2,4-D; Time-Limited Pesticide Tolerance

Federal RegisterMar 10, 1999

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-300800; FRL-6065-3]

RIN 2070-AB78

2,4-D; Time-Limited Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes a time-limited tolerance for

residues of 2,4-dichlorophenoxyacetic acid in or on soybeans. Industry

Task Force II on 2,4-D Research Data requested this tolerance under the

Federal Food, Drug, and Cosmetic Act, as amended by the Food Quality

Protection Act of 1996. The tolerance will expire on December 31, 2001.

DATES: This regulation is effective March 10, 1999. Objections and

requests for hearings must be received by EPA on or before May 10,

1999.

ADDRESSES: Written objections and hearing requests, identified by the

docket control number [OPP-300800], must be submitted to: Hearing Clerk

(1900), Environmental Protection Agency, Rm. M3708, 401 M St., SW.,

Washington, DC 20460. Fees accompanying objections and hearing requests

shall be labeled ``Tolerance Petition Fees'' and forwarded to: EPA

Headquarters Accounting Operations Branch, OPP (Tolerance Fees), P.O.

Box 360277M, Pittsburgh, PA 15251. A copy of any objections and hearing

requests filed with the Hearing Clerk identified by the docket control

number, [OPP-300800], must also be submitted to: Public Information and

Records Integrity Branch, Information Resources and Services Division

(7502C), Office of Pesticide Programs, Environmental Protection Agency,

401 M St., SW., Washington, DC 20460. In person, bring a copy of

objections and hearing requests to Rm. 119, Crystal Mall 2 (CM #2),

1921 Jefferson Davis Hwy., Arlington, VA.

A copy of objections and hearing requests filed with the Hearing

Clerk may also be submitted electronically by sending electronic mail

(e-mail) to: [email protected]. Copies of electronic objections and

hearing requests must be submitted as an ASCII file avoiding the use of

special characters and any form of encryption. Copies of objections and

hearing requests will also be accepted on disks in WordPerfect 5.1/6.1

or ASCII file format. All copies of electronic objections and hearing

requests must be identified by the docket control number [OPP-300800].

No Confidential Business Information (CBI) should be submitted through

e-mail. Copies of electronic objections and hearing requests on this

rule may be filed online at many Federal Depository Libraries.

FOR FURTHER INFORMATION CONTACT: By mail: Joanne I. Miller,

Registration Division (7505C), Office of Pesticide Programs,

Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.

Office location, telephone number, and e-mail address: Rm. 235, CM #2,

1921 Jefferson Davis Hwy., Arlington, VA, 703-305-6224,

[email protected].

SUPPLEMENTARY INFORMATION: In the Federal Register of December 11, 1998

(63 FR 68455) (FRL-6043-3), EPA issued a notice pursuant to section 408

of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a, as

amended by the Food Quality Protection Act of 1996 (FQPA) (Pub. L. 104-

170) announcing the filing of a pesticide petition (PP) for tolerance

by Industry Task Force II on 2,4-D Research Data, McKenna & Cuneo, 1900

K St., NW, Washington, DC 20006-1108. This notice included a summary of

the petition prepared by Industry Task Force II on 2,4-D Research Data,

the registrant. There were no comments received in response to the

notice of filing.

The petition requested that 40 CFR 180.142 be amended by

establishing a time-limited tolerance for residues of the herbicide

2,4-dichlorophenoxyacetic acid, in or on soybeans at 0.02 part per

million (ppm). This tolerance will expire on December 31, 2001.

I. Background and Statutory Findings

Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a

tolerance (the legal limit for a pesticide chemical residue in or on a

food) only if EPA determines that the tolerance is ``safe.'' Section

408(b)(2)(A)(ii) defines ``safe'' to mean that ``there is a reasonable

certainty that no harm will result from aggregate exposure to the

pesticide chemical residue, including all anticipated dietary exposures

and all other exposures for which there is reliable information.'' This

includes exposure through drinking water and in residential settings,

but does not include occupational exposure. Section 408(b)(2)(C)

requires EPA to give special consideration to exposure of infants and

children to the pesticide chemical residue in establishing a tolerance

and to ``ensure that there is a reasonable certainty that no harm will

result to infants and children from aggregate exposure to the pesticide

chemical residue. . . .''

