 6 ( wt: wt). The most recent Screening Level Usage Analysis ( SLUA) report from the Biological and Economic Analysis Division ( BEAD) indicates that the largest market for cacodylic acid is on cotton. Nationwide, < 2.5% of cotton acreage is treated with cacodylic acid ( Carter 2005a, b, c, d).

The tolerance currently established for residues of cacodylic acid, expressed as As2O3, in/ on cottonseed is 2.8 ppm ( 40 CFR § 180.311). Tolerances for residues of DMA in/ on meat, milk, poultry, and eggs ( MMPE) were revoked in 2004 ( 40 CFR Part 180 [ OPP 2003 0344; FRL 7338 3] Aldicarb, Atrazine, Cacodylic Acid, Carbofuran, et al.; Tolerance Actions. Federal Register/ Vol. 69, No. 28/ Wednesday, February 11, 2004/ Rules and Regulations, pp. 6561 6567) due to no expectation of finite residues in these commodities. If warranted, this may be revisited in the future. There are no Codex maximum residue levels ( MRL) established for cacodylic acid.

The qualitative nature of the residue for cacodylic acid and its sodium salt in plants and animals is adequately understood, but uncertainties remain. Based on the available data and published information, the Metabolism Committee concluded that the only residue of concern is cacodylic acid per se ( Swartz 1995). This decision was predicated on evidence available at the time that little or no demethylation of cacodylic acid is likely to occur in/ on cotton and animal commodities. It should be noted however, that additional data for plant residue analytical methods and ILV requirements to support the reregistration of cacodylic acid and its sodium salt are currently under review [ MRID# 459366 01 ( 03/ 04/ 2003) and MRID# 459366 02 ( 04/ 10/ 2002)]. In addition, unspeciated monitoring data, show measurable levels of total arsenic on food crops for which there are no registrations, including meat and milk, and it is unknown at this time how plants up take residues from contaminated soils and subsequently metabolize them. It is also unknown what species ( MMA, DMA, or iAs) may be present on these foodstuffs.

DSMA & MSMA Use: MMA and its salts are selective pre and post emergence organic arsenical herbicides registered for use for weed control. Tolerances have been established [ 40 CFR § 180.289( a)] for residues of MMA, calculated as arsenic trioxide ( As2O3), resulting from applications of the disodium and monosodium salts in/ on citrus fruit ( 0.35 ppm), cottonseed ( 0.7 ppm), and cottonseed hulls ( 0.9 ppm). Note   Bearing citrus use is no longer being supported. DMA is a MSMA/ DSMA Page 61 of 125 transformation product of concern, and was found in cotton and citrus raw agricultural commodities ( RACs) treated with MSMA and/ or DSMA. Tolerances have been established [ 40 CFR § 180.311] for residues of the DMA, also expressed as As2O3, in/ on cottonseed ( 2.8 ppm). According to 40 CFR § 180.3( d)( 4), where a tolerance is established for more than one pesticide containing arsenic found in/ on a RAC, the total amount of such pesticide shall not exceed the highest established tolerance, calculated as As2O3. There are no established Codex Maximum Residue Levels ( MRLs) for MMA. Therefore, issues of Codex harmonization do not exist.

The qualitative nature of the residue for DSMA, MSMA, and its transformation product, DMA, in plants is adequately understood, but uncertainties remain. Based on available data and published information, the HED Metabolism Committee concluded that the residue of concern associated with the use of MSMA and DSMA, are MSMA and cacodylic acid ( Swartz 1995). This conclusion was based on evidence available at the time concerning a low rate or lack of demethylation, and on the inability of the current enforcement method to distinguish between background arsenic and arsenic resulting from herbicidal use. The HED Metabolism Committee ( Swartz 1995) also concluded that there was no reasonable expectation of finite residues of concern in meat, milk, poultry, and eggs as a result of registered uses; that is, residues in meat, milk, poultry, and eggs can be classified under Category 3 of CFR § 180.6( a). Tolerances and feeding studies are not required at this time. However, if warranted, this may be revisited in the future. Speciated monitoring data are needed.

Co occurrence: Known agricultural practices with organic arsenics on cotton ( source of cottonseed commodities), for example, increase the likelihood that one might be exposed to co occurring residues of DMA from applications of DMA and MMA salts. There is potential for cooccurrence of DSMA or MSMA, and cacodylic acid from sequential treatments on cotton but cooccurrence from simultaneous use appears to be unlikely. DSMA and MSMA are used as earlyseason directed spray herbicides on cotton; cacodylic acid is used to defoliate cotton late in the growing season before harvest ( Carter 2006). Additional dietary sources of DMA and MMA residues may come from other food commodities ( background) and from drinking water. Since the percent crop treated (% CT) for the MMA salts ( Carter 2005e, f/ Dobbins 2005a, b, c) and DMA are < 20% and < 2.5% CT on cotton respectively, co occurring residues of DMA or MMA would not be expected to occur on more than 2.5% of the crop treated with the organic arsenicals; however, < 1% co occurrence of both residues is expected. Based on the submitted data and very limited speciation information, the residues on cottonseed resulting from the herbicidal uses would be expected to be primarily organic arsenic. Uptake of background residues in soils, depending on a variety of environmental conditions, may be a combination of organic and iAs species.

Rotational Crops: When assessing the herbicidal uses of the organic arsenicals, one must consider that what is applied ( registered uses) will contribute to background levels of arsenic over time. Therefore, over years of applications of the organic arsenical herbicides, background levels tend to increase and the arsenic species present interconvert between species depending on varying environmental conditions within the soil ( i. e., pH, microbial environment, etc.). Therefore, this constant contribution of arsenic could cause higher residues to be found not only in the registered Page 62 of 125 crop, but also in crops that are rotated. This may explain why the FDA TDS shows detectable residues in cereal grains more frequently than other crops since cereal grains are often rotated with cotton. Both cotton and cereal grains are also livestock feed commodities. Increased arsenic levels in the portions of cotton and cereal grains that are fed to livestock can result in an increase of arsenic residues in the edible tissues, thus increasing dietary exposure to arsenic. The FDA TDS has also found detectable residues of arsenic in the edible tissues of livestock ( mostly beef liver) as well as poultry. However, the detectable residues found in poultry meat are most likely due to arsenic use as a growth promoter in poultry and swine ( FDA tolerances for chicken, turkey, and swine are listed under 21 CFR 556.60). These uses also contribute to the dietary exposure to arsenic.

FDA Total Diet Study: Determining residues of arsenic in food and drinking water is extremely complex. There are insufficient data at this time to determine specific amounts of the various arsenic compounds in plants since the levels are dependent on so many different factors, all of which could be present in any given environment. The best available data to capture the total amount of arsenic in food commodities on a national level are the FDA TDS. However, though the data provided by the TDS are the best available data at this time, they are limited and are not designed for use in dietary exposure assessments. The commodities that were tested in the FDA TDS, though some RAC data are provided, are predominantly the processed and cooked commodities as eaten. Another limitation of using the FDA TDS data for a dietary assessment of organic or inorganic arsenic in food is that the method used for quantifying residues of arsenic in the study does not speciate; therefore, HED cannot determine how much of the total residues are inorganic versus organic arsenic. These factors contribute uncertainty and possible conservativeness, due to lack of speciation, to the assessment.

Residue Data Used for the Acute and Chronic Dietary Assessments: For both acute and chronic total organic arsenic assessments, field trial data combined with % CT estimates from BEAD ( Carter 2005a, b, c, d, e, f) were used for cotton, and the FDA Total Diet Study ( TDS) data were used directly in residue distribution files for all other commodities. HED notes that this may be an overestimation since it is assumed that there is a small amount of arsenic in all the commodities that were included. As mentioned above, the commodities that were tested are predominantly the processed and cooked commodities as eaten. Therefore, some non standard assumptions were used. For example, for almonds, the data that were used from the TDS are for mixed nuts, no peanuts, dry roasted. It was assumed that the residues found on the mixed nuts are representative of residues that one would expect to see on almonds. These types of assumptions were used throughout the assessment. Default processing factors were used unless there were data on the processed commodities, and then that data were used directly with no additional adjustments. Please refer to the dietary memo ( Kinard 2006) for details on how the data were translated and used.

6.1.2 Dietary Risk Assessment/ Characterization Acute and chronic dietary risk assessments for DMA and MMA resulting from food/ feed uses of cacodylic acid and salts, DSMA, and MSMA were conducted using the Dietary Exposure Evaluation Model ( DEEM FCID   , Version 2.03) which uses food consumption data from the Page 63 of 125 USDA's Continuing Surveys of Food Intakes by Individuals ( CSFII) from 1994 1996 and 1998. Consumption data are averaged for the entire U. S. population and within various population subgroups to conduct chronic and cancer risk estimates, but retained as individual daily consumption data points to conduct acute risk estimates ( which are based on distributions of consumption estimates for either deterministic or probabilistic type exposure estimates). The analyses were performed to support the reregistration eligibility decisions for cacodylic acid, DSMA, and MSMA.

Cacodylic acid is a registered herbicide as well as a common transformation product of DSMA, MSMA, and CAMA. The only registered use of cacodylic acid in/ on a food/ feed crop is cottonseed, and the only registered uses of DSMA and MSMA in/ on food/ feed crops are citrus and cottonseed commodities; however, the bearing citrus use is no longer being supported; therefore, citrus was not included as a registered use. There are currently no registered uses of CAMA in/ on food/ feed crops; therefore, it is not included in the dietary assessment.

Under the Food Quality Protection Act ( FQPA), the acute and chronic dietary exposure and risk estimates cannot be limited to residues of DMA and MMA and their salts on cotton seed but, must include all sources of dietary exposure. Arsenic residues incurred in/ on food from other potential sources of arsenic, including background levels, have been included. No monitoring data for residues of DMA or MMA per se are available from FDA and/ or USDA. The available monitoring data on total arsenic ( as As2O3) from the FDA TDS ( Market Baskets 91 3 through 7

1) are limited for the food/ food forms of concern and are likely to significantly overestimate dietary exposure to arsenic from agricultural applications of DMA and MMA. The FDA TDS includes residues of arsenic from all potential sources including background and are the best available data at this time for assessing dietary risk on a national level. The anticipated residue estimates are considered moderately refined, although are considered conservative based on assumptions that were made due to the lack of arsenic speciated data. Such anticipated residue estimates are likely to overestimate the dietary exposure and risk from the combined agricultural herbicidal use of cacodylic acid, DSMA, and MSMA.

<IP_ADDRESS> Acute Dietary Exposure Results and Characterization Several acute dietary assessments were performed for the organic arsenicals using field trial data, FDA's TDS data, % CT information, and default processing factors. Since arsenic is ubiquitous in the environment and was quantified as total arsenic in the best available data, it was not possible to determine where the arsenic originated from ( i. e., background or from herbicidal use) or to determine speciated residue values for use in a national dietary exposure assessment; therefore, these assessments contain assumptions that are not standard for HED dietary exposure assessments. A number of the assumptions that have been made in these assessments are considered to be conservative. However, when assuming that all arsenic found in the field trials, reported in the FDA TDS, and estimated in drinking water is either MMA or DMA, risks are below HED's level of concern for the U. S. population and all population subgroups at the 99.9th percentile of exposure. Commodities that contributed the most to the acute dietary assessments are fish and drinking water. Page 64 of 125 <IP_ADDRESS> Chronic Dietary Exposure Results and Characterization Several chronic dietary assessments were also performed for the organic arsenicals using field trial data, FDA's TDS data, % CT information, and default processing factors. As above ( <IP_ADDRESS>), a number of the assumptions that have been made in these assessments are considered to be conservative. However, when assuming that all arsenic found in the field trials, reported in the FDA TDS, and estimated in drinking water is either MMA or DMA, risks are below HED's level of concern for the U. S. population and all population subgroups. Commodities that contributed the most to the chronic dietary assessments are rice and cereal grains.

MMA, or its sodium or calcium salts, have been classified as " not likely" human carcinogens, and DMA is considered not carcinogenic up to doses resulting in regenerative proliferation; therefore, separate cancer assessments for MMA and DMA have not been performed.

