Glyphosate - Pesticide Petition Filing 8/98
[Federal Register: August 26, 1998 (Volume 63, Number 165)]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
ENVIRONMENTAL PROTECTION AGENCY
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
SUMMARY: This notice announces the initial filing of pesticide
petitions proposing the establishment of regulations for residues of
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-826, must
be received on or before September 25, 1998.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7502C), Office of Pesticides Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments
to: Rm. 119, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
Comments and data may also be submitted electronically to: opp-
email@example.com. Follow the instructions under "SUPPLEMENTARY
INFORMATION." No confidential business information should be submitted
Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
"Confidential Business Information" (CBI). CBI should not be
submitted through e-mail. Information marked as CBI will not be
disclosed except in accordance with procedures set forth in 40 CFR part
2. A copy of the comment 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. All written
comments will be available for public inspection in Rm. 1132 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: The product manager listed in the
Product Manager telephone number Address
Beth Edwards (PM 3)........... Rm. 206, CM #2, 703- 1921 Jefferson
305-5400, e- Davis Hwy,
mail:edwards.beth@epa Arlington, VA
Sidney Jackson (PM 22)........ Rm. 233, CM #2, 703- Do.
SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemicals in or on various food
commodities under section 408 of the Federal Food, Drug, and Comestic
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these petitions
contain data or information regarding the elements set forth in section
408(d)(2); however, EPA has not fully evaluated the sufficiency of the
submitted data at this time or whether the data supports granting of
the petition. Additional data may be needed before EPA rules on the
The official record for this notice of filing, as well as the
public version, has been established for this notice of filing under
docket control number [PF-826] (including comments and data submitted
electronically as described below). 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 official record is located at the address in
"ADDRESSES" at the beginning of this document.
Electronic comments can be sent directly to EPA at:
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Comments and data
will also be accepted on disks in Wordperfect 5.1 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket number (insert docket number) and appropriate
petition number. Electronic comments on notice may be filed online at
many Federal Depository Libraries.
List of Subjects
Environmental protection, Agricultural commodities, Food additives,
Feed additives, Pesticides and pests, Reporting and recordkeeping
Dated: August 13, 1998.
Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
Petitioner summaries of the pesticide petitions are printed below
as required by section 408(d)(3) of the FFDCA. The summaries of the
petitions were prepared by the petitioners and represent the views of
the petitioners. EPA is publishing the petition summaries verbatim
without editing them in any way. The petition summary announces the
availability of a description of the analytical methods available to
EPA for the detection and measurement of the pesticide chemical
residues or an explanation of why no such method is needed.
3. Interregional Research Project
EPA has received a pesticide petition (PP 7E4833) from the
Interregional Research Project Number 4 (IR-4), proposing pursuant to
section 408(d) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C.
346a(d), to amend 40 CFR part 180 by establishing tolerances for
residues of the herbicide glyphosate [N-phosphonomethyl)glycine] in or
on the raw agricultural commodities (RACs) durian at 0.2 ppm,
mangosteen at 0.2 ppm, and rambutan at 0.2 ppm. Durian, mangosteen, and
rambutan are tree fruits which are grown commercially in Hawaii and
EPA has determined that the petition contains data or information
regarding the elements set forth in section 408(d)(2) of the FFDCA;
however, EPA has not fully evaluated the sufficiency of the submitted
data at this time or whether the data support granting of the petition.
Additional data may be needed before EPA rules on the petition. This
notice includes a summary of the petition prepared by Monsanto
Agricultural Group (MAG), the registrant.
A. Residue Chemistry
1. Plant metabolism. The nature of the residue in plants and
animals is adequately understood. The residue to be regulated is the
2. Analytical method. There is a practical analytical method for
detecting and measuring levels of glyphosate in or on food with a
limits of detection (0.05 ppm) that allows monitoring of food with
residues at or above the levels set in these tolerances. EPA has
provided information on this method to FDA.
3. Magnitude of residues. 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 Monsanto expects no detectable residues of glyphosate in durian,
mangosteen or rambutan when glyphosate is applied in a similar manner.
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.
The Agency's Health Effects Division - Metabolism Committee 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.
B. Toxicological Profile
1. Acute toxicity. Results from an acute oral study in rats show a
combined lethal dose (LD)50 for glyphosate of >5,000
An acute dermal study in rabbit resulted in a LD50 of >
The results of 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.
A primary dermal sensitization study showed no sensitization. Based
on these data, Monsanto 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. While this assay was designed as a
genetic toxicity test, agents that can affect male reproduction
function will also cause effects in this assay. More importantly, the
multi-generation reproduction study in rodents is a complex study
design which measures a broad range of endpoints in the reproductive
system and in developing offspring that are sensitive to alterations by
chemical agents. Glyphosate has been tested in two separate multi-
generation studies and each time the results demonstrated that
glyphosate is not a reproductive toxin.