EPA performs a number of analyses to determine the risks from

aggregate exposure to pesticide residues. For further discussion of the

regulatory requirements of section 408 and a complete description of

the risk assessment process, see the final rule on Bifenthrin Pesticide

Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).

II. Aggregate Risk Assessment and Determination of Safety

Consistent with section 408(b)(2)(D), EPA has reviewed the

available scientific data and other relevant information in support of

this action. EPA has sufficient data to assess the hazards of 2,4-D and

to make a determination on aggregate exposure, consistent with section

408(b)(2), for a time-limited tolerance for residues of 2,4-

dichlorophenoxyacetic acid on soybeans at 0.02 ppm. EPA's assessment of

the dietary exposures and risks associated with establishing the

tolerance follows.

A. Toxicological Profile

EPA has evaluated the available toxicity data and considered its

validity, completeness, and reliability as well as the relationship of

the results of the studies to human risk. EPA has also considered

available information concerning the variability of the sensitivities

of major identifiable subgroups of consumers, including infants and

children. The nature of the toxic effects caused by 2,4-D are discussed

in this unit.

An oral LD50 of 2,4-D acid is 699 miligrams/kilograms

(mg/kg) in the rat.

[[Page 11793]]

The dermal LD50 in the rabbit is >2000 mg/kg. The acute

inhalation LC50 in the rat is >1.8 mg/liter. A primary eye

irritation study in the rabbit showed severe irritation. A dermal

irritation study in the rabbit showed moderate irritation. A dermal

sensitization study in the guinea pig showed no skin sensitization. An

acute neurotoxicity study in the rat produced a no observed advers

effect level (NOAEL) of 227 mg/kg for systemic toxicity and a

neurobehavioral NOAEL of 67 mg/kg with a lowest observed effect level

(LOEL) of 227 mg/kg.

Mutagenicity studies including gene mutation, chromosomal

aberrations, and direct DNA damage tests were negative for mutagenic

effects.

A 2-generation reproduction study was conducted in rats with

NOAELs for parental and developmental toxicity of 5 mg/kg/day. The

LOELs for this study are established at 20 mg/kg/day based on

reductions in body weight gain in F0 and F2b

pups, and reduction in pup weight at birth and during lactation. A

teratology study in rabbits given gavage doses at 0, 10, 30, and 90 mg/

kg on days 6 through 18 of gestation was negative for developmental

toxicity at all doses tested. A teratology study in rats given gavage

doses at 0, 8, 25, and 75 mg/kg on days 6 through 15 of gestation was

negative for developmental toxicity at all doses tested. A NOAEL for

fetotoxicity was established at 25 mg/kg/day based on delayed

ossification at the 75 mg/kg dose level. The effects on pups occurred

in the presence of parental toxicity.

A subchronic dietary study was conducted with mice fed diets

containing 0, 1, 15, 100, and 300 mg/kg/day with a NOAEL of 15 mg/kg/

day. The LOEL was established at 100 mg/kg/day based on decreased

glucose and thyroxine levels, increases in absolute and relative kidney

weights, and histopathological lesions in the liver and kidneys. A 90-

day dietary study in rats fed diets containing 0, 1, 15, 100, or 300

mg/kg/day resulted in a NOAEL of 15 mg/kg/day and an LOEL of 100 mg/kg/

day. The LOEL was based on decreases in body weight and food

consumption, alteration in clinical pathology, changes in organ

weights, and histopathological lesions in the kidney, liver, and

adrenal glands of both sexes of rats. A 90-day feeding study was

conducted in dogs fed diets containing 0, 0.3, 1, 3, and 10 mg/kg/day

with a NOAEL of 1 mg/kg/day. The LOEL was established at 3 mg/kg/day

based on histopathological changes in the kidneys of male dogs.

