UNITED STATES ENVIRONMENTAL PROTECTION AGENCY OFFICE OF PREVENTION, PESTICIDES, AND TOXIC SUBSTANCES WASHINGTON, D. C. 20460 MEMORANDUM DATE: July 20, 2004 SUBJECT: 2,4 DB and 2,4 DB DMA Human Health Risk Assessment PC Codes: 030801 ( 2,4 DB) and 030819 ( 2,4 DB DMA) DP Barcode: D290486 TO: Mika Hunter, Chemical Review Manager Special Review Branch Special Review and Reregistration Division ( 7508C)

FROM: Kit Farwell, D. V. M. Reregistration Branch 1 Health Effects Division ( 7509C)

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

This document is the Health Effects Division risk assessment for the reregistration of 2,4 DB [ 4( 2,4 dichlorophenoxy) butyric acid] and 2,4 DB DMA ( 2,4 DB dimethylamine salt). This assessment was revised in response to error only comments from the 2,4 DB Task Force.

Toxicologist: Kit Farwell, D. V. M Dietary Exposure: Felecia Fort Occupational Exposure: Timothy Dole, C. I. H. Chemistry: Danette Drew Water Exposure: Amer Al Mudallal Usage Data: Alan Halvorson Risk Assessor: Kit Farwell, D. V. M. TABLE OF CONTENTS 1.0 EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2.0 PHYSICAL/ CHEMICAL PROPERTIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 3.0 HAZARD CHARACTERIZATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 3.1 Hazard Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 3.2 FQPA Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 3.3 Dose Response Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3.4 Endocrine Disruption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 4.0 EXPOSURE ASSESSMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 4.1 Summary of Registered Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 4.2 Dietary Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 4.2.1 Residue Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 4.2.2 Acute and Chronic Dietary Exposure and Risk . . . . . . . . . . . . . . . . . . . . 13 4.3 Water Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 4.4 Residential Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 4.5 Aggregate Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 4.5.1 Acute Aggregate Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 4.5.2 Chronic Aggregate Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 4.6 Occupational Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 4.6.1 Handler Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 4.6.2 Postapplication Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 4.6.3 Incident Report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 5.0 CUMULATIVE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 6.0 DATA NEEDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 7.0 TOXICITY TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Table 22. Acute Toxicity of 2,4 DB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Table 23. Acute Toxicity of 2,4 DB DMA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Table 24. Toxicology Profile of 2,4 DB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Table 25. Toxicology Profile of 2,4 DB DMA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 8.0 BIBLIOGRAPHY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 1 1.0 EXECUTIVE SUMMARY Uses: 2,4 DB is a plant growth regulator and herbicide registered for use on alfalfa, clover, peanuts, soybean, peppermint, spearmint, and trefoil. It is manufactured as the acid and the dimethylamine salt; no other salt or ester products are currently registered. End use products are formulated either as soluble, emulsifiable, or flowable concentrates. 2,4 DB can be applied either as a broadcast application early season, or a directed spray late season. Ground or aerial applications may be made. Maximum label application rates for food/ feed crops range from 0.25 lb ae ( acid equivalents)/ A to 1.5 lb ae/ A. Total annual domestic usage of 2,4 DB is approximately 326 thousand pounds active ingredient. There are no current residential uses.

Because of similarities in metabolism and degradation in animals, plants, and the environment, 2,4 DB and 2,4 DB DMA were considered equivalent in this risk assessment. An exception is that 2,4 DB DMA is a severe eye irritant, whereas 2,4 DB is not a severe eye irritant.

Hazard: Liver toxicity, which occurred in all the subchronic and chronic toxicity studies, included increased liver weights, changes in clinical chemistry, gross changes visible at necropsy, and microscopic changes. Kidney toxicity in dog and rat studies included changes in kidney weights, changes in clinical chemistry, and microscopic changes. Decreased hematological parameters occurred in dogs and rats. No systemic toxicity was noted in dermal studies, although dermal irritation occurred with 2,4 DB DMA. No neurotoxicity was attributed to treatment. The cancer classification is " not likely to be a human carcinogen".

FQPA Assessment: Developmental toxicity in rats occurred at doses two fold higher than the doses which caused maternal toxicity, and included decreased fetal body weight, skeletal variations and malformations, early resorptions, microphthalmia, and retroesophageal aortic arches. No developmental toxicity occurred in rabbits. Offspring toxicity in the 2 generation reproduction study included mortality, decreased mean litter weight, and increased incidence of necropsy findings; parental toxicity occurred at the same dose; there was no effect upon reproductive parameters. There were no residual uncertainties for pre and/ or postnatal toxicity and no special FQPA Safety Factor was applied ( i. e. 1X).

Dose Response: An acute dietary endpoint was selected for females 13 50 years of age based on developmental abnormalities in rats; no acute effects were applicable to any other subpopulations. Chronic and long term endpoints were based on decreased body weight gain and food consumption in female rats. Short term incidental oral and inhalation endpoints were based on decreased body weight and related changes in rats. A short term dermal endpoint was not selected because no systemic toxicity occurred in the subchronic dermal toxicity study. Intermediate term endpoints were based on decreased body weight gain, organ weight changes, and microscopic changes in rats.

Tolerances: Tolerances for residues of 2,4 DB in plant commodities are currently expressed as Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 2 the combined residues of 2,4 DB and its metabolite, 2,4 D, which is also a registered active ingredient. Current tolerance levels are set at 0.2 ppm in alfalfa; clover; mint, hay; peanut; trefoil, birdsfoot; soybean; and soybean, hay. No tolerances in livestock commodities or food/ feed processed commodities have been established.

The reassessed tolerances for plants are: alfalfa, forage ( 0.70 ppm); alfalfa, hay ( 2.0 ppm); clover, forage and clover, hay ( insufficient data available); peppermint, tops and spearmint, tops ( 0.20 ppm); soybean, seed ( 0.50 ppm), soybean, forage ( 0.70 ppm), soybean, hay ( 2.0 ppm); peanut ( 0.05 ppm); trefoil, forage ( 0.70 ppm) and trefoil, hay ( 2.0 ppm). Sufficient data are available to determine that residues of 2,4 DB do not significantly concentrate in any peanut, soybean or mint processed food/ feed item; thus, tolerances are not required for the processed commodities of these crops.

For livestock, the appropriate tolerance for 2,4 DB is 0.05 ppm ( LOQ) in the meat byproducts of cattle, goats, hogs, horses, and sheep. There is no reasonable expectation of the transfer of residues of 2,4 DB from feedstuffs to milk, livestock meat or fat, poultry tissues or eggs; therefore, these commodities should be classified as Category 3 under 40 CFR 180.6( a) and tolerances for residues of 2,4 DB in milk, poultry tissues and eggs, and meat and fat of cattle, goats, hogs, horses, and sheep are not required.

The HED Metabolism Committee concluded that the residue to be regulated in plants and in meat, milk, poultry and eggs is 2,4 DB per se, and that 2,4 D need not be included in the tolerance expression because the 2,4 D metabolite was present at only low levels.

Dietary Risk: An unrefined acute dietary risk assessment ( tolerance level and 100% crop treated) was conducted for all supported 2,4 DB food uses. Dietary risk estimates are provided for females 13 to 49 years old, the population subgroup of concern. The results using the DEEM FCID and Lifeline models showed risk estimates of < 1% of the aPAD regardless of the model used and were therefore not of concern. This assessment was based on conservative residue estimates and could be further refined, however, based on the results of the assessment, further refinements are not warranted.

Tolerance level residues and 100% CT information were also used to determine the chronic dietary risk. This assessment concludes that for all included commodities, the chronic risk estimates are below the Agency's level of concern for the general U. S. population (< 1% of the cPAD) and all population subgroups (

2.2% cpad) when using the DEEM FCID or Lifeline models. The most highly exposed population subgroup was also All Infants (< 1 years old).

Residential Risk: There are no residential uses for 2,4 DB. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 3 Drinking Water: 2,4 DB was classified as very mobile to moderately mobile in mineral soils. The half life of 2,4 DB in terrestrial field dissipation studies was 2 to 6.7 days. Although 2,4 DB has been detected in ground and surface water, there were not enough detections for the results to be used in risk assessment. Because the monitoring data could not be used, EFED calculated estimated environmental concentrations ( EECs) using PRZM/ EXAMS and SCI GROW modeling software.

Aggregate Risk: Aggregate exposure included food and water exposure only because there are no residential uses for 2,4 DB. The EECs were much less than calculated drinking water levels of comparison ( DWLOCs) and there were no concerns for aggregate exposure to 2,4 DB in food and drinking water.

Occupational Risk: MOEs for occupational exposures were calculated for short term inhalation exposures and intermediate term combined dermal and inhalation exposures; quantification of short term dermal exposure was not required because no systemic toxicity developed in 21 day dermal toxicity studies. All of the MOEs for short term inhalation exceeded the target of 100 with baseline respiratory protection ( i. e. no respirators worn) and are not of concern. All of the intermediate term MOEs exceeded the target MOE with single layer PPE for mixer/ loaders and baseline PPE for applicators. However, intermediate term handler exposures are unlikely to occur because 2,4 DB is applied only once or twice per season.

Many of the labels require waterproof gloves instead of chemical resistant gloves. It is not known if these gloves provide adequate protection. It is recommended that mixers and loaders wear chemical resistant gloves made of waterproof material when handling 2,4 DB. The amine salt form of 2,4 DB is a severe eye irritant and eye protection is recommended.

Post Application Exposure: All of the MOEs are above 100 on Day 0 which indicates that the risks are not of concern. The post application risk estimates are highly conservative because they are based upon intermediate term exposure, which is less likely to occur because 2,4 DB is applied only once or twice per season. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 4 O Cl Cl O OH O Cl Cl O O

NH2( CH3) 2 + 2.0 PHYSICAL/ CHEMICAL PROPERTIES As shown by the structures below, 2,4 DB is an acid and 2,4 DB DMA is the dimethyl amine salt of the acid.

Table 1. Physical Properties 2,4 DB Acid 2,4 DB DMA Empirical Formula C10H10Cl2O3 C12H17Cl2NO3 Molecular Weight 249.1 293.9 CAS Registry No. 94 82 6 2758 42 1 PC Code 030801 030819 Color off white Light orange/ brown Physical State flakes/ powder Viscous liquid Melting Point 113.5 117.5

C

Water Solubility 46 ppm Miscible Vapor Pressure 7x10 7 mm Hg

Log KOW 3 4

Table 2. Chemical Structures.

