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dicamba (Banvel) Pesticide Tolerance 12/98


[Federal Register: January 6, 1999 (Volume 64, Number 3)]
[Rules and Regulations]               
[Page 759-769]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06ja99-8]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-300767; FRL-6049-2]
RIN 2070-AB78

Dicamba (3,6-dichloro-o-anisic acid); 

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes, revises and revokes tolerances 
for combined residues of Dicamba in or on various raw agricultural 
commodities. BASF Corporation requested this tolerance under the 
Federal Food, Drug and Cosmetic Act (FFDCA), as amended by the Food 
Quality Protection Act of 1996 (Pub. L. 104-170).

DATES: This regulation is effective January 6, 1999. Objections and 
requests for hearings must be received by EPA on or before March 8, 
1999.

ADDRESSES: Written objections and hearing requests, identified by the 
docket control number, [OPP-300767], 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-300767], 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, 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: opp-docket@epamail.epa.gov. Copies of 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 
file format or ASCII file format. All copies of objections and hearing 
requests in electronic form must be identified by the docket control 
number [OPP-300767]. No Confidential Business Information (CBI) should 
be submitted through e-mail. Electronic copies of 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: Crystal Mall #2, 
1921 Jefferson Davis Hwy., Arlington, VA, (703) 305-6224, e-mail: 
miller.joanne@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: In the Federal Register of November 20, 1998 
(63 FR 64481)(FRL-6043-9), EPA issued a notice pursuant to section 408 
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(e) 
announcing the filing of pesticide petitions (PP 6F4604, 4F3041 and FAP 
4H5428) for tolerances by BASF Corporation. This notice included a 
summary of the petitions prepared by BASF. There were no comments 
received in response to the notice of filing.
    These petitions requested that 40 CFR 180.40 CFR part 180.227 be 
amended by establishing, revising and revoking tolerances for combined 
residues of the herbicide dicamba (3,6-dichloro-o-anisic acid) and its 
metabolites 3,6-dichloro-5-hydroxy-o-anisic acid and 3,6-dichloro-2-
hydroxybenzoic acid in or on the commodities listed in the summary of 
this Final Rule

