[Federal Register Volume 63, Number 195 (Thursday, October 8, 1998)]
[Rules and Regulations]
[Pages 54058-54066]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-26906]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-300736; FRL 6036-1]
RIN 2070-AB78


Glyphosate; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for residues of 
glyphosate N-(phosphonomethyl) glycine in or on durian, mangosteen, and 
rambutan. The Interregional Research Project 4 (IR-4) requested these 
tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA), as 
amended by the Food Quality Protection Act of 1996.

DATES: This regulation is effective October 8, 1998. Objections and 
requests for hearings must be received by EPA on or before December 7, 
1998.

ADDRESSES: Written objections and hearing requests, identified by the 
docket control number, OPP-300736, 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

[[Page 54059]]

of any objections and hearing requests filed with the Hearing Clerk 
identified by the docket control number, OPP-300736, 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: [email protected]. 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 
or ASCII file format. All copies of objections and hearing requests in 
electronic form must be identified by the docket control number OPP-
300736. 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: Sidney Jackson, 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) 305-7610; e-mail: 
[email protected].

SUPPLEMENTARY INFORMATION: In the Federal Register of August 26, 1998 
(63 FR 45487) (6023-5) 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 a pesticide petition (PP) for tolerance by the 
Interregional Research Project 4. This notice included a summary of the 
petition prepared by Monsanto Agricultural Group (MAG), the registrant. 
There were no comments received in response to the notice of filing.
    The petition requested that 40 CFR 180.364 be amended by 
establishing tolerances for residues of the herbicide glyphosate N-
(phosphonomethyl) glycine, in or on durian at 0.2 part per million 
(ppm), mangosteen at 0.2 ppm, and rambutan at 0.2 ppm.

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 November 26, 1997 (62 FR 62961) (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 
glyphosate and to make a determination on aggregate exposure, 
consistent with section 408(b)(2), for tolerances for residues of 
glyphosate on durian at 0.2 ppm, mangosteen at 0.2 ppm, and rambutan at 
0.2 ppm. EPA's assessment of the dietary exposures and risks associated 
with establishing the tolerances 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 glyphosate are 
discussed below.
    1. Acute toxicity. The required battery of acute toxicity studies 
was submitted and found adequate. The findings were as follows: an 
acute oral study in rats shows a combined lethal dose (LD)50 
of > 5,000 milligram (mg)/kilogram (kg); an acute dermal study in 
rabbit resulted in a LD50 of > 5,000 mg/kg; a primary dermal 
irritation and a primary dermal sensitization study essentially showed 
no irritation and no sensitization, respectively. A primary eye 
irritation study in the rabbit showed severe irritation for glyphosate 
acid. However, glyphosate is normally formulated as one of several 
salts, and eye irritation studies on the salts showed essentially no 
irritation; a primary dermal irritation study showed essentially no 
irritation; and a primary dermal sensitization study showed no 
sensitization.
    Based on these results, the Agency concludes that the acute 
toxicity and irritation potential of glyphosate is low.
    2. Genotoxicity. A number of mutagenicity studies were conducted 
and were all negative. These studies included: chromosomal aberration 
in vitro (no aberrations in Chinese hamster ovary cells were caused 
with or without S9 activation); deoxyribonucleic acid (DNA) repair in 
rat hepatocyte; in vivo bone marrow cytogenic test in rats; rec-assay 
with B. subtilis; reverse mutation test with S. typhimurium; Ames test 
with S. typhimurium; and dominant-lethal mutagenicity test in mice. 
Negative results were obtained when glyphosate was tested in a 
dominant-lethal mutation assay.
    3. Reproductive and developmental toxicity. The oral rat and rabbit 
developmental studies and the oral rat reproduction study demonstrated 
no indication of increased sensitivity of rats or rabbits to in utero 
and postnatal exposure to glyphosate.
     4. Developmental toxicity study in rats. Sprague-Dawley rats were 
dosed by gavage at doses of 0, 300, 1,000, or 3,500 mg/kg/day during 
days 6-15 of gestation. The maternal (systemic) no-observed adverse 
effect level (NOAEL) is 1,000 mg/kg/day. The maternal (systemic) 
lowest-observed effect level (LOAEL) of 3,500 mg/kg/day was based on 
the following treatment-related effects: diarrhea, decreased mean body 
weight gain, breathing rattles, inactivity, red matter around the nose 
and mouth, and on forelimbs and dorsal head, and death (24% of the 
group). The developmental (fetal) NOAEL is 1,000 mg/kg/day. The 
developmental (fetal) LOAEL of 3,500 mg/kg/day was based on treatment-
related developmental effects observed only in the high-dose group of: 
decreases in total implantations/dam and inviable fetuses/