<IP_ADDRESS> Dietary Risk Results/ Discussion For acute and chronic assessments, HED is concerned when dietary risk exceeds 100% of the population adjusted dose ( PAD). The DEEM FCID   analyses estimate the dietary exposure of the U. S. population and various population subgroups. The dietary ( food and water) risk assessment was conducted in a stepwise fashion. The results presented here show the bounding ends ( Level 1 & 3) of the range of potential risks, but more details can be found in Kinard 2006. For all scenarios, drinking water estimates provided by EFED for both runoff from applications to cotton and applications to turf were included. All species of concern in this assessment ( MMA, DMA, and iAs) have distinct toxicities; exposures to each are considered individually. More discussion on potential risks from iAs exposure can be found in Section 7.7.

Level 1: Acute and chronic dietary exposure analyses include only the registered food commodity, cottonseed ( field trial data resulting from the max application of DSMA/ MSMA and cacodylic acid to cotton grown in non arsenic containing soil), and two different drinking water scenarios ( cotton and turf).

Level 2: Acute and chronic dietary exposure analyses include: a) cottonseed and meat ( residue estimates from FDA TDS); b) cottonseed, meat, and two different drinking water scenarios; c) cottonseed, meat, and fish ( residue estimates also from FDA TDS); and, d) cottonseed, meat, fish, and two different water scenarios ( details can be found in Kinard 2006).

Level 3: Acute and chronic dietary exposure analyses include: a) cottonseed and all commodities that were tested in the FDA TDS; b) cottonseed, all commodities that were tested in the FDA TDS and two different drinking water scenarios; c) cottonseed, all commodities that were tested in the FDA TDS, as well as all commodities for which translations could be made from the TDS data; and, d) cottonseed, all commodities that were tested in the FDA TDS, all translated commodities, and two different drinking water scenarios. Page 65 of 125 Results of Level 1 Acute and Chronic Dietary Exposure Analysis The acute results listed below assume 100% of the total arsenic concentration is either MMA ( Table <IP_ADDRESS>a) or DMA ( Table <IP_ADDRESS>b). The acute dietary risk estimates at the 99.9th percentile for food exposure to MMA are not of concern for the U. S. population and all population subgroups, nor are the acute risk estimates of concern for the food and water aggregate exposure to MMA. Similarly, the acute dietary risk estimates at the 99.9th percentile for food exposure and the food and water aggregate exposure to DMA are not of concern for the U. S. population and all population subgroups.

Table <IP_ADDRESS>a: Acute Dietary Risk Results at the 99.9th % tile of Exposure from the Cotton Use for the Organic Arsenical Herbicides Using DEEM FCID with the MMA aPAD of 0.1 mg/ kg/ day Food only Food + Cotton Water Food + Turf Water Population Subgroup Exposure ( mg/ kg/ day) % aPAD Exposure ( mg/ kg/ day) % aPAD Exposure ( mg/ kg/ day) % aPAD U. S. Population 0.000018 < 1 0.002229 2.2 0.021484 21.5 All Infants (< 1 yr.) 0.000009 < 1 0.007081 7.1 0.061812 61.8 Children 1 2 yrs. 0.000029 < 1 0.003145 3.1 0.028373 28.4 Children 3 5 yrs. 0.000040 < 1 0.002820 2.8 0.025179 25.2 Children 6 12 yrs. 0.000019 < 1 0.001973 2.0 0.017495 17.5 Youth 13 19 yrs. 0.000016 < 1 0.001709 1.7 0.016117 16.1 Adults 20 49 yrs. 0.000014 < 1 0.001911 1.9 0.017530 17.5 Adults 50+ yrs. 0.000006 < 1 0.001592 1.6 0.013899 13.9 Females 13 49 yrs. 0.000014 < 1 0.001890 1.9 0.017253 17.2 Table <IP_ADDRESS>b: Acute Dietary Risk Results at the 99.9th % tile of Exposure from the Cotton Use for the Organic Arsenical Herbicides Using DEEM FCID with the DMA aPAD of 0.12 mg/ kg/ day Food only Food + Cotton Water Food + Turf Water Population Subgroup Exposure ( mg/ kg/ day) % aPAD Exposure ( mg/ kg/ day) % aPAD Exposure ( mg/ kg/ day) % aPAD U. S. Population 0.000018 < 1 0.003347 2.8 0.014430 12.0 All Infants (< 1 yr.) 0.000009 < 1 0.008155 6.8 0.036330 30.3 Children 1 2 yrs. 0.000029 < 1 0.003763 3.1 0.016023 13.4 Children 3 5 yrs. 0.000040 < 1 0.003392 2.8 0.016081 13.4 Children 6 12 yrs. 0.000019 < 1 0.002265 1.9 0.009701 8.1 Youth 13 19 yrs. 0.000016 < 1 0.002426 2.0 0.011225 9.4 Adults 20 49 yrs. 0.000014 < 1 0.002623 2.2 0.010937 9.1 Adults 50+ yrs. 0.000006 < 1 0.001857 1.6 0.008014 6.7 Females 13 49 yrs. 0.000014 < 1 0.002526 2.1 0.010907 9.1 Page 66 of 125 The chronic results listed below assume 100% of the total arsenic concentration is either MMA ( Table <IP_ADDRESS>c) or DMA ( Table <IP_ADDRESS>d). The results for the chronic dietary risk estimates for food exposure to MMA and DMA, respectively, are not of concern for the U. S. population and all population subgroups, nor are the chronic risk estimates of concern for the food and drinking water aggregate exposure to MMA.

Table <IP_ADDRESS>c: Chronic Dietary Risk Results from the Cotton Use for the Organic Arsenical Herbicides Using DEEM FCID with the MMA cPAD of 0.03 mg/ kg/ day Food only Food + Cotton Water Food + Turf Water Population Subgroup Exposure ( mg/ kg/ day) % cPAD Exposure ( mg/ kg/ day) % cPAD Exposure ( mg/ kg/ day) % cPAD U. S. Population 0.000001 < 1 0.000233 < 1 0.002699 9.0 All Infants (< 1 yr.) 0.000000 < 1 0.000760 2.5 0.008845 29.5 Children 1 2 yrs. 0.000002 < 1 0.000346 1.2 0.004008 13.4 Children 3 5 yrs. 0.000002 < 1 0.000325 1.1 0.003753 12.5 Children 6 12 yrs. 0.000002 < 1 0.000224 < 1 0.002589 8.6 Youth 13 19 yrs. 0.000001 < 1 0.000169 < 1 0.001951 6.5 Adults 20 49 yrs. 0.000001 < 1 0.000217 < 1 0.002520 8.4 Adults 50+ yrs. 0.000000 < 1 0.000228 < 1 0.002651 8.8 Females 13 49 yrs. 0.000001 < 1 0.000216 < 1 0.002509 8.4 Table <IP_ADDRESS>d: Chronic Dietary Risk Results from the Cotton Use for the Organic Arsenical Herbicides Using DEEM FCID with the DMA cPAD of 0.014 mg/ kg/ day Food only Food + Cotton Water Food + Turf Water Population Subgroup Exposure ( mg/ kg/ day) % cPAD Exposure ( mg/ kg/ day) % cPAD Exposure ( mg/ kg/ day) % cPAD U. S. Population 0.000001 < 1 0.000148 1.1 0.000970 6.9 All Infants (< 1 yr.) 0.000000 < 1 0.000484 3.5 0.003179 22.7 Children 1 2 yrs. 0.000002 < 1 0.000221 1.6 0.001442 10.3 Children 3 5 yrs. 0.000002 < 1 0.000207 1.5 0.001350 9.6 Children 6 12 yrs. 0.000002 < 1 0.000143 1.0 0.000931 6.7 Youth 13 19 yrs. 0.000001 < 1 0.000108 < 1 0.000702 5.0 Adults 20 49 yrs. 0.000001 < 1 0.000138 1.0 0.000906 6.5 Adults 50+ yrs. 0.000000 < 1 0.000145 1.0 0.000953 6.8 Females 13 49 yrs. 0.000001 < 1 0.000138 1.0 0.000902 6.4 Page 67 of 125 Results of Level 3 Acute and Chronic Dietary Exposure Analysis The acute results listed below assume 100% of the total arsenic concentration is either MMA ( Tables <IP_ADDRESS>e) or DMA ( Tables <IP_ADDRESS>f). The acute dietary risk estimates at the 99.9th percentile for MMA and DMA in food are not of concern for the U. S. population and all population subgroups, nor are the acute risk estimates of concern for the food and drinking water aggregate exposures.

Table <IP_ADDRESS>e: Acute Dietary Risk Results at the 99.9th % tile of Exposure from Cotton Use and All TDS Commodities with Translations for the Organic Arsenical Herbicides Using DEEM FCID with the MMA aPAD of 0.1 mg/ kg/ day Food only Food + Cotton Water Food + Turf Water Population Subgroup Exposure ( mg/ kg/ day) % aPAD Exposure ( mg/ kg/ day) % aPAD Exposure ( mg/ kg/ day) % aPAD U. S. Population 0.036201 36.2 0.036779 36.8 0.047609 47.6 All Infants (< 1 yr.) 0.028218 29.2 0.031956 31.2 0.089358 89.4 Children 1 2 yrs. 0.067527 67.5 0.068276 68.3 0.073761 73.8 Children 3 5 yrs. 0.064264 64.3 0.066282 66.3 0.073885 73.9 Children 6 12 yrs. 0.043023 43.0 0.044156 44.2 0.049357 49.4 Youth 13 19 yrs. 0.027242 27.2 0.027821 27.8 0.033211 33.2 Adults 20 49 yrs. 0.026693 26.7 0.027229 27.2 0.034873 34.9 Adults 50+ yrs. 0.034951 34.9 0.035834 35.8 0.040919 40.9 Females 13 49 yrs. 0.026445 26.4 0.026685 26.7 0.034338 34.3 Table <IP_ADDRESS>f: Acute Dietary Risk Results at the 99.9th % tile of Exposure from Cotton Use and All TDS Commodities with Translations for the Organic Arsenical Herbicides Using DEEM FCID with the DMA aPAD of 0.12 mg/ kg/ day Food only Food + Cotton Water Food + Turf Water Population Subgroup Exposure ( mg/ kg/ day) % aPAD Exposure ( mg/ kg/ day) % aPAD Exposure ( mg/ kg/ day) % aPAD U. S. Population 0.036201 30.2 0.036537 30.4 0.038003 31.7 All Infants (< 1 yr.) 0.028218 23.5 0.030201 25.2 0.042138 35.1 Children 1 2 yrs. 0.067527 56.3 0.067877 56.6 0.069642 58.0 Children 3 5 yrs. 0.064264 53.6 0.066023 55.0 0.067773 56.5 Children 6 12 yrs. 0.043023 35.8 0.043792 36.5 0.045716 38.1 Youth 13 19 yrs. 0.027242 22.7 0.027681 23.1 0.028528 23.8 Adults 20 49 yrs. 0.026693 22.2 0.027062 22.6 0.028227 23.5 Adults 50+ yrs. 0.034951 29.1 0.035501 29.6 0.036965 20.8 Females 13 49 yrs. 0.026445 22.0 0.026591 22.2 0.027279 22.7 Page 68 of 125 The chronic results listed below assume 100% of the total arsenic concentration is either MMA ( Tables <IP_ADDRESS>g) or DMA ( Tables <IP_ADDRESS>h). The chronic risk estimates for MMA and DMA dietary exposure in food are not of concern for the U. S. population and all population subgroups nor are the chronic risk estimates of concern for the food and water aggregate exposures.