A 1-year dietary study was conducted in the dog using doses of 0,

1, 5, and 7.5 mg/kg/day. The NOAEL was 1 mg/kg/day and the LOEL was 5

mg/kg/day based on clinical chemistry changes and histopathological

lesions in the liver and kidney. A 2-year feeding/carcinogenicity study

was conducted in mice fed diets containing 0, 1, 15, and 45 mg/kg/day

with a NOAEL of 1 mg/kg/day. The systemic LOEL was established at 15

mg/kg/day based on increased kidney and adrenal weights and homogeneity

of renal tubular epithelium due to cytoplasmic vacuoles. No

carcinogenic effects were observed under the conditions of the study at

any dosage level tested. A second 2-year oncogenicity study was

conducted in mice fed diets containing 0, 5, 62.5, and 125 mg/kg/day

(males) and 0, 5, 150, and 300 mg/kg/day (females). No treatment-

related oncogenicity was observed. A 2-year feeding/carcinogenicity

study was conducted in rats fed diets containing 0, 1, 15, and 45 mg/

kg/day with a NOAEL of 1 mg kg/day. Although there appeared to be a

slight treatment-related incidence of benign brain tumors

(astrocytomas) in male rats fed diets containing 45 mg/kg/ day, two

different statistical evaluations found no strong statistical evidence

of carcinogenicity in male rats. There were no carcinogenic effects

observed in female rats. A second 2-year feeding/carcinogenicity study

was conducted in rats fed diets containing 0, 5, 75, and 150 mg/kg/day.

The NOAEL was 5 mg/kg/day and the LOEL was 75 mg/kg/day based on

decreased body weight, body weight gain and food consumption; clinical

chemistry changes; organ weight changes and histopathological lesions.

No treatment-related carcinogenic effects or increased incidences of

astrocytomas were observed.

The metabolism of phenyl ring labeled 14C-2,4-D was

studied in the rat following a single intravenous or oral dose of

approximately 1 mg/kg/day. At 48 hours after treatment, recovery of

radioactivity in urine was in excess of 98%. Parent 2,4-D was the major

metabolite (72.9% to 90.5%) found in the urine.

B. Toxicological Endpoints

1. Acute toxicity. EPA has used an acute neurotoxicity study in

rats for endpoint for acute toxicity. The NOAEL of 67 mg/kg/day was

based on the increased incidence of incoordination, slight gait

abnormalities, and decreased motor activity in both sexes at the lowest

observed adverse effect (LOAEL) of 227 mg/kg/day. This risk assessment

will evaluate acute dietary risk to all population subgroups.

2. Short - and intermediate-term toxicity. For short-term dermal

Margin of Exposure (MOE) calculations, EPA used the maternal NOAEL of

30 mg/kg/day from an oral developmental toxicity study in rabbits. The

MOE is a measure of how close the high end of exposure comes to the

NOAEL (or LOAEL, as the case may be) and is calculated as the ratio of

the NOAEL to the exposure. The LOAEL of 90 mg/kg/day was based on

abortions, clinical signs (ataxia, decreased motor activity, and cold

extremities during gestation), and decreased body weight gain. For

acute toxicity, EPA decided that FQPA factor of 10 should be reduced to

3 for females 13 years old and older (13+) and removed for all other

population subgroups. As the short-term and acute endpoints are based

on the oral developmental toxicity study, this decision is also

applicable to the short-term, nonoccupational assessment. Therefore,

based on this recommendation, the MOE needed for females 13+ is 300.

For intermediate-term dermal MOE calculations, EPA used the NOAEL

of 1.0 mg/kg/day from a 90-day oral toxicity study in dogs. The LOAEL

of 3 mg/kg/day was based on clinical chemistry changes (increased BUN

and creatinine levels) and lesions in the kidneys. An MOE of 100 is

required.

3. Chronic toxicity. EPA has established the RfD for 2,4-D at 0.01

mg/kg/day. This RfD is based on a 1-year oral toxicity study in dogs

with a NOAEL of 1 mg/kg/day and an uncertainty factor (UF) of 100,

based on alterations in serum chemistry with corroborative

histopathological lesions in the liver and kidneys.

4. Carcinogenicity. EPA has classified 2,4-D as a Group D chemical

(``not classifiable as to human carcinogenicity'') on the basis that

``the evidence is inadequate and cannot be interpreted as showing

either the presence or absence of a carcinogenic effect''.