I. Risk Assessment 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 Dicamba (3,6-dichloro-
o-anisic acid) and to make a determination on aggregate exposure, consistent 
with section 408(b)(2), for revising and establishing tolerances for combined 
residues of Dicamba as described as follows:
    1. Establishing new tolerances for residues of dicamba and its 
metabolite 3,6-dichloro-5-hydroxy-o-anisic acid in or on: barley hay at 
2 ppm, corn, field, forage at 3 ppm; corn, field, stover at 3 ppm, 
corn, pop, stover at 3 ppm; cottonseed meal at 5 ppm; Crop Group 17 
(grass forage, fodder, and hay) forage at 125 ppm and hay at 200 ppm; 
oats forage at 80 ppm, oats hay at 20 ppm; wheat forage at 80 ppm, 
wheat hay at 20 ppm.
    2. Establishing new tolerances for residues of dicamba and its 
metabolites 3,6-dichloro-2-hydroxybenzoic acid and 3,6-dichloro-5-
dichloro-5-hydroxy-o-anisic acid in or on aspirated grain fractions at 
5100 ppm, and soybean hulls at 13 ppm.
    3. Revising tolerances for residues of dicamba (3,6-dichloro-o-
anisic acid) and its metabolite 3,6-dichloro-5-hydroxy-o-anisic acid in 
or on: barley grain to 6 ppm, barley straw at 15 ppm; cottonseed to 3 
ppm; wheat grain to 2 ppm, wheat straw to 30 ppm.
    4. Revising tolerances for residues of dicamba and its metabolite 
3,6-dichloro-2-hydroxybenzoic acid in or on: asparagus to 4 ppm.
    5. Revise tolerances for residues of dicamba and its metabolites 
3,6-dichloro-2-hydroxybenzoic acid and 3,6-dichloro-5-hydroxy-o-anisic 
acid in or on soybeans seed to 10 ppm, changing the name of the 
commodity from soybean grain to soybean seed.
    6. Revoking the following tolerances: grasses, hay at 40 ppm; 
grasses, pasture at 40 ppm and grasses, rangeland at 40 ppm as these 
tolerances are being replaced by Crop Group 17.
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 Dicamba (3,6-
dichloro-o-anisic acid) are discussed below.
    1. Acute toxicity. The following acute toxicity studies with 
technical dicamba were submitted in support of this regulatory action:
    \Acute oral in rats with an LD<INF>50</INF> 2,740 mg/kg
    \Acute dermal in rabbits with an LD<INF>50</INF> > 2,000 
mg/kg
    \Acute inhalation in rats with an LD<INF>50</INF> > 5.3 mg/L
    \Acute eye irritation in rabbits with mild to moderate eye 
irritation
    \Acute dermal irritation in rabbits with irritation
    \Dermal Sensitization in guinea pigs with no dermal sensitization
    The results from the eye irritation study and the dermal irritation 
study placed technical in category II as an acute toxicant.
    2. In a 13-week oral toxicity study, Charles River CD rats were 
exposed to dicamba (86.8% a.i.) at 0, 5,000, 10,000, 12,500 or 15,000 
ppm (approximately 500, 1,000, 1,250 or 1,500 mg/kg/day). At 10,000 ppm 
and above, a reduction of cytoplasmic vacuolization of hepatocyte was 
observed, along with slight decreases in body weight and food 
consumption. The NOAEL = approximately 500 mg/kg/day, the LOAEL = 
approximately 1,000 mg/kg/day based on body weight changes and liver 
effects.
    3. In a 21-day dermal study Dicamba was administered to New Zealand 
white rabbits (5/sex/group) at levels of 0, 40, 200, or 1,000 mg/kg/day 
for 3 weeks. Administration was 6 hr/day to an area approximately 10 x 
15 cm (10% of body surface area). No systemic toxicity was observed at 
any dose level. Dose-related dermal irritation was observed at the 
application sites. Desquamation was seen predominantly in the 1,000 mg/
kg/day group while moderate erythema, moderate edema and atonia were 
observed exclusively in the 1,000 mg/kg/day group. A dose-related 
incidence of fissuring was noted in the 200 and 1,000 mg/kg/day groups. 
The severity of acanthosis and the incidence of hyperkeratosis was 
increased at these sites among rabbits in the 200 and 1,000 mg/kg 
groups. Based on these findings, the systemic NOAEL for males and 
females is 1,000 mg/kg/day. A systemic LOAEL could not be established. 
The NOAEL for dermal irritation is 40 mg/kg/day and the LOAEL is 200 
mg/kg/day.
    4. In the combined chronic toxicity/carcinogenicity study in rats, 
Dicamba 86.8% a.i. was administered to 50 Charles River CD rats/sex/
dose via the diet at dose levels of 0, 50, 250 or 2,500 ppm/day 
(approximately 2.5, 12.5, or 125 mg/kg/day) for 24 months. There were 
no effects of dosing on clinical signs of toxicity, survival, mean body 
weights or weight gains, food consumption, and hematologic, clinical 
chemistry, or urinary parameters. Organ weights, macroscopic findings, 
and non-neoplastic histologic findings were similar among dosed and 
control groups.The NOAEL is approximately 125 mg/kg/day, the highest 
dose level tested. A LOAEL was not established. As an effect level was 
not achieved, it is possible that the animals may have tolerated a 
higher dose.
    5. In the carcinogenicity study in mice, dicamba 86.8% a.i. was 
administered to 52 CD-1 mice/sex/dose via the diet at dose levels of 0, 
50, 150, 1,000, and 3,000 ppm (approximately 0, 6, 18, 115 or 361 mg/
kg/day) for 24 months. There was no significant biological evidence of 
oncogenicity from ingestion of dicamba. A statistically significant 
increase (p<0.05) in the mortality rate (-31%) in 3,000 ppm males could 
not clearly be associated with treatment because a statistically 
significant increase was also observed in males at 150 ppm. Also, 
decreased body weight gain and an increased ratio of lymphocytes to 
neutrophils in high-dose females could not be related to treatment with 
any degree of certainty.The LOAEL is 3,000 ppm (approximately 360 mg/
kg/day) based on increased mortalities in males and decreased body 
weight gain in females. The NOAEL is 1,000 ppm (approximately 115 mg/
kg/day. There was no evidence of a treatment related oncogenic 
response.
    6. In a 1-year chronic feeding study, dicamba 86.8% a.i. was 
administered to Beagle dogs (4/sex/group) in the diet at 0, 10, 500 or 
2,500 ppm (0, 2, 11 or 52 mg/kg/day) for 12 months. No adverse effects 
were observed at any dose level. No abnormalities in clinical signs, 
hematology, clinical chemistry or urinalysis were reported. No abnormal 
findings were made at necropsy, nor were there any significant changes 
in food consumption or body weight. The NOAEL for this study is 52 mg/
kg/day, the highest dose level tested. The LOAEL could not be 
established.
    7. In a developmental toxicity study CD (Charles River) pregnant 
rats (25/dose group) were administered dicamba (85.8% a.i.) at oral 
dose levels of 0, 64, 160 or 400 mg/kg/day in corn oil on days 6 
through 19 of gestation. Maternal toxicity, limited to the high-dose 
group, was characterized by mortality in three gravid and one non-
gravid dams that exhibited neurotoxic signs prior to death; clinical 
signs of nervous system toxicity that included ataxia, salivation, 
stiffening of the body when held, and decreased motor activity; 
statistically significant (p<ls-thn-eq>0.05) decreases in body weight gain 
during the dosing period (days 0 to 20); and concomitant decreases in food 
consumption. Dicamba had no effect on any of the cesarean parameters. 
The maternal LOAEL is 400 mg/kg/day, based on mortality, clinical 
signs, body weight changes and decreases in food consumption. The 
maternal NOAEL is 160 mg/kg/day. No treatment-related fetal gross 
external, skeletal or visceral anomalies (malformations or variations) 
were seen at any dose level. The developmental LOAEL is not 
established. The developmental NOAEL is > 400 mg/kg/day, the highest 
dose level tested.
    8. In a developmental toxicity study inseminated New Zealand White 
rabbits (19 or 20/dose group) were administered dicamba (90.5% a.i.) at 
oral (capsule) dose levels of 0, 30, 150, or 300 mg/kg/day on days 6 
through 18 of gestation.No maternal toxicity was observed at 30 mg/kg/
day. At 150 mg/kg/day maternal toxicity was characterized by abortion 
(5%) and clinical signs such as ataxia, rales, decreased motor 
activity. At 300 mg/kg/day maternal toxicity was manifested by 
abortions, clinical signs, decreased body.
    9. In a 2-generation reproduction study, Sprague-Dawley rats (32 or 
28/group) received dicamba technical (86.5% a.i.) in the diet at dose 
levels of 0, 500, 1,500, or 5,000 ppm (0, 40, 122, or 419 mg/kg/day 
(male) and 0, 45, 136 or 450 mg/kg/day (female). Systemic toxicity was 
observed at 5,000 ppm, manifested as clinical signs in dams from both 
generations during lactation (tense/stiff body tone and slow righting 
reflex) and significantly increased relative liver to body weights 
ratios (112% of control) in both generations and sexes, adults as well 
as weanlings. Relative kidney to body weights (107%) at 1,500 and/or 
5,000 ppm were not considered to be toxicologically relevant since 
there were no gross or histopathological findings. Based on these 
results, the NOAEL for systemic toxicity was 1,500 ppm (122 and 136 mg/
kg/day for males and females (M/F), respectively). The LOAEL was 5,000 
ppm (M/F: 419/450 mg/kg/day) based on clinical signs of neurotoxicity. 
Reproductive and/or offspring toxicity was observed at 1,500 and 5,000 
ppm, manifested as significantly decreased pup growth (decreased body 
weight gain) in all generations and matings at 1,500 ppm (86 - 90% of 
control) and at 5,000 ppm (74 - 94% of control). In addition, delayed 
sexual maturation was noted in F1 males at 5,000 ppm. Based on these 
results, the NOAEL for reproductive toxicity was 500 ppm (45 mg/kg/day) 
and the LOAEL was 1,500 ppm (136 mg/kg/day based on decreased pup 
growth. Lastly, the NOAEL for offspring toxicity was 45 mg/kg/day and 
the LOAEL was 136 mg/kg/day, based on significantly decreased pup 
growth.
    10. In an acute neurotoxicity study in rats, Dicamba was 
administered by gavage in a single dose to Crl: CD BR rats at doses of 
0, 300, 600, or 1,200 mg/kg. Vehicle controls received corn oil only. 
Positive controls received acrylamide at 50 mg/kg/day by i.p. injection 
on seven consecutive days. At 300 mg/kg, transiently impaired 
respiration; rigidity upon handling, prodding or dropping; freezing of 
movement when touched; decreased arousal and fewer rears/minute 
compared to controls; impaired of gait and righting reflex were 
observed in both sexes. In addition, males showed decreased forelimb 
grip strength. With the exception of the decrease in forelimb grip 
strength, which persisted until day seven, these effects were observed 
only on the day of dosing. In addition, at 600 mg/kg, both sexes showed 
decreases in locomotor activity and males showed significant decreases 
in tail flick reflex and a raised posture when placed in an open field. 
These effects were also observed only on the day of dosing. At the 