Table <IP_ADDRESS>g: Chronic Dietary Risk Results from Cotton Use and All TDS Commodities with Translations for the Organic Arsenical Herbicides Using DEEM FCID with the MMA cPAD of 0.03 mg/ kg/ day Food only Food + Cotton Water Food + Turf Water Population Subgroup Exposure ( mg/ kg/ day) % cPAD Exposure ( mg/ kg/ day) % cPAD Exposure ( mg/ kg/ day) % cPAD U. S. Population 0.000795 2.6 0.001027 3.4 0.003493 11.6 All Infants (< 1 yr.) 0.000611 2.0 0.001371 4.6 0.009456 31.5 Children 1 2 yrs. 0.001828 6.1 0.002172 7.2 0.005835 19.4 Children 3 5 yrs. 0.001580 5.3 0.001903 6.3 0.005331 17.8 Children 6 12 yrs. 0.001000 3.3 0.001223 4.1 0.003587 12.0 Youth 13 19 yrs. 0.000602 2.0 0.000770 2.6 0.002552 8.5 Adults 20 49 yrs. 0.000635 2.1 0.000851 2.8 0.003154 10.5 Adults 50+ yrs. 0.000807 2.7 0.001034 3.4 0.003457 11.5 Females 13 49 yrs. 0.000595 2.0 0.000810 2.7 0.003103 10.3 Table <IP_ADDRESS>h. Chronic Dietary Risk Results from Cotton Use and All TDS Commodities with Translations for the Organic Arsenical Herbicides Using DEEM FCID with the DMA cPAD of 0.014 mg/ kg/ day Food only Food + Cotton Water Food + Turf Water Population Subgroup Exposure ( mg/ kg/ day) % cPAD Exposure ( mg/ kg/ day) % cPAD Exposure ( mg/ kg/ day) % cPAD U. S. Population 0.000795 5.7 0.000942 6.7 0.001764 12.6 All Infants (< 1 yr.) 0.000611 4.4 0.001094 7.8 0.003790 27.1 Children 1 2 yrs. 0.001828 13.1 0.002047 14.6 0.003268 23.3 Children 3 5 yrs. 0.001580 11.3 0.001785 12.8 0.002928 20.9 Children 6 12 yrs. 0.001000 7.1 0.001142 8.2 0.001930 13.8 Youth 13 19 yrs. 0.000602 4.3 0.000709 5.1 0.001303 9.3 Adults 20 49 yrs. 0.000635 4.5 0.000772 5.5 0.001540 11.0 Adults 50+ yrs. 0.000807 5.8 0.000952 6.8 0.001759 12.6 Females 13 49 yrs. 0.000595 4.2 0.000732 5.2 0.001496 10.7 Page 69 of 125 6.2 Water Exposure/ Risk Pathway Both the MMA and DMA water exposure assessments conducted by EFED ( Moore 2006) were based primarily on 1) submitted environmental fate studies on MSMA and DMA, 2) modeling, 3) limited monitoring for speciated forms of arsenic, 4) extensive monitoring for total arsenic, and 5) peer reviewed literature. Monitoring sources included United States Geological Survey ( USGS) ( groundwater and surface water), BASINS, STORET ( surface water only), and published literature. In most cases, monitoring was for total arsenic ( unspeciated) in areas not targeted for organic arsenic use. Thus, most monitoring data are useful for assessing total exposure to arsenic ( inorganic and organic), but are generally not useful for estimating MMA or DMA exposure resulting from pesticide exposure as such.

Based on 2005 estimates from BEAD, the major use of cacodylic acid is as a cotton defoliant. The major use of DSMA is as an herbicide on cotton and the major uses of MSMA are as an herbicide on cotton (~ 65% total use) and on turf (~ 30%).

The maximum labeled rates for these uses were modeled using PRZM 3.12/ EXAMS 2.98.04 to determine estimated drinking water concentrations ( EDWCs) in surface water. According to the master labels provided by the registrant, the maximum labeled rate for these uses are:

Turf: 4 applications of MSMA at 3.35 lbs ae. / A with a 10 day interval Cotton: 2 applications of DSMA at 1.74 lbs ae. / A with a 7 day interval AND 1 application of DMA at 1.2 lbs a. i. / A.

In aqueous solution, the salts MSMA and DSMA are present in the dissociated form, as sodium ions and monomethylarsonic acid ( MMA), a. k. a. MAA. These compounds are therefore both modeled as MMA, using application rates in lbs MMA per acre.

Both MMA and DMA can degrade to inorganic arsenic ( iAs), and DMA can be produced as a degradate of MMA, as well as from direct application. Estimated concentrations for all three compounds are provided for each use. EDWCs for the directly applied parent compound, either MMA or DMA, were determined by modeling that compound at the applied rate. Estimates of the amount of DMA present as a degradate of MMA were determined by modeling as if DMA had been applied directly at 35% of the MMA application rate. This value was chosen because in all reviewed lab and field studies, no more than 35% of the applied MMA has been present as DMA at any time up to one year. Inorganic arsenic was calculated as a direct molar conversion from EDWCs of the applied compound( s). These estimates represent worst case situations with maximum exposures at different times. Logically, it is not expected that the maximum concentration for each compound will all be present at the same time ( i. e. concurrently).

The maximum area planted with cotton in any watershed is 20%. This percent cropped area ( PCA) factor is used in calculations estimating exposure from use on cotton. Based on EFED policy, no PCA factor is used in estimating exposure from use on turf. Because turf uses are not limited to golf courses, the golf course adjustment factor was also not applied. Modeling was carried out with the Mississippi cotton and Florida turf scenarios, the most vulnerable scenarios Page 70 of 125 available for these uses. Half lives, sorption coefficients, and other inputs into the modeled drinking water estimates can be found in Moore 2006.

6.2.1 Surface Water Modeling for Drinking Water Estimates Modeling of the application of arsenical pesticides was performed to predict acute and chronic concentrations that may reach drinking water. Although there are extensive monitoring data available for arsenic, some of it even targeted to heavy use areas, modeling remains a valuable tool to supplement the limitations of monitoring. Most monitoring measures total arsenic and does not provide information on speciation. Monitoring data do not generally allow for determination of the source of contamination. This is particularly important for arsenic, which has multiple potential sources, both from natural background and from various anthropogenic activities. Even for those monitoring studies targeted to heavy use areas, specific information about application rates and land use history are not always available. Additionally, even targeted studies cannot be expected to capture short lived peak concentrations. In light of these factors, and considering the variability of arsenic's environmental behaviour with variable environmental conditions, modeling is useful for providing high end estimates of speciated arsenic concentrations resulting from pesticide applications under the most vulnerable conditions.

To determine EDWCs in surface water, the Pesticide Root Zone Model ( PRZM 3.12; 5/ 7/ 98), which simulates transport off the agricultural field, is run in tandem with the Exposure Analysis Modeling System, ( EXAMS 2.98.04; 6/ 13/ 97), which simulates the fate of chemicals in a body of water. The simulated watershed is based on an Index Reservoir ( IR) scenario, and a PCA adjustment factor is used to adjust for the area within the watershed that is planted to the modeled crop ( OPP, 2000). Models are run for 30 years and the reported EDWCs represent the values that are expected once every ten years, based on the 30 years of daily values generated during the simulation. The crop scenarios used in PRZM/ EXAMS represent sites that are highly vulnerable to runoff. In this assessment, the Mississippi cotton and Florida turf scenarios are modeled to represent the major uses of arsenicals ( see Moore 2006).

All species of concern in this assessment ( MMA, DMA, and iAs) have distinct toxicities ( see Section 4.0) therefore, exposure to each needs to be considered individually. Estimated concentrations of each of these compounds are therefore provided for each use. Compounds resulting from degradation are considered as well as the directly applied herbicides. Applied MMA may metabolize to DMA. On cotton, MMA and DMA can be applied to the same field. Reported cotton MMA EDWCs, therefore, result from direct application while cotton DMA EDWCs result both from direct application and from transformation of MMA. On turf, all EDWCs are the result of MMA application. Both MMA and DMA may also metabolize to inorganic arsenic. It is impossible to determine the exact concentration of each species that will be present at any one time and each species will reach its highest level at different times. An EDWC for " total arsenic" has been reported to indicate the maximum amount of arsenic that may be in surface water as a sum of all species present. It is this EDWC that would be compared to regulatory levels, which are set as total arsenic. Since it is possible that all arsenic would be present in the form of inorganic arsenic, this EDWC also represents the maximum potential concentration of inorganic arsenic. EDWCs resulting from the maximum labeled application rates for cotton and turf are presented in Table 6.2.1. Page 71 of 125 Table 6.2.1: EDWCs ( ppb) from maximum labeled rates for major uses of arsenicals.

Acute Chronic Cancer TURF1 MMA 250.5 127.5 74.6 DMA 102.3 46.5 28.1 Total As3 135.2 68.8 40.3 COTTON2 MMA 37.4 11.0 5.3 DMA 23.6 7.4 4.3 Total As3 20.9 7.2 3.9 1 MSMA applied 4 times at 3.35 lbs ae/ A. 2 DSMA applied 2 times at 1.74 lbs ae/ A & DMA applied 1 time at 1.2 lb ai/ A. 3 Total arsenic is the sum, reported as ppb As, of arsenic that may be present from all applied and degradate species. It also represents the maximum EDWC of inorganic arsenic.

<IP_ADDRESS> Inputs/ Characterization The reported EDWCs are based on maximum labeled application rates under the most vulnerable circumstances. A variety of management practices, environmental conditions, and application rates are possible and can lead to different concentrations. Exposure to arsenicals may be affected by less vulnerable soils, typical application rates, application to minor crops, or practices such as irrigation or spot treatment. Sorption of arsenical pesticides varies with soil characteristics, which in turn affects migration through soil to sources of drinking water. Sorption is expected to be higher in soils with a higher percentage of clay or with more iron or aluminum content ( Moore 2006). Additional estimates of surface water concentrations were modeled using higher Kd values to characterize possible exposure from application to less vulnerable soils. These results suggest that in soils with median sorption, the acute EDWCs would be reduced with less change in the chronic EDWCs.

MMA degradation to DMA was simulated by modeling DMA applied at 35% of the MMA rate with DMA input parameters. This simulation is based on the assumption that a maximum of 35% of applied MMA may be present as DMA at any one time ( see Moore 2006). For cotton, where DMA and MMA can both be applied to the same field at different times in the same season, the time series of concentrations resulting from DMA applied directly was added to that resulting from DMA as a degradate of MMA. The upper 90% confidence limit was determined for peak and average annual values from this 30 year time series.

There is uncertainty associated with this assumption, which is based on the results of a lab study on the degradation of MMA and on calculations using the modeled half lives of MMA and DMA. In both of these approaches, the DMA present is being degraded as it is formed and so, without degradation, would be present in higher amounts. Additional uncertainty results from modeling the DMA degradate as if it were applied at the same time as the MMA parent. Page 72 of 125 Degradation to DMA is not a rapid transformation and so in fact, when present, the degradate will appear at a later date, dependent on the environmental conditions. See Moore 2006.

Total arsenic levels were estimated as a direct molar conversion of the EDWC predicted for the applied organic arsenical( s), and this value also represents the maximum amount of inorganic arsenic that may reach surface water. The calculation of maximum inorganic arsenic as a direct molar conversion of the parent compound's aquatic concentration does not necessarily represent the actual physical process   inorganic arsenic is likely formed through degradation in the soil, rather than after reaching surface water. This calculation still provides a conservative estimate of the amount of inorganic arsenic that may reach surface water. The estimate is supported by a targeted monitoring study in cotton growing areas which found that typically, one arsenic species at a time was dominant. Immediately following the period of typical application, MMA was the dominant species and several weeks to months later, the primary form of arsenic was inorganic, present at approximately the same total arsenic concentration as the earlier MMA.

For cotton, a 20% PCA is applied to the modeling results, according to EFED policy which estimates that 20% is the maximum area of any watershed planted in cotton ( OPP, 2000). It is possible that arsenicals are applied to other crops within the same watershed, which could lead to higher amounts of pesticide reaching surface water. Use as an herbicide on turf is the only other application of arsenicals extensive enough to potentially increase watershed scale concentrations. Monitoring data from heavy cotton use areas suggest, however, that the 20% PCA still leads to protective estimates of exposure.

No appropriate PCA has been determined for application of pesticides to turf. In order to be protective, at this time EFED policy is to not apply any PCA for turf. The modeled EDWCs for turf are therefore based on the assumption that the entire modeled watershed has been treated with pesticide, which may lead to overestimation of potential exposure. Limited surface water monitoring data targeted to golf course use are available. Available monitoring data involves relatively small surface water bodies that are completely surrounded by turf that may be treated with arsenicals, so they represent high potential exposure relative to the index reservoir. Nevertheless, the data demonstrate that a significant amount of arsenic may reach surface water from turf applications of arsenicals and provide a basis for evaluating the potential overestimation of the modeled EDWCs. The modeled chronic EDWC, as total arsenic, is approximately two times the highest concentration found in this limited monitoring of a high exposure situation.