2,4 DB 2,4 DB DMA Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 5 3.0 HAZARD CHARACTERIZATION 3.1 Hazard Profile 2,4 DB is manufactured as an acid and the dimethylamine salt, 2,4 DB DMA. The data showed that 2,4 DB DMA dissociates to 2,4 DB in rats, after which they shared the same metabolic pathway. Urine was the major route of excretion; 2,4 D and conjugated dichlorophenol were the major metabolites for both chemicals. Most toxicity studies were conducted with 2,4 DB; studies with 2,4 DB DMA included subchronic feeding in rats, developmental toxicity in rats, dermal toxicity in rabbits, mutagenicity, and metabolism. The toxicity and LOAELs of 2,4 DB and 2,4 DB DMA were similar in the studies which were conducted with both chemicals. For the above reasons, the same endpoints were selected for both 2,4 DB and 2,4 DB DMA and the database was adequate for establishing toxicity endpoints for risk assessment.

A minor difference in toxicity between the acid and DMA salt was that 2,4 DB DMA was more irritating than 2,4 DB. 2,4 DB DMA caused inflamed lacrimal glands and gastric mucosal irritation in the subchronic rat feeding study, dermal irritation in the subchronic dermal toxicity study, and eye irritation in the acute eye irritation study; these effects were not noted with 2,4 DB.

Some form of liver toxicity was noted in all the subchronic and chronic toxicity studies with 2,4 DB and in the subchronic rat study with 2,4 DB DMA. Liver weights were increased in subchronic rat studies with 2,4 DB and 2,4 DB DMA, the subchronic dog study, and the mouse carcinogenicity study. Liver enzymes ( ALT, AST, and/ or alkaline phosphatase) were elevated in the subchronic and chronic dog studies with 2,4 DB and in the subchronic rat study with 2,4 DBDMA Hepatocyte hypertrophy was noted in the subchronic rat study with 2,4 DB. In the subchronic dog study with 2,4 DB, BSP retention was increased, and icterus and pale livers were noted.

Kidney toxicity was noted in several studies. Kidney weights were increased in the subchronic dog study and decreased in the subchronic and chronic rat studies with 2,4 DB. Kidney infarcts were noted in the chronic rat study. Kidney tubular degeneration was noted in the subchronic rat study with 2,4 DB DMA. BUN was increased in the subchronic and chronic dog studies with 2,4 DB.

Other toxicity included decreased hematological parameters in the chronic rat study and the subchronic and chronic dog studies with 2,4 DB and in the subchronic rat study with 2,4 DBDMA Heart weights were decreased in the subchronic and chronic rat studies and increased in the mouse carcinogenicity study with 2,4 DB. Light foci in the heart were also noted in the mouse carcinogenicity study. Inflamed lacrimal glands were noted in the subchronic rat study with 2,4 DB DMA. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 6 No systemic toxicity was noted in 21 day dermal studies in rabbits with either 2,4 DB or 2,4 DBDMA although local dermal irritation occurred in the dermal study with 2,4 DB DMA.

Although neurotoxicity has been noted with other phenoxy herbicides, clinical signs suggestive of neurotoxicity with 2,4 DB and 2,4 DB DMA only occurred at lethal doses, and were considered agonal in nature.

Decreased fetal body weight, increased incidence of skeletal variations/ malformations, early resorptions, microphthalmia, and retroesophageal aortic arches occurred in developmental rat toxicity studies with 2,4 DB and/ or 2,4 DB DMA. Maternal mortality occurred at the same dose as did the developmental toxicity. No developmental toxicity occurred in the developmental study in rabbits.

Offspring toxicity in the 2 generation reproduction study with 2,4 DB included mortality, decreased mean litter weight, and increased incidence of necropsy findings ( small thymus, distended bladder with bloody/ dark urine and ocular opacity); parental effects at the same dose included decreased food consumption and body weight, increased food conversion ratio, increased water consumption, organ weight changes, and macroscopic renal findings ( kidney pallor and cortical scarring). There was no effect upon reproductive parameters.

Toxicity endpoints were selected from rat studies, rather than dog studies, because of differences in elimination of phenoxyacetic compounds in dogs compared to other mammalian species. The dog is more sensitive to toxicity from 2,4 DB than is the rat, as is the case for 2,4 D and MCPA. Pharmacokinetic data on dogs are not available for 2,4 DB. However, compounds closely related structurally to 2,4 DB, including 2,4 D, triclopyr, MCPA, and other organic acids have been shown to have a decreased clearance in dogs relative to humans and rats. Consequently, effects are seen at lower dose levels in the dog than in other species. The difference in the elimination pattern between dogs and humans makes the rat more relevant to humans than the dog. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 7 3.2 FQPA Considerations There are acceptable developmental toxicity studies in rats with 2,4 DB and 2,4 DB DMA and an acceptable developmental study in rabbits and a 2 generation reproduction study in rats with 2,4 DB. The HIARC concluded that the toxicology database for 2,4 DB and 2,4 DB DMA was complete for evaluation of residual concerns under FQPA.

Determination of Susceptibility: There was no indication of prenatal susceptibility in the developmental rat studies with 2,4 DB and 2,4 DB DMA; with both chemicals, developmental effects occurred at doses two fold higher than the doses that caused maternal toxicity. There was no prenatal susceptibility in the rabbit developmental toxicity study with 2,4 DB because no developmental toxicity occurred.

There was qualitative, but not quantitative susceptibility in the 2 generation reproduction study with 2,4 DB because offspring mortality occurred at a dose where parental toxicity was less severe. The parental NOAEL was 30 mg/ kg/ day and the parental LOAEL was 133 mg/ kg/ day based on decreased food consumption and body weight, increased food conversion ratio, increased water consumption, organ weight changes, and macroscopic renal findings ( kidney pallor and cortical scarring). The offspring NOAEL was 30 mg/ kg/ day and the offspring LOAEL was 133 mg/ kg/ day based on mortality, decreased mean litter weight, and increased incidence of necropsy findings ( small thymus, distended bladder with bloody/ dark urine and ocular opacity). There was no effect upon reproductive parameters.

Degree of Concern Analysis and Residual Uncertainties: Since there was evidence of increased susceptibility of offspring following exposure to 2,4 DB in the reproduction study, a Degree of Concern Analysis was performed to: 1) determine the level of concern for the effects observed when considered in the context of all available toxicity data; and 2) identify any residual uncertainties after establishing toxicity endpoints and traditional uncertainty factors to be used in the risk assessment for this chemical.

It was concluded that there was low concern for the qualitative susceptibility because: the offspring toxicity was well characterized and was accompanied by maternal toxicity; there was a clear NOAEL/ LOAEL for offspring toxicity; and the dose/ endpoint selected for long term risk assessments ( NOAEL = 3mg/ kg/ day based on decreased body weight gain/ food consumption at 30 mg/ kg/ day) was considerably lower and would address the concerns for offspring toxicity seen in this study. Therefore, there were no residual uncertainties for pre and/ or postnatal toxicity.

Special FQPA Safety Factors: Based upon the above analysis, the Hazard Identification Assessment Review Committee ( HIARC) determined that no special FQPA Safety Factor was needed ( i. e. 1X) since there were no residual uncertainties for pre and/ or postnatal toxicity. The Special FQPA Safety Factor recommended by the HIARC assumes that the exposure databases ( dietary food, drinking water, and residential) are complete and that the risk assessment for each Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 8 potential exposure scenario includes all metabolites and/ or degradates of concern and does not underestimate the potential risk for infants and children.

3.3 Dose Response Assessment Table 3. Toxicological Endpoints for 2,4 DB ( Dietary)

Exposure Scenario Dose for Risk Assessment and Uncertainty Factor Special FQPA Safety Factor and Level of Concern Study and Toxicological Effects Acute Dietary ( Females 13 50 years of age) NOAEL = 62.5 mg/ kg/ day UF = 100 Acute RfD = 0.6 mg/ kg/ day FQPA SF = 1X aPAD = acute RfD FQPA SF = 0.6 mg/ kg/ day Rat developmental toxicity. LOAEL = 125 mg/ kg/ day based on skeletal variations/ malformations, microphthalmia, post implantation loss Acute Dietary ( General population including infants and children) None N/ A No appropriate endpoint attributable to a single dose from oral toxicity studies.

Chronic Dietary ( All populations) NOAEL= 3 mg/ kg/ day UF = 100 Chronic RfD = 0.03 mg/ kg/ day FQPA SF = 1X cPAD = chronic RfD FQPA SF = 0.03 mg/ kg/ day Chronic/ carcinogenicity study in rats. LOAEL = 30 mg/ kg/ day based on decreased body weight gain and food consumption in females.

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 Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 9 Table 4. Toxicological Endpoints for 2,4 DB ( Non dietary)

Exposure Scenario Dose for Risk Assessment and Uncertainty Factor Special FQPA Safety Factor and Level of Concern Study and Toxicological Effects Short Term Dermal ( 1 to 30 days) None N/ A Quantitation not required. No systemic toxicity via the dermal route and there are no developmental concerns.

Intermediate Term Dermal ( 1 to 6 months) Oral NOAEL = 15.8 mg/ kg/ day Residential LOC for MOE = 100 Occupational = 100 Subchronic rat toxicity ( 2,4 DB study) LOAEL = 50 mg/ kg/ day based on decreased body weight gain, increased relative liver/ kidney weight, and microscopic changes Long Term Dermal (> 6 months) Oral NOAEL = 3 mg/ kg/ day ( dermal absorption = 23%) Residential LOC for MOE = 100 Occupational LOC for MOE = 100 Chronic/ carcinogenicity study in rats. LOAEL = 30 mg/ kg/ day based on decreased body weight gain and food consumption in females.

Short Term Inhalation ( 1 to 30 days) Oral NOAEL = 31 mg/ kg/ day ( inhalation absorption = 100%) Residential LOC for MOE = 100 Occupational LOC for MOE = 100 Rat developmental toxicity. LOAEL = 62.5 mg/ kg/ day based on decreased maternal body weight, body weight gain, and food consumption, and clinical signs ( emaciation, few feces)

Intermediate Term Inhalation ( 1 to 6 months) Oral NOAEL = 15.8 mg/ kg/ day ( inhalation absorption = 100%) Residential LOC for MOE = 100 Occupational LOC for MOE = 100 Subchronic rat toxicity ( 2,4 DB study). LOAEL = 50 mg/ kg/ day based on decreased body weight gain, increased relative liver/ kidney weight, and microscopic changes Long Term Inhalation (> 6 months) Oral NOAEL = 3 mg/ kg/ day ( inhalation absorption = 100%) Residential LOC for MOE = 100 Occupational LOC for MOE = 100 Chronic/ carcinogenicity study in rats. LOAEL = 30 mg/ kg/ day based on decreased body weight gain and food consumption in females.

Cancer None N/ A Classified " not likely to be a human carcinogen".

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 Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 10 3.4 Endocrine Disruption EPA is required under the Federal Food Drug and Cosmetic Act ( 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 the recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee ( EDSTAC), EPA determined that there were scientific bases for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA authority to require the wildlife evaluations. As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program ( EDSP).