highest dose level tested (1,200 mg/kg), both males and females showed 
an impaired startle response to an auditory stimulus. The effect was 
significant in males on day seven and in females on the day of dosing. 
In addition, males showed decreases in body weight (5 - 9%), body 
weight gain (24%) and food consumption (13% between days 0 and 7. The 
LOAEL for this study was 300 mg/kg based on the several neurologic 
signs listed above; the NOAEL was < 300 mg/kg/day.
    11. In a subchronic neurotoxicity study Sprague-Dawley rats (10/
sex/dose) were fed test diets containing 0, 3,000, 6,000, or 12,000 ppm 
(0, 197.1, 401.4, 767.9 mg/kg/d (M) and 0, 253.4, 472.0 or 1,028.9 mg/
kg/day (F)) Dicamba (86.9% a.i.) for 13 weeks. Neurobehavioral 
evaluations, consisting of FOB, locomotor activity, and auditory 
startle response, were conducted at prestudy and during Weeks 4, 8 and 
13. No toxicologically significant differences were noted in either the 
mean body weights or food consumption of the treated animals. 
Neurobehavioral evaluations at the 4-, 8-, and 13-week evaluations 
revealed abnormal FOB observations consisting of rigid body tone, 
slightly impaired righting reflex and impaired gait. At Week 13 the 
incidences of these findings were decreased. Rigid body tone was also 
noted during evaluation of the righting reflex and landing foot splay. 
The NOAEL is 401.4/472.0 mg/kg/day (M/F), and the LOAEL is 767.9/
1,028.9 mg/kg/day (M/F) based on rigid body tone, slightly impaired 
righting reflex and impaired gait.
    12. In a microbial mutagenicity assay, Salmonella typhimurium 
strains TA98, TA100, TA1535, TA1537, or TA1538 were exposed to the 
dimethylamine (DMA) salt of dicamba (40.3% a.i.) in deionized distilled 
water at concentrations of 100, 333, 1,000, 3,333, or 5,000 <greek-m>g/
plate in the presence and absence of mammalian metabolic activation. 
Preparations for metabolic activation were made from induced rat 
livers. The DMA salt of dicamba was tested up to the limit 
concentration of 5,000 <greek-m>g/plate and no cytotoxicity was 
observed. The positive controls induced the appropriate responses in 
the corresponding strains. There was no evidence of induced mutant 
colonies over background (reversion to prototrophy).
    13. In a microbial mutagenicity assay, Salmonella typhimurium 
strains TA98, TA100, TA1535, TA1537, or TA1538 were exposed to the 
diglycolamine (DGA) salt of dicamba (39.7% a.i.) in deionized distilled 
water at concentrations of 100, 333, 1,000, 3,333, or 5,000 <greek-m>g/
plate in the presence and absence of mammalian metabolic activation. 
Preparations for metabolic activation were made from induced rat 
livers. The DGA salt of dicamba was tested up to the limit 
concentration of 5,000 <greek-m>g/plate, but no cytotoxicity was 
observed. The positive controls induced the appropriate responses in 
the corresponding corresponding strains. There was no evidence of 
induced mutant colonies over background (reversion to prototrophy).
    14. In a microbial mutagenicity assay, Salmonella typhimurium 
strains TA98, TA100, TA1535, TA1537, or TA1538 were exposed to the 
isopropylamine (IPA) salt of dicamba (32.3% a.i.) in deionized 
distilled water at concentrations of 100, 333, 1,000, 3,333, or 5,000 
<greek-m>g/plate in the presence and absence of mammalian metabolic 
activation. Preparations for metabolic activation were made from 
induced rat livers. The IPA salt of dicamba was tested up to the limit 
concentration of 5,000 <greek-m>g/plate and no cytotoxicity was 
observed. The positive controls induced the appropriate responses in 
the corresponding strains. There was no evidence of induced mutant 
colonies over background (reversion to prototrophy).
    15. In a mammalian cell gene mutation assay at the thymidine kinase 
locus, L5178Y mouse lymphoma cells cultured in vitro were exposed to 
dicamba dimethylamine (DMA) salt (40.3% a.i.) in distilled water at 
concentrations of 900, 1,000, 1,500, 2,000, 2,500, 3,000, 3,500, 4,000, 
4,500, and 5,000 <greek-m>g/mL in the presence and absence of S9 
mammalian metabolic activation. Dicamba DMA salt was tested up to the 
limit dose. Under nonactivation conditions, the percent total growth 
values over the evaluated dose range were from 69-109% (initial assay) 
and 65-111% (confirmatory assay). The mutation frequencies (MFs) for 
all of the treated cultures were <2x the solvent controls; the 
exception was the 4,500 <greek-m>g/mL dose, which had a MF of 
approximately 2x background in the confirmatory trial. However, the 
4,500 <greek-m>g/mL response was not reproducible. The S9-activation 
assay confirmed the findings of the nonactivation assay. The percent 
total growth values were 26-109% (initial assay) and 23-113% 
(confirmatory assay). The MFs for all of the treated cultures were <2x 
the solvent controls with the exception of the 3,000 <greek-m>g/mL dose 
in the confirmatory trial which had a MF of approximately 2x 
background; this result was not reproducible. It was determined that 
dicamba DMA salt was not mutagenic under either nonactivation or S9-
activation conditions. In both the nonactivated and activated 
conditions, the positive controls induced the appropriate response.
    16. In a mammalian cell gene mutation assay at the thymidine kinase 
locus (MRID 43310305), L5178Y mouse lymphoma cells cultured in vitro 
were exposed to dicamba diglycolamine (DGA) salt (39.7% a.i.) in 
distilled water at concentrations of 900, 1,000, 1,500, 2,000, 2,500, 
3,000, 3,500, 4,000, 4,500, and 5,000 <greek-m>g/mL in the presence and 
absence of S9 mammalian metabolic activation. Dicamba DGA salt was 
tested up to the limit dose. Under nonactivation conditions, the 
percent total growth values over the evaluated dose range were from 68-
116% (initial assay) and 72-105% (confirmatory assay). The mutation 
frequencies (MFs) forall of the treated cultures were <2x the solvent 
controls. The S9-activation assay confirmed the findings of the 
nonactivation assay. The percent total growth values were 43-102% 
(initial assay) and 46-99% (confirmatory assay). The MFs for all of the 
treated cultures were <2x the solvent controls with the exception of 
the 4,500 <greek-m>g/mL dose in the initial trial, which had a MF of 
approximately 2x background. However, this result was not reproducible. 
Therefore, it was determined that dicamba DGA salt was not mutagenic 
under either nonactivation or S9-activation conditions. In both the 
nonactivated and activated conditions, the positive controls induced 
the appropriate response.
    17. In a mammalian cell gene mutation assay at the thymidine kinase 
locus, L5178Y mouse lymphoma cells cultured in vitro were exposed to 
dicamba isopropyl amine (IPA) salt (32.3% a.i.) in distilled water at 
concentrations of 900, 1,000, 1,500, 2,000, 2,500, 3,000, 3,500, 4,000, 
4,500, and 5,000 <greek-m>g/mL in the presence and absence of S9 
mammalian metabolic activation. Dicamba IPA salt was tested up to the 
limit dose. Under nonactivation conditions, the percent total growth 
values over the evaluated dose range were from 92-101% (initial assay) 
and 51-107% (confirmatory assay). The mutation frequencies (MFs) for 
all of the treated cultures were <2x the solvent controls. The S9-
activation assay confirmed the findings of the nonactivation assay. The 
percent total growth values were 75-126% (initial assay) and 49-114% 
(confirmatory assay). The MFs for all of the treated cultures were <2x 
the solvent controls. Therefore, it was determined that dicamba IPA 
salt was not mutagenic under either nonactivation or S9-activation 
conditions. In both the nonactivated and activated conditions, the 
positive controls induced the appropriate response.
    18. In an in vivo mouse bone marrow micronucleus assay, groups of 
five ICR mice/sex received a single IP injection of 525, 1,050, or 
2,100 mg/kg of the diglycolamine DGA salt formulation of dicamba (39.7% 
a.i.). Bone marrow cells were harvested at 24, 48, or 72 hours post 
treatment and scored for micronucleated polychromatic erythrocytes 
(MPCEs). Mortality occurred in 3/20 male and 1/20 female mice dosed at 
2,100 mg/kg. Lethargy was observed in male and female mice at all dose 
levels. Cytotoxicity by the DGA salt formulation was observed by a 
reduction in the ratio of PCEs to total erythrocytes in males dosed at 
2,100 mg/kg 48 and 72 hours following dosing. The positive control 
induced significant increases in MPCEs in both sexes. The DGA salt of 
dicamba was non-mutagenic. There was no significant increase in the 
frequency of MPCEs in bone marrow after any treatment time.
    19. In an in vivo mouse bone marrow micronucleus assay, groups of 
five ICR mice/sex received a single IP injection of 500, 1,000, or 
2,000 mg/kg of the isopropylamine (IPA) salt formulation of dicamba 
(32.3% a.i.). Bone marrow cells were harvested at 24, 48, or 72 hours 
post-treatment and scored for micronucleated polychromatic erythrocytes 
(MPCEs). Mortality occurred in 2/20 male and 0/20 female mice dosed at 
2,000 mg/kg. Lethargy was observed in male and female mice at all dose 
levels. The IPA salt formulation of dicamba was not cytotoxic to the 
target cell. The positive control induced significant increases in 
MPCEs in both sexes. The IPA salt of dicamba was non-mutagenic. There 
was no significant increase in the frequency of MPCEs in bone marrow 
after any treatment time.
    20. In a metabolism, distribution and excretion study, (1) groups 
of four males and eight females per dose of Charles River CD rats 
received a single oral dose (0.1 or 0.93 gm/kg) in peanut oil by 
esophageal intubation. The rats were sacrificed at intervals ranging 
from one hour to 72 hours after dosing. Tissues, urine and blood were 
retained for subsequent analysis. (2) One male and one female each 
received a single injection subcutaneously of C<INF>14</INF> labeled 
dicamba. The rats were sacrificed at 72 hours. (3) Groups of five male 
and five female rates per dose housed in individual metabolic cages 
were fed C<INF>14</INF> labeled dicamba at 10, 100, 1,000, 10,000 
and 20,000 ppm for 24 days. Rats were sacrificed at 1, 3, 6, 13 and 24 
days. Dietary ingestion resulted in 96% urinary excretion in 48 hours 
and 4% via the feces. Fairly equal tissue distribution occurred 
initially but tissue levels did not persist beyond a few hours, 
indicating no bioaccumulation. It was concluded that when administered 
orally to rats, C<INF>14</INF> labeled dicamba is rapidly absorbed 
and excreted. Over 95% is excreted in the urine and the compound is not 
metabolized or appreciable accumulated by the tissues. A fraction of 
the dicamba in the urine (ca. 13%) is conjugated to the glucuronide.