C. Exposures and Risks

1. From food and feed uses. Tolerances have been established (40

CFR 180.142) for the residues of 2,4-dichlorophenoxyacetic acid, in or

on a variety of raw agricultural commodities. A time limited tolerance

of 0.1 ppm was previously established for residues of 2,4-D on soybeans

resulting from the preplant use of 2,4-D ester or amine 40 CFR

180.142(a)(11). In order for EPA to recommend favorably for the

establishment of permanent tolerances on soybeans, additional field

trial data and processing data were required. In response, the Industry

Task Force II on

[[Page 11794]]

2,4-D Research Data (Task Force II) submitted field residue data on

soybeans. EPA reviewed these data and concluded that a tolerance of

0.02 ppm was appropriate for soybean seed. Task Force II has thus

proposed to extend the soybean tolerance to December 31, 2001 at a

level of 0.02 ppm. Risk assessments were conducted by EPA to assessed

dietary exposures from 2,4-D as follows:

i. Acute exposure and risk. Acute dietary risk assessments are

performed for a food-use pesticide if a toxicological study has

indicated the possibility of an effect of concern occurring as a result

of a 1-day or single exposure. The Dietary Exposure Evaluation Model

(DEEM ) analysis evaluated the individual food consumption as reported

by respondents in the USDA 1989-91 Nationwide Continuing Surveys for

Food Intake by Individuals (CSFII) and accumulated exposure to the

chemical for each commodity. Each analysis assumes uniform distribution

of 2,4-D in the commodity supply.

The acute exposure analysis for all subgroup was performed using

anticipated and tolerance-level residues and 100 percent crop treated.

The high end MOE for the subgroup of Females (13+) was 399, and is no

cause for concern given the need of a MOE of 300. The high end MOEs for

the remaining populations ranged from 214 (infants less than one year

old) to 321 (overall U.S. population, 48 states), and demonstrate no

cause for concern given the need of a MOE of 100. Therefore, EPA does

not consider the acute food risk to exceed the level of concern.

ii. Chronic exposure and risk. A chronic dietary risk assessment

was performed for 2,4-D using the RfD for the chronic dietary analysis

of 0.01 mg/kg bwt/day. Chronic dietary exposure estimates (DEEM ) used

mean consumption (3 day average) and anticipated or tolerance-level

residues for all commodities. Exposure estimates used 25.6% of the RfD

for the general U.S. population (48 states) and 49.2% of the RfD for

the most exposed population of non-nursing infants (less than one year

old). Since estimated exposures did not exceed the RfD for any

subgroup, EPA does not consider the chronic food risk to exceed the

level of concern.

2. From drinking water. A Maximum Contaminant Level (MCL) of 0.07

mg/L and Health Advisories (HAs) as follows are established for 2,4-D

in drinking water: for a 10-kg child, a range of 1 mg/L from 1-day

exposure to 0.1 mg/L for longer-term exposure up to 7 years; for a 70-

kg adult, a range of 0.4 mg/L for longer-term exposure to 0.07 mg/L for

lifetime exposure.

Information in the Pesticides in Groundwater Database (EPA 734-12-

92-001, 9/92) indicates that 6,142 wells in 32 States were sampled for

residues of 2,4-D during the period 1979-91. Detectable residues were

reported (0.0079-57.1 g/L) in 2.3% (139) of those sampled wells.

An FQPA water assessment was conducted by the Environmental Fate

and Effects Division (EFED) to support an FQPA tolerance reassessment

for the use of 2,4-D dimethylamine salt (DMA), 2,4-D ethylhexyl ester

(EHE), and 2,4-D (acid) as a soybean burndown product. Since laboratory

environmental fate data indicate that 2,4-D DMA and 2,4-D EHE degrade

rapidly to form 2,4-D, the water assessment is focused on the

environmental fate and transport of the 2,4-D. The strategy assumes

that the 2,4-D DMA and 2,4-EHE are not persistent in the environment,

and the environmental fate of these compounds is dependent on the fate

properties of the degradate 2,4-D.

It is noteworthy that water treatment processes affect the removal

of 2,4-D from raw water (Versar, 1992). These treatments include

granulated activated carbon (70-100% removal), packed tower aeration

(0-29% removal), and ozone oxidation (30-69% removal).