Modeling relies on estimated fate parameters and assumed agricultural practices to predict concentrations of pesticides to which humans may be exposed. There is uncertainty in all fate inputs used in this assessment, many of which are based on non GLP studies with various deficiencies. There is also uncertainty associated with the method of estimating concentrations of the major degradates, DMA and inorganic arsenic. The estimate of degradation to DMA is based on the assumption that 35% is the maximum amount of MAA that may be present as DMA at any one time. Because this value is based on data that already includes some degradation, it may lead to some underestimation of DMA concentrations. The estimation of concentrations of inorganic arsenic is also uncertain. Inorganic arsenic EDWCs are calculated as a molar conversion of the EDWCs of parent compounds. This is a general estimate of the amount of Page 73 of 125 inorganic arsenic that may reach surface water rather than a direct calculation based on specific physical processes. Transformation of applied organic arsenicals to inorganic arsenic is a long term process that occurs primarily through microbial activity in the soil, not a rapid conversion upon reaching water. Because of the nature of these transformation processes and because of inorganic arsenic's tendency to bind more strongly to soil than the organic arsenicals do, the EDWC of the parent compounds represents a reasonable upper bound on the EDWCs of inorganic arsenic. This assumption is supported by empirical evidence from a targeted monitoring study which found that the maximum concentrations of inorganic arsenic found in surface water in areas of heavy application was similar to the total arsenic resulting from parent compounds ( Moore 2006).

6.2.2 Drinking Water from Ground Water Total arsenic in groundwater can reach very high levels from natural sources alone. It is extremely variable, with national sampling results ranging from less than the detection limit to as high as 900 ppb. A USGS study of around 30,000 locations found that about 10% of them had groundwater concentrations exceeding 10 ppb total arsenic, but found no correlation between total arsenic levels and pesticide use. Arsenic compounds sorb strongly to soil and are relatively immobile in most environments, suggesting that significant leaching is unlikely. This conclusion is supported by several field studies which have not detected arsenic from pesticide application below the top layers of soil. In most situations, labeled use of arsenical pesticides should not contribute significantly to the already existing burden of arsenic in groundwater from all sources, natural and anthropogenic.

Recent investigations in Florida have detected elevated groundwater arsenic levels below golf courses and have demonstrated that leaching from golf course soils may be an important process. In general, soils in Florida tend to be very sandy, and golf courses are usually further engineered to promote drainage. In extreme environments like this, applied arsenicals may leach to groundwater. Especially in areas like Florida where natural background arsenic levels are low, this may lead to an increase in groundwater arsenic. A prospective groundwater study is being implemented in Florida to examine the potential for leaching in these environments.

6.3 Residential ( Non occupational) Exposure/ Risk Pathway It has been determined there is a potential for exposure in residential settings during the application process for homeowners who use products containing DMA, CAMA, DSMA, or MSMA. There is also a potential for exposure from entering DMA, CAMA, DSMA, or MSMAtreated areas, such as lawns and golf courses. Risk assessments have been completed for both residential handler and postapplication scenarios.

In addition to homeowner uses in residential settings, DMA, CAMA, DSMA, and MSMA are labeled for weed control by commercial ( occupational) applicators in residential settings, which may result in postapplication exposures to homeowners and children in residential settings. These potential postapplication exposures have also been considered in this assessment. Page 74 of 125 6.3.1 Residential Handler Exposures and Risks HED uses the term " handlers" to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct tasks related to applications and that exposures can vary depending on the specifics of each task.

<IP_ADDRESS> Inputs and Assumptions for Residential Handler Risks   Residential handler exposure scenarios are considered to be short term only, due to the infrequent use patterns associated with homeowner products.

  A tiered approach for personal protection using increasing levels of PPE is not used in residential handler risk assessments. Homeowner handler assessments are based on the assumption that individuals are wearing shorts, short sleeved shirts, socks, and shoes.

  Homeowner handlers are expected to complete all tasks associated with the use of a pesticide product including mixing/ loading if needed as well as the application.

HED has determined that there are potential exposure to residential mixer, loader, and applicators ( handlers) during the usual use patterns associated with cacodylic acid, CAMA and DSMA/ MSMA. Based on the supported use patterns, HED has determined that there are a number of potential exposure scenarios associated with the use of the organic arsenicals ( see Smith 2006).

The duration of exposure for residential populations is assumed to be short term only, since lawn renovation occurs only once a year, every five years or more and weed control occurs about once a month during the weed growing season of 3 months. Page 75 of 125 Table <IP_ADDRESS>a: Residential Handler Short and Intermediate term Dermal and Inhalation Exposure to DMA Baseline Unit Exposures Baseline MOEs Exposure Scenario Crop or Target Application Rate ( lb ai/ acre) Area Treated Daily ( acres) Dermal ( mg/ lb ai) Inhalation ( ug/ lb ai) Dermal Inhalation Mixer/ Loader/ Applicator Lawn edging 7.72 0.5 38 2.7 140 29000 Mixing/ Loading/ Applying Liquid Concentrates with Low Pressure Handwand ( ORETF) ( 1) Lawn renovation 7.3 0.5 38 2.7 150 31000 Lawn edging 7.72 0.5 11 17 490 4700 Lawn renovation 7.3 0.5 11 17 520 4900 Mixing/ Loading/ Applying Liquid Concentrates with Hose End Sprayer ( Residential ORETF data) ( 2) Non crop 7.3 0.5 11 17 520 4900 Lawn edging 7.72 0.5 2.6 11 2100 7200 Lawn renovation 7.3 0.5 2.6 11 2200 7600 Loading/ Applying Liquid Concentrates with RTU Hose End Sprayer ( Residential ORETF data) ( 3) Non crop 7.3 0.5 2.6 11 2200 7600 Lawn edging 0.00018 0.023 11 16 11000 110000 Mixing/ Loading/ Applying Liquid Concentrates with a Watering Can ( using ORETF residential hoseend data) ( 4) Lawn renovation 0.00017 0.023 11 16 11000 110000 Lawn edging 0.00018 0.023 54 19 2200 91000 Lawn renovation 0.00017 0.023 54 19 2300 96000 Applying Ready to Use Formulations via Trigger Pump Sprayer ( ORETF) ( 5) Non crop 0.00017 0.023 54 19 2300 96000 Page 76 of 125 Table <IP_ADDRESS>b: Residential Handler Short and Intermediate term Dermal and Inhalation Exposure to CAMA Baseline Unit Exposure Baseline MOEs Exposure Scenario Crop or Target App Rate ( lb ai/ A) App Rate of MMA ( lb ai/ A) Area Treated Daily ( acres) Dermal ( mg/ lb ai) Inhalation ( ug/ lb ai) Dermal Inhalation Mixer/ Loader/ Applicator Lawn and ornamental turf ( on grasses other than Bent) 5 4.4 0.5 38 2.7 840 52000 Lawn and ornamental turf ( on Bermuda and Zoysia grass) 4.182 3.7 0.5 38 2.7 1000 62000 Mixing/ Loading/ Apply ing Liquid Concentrates with Low Pressure Handwand ( ORETF) ( 1) Lawn and ornamental turf ( on bentgrass) 2.5 2.2 0.5 38 2.7 1700 100000 Lawn and ornamental turf ( on grasses other than Bent) 5 4.4 0.5 11 17 2900 8200 Lawn and ornamental turf ( on Bermuda and Zoysia grass) 4.182 3.7 0.5 11 17 3500 9800 Mixing/ Loadin g/ Applying Liquid Concentrates with Hose End Sprayer ( Residential ORETF data) ( 2) Lawn and ornamental turf ( on bentgrass) 2.5 2.2 0.5 11 17 5800 16000 Lawn and ornamental turf ( on grasses other than Bent) 5 4.4 0.023 54 19 13000 160000 Lawn and ornamental turf ( on Bermuda and Zoysia grass) 4.182 3.7 0.023 54 19 15000 190000 Applying Ready to Use Formulations via Trigger Pump Sprayer ( ORETF) ( 3)

Lawn and ornamental turf ( on bentgrass) 2.5 2.2 0.023 54 19 26000 320000 Page 77 of 125 Table <IP_ADDRESS>c: Residential Handler Short and Intermediate term Dermal and Inhalation Exposure to DSMA Baseline Unit Exposure Baseline MOEs Exposure Scenario Crop or Target App Rate of MSMA or DSMA ( lb ai/ acre) App Rate of MMA ( lb ai/ acre) Area Treated Daily ( acres) Dermal ( mg/ lb ai) Inhalation ( ug/ lb ai) Dermal Inhalation Mixer/ Loader/ Applicator Mixing/ Loading/ Applying Liquid Concentrates with Low Pressure Handwand ( ORETF  ground directed) ( 1) lawns and ornamental turf 3.293 2.5 0.5 38 2.7 1500 91000 Mixing/ Loading/ Applying Liquid Concentrates with Hose End Sprayer ( Residential ORETF data) ( 2) lawns and ornamental turf 3.293 2.5 0.5 11 17 5100 14000 Loading/ Applying Liquid Concentrates with RTU Hose End Sprayer ( Residential ORETF data) ( 3) lawns and ornamental turf 3.293 2.5 0.5 2.6 11 21000 22000 Loading/ Applying Granulars via Push Type Spreader ( ORETF LCO data) ( 4) lawns and ornamental turf 3.293 2.5 0.5 0.67 0.88 83000 280000 Loading/ Applying Granulars via Belly Grinder ( 5) lawns and ornamental turf 3.293 2.5 0.5 110 62 510 3900 Page 78 of 125 Table <IP_ADDRESS>d: Residential Handler Short and Intermediate term Dermal and Inhalation Exposure to MSMA Baseline Unit Exposure Baseline MOEs Exposure Scenario Crop or Target App Rate of MSMA ( lb ai/ acre) App Rate of MMA ( lb ai/ acre) Area Treated Daily ( acres) Dermal ( mg/ lb ai) Inhalation ( ug/ lb ai) Dermal Inhalation Mixer/ Loader/ Applicator lawns and ornamental turf 3.9204 3.4 0.5 38 2.7 1100 67000 lawns and ornamental turf 2.6136 2.3 0.5 38 2.7 1600 100000 Mixing/ Loading/ Applying Liquid Concentrates with Low Pressure Handwand ( ORETF  ground directed) ( 1) lawns and ornamental turf 2.178 1.9 0.5 38 2.7 2000 120000 lawns and ornamental turf 3.9204 3.4 0.5 11 17 3800 11000 lawns and ornamental turf 2.6136 2.3 0.5 11 17 5600 16000 Mixing/ Loading/ Applying Liquid Concentrates with Hose End Sprayer ( Residential ORETF data) ( 2) lawns and ornamental turf 2.178 1.9 0.5 11 17 6800 19000 3.9204 3.4 0.5 2.6 11 16000 17000 2.6136 2.3 0.5 2.6 11 24000 25000 Loading/ Applying Liquid Concentrates with RTU Hose End Sprayer ( Residential ORETF data) ( 3) lawns and ornamental turf 2.178 1.9 0.5 2.6 11 29000 30000 <IP_ADDRESS> Summary of Residential Handler Risks All risks ( i. e., MOEs) associated with the scenarios are not of concern; all MOEs were > 100 for DMA, CAMA, MSMA, and DSMA.

In order to refine this residential risk assessment, more data on actual use patterns including rates, timing, and areas treated would better characterize cacodylic acid, CAMA and MSMA/ DSMA risks. Exposure studies for many equipment types that lack data or that are not well represented in PHED ( e. g., because of low replicate numbers or data quality) should also be Page 79 of 125 considered based on the data gaps identified above and based on a review of the quality of the data used in this assessment.

6.3.2 Residential/ Non occupational Postapplication Exposures and Risks HED uses the term " postapplication" to describe exposures to individuals that occur as a result of being in an environment that has been previously treated with a pesticide. Cacodylic acid, CAMA, and MSMA/ DSMA can be used in many areas that can be frequented by the general population including residential areas ( e. g., home lawns and gardens). As a result, individuals can be exposed by entering these areas, if they have been previously treated. In addition, all of these arsenic compounds are expected to accumulate in the soil and not degrade over time.