When the appropriate screening and/ or testing protocols being considered under the Agency's EDSP have been developed, 2,4 DB and 2,4 DB DMA may be subjected to additional screening and/ or testing to better characterize effects related to endocrine disruption. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 11 4.0 EXPOSURE ASSESSMENT 4.1 Summary of Registered Uses 2,4 DB is a plant growth regulator and herbicide registered for use on alfalfa, clover, peanuts, soybean, peppermint, spearmint, and trefoil. It is manufactured as the acid and the dimethylamine salt; no other salt or ester products are currently registered. End use products are formulated either as soluble, emulsifiable, or flowable concentrates. 2,4 DB can be applied either as a broadcast application early season, or a directed spray late season. Ground or aerial applications may be made. Maximum label application rates for food/ feed crops range from 0.25 lb ae ( acid equivalents)/ A to 1.5 lb ae/ A ( alfalfa). Total annual domestic usage of 2,4 DB is approximately 326 thousand pounds active ingredient, based upon pesticide use surveys for 1992 2000. There are no current residential uses.

4.2 Dietary Exposure Tolerances for residues of 2,4 DB in plant commodities are currently expressed as the combined residues of the herbicide 4( 2,4 dichlorophenoxy) butyric acid and its metabolite, 2,4 D ( 2,4 dichlorophenoxyacetic acid), which is also a registered active ingredient. Current tolerance levels are set at 0.2 ppm ( based on negligible residues) in alfalfa; clover; mint, hay; peanut; trefoil, birdsfoot; soybean; and soybean, hay. No tolerances in livestock commodities or food/ feed processed commodities have been established.

The reassessed tolerances for plants are listed as follows: alfalfa, forage ( 0.70 ppm); alfalfa, hay ( 2.0 ppm); clover, forage and clover, hay ( insufficient data available); peppermint, tops and spearmint, tops ( 0.20 ppm); soybean, seed ( 0.50 ppm), soybean, forage ( 0.70 ppm), soybean, hay ( 2.0 ppm); peanut ( 0.05 ppm); trefoil, forage ( 0.70 ppm) and trefoil, hay ( 2.0 ppm). For livestock, the appropriate tolerance for 2,4 DB is 0.05 ppm ( LOQ) in the meat byproducts of cattle, goats, hogs, horses, and sheep. There is no reasonable expectation of the transfer of residues of 2,4 DB from feedstuffs to milk, livestock meat or fat, poultry tissues or eggs; therefore, these commodities should be classified as Category 3 under 40 CFR 180.6( a) and tolerances for residues of 2,4 DB in milk, poultry tissues and eggs, and meat and fat of cattle, goats, hogs, horses, and sheep are not required.

4.2.1 Residue Profile Nature of the Residue Plants: The qualitative nature of the 2,4 DB residue in plant commodities is adequately understood based on acceptable metabolism studies in alfalfa, peanuts and soybeans. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 12 2,4 DB is metabolized in several ways including side chain degradation [ to form 2,4 dichlorophenoxyacetic acid ( 2,4 D) and related products], ring hydroxylation, position shift of the chlorine atoms on the ring, and dechlorination. Incorporation of radioactivity into sugar, protein, and other natural constituents also resulted from metabolism of the ring labeled compound. 1,4 benzoquinone is a major metabolite in soybean hay, pods, and vines. However, the parent is the primary residue found in most crop matrices.

The HED Metabolism Committee ( D. Miller, 1/ 29/ 96) concluded that the residue to be regulated in plants is 2,4 DB per se, and that 2,4 D need not be included in the tolerance expression. This is because 2,4 DB parent was the major compound in plant matrices, and the 2,4 D metabolite was present at only low levels. 1,4 benzoquinone was to be excluded from the tolerance expression because it is significant only in certain animal feeds, and other residues were excluded because they each comprise only a small portion of the total residue. If additional crops with direct human consumption are registered, additional metabolism studies may be required.

Residues of 2,4 DB are not expected to be taken up in rotational crops based on confined studies. Therefore, field studies and tolerances in rotational crops are not required and dietary exposure to 2,4 DB in rotational crops is not expected to occur.

Plant metabolism studies for 2,4 DB utilized the acid form ( 030801). The Agency granted a waiver ( 5/ 11/ 94 Greybeard Committee memorandum) for metabolism studies for the DMA salt concluding that studies for the acid will characterize metabolism for both the salt and the acid.

Nature of the Residue  Livestock The qualitative nature of the residue in ruminants and poultry is adequately understood based on adequate studies in dairy cows and laying hens. In the hen study, the highest radioactivity was found in eggs, fat, and liver. Most of the residue was identified as the unchanged parent compound. In dairy cows, the highest radioactivity was found in milk, liver, and kidney; residues in muscle and fat were very low. Metabolites included the glycine conjugate of 2,4 DB, 2,4 DB per se, and 2,4 dichlorophenol.

Based on these data, the HED Metabolism Committee ( D. Miller, 11/ 14/ 95 and 1/ 29/ 96) concluded that the residue to be regulated in meat, milk, poultry and eggs is 2,4 DB per se, and that 2,4 D need not be included in the tolerance expression. This is because 2,4 DB parent was the major compound in many of the animal matrices, and the 2,4 D metabolite was present at only low levels. Other metabolites were excluded due to either lower potential for toxicity or relatively insignificant residue levels.

Livestock metabolism studies for 2,4 DB utilized the parent compound ( acid, 030801). The Agency granted a waiver ( 5/ 11/ 94 Greybeard Committee memorandum) for metabolism studies for the DMA salt concluding that studies for the acid will suffice to characterize metabolism for both the salt and the acid. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 13 4.2.2 Acute and Chronic Dietary Exposure and Risk Introduction: Dietary risk assessment incorporates both exposure and toxicity of a given pesticide. The risk is expressed as a percentage of a maximum acceptable dose ( i. e., the dose which HED has concluded will result in no unreasonable adverse health effects). This dose is referred to as the population adjusted dose ( PAD). The PAD is equivalent to the Reference Dose ( RfD) divided by the special FQPA Safety Factor. HED is concerned when estimated dietary risk exceeds 100% of the PAD.

Exposure: The magnitude of the residue data for processed commodities of food/ feed crops that are from presently registered use sites have been evaluated and deemed adequate. Residues of 2,4 DB do not significantly concentrate upon processing. Based on the submitted studies, a processing factor of 0.72x was used for peanut oil in the dietary assessment and a 1x processing factor was used for mint oil and soybean oil.

Several peer reviewed programs have recently been emerging for modeling dietary exposure to pesticides. For technical and historical reasons, DEEM   was the preferred program for EPA through 2003. Lifeline   , which is capable of performing a probabilistic aggregate assessment ( food, water, and residential exposure), is currently being evaluated by EPA. This evaluation includes the comparison of dietary exposure estimates for a given chemical using both DEEM   and Lifeline   . The following paragraphs are summaries of each program.

2,4 DB acute and chronic dietary exposure assessments were conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database ( DEEMFCID   , Version 1.30), which incorporates consumption data from USDA's Continuing Surveys of Food Intakes by Individuals ( CSFII), 1994 1996 and 1998. The 1994 96, 98 data are based on the reported consumption of more than 20,000 individuals over two non consecutive survey days. Foods " as consumed" ( e. g., apple pie) are linked to EPA defined food commodities ( e. g. apples, peeled fruit  cooked; fresh or N/ S; baked; or wheat flour  cooked; fresh or N/ S, baked) using publicly available recipe translation files developed jointly by USDA/ ARS and EPA. For chronic exposure assessment, consumption data are averaged for the entire U. S. population and within population subgroups, but for acute exposure assessment are retained as individual consumption For chronic dietary exposure assessment, an estimate of the residue level in each food or foodform ( e. g., orange or orange juice) on the food commodity residue list is multiplied by the average daily consumption estimate for that food/ food form. The resulting residue consumption estimate for each food/ food form is summed with the residue consumption estimates for all other food/ food forms on the commodity residue list to arrive at the total average estimated exposure. Exposure is expressed in mg/ kg body weight/ day and as a percent of the cPAD. This procedure is performed for each population subgroup.

For acute exposure assessments, individual one day food consumption data are used on an Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 14 individual by individual basis. The reported consumption amounts of each food item can be multiplied by a residue point estimate and summed to obtain a total daily pesticide exposure for a deterministic exposure assessment, or " matched" in multiple random pairings with residue values and then summed in a probabilistic assessment. The resulting distribution of exposures is expressed as a percentage of the aPAD on both a user ( i. e., those who reported eating relevant commodities/ food forms) and a per capita ( i. e., those who reported eating the relevant commodities as well as those who did not) basis. In accordance with HED policy, per capita exposure and risk are reported for all tiers of analysis. However, for tiers 1 and 2, significant differences in user vs. per capita exposure and risk are identified and noted in the risk assessment.

Acute and chronic dietary exposure estimates were also conducted using the Lifeline   model ( Version 2.0). These Lifeline   assessments were also conducted using the same consumption data as the DEEM FCID   ( CSFII, 1994 1996 and 1998 consumption data with FCID). Lifeline   uses the recipe file to relate RACs to foods " as eaten." Lifeline   converts the RAC residues into food residues by randomly selecting a RAC residue value from the " user defined" residue distribution ( created from the residue, percent crop treated, and processing factors data), and calculating a net residue for that food based on the ingredient's mass contribution to that food item. For example, ` apple pie' will have a residue distribution based on the residues provided for apples ( adjusted by the appropriate processing factors and percent crop treated), as well as the residues for each of the other ingredients in the apple pie recipe for which there may be tolerances. Lifeline   calculates dietary exposure from ` apple pie' based on the amount eaten, and the residue drawn from the ` apple pie' residue distribution for that eating occasion.

Lifeline   models the individual's dietary exposures over a season by selecting a new CSFII diary each day from a set of similar individuals based on age, season and socioeconomic attributes Lifeline   groups CSFII diaries based on the respondent's age and the season during which the food diary was recorded.

An unrefined ( tolerance level and 100% crop treated) dietary risk assessment was conducted for all supported 2,4 DB food uses for both acute and chronic dietary risk. There was high confidence in the residue chemistry database and the required studies are considered confirmatory data. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 15 Acute Dietary Risk: Dietary risk estimates are provided for females 13 to 49 years old, the population subgroup of concern. The results using the DEEM FCID and Lifeline models showed risk estimates at the 95th percentile of exposure to be < 1% of the aPAD regardless of the model used and were therefore not of concern.

This assessment was based on conservative residue estimates ( tolerance level and 100% crop treated). The dietary risk estimate could be further refined with the incorporation of anticipated residues, percent crop treated data, and cooking/ processing factors. Based on the results of the assessment, further refinements are not warranted.