A review of the labels indicate that the highest single application

rate in terrestrial environments (e.g., terrestrial noncrop and

terrestrial crop use patterns) for 2,4-D occur at 3.74 pounds of active

ingredient per acre (lbs ai/A), for 2,4-D EHE occur at 10 lbs ai/A, and

for 2,4-D DMA occur at 2 lbs ai/A. These rates represent seasonal

maximum application rates as part of 2,4-D exposure reduction agreement

to support 2,4-D use on pasture/rangeland, forestry, and residential

and turf (excluding sod farm) sites. It is noteworthy that the 10 lbs

ai/A rate corresponds to a basal bark spot treatment. Since this type

of application cannot be simulated from Tier 1 models, EFED conducted

modeling on the label rate from the 2,4-D label.

For groundwater, SCIGROW modeling indicates that the 2,4-D

concentration in ground water is not likely to exceed 0.014 g/

L for both peak (acute) and annual average (chronic) concentration.

Since this estimation was less than the actual monitoring

concentrations noted above, the actual monitoring concentrations were

used in the risk assessment.

For surface water estimates were made using the generic expected

environmental concentration (GENEEC) model. GENEEC modeling indicates

that 2,4-D concentrations in raw surface water are not likely to exceed

132 g/L for annual peak (acute) and 48 g/L for 56 day

average (chronic) concentrations. Since Office of Pesticide Program

(OPP) policy recommends that the 90/56-day GENEEC value be divided by 3

to obtain a value for chronic risk assessment calculations, the surface

water value for use in the chronic risk assessment would be 16 ppb or

g/L.

A Drinking Water Level of Comparison (DWLOC) is a theoretical upper

limit on a pesticide's concentration in drinking water in light of

total aggregate exposure to a pesticide in food, drinking water, and

through residential uses. A DWLOC will vary depending on the toxic

endpoint, with drinking water consumption, and body weights. Different

populations will have different DWLOCs. OPP uses DWLOCs internally in

the risk assessment process as a surrogate measure of potential

exposure associated with pesticide exposure through drinking water. In

the absence of monitoring data for pesticides, it is used as a point of

comparison against conservative model estimates of a pesticide's

concentration in water. DWLOC values are not regulatory standards for

drinking water. They do have an indirect regulatory impact through

aggregate exposure and risk assessments. Because EPA considers the

aggregate risk resulting from multiple exposure pathways associated

with a pesticide's uses, levels of comparison in drinking water may

vary as those uses change. If new uses are added in the future, EPA

will reassess the potential impacts of 2,4-D on drinking water as a

part of the aggregate risk assessment process.

i. Acute exposure and risk. EPA has calculated drinking water

levels of comparison (DWLOCs) for acute exposure to 2,4-D in drinking

water for the females (13+ years old, nursing) to be 1700 ppb. To

calculate the DWLOC for acute exposure relative to an acute toxicity

endpoint, the acute dietary food exposure (from the DEEM analysis) was

subtracted from the RfD to obtain the acceptable acute exposure to 2,4-

D in drinking water. DWLOCs were then calculated using default body

weights and drinking water consumption figures. EPA has determined that

the maximum estimated concentrations of 2,4-D in surface and/or ground

water is not likely to exceed EPA's levels of consideration for 2,4-D

in drinking water as a contribution to acute exposure. EPA concludes

with reasonable certainty that residues of 2,4-D in drinking water

(when considered along with other sources of exposure for which EPA has

reliable data) would not result in unacceptable levels of aggregate

human health risk at this time.

[[Page 11795]]

ii. Chronic exposure and risk. For chronic (non-cancer), the

drinking water levels of concern are 260 and 51 ppb for the U.S.

population and non-nursing infants (less than 1 year old),

respectively. To calculate the DWLOC for chronic (non-cancer, cancer)

exposure relative to a chronic toxicity endpoint, the chronic dietary

food exposure (from DEEM) was subtracted from the RfD to obtain the

acceptable chronic (non-cancer) exposure to 2,4-D in drinking water.

DWLOCs were then calculated using default body weights and drinking

water consumption figures. EPA has determined that the maximum

estimated concentrations of 2,4-D in surface and/or ground water is not

likely to exceed EPA's levels of consideration for 2,4-D in drinking

water as a contribution to chronic aggregate exposure. EPA concludes

with reasonable certainty that residues of 2,4-D in drinking water

(when considered along with other sources of exposure for which EPA has

reliable data) would not result in unacceptable levels of aggregate

human health risk at this time.