B. Toxicological Endpoints

    1. Acute dietary (1-day). In an acute neurotoxicity study in rats 
groups of Crl: CD BR rats (10/sex/dose) received a single oral (gavage) 
administration of Dicamba (86.9%) in corn oil at doses of 0, 300, 600, 
or 1,200 mg/kg. Vehicle controls received corn oil only. Positive 
controls received Acrylamide at 50 mg/kg/day by intra peritoneal 
injection on seven consecutive days. At 300 mg/kg, transiently impaired 
respiration; rigidity upon handling, prodding or dropping; freezing of 
movement when touched; decreased arousal and fewer rears/
minute compared to controls; impairment of gait and righting reflex 
were observed in both sexes. In addition, males showed decreased 
forelimb grip strength. With the exception of the decrease in forelimb 
grip strength, which persisted until day seven, these effects were 
observed only on the day of dosing. In addition, at 600 mg/kg, both 
sexes showed decreases in locomotor activity and males showed 
significant decreases in tail flick reflex and a raised posture when 
placed in an open field. These effects were also observed only on the 
day of dosing. At the highest dose level tested (1,200 mg/kg), both 
males and females showed an impaired startle response to an auditory 
stimulus. The effect was significant in males on day seven and in 
females on the day of dosing. In addition, males showed decreases in 
body weight (5 - 9%), body weight gain (24%) and food consumption (13% 
between days 0 and 7). The LOAEL was 300 mg/kg based on the several 
neurologic signs listed above; a NOAEL was not established.
    i. Dose and Endpoint for Risk Assessment: LOAEL=300 mg/kg/day based 
on severe neurologic signs described above.
    ii. Comments about Study and Endpoint: Neurotoxicity was seen in 
both sexes at the lowest dose tested. With the exception of the 
decrease in forelimb grip strength, which persisted until day seven, 
the other neurologic signs were seen only on the day of dosing. The 
Acute Dietary RfD is 0.10 mg/kg/day, based on the LOAEL of 300 mg/kg/
day and an uncertainty factor of 3,000 for infants and children (10x 
for intra species variations, 10x for inter species variations, 10x 
because a LOAEL was used instead of a NOAEL, and 3x for FQPA 
considerations). The EPA used 10x because a LOAEL was used, not 3x, 
because of the severity of neurotoxic signs exhibited by all animals in 
both sexes at the lowest dose level used.
    2. Chronic dietary Reference Dose (RfD). In a 2-generation 
reproduction study, Sprague-Dawley rats (32 or 28/group) received 
Dicamba technical (86.5%) in the diet at dose levels of 0, 500, 1,500, 
or 5,000 ppm (0, 40, 122, or 419 mg/kg/day for males and 0, 45, 136 or 
450 mg/kg/day for females, respectively) for two generations. Systemic 
toxicity was observed at 5,000 ppm, manifested as clinical signs in 
dams from both generations during lactation (tense/stiff body tone and 
slow righting reflex) and significantly increased relative liver to 
body weights (112% of control) in both generations and sexes, adults as 
well as weanlings. The increase (107%) in relative kidney weights 
observed at 1,500 and/or 5,000 ppm were not considered to be 
toxicologically significant due to lack of corroborative gross or 
histopathological lesions in the kidneys. For parental systemic 
toxicity, the NOAEL was 122 and 136 mg/kg/day for males and females, 
respectively and the LOAEL was 419 and 450 mg/kg/day in males and 
females based on clinical signs of neurotoxicity. Reproductive toxicity 
at 1,500 and 5,000 ppm, manifested as significantly decreased pup 
growth in all generations and matings at 1,500 ppm (86 - 90% of 
control) and at 5,000 ppm (74 - 94% of control). In addition, delayed 
sexual maturation was noted in F1 males at 5,000 ppm. For offspring 
toxicity, the NOAEL was 45 mg/kg/day and the LOAEL was 136 mg/kg/day 
based on significantly decreased pup growth.
    i. Dose and endpoint for establishing the RfD. NOAEL = 45 mg/kg/day 
based on significant decreases in pup growth in all generations and 
mating at 136 mg/kg/day (LOAEL).
    ii. Comments about study and endpoint. The NOAEL/LOAEL in the two-
generation study is supported by the maternal NOAEL of 30 mg/kg/day and 
the LOAEL of 150 mg/kg/day established in the developmental toxicity 
study in rabbits; the maternal LOAEL was based on abortions (5%) and 
clinical signs of neurotoxicity (ataxia, rales, and decreased motor 
activity) Uncertainty Factor (UF): An UF of 1,000 was applied to 
account for inter (10x)-and intra-(10x) species variation and 10 for F 
PA.
    RfD = 45 mg/kg/day (NOAEL)/1,000 (UF) = 0.045 mg/kg/day

    3. Occupational and residential exposure (dermal). Short-Term (1 - 
7 days) Dermal In a 21-day dermal study (MRID No. 40547901) New Zealand 
white rabbits (5/sex/group) received 15 repeated dermal applications of 
dicamba in deionized water at dose levels of 0, 40, 200, or 1,000 mg/
kg/day, 6 hours/day, 5 days/week over a 3-week period. No systemic 
toxicity was observed at any dose level. Dose-related dermal irritation 
was observed at the application sites. Desquamation was seen 
predominantly in the 1,000 mg/kg/day group while moderate erythema, 
moderate edema and atonia were observed exclusively in the 1,000 mg/kg/
day group. A dose-related incidence of fissuring was noted in the 200 
and 1,000 mg/kg/day groups. The severity of acanthosis and the 
incidence of hyperkeratosis was increased at these sites in rabbits at 
200 and 1,000 mg/kg. For systemic toxicity, the NOAEL was 1,000 mg/kg/
day (HDT); a systemic LOAEL was not established. For dermal irritation, 
the NOAEL was 40 mg/kg/day and the LOAEL was 200 mg/kg/day.
    i. Dose and endpoint for risk assessment. Systemic NOAEL = 1,000 
mg/kg/day, the highest dose tested.
    ii. Comments about study and endpoint. Although no systemic 
toxicity was observed at the Limit-Dose, the EPA recommended this dose 
for risk assessment because:
    a. Dicamba is used in residential lawns and thus there is potential 
exposure by children and infants.
    b. Increased sensitivity to offspring was demonstrated in the 2-
generation reproduction study. A systemic toxicological end point was 
not determined from the study; however, for the risk assessment for the 
exposures involving these tolerance actions, a conservative default 
NOAEL of 1,000 was used.
    4. Intermediate-term (7 days to several months) dermal. Summarized 
under short term in Unit above. Dose and Endpoint for Risk Assessment: 
Systemic NOAEL = 1,000 mg/kg/day, the highest dose tested. Comments 
about Study and Endpoint: Although no systemic toxicity was observed at 
the Limit-Dose, the EPA recommended this dose for risk assessment 
because (1) Dicamba is used in residential lawns and thus there is 
potential exposure by children and infants and (2) increased 
sensitivity to offspring was demonstrated in the 2-generation 
reproduction study.
    5. Long term (Several months to life-time) dermal. Based on the 
current use pattern, long-term dermal exposure is not anticipated. 
Therefore, a dose and endpoint was not identified.
    6. Inhalation exposure (Any-time period). Based on the 
LC<INF>50</INF> of >5.3 mg/L, Dicamba is placed in Toxicity 
Category 
IV. The EPA determined that a risk assessment via the inhalation route 
is not required because of the low acute inhalation toxicity and the 
use pattern/application method does not indicate high exposure via this 
route.
    7. Margin of exposure for residential exposures. For Short-and 
Intermediate Term dermal exposures a MOE of 300 is required for 
residential exposures because: (a) Although developmental toxicity 
studies showed no increased sensitivity in fetuses as compared to 
maternal animals following in utero exposures in rats and rabbits, 
increased sensitivity to offspring, however, was demonstrated in the 2-
generation reproduction toxicity study in rats (See Section III.2).
    (b) There is evidence of neurotoxicity in the following studies: 
acute and subchronic neurotoxicity, combined chronic toxicity/
carcinogenicity, developmental toxicity (rats and rabbits) and the 2-generation 
reproduction (See Section III.1).
    (c) A weight-of-the-evidence evaluation of the data base indicates 
the need for a developmental neurotoxicity study.