Table 5. Acute Dietary Exposure and Risk Population Subgroup Acute Dietary ( 95th Percentile)

DEEM FCID Lifeline Dietary Exposure ( mg/ kg/ day) % aPAD Dietary Exposure ( mg/ kg/ day) % aPAD Females 13 49 years old 0.000467 0.08 0.000614 0.102 Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 16 Chronic dietary risk: The chronic risk estimates are below the Agency's level of concern for the general U. S. population (< 1% of the cPAD) and all population subgroups (

2.2% cPAD). The most highly exposed population subgroup was All Infants (< 1 years old). Similar results were found using the Lifeline Model, with < 1% of the cPAD occupied for the U. S. population.

This assessment was based on conservative residue estimates ( tolerance level and 100% crop treated). The dietary risk estimate could be further refined with the incorporation of anticipated residues, percent crop treated data, and cooking/ processing factors. Based on the results of the assessment, further refinements are not warranted.

Table 6. Chronic Dietary Exposure and Risk Population Subgroup* Chronic Dietary DEEM FCID Lifeline Dietary Exposure ( mg/ kg/ day) % cPAD Dietary Exposure ( mg/ kg/ day) % cPAD General U. S. Population 0.000242 0.8 0.000232 0.8 All Infants (< 1 year old) 0.000661 2.2 0.000554 1.8 Children 1 2 years old 0.000548 1.8 0.000539 1.8 Children 3 5 years old 0.000535 1.8 0.000505 1.7 Children 6 12 years old 0.000373 1.2 0.000346 1.2 Youth 13 19 years old 0.000238 0.8 0.000224 0.7 Adults 20 49 years old 0.000197 0.7 0.000198 0.7 Adults 50+ years old 0.000153 0.5 0.000191 0.6 Females 13 49 years old 0.000185 0.6 0.000228 0.8 * * The values for the highest exposed population for each type of risk assessment are bolded. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 17 4.3 Water Exposure Environmental Fate: Because 2,4 DB DMA rapidly dissociates in water to form 2,4 DB, EFED used ecotoxicity data for 2,4 DB as bridging data for 2,4 DB DMA.

The mobility of 2,4 DB in mineral soils was classified as very mobile to moderately mobile. The half life of 2,4 DB in terrestrial field dissipation studies was 2 to 6.7 days. The primary route of dissipation was by transformation, major transformation products being 2,4 dichlorophenoxyacetic acid ( 2,4 D acid, 5.0 15 % of the applied) and 2,4 D Phenol ( 5.0 27.3 % of the applied). 2,4 D acid has been identified as a degradate of 2,4 DB in an aerobic soil metabolism study.

Monitoring Data: There were monitoring data for 2,4 DB from the United States Geological Survey ( USGS) National Water Quality Assessment ( NAWQA) Program, USEPA STOrage and RETrieval System for Water and Biological Monitoring Data ( STORET), and from the USGS Pilot Reservoir Monitoring Study. Frequency of detections were not sufficient to calculate time weighted means.

The highest annual maximum concentration of 2,4 DB detected in surface water monitoring data was 0.83  g/ L from the NAWQA data at Reed Wash near Mack, Colorado with the next highest being 0.81  g/ L from the STORET data at Big Limestone Creek near Limestone, Tennessee. 2,4 DB was reported once in the NAWQA ground water data at a concentration of 0.06  g/ L and was not detected in the STORET data.

Modeling: Modeling of surface water concentrations of 2,4 DB was performed by PRZM/ EXAMS using alfalfa, peanuts, and soybean applications. Several scenarios for each crop were chosen to represent a geographically dispersed range of surface water concentrations in areas representative of where 2,4 DB is used. EFED recommended using 318.68  g/ L for the 1 in 10 year peak concentration ( acute) and 72.40  g/ L for the 1 in 10 year annual daily average concentration ( chronic non cancer). These estimated concentrations were from the Texas alfalfa IR/ PCA scenario.

The SCI GROW model estimated the concentration of 2,4 DB in drinking water from shallow ground water sources to be 0.51  g/ L. This concentration can be used for both acute and chronic exposure.

No degradation products of 2,4 DB were included in this assessment. The major degradate of 2,4 DB is 2,4 D, which was a maximum of 5.0 15 % of applied 2,4 DB in soil dissipitation studies. The annual use of 2,4 DB is less than 1% of the annual use of 2,4 D ( 326,000 pounds vs 46 million pounds). According to data from the US Geographical Survey reported in the EFED water memo, 2,4 D is used in virtually the entire country, whereas 2,4 DB use is restricted to discrete areas of the country, which overlap areas of 2,4 D use. Since 2,4 DB Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 18 accounts for a small percentage of 2,4 D water exposure, both in terms of usage and environmental transformation, water exposure to 2,4 D will be addressed in the 2,4 D RED. For more information on 2,4 D water exposure, see the EFED water memo for 2,4 D ( D286666) and the HED risk assessment for 2,4 D ( D287199).

4.4 Residential Exposure There are no residential uses for 2,4 DB.

4.5 Aggregate Exposure Aggregate exposure to a pesticide combines exposure from food, drinking water, and residential sources of exposure. Since there are no residential uses for 2,4 DB, aggregate assessments included exposure via food and drinking water.

Drinking water levels of comparison ( DWLOCs) were calculated because the monitoring data for 2,4 DB did not have enough detects to calculate means. The DWLOC is the concentration in drinking water as a part of the aggregate acute exposure that occupies no more than 100% of the PAD. In other words, the DWLOC for 2,4 DB is the maximum potential concentration that may be present in drinking water without exceeding a level of concern when exposure from food and water were considered together.

As shown below, the concentrations of 2,4 DB estimated in water were less than the DWLOCs and there were no concerns for acute or chronic aggregate exposure.

4.5.1 Acute Aggregate Risk Assessment An acute DWLOC was calculated only for females 13 49 years of age because this was the only population subgroup for which an endpoint was selected. As shown below, the DWLOC was 18,000 ug/ L and the EEC ( estimated environmental concentration) was 0.51 ug/ L for ground water and 318 ug/ L for surface water, thus there were no concerns for acute aggregate exposure.

Table 7. DWLOCs for Acute Exposure to 2,4 DB Population Subgroup Acute PAD mg/ kg/ day Food Exposure mg/ kg/ day Target Max Water Exposure mg/ kg/ day Ground Water EEC  g/ L Surface Water EEC  g/ L DWLOC  g/ L Females 13 49 0.6 mg/ kg 0.000467 0.600 0.51 318.68 18,000 Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 19 4.5.2 Chronic Aggregate Risk Assessment The most highly exposed population subgroup was all infants < 1 year old. As shown below, the DWLOC for this subgroup was 290 ug/ L and the EEC for ground water was 0.51 ug/ L for ground water and was 72 ug/ L for surface water, thus there were no concerns for chronic aggregate exposure for any population subgroup.

Table 8. DWLOCs for Chronic Exposure Population Subgroup Chronic PAD mg/ kg/ day Food Exposure mg/ kg/ day Target Max Water Exposure mg/ kg/ day Ground Water EEC  g/ L Surface Water EEC  g/ L DWLOC  g/ L U. S. Population ( total) 0.03 0.000242 0.030 0.51 72.40 1050 All infants (< 1 year) 0.03 0.000661 0.029 0.51 72.40 290 Target Maximum Water Exposure = PAD  food exposure DWLOC = maximum water exposure ( mg/ kg/ day) x body weight ( kg) water consumption ( L/ day) x 10 3 mg/  g body weight = 70 kg for adult males, 60 kg for adult females, 10 kg for children and infants water consumption = 2 L/ day for adult males and females, 1 L/ day for children and infants Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 20 4.6 Occupational Exposure Ground or aerial applications may be made, however, labels do not allow chemigation. BEAD reports that only one application is typically made per season, although labels allow two applications per growing season. 2,4 DB can be applied either as a broadcast application early season, or a directed spray late season. Maximum label application rates for food/ feed crops range from 0.25 to 1.5 lb acid equivalents/ acre. For most crops, post emergent applications can be made well into the growing season. In peanuts, for example, applications can be made from 2 to 12 weeks after planting. 2,4 DB can be applied over the top to all the labeled crops, however, some of the crops such as soybeans can be damaged and require directed sprays when the higher rates are used. The pre harvest interval is 30 or 60 days for peanuts and 60 days for soybeans. The pre grazing interval for alfalfa and forage legumes is 30 and 60 days, respectively.

Chronic occupational exposures to 2,4 DB are not expected to occur. 2,4 DB is only applied once or twice during the growing season and rapidly dissipates from the foliage Application Rates: The label application rates are shown in Table 9 and are given in terms of acid equivalent ( ae) which is based upon the molecular weight of the acid excluding the amine salt. The average application rates from the 2,4 DB QUA report ( EPA BEAD 2001) are shown for comparison. The QUA data indicate that only one application is typically made per season.

Table 9. 2,4 DB Application Rates Crop or Site Acid Equivalent Application Rates Per Application ( lb ae/ acre)

Label Application Rate Average Rate1 Percent Crop Treated1 Alfalfa, Clover 1.5 0.55 0.2%

Mint 0.75 0.80 1.0%

Peanuts 0.25 to 0.40 0.24 38%

Soybeans 0.40 0.13 0.4%

1. Average rate and PCT from 2,4 DB QUA Report ( 10/ 31/ 01) which includes usage data from 1992 to 2000. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 21 The Phenoxy Herbicide NAPIAP report ( Burnside et. al. 1996) has some information regarding the use of 2,4 DB. Selected information that is relevant for 2,4 DB occupational exposure assessment is summarized in Table 10.

Table 10. 2,4 DB Use Information in the Phenoxy Herbicide NAPIAP Report Use Site NAPIAP Findings Alfalfa The only phenoxy used on alfalfa is 2,4 DB.

Peanuts 2,4 DB is an important tool in peanut production and was used on 83% of the total US acreage in 1992. It is the only phenoxy herbicide used on peanuts.

Soybeans There is little use of 2,4 DB prior to planting no till soybeans because there is little to no advantage over 2,4 D and it costs more. To broaden the spectrum of control, 2,4 DB has been added to some other post emergent herbicides. However, because of some risk of soybean injury, the use of 2,4 DB has declined as more selective herbicides have been introduced.

Application Methods : The 2,4 DB labels allow ground and aerial application, however, they do not allow chemigation. A listing of application methods and amounts of acreage treated per 8 hour day is included in Table 11.

Table 11. 2,4 DB Application Methods Application Method Typical Crops Treated Treated Areaa 1  Groundboom Alfalfa, Mint, Peanuts, Soybeans 200 2  Fixed Wing Aircraft Same as above 1200 a. Based upon HED ExpoSAC SOP # 9 " Standard Values for Daily Acres Treated in Agriculture", Revised July 5, 2000 Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 22 4.6.1 Handler Exposure The following assumptions and factors were used in order to complete the exposure and risk assessments for occupational handlers/ applicators:

 The average work day was 8 hours.