Section 408(b)(2)(E) authorizes EPA to use available data and

information on the anticipated residue levels of pesticide residues in

food and the actual levels of pesticide chemicals that have been

measured in food. If EPA relies on such information, EPA must require

that data be provided 5 years after the tolerance is established,

modified, or left in effect, demonstrating that the levels in food are

not above the levels anticipated. Following the initial data

submission, EPA is authorized to require similar data on a time frame

it deems appropriate. As required by section 408(b)(2)(E), EPA will

issue a data call-in for information relating to anticipated residues

to be submitted no later than 5 years from the date of issuance of this

tolerance.

3. From non-dietary exposure. 2,4-D is currently registered for use

on the following residential non-food sites: ornamental turf, lawns,

and grasses, golf course turf, recreational areas, and several other

indoor and outdoor uses. There are chemical-specific and site-specific

data available to determine the potential risks associated with

residential exposures from the registered uses of 2,4-D. Dislodgeable

residues of 2,4-D taken during exposure sessions showed a rapid decline

from 1 hour following application (8%) to 24 hours following

applications (1%). No detectable residues were found in urine samples

supplied by volunteers exposed to sprayed turf 24 hours following

application. Intermediate-term postapplication exposure is thus not

expected. The following assessments are based on the available chemical

specific data.

i. Chronic exposure and risk. Although a chronic endpoint was

chosen, this risk assessment is not required because there is no

chronic exposure scenario for this use.

ii. Short- and intermediate-term exposure and risk. For short-term

dermal MOE calculations, EPA used the maternal NOAEL of 30 mg/kg/day

from the oral developmental toxicity study in rabbits. The LOAEL of 90

mg/kg/day was based on abortions, clinical signs (ataxia, decreased

motor activity, and cold extremities during gestation), and decreased

body weight gain. For acute toxicity, EPA reduce the FQPA factor of 10

to 3 for females 13+ and removed for all other population subgroups. As

the short-term and acute endpoints are based on the oral developmental

toxicity study, this decision is also applicable to the short-term,

nonoccupational assessment. Therefore, based on this recommendation,

the MOE needed for females 13+ is 300.

For intermediate-term dermal MOE calculations, EPA used the NOAEL

of 1.0 mg/kg/day from the 90-day oral toxicity study in dogs. The LOAEL

of 3 mg/kg/day was based on clinical chemistry changes (increased BUN

and creatinine levels) and lesions in the kidneys. An MOE of 100 is

required.

4. Cumulative exposure to substances with common mechanism of

toxicity. Section 408(b)(2)(D)(v) 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.''

EPA does not have, at this time, available data to determine

whether 2,4-D has a common mechanism of toxicity with other substances

or how to include this pesticide in a cumulative risk assessment.

Unlike other pesticides for which EPA has followed a cumulative risk

approach based on a common mechanism of toxicity, 2,4-D does not appear

to produce a toxic metabolite produced by other substances. For the

purposes of this tolerance action, therefore, EPA has not assumed that

2,4-D has a common mechanism of toxicity with other substances. For

information regarding EPA's efforts to determine which chemicals have a

common mechanism of toxicity and to evaluate the cumulative effects of

such chemicals, see the final rule for Bifenthrin Pesticide Tolerances

(62 FR 62961, November 26, 1997).

D. Aggregate Risks and Determination of Safety for U.S. Population

1. Acute risk. The acute dietary MOE was calculated to be 321 for

the U.S. population and 399 for females 13+ years/nursing (accounts for

both maternal and fetal exposure). These MOE calculations were based on

the acute neurotoxicity NOAEL of 67 mg/kg/day. This risk assessment

assumed 100% crop-treated with anticipated (blended commodities) or

tolerance-level residues on all treated crops consumed, resulting in a

significant over estimation of dietary exposure. The acute dietary MOE

calculated for the U.S. population and for females 13+ years/nursing

provides assurance that there is a reasonable certainty of no harm for

acute exposure to 2,4-D.