<IP_ADDRESS> Residential Postapplication Inputs and Assumptions A wide array of individuals of varying ages can potentially be exposed to cacodylic acid, CAMA or MSMA/ DSMA when they are in areas that have been previously treated. Postapplication exposure scenarios were developed for each residential setting where cacodylic acid, CAMA or MSMA/ DSMA can be used. The scenarios likely to result in postapplication exposures are as follows:

  Dermal exposure from residue on lawns ( adult and toddler);   Hand to mouth transfer of residues on lawns ( toddler);   Ingestion of pesticide treated grass ( toddler); and   Incidental ingestion of soil from pesticide treated residential areas ( toddler).

HED relies on a standardized approach for completing residential risk assessments that is based on current labels and Agency guidance. When the guidance in current labels and these documents is considered, it is clear that HED should consider children of differing ages as well as adults in its assessments. It is also clear that different age groups should be considered in different situations. The populations that were considered in the assessment include:

  Residential Adults: these individuals are members of the general population that are exposed to chemicals by engaging in activities at their residences ( e. g., in their lawns or gardens) and also in areas not limited to their residence ( e. g., golf courses or parks) previously treated with a pesticide. These kinds of exposures are attributable to a variety of activities and are usually addressed by HED in risk assessments by considering a representative activity as the basis for the exposure calculation.

  Residential Children: children are members of the general population that can also be exposed in their residences ( e. g., on lawns and other residential turf grass areas). These kinds of exposures are attributable to a variety of activities such as playing outside. Toddlers have been selected as the sentinel ( representative) population for the turf assessment. Youth aged children ( ages 10 to 12) are considered the sentinel population for a golfing assessment, because it is likely that children of this age would be playing golf. Page 80 of 125 <IP_ADDRESS> Residential/ Non occupational Postapplication Risk Summary Adults The following tables show the postapplication MOE values calculated for adults after lawn and home garden applications of cacodylic acid, CAMA or DSMA/ MSMA. For all adult scenarios for DMA, CAMA, DSMA, and MSMA, short term MOEs are > 100 for all scenarios.

Table <IP_ADDRESS>a: Adult Residential Risk Estimates for Postapplication Exposure to DMA Exposure Scenario Route of Exposure Application Type Application Rate ( lb ai/ acre) MOE at Day 0 Spray   Lawn Edging 7.72 170 Residential Turf ( High Contact Activities) Spray   Broadcast 7.3 180 Spray   Lawn Edging 7.72 710 Residential Turf ( Mowing) Spray   Broadcast 7.3 750 Spray   Lawn Edging 7.72 180 Home Garden ( Ornamentals) Spray   Broadcast 7.3 190 Spray   Lawn Edging 7.72 2,400 Golfer Dermal Spray   Broadcast 7.3 2,600 Table <IP_ADDRESS>b: Adult Residential Risk Estimates for Postapplication Exposure to CAMA Exposure Scenario Route of Exposure Application Type MMA Application Rate ( lb ai/ acre) MOE at Day 0 Residential Turf ( High Contact Activities) 4.4 980 Residential Turf ( Mowing) 4.4 4,200 Home Garden ( Ornamentals) 4.4 1,100 Golfer Dermal Liquid 4.4 14,000 Page 81 of 125 Table <IP_ADDRESS>c: Adult Residential Risk Estimates for Postapplication Exposure to DSMA Exposure Scenario Route of Exposure Application Type MMA Application Rate ( lb ai/ acre) MOE at Day 0 Residential Turf ( High Contact Activities) 2.5 1,700 Residential Turf ( Mowing) 2.5 7,300 Home Garden ( Ornamentals) 2.5 1,900 Golfer Dermal Spray 2.5 25,000 Table <IP_ADDRESS>d: Adult Residential Risk Estimates for Postapplication Exposure to MSMA Exposure Scenario Route of Exposure Application Type MMA Application Rate ( lb ai/ acre) MOE at Day 0 Residential Turf ( High Contact Activities) 3.4 1,300 Residential Turf ( Mowing) 3.4 5,400 Home Garden ( Ornamentals) 3.4 1,400 Golfer Dermal Spray 3.4 18,000 Youths ( 11 12 years old) Risks ( MOEs) to youths were calculated for postapplication risks following the application of DMA, CAMA, DSMA, and MSMA to home lawns. The tables below summarize the risk assessment for youths. Short term MOEs for DMA, CAMA, DSMA, and MSMA for these youths were > 100 for all scenarios considered.

Table <IP_ADDRESS>e: Youths Residential Risk Estimates for Postapplication Exposure to DMA Exposure Scenario Route of Exposure Application Type Application Rate ( lb ai/ acre) MOE at Day 0 Spray   Lawn Edging 7.72 400 Residential Turf ( Mowing) Spray   Broadcast 7.3 420 Spray   Lawn Edging 7.72 410 Home Garden ( Ornamentals) Spray   Broadcast 7.3 430 Spray   Lawn Edging 7.72 1,400 Golfer Dermal Spray   Broadcast 7.3 1,400 Page 82 of 125 Table <IP_ADDRESS>f: Youths Residential Risk Estimates for Postapplication Exposure to CAMA Exposure Scenario Route of Exposure Application Type MMA Application Rate ( lb ai/ acre) MOE at Day 0 Residential Turf ( Mowing) 4.4 2,300 Home Garden ( Ornamentals) 4.4 2,400 Golfer Dermal Spray 4.4 7,900 Table <IP_ADDRESS>g: Youths Residential Risk Estimates for Postapplication Exposure to DSMA Exposure Scenario Route of Exposure Application Type MMA Application Rate ( lb ai/ acre) MOE at Day 0 Residential Turf ( Mowing) 2.5 4,100 Home Garden ( Ornamentals) 2.5 4,200 Golfer Dermal Spray 2.5 14,000 Table <IP_ADDRESS>h: Youths Residential Risk Estimates for Postapplication Exposure to MSMA Exposure Scenario Route of Exposure Application Type MMA Application Rate ( lb ai/ acre) MOE at Day 0 Residential Turf ( Mowing) 3.4 3,000 Home Garden ( Ornamentals) 3.4 3,100 Golfer Dermal Spray 3.4 10,000 Toddler ( 3 year old) Risks ( MOEs) to toddlers were calculated for postapplication risks following the application of DMA, CAMA, DSMA, and MSMA to home lawns. The tables below summarize the risk assessment for toddlers. The target level of concern for DMA, CAMA, DSMA, and MSMA dermal scenarios and for CAMA, DSMA, and MSMA incidental oral scenarios is 100 ( i. e., MOEs   100 is not of concern to HED). The target level of concern for DMA incidental oral scenarios is 30 ( i. e., MOEs   30 is not of concern to HED), since the endpoint is a BMDL10. Short term incidental oral MOEs for DMA for toddlers were < 30 for the hand to mouth activity and object to mouth activities on turf. Short term incidental oral MOEs for incidental soil ingestion of DMA were greater than 30 and not of concern. Short term dermal MOEs for DMA were > 100 and were also not of concern. Short term dermal and incidental oral MOEs for CAMA, DSMA, and MSMA for toddlers were > 100 for all scenarios considered. Page 83 of 125 Table <IP_ADDRESS>i: Toddler Residential Risk Estimates for Postapplication Exposure to DMA Exposure Scenario Route of Exposure Application Type Application Rate ( lb ai/ A) MOE  Day 0 Spray   Lawn Edging 7.72 100 Residential Turf ( High Contact Activities) Dermal Spray   Broadcast 7.3 110 Spray   Lawn Edging 7.72 4 Hand to Mouth Activity on Turf Spray   Broadcast 7.3 4 Spray   Lawn Edging 7.72 15 Object to Mouth Activity on Turf Spray   Broadcast 7.3 16 Spray   Lawn Edging 7.72 1,100 Incidental Soil Ingestion Oral Spray   Broadcast 7.3 1,200 Table <IP_ADDRESS>j: Toddler Residential Risk Estimates for Postapplication Exposure to CAMA Exposure Scenario Route of Exposure Application Type MMA Application Rate ( lb ai/ A) MOE  Day 0b Residential Turf ( High Contact Activities) Dermal 4.4 580 Hand to Mouth Activity on Turf 4.4 110 Object to Mouth Activity on Turf 4.4 430 Incidental Soil Ingestion Oral Spray 4.4 32,000 Table <IP_ADDRESS>k: Toddler Residential Risk Estimates for Postapplication Exposure to DSMA Exposure Scenario Route of Exposure Application Type MMA Application Rate ( lb ai/ A) MOE  Day 0b Residential Turf ( High Contact Activities) Dermal 2.5 1,000 Hand to Mouth Activity on Turf 2.5 190 Object to Mouth Activity on Turf 2.5 750 Incidental Soil Ingestion Oral Spray 2.5 56,000 Page 84 of 125 Table <IP_ADDRESS>l: Toddler Residential Risk Estimates for Postapplication Exposure to MSMA Exposure Scenario Route of Exposure Application Type MMA Application Rate ( lb ai/ A) MOE  Day 0b Residential Turf ( High Contact Activities) Dermal 3.4 760 Hand to Mouth Activity on Turf 3.4 140 Object to Mouth Activity on Turf 3.4 550 Incidental Soil Ingestion Oral Spray 3.4 41,000 HED considered a number of exposure scenarios for products that can be used in the residential environment representing different segments of the population including toddlers, youth aged children, and adults. Short term noncancer MOEs were calculated for all scenarios. Cancer risks were not calculated, since no toxicological endpoint for cancer was selected. In residential settings, HED does not use restricted entry intervals or other mitigation approaches to limit postapplication exposures, because they are viewed as impractical and not enforceable. As such, risk estimates on the day of application are the key concern.

In the assessment for residential postapplication exposure and risk, there are risks of concern for DMA, as they are currently used in a residential environment. The endpoint used to assess these incidental oral exposures ( BMDL10) comes from data measured at 10 weeks of DMA exposure in the feed to female rats ( Arnold et al, 1999). However, Cohen et al, ( 2001) shows that regenerative proliferation occurred as early as 1 week into the DMA exposure. HED believes that using the Arnold ( 1999) study ( with the Cohen 2001 study as characterization) in conjunction with Day 0 DMA residues ( calculated from the labeled application rates), constitutes the use of the best available data and that the results can be considered conservative for risk assessment purposes.

In order to refine this residential assessment, data on actual use patterns including rates, timing, and the kinds of tasks performed are required to better characterize DMA, CAMA, DSMA, and MSMA risks.

7.0 Aggregate Risk Assessments and Risk Characterization In accordance with the FQPA, HED must consider and aggregate ( add) pesticide exposures and risks from three major sources: food, drinking water, and residential exposures ( oral, dermal, and inhalation exposures). In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard ( e. g., a NOAEL or PAD), or the risks themselves can be aggregated. When aggregating exposures and risks from various sources, HED considers both the route and duration of exposure.

In general, exposures from various sources ( routes) are aggregated only when the toxic effects, determined by the endpoint selected for that route, are the same. In this case, exposure/ risks Page 85 of 125 from the dermal and inhalation routes could not be aggregated with exposures/ risks by the oral route since the toxic effects/ target organs are not the same.

HED combines residential risks resulting from exposures to individual applications when it is likely they can occur simultaneously based on the use pattern and the behavior associated with the exposed population. For DMA, CAMA, DSMA, and MSMA, HED has combined risks ( i. e., MOEs) for different kinds of exposures for the following scenario: for toddlers on turf scenarios   hand to mouth plus object to mouth plus soil ingestion.

The exposures of interest, as required under FQPA, are dietary ( food and water) and residential/ recreational exposures to a common species of arsenic that any one individual or group of individuals might be subject. As noted in section 4.0, the toxicities and target organs of the different species of arsenic ( MMA, DMA, iAs) are dissimilar and the potential risks from multiple sources must be viewed as one species or the other to give a range of possibilities. Since DMA is used on cotton, and MSMA/ DSMA are used on cotton ( cottonseed), and all the MMA salts and DMA have residential/ recreational uses, an individual could have multiple exposures to organic arsenic concurrently from several chemicals ( Cacodylic acid, MSMA, DSMA and CAMA), by a variety of sources ( food, water, residential), and by all routes ( oral, dermal, inhalation).