[[Page 54060]]

dam, increased number of litters and fetuses with unossified 
sternebrae, and decreased mean fetal body weights.
    5. Developmental toxicity study in rabbit. Dutch Belted rabbits 
were gavaged during gestation days 6-27 at doses of 0, 75, 175, or 350 
mg/kg/day. The maternal (systemic) NOAEL is 175 mg/kg/day. The maternal 
(systemic) LOAEL of 350 mg/kg/day was based on treatment-related 
effects that included: diarrhea, nasal discharge, and death (62.5% of 
doses died by gestation day 21). The developmental (pup) NOAEL is 
 175 mg/kg/day (insufficient litters were available at 350 
mg/kg/day to assess developmental toxicity). Developmental toxicity was 
not observed at any dose.
    6. Three-generation reproduction study in rat. Sprague-Dawley rats 
were dosed at 0, 3, 10, or 30 mg/kg/day (equivalent to 0, 30, 100 or 
300 ppm). The parental NOAEL is  30 mg/kg/day highest dose 
tested (HDT). The reproductive NOAEL was 10 mg/kg/day based on an 
increased incidence of focal tubular dilation of the kidney (both 
unilateral and bilateral combined) in the 30 mg/kg/day group high-dose 
male F3b pups.
    Since the focal tubular dilation of the kidneys was not observed at 
the 1,500 mg/kg/day level, HDT in the 2-generation rat reproduction 
(see below), but was observed at the 30 mg/kg/day level HDT in the 3-
generation rat reproduction study, the Agency's Reference Dose (RfD) 
Committee concluded that the latter was a spurious rather than 
glyphosate-related effect. Therefore, the parental and reproductive 
(pup) NOAELs are  30 mg/kg/day.
     7. Two-generation reproduction study in rats. Sprague-Dawley rats 
were tested at doses of 0, 2,000, 10,000, or 30,000 ppm (100, 500, or 
1,500 mg/kg/day). Treatment-related effects observed in the high dose 
group included: soft stools, very frequent, in the Fo and 
F1 males and females, decreased food consumption and body 
weight gain of the Fo and F1 males and females 
during the growth premating period, and decreased body weight gain of 
the F1a, F2a and F2b male and female 
pups during the second and third weeks of lactation. Focal tubular 
dilation of the kidneys, observed in the 3-generation study, was not 
observed at any dose level in this study.
    Based on the above findings, the parental and developmental (pup) 
NOAEL's are 500 mg/kg/day and the parental and developmental (pup) 
LOAEL's are 1,500 mg/kg/day. There were no adverse reproductive effects 
at any dose level.
    8. Subchronic toxicity--i. In a 90-day feeding study in Sprague-
Dawley rats at dietary levels of 0, 1,000, 5,000, or 20,000 ppm (50, 
250, and 1,000 mg/kg/day) of glyphosate technical, the NOAEL for 
systemic toxicity was considered less than 1,000 ppm due to increased 
serum phosphorus and potassium at all treated doses in both sexes and 
the occurrence of high dose pancreatic lesions in males (pancreas not 
examined for low and mid-dose groups).
     ii. In a 90-day feeding study in CD-1 mice, dietary levels of 750, 
1,500, or 7,500 mg/kg/day (8,000, 30,000, or 50,000 ppm) of technical 
glyphosate resulted in a systemic NOAEL of 1,500 mg/kg/day with the 
high dose LOAEL based on decreased weight gains of 24% and 18% in males 
and females, respectively.
     iii. In a 21-day dermal toxicity study in New Zealand white 
rabbits, glyphosate was applied to 10/sex/dose 5 with intact and 5 with 
abraded skin at levels of 0, 10, 1,000, or 5,000 mg/kg/day. The rabbits 
were exposed for 6 hours/day, 5 days/week, for 3 weeks. The systemic 
NOAEL was 1,000 mg/kg/day and the LOAEL was 5,000 mg/kg/day, based on 
decreased food consumption in males. Although serum lactate 
dehydrogenase was decreased in both sexes at the high dose, this 
finding was not considered to be toxicologically significant.
    The required 90-day feeding study in dogs is satisfied by the 1-
year dog feeding study.
    9. Chronic toxicity. A chronic feeding/carcinogenicity feeding 
study in Sprague-Dawley rats was conducted for 26 months at dietary 
levels of 0, 30, 100, or 300 ppm (3, 10, or 31 mg/kg/day). There were 
no systemic effects in any of the parameters examined body weight, food 
consumption, clinical signs, mortality, clinical pathology, organ 
weights and histopathology. The systemic NOAEL was established at > 31 
mg/kg/day.
    10. A second chronic toxicity/carcinogenicity study in Sprague-
Dawley rats was conducted at dietary levels of 0, 2,000, 8,000, or 
20,000 ppm (89, 362, or 940 mg/kg/day) for males and 113, 457, or 1,183 
mg/kg/day for females for 24 months. The systemic NOAEL was established 
at 8,000 ppm and the LOAEL was identified at 20,000 ppm based on 
decreased weight gains in the females and increased incidence of 
cataracts and lens abnormalities, decreased urinary pH, increased 
absolute liver weight and increased relative liver weight/brain weight 
in males.
    11. In a 1-year chronic toxicity study in beagle dogs, glyphosate 
technical was administered by gelatin capsule at levels of 0, 20, 100, 
or 500 mg/kg/day. There were no systemic effects in all examined 
parameters and the systemic NOAEL was established at > 500 mg/kg/day.