3. Reproductive and developmental toxicity. An oral developmental
toxicity study with rats given doses of 0, 300, 1,000 and 3,500
milligram/kilogram/day (mg/kg/day) with a maternal no-observed-effect
level (NOEL) of 1,000 mg/kg/day based on clinical signs of toxicity,
body weight effects and mortality, and a fetal NOEL of 1,000 mg/kg/day
based on reduced body weights and delayed sternebrae maturation at the
highest dose tested (HDT) of 3,500 mg/kg/day.
An oral developmental toxicity study with rabbits given doses of
0,75, 175 and 350 mg/kg/day with a maternal of NOEL of 175 mg/kg/day
based on clinical signs of toxicity and mortality, and a fetal NOEL of
350 mg/kg/day based on no developmental toxicity at any dose tested.
A 3-generation reproduction study with rats fed dosage levels of 0,
3, 10 and 30 mg/kg/day with a NOEL for systemic and reproductive/
developmental parameters of 30 mg/kg/day based on no adverse effects
noted at any dose level.
A 2-generation reproduction study with rats fed dosage levels of 0,
100, 500 and 1,500 mg/kg/day with a NOEL for systemic and developmental
parameters of 500 mg/kg/day based on body weight effects, clinical
signs of toxicity in adult animals and decreased pup body weights, and
a reproductive NOEL of 1,500 mg/kg/day.
4. Subchronic toxicity. A 90-day feeding study in mice fed dosage
levels of 0, 5,000, 10,000 and 50,000 with a NOEL of 10,000 ppm based
on body weight effects at the high dose.
A 90-day feeding study in rats fed dosage levels of 0, 1,000, 5,000
and 20,000 ppm with a NOEL of 20,000 ppm based on no effects even at
A 90-day feeding study in dogs given glyphosate, via capsule, at
doses of 0, 200, 600 and 2,000 mg/kg/day with a NOEL of 2,000 mg/kg/day
based on no effects even at the HDT.
5. Chronic toxicity. The reference dose (RfD) for glyphosate based
on maternal effects in a developmental study with rabbits (NOEL of 175
milligram/killogram/body weight day (mg/kg/bwt/day)) and using a
hundred-fold safety factor is calculated to be 2.0 mg/kg/bwt/day.
The EPA Carcinogenicity Peer Review Committee has classified
glyphosate in Group E (evidence of non-carcinogenicity for humans),
based upon lack of convincing carcinogenicity evidence in adequate
studies in two animal species. There was no evidence of carcinogenicity
in an 18-month feeding study in mice and a 2 year feeding study in rats
at the dosage levels tested (DLT). The doses tested were adequate for
identifying a cancer risk.
A mouse carcinogenicity study with mice fed dosage levels of 0,
150,750 and 4,500 mg/kg/day with a NOEL of 750 mg/kg/day based on body
weight effects and microscopic liver changes at the high dose. There
was no carcinogenic effect at the HDT of 4,500 mg/kg/day.
A 12-month oral study in dogs given glyphosate, via capsule, at
doses of 0, 20, 100 and 500 mg/kg/day with a NOEL of 500 mg/kg/day
based on no adverse effects at any dose level.
A 24-month chronic/feeding carcinogenicity study with rats fed
dosage levels of 0, 89, 362 and 940 mg/kg/day (males) and 0, 113, 457
and 1,183 mg/kg/day (females) with a systemic NOEL of 362 mg/kg/day
based on body weight effects in the female and eye effects in males.
There was no carcinogenic response at any dose level.
A 26-month chronic/feeding carcinogenicity study with rats fed
dosage levels of 0, 3, 10 and 31 mg/kg/day (males) and 0, 3, 11 and 34
mg/kg/day (females) with a systemic NOEL of 31 mg/kg/day (males) and 34
mg/kg/day (females) based on no carcinogenic or other adverse effects
at any dose level.
Monsanto believes that these data support their conclusion that
glyphosate does not produce adverse reproductive effects and is not a
developmental toxin, mutagen, carcinogen or a neurotoxin.
6. Animal metabolism. Animal metabolism data were not submitted
with this petition. However, Monsanto believes that the treated
commodities are not fed to animals, therefore, there will be no
residues transferred to meat, milk, poultry, or eggs.
C. Aggregate Exposure
1. Dietary exposure--Food. For purposes of assessing the potential
dietary exposure, Monsanto has estimated aggregate exposure based on
the tolerances for glyphosate on jackfruit, sugar apple and lychee, all
with established 0.2 ppm tolerances. As the consumption of durian,
mangosteen and rambutan is so limited, the theoretical maximum residue
contribution (TMRC) calculations were based on similar or related
tropical fruit: durian and jackfruit are similar in size, with thick
rinds and similar growth habit; mangosteen and sugar apple fruit are
also similar in size and growth habit: and rambutan and lychee are from
the same botanical family, the Sapindaceae. The fruit are not fed to
animals, therefore, there will be no exposure of humans to residues
transferred to meat, milk, poultry, or eggs. Other potential sources of
exposure of the general population to residues of pesticides are
residues in drinking water and exposure from non-occupational sources.