C. Exposures and Risks

    1. Food and feed. Tolerances have been established (40 CFR 180.227) 
for the combined residues of Dicamba, in or on a variety of raw 
agricultural commodities, including meat, milk and poultry and eggs. 
Risk assessments were conducted by EPA to assessed dietary exposures 
from Dicamba (3,6-dichloro-o-anisic acid) 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 one day or single exposure. The endpoint selected by EPA for 
assessment of acute dietary risk is severe neurological effects in both 
sexes at 300 mg/kg/day (LOAEL, a NOAEL was not established) in a rat 
acute neurotoxicity study. Thus, this risk assessment is required for 
all population subgroups. This acute dietary (food) risk assessment 
used the Dietary Exposure Evaluation Model (DEEM). This program 
utilizes individual food consumption as reported by respondents in the 
USDA 1989-1991 nationwide Continuing Surveys for Food Intake by 
Individuals (CSFII) and food residue levels to estimate possible 
exposure levels of various population subgroups. Regulating at the 95th 
percentile, acute dietary exposure values and percent of the acute RfD 
are shown in following table:

                    Acute Dietary Exposure and Risks
------------------------------------------------------------------------
                                      Acute       High-end
       Population Subgroup         RfD\1\ (mg/    Exposure   % Acute RfD
                                     kg/day)    (mg/kg/day)
------------------------------------------------------------------------
US Population....................       0.1      0.02860         28.6
Nursing Infants (<1 yr old)......    0.1      0.02610         26.1
Non-nursing Infants (<1 yr old)..    0.1      0.06315         63.2
Children (1-6)...................       0.1      0.04581         45.8
Children (7-12)..................       0.1      0.03116         31.2
------------------------------------------------------------------------
\1\ Based on LOAEL of 300 mg/kg/day and an uncertainty factor of 3,000.
  Adjusted for FQPA.

    These estimates indicate that risks from acute dietary exposures to 
dicamba do not exceed EPA's level of concern.
    ii. Chronic exposure and risk. The chronic dietary exposure 
analysis from food sources was conducted using the reference dose (RfD) 
of 0.045 mg/kg/day. The RfD is based on the NOAEL of 45 mg/kg/day, 
which in turn is based on reduced pup weights in all generations and 
matings at 136 mg/kg/day in a multi-generation reproduction study in 
rats; and an uncertainty factor of 1,000 applicable to all populations 
which include infants and children. In conducting this chronic dietary 
risk assessment, EPA has made very conservative assumptions: 100% of 
RACs having dicamba tolerances will contain dicamba residues and those 
residues will be at the level of the established tolerance. This 
results in an overestimate of human dietary exposure. Thus, in making a 
safety determination for this tolerance, EPA is taking into account 
this conservative exposure assessment.
    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. 
The chronic DEEM analysis used mean consumption (3 day average) data 
and gave the results listed below:


------------------------------------------------------------------------
                      Subgroups                                %RfD
------------------------------------------------------------------------
U.S. Population (48 states)..........................          23.9
Nursing Infants (< 1 year old)....................          16.5
Non-Nursing Infants (< 1 year old)................          71.1
Children (6 years old)...............................          54.8
Children (7-12 years old)............................          36.8
Non-Hispanic Whites..................................          24.1
Males (13-19 years old)..............................          25.6
------------------------------------------------------------------------

    The subgroups listed above are: (1) the U.S. population (48 
states); (2) those for infants and children; and (3) the other 
subgroups for which the percentage of the RfD occupied is greater than 
that occupied by the subgroup U.S. population (48 states). These 
estimates indicate that risks from chronic dietary exposures to dicamba 
do not exceed EPA's level of concern.
    iii. Carcinogenic risk. In the chronic toxicity/carcinogenicity 
study in rats there were no observed clinical signs of toxicity, 
including survival, mean body weights or body gains, food consumption, 
hematologic clinical chemistry, urinary parameters, organ weights, 
macroscopic findings, and non-neoplastic histology findings at 125 mg/
kg/day, the highest dose tested. A LOAEL was not established. In the 
mouse carcinogenicity study at the highest dose tested, 361 mg/kg/day, 
there were no clinical signs of carcinogenicity. A NOAEL of 115 mg/kg/
day was determined for increased mortalities in males and decreased 
body weight gains in females. Based on these studies, a finding of 
carcinogenicity in rats or mice would not change the Rfd previously 
stated.
    In accordance with the EPA Proposed Guidelines for Carcinogen Risk 
Assessment (10-APR-1996), the EPA classified dicamba as a "not 
classifiable" human carcinogen. This was based on the mouse 
carcinogenicity study and the rat combined chronic toxicity/
carcinogenicity study, being classified as supplemental because an MTD 
was not achieved in both studies. However, these studies were adequate 
to indicate that dicamba has either a low or no cancer potential in 
mammals. A pharmacokinetics study pending EPA review indicates that the 
MTD for both the rat and mouse studies was reached. If this is 
corroborated by EPA's review, a quantitative cancer risk will not be 
made for dicamba and its metabolites, on the other hand, if the review 
does not corroborate this indication, replacement studies will be 
required.
    2. From drinking water. EPA does not have monitoring data available 
to perform a quantitative drinking water risk assessment for dicamba at 
this time. A Tier 1 drinking water assessment of dicamba is given 
below.. This assessment utilized the GENEEC and SCI-GROW screening 
models to provide estimates of ground and surface water contamination 
from dicamba and its metabolite, 3,6-dichlorosalicylic acid (DCSA). 
Concentrations of the 5-hydroxy metabolite of dicamba (3,6-
dichloro-5-hydroxy-o-anisic acid) in surface and ground water could not 
be estimated; however, based on the available environmental fate data, 
it is not likely that this metabolite would be found in surface and 
ground water.
    EPA followed an Interim Approach for Addressing Drinking Water 
Exposure in Tolerance Decision making issued on 17-NOV-1997. Thus, the 
GENEEC model and the SCI-GROW model were run to produce estimates of 
dicamba concentrations in surface and ground water respectively. The 
primary use of these models is to provide a coarse screen for sorting 
out pesticides for which OPP has a high degree of confidence that the 
true levels of the pesticide in drinking water will be less than the 
human health drinking water levels of concern (DWLOCs). A human health 
DWLOC is the concentration of a pesticide in drinking water which would 
result in unacceptable aggregate risk, after having already factored in 
all food exposures and other non-occupational exposures.
DWLOC<INF>acute</INF> = [acute water exposure (mg/kg/day) x (body 
weight)]/[consumption (L) x 10<SUP>-3</SUP> mg/<greek-m>g]
    where acute water exposure (mg/kg/day) = acute RfD - acute food 
exposure (mg/kg/day)

DWLOC<INF>chronic</INF> = [chronic water exposure (mg/kg/day) x 
(body weight)]/[consumption (L) x 10<SUP>-3</SUP> mg/<greek-
m>g] where chronic water exposure (mg/kg/day) = [RfD - (chronic food 
exposure + chronic residential exposure) (mg/kg/day)].
There is no chronic residential exposure for dicamba. The 
DWLOC<INF>chronic</INF> is the concentration in drinking water as 
part of the aggregate chronic exposure that results in a negligible cancer 
risk. The Agency's default body weights and consumption values used to 
calculate DWLOCs are as follows: 70 kg/2L (adult male), 60 kg/2L (adult 
female), and 10 kg/1L (child).