B. Toxicological Endpoints

    1. Acute toxicity. 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. In glyphosate studies, an acute dietary endpoint 
and dose was not identified in the toxicology data base. A review of 
the rat and rabbit developmental studies did not provide a dose or 
endpoint that could be used for acute dietary risk purposes. 
Additionally, there were no data requirements for acute or subchronic 
rat neurotoxicity studies since there was no evidence of neurotoxicity 
in any of the toxicology studies at very high doses.
    The Agency concludes with reasonable certainty that glyphosate does 
not elicit an acute toxicological response. An acute dietary risk 
assessment is not required.
    2. Short - intermediate - and long- term toxicity dermal. In a 21-
day dermal toxicity study in rabbits with technical glyphosate, the 
NOAEL was 1,000 mg/kg/day and the LOAEL was 5,000 mg/kg/day based on 
decreased food consumption in females. Although the rabbit 
developmental study had a maternal toxicity NOAEL of 175 mg/kg/day, use 
of the 3% dermal absorption with this oral NOAEL of 175 mg/kg/day 
yields a dermal NOAEL > 5,000 mg/kg/day. A LD50 > 2,000 and 
Toxicity Category III were determined in acute dermal toxicity testing. 
Doses and endpoints were not identified for dermal and inhalation route 
of exposure. This risk assessment is not required and a dermal 
absorption factor is not applicable here in evaluating exposure/risk.
     3. Chronic toxicity. EPA has established the RfD for glyphosate at 
2.0 mg/kg/day. The chronic RfD is based on a NOAEL = 175 mg/kg/day 
based on death, diarrhea, and nasal discharge at 350 mg/kg/day LOAEL 
with an uncertainty factor of 100. The data base for RfD determination 
was developed from multiple species testing.
    Groups of 16/dose Dutch Belted rabbits were dosed with technical 
glyphosate at doses of 0, 75, 175, or 350 mg/kg/day between gestation 
days 6 to 27. Maternal effects were seen at only the high dose and 
consisted of diarrhea, nasal discharge and death 10/16.