 The daily acreage treated was taken from EPA Science Advisory Council for Exposure Standard Operating Procedure # 9 " Standard Values for Daily Acres Treated in Agriculture," Revised July 5, 2000.

 The maximum label application rates were used to assess short term risks because it is possible that these rates could be used for one to thirty consecutive days.

 The average application rates were used to assess intermediate term risks because it is highly unlikely that maximum label rates would be used for more than thirty consecutive days.

 A body weight of 70 kg was assumed because the endpoint is not gender specific.

 The inhalation absorption rate is 100%.

 Baseline PPE includes long sleeve shirts, long pants and no gloves or respirator.\

 Single Layer PPE includes baseline PPE with chemical resistant gloves.

 Aerial applicators utilize closed cockpit aircraft and do not wear chemical resistant gloves.

Exposure Data Sources: Exposure analyses were performed using the Pesticide Handlers Exposure Database ( PHED) as tabulated in the PHED Surrogate Exposure Guide of August 1998. The unit exposure values calculated by PHED generally range from the geometric mean to the median of the selected data set. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 23 Risks: The target Margin of Exposure ( MOE) for occupational populations is 100, which includes the standard safety factors of 10X for intraspecies variability ( i. e. differences among humans) and 10X for interspecies variability ( differences between humans and animals).

The MOEs for occupational exposures were calculated for short term inhalation exposures and for intermediate term combined dermal and inhalation exposures and are summarized in Tables 12 and 13. All of the short term inhalation MOEs exceed 100 at baseline and respiratory protection is not needed. All of the intermediate term mixer/ loader combined MOEs exceed 100 if single layer PPE ( i. e. baseline clothing with chemical resistant gloves) is worn. The intermediate term MOEs for applicators exceed 100 with baseline PPE.

Occupational Handler Risk Characterization: Intermediate term handler exposures are less likely to occur because 2,4 DB is applied only once or twice per season. Metabolism studies in rats also indicated that most of the 2,4 DB dose is excreted within 24 hours through the urine and feces.

Many of the labels require waterproof gloves instead of chemical resistant gloves. It is not known if these gloves provide adequate protection. It is recommended that mixers and loaders wear chemical resistant gloves made of waterproof material when handling 2,4 DB.

The amine salt form of 2,4 DB is a severe eye irritant and eye protection is recommended. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 24 Table 12. 2,4 DB Short Term MOEs for Handlers Exposure Scenario Crop Label Application Rate ( lb ae/ acre) Acres/ Day Baseline Inhalation MOE Mix/ Load Liquids for Aerial Alfalfa, Clover Mint Peanuts ( SW), Soybeans Peanuts ( SE) 1.5 0.75 0.4 0.25 1200 1200 1200 1200 1,000 2,000 3,800 6,000 Mix/ Load Liquids for Groundboom Alfalfa, Clover, CRPA Mint Peanuts ( SW), Soybeans Peanuts ( SE) 1.5 0.75 0.4 0.25 200 200 200 200 6,000 12,000 23,000 36,000 Aerial Application Alfalfa, Clover Mint Peanuts ( SW), Soybeans Peanuts ( SE) 1.5 0.75 0.4 0.25 1200 1200 1200 1200 18,000 35,000 66,000 110,000 Groundboom Application Alfalfa, Clover, CRPA Mint Peanuts ( SW), Soybeans Peanuts ( SE) 1.5 0.75 0.4 0.25 200 200 200 200 9,800 20,000 37,000 59,000 Flag Aerial Application Alfalfa, Clover Mint Peanuts ( SW), Soybeans Peanuts ( SE) 1.5 0.75 0.4 0.25 1200 1200 1200 1200 3,400 6,900 13,000 21,000 Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 25 Table 13. 2,4 DB Intermediate Term MOEs for Handlers Exposure Scenario Crop Average Application Rate ( lb ae/ acre) Acres/ Day Baseline Combined Dermal/ Inhala tion MOE Single Layer Combined MOE Mix/ Load Liquids for Aerial Alfalfa, Clover Mint Peanuts Soybeans 0.55 0.75 0.24 0.13 1200 1200 1200 1200 2.5 1.8 5.7 11 260 190 590 1100 Mix/ Load Liquids for Groundboom Alfalfa, Clover Mint Peanuts Soybeans 0.55 0.75 0.24 0.13 200 200 200 200 15 11 34 64 1500 1100 3600 6600 Aerial Application Alfalfa, Clover Mint Peanuts Soybeans 0.55 0.75 0.24 0.13 1200 1200 1200 1200 1400 1000 3200 5800 NA NA NA NA Groundboom Application Alfalfa, Clover Mint Peanuts Soybeans 0.55 0.75 0.24 0.13 200 200 200 200 2500 1900 5800 11000 2500 1900 5800 11000 Flag Aerial Application Alfalfa, Clover Mint Peanuts Soybeans 0.55 0.75 0.24 0.13 1200 1200 1200 1200 580 430 1300 2500 540 400 1200 2300 Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 26 4.6.2 Postapplication Exposure Post application 2,4 DB exposures can occur in the agricultural environment when workers enter fields recently treated with 2,4 DB to conduct tasks such as scouting and irrigation. Postapplication exposure to re entry workers is possible because 2,4 DB can be applied over the top to most of the labeled crops.

Occupational Post Application Exposure Scenarios: Broadcast applications can be made to the labeled crops, which are tolerant of 2,4 DB. Because 2,4 DB is typically applied once or twice per season it is anticipated that 2,4 DB exposures would be primarily short term. Because there is no endpoint for short term dermal exposures, short term post application risks were not assessed. To address the limited possibility that intermediate exposures could occur, intermediate term risks were assessed using the intermediate term dermal endpoint. Potential inhalation exposures are not anticipated for the post application worker scenarios because of the low vapor pressure of 2,4 DB ( 7.1e 07 mm Hg at 23.6o C).

Assumptions and Transfer Coefficients for Post Application: There were no data submitted for 2,4 DB, therefore, standard values and assumptions were used as discussed below. The following assumptions were made regarding occupational post application:

 The average application rates were used because it is highly unlikely workers would be exposed to day zero residues for more than thirty consecutive days following the application of maximum label rates.

 The risks for alfalfa, peanuts and soybeans were assessed using average rates as reported in the QUA report. The risks for mint were assessed at the maximum label rate of 0.75 lb ai/ acre which is slightly less than the rate of 0.8 lb ai/ acre reported in the QUA report.

 The transfer coefficients as listed in Table 14 are from an interim transfer coefficient policy developed by HED's Science Advisory Council for Exposure using proprietary data from the Agricultural Re entry Task Force ( ARTF) database ( US EPA, August 7, 2001).

 The initial percent of application rate as Dislodgeable Foliar Residue ( DFR) was assumed to be 20% for all crops. This a standard value. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 27 Table 14. Post Application Exposure Scenarios and Transfer Coefficients for 2,4 DB Crop Transfer Coefficient Group Post Application Exposure Scenarios Transfer Coefficient ( cm2/ hr)

Alfalfa Field/ row crop, low/ medium Low Exposure Scenarios  Irrigation, scouting, immature plants Medium Exposure Scenarios  Scouting mature plants 100 1500 Mint Field/ row crop, low/ medium Low Exposure Scenarios  Scouting, immature plants Medium Exposure Scenarios  Scouting mature plants 100 1500 Peanuts, Soybeans Field/ row crop, low/ medium Low Exposure Scenarios  Scouting, immature plants Medium Exposure Scenarios  Scouting mature plants 100 1500 Calculation Methodology for Post Application Exposures: The calculations used to estimate the exposures for the post application scenarios are similar to those described previously for the handler/ applicator scenarios. Daily dermal exposure is calculated by multiplying the residue level ( ug/ cm2 of leaf area) times a transfer coefficient ( amount of leaf area contacted per unit time). The MOEs are then calculated using the intermediate term dermal NOAEL. It should be noted that MOEs were not calculated for short term exposures because there was no short term dermal endpoint.

Occupational Post Application Risk Estimates: A summary of the worker risks for intermediateterm post application exposures is given in Table 15. All of the MOEs are above 100 on Day 0 which indicates that the risks are not of concern.

Occupational Post Application Risk Characterization: The post application risk estimates are highly conservative because they are based upon an intermediate term endpoint. Intermediateterm exposures are unlikely to occur because 2,4 DB is applied only once or twice per season. Turf Transferable residue data for the other phenoxy herbicides such as 2,4 D and MCPA have indicated that the dissipation is fairly rapid.

Table 15. 2,4 DB Post Application Worker Risks Crop Transfer Coefficient Group Application Rate ( lb a. i./ acre) Intermediate term MOE on Day 0 Low Exposure Scenarios * Medium Exposure Scenarios* High Exposure Scenarios*

Alfalfa Field/ row crop, low/ medium 0.55 4900 325 NA Mint Field/ row crop, low/ medium 0.75 3600 240 NA Peanuts Field/ row crop, low/ medium 0.24 11000 740 NA Soybeans Field/ row crop, low/ medium 0.13 22000 1500 NA * Task descriptions for each crop and exposure scenario are included in Table 14. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 28 4.6.3 Incident Report The incident report is being prepared under a separate memo by Monica Spann, M. P. H. and Jerome Blondell, PhD. of the Office of Pesticide Programs. No incidents were reported in California.

5.0 CUMULATIVE Section 408( b)( 2)( D)( v) of the FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider " available information" concerning the cumulative effects of a particular pesticide's residues and " other substances that have a common mechanism of toxicity."

2,4 DB is a member of the alkylphenoxy herbicide class of pesticides. This class also includes MCPA, 2,4 D, and 2,4 DP. A cumulative risk assessment has not been performed as part of this human health risk assessment because the Agency has not yet made a determination as to which compounds humans may be exposed, if any, and whether or not these compounds have a common mechanism of toxicity. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 29 6.0 DATA NEEDS Toxicology Data Gap: A 28 day inhalation study is required because the use pattern indicates potential repeated exposure via this route. This study should be conducted with 2,4 DB DMA because of irritancy from this compound.

Residue Chemistry Deficiencies Labels for EPA Reg. No. 56077 26 ( now 66222 76) and EPA Reg No. 56077 52 ( now 66222 80) only prohibit the grazing of forage or feeding of hay within 60 days of the application of a tank mix with Lorax 50W application, and there is no indication of any restriction when 2,4 DB is applied alone. The restriction should be against feeding/ grazing soybean forage and harvesting hay for 60 days following any 2,4 DB application.