--------------------------------------------------------------------------------
------------------------------------------------------------------------
                                                                    Acute 
Scenario                                     Chronic Scenario
                                                 -------------------------------
------------------------------------------------------------------------
                                                                               
Ground      Surface
                                                                             
Water SCI-     Water                                 SCI-GROW2   GENEEC EEC
             Population Subgroup\1\                  Acute        DWLOC      
GROW2 EEC    GENEEC EEC  RfD2 mg/kg/     DWLOC        EEC in     in <greek-
                                                   RfD\2\ mg/  <greek-m>g/   
in <greek-   in <greek-      day      <greek-m>g/  <greek-m>g/     
m>g/L
                                                     kg/day         L          
m>g/L        m>g/L                       L            L

--------------------------------------------------------------------------------
------------------------------------------------------------------------
U.S. Population.................................         0.10        25000        
0.013           98        0.045         1200        0.013           66
Children (1-6 yrs)..............................         0.10          540        
0.013           98        0.045          200        0.013           66
--------------------------------------------------------------------------------
------------------------------------------------------------------------
\1\ DEEM TMRCs in mg/kg/day: U.S. Population = 0.01075, children (1-6 yrs) = 
0.02465
\2\ Adjusted for FQPA

    For chronic (non-cancer) exposure to dicamba in surface and ground 
water, the drinking water levels of concern are 1,200 <greek-m>g/L for 
U.S. population, and 200 <greek-m>g/L for children (1-6 yrs). To 
calculate the DWLOC for chronic (non-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 dicamba in drinking water. DWLOCs were then 
calculated using default body weights and drinking consumption figures.
    Estimated maximum concentrations of dicamba in surface and ground 
water are 98 and 0.013 ppb, respectively. The estimated concentrations 
of dicamba in surface and ground water are less than OPP's level of 
concern for dicamba in drinking water as a contribution to chronic 
aggregate exposure. Therefore, taking into account present uses and 
uses proposed in this action, EPA concludes with reasonable certainty 
that residues of dicamba in drinking water (when considered along with 
other sources of exposure for which there are reliable data) would not 
result in unacceptable levels of aggregate human health risk at this 
time.
    The dietary (food and water) exposure database for dicamba is 
adequate to assess infants' and children's exposure.
    3. From non-dietary exposure. Dicamba (3,6-dichloro-o-anisic acid) 
is currently registered for use on outdoor residential and recreational 
turf. Application is made by both homeowners and professional 
applicators. There is a potential oral, inhalation, eye and dermal 
exposure to infants and children to dicamba from the registered uses 
for lawn and turfgrass weed control These exposures are considered to 
be very low. Currently there are no inhalation or eye exposure data 
required for post-application of pesticides to lawns and turf. As 
inhalation exposure for mixer/loaders is acceptable, the risk to 
infants and children from inhalation exposure under a much lower 
exposure scenario is characterized qualitatively as being extremely 
low. Exposure data are required for hand to mouth movements of infants 
and children. As there are no chemical-specific or site-specific data 
available to determine the potential risks associated with residential 
exposures, the EPA has determined that residential exposure and risk 
are acceptable for dosages of 0.5 lb/A, based on a dermal NOAEL of 
1,000 mg/kg/day and exposures of 0.051 mg/kg/day for low pressure hand 
wand, liquid formulations; and 0.079 mg/kg/day for granular 
formulations. For residential post-application exposure and risk 
assessment, EPA determined that the potential residential post-
application risks for short-term and intermediate exposures did not 
exceed their level of concern. In this analysis both oral and dermal 
exposures and risks for adults and infants from post-applications were 
determined. This analysis was based on assumptions and generic data 
from the Draft HED Standard Operating Procedures (SOPs) for Residential 
Exposure Assessments (December 18, l997. These SOPs rely on what are 
considered to be upper-percentile assumptions and intended to represent 
Tier 1 assessments.
    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." The Agency believes that "available 
information" in this context might include not only toxicity, 
chemistry, and exposure data, but also scientific policies and 
methodologies for understanding common mechanisms of toxicity and 
conducting cumulative risk assessments. For most pesticides, although 
the Agency has some information in its files that may turn out to be 
helpful in eventually determining whether a pesticide shares a common 
mechanism of toxicity with any other substances, EPA does not at this 
time have the methodologies to resolve the complex scientific issues 
concerning common mechanism of toxicity in a meaningful way. EPA has 
begun a pilot process to study this issue further through the 
examination of particular classes of pesticides. The Agency hopes that 
the results of this pilot process will increase the Agency's scientific 
understanding of this question such that

[[Page 766]]

EPA will be able to develop and apply scientific principles for better 
determining which chemicals have a common mechanism of toxicity and 
evaluating the cumulative effects of such chemicals. The Agency 
anticipates, however, that even as its understanding of the science of 
common mechanisms increases, decisions on specific classes of chemicals 
will be heavily dependent on chemical specific data, much of which may 
not be presently available.
    Although at present the Agency does not know how to apply the 
information in its files concerning common mechanism issues to most 
risk assessments, there are pesticides as to which the common mechanism 
issues can be resolved. These pesticides include pesticides that are 
toxicologically dissimilar to existing chemical substances (in which 
case the Agency can conclude that it is unlikely that a pesticide 
shares a common mechanism of activity with other substances) and 
pesticides that produce a common toxic metabolite (in which case common 
mechanism of activity will be assumed).
    EPA does not have, at this time, available data to determine 
whether dicamba and its metabolites (3,6-dichloro-5-hydroxy-o-anisic 
acid and 3,6-dichloro-o-2-hydroxybenzoic acid) have a common mechanism 
of toxicity with other substances or how to include this pesticide or 
its metabolites in a cumulative risk assessment. For the purposes of 
this tolerance action, therefore, EPA has not assumed that dicamba and 
its metabolites have a common mechanism of toxicity with other 
substances.

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

    1. Acute risk. Under Unit II.C.1.i of this preamble an acute risk 
assessment using a high-end exposure estimate for dicamba was 
determined for the general U.S. population, infants (<1 year), children 
(1-6 years), children (7 -12) years). None of the population subgroups 
yielded percent RfDs (adjusted for FQPA) above 100.
    Based on the drinking water risk assessment under Unit II.C.2 of 
this preamble, the maximum estimated concentrations of dicamba in 
surface and ground water are less than levels of concern in drinking 
water as a contribution to acute aggregate exposure.
    2. Chronic risk. Using the exposure assumptions described Unit 
II.C.1.ii of this preamble, EPA has concluded that aggregate exposure 
to dicamba from food will utilize 23.9% of the RfD for the U.S. 
population. The major identifiable subgroup with the highest aggregate 
exposure is children (1-6 years old). The percent of the RfD utilized 
by this subgroup was determined to be 71.1%. 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 dicamba in drinking water and from non-
dietary, non-occupational exposure, EPA does not expect the aggregate 
exposure to exceed 100% of the RfD.
    3. Short and intermediate-term aggregate risk. Dicamba is currently 
registered for use on turfgrass including sod production, commercial 
and residential turf. Short- or intermediate-term dermal toxicity 
endpoints have been identified for dicamba, and was quantified at 1,000 
mg/kg/day. Using EPA Standard Operating Procedures for Residential 
Exposure Assessments, including post-application exposures and risk 
assessments; the Margin of Exposure (MOE) did not exceed 300 the level 
of concern.
    4. Aggregate cancer risk for U.S. population. EPA has classified 
dicamba as a "not classifiable" human carcinogen. Available 
oncogenicity studies have been classified as supplemental because the 
studies did not achieve an MTD. However, the studies indicate no 
carcinogenicity potential at the highest dose tested, 2,500 ppm (rat) 
and 3,000 ppm (mice). A quantitative cancer risk can not be made based 
on the supplemental rat and mouse carcinogenicity studies. However, 
these studies were adequate to indicate that dicamba has either a low 
cancer risk or no cancer risk. A pharmacokinetics study presently 
pending review by EPA indicates that the MTD of these carcinogenicity 
studies was reached, thus changing these carcinogenicity studies to be 
acceptable studies. No quantitative cancer risk will be made for 
dicamba and its metabolites if the pending study is corroborated by 
EPA's review. Alternatively, if the study is not corroborated, 
replacement carcinogenicity studies will be required.
    5. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
from aggregate exposure to dicamba residues.