[[Page 54061]]

Developmental effects were not seen at any dose tested. Therefore, the 
NOAEL and LOAEL for maternal toxicity were 175 mg/kg/day and 350 mg/kg/
day, respectively. The NOAEL for maternal toxicity in the rabbit 
developmental study was the lowest NOAEL of all the major studies which 
include the 24-month mouse carcinogenicity study NOAEL = 750 mg/kg/day, 
the 1-year dog study NOAEL = 500 mg/kg/day, 2-year chronic/onco rat 
study NOAEL = 400 mg/kg/day, 2-generation rat reproduction study NOAEL 
= 500 mg/kg/day and rat developmental study NOAEL = 1000 mg/kg/day
    An uncertainty factor (UF) of 100 was applied to account for inter-
(10x) and intra-(10x) species variation. The 10X factor to protect 
infants and children as required by FQPA was removed, since there was 
no special sensitivity for infants and children and the database is 
complete.
    4. Carcinogenicity. EPA's Cancer Peer Review Committee classified 
glyphosate as a ``Group E'' pesticide which shows no evidence for 
carcinogenicity in rats and mice.
    A chronic feeding/carcinogenicity study in Sprague-Dawley rats was 
performed at doses of 0, 30, 100, or 300 ppm (3, 10, or 31 mg/kg/day) 
for males and 3, 14, or 34 mg/kg/day for females for 26 months. At the 
high-dose, in comparison to concurrent controls, the following results 
were observed: increased incidence of C-cell thyroid carcinomas in 
females and an increased incidence of interstitial cell Leydig cell 
testicular tumors. The thyroid tumors were not statistically 
significant by pairwise comparison to controls and the testicular 
tumors were within the range of historical controls for studies of 
comparable duration. It was concluded that the study results were 
negative for carcinogenicity, but that the dose levels were not high 
enough to assess carcinogenic potential.
    A second chronic feeding/carcinogenicity study was conducted in 
Sprague-Dawley rats for 24 months at dose levels of 2,000, 8,000, or 
20,000 ppm (89, 362, or 940 mg/kg/day) for males and 113, 457, or 1,183 
mg/kg/day in females. The results showed increased incidence of 
pancreatic islet cell adenomas at the low and high dose in males, 
hepatocellular adenomas at the low and high dose in males, and C-cell 
thyroid adenomas in both sexes at the mid and high dose group. Each of 
the tumor types was not considered treatment-related for the following 
reasons:
    i. The pancreatic islet cell tumors had no statistically 
significant dose-related trend, there was no progression to carcinomas, 
and the incidence of pancreatic hyperplasia was not dose-related.
    ii. The hepatocellular adenomas were within the range of historical 
controls, these liver tumors were not statistically significant by 
pairwise comparison to concurrent controls, there was no progression to 
carcinoma, and the incidence of hyperplasia was not considered 
compound-related.
    iii. The C-cell thyroid tumors were not statistically significant 
by pairwise comparison and positive dose-related trend, there was no 
progression to carcinoma, and there was no statistically significant 
dose-related increase in either incidence or severity of hyperplasia in 
either sex.
    A carcinogenicity study in CD-1 mice was conducted for 24 months at 
doses of 0, 150, 750, or 4,500 mg/kg/day (0, 1,000, 5,000, or 30,000 
ppm). There were no effects at the low and mid-doses. At the high dose, 
an increased incidence of renal tubular adenomas was seen in males, but 
not in females zero incidence for all groups. In males, the incidence 
was 1, 0, 1, and 3 out of 50/sex/dose. The occurrence of this rare 
tumor was not statistically significant by pairwise comparison to 
concurrent controls, but had a statistically significant dose-related 
trend. There was no tumor associated non-neoplastic lesions in males, 
but females had an increased incidence of proximal tubule epithelial 
basophilia and hypertrophy in the absence of any renal tubular 
neoplasms. In males, there was an increased incidence of interstitial 
nephritis, hepatocellular hypertrophy and hepatocellular necrosis. 
There was also statistically significant decreased weight gain in both 
sexes. The high dose of 30,000 ppm exceeded the limit dose 7,000 ppm 
for mice. The Agency concluded, based on a weight of the evidence 
evaluation, that the renal tubular adenomas were not compound related 
due to the absence of pairwise statistical significance for males, the 
absence of related non-neoplastic lesion in males, and the presence of 
related non-neoplastic lesions in females in the absence of renal 
tubular adenomas. Additionally, the high dose exceeded the limit dose 
required for testing in mice.
     5. Inhalation exposure general and long-term considerations. 
Formulations of glyphosate are Toxicity Category III or IV and 
technical glyphosate is a wetcake. The acute inhalation study was 
waived for technical glyphosate. A dose and endpoint were not 
identified for this risk assessment. This risk assessment is not 
required.