The submitted plant analytical methods are adequate for data collection but must be adequately validated for each study for which it is used. If any of the submitted analytical methods for plant commodities are proposed as a 2,4 DB tolerance enforcement method then the method should be modified to include determination of free and conjugated 2,4 DB. An ILV should be performed.

The submitted methods for livestock commodities are adequate for data collection. If the submitted method is proposed as the enforcement method for determining 2,4 DB in livestock commodities then an ILV of the method should be performed.

Additional field trials on clover forage and hay are required at the maximum label rate ( 1.3 lb ae/ A) with a 60 day PHI to reassess the 2,4 DB tolerances. Ten additional trials are recommended in the following regions: 1 ( Region1), 1 ( Region 2), 1 ( Region 4), 3 ( Region 5), 1 ( Region 6), 1 ( Region 7), 1 ( Region 8), 1 ( Region 9).

Analytical reference standards must be supplied as requested by the EPA National Pesticide Standards Repository for 2,4 DB.

Product Chemistry Deficiencies There are a number of product chemistry deficiencies for various registrants which are listed in the following tables 16 21. Registrants should also submit required data for dibenzo p dioxins and dibenzofurans, and either certify that the suppliers of beginning materials and the manufacturing process for the 2,4 DB products have not changed since the last comprehensive product chemistry review or submit a complete updated product chemistry data package. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 30 Table 16. Product Deficiency: Aceto Agricultural Chemicals Corp. 2,4 DB: 98% T ( EPA Reg. No. 2749 93)

Guideline Requirement 830.1550 Product identity and composition,

830.1600 Description of materials used to produce the product 830.1620 Description of production process 830.1670 Discussion of formation of impurities 830.1700 Preliminary analysis 830.1750 Certified limits 830.1800 Enforcement analytical method Table 17. Product Deficiency: Drexel Chemical Co. 2,4 DB: 98% T ( EPA Reg. No. 19713 124)

Guideline Requirement 830.1550 Product identity and composition 830.1600 Description of materials used to produce the product 830.1620 Description of production process 830.1670 Discussion of formation of impurities 830.1700 Preliminary analysis 830.1750 Certified limits 830.1800 Enforcement analytical method 830.6302 Color 830.6303 Physical state 830.6304 Odor 830.6313 Stability to normal and elevated temperatures, metals, and metal ions 830.6314 Oxidation/ reduction: chemical incompatibility 830.6316 Explodability 830.6317 Storage stability 830.6320 Corrosion characteristics 830.7000 pH Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 31 830.7050 UV/ visible absorption 830.7200 Melting point/ melting range 830.7300 Density/ relative density/ bulk density 830.7370 Dissociation constant 30.7550/ 7560/ 7570 Partition coefficient ( n octanol/ water)

830.7840/ 7860 Water solubility 830.7950 Vapor pressure Table 18. Product Deficiency: Atanor S. A.. 2,4 DB: 98% T ( EPA Reg. No. 46146 1)

Guideline Requirement 830.6316 Explodability 830.6317 Storage stability 830.6320 Corrosion characteristics Table 19. Product Deficiency: Makhteshim Agan of North America Inc 2,4 DB: 97% T ( EPA Reg. No. 66222 78)

Guideline Requirement 830.1550 Product identity and composition 830.1600 Description of materials used to produce the product 830.1620 Description of production process 830.1670 Discussion of formation of impurities 830.1700 Preliminary analysis 830.1750 Certified limits 830.1800 Enforcement analytical method 830.6302 Color 830.6303 Physical state 830.6304 Odor 830.6313 Stability to normal and elevated temperatures, metals, and metal ions 830.6314 Oxidation/ reduction: chemical incompatibility Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 32 830.6316 Explodability 830.6317 Storage stability 830.6320 Corrosion characteristics 830.7000 pH 830.7050 UV/ visible absorption 830.7200 Melting point/ melting range 830.7300 Density/ relative density/ bulk density 830.7370 Dissociation constant 830.7550/ 7560/ 7570 Partition coefficient ( n octanol/ water)

830.7840/ 7860 Water solubility 830.7950 Vapor pressure Table 20. Product Deficiency: Makhteshim Agan of North America. 2,4 DB: 75% T ( EPA Reg. No. 66222 80; transferred from Cedar Chemical Co 2/ 3/ 03, EPA Reg. No. 56077 85)

Guideline Requirement 830.1750 Certified limits Table 21. Product Deficiency: A. H. Marks & Co. Ltd 2,4 DB DMA: 49.2% FI ( EPA Reg. No. 15440 33)

Guideline Requirement 830.6302 Color 830.6304 Odor 830.6317 Storage stability 830.7000 pH Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 33 7.0 TOXICITY TABLES Table 22. Acute Toxicity of 2,4 DB Technical.

Guideline No. Study Type MRID # s Results Toxicity Category 81 1 Acute Oral 00128854 0092159 LD50 = 1935 mg/ kg LD50 = 1715 mg/ kg III 81 2 Acute Dermal 0128854 LD50 = > 2000 mg/ kg III 81 3 Acute Inhalation 41774001 LC50 > 2.3 mg/ L IV 81 4 Primary Eye Irritation 0128854 00092160 Eye irritation with complete clearing by day 7 III 81 5 Primary Skin Irritation 0128854 No irritation IV 81 6 Dermal Sensitization 43593904 Under review   Table 23. Acute Toxicity of 2,4 DB DMA ( 26%)

Guideline No. Study Type MRID # Results Toxicity Category 81 1 Acute Oral 41224401 LD50 = 3583 mg/ kg III 81 2 Acute Dermal ( rabbit) 41224402 LD50 > 2000 mg/ kg III 81 3 Acute Inhalation 41370101 LC50 > 7.98 mg/ L IV 81 4 Primary Eye Irritation 41958001 Persistent corneal opacity, iritis, erythema I 81 5 Primary Skin Irritation 250871 Irritation score = 0.99 IV 81 6 Dermal Sensitization 43968911 Under review   Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 34 Table 24. Toxicology Profile of 2,4 DB Guideline No./ Study Type MRID No. ( year)/ Classification / Doses Results 870.3100 90 Day oral toxicity rats 00104739 ( 1969) acceptable/ guideline 0, 316, 1000 or 3160 ppm ( 0, 15.8, 50 or 158 mg/ kg/ day LOAEL = 1000 ppm ( 50 mg/ kg/ day)., based on decreased body weight gain, increased relative liver and kidney weight, microscopic alterations in the liver, kidneys and stomach.

NOAEL = 316 ppm ( 15.8 mg/ kg/ day)

870.3150 90 Day oral toxicity dogs 00092165 ( 1969) acceptable/ guideline capsules at 8, 25 or 80 mg/ kg/ day; group of 4 dogs/ sex was also treated with capsules at 2.5 mg/ kg/ day for three months. LOAEL = 25 mg/ kg/ day, based on death ( sacrifice in extremis), clinical signs of toxicity, decreased body weight, decreased hematology parameters, altered clinical chemistry parameters, increased relative weight of liver, kidney and spleen, and gross and microscopic necropsy evidence of generalized toxicity.

NOAEL = 8 mg/ kg/ day 870.3200 21 day dermal  rabbit 41551301 ( 1989) acceptable/ guideline 0, 500, 1000, 2000 mg/ kg/ day The LOAELs for systemic toxicity and dermal irritation were not established. The NOAELs for systemic toxicity and dermal irritation were 2000 mg/ kg/ day ( HDT). Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 Table 24. Toxicology Profile of 2,4 DB Guideline No./ Study Type MRID No. ( year)/ Classification / Doses Results 35 870.3700a Prenatal developmental in rats MRID 41382701 ( 1990) acceptable/ guideline 0, 31.25, 62.5 or 125 mg/ kg/ day Maternal LOAEL = 62.5 mg/ kg bw/ day, based on decreased body weight ( days 6 16) and body weight gain ( days 0 20). One maternal death was attributed to treatment at 125 mg/ kg/ day. Maternal NOAEL = 31.25 mg/ kg bw/ day.

Developmental LOAEL = 125 mg/ kg bw/ day, based on decreased fetal body weight, skeletal malformations/ variations, microphthalmia, retroesophageal aortic arches. Developmental NOAEL = 62.5 mg/ kg bw/ day.

870.3700b Prenatal developmental in rabbits MRID 41529902 ( 1990) acceptable/ guideline 0, 15, 30 or 60 mg/ kg/ day Maternal LOAEL = 60 mg/ kg bw/ day, based on mortality, clinical signs of toxicity and decreased body weight gains. Maternal NOAEL = 30 mg/ kg bw/ day.

Developmental LOAEL was not determined. Developmental NOAEL = 60 mg/ kg/ day ( HDT).

870.3800 Reproduction and fertility effects MRID 40257503 ( 1986) acceptable/ guideline 0,60, 300 or 1500 ppm ( Males: 0, 5, 25 or 112 mg/ kg/ day and Females: 0, 6, 30 and 133 mg/ kg/ day) Parental LOAEL = 1500 ppm ( 112 mg/ kg/ day in males and 133 mg/ kg/ day in females), based on increased water consumption, decreased food consumption and body weight, increased food conversion ratio, organ weight changes and macroscopic renal findings. Parental NOAEL = 300 ppm ( 25 mg/ kg/ day in males and 30 mg/ kg/ day in females).

Offspring LOAEL = 1500 ppm ( 112 mg/ kg/ day in males and 133 mg/ kg/ day in females), based on increased mortality, decreased mean litter weight and increased incidence of necropsy findings ( small thymus, distended bladder with bloody/ dark urine and ocular opacity). Offspring NOAEL = 300 ppm ( 25 mg/ kg/ day in males and 30 mg/ kg/ day in females).

No effect upon reproductive parameters. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 Table 24. Toxicology Profile of 2,4 DB Guideline No./ Study Type MRID No. ( year)/ Classification / Doses Results 36 870.4100b Chronic toxicity in dogs MRID 42006301 ( 1990) acceptable/ guideline 0, 75, 225 or 450 ( reduced from 675 ppm after week 6) ( 0, 2.39, 6.07 and 12.94 mg/ kg/ day for males; 2.15, 7.06 and 14.16 mg/ kg/ day for females) LOAEL = 75 ppm ( 2.39 and 2.15 mg/ kg/ day in males and females, respectively) based on clinical pathology changes ( increased BUN, ALT and AST), decreased liver and kidney weights ( females) and microscopic changes in the kidney. NOAEL has not been established.

870.4200 Carcinogenicity in mice 40257502 ( 1987) acceptable/ guideline 0, 25, 250 or 750 ppm ( equivalent to 0, 3.75, 37.5 and 112.5 mg/ kg bw/ day based on 7 ppm in the diet equals 1 mg/ kg/ day) LOAEL = 750 ppm ( 112.5 mg/ kg/ day), based on increased mortality in males and increased absolute and relative organ weights ( liver and kidney in both sexes, heart in males), gross pathological changes in liver and kidney ( males) and increased amyloidosis and hepatocellular enlargement ( males).