Based on the available acute toxicity data, Monsanto believes that
glyphosate does not pose any acute dietary risks.
2. Drinking water. A Maximum Concentration Level (MCL) has been
established for residues of glyphosate in drinking water at 0.7 mg/l
since glyphosate is approved for direct application to water. The MCL
represents the level at which no known or anticipated adverse health
effects occur, allowing for an adequate margin of safety (MOE), and is
based on the RfD.
Monsanto reports that glyphosate adsorbs strongly to soil and is
not expected to move vertically below the 6-inch soil layer; residues
are expected to be immobile in soil. Glyphosate is readily degraded by
soil microbes to AMPA, which is degraded to carbon dioxide. Monsanto
believes that glyphosate and AMPA are not likely to move to ground
water due to their strong adsorptive characteristics. However, due to
its aquatic use patterns and through erosion, glyphosate does have the
potential to enter surface waters, where, according to Monsanto, it
will adsorb to sediment and undergo microbial degradation.
3. Non-dietary exposure. Exposure (non-occupational) of the general
population to glyphosate is expected based on the currently-registered
uses; however, due to the low acute toxicity and lack of other
toxicological concerns, Monsanto believes that the risk posed by non-
occupational exposure (NOE) to glyphosate is minimal.
D. Cumulative Effects
Because the existing data base is insufficient to fully assess
cumulative toxic effects that may be caused by glyphosate along with
other chemical compound(s) that may share a common mechanism of
toxicity, Monsanto believes that any consideration of such an analysis
of toxicity is inappropriate at this time.
E. Safety Determination
1. U.S. population. The TMRC for existing, published tolerances for
glyphosate is 0.021460 mg/kg/bwt/day or 1.0% of the RfD for the overall
U.S. population. Even using conservative exposure assumptions and
substituting the more widely consumed jackfruit, sugar apple and
lychee, there is not enough exposure to calculate a significant
contribution to the TMRC. As the exposure from durian, mangosteen and
rambutan would be even less, the aggregate exposure of these three
fruits will not add to the RfD for the overall U.S. population. EPA
generally has no concern for exposures below 100% of the RfD.
Therefore, based on the completeness and reliability of the toxicity
data and the conservative exposure assessment, Monsanto concludes that
there is a reasonable certainty that no harm will result from aggregate
exposure to residues of glyphosate, including all anticipated dietary
exposure and all other non-occupational exposures.
2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of glyphosate, data
were considered from developmental toxicity studies in the rat and
rabbit and multi-generation reproduction studies in rats.
No birth defects were observed in the offspring of rats given
glyphosate by gavage at dose levels of 0, 300, 1,000, and 3,500 mg/kg/
day on days 6 through 19 of gestation. The NOEL for this study was
1,000 mg/kg/day based on maternal and developmental toxicity observed
at the HDT, 3,500 mg/kg/day. The high-dose in this study was 3.5 times
higher than the limit dose that is currently required by the
No birth defects were observed in the offspring of rabbits given
glyphosate by gavage at dose levels of 0, 75, 175, and 350 mg/kg/day on
days 6 through 27 of gestation. The NOEL for this study is considered
to be 175 mg/kg/day based on maternal toxicity at the high-dose of 350
mg/kg/day. Because no developmental toxicity was observed at any dose
level, the developmental NOEL is considered to be 350 mg/kg/day.
Male and female rats were fed glyphosate at dose levels of 0, 3,
10, and 30 mg/kg/day every day throughout the production of three
successive generations. No adverse treatment-related effects on
reproduction were observed. Because no toxicity was noted even at the
HDT, a second reproduction study at higher dose levels (HDLs) was
performed and is described below.
Male and female rats were fed glyphosate at dose levels of 0, 100,
500, and 1,500 mg/kg/day every day throughout the production of two
successive generations. Reduced body weights and soft stools occurred
at 1,500 mg/kg/day (3% of the diet); therefore, the systemic NOEL is
considered to be 500 mg/kg/day. Glyphosate did not affect the ability
of rats to mate, conceive, carry or deliver normal offspring at any
3. Reference dose. The TMRC for existing, published and pending
tolerances (including durian, mangosteen, and rambutan) for glyphosate
range from 0.015 for nursing infants to 0.049 for non-nursing infants
(0.8 to 2.5% of the RfD). EPA generally has no concern for exposures
below 100% of the RfD. Therefore, based on the completeness and
reliability of the toxicity data and the conservative exposure
assessment, Monsanto concludes that there is a reasonable certainty
that no harm will result from aggregate exposure to residues of
glyphosate, including all anticipated dietary exposure and all other
4. Endocrine effects. No known factors were identified in sub-
chronic, chronic or developmental toxicity studies to indicate any
endocrine-modulating activity by glyphosate.
F. International Tolerances
Codex maximum residue levels (MRLs) have not been established for
residues of glyphosate on durian, mangosteen and rambutan. (Sidney
[FR Doc. 98-22430 Filed 8-25-98; 8:45 am]
BILLING CODE 6560-50-F