C. Exposures and Risks

    1. From food and feed uses. Tolerances have been established (40 
CFR 180.364) for the residues of glyphosate, in or on a variety of raw 
agricultural commodities. Existing glyphosate tolerances are numerous 
with values ranging from a low of 0.1 to a high of 200 ppm. Glyphosate 
residues could possibly be transferred to meat and milk. However, in 
feeding studies, no residues of glyphosate were found in milk or fat at 
any dosing level and only minimal residues were found in eggs and 
muscle (at the highest dose of 400 ppm). Significant residue levels 
were found in animal liver and kidney, however, secondary residues are 
not expected to exceed currently established animal tolerances. Risk 
assessments were conducted by EPA to assessed dietary exposures from 
glyphosate as follows:
     Dietary exposure to residues of a pesticide in a food commodity 
are estimated by multiplying the average daily consumption of the food 
forms of that commodity by the tolerance level or the anticipated 
pesticide residue level. The Theoretical Maximum Residue Contribution 
(TMRC) is an estimate of the level of residues consumed daily if each 
food item contained pesticide residues equal to the tolerance. In 
evaluating food exposures, EPA takes into account varying consumption 
patterns of major identifiable subgroups of consumers, including 
infants and children. The TMRC is a ``worst case'' estimate since it is 
based on the assumptions that food contains pesticide residues at the 
tolerance level and that 100% of the crop is treated by pesticides that 
have established tolerances.
    The Agency's dietary risk evaluation system (DRES) analysis was 
used for the chronic dietary exposure estimate for glyphosate. Using 
permanent and time-limited tolerances, dietary exposure to residues of 
glyphosate resulted in a TMRC equivalent to  3% of the RfD 
for all population subgroups. No percent crop treated or anticipated 
residue data were used in the analysis. By using the TMRC, the Agency 
is reasonably certain that exposure is not underestimated for any 
significant subpopulation. An uncertainty factor of 100 is used for all 
subgroups. The proposed tolerances are for uses considered as Low 
Dietary Intake (LDI) crops since the total acreage for all three crops 
is less than 100 acres.
    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

[[Page 54062]]