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 dicamba, EPA considered data from developmental 
toxicity studies in the rat and rabbit and a two-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. Pre- and post-natal sensitivity.  There was evidence of 
increased susceptibility to the offspring following pre- and/or 
postnatal exposure in the 2-generation reproduction study in rat. In 
this study, offspring toxicity was manifested as significantly 
decreased pup growth in all generations and mating at a dose lower than 
that which caused parental systemic toxicity(abortions and clinical 
signs of neurotoxicity). Available studies indicated no increase 
susceptibility of rats or rabbits in in utero exposure to dicamba. In a 
prenatal developmental toxicity study in rats, there was no evidence of 
developmental toxicity at the highest dose tested. In a prenatal 
developmental toxicity study in rabbits, developmental toxicity 
(irregular ossification of internasal bones) were only seen at the dose 
that caused maternal toxicity (abortions and neurotoxic clinical 
signs).
    iii. Conclusion. There is a adequate toxicity database for dicamba 
and exposure data is complete or is estimated based on data that 
reasonably accounts for potential exposures. A ten-

[[Page 767]]

fold safety factor for increased susceptibility of infants and children 
was applied for chronic (long-term) exposure, and a three-fold safety 
factor was applied for acute (short- and intermediate-term) exposures 
to dicamba, due to evidence of increased susceptibility to the 
offspring following pre- and/or postnatal exposure in the 2-generation 
reproduction study in rats. The uncertainty factor (FQPA Safety Factor) 
of ten-fold was reduced for acute dietary and short- and Intermediate-
term residential exposures because the increased susceptibility was 
only observed in the reproduction study and not in the prenatal 
developmental studies. The FQPA Safety Factor was reduced to 3x for 
acute dietary risk assessment for all populations, including infants 
and children, because: (1) the endpoint of concern is clinical signs of 
neurotoxicity (in the absence of neuropathology) observed following a 
single oral exposure in an acute neurotoxicity study; (2) the increased 
susceptibility was seen in the offspring of parental animals receiving 
repeated oral exposures in a 2-generation reproduction toxicity study; 
(3) no increased susceptibility was observed following in utero 
exposures to rats or rabbits in the developmental studies; and (4) a 
developmental neurotoxicity study in rats is required.
    2. Acute risk. Acute dietary risks were discussed under 
B<INF>1</INF> above. As stated there, an acute dietary RfD was 
determined to be 0.10 mg/kg/day, based on the LOAEL of 300 mg/kg/day 
and and uncertainty factor of 3,000 for infants and children. The 
assessment made by EPA included only exposure from food. Based on high-
end exposures, the percent of the RfD occupied for the U.S population, 
Nursing Infants, Non-nursing Infants, Children (ages 1-6 years) and 
Children (ages 7-12 years) were less than 100%. The subgroup with the 
highest exposure was the Non-nursing Infants which occupied 63.2% of 
the RfD. The EPA concluded that with reasonable certainty the residues 
of dicamba in food and 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 Final Rule.
    3. Chronic risk. Using the exposure assumptions described above, 
EPA has concluded that aggregate exposure to dicamba from food will 
utilize 16.5% of the RfD for nursing infants, 71.1% for non-nursing 
infants, 54.8% for children (1-6 years old ), and 36.8% for children 
(7-12 years old). 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 
dicamba.... in drinking water and from non-dietary, non-occupational 
exposure, EPA does not expect the aggregate exposure to exceed 100% of 
the RfD
    4. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to infants and children from aggregate exposure to dicamba residues.

III. Other Considerations

A. Endocrine Disrupter Effects

    EPA is required to develop a screening program to determine whether 
certain substances (including all pesticides and inerts) "may have an 
effect in humans that is similar to an effect produced by a naturally 
occurring estrogen, or such other endocrine effect...." The Agency is 
currently working with interested stakeholders, including other 
government agencies, public interest groups, industry and research 
scientists in developing a screening and testing program and a priority 
setting scheme to implement this program. Congress has allowed 3 years 
from the passage of FQPA (August 3, l999) to implement this program. At 
that time, EPA may require further testing of this active ingredient 
and end use products for endocrine disrupter effects.

B. Analytical Enforcement Methodology.

    An adequate analytical method for determining the magnitude of 
residues in the raw agricultural commodities listed in this Final Rule 
has been evaluated by EPA and is published in the Pesticide Analytical 
Manual (PAM II). The method may be requested from: Calvin Furlow, 
Public Information Branch, Field Operations Division (7502C), Office of 
Pesticide Programs, Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460. Office location and telephone number: Room 1130A, 
CM #2, 1921 Jefferson Davis Highway, Arlington, VA 22202, (703-305-
5937).

C. Magnitude of Residues.

    The nature of the residue in plants is adequately understood for 
the purposes of this time-limited tolerance.

D. International Residue Limits

    No CODEX Maximum Residue Levels (MRLs) have been established for 
dicamba in or on wheat, barley, soybeans, corn, cotton or asparagus. 
Compatibility cannot be achieved with the Canadian, Mexican, German or 
Australian tolerances because their levels are expressed in terms of 
parent compound only.

IV. Conclusion

    The scientific evaluation of data supporting dicamba using 100% 
crop treated and anticipated residues for all population subgroups 
examined by EPA shows the use on the raw agricultural commodities for 
which tolerances are established or revised by this Final Rule will not 
cause exposure at which the Agency believes there is an appreciable 
risk and thus EPA concludes there is a reasonable certainty of no harm 
from aggregate exposure to dicamba. Based on the information cited 
above, EPA has determined that the tolerances for residues of dicamba 
in the raw agricultural commodities listed in this Final Rule will be 
safe; therefore, the tolerances are established as set forth below.

V. Objections and Hearing Requests

    The new FFDCA section 408(g) provides essentially the same process 
for persons to "object" to a tolerance regulation issued by EPA under 
new section 408(e) and (l)(6) as was provided in the old section 408 
and in section 409. However, the period for filing objections is 60 
days, rather than 30 days. EPA currently has procedural regulations 
which govern the submission of objections and hearing requests. These 
regulations will require some modification to reflect the new law. 
However, until those modifications can be made, EPA will continue to 
use those procedural regulations with appropriate adjustments to 
reflect the new law.
    Any person may, by March 8, 1999, file written objections to any 
aspect of this regulation and may also request a hearing on those 
objections. Objections and hearing requests must be filed with the 
Hearing Clerk, at the address given above (40 CFR 178.20). A copy of 
the objections and/or hearing requests filed with the Hearing Clerk 
should be submitted to the OPP docket for this rulemaking. The 
objections submitted must specify the provisions of the regulation 
deemed objectionable and the grounds for the objections (40 CFR 
178.25). Each objection must be accompanied by the fee prescribed by 40 
CFR 180.33(i). If a hearing is requested, the objections must include a 
statement of the factual issues on which a hearing is requested, the 
requestor's contentions on such issues, and a summary of any evidence 
relied upon by the requestor (40 CFR 178.27). A request for a hearing 
will be granted if the Administrator determines that the

[[Page 768]]

material submitted shows the following: There is genuine and 
substantial issue of fact; there is a reasonable possibility that 
available evidence identified by the requestor would, if established, 
resolve one or more of such issues in favor of the requestor, taking 
into account uncontested claims or facts to the contrary; and 
resolution of the factual issues in the manner sought by the requestor 
would be adequate to justify the action requested (40 CFR 178.32). 
Information submitted in connection with an objection or hearing 
request may be claimed confidential by marking any part or all of that 
information as Confidential Business Information (CBI). Information so 
marked will not be disclosed except in accordance with procedures set 
forth in 40 CFR part 2. A copy of the information that does not contain 
CBI must be submitted for inclusion in the public record. Information 
not marked confidential may be disclosed publicly by EPA without prior 
notice.

VI. Public Record and Electronic Submissions

    EPA has established a record for this rulemaking under docket 
control number [OPP-300767] (including any comments and data submitted 
electronically). A public version of this record, including printed, 
paper versions of electronic comments, which does not include any 
information claimed as CBI, is available for inspection from 8:30 a.m. 
to 4 p.m., Monday through Friday, excluding legal holidays. The public 
record is located in Room 119 of the Public Information and Records 
Integrity Branch, Information Resources and Services Division (7502C), 
Office of Pesticide Programs, Environmental Protection Agency, Crystal 
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
    The official record for this rulemaking, as well as the public 
version, as described above will be kept in paper form. Accordingly, 
EPA will transfer any copies of objections and hearing requests 
received electronically into printed, paper form as they are received 
and will place the paper copies in the official rulemaking record which 
will also include all comments submitted directly in writing. The 
official rulemaking record is the paper record maintained at the 
Virginia address in "ADDRESSES" at the beginning of this document.