NOAEL = 250 ppm ( 37.5 mg/ kg/ day)

870.4300 Chronic Toxicity/ Carcinogenicity in rats MRID 40257501( 1987) acceptable/ guideline 0, 60, 600 or 1800 ppm ( equivalent to 0, 3, 30 or 90 mg/ kg bw/ day based on 1 ppm equals 0.05 mg/ kg) LOAEL in males = 1800 ppm ( 90 mg/ kg/ day) based on decreased body weight, body weight gain and food consumption, clinical pathology changes and necropsy alterations ( decreased kidney weights, increased incidence of kidney foci and infarcts and liver mononuclear infiltration and spongy degeneration). LOAEL in females = 600 ppm ( 30 mg/ kg/ day), based on decreased body weight gain and food consumption. NOAEL in males = 600 ppm ( 30 mg/ kg/ day) NOAEL in females = 60 ppm ( 3 mg/ kg/ day) .

870.7485 Metabolism and pharmacokinetics in rats 41981601 ( 1991) acceptable/ guideline Single i. v. and oral doses and multiple oral dosing. Radioactivity recovery in urine was 71.5 97.6% of dose and 3.5 13.8% in feces. Major metabolites were 2,4 D and conjugated 2,4 DCP.

870.7485 Metabolism and pharmacokinetics in rats MRID 44774101( 1999) acceptable/ guideline Single oral dose and 2 bile duct cannulated males. Biliary excretion and enterohepatic recirculation occurred. Metabolite G was identified 4( 2,4 dichlorophenoxy) 3 hydroxybutyric acid. The distribution of metabolites in the present study was comparable to the distribution observed in the previous rat metabolism study. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 37 Table 25. Toxicology Profile of 2,4 DB DMA Guideline No./ Study Type MRID No. ( year)/ Classification / Doses Results 870.3200 21 day dermal  rabbit 41529901 ( 1990) acceptable/ guideline 0, 250, 750 or 1500 mg/ kg bw/ day The systemic LOAEL was not established. The systemic NOAEL was 1500 mg/ kg/ day. The dermal irritation LOAEL was 750 mg/ kg/ day based on erythema, desquamation and fissuring which were more severe than control lesions. The dermal NOAEL was 250 mg/ kg/ day.

870.3100 90 Day oral toxicity rodents 41775401 ( 1990) acceptable/ guideline 0, 60, 600 or 1800 ppm ( 0, 4.16, 41.86 and 130.37 mg/ kg/ day for males and 0, 4.96, 51.36 and 153.64 mg/ kg/ day for females) The LOAEL is 600 ppm ( 41.86 mg/ kg/ day in males and 51.36 mg/ kg/ day in females), based on decreased body weight and body weight gain ( females), increased kidney weights and increased incidence of tubular degeneration ( females). The NOAEL is 60 ppm ( 4.16 mg/ kg/ day in males and 4.96 mg/ kg/ day in females).

870.3700a Prenatal developmental in rats 42536101, 42595201 ( 1991) acceptable/ guideline 0, 31.25, 62.5 or 125 mg/ kg/ day The maternal LOAEL was 62.5 mg/ kg bw/ day, based on emaciation and decreased body weight gain and food consumption. There were 3 maternal deaths attributed to treatment at 125 mg/ kg/ day. The maternal NOAEL was 31.25 mg/ kg bw/ day.

The developmental LOAEL was 125 mg/ kg/ day based on an increase in early resorptions per dam, skeletal malformations, microphthalmia, and a decrease in fetal weight. The developmental NOAEL was 62.5 mg/ kg/ day. Human Health Risk Assessment for 2,4 DB and 2,4 DB DMA July 20, 2004 38 8.0 BIBLIOGRAPHY Toxicology: 2,4 DB and 2,4 DB DMA. Toxicology Chapter for RED. Kit Farwell, D. V. M. July 11, 2003. TXR 0052015.

Hazard Identification: 2,4 DB and 2,4 DB DMA  Report of the Hazard Identification Assessment Review Committee. Kit Farwell, D. V. M. June 13, 2003. TXR 0051956.

Chemistry: 2,4 DB [ 4( 2,4 dichlorophenoxy) butyric acid] and 2,4 DB dimethylamine salt ( PC Codes 030801, 030819): Product Chemistry and Residue Chemistry Summary Documents for the Reregistration Eligibility Decision Document ( RED). Danette Drew, Chemist. December 11, 2003. D290793.

Metabolism: 2,4 DB. Results of the 1/ 16/ 96 Meeting of the HED Metabolism Committee. David J. Miller, HSO, US Public Health Service. January 29, 1996. TXR 0051087.

2,4 DB. Metabolism Committee Question Re: Regulation of Metabolites in Plant and Animal Commodities. 1995. D220888.

Dietary Exposure: 2,4 DB Acute and Chronic Dietary Exposure Assessments for the Reregistration Eligibility Decision. Felecia Fort. April 20, 2004. D300627.

Water Exposure: 2,4 DB   Drinking Water Assessment for the Health Effects Division ( HED) Reregistration Eligibility Decision Document. Amer Al Mudallal, Chemist. July 8, 2003. D279637.

Environmental Fate and Effects Division's Risk Assessment for the Reregistration Eligibility Document for 4( 2,4 dichlorophenoxy) Butyric Acid ( 2,4 DB) and Dimethylamine 4( 2,4 dichlorophenoxy) butyrate ( 2,4 DB DMAS). Amer Al Mudallal and Lewis Brown.

Occupational Exposure: 2,4 DB: Occupational and Residential Exposure and Risk Assessments for the Reregistration Eligibility Decision ( RED) Document. D300629.

Usage Analysis : Quantitative Usage Analysis for 2,4 DB Acid and DMA Salt. Alan Halvorson. October 31, 2001. Office of Pesticide Programs, Biological and Economic Analysis Division.


[Federal Register: December 1, 2009 (Volume 229, Number 74)]
[Notices]
[Page 62882-62883]
[DOCID:fr01de09-156]

-----------------------------------------------------------------------

DEPARTMENT OF TRANSPORTATION

Federal Motor Carrier Safety Administration

[Docket No. FMCSA-2006-26367]

Motor Carrier Safety Advisory Committee Public Meeting

AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT.

ACTION: Notice of Motor Carrier Safety Advisory Committee meeting.

-----------------------------------------------------------------------

SUMMARY: FMCSA announces that the Agency's Motor Carrier Safety
Advisory Committee (MCSAC) will hold a committee meeting via conference
call on December 7, 2009. The conference call is open to the public.

DATES: The meeting will be held by conference call on December 7, 2009,
from 8:30 a.m. to 9:30 a.m. Eastern Standard Time.
    Matters To Be Considered: The MCSAC will be requested to begin work
on a new task: as part of FMCSA's broad efforts to gather information
and recommendations on hours-of-service requirements for drivers of
property-carrying vehicles, FMCSA is asking MCSAC to provide advice and
recommendations on the hours of service requirements.

FOR FURTHER INFORMATION CONTACT: Mr. Jack Kostelnik, Acting Chief,
Strategic Planning and Program Evaluation Division, Office of Policy
Plans and Regulation, Federal Motor Carrier Safety Administration, U.S.
Department of Transportation, 1200 New Jersey Avenue, SE., Washington,
DC 20590,<PHONE_NUMBER><EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. Background

MCSAC

    Section 4144 of the Safe, Accountable, Flexible, Efficient
Transportation Equity Act: A Legacy for Users (SAFETEA-LU) (Pub. L.
109-59, 119 Stat. 1144, August 10, 2005) required the Secretary of
Transportation to establish a Motor Carrier Safety Advisory Committee.
The committee provides advice and recommendations to the FMCSA
Administrator on motor carrier safety programs and regulations, and
operates in accordance with the Federal Advisory Committee Act (5
U.S.C. App 2).

Hours-of-Service Task

    On October 26, 2009, Public Citizen, et al. (Petitioners) and FMCSA
entered into a settlement agreement under which Petitioners' petition
for judicial review of the November 19, 2008 Final Rule on drivers'
hours of service will be held in abeyance pending the publication of a
Notice of Proposed Rulemaking (NPRM). The settlement agreement states
that FMCSA will submit the draft NPRM to the Office of Management and
Budget (OMB) within nine months of the date of the settlement agreement
and that FMCSA will publish a Final Rule within 21 months of the date
of the settlement agreement. The current rule will remain in effect
during the rulemaking proceedings.
    Assigning MCSAC this task is one of several steps that FMCSA will
be undertaking in its process of proposing hours-of-service
requirements for drivers of property-carrying vehicles. Other steps
will include public listening sessions across the country and the
opportunity for public comment on the forthcoming NPRM.

II. Meeting Participation

    The meeting is open to the public and FMCSA seeks participation by
all interested parties, including safety advocacy groups, State safety
agencies, motor carriers, motor carrier associations, owner-operators,
drivers, and labor unions. For information on the agenda, bridge line
and web link for the conference call, please send an e-mail to
<EMAIL_ADDRESS>For information on services for individuals with
disabilities or to request special assistance, please e-mail your
request to<EMAIL_ADDRESS>by December 4, 2009.
    Please note that oral comments will not be taken during this
conference call from the public due to time limitations. Members of the
public may submit written comments on this topic by December 3, 2009,
to Federal Docket Management System (FDMC) Docket Number FMCSA-2006-
26367 using any of the following methods:
     Federal eRulemaking Portal: Go to http://
www.regulations.gov. Follow the online instructions for submitting
comments.
     Fax:<PHONE_NUMBER>.
     Mail: Docket Management Facility; U.S. Department of
Transportation, 1200 New Jersey Avenue, SE., West Building, Room W12-
140, Washington, DC 20590.
     Hand Delivery: U.S. Department of Transportation, 1200 New
Jersey Avenue, SE., Room W12-140, Washington, DC, between 9 a.m. and 5
p.m., Monday through Friday, except Federal holidays.

    Issued on: November 24, 2009.
Larry W. Minor,
Associate Administrator for Policy and Program Development.
[FR Doc. E9-28672 Filed 11-30-09; 8:45 am]

BILLING CODE 4910-EX-P


[Federal Register Volume 88, Number 164 (Friday, August 25, 2023)]
[Proposed Rules]
[Pages 58176-58178]
[FR Doc No: 2023-18322]

-----------------------------------------------------------------------

DEPARTMENT OF HOMELAND SECURITY

Coast Guard

33 CFR Part 117

[Docket No. USCG-2022-0854]
RIN 1625-AA09

Drawbridge Operation Regulation; Reynolds Channel, Atlantic
Beach, NY

AGENCY: Coast Guard, DHS.

ACTION: Notice of proposed rulemaking.