The maximum estimated concentrations of 2,4-D in surface and ground

water are less than EPA's DWLOCs for 2,4-D as a contribution to acute

aggregate exposure. Therefore, EPA concludes with reasonable certainty

that residues of 2,4-D in drinking water do not contribute

significantly to the aggregate acute human health risk at the present

time considering the present uses and uses proposed in this action.

EPA bases this determination on a comparison of estimated

concentrations of 2,4-D in surface waters and ground waters to levels

of comparison for 2,4-D in drinking water. The estimates of 2,4-D in

surface and ground waters are derived from water quality models that

use conservative assumptions regarding the pesticide transport from the

point of application to surface and ground water. Because EPA considers

the aggregate risk resulting from multiple exposure pathways associated

with a pesticide's uses, DWLOCs may vary as those uses change. If new

uses are added in the future, EPA will reassess the potential impacts

of 2,4-D on drinking water as a part of the aggregate acute risk

assessment process.

2. Chronic risk. Using the ARC exposure assumptions described in

this unit, EPA has concluded that aggregate exposure to 2,4-D from food

will utilize 26% of the RfD for the U.S. population. The major

identifiable subgroup with the highest aggregate exposure is discussed

below. EPA generally has no concern for exposures below 100% of the RfD

because the RfD represents the level at or below which daily aggregate

dietary exposure over a lifetime will not pose appreciable risks to

human health. Despite the potential for exposure to 2,4-D in drinking

water and from non-dietary, non-occupational exposure, EPA does not

expect the aggregate

[[Page 11796]]

exposure to exceed 100% of the RfD. EPA concludes that there is a

reasonable certainty that no harm will result from aggregate exposure

to 2,4-D residues.

3. Short- and intermediate-term risk. Short- and intermediate-term

aggregate exposure takes into account chronic dietary food and water

(considered to be a background exposure level) plus indoor and outdoor

residential exposure.

The short-term NOAEL for dermal exposure is based on the maternal

NOAEL of 30 mg/kg/day from the oral developmental toxicity study in

rabbits. After factoring in residential exposure, the high end total

MOE for females 13+ was 750, and does not exceed EPA's level of

concern.

The intermediate-term NOAEL for dermal exposure is based on the

NOAEL of 1.0 mg/kg/day from the 90-day oral toxicity study in dogs. As

homeowner use of 2,4-D is not expected to result in intermediate-term

dermal exposure, only dietary and water exposures need to be considered

in this assessment.

There is a potential for short- and intermediate-term exposure from

drinking water. However, as estimated average concentrations of 2,4-D

in surface and ground water are less than EPA's levels of concern for

drinking water as a contribution to chronic aggregate and acute

aggregate exposures, contribution to short- and intermediate-term

exposure should not exceed EPA's levels of concern.

4. Aggregate cancer risk for U.S. population. EPA has classified

2,4-D as a Group D chemical (``not classifiable as to human

carcinogenicity'') on the basis that ``the evidence is inadequate and

cannot be interpreted as showing either the presence or absence of a

carcinogenic effect.'' Based on these risk assessments, EPA concludes

that there is a reasonable certainty that no harm will result from

aggregate exposure to 2,4-D residues.

5. Determination of safety. Based on these risk assessments, EPA

concludes that there is a reasonable certainity that no harm will

result from aggregate exposure to residues of 2,4-D.

E. Aggregate Risks and Determination of Safety for Infants and Children

1. Safety factor for infants and children-- i. In general. In

assessing the potential for additional sensitivity of infants and

children to residues of 2,4-D, EPA considered data from developmental

toxicity studies in the rat and rabbit and a 2-generation reproduction

study in the rat. The developmental toxicity studies are designed to

evaluate adverse effects on the developing organism resulting from

maternal pesticide exposure gestation. Reproduction studies provide

information relating to effects from exposure to the pesticide on the

reproductive capability of mating animals and data on systemic

toxicity.