It is generally accepted that there is potential for persons consuming a variety of fruits, vegetables, and meat products to have exposures to multiple pesticides over the course of a day, a season, or a year, many with a common degradates or transformation product. Add to this the exposures from residential/ recreational uses and the potential health risks are increased. Known agricultural practices with organic arsenics on cotton ( source of cotton seed commodities), for example, increase the likelihood that one might be exposed to co occurring residues of DMA from applications of DMA and of MMA salts. Conversely, as discussed in Section 3.0, under specific conditions one might be exposed to residues of MMA from applications of DMA and MMA salts. There is potential for co occurrence of DSMA, MSMA, and DMA from sequential treatments on cotton but co occurrence from simultaneous use appears to be unlikely. DSMA and MSMA are used as early season directed spray herbicides on cotton; DMA is used to defoliate cotton late in the growing season before harvest ( Carter 2006). Additional dietary sources of DMA and MMA residues may come from drinking water.

7.1 Acute Aggregate Risk The acute aggregate risk estimate includes the contribution of risk from dietary ( food + drinking water) sources only. Acute risk estimates based on exposures to residues of MMA or DMA in food alone do not exceed the Agency's level of concern, even when commodities from the Total Diet Study and translations are included. The maximum estimated acute dietary ( food alone) risk is 68% of the aPAD at the 99.9th percentile for children 1 2 years of age, assuming all exposure is to MMA, and 56% aPAD when one assumes that all exposure is to DMA.

Though some arsenic water monitoring data are available ( measured as total arsenic), they are extremely limited, not nationally representative, and not at the tap data. Hence, they are unsuitable to be quantitatively included in an aggregate risk assessment. Therefore, EDWCs Page 86 of 125 were calculated from models, for risk assessment purposes, based on maximum application rates. The EDWCs were combined directly with exposures from food into the acute dietary exposure assessment to calculate aggregate dietary ( food + water) risk. The advantage of this approach is that the actual individual body weight and water consumption data from the CSFII are used, rather than assumed weights and consumption for broad age groups. Surface water EDWCs were combined with estimated food exposure for aggregate risk assessment purposes since the calculated surface water estimates exceed any potential ground water estimates and therefore, are more conservative.

The acute aggregate food and water analysis provides a range of risk possibilities when all residues are assumed to be MMA or DMA to estimate dietary exposure and risk. The drinking water estimate used in this aggregate ( food and water) analysis was calculated from turf uses, since that allows for the most conservative exposure estimate. Assuming that all exposures are either to MMA or DMA, the maximum aggregate dietary risk estimates are for infants/ children at the 99.9th percentile of exposure and are 89% of the aPAD for MMA and 58% aPAD for DMA and therefore, not of concern.

Table 7.1a: Results of Acute Aggregate Dietary Exposure Analysis for MMA Using DEEM FCID 95TH % TILE 99TH % TILE 99.9TH % TILE Population Subgroup aPAD ( mg/ kg/ day) Exposure % aPAD Exposure % aPAD Exposure % aPAD General U. S. Population 0.1 0.012324 12 0.023316 23 0.047609 48 All Infants (< 1 year old) 0.1 0.37384 37 0.055942 56 0.089358 89 Children 1 2 years old 0.1 0.019697 20 0.034666 35 0.073761 74 Children 3 5 years old 0.1 0.017891 18 0.032945 33 0.073885 74 Children 6 12 years old 0.1 0.012480 13 0.022630 23 0.049357 49 Youth 13 19 years old 0.1 0.009595 10 0.018331 18 0.033211 33 Females 13 49 years old 0.1 0.010871 11 0.018447 18 0.034338 34 Page 87 of 125 Table 7.1b: Results of Acute Aggregate Dietary Exposure Analysis for DMA Using DEEM FCID 95TH % TILE 99TH % TILE 99.9TH % TILE Population Subgroup aPAD ( mg/ kg/ day) Exposure % aPAD Exposure % aPAD Exposure % aPAD General U. S. Population 0.12 0.006496 5 0.014781 12 0.038003 32 All Infants (< 1 year old) 0.12 0.015443 13 0.023642 20 0.042138 35 Children 1 2 years old 0.12 0.010331 9 0.024297 20 0.069642 58 Children 3 5 years old 0.12 0.009143 8 0.026110 22 0.067773 56 Children 6 12 years old 0.12 0.006389 5 0.17107 14 0.045716 38 Youth 13 19 years old 0.12 0.004633 4 0.012879 11 0.028528 24 Females 13 49 years old 0.12 0.005356 4 0.011678 10 0.027279 23 7.2 Short term Aggregate Risk Aggregate short term risk estimates include the contribution of risk from chronic dietary sources ( food + water) and short term residential or recreational sources. Though estimated aggregate chronic ( long term) dietary risks are not of concern ( see Section 7.4), residential exposures, alone, pose potential risks of concern to children, specifically toddlers, from postapplication exposures to DMA. Aggregation with dietary exposures would increase these concerns and, therefore, for purposes of this assessment, dietary and residential exposures were not aggregated. Information on residential use patterns needs to be addressed for any further refinement of the assessment to occur.

HED combines risk values resulting from separate residential postapplication exposure scenarios when it is likely they can occur simultaneously based on the use pattern and the behavior associated with the exposed population. The tables below present a summary of the combined MOE estimates for cacodylic acid ( DMA), CAMA or DSMA/ MSMA, respectively.

The combined risk assessment for exposures to toddlers following home lawn applications was calculated:

Combined MOE = NOAEL/( ADDhand to mouth + ADDobject to mouth + ADDincidental soil ingestion + ADDdermal)

In the aggregate assessment for residential postapplication exposure and risk, there are risks of concern for DMA and CAMA, as they are currently used in a residential environment. Page 88 of 125 Table 7.2a: DMA Residential Scenarios for Combined Risk Estimates  Toddlers Margins of Exposure ( MOEs) ( UF= 30) Postapplication Exposure Scenario Short Term ( Non Dietary) Total Non Dietary Risk Turf Hand to Mouth 4 Object to Mouth 15 Turf ( 7.72 lb ai/ acre)

Incidental Soil Ingestion 1,100 3 Hand to Mouth 4 Object to Mouth 16 Toddler Turf ( 7.3 lb ai/ acre)

Incidental Soil Ingestion 1,200 3 Table 7.2b: CAMA Residential Scenarios for Combined Risk Estimates  Toddlers Margins of Exposure ( MOEs) ( UF= 100) Postapplication Exposure Scenario Short Term ( Non Dietary) Total Non Dietary Risk Turf Hand to Mouth 110 Object to Mouth 430 Turf ( 4.4 lb ai/ acre)

Incidental Soil Ingestion 32,000 85 Hand to Mouth 130 Object to Mouth 510 Turf ( 3.7 lb ai/ acre)

Incidental Soil Ingestion 38,000 101 Hand to Mouth 210 Object to Mouth 850 Toddler Turf ( 2.2 lb ai/ acre)

Incidental Soil Ingestion 64,000 170 Page 89 of 125 Table 7.2c: DSMA Residential Scenarios for Combined Risk Estimates  Toddlers Margins of Exposure ( MOEs) ( UF= 100) Postapplication Exposure Scenario Short Term ( Non Dietary) Total Non Dietary Risk Turf Hand to Mouth 190 Object to Mouth 750 Toddler Turf ( 2.5 lb ai/ acre)

Incidental Soil Ingestion 56,000 149 Table 7.2d: MSMA Residential Scenarios for Combined Risk Estimates  Toddlers Margins of Exposure ( MOEs) ( UF= 100) Postapplication Exposure Scenario Short Term Oral ( Non Dietary) Total Non Dietary Risk Turf Hand to Mouth 140 Object to Mouth 550 Toddler Turf ( 3.4 lb ai/ acre)

Incidental Soil Ingestion 41,000 110 7.3 Intermediate term Aggregate Risk All residential/ recreational exposures are expected to be short term in duration.

7.4 Long term Aggregate Risk Long term ( noncancer) aggregate risk estimates include the contribution of risk from chronic dietary sources ( food + water) and residential sources. However, based on the labeled uses, no long term or chronic residential exposures are expected. Chronic risk estimates from exposures to food alone, associated with the use of DMA and MMA, do not exceed HED's level of concern for any exposed population, based on conservative estimates of exposure that include the Total Diet Study and translations to other commodities, as well as EDWCs resulting from turf uses. As in the acute aggregate assessment, surface water EDWCs were calculated by EFED to estimate the potential contribution to the chronic exposure from drinking water, and the EDWCs were combined with chronic food exposures to estimate potential long term aggregate risks from the uses of DMA and MMA. The drinking water estimate used in this analysis was the 1 in 10 year average. Page 90 of 125 Table 7.4a: Results of the Aggregate Chronic Dietary Exposure Analysis for MMA Using DEEM FCID Population Subgroup cPAD ( mg/ kg/ day) Exposure ( mg/ kg/ day) % cPAD General U. S. Population 0.03 0.003493 12 All Infants (< 1 year old) 0.03 0.009456 32 Children 1 2 years old 0.03 0.005835 19 Children 3 5 years old 0.03 0.005331 18 Children 6 12 years old 0.03 0.003587 12 Youth 13 19 years old 0.03 0.002552 9 Females 13 49 years old 0.03 0.003103 10 Table 7.4b: Results of the Aggregate Chronic Dietary Exposure Analysis for DMA Using DEEM FCID Population Subgroup cPAD ( mg/ kg/ day) Exposure ( mg/ kg/ day) % cPAD General U. S. Population 0.014 0.001764 13 All Infants (< 1 year old) 0.014 0.003790 27 Children 1 2 years old 0.014 0.003268 23 Children 3 5 years old 0.014 0.002928 21 Children 6 12 years old 0.014 0.001930 14 Youth 13 19 years old 0.014 0.001303 9 Females 13 49 years old 0.014 0.001496 11 7.5 Aggregate Cancer Risk MMA was classified as " no evidence for carcinogenicity," based on the lack of evidence of carcinogenicity in rats and mice and DMA was classified as " not carcinogenic up to doses resulting in regenerative proliferation;" therefore, a cancer dietary analysis was not performed.

7.6 Aggregate Risk Summary OPP is confident that the dietary ( food + water) risk estimates do not underestimate the potential dietary exposures. Since there are no reliable methods to predict what species of arsenic may be present at any point in time, and the toxicities and target organs of the different species are dissimilar, estimated risks may, at the same time, both under estimate and over estimate the potential risks from any one species of arsenic. Page 91 of 125 Residential exposures, alone, pose potential risks of concern to toddlers from residential postapplication exposures to DMA and CAMA. Aggregation with dietary exposures would increase these concerns.

7.7 " Total Arsenic" and Exposure to Inorganic Arsenic The Federal Government and most states have established limits and/ or screening levels for " total arsenic" ( unspeciated) exposure from a variety of sources; drinking water, air, and soil. Typically in monitoring programs, arsenic is measured and reported as total arsenic, regardless of what species ( DMA, MMA, iAs), or mixture of species, may be present, or what the source is of the arsenic. These limits or screening levels are established based on risks ( cancer) from exposure to iAs. As mentioned previously, the differing species ( DMA, MMA, iAs) of arsenic have dissimilar toxicities and target organs; iAs being the most toxic. An extensive review of the literature, have shown that exposure to iAs can occur from the registered uses of the organic arsenicals and background residues, given time and under environmental conditions that favor the transformation to iAs. In some media ( food, water, soil) and in some parts of the United States, the likelihood of exposure to iAs is higher than in others. Under FQPA, the Agency is required to consider all potential sources of exposure to the organic arsenicals, and their metabolites and/ or transformation products. Since the limits and/ or screening levels are established for total arsenic ( all species included) and there is potential for transformation and exposure to iAs from the registered uses of the organic arsenicals, an analysis for potential risks from exposure to iAs was performed, which included a comparison of estimated exposures from registered uses to existing regulatory limits or screening levels.

7.7.1 Dietary Since the dominant species of arsenic found in soil is iAs, conversion from applied MMA and DMA to iAs is expected, and it is unclear if plants would methylate iAs or just pick it up from the soil, HED must also consider the possible dietary exposure to iAs resulting from the herbicidal uses. HED has not performed a conventional dietary assessment to iAs, but has determined what percentage of the estimated dietary exposure would need to be to iAs to reach our level of concern.