-----------------------------------------------------------------------

SUMMARY: The Coast Guard proposes to modify the operating schedule that
governs the Atlantic Beach Bridge across the Reynolds Channel, mile
0.4, at Atlantic Beach, NY. The bridge owner, Nassau County Bridge
Authority, submitted a request on September 22, 2022 to modify the
regulation to decrease the amount of openings on signal from October
through May. It is expected that this change to the regulations will
better serve the needs of the community while continuing to meet the
reasonable needs of navigation. We invite your comments on this
proposed rulemaking.

DATES: Comments and relate material must reach the Coast Guard on or
before September 25, 2023.

ADDRESSES:  You may submit comments identified by docket number USCG-
2022-0854 using Federal Decision Making Portal at https://www.regulations.gov.
    See the ``Public Participation and Request for Comments'' portion
of the SUPPLEMENTARY INFORMATION section below for instructions on
submitting comments.

FOR FURTHER INFORMATION CONTACT: If you have questions on this proposed
rule, call or email Ms. Stephanie E. Lopez, First Coast Guard District,
Project Officer, telephone<PHONE_NUMBER>, email
[email protected].

SUPPLEMENTARY INFORMATION:

I. Table of Abbreviations

CFR Code of Federal Regulations
DHS Department of Homeland Security
FR Federal Register
OMB Office of Management and Budget
NPRM Notice of Proposed Rulemaking (Advance, Supplemental)
Sec.  Section
U.S.C. United States Code

II. Background, Purpose and Legal Basis

    The Atlantic Beach Bridge at mile 0.4, across Reynolds Channel,
Atlantic Beach, NY, has a vertical clearance of 25 feet at mean high
water and a horizontal clearance of 125 feet. Waterway users include
recreational and commercial vessels, including fishing vessels.
    The existing drawbridge operating regulations are listed at 33 CFR
117.799(e). Under the current regulation, the bridge shall open on
signal from October 1 through May 14. Nassau County is requesting the
bridge shall open on signal from 8 a.m. to midnight October 1 through
May 14; and from midnight to 8 a.m. year-round the draw shall open on
signal if at least eight hours advance notice is given.
    The Reynolds Channel is transited by recreational vessels and
commercial vessels. In recent years, a significant amount of industrial
and commercial business has closed along the waterfront. This change
has caused a decrease in the amount of bridge opening requests from
midnight to 8 a.m.
    Nassau County Bridge Authority held two public meetings on August
18, 2022 and August 25, 2022. No one from the public attended.

III. Discussion of Proposed Rule

    The proposed rule provides the draw to open on signal from 8 a.m.
to midnight October 1 through May 14; and from midnight to 8 a.m. year-
round the draw shall open on signal if at least eight hours notice is
given. The reason for these changes is to reduce openings on signal
during off peak hours due to a significant reduction of commercial
business on the waterway.

IV. Regulatory Analyses

    We developed this proposed rule after considering numerous statutes
and Executive orders related to rulemaking. Below we summarize our
analyses based on these statutes and we discuss First Amendment rights
of protestors to the end of Executive order.

A. Regulatory Planning and Review

    Executive Orders 12866 and 13563 direct agencies to assess the
costs and benefits of available regulatory alternatives and, if
regulation is necessary, to select regulatory approaches that maximize
net benefits. This NPRM has not been designated a ``significant
regulatory action,'' under Executive Order 12866. Accordingly, the NPRM
has not been reviewed by the Office of Management and Budget (OMB).
    This regulatory action determination is based on the ability that
vessels can still transit the bridge given advanced notice.

B. Impact on Small Entities

    The Regulatory Flexibility Act of 1980 (RFA), 5 U.S.C. 601-612, as
amended, requires Federal agencies to consider the potential impact of
regulations on small entities during rulemaking. The term ``small
entities'' comprises small businesses, not-for-profit organizations
that are independently owned and operated and are not dominant in their
fields, and governmental jurisdictions with populations of less than
50,000. The Coast Guard certifies under 5 U.S.C. 605(b) that this
proposed rule would not have a significant economic impact on a
substantial number of small entities.
    While some owners or operators of vessels intending to transit the
bridge may be small entities, for the reasons stated in section IV.A.
above, this proposed rule would not have a significant economic impact
on any vessel owner or operator.
    If you think that your business, organization, or governmental
jurisdiction qualifies as a small entity and that this rulemaking would
have a significant economic impact on it, please submit a comment (see
ADDRESSES) explaining why you think it qualifies and how and to what
degree this rulemaking would economically affect it.
    Under section 213(a) of the Small Business Regulatory Enforcement
Fairness Act of 1996 (Pub. L. 104-121), we want to assist small
entities in understanding this proposed rule. If the rulemaking would
affect your small business, organization, or governmental jurisdiction
and you have questions concerning its provisions or options for
compliance, please contact the person listed in the FOR FURTHER
INFORMATION CONTACT section. The Coast Guard will not retaliate against
small entities that question or complain about this proposed rule or
any policy or action of the Coast Guard.

C. Collection of Information

    This proposed rule would call for no new collection of information
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520.).

D. Federalism and Indian Tribal Governments

    A rule has implications for federalism under Executive Order 13132
(Federalism), if it has a substantial direct effect on the States, on
the relationship between the National Government and the States, or on
the distribution of power and responsibilities among the various levels
of government. We have analyzed this proposed rule under that Order and
have determined that it is consistent with the fundamental federalism
principles and preemption requirements described in Executive Order
13132.
    Also, this proposed rule does not have tribal implications under
Executive Order 13175 (Consultation and Coordination with Indian Tribal
Governments) because it would not have a substantial direct effect on
one or more Indian tribes, on the relationship between the Federal
Government and Indian tribes, or on the distribution of power and
responsibilities between the Federal Government and Indian tribes. If
you believe this proposed rule has implications for federalism or
Indian tribes, please contact the person listed in the FOR FURTHER
INFORMATION CONTACT section.

E. Unfunded Mandates Reform Act

    The Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1531-1538)
requires Federal agencies to assess the effects of their discretionary
regulatory actions. In particular, the Act addresses actions that may
result in the expenditure by a State, local, or tribal government, in
the aggregate, or by the private sector of $100,000,000 (adjusted for
inflation) or more in any one year. Though this proposed rule will not
result in such an expenditure, we do discuss the effects of this
proposed rule elsewhere in this preamble.

F. Environment

    We have analyzed this proposed rule under Department of Homeland
Security Management Directive 023-01, Rev.1, associated implementing
instructions, and Environmental Planning Policy COMDTINST 5090.1
(series), which guide the Coast Guard in complying with the National
Environmental Policy Act of 1969 (NEPA)(42 U.S.C. 4321-4370f). The
Coast Guard has determined that this action is one of a category of
actions that do not individually or cumulatively have a significant
effect on the human environment. This proposed rule promulgates the
operating regulations or procedures for drawbridges. Normally such
actions are categorically excluded from further review, under paragraph
L49, of Chapter 3, Table 3-1 of the U.S. Coast Guard Environmental
Planning Implementation Procedures.
    Neither a Record of Environmental Consideration nor a Memorandum
for the Record are required for this proposed rule. We seek any
comments or information that may lead to the discovery of a significant
environmental impact from this proposed rule.

G. Protest Activities

    The Coast Guard respects the First Amendment rights of protesters.
Protesters are asked to contact the person listed in the FOR FURTHER
INFORMATION CONTACT section to coordinate protest activities so that
your message can be received without jeopardizing the safety or
security of people, places or vessels.

V. Public Participation and Request for Comments

    We view public participation as essential to effective rulemaking
and will consider all comments and material received during the comment
period. Your comment can help shape the outcome of this rulemaking. If
you submit a comment, please include the docket number for this
rulemaking, indicate the specific section of this document to which
each comment applies, and provide a reason for each suggestion or
recommendation.
    We encourage you to submit comments through the Federal Decision
Making Portal at https://www.regulations.gov. To do so, go to https://www.regulations.gov, type USCG-2022-0854 in the search box and click
``Search.'' Next, look for this document in the Search Results column,
and click on it. Then click on the Comment option. If your material
cannot be submitted using https://www.regulations.gov, contact the
person in the FOR FURTHER INFORMATION CONTACT section of this document
for alternate instructions.
    To view documents mentioned in this proposed rule as being
available in the docket, find the docket as described in the previous
paragraph, and then select ``Supporting & Related Material'' in the
Document Type column. Public comments will also be placed in our online
docket and can be viewed by following instructions on the https://www.regulations.gov Frequently Asked Questions web page. We review all
comments received, but we will only post comments that address the
topic of the proposed rule. We may choose not to post off-topic,
inappropriate, or duplicate comments that we receive. Additionally, if
you click on the'' Dockets'' tab and then the proposed rule, you should
see a ``Subscribe'' option for email alerts. Selecting this option will
enable notifications when comments are posted, or if/when a final rule
is published.
    We accept anonymous comments. Comments we post to https://www.regulations.gov will include any personal information you have
provided. For more about privacy and

submissions in response to this document, see DHS's eRulemaking System
of Records notice (85 FR 14226, March 11, 2020).

List of Subjects in 33 CFR Part 117

    Bridges.

    For the reasons discussed in the preamble, the Coast Guard proposes
to amend 33 CFR part 117 as follows:

Part 117--Drawbridge Operation Regulations

0
1. The authority citation for part 117 continues to read as follows:

    Authority: 33 U.S.C. 499; 33 CFR 1.05-1; DHS Delegation No.
00170.1, Revision No. 01.3.

0
2. Revise Sec.  117.799(e) to read as follows:

Sec.  117.799  Long Island, New York Inland Waterway from East Rockaway
Inlet to Shinnecock Canal.

* * * * *
    (e) The draw of the Atlantic Beach Bridge across Reynolds Channel,
mile 0.4, shall operate as follows:
    (1) From October 1 through May 14 the draw shall open on signal
from 8 a.m. to midnight.
    (2) From midnight to 8 a.m. year-round, the draw shall open on
signal if at least eight hours notice is given.
    (3) From May 15 through September 30, except that it need be opened
only on the hour and half-hour from 4 p.m. to 7 p.m. on weekdays and
from 11 a.m. to 9 p.m. on Saturdays, Sundays, Memorial Day,
Independence Day, and Labor Day.
    (4) From May 15 through September 30, from two hours before to one
hour after predicted high tide. Predicted high tide occurs 10 minutes
earlier than that predicted for Sandy Hook, as given in the tide table
published by the National Oceanic and Atmospheric Administration.
* * * * *

    Dated: August 20, 2023.
J. W. Mauger,
Rear Admiral, U.S. Coast Guard, Commander, First Coast Guard District.
[FR Doc. 2023-18322 Filed 8-24-23; 8:45 am]
BILLING CODE 9110-04-P