VII. Regulatory Assessment Requirements

A. Certain Acts and Executive Orders

    This final rule establishes tolerances under FFDCA section 408(d) 
in response to a petition submitted to the Agency. The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Order 12866, entitled Regulatory Planning and 
Review (58 FR 51735, October 4, 1993). This final rule does not contain 
any information collections subject to OMB approval under the Paperwork 
Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose any enforceable 
duty or contain any unfunded mandate as described under Title II of the 
Unfunded Mandates Reform Act of 1995 (UMRA) (Pub. L. 104-4). Nor does 
it require any special considerations as required by Executive Order 
12898, entitled Federal Actions to Address Environmental Justice in 
Minority Populations and Low-Income Populations (59 FR 7629, February 
16, 1994), or require OMB review in accordance with Executive Order 
13045, entitled Protection of Children from Environmental Health Risks 
and Safety Risks (62 FR 19885, April 23, 1997).
    In addition, since tolerances and exemptions that are established 
on the basis of a petition under FFDCA section 408(d), such as the 
tolerances in this final rule, do not require the issuance of a 
proposed rule, the requirements of the Regulatory Flexibility Act (RFA) 
(5 U.S.C. 601 et seq.) do not apply. Nevertheless, the Agency has 
previously assessed whether establishing tolerances, exemptions from 
tolerances, raising tolerance levels or expanding exemptions might 
adversely impact small entities and concluded, as a generic matter, 
that there is no adverse economic impact. The factual basis for the 
Agency's generic certification for tolerance actions published on May 
4, 1981 (46 FR 24950) and was provided to the Chief Counsel for 
Advocacy of the Small Business Administration.

B. Executive Order 12875

    Under Executive Order 12875, entitled Enhancing the 
Intergovernmental Partnership (58 FR 58093, October 28, 1993), EPA may 
not issue a regulation that is not required by statute and that creates 
a mandate upon a State, local, or tribal government, unless the Federal 
government provides the funds necessary to pay the direct compliance 
costs incurred by those governments. If the mandate is unfunded, EPA 
must provide to OMB a description of the extent of EPA's prior 
consultation with representatives of affected State, local, and tribal 
governments, the nature of their concerns, copies of any written 
communications from the governments, and a statement supporting the 
need to issue the regulation. In addition, Executive Order 12875 
requires EPA to develop an effective process permitting elected 
officials and other representatives of State, local, and tribal 
governments "to provide meaningful and timely input in the development 
of regulatory proposals containing significant unfunded mandates."
    Today's rule does not create an unfunded Federal mandate on State, 
local, or tribal governments. The rule does not impose any enforceable 
duties on these entities. Accordingly, the requirements of section 1(a) 
of Executive Order 12875 do not apply to this rule.

C. Executive Order 13084

    Under Executive Order 13084, entitled Consultation and Coordination 
with Indian Tribal Governments (63 FR 27655, May 19,1998), EPA may not 
issue a regulation that is not required by statute, that significantly 
or uniquely affects the communities of Indian tribal governments, and 
that imposes substantial direct compliance costs on those communities, 
unless the Federal government provides the funds necessary to pay the 
direct compliance costs incurred by the tribal governments. If the 
mandate is unfunded, EPA must provide to OMB, in a separately 
identified section of the preamble to the rule, a description of the 
extent of EPA's prior consultation with representatives of affected 
tribal governments, a summary of the nature of their concerns, and a 
statement supporting the need to issue the regulation. In addition, 
Executive Order 13084 requires EPA to develop an effective process 
permitting elected officials and other representatives of Indian tribal 
governments "to provide meaningful and timely input in the development 
of regulatory policies on matters that significantly or uniquely affect 
their communities."
    Today's rule does not significantly or uniquely affect the 
communities of Indian tribal governments. This action does not involve 
or impose any requirements that affect Indian tribes. Accordingly, the 
requirements of section 3(b) of Executive Order 13084 do not apply to 
this rule.

VIII. Submission to Congress and the Comptroller General

    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the 
Small Business Regulatory Enforcement

[[Page 769]]

Fairness Act of 1996, generally provides that before a rule may take 
effect, the agency promulgating the rule must submit a rule report, 
which includes a copy of the rule, to each House of the Congress and to 
the Comptroller General of the United States. EPA will submit a report 
containing this rule and other required information to the U.S. Senate, 
the U.S. House of Representatives, and the Comptroller General of the 
United States prior to publication of the rule in the Federal Register. 
This rule is not a "major rule" as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: December 22, 1998.

James Jones,

Director, Registration Division, Office of Pesticide Programs.
    Therefore, 40 CFR chapter I is amended as follows:

PART 180-[AMENDED]

    1. The authority citation for part 180 continues to read as 
follows:
    Authority: 21 U.S.C. 346a and 371.


    2. Section 180.227 is amended by adding a paragraph heading to 
paragraph (a), designating the text following the paragraph heading as 
paragraph (a)(1), redesignating paragraphs (b) and (c) as paragraphs 
(a)(2) and (a)(3), respectively, and by adding and reserving with 
paragraph headings new paragraphs (b), (c) and (d).
    3. Section 180.227 is further amended as follows:
    i. In newly designated paragraph (a)(1), by revising the entries 
for the following commodities: barley, grain; barley, straw; wheat, 
grain; and wheat, straw; by adding alphabetically entries for barley, 
hay; corn, field, forage; corn, field, stover; corn, pop stover; 
cottonseed; cottonseed, meal; crop Group 17 (grass, forage, fodder and 
hay); grass, forage; grass, hay; oats, forage; oats, hay; wheat, 
forage; and wheat, hay; and by removing the entries for asparagus; 
grasses, pasture; and grasses, rangeland.
    ii. In newly designated paragraph (a)(2) by removing the entries 
for soybeans; soybeans, forage; and soybeans, hay; and by adding an 
entry in alphabetical order for asparagus.
    iii. By revising newly designated paragraph (a)(3).
    The added and revised text reads as follows:


Sec. 180.227   Dicamba; tolerances for residues.

    (a)  General. (1) *  *  *


------------------------------------------------------------------------
                 Commodity                        Parts per million
------------------------------------------------------------------------

Barley, grain.............................  6.0
Barley, hay...............................  2.0
Barley, straw.............................  15.0

                  *        *        *        *        *
Corn, field, forage.......................  3.0
Corn, field, stover.......................  3.0

                  *        *        *        *        *
Corn, pop, stover.........................  3.0
Cottonseed................................  3.0
Cottonseed, meal..........................  5.0
Crop Group 17 (grass, forage, fodder and
 hay).
Grass, forage.............................  125.0
Grass, hay................................  200.0

                  *        *        *        *        *
Oats, forage..............................  80.0

                  *        *        *        *        *
Oats, hay.................................  20.0

                  *        *        *        *        *
Wheat, forage.............................  80.0
Wheat, grain..............................  2.0
Wheat, hay................................  20.0
Wheat, straw..............................  30.0
------------------------------------------------------------------------

    (2) *  *  *

------------------------------------------------------------------------
                                                              Parts Per
                         Commodity                             million
------------------------------------------------------------------------
Asparagus..................................................          4.0

                  *        *        *        *        *
------------------------------------------------------------------------

    (3) Tolerances are established for the combined residues of dicamba 
(3,6-dichloro-o-anisic and its metablites 3,6-dichloro-5-hydroxy-o-
anisic acid and 3,6-dichloro-o-2-hydroxy-benzoic acid in or on the raw 
agricultural commodities as follows:


------------------------------------------------------------------------
                                                              Parts Per
                         Commodity                             million
------------------------------------------------------------------------
Aspirated grain fractions..................................       5100.0
Soybean, hulls.............................................         13.0
Soybean, seed..............................................         10.0
------------------------------------------------------------------------

    (b) Section 18 emergency exemptions. [Reserved]
    (c) Tolerances with regional registrations. [Reserved]
    (d) Indirect or inadvertent residues. [Reserved]

[FR Doc. 99-109 Filed 1-5-99; 8:45 am]
BILLING CODE 6560-50-F