For exposure to the registered food commodity only, cottonseed ( field trial data resulting from the max application of DSMA/ MSMA and cacodylic acid to cotton grown in non arsenic containing soil), > 100% of the exposure would need to be from iAs before HED's level of concern was reached ( 1x10 6); however, for exposure to cottonseed and cotton water, a maximum of ~ 0.20% of the exposure could be from iAs before HED's level of concern was reached, and for exposure to cottonseed and turf water, a maximum of ~ 0.03% of the exposure could be from iAs before the level of concern was reached. For exposure to the registered uses and meat, ~ 0.26% of the exposure would need to be from iAs before HED's level of concern was reached. Though it is unlikely that all of the exposure is to organic arsenic or iAs, this analysis demonstrates that only a small amount of the total exposure needs to be from iAs to reach HED's level of concern. Page 92 of 125 Table 7.7.1: Cancer Dietary Exposure Estimates from the Cotton Use for the Organic Arsenical Pesticides Using DEEM FCID with the iAs Q* of 3.67 Cotton only Cotton + Cotton Water Cotton + Turf Water Cotton and Meat only Population Subgroup % Exposure from iAs Cancer Risk % Exposure from iAs Cancer Risk % Exposure from iAs Cancer Risk % Exposure from iAs Cancer Risk > 100% 1.0E 04 ~ 11% for MMA1 ~ 18% for DMA2 1.0E 04 ~ 1% for MMA1 ~ 2% for DMA2 1.0E 04 ~ 24% 1.0E 04 U. S. Population > 100% 1.0E 06 ~ 0.11% for MMA1 ~ 0.18% for DMA2 1.0E 06 ~ 0.01% for MMA1 ~ 0.02% for DMA2 1.0E 06 ~ 0.24% 1.0E 06 1. The percent of exposure for MMA is calculated as follows: MMA exp/ iAs exp needed to reach target x 100. 2. The percent of exposure for DMA is calculated as follows: DMA exp/ iAs exp needed to reach target x 100.

7.7.2 Drinking Water All species of concern in this assessment ( MMA, DMA, and iAs) have distinct toxicities ( see Section 4.0) therefore, EFED estimated exposure to each individually ( see Table 6.2.1). Compounds resulting from degradation are considered as well as the directly applied herbicides. It is impossible to determine the exact concentration of each species that will be present at any one time. Each species will reach its highest level at different times, and it is concentrations from these worst case situations which EFED reported. It is not expected that the maximum concentrations for each compound would all be present at the same time. EDWCs were also reported as total arsenic, therefore, to indicate the maximum amount of arsenic that may be in surface water as a sum of all species present. Total arsenic levels were estimated as a direct molar conversion of the EDWC predicted for the applied organic arsenical( s), and this value also represents the maximum amount of iAs that may reach surface water. This calculation of maximum iAs as a direct molar conversion of the parent compound's aquatic concentration does not necessarily represent the actual physical process   iAs is likely formed through degradation in the soil, rather than after reaching surface water. The concentrations listed in Table 6.2.1 provide a conservative estimate of the amount of iAs that may reach surface water.

The Agency's Office of Water has established a Maximum Concentration Level ( MCL) for total arsenic of 10 ppb ( 66 FR 6976 January 22, 2001) based on iAs toxicity and current technologies ( http:// www. epa. gov/ safewater/ arsenic/ mcl. html). As is shown in Table 6.2.1, estimates of exposure to iAs alone may possibly exceed the MCL. Since the MCL was established for total arsenic, exposures to any of the arsenic species in water are potentially subject to regulation.

7.7.3 Residential Postapplication Exposure The active ingredients DMA, CAMA, DSMA, and MSMA are all organic species of arsenic. Since arsenic is an element, it is not subject to biological or chemical degradation in the environment. CAMA, DSMA, and MSMA are salts of MMA and quickly covert to MMA when mixed in water before application. Following application, under certain conditions, MMA converts to DMA and/ or to iAs. Similarly, following application, under certain conditions, DMA converts to iAs. Data available to date indicate that MMA and DMA are stable in the environment when they remain on the outside of the treated foliage of plants. They transform to other species in the environment only when inside a plant or in the soil, suggesting microbial or Page 93 of 125 enzymatic involvement. Therefore, for the purposes of HED's assessment of occupational and residential postapplication exposures and risks, the dermal and incidental oral exposures to foliar surfaces are conducted using the form that was applied ( i. e., MMA when CAMA, DSMA, or MSMA was applied or DMA when DMA was applied). Postapplication inhalation exposures are not a concern due to the low vapor pressure of the organic and inorganic forms and the infinite dilution in outdoor environments.

HED must consider the possible in soil conversion of MMA to DMA or to iAs and the possible conversion of DMA to iAs to accurately assess risks from postapplication dermal exposures to the soil ( i. e., in harvesting/ transplanting sod or lawn renovation) and from postapplication incidental oral exposures to toddlers ingesting soil. Several factors appear to influence the conversion of organic arsenic to the inorganic form in soil, including soil organic matter, soil moisture, soil temperature and the concentration and species of the arsenic in the soil.

HED generally assumes a degradation curve where the pesticide residues degrade over time to nontoxic byproducts when assessing postapplication exposure and risk. However, with the organic arsenical herbicides, the degradates, when formed, may be more toxic than the initial residue ( i. e., iAs is more toxic than DMA and DMA is more toxic dermally and orally than MMA). Also, pesticide residues typically degrade over time to nondetectable levels. However, arsenic in its inorganic form does not degrade and evidence indicates that it may build up in soil over time as applications are repeated.

For postapplication dermal exposures and incidental ingestion of soil, HED is concerned both about the build up of arsenicals in the soil ( of any species) and the possible degradation in soil to more toxic forms. At this time, HED has no data to estimate either the percent of conversion from one form of arsenic to another ( i. e., from a less toxic to more toxic form) or the amount of time necessary for the conversion to take place. Consequently, it is not possible at this time to perform a quantitative risk assessment from soil treated repeatedly with organic arsenical herbicides. HED notes that incidental ingestion of soil by toddlers results in risks not of concern when assessed for exposures following a single application of either MMA or DMA. Even assuming that all residues from four applications per year ( maximum allowed) converted to iAs in the soil were 100% bioavailable from the soil   both very conservative assumptions   the risks would not be a concern when compared to dermal and incidental oral endpoints established for iAs by EPA/ OPP's Antimicrobial Division ( Chen 2001). However, the potential risks to toddlers incidentally ingesting soil from an area that had been treated with compounds that transformed to iAs for several years might be a concern, depending on the amount of arsenic that remained onsite ( versus runoff or leaching) and the degree of conversion to the more toxic iAs that had occurred. Likewise, the risks to adults dermally exposed while performing tasks involving high contact with the soil, such as turf transplanting or harvesting, would not be a concern assuming established soil adherence factors for dermal exposures, and that all residues from four applications per year ( maximum allowed) converted to iAs in the soil and were 100 percent bioavailable from the soil. However, the risks to adults contacting soil from an area that had been treated with compounds that transformed to iAs for several years might be a concern, depending on the amount of arsenic that remained on site ( versus runoff or leaching) and the degree of conversion to the more toxic iAs that has occurred. Page 94 of 125 HED has also attempted to estimate arsenic levels in soil and then compare these values to the Office of Solid Waste and Emergency Response's ( OSWER) arsenic soil screening levels ( SSLs). SSLs are not national clean up standards and SSLs alone do not define " unacceptable" levels of contaminants in soil. Screening refers to the process of identifying and defining areas, contaminants, and conditions, at a particular site that do not require further Federal attention. Generally, at sites where contaminant concentrations fall below SSLs, no further action or study is warranted under the Comprehensive Environmental Response, Compensation, and Liability Act ( CERCLA), commonly known as " Superfund." When contaminant concentrations equal or exceed SSLs, further study or investigation, but not necessarily clean up, is warranted. Detailed information on SSLs is available at: http:// www. epa. gov/ superfund/ resources/ soil.

The SSL for total arsenic ( unspeciated) is 0.4 ppm. State cleanup levels for total arsenic vary by state and site from 0.1 ppm to 200 ppm depending on land use ( i. e., residential, industrial, agricultural, recreational), background level, and other factors. The arsenic SSL is based on a value that corresponds to a 10 6 excess risk level using the iAs cancer slope factor. This " target" hazard quotient is used to calculate the 0.4 ppm total arsenic soil screening level, below which, it is unlikely that sensitive populations will experience adverse health effects resulting from exposure to total arsenic.

In order to estimate arsenic levels in soil, HED assumed that all residues from an application of either MMA or DMA converted to iAs and were 100% bioavailable from the soil ( both very conservative assumptions). In all cases, after one application, the arsenic levels in soil exceeded the 0.4 ppm SSL for total arsenic. HED believes the possibility of exceeding the arsenic SSL would increase with the number of arsenic applications as arsenic in its inorganic form does not degrade and evidence indicates that it may build up in soil overtime as applications are repeated. More detailed information regarding arsenic degradation, mobility, and soil buildup can be found in Moore 2006.

8.0 Cumulative Risk Characterization/ Assessment The Food Quality Protection Act ( 1996) stipulates that when determining the safety of a pesticide chemical, EPA shall base its assessment of the risk posed by the chemical on, among other things, available information concerning the cumulative effects to human health that may result from dietary, residential, or other non occupational exposure to other substances that have a common mechanism of toxicity. The reason for consideration of other substances is due to the possibility that low level exposures to multiple chemical substances that cause a common toxic effect by a common mechanism could lead to the same adverse health effect as would a higher level of exposure to any of the other substances individually. A person exposed to a pesticide at a level that is considered safe may in fact experience harm if that person is also exposed to other substances that cause a common toxic effect by a mechanism common with that of the subject pesticide, even if the individual exposure levels to the other substances are also considered safe.

Guidance for conducting cumulative risk assessments on substances that have a common mechanism of toxicity is available from the OPP website ( http:// www. epa. gov/ pesticides). In the guidance, it is stated that a cumulative risk assessment of substances that cause a common toxic effect by a common mechanism will not be conducted until an aggregate exposure assessment of Page 95 of 125 each substance has been completed. Before undertaking a cumulative risk assessment, HED will follow procedures for identifying chemicals that have a common mechanism of toxicity as set forth in the " Guidance for Identifying Pesticide Chemicals and Other Substances that Have a Common Mechanism of Toxicity" ( 64 FR 5795 5796, February 5, 1999).

HED did not perform a cumulative risk assessment as part of this risk assessment for organic arsenics because HED has not yet initiated a review to determine if MMA, or DMA, have a common mechanism of toxicity in humans with any other chemical substances.

In vivo and in vitro toxicity studies indicate that the various arsenical compounds ( MMA, DMA, and iAs) have distinct toxicological profiles. Though the arsenical compounds may transform to each other under certain conditions, they have distinct PK and PD differences that are observed following direct oral exposure. Therefore, they neither have a common mechanism of toxicity with each other, nor is it currently apparent that any of them have a common mechanism of toxicity with other chemical substances.

9.0 Occupational Exposure/ Risk Pathway DMA ( cacodylic acid or dimethylarsenic acid) is a cotton defoliant and is also an herbicide used in agricultural, commercial, and residential settings for the postemergent control of annual grasses and broadleaf weeds. It is registered as a liquid concentrate, a pressurized liquid, and a ready to use solution; and is applied using: aircraft, groundboom sprayer, rights of way sprayer, handgun sprayer, low pressure handwand sprayer, and sprinkling can.

CAMA is an organic arsenical herbicide registered for postemergent weed control on lawns and turf grass. CAMA is formulated as a liquid concentrate and a ready to use solution. CAMA is applied by commercial applicators using a low pressure handwand sprayer or handgun sprayer. It is applied by homeowner applicators using a low pressure handwand sprayer, hose end sprayer, and ready to use " trigger pump" sprayer.

MSMA and DSMA are organic arsenical herbicides registered for weed control on cotton, under trees, vines and shrubs, and for lawn care. MSMA technical is formulated as a liquid concentrate, a ready to use liquid, and a dry flowable. DSMA is formulated as a liquid concentrate, and a wettable powder. MSMA and DSMA are applied by aircraft, groundboom, rights of way sprayer, turf handgun sprayer, low pressure handwand sprayer, and sprinkler can.