a one day or single exposure. An acute dietary endpoint and dose was 
not identified in the toxicology data base. A review of the rat and 
rabbit developmental studies did not provide a dose or endpoint that 
could be used for acute dietary risk purposes. Additionally, there were 
no data requirements for acute or subchronic rat neurotoxicity studies 
since there was no evidence of neurotoxicity in any of the toxicology 
studies at very high doses.
    ii. Chronic exposure and risk. The chronic dietary exposure 
analysis from food sources was conducted using the reference dose (RfD) 
of 2.0 mg/kg/day. The RfD is based on the maternal NOAEL of 175 mg/kg/
day in female rabbits from the developmental study in rabbits, and an 
uncertainty factor of 100 which is applicable to all population 
subgroups.
    Durian, mangosteen, and rambutan all qualify as Low Dietary Intake 
(LDI) crops since the total acreage for all three is less than 100 
acres. Consequently, no data on these tropical fruits are included in 
the current version of the DRES system. In conducting this chronic 
dietary risk assessment, the Agency has assumed that inclusion of these 
tropical fruits would not significantly change the resulting % RfD 
values because glyphosate currently has tolerances on a large number of 
non-LDI crops. In addition, EPA would note the exposure estimate for 
existing tolerances is in an overestimate of human dietary exposure due 
to the conservative assumptions built into the system.
    The existing glyphosate tolerances result in a TMRC that is 
equivalent to the following percentages of the RfD:
     For subgroups, U.S. population (48 states), nursing infants (<1 
year old) and non-nursing infants (<1 year old) the % RfD is 1.2, 1.2, 
and 3.3, respectively. For the subgroups, children (1-6 years old), 
children (7-12 years old), and males (13-19 years old) the % RfD is 
2.6, 1.8, and 1.2, respectively.
    2. From drinking water. The GENEEC model and the SCI-GROW model 
were run to produce estimates of glyphosate 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 EPA 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 that would be acceptable as an upper limit 
in light of total aggregate exposure to that chemical from food, water, 
and non-occupational (residential) sources.
     DWLOCchronic 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(liter) (adult male), 
60 kg/2L (adult female), and 10 kg/1L (child).
    i. Acute exposure and risk. An acute dietary endpoint and dose was 
not identified in the toxicology data base. Adequate rat and rabbit 
developmental studies did not provide a dose or endpoint that could be 
used for acute dietary risk purposes. Additionally, there were no data 
requirements for acute or subchronic rat neurotoxicity studies since 
there was no evidence of neurotoxicity in any of the toxicology studies 
at very high doses.
    The Agency concludes that no harm to public would result due to 
acute risk for the proposed uses of glyphosate.
    ii. Chronic exposure and risk. For chronic (non-cancer) exposure to 
glyphosate in surface and ground water, the drinking water levels of 
concern are 69,000 g/L for males (13 yrs+), 59,000 g/
L for females (13 yrs+) and 19,000 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 
DRES) was subtracted from the RfD to obtain the acceptable chronic 
(non-cancer) exposure to glyphosate in drinking water. DWLOCs were then 
calculated using default body weights and drinking consumption figures.
    Estimated average concentrations of glyphosate in surface and 
ground water are 0.063 ppb (after adjustment for the highly 
conservative nature of the GENEEC model) and 0.0011 ppb, respectively. 
The estimated average concentrations of glyphosate in surface and 
ground water are less than EPA's level of concern for glyphosate 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 
glyphosate 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.
    3. From non-dietary exposure. Glyphosate is currently registered 
for use on the following residential non-food sites: non-food crops and 
a variety of other uses including ornamentals, greenhouses, residential 
areas, lawns, and industrial rights of way. Glyphosate is formulated in 
liquid and solid forms and it is applied using ground or aerial 
equipment. Based on the registered uses of glyphosate, the potential 
for occupational and residential exposures exists. However, based on 
the low acute toxicity and the lack of other toxicological concerns, 
glyphosate does not meet the Agency's criteria for occupational and 
residential data requirements. The Agency believes that no significant 
harm to public health would result due to non-dietary exposure from 
proposed uses of glyphosate.
    i. Acute exposure and risk. There are no acute toxicological 
concerns for glyphosate.
    ii. Chronic exposure and risk. Although there are registered 
residential uses for glyphosate, glyphosate does not meet the Agency's 
criteria for residential data requirements, due to the lack of 
toxicological concerns. Incidental acute and/or chronic dietary 
exposures from residential uses of glyphosate are not expected to pose 
undue risks to the general population, including infants and children.
    iii. Short- and intermediate-term exposure and risk. EPA identified 
no toxicological concerns for determined that short- intermediate- and 
long-term dermal or inhalation routes of exposures. The Agency 
concludes that exposures from residential uses of glyphosate are not 
expected to pose undue risks.
    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 glyphosate 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, 
glyphosate 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 glyphosate 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

[[Page 54063]]

Pesticide Tolerances November 26, 1997 (62 FR 62961) (FRL 6023-5).