FFDCA section 408 provides that EPA shall apply an additional

tenfold margin of safety for infants and children in the case of

threshold effects to account for pre-and post-natal toxicity and the

completeness of the database unless EPA determines that a different

margin of safety will be safe for infants and children. Margins of

safety are incorporated into EPA risk assessments either directly

through use of a margin of exposure (MOE) analysis or through using

uncertainty (safety) factors in calculating a dose level that poses no

appreciable risk to humans. EPA believes that reliable data support

using the standard uncertainty factor (usually 100 for combined inter-

and intra-species variability) and not the additional tenfold MOE/

uncertainty factor when EPA has a complete data base under existing

guidelines and when the severity of the effect in infants or children

or the potency or unusual toxic properties of a compound do not raise

concerns regarding the adequacy of the standard MOE/safety factor.

ii. Developmental toxicity studies. In a developmental toxicity

study in rats, the maternal (systemic) NOAEL was >75 mg/kg/day at the

highest dose tested (HDT). The developmental (fetal) NOAEL was 25 mg/

kg/day, based on delayed ossification at the developmental LOAEL of 75

mg/kg/day. In a developmental toxicity study in rabbits, the maternal

(systemic) NOAEL was 30 mg/kg/day, based on ataxia, decreased motor

activity, cold extremities, and decreased body weight gain at the LOAEL

OF 90 mg/kg/day. The developmental (fetal) NOAEL was 90 mg/kg/day

(HDT).

iii. Reproductive toxicity study. In the 2-generation reproductive

toxicity study in rats, the parental (systemic) NOAEL of 5 mg/kg/day

was based on degenerative effects in the kidneys of males and decreased

body weight gain in females at the LOAEL of 20 mg/kg/day. The

reproductive (pup) NOAEL was 5 mg/kg/day, based on decreased pup weight

at the LOAEL of 20 mg/kg/day. The reproductive effects occurred in the

presence of parental toxicity.

iv. Pre- and post-natal sensitivity. The toxicological data base

for evaluating pre- and post-natal toxicity for 2,4-D is complete with

respect to current data requirements. There are pre-natal toxicity

concerns for infants and children, based on the results of the rat

developmental toxicity study in which developmental toxicity occurred

in the absence of maternal toxicity. Based on the developmental and

reproductive toxicity studies discussed above, for 2,4-D there does

appear to be an extra sensitivity for pre-natal effects.

EPA decided that the FQPA factor of 10 should be reduced to 3 for

females 13+ and removed for all other population subgroups. The

recommendation was based on the presence of developmental effects in

the absence of maternal effects for 2,4 D in the rat developmental

study. There was no indication of increased susceptibility in a rabbit

developmental study or a multigeneration reproduction study in rats.

Currently, the acute dietary risk assessment is based on the NOAEL

results of the acute neurotoxicity study and applies to all population

subgroups with an MOE requirement of 100. However, due to the FQPA

concerns discussed above, females 13+ will require an MOE of 300 (100 x

3 for FQPA), in contrast to the other population subgroups which will

continue to require the usual MOE of 100 (FQPA does not apply). In

practical terms, the acute dietary risk assessment will be performed

for all population subgroups using the NOAEL from the acute

neurotoxicity study. However, only females 13+ will require an MOE of

300 and all other population subgroups will require an MOE of 100.

v. Conclusion. There is a complete toxicity database for 2,4-D and

exposure data is complete or is estimated based on data that reasonably

accounts for potential exposures.

2. Acute risk. The acute dietary MOE was calculated to be 214 for

infants (less than 1 year old), and 399 for females 13+ years (accounts

for both maternal and fetal exposure). These MOE calculations were

based on the acute neurotoxicity NOAEL of 67 mg/kg/day. This risk

assessment assumed 100% crop-treated with anticipated or tolerance-

level residues on all treated crops consumed, resulting in a

significant over estimation of dietary exposure. The large acute

dietary MOE calculated for females 13+ years and infants (less than 1

year old) provides assurance that there is a reasonable certainty of no

harm for both females 13+ years and the pre-natal development of

infants or infants and children and post-natal exposure to 2,4-D.

The maximum estimated concentrations of 2,4-D in surface and ground

water are less than EPA's DWLOCs for 2,4-D as a contribution to acute

aggregate exposure. Therefore, EPA concludes with reasonable certainty

that residues of 2,4-D in

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drinking water do not contribute significantly to the aggregate acute

human health risk at the present time considering the present uses and

uses proposed in this action.