At this time, products containing DMA, CAMA or MSMA/ DSMA are intended for both occupational and homeowner uses. DMA is an organic arsenical cotton defoliant and herbicide registered for weed control under non bearing citrus trees, around buildings, and sidewalks and for lawn renovation. CAMA is an organic arsenical herbicide registered for postemergent weed control on lawns. Both MSMA and DSMA are organic arsenical herbicides registered for weed control on cotton, for turf grass and lawns, and under trees, vines, and shrubs.

The MAA ( Methanearsonic Acid) Task Force consists of the primary registrants for DMA, CAMA, DSMA, and MSMA, which are Luxembourg Pamol, Inc., Zeneca Agricultural Products/ GP Biosciences, Drexel/ APC Holdings, and Albaugh Inc. This Task Force provided a Page 96 of 125 Master Label review that contains maximum application rates and use parameters for each active ingredient. This assessment examines exposures using the maximum application rates obtained from the Master Label ( ML).

DMA is formulated as a liquid concentrate ( 0.6 to 4.9 percent active ingredient), a pressurized liquid ( 0.21 percent active ingredient), and a ready to use solution ( 0.09 to 0.39 percent active ingredient). CAMA is formulated as a liquid concentrate ( 8.4 10.3% active ingredient) and a ready to use solution ( 0.5 percent active ingredient). DSMA is formulated as a liquid concentrate ( 12.5 36.9%), and a wettable powder ( 63 81%). MSMA technical is formulated as a liquid concentrate ( 7.2 58.2%), a ready to use liquid ( 0.4 2.5%) and a dry flowable ( 2.3 55%).

9.1 Short/ Intermediate term Occupational Handler Exposure and Risk HED uses the term " handlers" to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to applications and that exposures can vary depending on the specifics of each task. Job requirements ( e. g., amount of chemical to be used in an application), the kinds of equipment used, the target being treated, and the level of protection used by a handler can cause exposure levels to differ in a manner specific to each application event.

9.1.1 Inputs/ Assumptions into Handler Exposure/ Risk Estimates HED uses exposure scenarios to describe the various types of handler exposures that may occur for a specific active ingredient. The use of scenarios as a basis for exposure assessment is very common as described in the U. S. EPA Guidelines for Exposure Assessment ( U. S. EPA; Federal Register Volume 57, Number 104; May 29, 1992). Information from the current labels, use and usage information, toxicology data, and exposure data were all key components in the development of the exposure scenarios. HED has developed a series of general descriptions for tasks that are associated with pesticide applications. Tasks associated with occupational pesticide handlers are categorized using one of the following terms:

  Mixers and/ or Loaders: these individuals perform tasks in preparation for an application. For example, prior to application, mixer/ loaders would mix the chemical and load it into the holding tank of the airplane or groundboom.

  Applicators: these individuals operate application equipment during the release of a pesticide product into the environment. These individuals can make applications using equipment such as airplanes or groundboom.

  Mixer/ Loader/ Applicators and or Loader/ Applicators: these individuals are involved in the entire pesticide application process ( i. e., they do all job functions related to a pesticide application event). These individuals would transfer the chemical into the application equipment and then also apply it.

  Flaggers: these individuals provide ground support to aerial applicators by indicating where the swath ends and the next one should begin. Page 97 of 125 A chemical can produce different effects based on how long a person is exposed, how frequently exposures occur, and the level of exposure. HED classifies exposures up to 30 days as shortterm and exposures greater than 30 days up to several months as intermediate term. HED completes both short and intermediate term assessments for occupational scenarios in essentially all cases, because these kinds of exposures are likely and acceptable use/ usage data are not available to justify deleting intermediate term scenarios. Based on use data and label instructions, HED believes that occupational MMA and DMA exposures may occur over a single day or up to weeks at a time for many use patterns and that intermittent exposures over several weeks also may occur. Some applicators may apply MMA ( CAMA, MSMA, and/ or DSMA) or DMA over a period of weeks, because they are custom or commercial applicators who are completing a number of applications for a number of different clients. Long term handler exposures are not expected to occur for MMA and DMA.

Other parameters are also defined from use and usage data such as application rates and application frequency. HED always completes non cancer risk assessments using maximum application rates for each in order to ensure there are no concerns for each specific use. Occupational handler exposure estimates were based on surrogate data from: ( 1) the Pesticide Handlers Exposure Database ( PHED) and ( 2) the Outdoor Residential Exposure Task Force ( ORETF). Generic protection factors ( PFs) were used to calculate exposures when data were not available. For example, an 80 percent protection factor was assumed for the use of a respirator equipped with a dust/ mist filter.

Occupational handler exposure assessments are completed by HED using different levels of risk mitigation. Typically, HED uses a tiered approach. The lowest tier is designated as the baseline exposure scenario ( i. e., long sleeve shirt, long pants, shoes, socks, and no respirator). If risks are of concern at baseline attire, then increasing levels of personal protective equipment or PPE ( e. g., gloves, double layer body protection, and respirators) are evaluated. If risks remain a concern with maximum PPE, then engineering controls ( e. g., enclosed cabs or cockpits, water soluble packaging, and closed mixing/ loading systems) are evaluated. This approach is used to ensure that the lowest level of risk mitigation that provides adequate protection is selected, since the addition of PPE and engineering controls involves an additional expense to the user and   in the case of PPE   also involves an additional burden to the user due to decreased comfort and dexterity and increased heat stress and respiratory stress.

It has been determined that exposure to pesticide handlers is likely during the occupational use of MMA or DMA on agricultural crops, non crop areas and on turf grass. The anticipated use patterns and current labeling indicate occupational exposure scenarios based on the types of equipment and techniques that can potentially be used for MMA or DMA applications. Risk values are presented for each route of exposure ( i. e., dermal or inhalation) in each scenario, because risk mitigation measures are specific to the route of exposure. A total MOE was not calculated for MMA or DMA because the dermal and inhalation toxicological endpoints of concern are based on different adverse effects. The following tables present the risk estimates for short and intermediate term dermal and inhalation exposures at baseline, with additional personal protective equipment ( PPE), and with engineering controls, for DMA, CAMA and MSMA/ DSMA, respectively. Page 99 of 125 Table 9.1a: Occupational Handler Short and Intermediate term Dermal and Inhalation Exposure and Risks to DMA MOEs Baseline PPE Engineering Controls Exposure Scenario Crop or Target Application Rate ( lb ai/ A) Area Treated Daily ( acres) Dermal Inhalation Dermal

single layer w/ gloves Dermal

double layer w/ gloves Inhalation

80% Respirator Dermal Inhalation Mixer/ Loader Cotton ( defoliation) 0.8 1200 7.5 270 950 1300 1300 2500 3800 Mixing/ Loading Liquid Concentrates for Aerial Applications ( 1a) Cotton ( preconditioning for defoliation) 0.3 1200 20 710 2500 3400 3500 6800 10000 Cotton ( defoliation) 0.8 200 45 1600 5700 7700 8000 15000 23000 Cotton ( preconditioning for defoliation) 0.3 200 120 4300 15000 21000 21000 41000 62000 Non crop 7.3 100 9.9 350 1300 1700 1800 3300 5100 Mixing/ Loading Liquids Concentrates for Groundboom Applications ( 1b) Non bearing citrus orchards 4.96 80 18 640 2300 3100 3200 6200 9300 Lawn edging 7.72 100 9.4 330 1200 1600 1700 3200 4800 Mixing/ Loading Liquid Concentrates to Support LCO Handgun Applications ( mixing/ loading supports 20 LCOs) ( 1c) Lawn renovation 7.3 100 9.9 350 1300 1700 1800 3300 5100 Page 100 of 125 Table 9.1a: Occupational Handler Short and Intermediate term Dermal and Inhalation Exposure and Risks to DMA MOEs Baseline PPE Engineering Controls Exposure Scenario Crop or Target Application Rate ( lb ai/ A) Area Treated Daily ( acres) Dermal Inhalation Dermal

single layer w/ gloves Dermal

double layer w/ gloves Inhalation

80% Respirator Dermal Inhalation Mixing/ Loading Liquid Concentrates to Support Rights of Way ( 1d) Non crop 7.3 80 12 440 1600 2100 2200 4200 6300 Applicator Cotton ( defoliation) 0.8 1200 No Data No Data No Data No Data No Data 4400 4700 Applying Sprays via Aerial Equipment ( 2) Cotton ( preconditioning for defoliation) 0.3 1200 No Data No Data No Data No Data No Data 12000 13000 Cotton ( defoliation) 0.8 200 9400 2600 9400 12000 13000 26000 45000 Cotton ( preconditioning for defoliation) 0.3 200 25000 6900 25000 32000 35000 70000 120000 Non crop 7.3 100 2100 570 2100 2600 2800 5800 9800 Applying Sprays via Groundboom Equipment ( 3) Non bearing citrus orchards 4.96 80 3800 1000 3800 4800 5200 11000 18000 Lawn edging 7.72 80 No Data 350 100 180 1800 No Data No Data Applying Sprays via Handgun Equipment ( 4) Lawn renovation 7.3 80 No Data 380 110 190 1900 No Data No Data Page 101 of 125 Table 9.1a: Occupational Handler Short and Intermediate term Dermal and Inhalation Exposure and Risks to DMA MOEs Baseline PPE Engineering Controls Exposure Scenario Crop or Target Application Rate ( lb ai/ A) Area Treated Daily ( acres) Dermal Inhalation Dermal

single layer w/ gloves Dermal

double layer w/ gloves Inhalation

80% Respirator Dermal Inhalation Applying Sprays via Rights of Way Equipment ( 5) Non crop 7.3 80 28 130 92 120 670 No Data No Data Flagger Cotton ( defoliation) 0.8 350 6800 3100 No Data 7500 16000 340000 160000 Flagging for Aerial Sprays Applications ( 6) Cotton ( preconditio ning for defoliation) 0.3 350 18000 8300 No Data 20000 42000 910000 420000 Mixer/ Loader/ Applicator Non bearing citrus orchards 4.96 5 56 4600 2600 No Data 23000 NF NF Lawn edging 7.72 5 36 2900 1600 No Data 15000 NF NF Lawn renovation 7.3 5 38 3100 1700 No Data 16000 NF NF Mixing/ Loading/

Applying Liquid Concentrates with Low Pressure Handwand ( ORETF) ( 7) Non crop 7.3 5 38 3100 1700 No Data 16000 NF NF Page 102 of 125 Table 9.1a: Occupational Handler Short and Intermediate term Dermal and Inhalation Exposure and Risks to DMA MOEs Baseline PPE Engineering Controls Exposure Scenario Crop or Target Application Rate ( lb ai/ A) Area Treated Daily ( acres) Dermal Inhalation Dermal

single layer w/ gloves Dermal

double layer w/ gloves Inhalation

80% Respirator Dermal Inhalation Non bearing citrus orchards 4.96 5 No Data 6900 1900 3500 34000 NF NF Lawn edging 7.72 5 No Data 4400 1200 2200 22000 NF NF Lawn renovation 7.3 5 No Data 4700 1300 2300 23000 NF NF Mixing/ Loading/

Applying Liquid Concentrates with a Handgun Sprayer ( LCO ORETF data) ( 8) Non crop 7.3 5 No Data 4700 1300 2300 23000 NF NF Applying Ready to Use Formulations via Trigger Pump Sprayer ( ORETF) ( 9) Non crop 0.00017 1000 3000 96000 70000 No Data 480000 NF NF Lawn edging 0.00018 1000 11000 100000 No Data No Data 510000 NF NF Mixing/ Loading/

Applying Liquids with a Watering Can ( using ORETF residential hoseend data) ( 10) Lawn renovation 0.00017 1000 11000 110000 No Data No Data 540000 NF NF Page 103 of 125 Table 9.1b: Occupational Handler Short and Intermediate term Dermal and Inhalation Exposure and Risks to CAMA MOEs Baseline PPE Engineering Controls Exposure Scenario Crop or Target App Rate of CAMA ( lb ai/ acre) App Rate of MMA ( lb ai/ acre) Area Treated Daily ( acres) Dermal Inh Dermal

single layer w/ gloves Dermal

double layer w/ gloves Inhalation