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

    1. Acute risk. There was no acute dietary endpoint identified, 
therefore no acute toxicological concerns for glyphosate.
    2. Chronic risk. Using the TMRC exposure assumptions described 
above, EPA has concluded that aggregate exposure to glyphosate from 
food will utilize 1.2% of the RfD for the U.S. population. The major 
identifiable subgroup with the highest aggregate exposure is non-
nursing infants less than 1 year old, which utilizes 3.3% of the RfD). 
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 glyphosate 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 risk. Short-term and intermediate-
term dermal and inhalation risk is not a concern due to the lack of 
significant toxicological effects observed with glyphosate under these 
exposure scenarios.
    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.
    4. Aggregate cancer risk for U.S. population. Glyphosate has been 
classified as a Group E chemical, with no evidence of carcinogenicity 
for humans in two acceptable animal studies.
    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 glyphosate 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 glyphosate, 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 during 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 oral rat and rabbit 
developmental studies and the oral rat reproduction study demonstrated 
no indication of increased sensitivity of rats or rabbits to in utero 
and postnatal exposure to glyphosate. In the rat developmental study, 
the developmental NOAEL was 1,000 mg/kg/day and the maternal NOAEL was 
1,000 mg/kg/day. Therefore, there was no prenatal developmental 
toxicity in the absence of maternal toxicity. Similarly in rabbits, the 
prenatal developmental NOAEL was 350 mg/kg/day and the maternal NOAEL 
was 175 mg/kg/day. Therefore, prenatally exposed fetuses were not more 
sensitive to the effects of glyphosate than maternal animals.
    iii. Reproductive toxicity study. In a rat reproduction study, the 
parental NOAEL of 10,000 ppm was identical to the pup NOAEL of 10,000 
ppm and decreased body weight was seen in both pup and parental 
animals. This finding demonstrates that there are no extra 
sensitivities with respect to pre- and post-natal toxicity between 
adult and infant animals.
    iv. Pre- and post-natal sensitivity. The oral perinatal and 
prenatal data demonstrated no indication of increased sensitivity of 
rats or rabbits to in utero and postnatal exposure to glyphosate.
    v. Conclusion. There is a complete toxicity database for glyphosate 
and exposure data are complete or estimated based on data that 
reasonably accounts for potential exposures. Based on these data, there 
is no indication that the developing fetus or neonate is more sensitive 
than adult animals. No developmental neurotoxicity studies are being 
required at this time. A developmental neurotoxicity data requirement 
is an upper tier study and required only if effects observed in the 
acute and 90-day neurotoxicity studies indicate concerns for frank 
neuropathy or alterations seen in fetal nervous system in the 
developmental or reproductive toxicology studies. The Agency believes 
that reliable data support the use of the standard 100-fold uncertainty 
factor, and that a tenfold (10x) uncertainty factor is not needed to 
protect the safety of infants and children.
    2. Acute risk. Although there are no acute toxicological endpoints 
for glyphosate, there exist an adequate exposure database to assess 
potential adverse effects on infants and children, the most highly 
exposed subgroup which utilize 3.3% of the RfD. The Agency concludes 
that the establishment of the proposed tolerances would not pose an 
unacceptable aggregate risk.
    3. Chronic risk. Using the exposure assumptions described above, 
EPA has concluded that aggregate exposure to glyphosate from food will 
utilize 3.3% of the RfD for infants and children. For the general 
population, aggregate exposure to glyhosate from food is 1.2% of the 
RFD. 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 glyphosate in 
drinking water and from non-dietary, non-occupational exposure, EPA 
does not expect the aggregate exposure to exceed 100% of the RfD.
    4. Short- or intermediate-term risk. Short-term and intermediate-
term dermal and inhalation risk is not a concern due to the lack of 
significant toxicological effects observed with glyphosate under these 
exposure scenarios.
    5. 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 glyphosate residues.

III. Other Considerations

A. Metabolism In Plants and Animals

     The qualitative nature of the residue in plants is adequately 
understood. Studies with a variety of plants

[[Page 54064]]

including corn, cotton, soybeans, and wheat indicate that the uptake of 
glyphosate or its metabolite, aminomethylphosphonic acid (AMPA), from 
soil is limited. The material which is taken up is readily 
translocated. Foliarly applied glyphosate is readily absorbed and 
translocated throughout the trees of vines to the fruit of apples, 
coffee, dwarf citrus (calamondin), pears and grapes. Metabolism via N-
methylation yields N-methylated glycines and phosphonic acids. For the 
most part, the ratio of glyphosate to AMPA is 9 to 1 but can approach 1 
to 1 in a few cases (e.g., soybeans and carrots). Much of the residue 
data for crops reflects a detectable residue of parent (0.05 - 0.15 
ppm) along with residues below the level of detection (< 0.05 ppm) of 
AMPA. The terminal residue to be regulated in plants is glyphosate per 
se.
    The qualitative nature of the residue in animals is adequately 
understood. Studies with lactating goats and laying hens fed a mixture 
of glyphosate and AMPA indicate that the primary route of elimination 
was by excretion (urine and feces). These results are consistent with 
metabolism studies in rats, rabbits, and cows. The terminal residues in 
eggs, milk, and animal tissues are glyphosate and its metabolite AMPA; 
there was no evidence of further metabolism. The terminal residue to be 
regulated in livestock is glyphosate per se.

B. Analytical Enforcement Methodology

     Adequate enforcement methods are available for analysis of 
residues of glyphosate in or on plant commodities. These methods 
include GLC (Method I in Pesticides Analytical Manual (PAM) II; the 
limit of detection is 0.05 ppm) and HPLC with fluorometric detection. 
Use of the GLC method is discouraged due to the lengthiness of the 
experimental procedure. The HPLC procedure has undergone successful 
Agency validation and was recommended for inclusion in PAM II. A GC/MS 
method for glyphosate in crops has also been validated by EPA's 
Analytical Chemistry Laboratory (ACL).
    Adequate analytical methods are available for residue data 
collection and enforcement of the proposed tolerances of glyphosate in 
or on durian, mangosteen, and rambutan.

C. Magnitude of Residues

     Residue studies for glyphosate were not submitted for review with 
this petition. However, the Agency believes that data submitted 
previously in support of petitions may be used to support proposed 
uses.
    The proposed use for glyphosate is for orchard floor treatment. The 
registrant referenced extensive experience and data with glyphosate in/
on tree fruit and nuts crops which show that when orchard floor 
applications are made, no detectable residues of the herbicide are 
recovered in the harvested fruit. Based on these data EPA expects no 
detectable residues of glyphosate in durian, mangosteen or rambutan 
when glyphosate is applied in a similar manner. Glyphosate is known to 
be a water soluble chemical and does not rapidly transport into trees 
from soil. Residues are expected to be mainly due to contamination 
(e.g., spray drift). Therefore, significant amounts of residues are not 
expected to be detected in tree crops.
    Tolerances for the combined residues of glyphosate and its 
metabolite, aminomethylphosphonic acid (AMPA), have been established at 
0.2 ppm on a number of tree fruit and nuts, as well as a variety of 
tropical fruit: acerola, atemoya, avocado, banana, breadfruit, 
canistel, carambola, cherimoya cocoa beans, coconuts, dates, figs, 
genip, jaboticaba, jackfruit, longan, lychee, mango, mayhaw, passion 
fruit, persimmon, pomegranate, sapodilla, sapote, soursop, sugar apple 
and tamarind. Any secondary residues occurring in milk, eggs, meat, 
fat, liver and kidney of cattle, goats, horses, hogs, poultry and sheep 
are covered by existing tolerances.
    EPA has determined that AMPA should be dropped from the tolerance 
expression. Tolerances that are the subject of this notice are based 
solely on residues of glyphosate.

D. International Residue Limits

     There are no CODEX, Canadian, or Mexican tolerances for glyphosate 
residues on durian, mangosteen, or rambutan. Therefore, international 
harmonization is not an issue at this time.

IV. Conclusion

    Therefore, the tolerance is established for residues of glyphosate 
N-(phosphonomethyl) glycine in durian commodity at 0.2 ppm, mangosteen 
at 0.2 ppm, and rambutan at 0.2 ppm.

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 December 7, 1998, 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 or a fee waiver 
request as specified prescribed by 40 CFR 180.33. 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 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-300736 (including any comments and data submitted 
electronically). A public version of this

[[Page 54065]]

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.
    Electronic comments may be sent directly to EPA at:
    [email protected].

    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption.
    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 prior consultation as specified by Executive Order 
12875, entitled Enhancing the Intergovernmental Partnership (58 FR 
58093, October 28, 1993), or 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 /exemption] 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 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.


[[Page 54066]]


    Dated: September 29, 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. In Sec.  180.364, paragraph (a), by designating the text 
following the paragraph heading as paragraph (a)(1), and by adding 
paragraph (a)(2) to read as follows:


Sec.  180.364   Glyphosate; residues for tolerances.

    (a) *    *    *
    (2) Tolerances are established for residues of glyphosate N-
(phosphonomethyl) glycine in or on the commodities list in the table as 
follows:

------------------------------------------------------------------------
                                                                  Parts
                           Commodity                               per
                                                                 million
------------------------------------------------------------------------
Durian.........................................................    0.2
Mangosteen.....................................................    0.2
Rambutan.......................................................    0.2
------------------------------------------------------------------------

*    *    *    *    *

[FR Doc. 98-26906 Filed 10-7-98; 8:45 am]
BILLING CODE 6560-50-F